[
  {
    "caption": "(B) P2 MRI  images (axial, sagittal  and coronal plane) showing ventriculomegaly  (red asterisk), slightly thickened cortex  and bilateral enlarged gyri  (white asterisk).",
    "diseases": "ventriculomegaly"
  },
  {
    "caption": "I. Caspase-3 activity in tumors from control (n=4) or netrin-1-interfering antibody (n=4) treated mice. Tumors resection was performed at the end of the treatment. Results are means +/-std of caspase-3 activity. *:p=0.02; two-sided Mann-Whitney test.",
    "diseases": "Tumors, tumors"
  },
  {
    "caption": "(a) Associations between chromatin accessibility DA-peaks and GWAS summary statistics. All DA-peaks (DA), gained DA-peaks (gained), closing DA-peaks, and consensus peaks (all) are fitted to summary statistics data of multiple GWAS studies (y-axis). Circle color indicates LDSC regression coefficient (effect size), and circle size indicates association significance. Shadings indicate treatments. Time points are shown (orange = 1h, brown = 6h). Red lines indicate LD score regression coefficient adjusted P < 0.1 after BH correction. Orange lines indicate P < 0.1. (BD = Bipolar Disorder; SZ = Schizophrenia; BD+SZ: BP and SZ samples combined; MDD = Major Depressive Disorder; ADHD = Attention deficit hyperactivity disorder; AD = Alzheimer's Disease).",
    "diseases": "AD, Alzheimer's Disease, ADHD, Attention deficit hyperactivity disorder, BD, Bipolar Disorder, BP, Major Depressive Disorder, MDD, Schizophrenia, SZ"
  },
  {
    "caption": "A. Measurement of oxygen consumption rate (OCR), extracellular acidification rate (ECAR) and oxidative burst of monocytes from COVID-19 patients (COVID) and healthy controls (CTR). OCR was measured in real time, under basal condition and in response to mitochondria inhibitors: oligomycin (Oligo, 2 μM), cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP, 0.5 μM), and antimycin A plus rotenone (Rot/AA, 0.5 μM). Oxidative burst was measured in response to PMA/ionomycin (PMA/Iono, 1 μg/mL). Scatter plots show the quantification of basal respiration (indicated as Basal OCR), ATP-linked respiration (ATP-linked), maximal respiration (Max Resp), proton-leak, spare respiratory capacity (Spare), oxidative burst immediate response and basal ECAR. The maximal respiration kinetic range and the oxidative burst kinetic range are also reported and were obtained by analyzing the area under the curve (AUC) from the sixth to the tenth measurement and from the tenth to the thirteenth measurement, respectively. Data represent individual values, mean and standard error of the mean (CTR, n=12; COVID, n=13). Mann-Whitney test was used for statistical analysis. Exact p values are reported in the figure. Representative traces of OCR of monocytes from COVID-19 patients (COVID) and healthy controls (CTR) are also reported.",
    "diseases": "COVID, COVID-19"
  },
  {
    "caption": "B. Representative electron micrographs of mitochondrial ultrastructural changes observed in COVID-19 monocytes. Panels \"a\" and \"c\" are representative electron micrographs of monocytes from healthy controls, whereas panels \"b\", \"d\" and \"e\" are representative electron micrographs of monocytes from COVID-19 patients. In panel \"f\" the quantification of mitochondrial area, external perimeter, Feret's diameter, aspect ratio circularity and roundness are reported (n=225 mitochondria for each group). Black arrows in panel \"d\" indicate mitochondria; N refers to nucleus. Exact p values are reported in panel \"f\".",
    "diseases": "COVID-19"
  },
  {
    "caption": "B. Heatmaps representing different monocyte clusters identified by FlowSOM, with percentages in healthy donors (CTR) and COVID-19 patients. The colors in the heat map represent the median of the arcsinh, 0-1 transformed marker expression calculated over cells from all the samples, varying from blue for lower expression to red for higher expression. Each cluster has a unique color assigned (bar on the left which colors correspond to those used in panel A).",
    "diseases": "COVID-19"
  },
  {
    "caption": "C. Differential analysis between healthy donors (CTR, n=8) and COVID-19 (COVID, n=7). The heatmap represents arcsine-square-root transformed cell frequencies that were subsequently normalized per cluster (rows) to mean of zero and standard deviation of one. The color of the heat varies from blue, indicating relative under-representation, to red indicating relative over-representation. Bar and numbers at the right indicate significant differentially abundant clusters (green) and adjusted p values (Differential analysis performed by diffcyt package present in the Catalyst package). The statistical analyses was done using GLMM (according to the actual guidelines) and all p-values were Bonferroni corrected. Clusters were sorted according to the adjusted p values, so that the cluster at the top shows the most significant abundance changes between the two conditions. D. Boxes and whiskers plots representing maximum, minimum, median value, 25 and 75 percentile of different subpopulations of monocytes in healthy donors (CTR, n=8) and COVID-19 patients (COVID, n=7).",
    "diseases": "COVID, COVID-19"
  },
  {
    "caption": "E. Scatter plots showing the frequency of PD-1+ cells, PD-L1+ cells among total monocytes in healthy controls (CTR, n=8) and COVID-19 patients (COVID, n=7). A scatter plot reporting the median fluorescence intensity (MFI) of PD-L1 in total monocytes is also shown. Data represent individual values, mean ± standard error of the mean. Mann-Whitney test was used for statistical analysis. Exact p values are reported in the figure.",
    "diseases": "COVID, COVID-19"
  },
  {
    "caption": "A. Quantification of cytokines and other mediators in plasma obtained from COVID-19 patients (COVID, n=15) and healthy controls (CTR, n=15). Data represent individual values, mean ± standard error of the mean. Mann-Whitney test was used for statistical analysis. Exact p values are reported in the figure.",
    "diseases": "COVID, COVID-19"
  },
  {
    "caption": "B. Representative dot plots showing percentages of immature and mature circulating monocytes in CTR and COVID-19 patients. Scatter plots showing the quantification of immature and mature monocytes in healthy controls (CTR, n=6) and COVID-19 patients (COVID, n=7) are reported. Mann-Whitney test was used for statistical analysis. Exact p values are reported in the figure.",
    "diseases": "COVID, COVID-19"
  },
  {
    "caption": "(E) Expression of the indicated eIF3 proteins in 97 colon adenocarcinomas versus 100 normal colonic mucosae and 110 clear cell renal cell carcinomas versus 84 normal kidney samples. Log2 spectral count data from CPTAC via UALCAN portal",
    "diseases": "clear cell renal cell carcinomas, colon adenocarcinomas"
  },
  {
    "caption": "RT plus anti-PD-L1 (B) reverses T-cell exhaustion . Bar graphs show quantitation of T cell activation markers in tumor samples based on flow cytometry analysis, as indicated (n=5 per group; means ± SD, n=1, One-way ANOVA, Bonferroni test).",
    "diseases": "tumor"
  },
  {
    "caption": "RT plus anti-PD-L1 (C) increases CD8:Treg ratio. Bar graphs show ratio of CD8:Treg ratio in tumor samples based on flow cytometry analysis, as indicated (n=5 per group; means ± SD, n=1, One-way ANOVA, Bonferroni test).",
    "diseases": "tumor"
  },
  {
    "caption": "LSM images of cross-sections through the heart of an adult control and ILK K.O. mouse four weeks after myocardial ischemia and reperfusion (MI/R), showing the outer lateral region of the LV. Scale bars: 100 µm Overall cardiac lymph vessel and blood vessel density in heart sections as determined by Lyve1-positive and CD31-positive area (normalised to total analysed myocardial area), respectively. (n = 5 control and n = 7 ILK K.O. mice), P = 0.051 (cardiac lymph vessel density in adult control versus adult ILK K.O.), *P = 0.025 (cardiac blood vessel density in adult control versus adult ILK K.O.)",
    "diseases": "MI, myocardial ischemia, R, reperfusion"
  },
  {
    "caption": " A Kaplan-Meier survival analysis of humanpatients (n = 3,935) with invasive breast cancers divided into two groups based on the gene expression level of Shp2 (see ). ",
    "diseases": "breast cancers"
  },
  {
    "caption": "The antibody response of vaccinated naïve (plasma: n=64; saliva n=66) or SARS-CoV-2-Exp (plasma: n= 21; saliva: n=18) subjects at 7-10 days after the second dose (T2) was compared to that obtained in COVID-19 patients (plasma n=28; saliva n=26). As a control, SARS-CoV-2 specific antibody response was analyzed in non-vaccinated subjects (n=19, Control). Plasma and saliva were tested for IgA to full-length spike and its receptor binding domain (RBD). For plasma samples the titers of antigen specific Ig are expressed in IU/ml. LoD is indicated by a dotted line: LoD (spike IgG)=12, LoD (RBD IgG)=13.8, LoD (spike IgA)=54.22, LoD (RBD IgA)=54.08. For saliva samples the titers of antigen specific Ig were normalized by dividing the values of SARS-CoV-2 specific Ig by total IgA or total IgG concentrations of each sample. The normalization was applied only to values higher than LoD. The adjusted values are expressed in AU.",
    "diseases": "COVID-19"
  },
  {
    "caption": "B, IgA1 and IgA2 subtypes specific for spike protein were measured in plasma and saliva of vaccinated naïve and SARS-CoV-2-Exp subjects 7-10 days after second dose (T2) and the antibody response was compared to that obtained in COVID-19 patients (plasma: n=28; saliva: n=26) and in non-vaccinated subjects (n=19, Control).",
    "diseases": "COVID-19"
  },
  {
    "caption": "e. H&E-stained sections of high grade external sarcomas in Trp53del, Trp53del; Fbxw7mut, Trp53mut and Trp53mut; Fbxw7mut mice. Images are representative of minimum of 3 mice examined for each genotype. Scale bar indicates 100μm.",
    "diseases": "sarcomas"
  },
  {
    "caption": "d. Immunohistochemistry for LEF1 and β-catenin from endometrial carcinomas in Ptendel ± Fbxw7mut mice. High power images show representative staining in LEF1 negative and positive glands. Scale bar bar indicates 1000μm. ",
    "diseases": "endometrial carcinomas"
  },
  {
    "caption": "Dose-dependent viability assays of Brca1+/+ and Brca1-/- mouse mammary tumour-derived cell lines treated with drugs at the indicated concentrations for six days.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "Dose-dependent viability assays of BRCA2-deficient (Capan-1) or -proficient (MIA PaCa-2) human pancreatic carcinoma-derived cells treated with drugs at the indicated concentrations for six days.",
    "diseases": "pancreatic carcinoma"
  },
  {
    "caption": "Dose-dependent viability assays of BRCA2-deficient (PEO1) or -proficient (C4-2) human ovarian tumour-derived cells treated with drugs at the indicated concentrations for six days.",
    "diseases": "ovarian tumour"
  },
  {
    "caption": "BRCA2-deficient (PEO1) or -proficient (C4-2) human ovarian tumour-derived cells were infected with lentiviruses expressing control or CHD4 shRNAs, followed by selection with puromycin for 72 hours. Dose-dependent viability assays were performed on cells treated with drugs at the indicated concentrations for six days.",
    "diseases": "ovarian tumour"
  },
  {
    "caption": "PDTCs derived from breast cancer samples as previously described (Bruna et al, 2016) were treated with chlorambucil at the indicated doses. Cell survival is represented relative to DMSO control. AB521, ER-negative tumour, no BRCA1 alteration; STG201, tumour with BRCA1 promoter methylation and loss of BRCA1 expression; VHIO179, tumour with BRCA1 germline mutation and MAD2L2 inactivating mutation (olaparib-resistant)",
    "diseases": "breast cancer"
  },
  {
    "caption": "A) ALS patients from the UPenn Biobank neuroimaging cohort with higher wPRS exhibited greater reduction of cortical thickness in the orbital prefrontal cortex, anterior cingulate cortex, premotor cortex, lateral temporal cortex, and hippocampus. The heatmap indicates the associated T-statistic for each voxel, with light blue representing the highest value.",
    "diseases": "ALS"
  },
  {
    "caption": "G, AGO1x staining of tissue sections from breast cancers, classified as low-proliferating or high-proliferating based on Ki-67 staining. The upper and lower panel represents two different tissue sections. H, Mean (+/- s.d.) percentage of AGO1x positive cells in breast tumors with low (n=7) and high (n=9) proliferation index, assessed by the expression level of Ki-67. P-value was determined using an unpaired two-tailed t-test. ",
    "diseases": "breast cancers, breast tumors"
  },
  {
    "caption": "(A)-(B) Hepatocytes accumulate apical bulkheads in the liver tissue of primary sclerosing cholangitis (PSC) patients (N=3 control patients and N=4 PSC patients). (A) Overview images in liver tissue of control and PSC patients. Immunofluoresence for the apical membrane marker BSEP (magenta), F-Actin (green) and nuclei (grey). Scale bar 10 µm. (B) High-resolution imaging of F-Actin (green) showing individual bile canaliculi in control or PSC liver tissue. Red arrowheads mark apical bulkheads. Scale bar 2 µm.",
    "diseases": "primary sclerosing cholangitis, PSC"
  },
  {
    "caption": "(C) Different lumen morphologies of a typical bile canaliculus (left column) and bile duct (middle column) in control patients and rosette (right column) in PSC patients. Immunofluorescence for BSEP (magenta) and F-Actin (green). Shows also differences dependent on the imaging plane i.e. transversal (top row) or longitudinal (bottom row) cut of the lumen. White dashed lines mark the lumen. Scale bar 2 µm.",
    "diseases": "PSC"
  },
  {
    "caption": "(F) Liver cell rosettes in PSC patients are formed by hepatocyte-like cells (N=3 control patients and N=4 PSC patients). Immunofluoresence for BSEP (magenta), F-Actin (green) and nuclei (grey) in healthy parenchyma (left) and bile duct (middle) in control patients and liver cell rosettes in PSC patients (right). Scale bar 10 µm.",
    "diseases": "PSC"
  },
  {
    "caption": "(A)-(D)Liver cell rosettes in PSC patients do not acquire other markers of bile duct cells or intermediate hepatobiliary cells. Immunofluoresence for different bile duct cell or intermediate hepatobiliary cell type marker (magenta), F-Actin (green) and nuclei (grey) in healthy parenchyma (left) and bile duct (middle) in control patients and liver cell rosettes (right) in PSC patients (N=3 control patients and N=4 PSC patients). Scale bar 10 µm. (A) SOX9, (B) Pan-CK, Representative images are shown.",
    "diseases": "PSC"
  },
  {
    "caption": "(A)-(D)Liver cell rosettes in PSC patients do not acquire other markers of bile duct cells or intermediate hepatobiliary cells. Immunofluoresence for different bile duct cell or intermediate hepatobiliary cell type marker (magenta), F-Actin (green) and nuclei (grey) in healthy parenchyma (left) and bile duct (middle) in control patients and liver cell rosettes (right) in PSC patients (N=3 control patients and N=4 PSC patients). Scale bar 10 µm. TROP2 CD133/PROM1. Representative images are shown.",
    "diseases": "PSC"
  },
  {
    "caption": "3D reconstruction of the bile canaliculi network reveals fundamental changes in the network architecture of PSC patients. (A) Top panel: 3D reconstructed bile canaliculi network across full central vein to portal vein (CV-PV) axes in control (left) and PSC (right) patients. Bottom panel: Projection of the 3D reconstruction. Colours correspond to the mean bile canaliculi diameter in µm. Scale bar 100 µm. (B)-(I) Quantification of bile canaliculi network characteristics from the 3D reconstruction. Represented are mean values with standard deviation of control and PSC patients at different zones across the CV-PV axis. 0 represents the zone surrounding the CV and 10 the area surrounding the PV. N=3 with 1x axis/patient for control patients and N=4 with 3x axis/patient for PSC patients. Paired t-test *P < 0.05, **P < 0.01, ***P < 0.001. (B) bile canaliculi radius [µm], (C) volume fraction [%], (D) surface area/volume (µm2/mm3), (E) connectivity (1/# disjointed bile canaliculi), (F) branches crossing regions [#/mm2]. (G) junctions/length [#/µm",
    "diseases": "PSC"
  },
  {
    "caption": "(A) Liver cell rosettes occur in early- and late-stage PSC patients and in end-stage alcoholic liver disease (ALD) patients. Immunofluorescence of Fibronectin (magenta), F-actin (green) and nuclei (grey) in early-stage PSC (N=3), late-stage PSC (N=5) and end-stage ALD (N=5) patients showing liver cell rosettes. Representative images are shown. Scale bar 50 µm. Examples of rosettes are labelled with a red asterisk and examples of sinusoids are labelled with a red arrowhead. (B) Similar numbers of liver cell rosettes in early-stage and end-stage PSC patients. Quantification of the total number of rosettes in early-stage PSC (N=3), late-stage PSC (N=5) and end-stage ALD (N=5) patients. Unpaired t-test *P < 0.05. (C) Similar mean diameter of analysed liver cell rosettes in different liver diseases. Quantification of the mean rosette diameter in early-stage PSC (N=3), late-stage PSC (N=5) and end-stage ALD (N=5). Unpaired t-test. Data information: Boxplot shows the 25th and 75th percentiles and the central band shows the median value. Whiskers extend to the min and max values.",
    "diseases": "liver diseases, alcoholic liver disease, ALD, PSC"
  },
  {
    "caption": "(C) -(D) DCA treatment induces a cholestatic response in primary hepatocytes. Gene expression analysis of genes involved in bile acid metabolism and transport in primary hepatocytes treated with DMSO or 200 µM DCA for 16h. Represented are mean Cq values normalized to Gapdh expression (N=4 biological replicates). One sample t-test *P < 0.05, ***P < 0.001. (C) Abcb11/Bsep, (D) Cyp7a1/Cyp7. Data information: Boxplots show the 25th and 75th percentiles and the central band shows the median value. Whiskers extend to the min and max values.",
    "diseases": "cholestatic"
  },
  {
    "caption": "Left panel, a scheme of chromosome 18 copy number alterations depicting the distal long arm loss across TCGA Pan-Cancer dataset. Vertical red line indicates the localization of VPS4B. Right panel, enlarged fragment of chromosome 18 showing frequent deletions of VPSB locus in cancer samples. Deletions are marked in blue, amplified regions are marked in red. Analysis of VPS4B copy number alterations in TCGA Pan-Cancer dataset. Cancer types were sorted according to the mean VPS4B copy number after removing germline values.",
    "diseases": "cancer, Cancer"
  },
  {
    "caption": "Scatter plot, analysis of VPS4B mRNA expression (number of transcripts per million) plotted against VPS4B copy number from TCGA CRC patient samples (n=376); plot generated using cBioPortal Gao et al, 2013(). Pie chart, summary of all types of VPS4B copy number alterations based on the analysis of data from 615 CRC samples deposited in the Colorectal Adenocarcinoma (TCGA, Provisional)",
    "diseases": "Colorectal Adenocarcinoma, CRC"
  },
  {
    "caption": "qPCR analysis of VPS4B mRNA abundance in normal colon, adenoma and CRC samples. Adenocarcinoma (n=26); adenoma (n=42); normal colon (n=24). Green horizontal bars indicate means and red whiskers indicate SD.",
    "diseases": "Adenocarcinoma, adenoma, CRC"
  },
  {
    "caption": "Examples of immunohistochemical staining of VPS4B in normal colon and matched CRC samples as an illustration of the scoring system used for the evaluation presented in (F). 3+ - very intensive staining, 2+ - medium-intensive staining, 1+ - weak staining, 0 - no staining. Scale bar, 50 µm.",
    "diseases": "CRC"
  },
  {
    "caption": "Analysis of viability of HOP62 lung cancer cells assessed 144 h after transfection with independent non-targeting siRNA (two different duplexes used, siCTRL#1 or #2) or targeting VPS4A (duplexes #2 or #5), VPS4B (duplexes #1 or #2) or both VPS4 (various combinations of siVPS4A+siVPS4B duplexes). Data are means of 4 independent experiments ±SEM. All values were normalized, cell viability of averaged (avrg) siCTRL#1- and #2-transfected cells was set as 100%. Two-tailed unpaired t-test; ****p<0.0001.",
    "diseases": "lung cancer"
  },
  {
    "caption": "Analysis of viability of SNU410 pancreatic cancer cells assessed 168 h after transfection with independent non-targeting siRNA (three different duplexes used, siCTRL#1, #2 or #3) or targeting VPS4A (duplexes #2, #4 or #5), VPS4B (duplexes #1 or #2) or both VPS4 (various combinations of siVPS4A+siVPS4B duplexes). Data are means of 3 independent experiments ±SEM. All values were normalized, cell viability of averaged (avrg) siCTRL#1-, #2- and #3-transfected cells was set as 100%. Two-tailed unpaired t-test; ****p<0.0001.",
    "diseases": "pancreatic cancer"
  },
  {
    "caption": "(D,E) ABCA12 immunostaining and the development of hyperkeratotic skin disease in E18.5 Abca12tm1a/tm1a mouse embryos (brackets indicate thickened epidermis, dashed line indicates epidermal basement membrane, scale bar = 50μm).",
    "diseases": "hyperkeratotic skin disease"
  },
  {
    "caption": "(J) Fasting blood glucose levels coincident with the emergence of inflammatory phenotypes (mean±SEM, n=3, 4 and 5 mice per genotype respectively, *p=<0.05, Students t-test).",
    "diseases": "inflammatory"
  },
  {
    "caption": "Significant genomic co-occupancy between AIB1 and TEAD in normal breast and breast cancer cells. Overlap of AIB1 and TEAD4 ChIP-seq peaks in MCF10A and MCF7 cell lines. Select peaks from MCF10A ChIP-seq shown. ChIP-sequencing performed in triplicate.",
    "diseases": "breast cancer"
  },
  {
    "caption": "AIB1 is engaged with TEAD on co-activated target promoters in early stage breast cancer cells. Sequential ChIP-reChIP performed with indicated antibodies in MCFDCIS cells. Levels of precipitated chromatin assessed by qPCR.",
    "diseases": "breast cancer"
  },
  {
    "caption": "Invasive lesions have significantly less ANCO1 than encapsulated DCIS lesions. Representative images of H&E, p63, and ANCO1 stained MCFDCIS xenografts as DCIS and invasive lesions. Yellow circles indicate DCIS lesions and black arrows indicate invasive lesions. 20x magnification; Scale bar = 100μm. Quantification of ANCO1 positivity in DCIS and Invasive lesions shown in panel (E).",
    "diseases": "DCIS"
  },
  {
    "caption": "ANCO1 levels decrease in breast cancer. ANCO1 mRNA expression from normal tissue (GTEX) and Tumor (TCGA) for breast samples.",
    "diseases": "breast cancer"
  },
  {
    "caption": "Representative IHC images of ANCO1 staining in normal human breast and DCIS lesions. DCIS lesions can be stratified to either ANCO1 negative (center panel), ANCO1 positive (right panel). Scale bar = 50μm.",
    "diseases": "DCIS"
  },
  {
    "caption": "High ANCO1 levels are a good prognostic indicator in Basal Breast Cancer in patients. KM plot showing progression free survival in patients with stratified ANCO1 expression. n= 360 patients.",
    "diseases": "Breast Cancer"
  },
  {
    "caption": "Patient breast tumor samples with reduced ANCO1 levels have high expression of 1q21.3 genes, without altered AIB1-YAP co-activated gene expression. Dot plots showing TCGA Pan-Cancer data accessed via Xenabroswer. Patients were stratified to high or low expression of ANCO1 by median expression.",
    "diseases": "breast tumor"
  },
  {
    "caption": "A Phenotypes of given genotypes subjected to 5 days of illumination at 8 µmol.m-2.s-1 660-nm red light. PBG, pCaMV35S::PHYB-GFP transformed in pap8-1/+ (among 25 lines selected for GFP expression see data source; 2 doubly heterozygous pap8-1/+; PBG/- lines #6 and #7 segregated the photobodies alteration with the albinism).",
    "diseases": "albinism"
  },
  {
    "caption": "Immunoblot analysis of CEP55 expression in a panel of human breast cancer lines (n=25) Tubulin served as loading controls.",
    "diseases": "breast cancer"
  },
  {
    "caption": "A panel of selected breast cancer and near normal cell lines was reverse-transfected with 5 nM pooled CEP55 siRNAs and cell viability determined after 6 days. Cell viability relative to its own respective control transfected with scramble siRNA was calculated. Graph represents the mean± SEM of three independent experiments.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(I) Analysis of Pearson correlation coefficients (PCC) of CEP55 vs. MYC transcriptional activity in breast cancer TCGA tumor data with R=0.4157, p<0.0001.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(A) Heat map showing relative cell viability of a panel of human breast cancer lines treated single or in combination with AZD6244 (1 µM) and BI2536 (2.5 nM) inhibitors and cell viability was determined after 6 days. DMSO treated control was used to calculate percentage of cells affected by individual or combination treatment. NN: near normal. Heat map represents data derived from three independent experiments.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(A) Left, Six week-old female BALB/c cohorts of mice were injected in the 4th inguinal mammary fat pad with the Cep55-ovexpressing mammary carcinoma cell line 4T1.2. Tumor size (area, mm2) was measured using a digital calliper and mean tumor size of each cohort is presented. Mice were treated with vehicle, AZD6244 (12.5mg/kg BID), BI6727 (12.5mg/kg thrice weekly), or combined AZD6244 and BI2536 treatment. Right, representative excised tumor images are shown. Graph represents the mean tumor area±SEM from six mice/group.",
    "diseases": "mammary carcinoma"
  },
  {
    "caption": "C: Nuclear  extracts from  Kms27 MM   cells treated or not with RNase A were subjected to immunoprecipitation  with the indicated antibodies (abs) and analyzed by  western blot  (WB) with the indicated abs. Input corresponds to 5% of the total extract used for immunoprecipitation.",
    "diseases": "MM"
  },
  {
    "caption": "D: (Top) qRT-PCR approach described in the schematic representation. (Bottom) RIP-qPCR  analysis with anti-Che-1 specific antibody or control rabbit IgG of Kms27 MM  cells. Data are expressed as percent of Input. Error bars represent the standard error of three different biological experiments performed in technical duplicate (Two Tailed T test ***P<0.005, ****P<0.001, n.s. = not significant).",
    "diseases": "MM"
  },
  {
    "caption": "E: Colocalization  assays in Kms27  and RPMI8226 MM  cell lines by combining  In Situ Hybridization (FISH) staining  of NEAT1   (Stellaris) with immunofluorescence  of Che-1. Scale bar 10 μm.",
    "diseases": "MM"
  },
  {
    "caption": "F: (Left) RT-qPCR analysis of NEAT1  expression levels in Kms27 MM  cells transiently transfected with LNA GapmeR NEAT1A  or GapmeR Control oligonucleotides. Values were normalized to Actin  expression. Error bars represent the standard error of three different biological experiments performed in technical duplicate (Two Tailed T test ****P<0.001). (Right) Nuclear  extracts from KMS27 MM  cells were immunoprecipitated  with the indicated abs and analyzed by WB with the indicated abs.",
    "diseases": "MM"
  },
  {
    "caption": "A: Quantitative RT-PCR (RT-qPCR) of Kms27 MM  cells transiently transfected with two different LNA GapmeR NEAT1   or GapmeR Control oligonucleotides. Values were normalized to Actin  expression. Error bars represent the standard error of three different experiments performed in duplicate (Two Tailed T test ****P<0.001).",
    "diseases": "MM"
  },
  {
    "caption": "B: WB analysis with indicated abs of total extracts from Kms27 MM cells transiently transfected as in A.",
    "diseases": "MM"
  },
  {
    "caption": "C: Representative confocal  images of Kms27 MM  cells transiently transfected with LNA GapmeR NEAT1A, GapmeR NEAT1B  or GapmeR Control oligonucleotides and immunostained  with anti-Che-1 antibody. Scale bar 10 μm.",
    "diseases": "MM"
  },
  {
    "caption": "D: Isolated cell compartments from Kms27 MM  cells transfected with LNA GapmeR NEAT1A  or GapmeR Control oligonucleotides, were subjected to WB  with the indicated abs.",
    "diseases": "MM"
  },
  {
    "caption": "F: FISH  images of Kms27 MM  cells depleted or not for  Che-1  expression (siChe-1A) labeled with Hoechst  (cell nuclei) and Quasar 670 (NEAT1  RNA). Scale bar 10 μm.",
    "diseases": "MM"
  },
  {
    "caption": "G: NEAT1 ChIRP-seq signal intensity of Kms27 MM  cells transiently transfected with siChe-1A or siControl at co-localizing Che-1/NEAT1  sites (N=14654 sites). Signal intensity from 1 (weak) to 14 (strongest).",
    "diseases": "MM"
  },
  {
    "caption": "B: Chromatin  extracts from Kms27  and RPMI8226 MM cells treated or not with  RNase H, were subjected to immunoprecipitation  with S9.6  antibody and analyzed by WB  with the indicated abs. Input corresponds to 5% of the total extract used for immunoprecipitation.",
    "diseases": "MM"
  },
  {
    "caption": "C: Representative confocal  images showing the interaction  between  Che-1 and S9.6  revealed by PLA  in Kms27 MM  cells. Negative controls were performed by omitting Che-1 or S9.6  primary antibody. Scale bar 10 μm.",
    "diseases": "MM"
  },
  {
    "caption": "D: Chromatin  extracts from Kms27 MM  cells transfected with LNA GapmeR NEAT1A  or GapmeR Control oligonucleotides were immunoprecipitated  with  S9.6 antibody and analyzed by WB  with the indicated antibodies. Input corresponds to 5% of the total extract used for immunoprecipitation.",
    "diseases": "MM"
  },
  {
    "caption": "E: (Left) Representative confocal  images of Kms27 MM  cells treated or not with RNase H, transiently transfected with siChe-1A or siControl and immunostained  with  S9.6 antibody and. Scale bar 10 μm. (Right) Box plot showing S9.6  signal nuclear  intensity per cell (Arbitrary Unit-AU). siChe-1A  cells are described in green color, while siControl in grey color. 100 cells were counted in each replicate. Each dot represents a cell. Median scores per sample are written at the top of the median red line. P value: <1.02-18. ANOVA test was performed to evaluate statistical significance. The red center line denotes the median value (50th percentile) while the black box contains the 25th to 75th percentiles of data. The whiskers mark the 5th and 95th percentiles.",
    "diseases": "MM"
  },
  {
    "caption": "F: (Top) S9.6 antibody was used for dot blot analysis to evaluate RNA:DNA hybrids  formation in Kms27 MM  cells by serial dilutions of genomic DNA starting at 1.5 micrograms. (Bottom) Quantification of S9.6 levels by densitometric analysis. Values were normalized to a Methylene blue loading control. Error bars represent the standard error of three different biological experiments (Two Tailed T test ***P<0.005, ****P<0.001).",
    "diseases": "MM"
  },
  {
    "caption": "G: Enrichment density of DRIP-seq  signals at NEAT1/Che1 co-localizing sites in Kms27 MM  cells identified in siRNA control (siControl) (grey) and siRNA Che-1 (siChe-1A) (dark green) samples. Enrichment density was calculated on the relative size of each peak (start to end of each fragment) extended 2000 bp upstream and downstream. Right frame represents the signal obtained from 14654 randomly selected sites from the same experiments.",
    "diseases": "MM"
  },
  {
    "caption": "D: (Top) Representative confocal   images of Kms27 MM   cells transfected and treated as in C and immunostained   with S9.6  antibody. Scale bar 10 μm. (Bottom) Box plot showing S9.6  signal nuclear   intensity per cell (Arbitrary Unit-AU). siChe-1A cells are described in dark grey, siChe1A plus CX5461   in green color, while siControl in grey color. Median scores per sample are written at the top of the median red line. P value: <1.30-54. ANOVA test was performed to evaluate statistical significance. The red center line denotes the median value (50th percentile) while the black box contains the 25th to 75th percentiles of data. The whiskers mark the 5th and 95th percentiles.",
    "diseases": "MM"
  },
  {
    "caption": "E: (Top) Dot blot  analysis of decreasing amounts of genomic DNA   extracts from Kms27 MM  cells depleted or not for Che-1 expression (siChe-1A) and treated with CX5461, were probed using abs directed against RNA:DNA hybrids. (Bottom) Quantification of S9.6 levels by  densitometric analysis. Values were normalized to a Methylene blue  loading control. Error bars represent the standard error of three different biological experiments (Two Tailed T test ****P<0.001).",
    "diseases": "MM"
  },
  {
    "caption": "A: Differential analysis of siControl vs. siChe1A transcriptome in Kms27 MM  cells. Volcano plot shows 135 significantly upregulated (dark green) and 392 downregulated genes (dark grey). x-axis reports the base-2 logarithm of fold change which is approximated to the B value coming from the statistical Wald test. y-axis reports the base-10 logarithm of Q value of significant genes.",
    "diseases": "MM"
  },
  {
    "caption": "D: WB  analysis of total extracts of Kms27 MM  cells depleted or not for Che-1 (siChe-1A) and probed for the indicated abs.",
    "diseases": "MM"
  },
  {
    "caption": "E: (Left) Luciferase activity of human NF-kB promoter was measured in Kms27 MM  cells transiently transfected with siChe-1A  or siControl oligonucleotides or with empty vector or p65/RelA   protein expressing vector. Error bars represent the standard error of three different biological experiments performed in duplicate (Two Tailed T test ***P<0.005, ****P<0.001). (Right) WB  analysis of total extracts of Kms27 MM  cells transiently transfected as described in E and incubated with the indicated antibodies.",
    "diseases": "MM"
  },
  {
    "caption": "RT-qPCR  analysis of the levels of the indicated genes in Kms27 MM  cells transiently transfected with siChe-1A or siControl. Values were normalized to Actin  expression. Error bars represent the standard error of three different experiments in duplicate (Two Tailed T test ***P<0.001, ****P<0.001).",
    "diseases": "MM"
  },
  {
    "caption": "G: RT-qPCR analysis of the levels of the indicated genes in Kms27 MM cells transiently transfected with siChe-1A or siControl. Values were normalized to Actin  expression. Error bars represent the standard error of three different experiments in duplicate (Two Tailed T test ***P<0.001, ****P<0.001).",
    "diseases": "MM"
  },
  {
    "caption": "H: WB  analysis for the indicated antibodies of total extracts from Kms27 MM  cells with siChe-1A or siControl and where indicated with GFP-tagged RNaseH  expression vectors.",
    "diseases": "MM"
  },
  {
    "caption": "I: RT-qPCR analysis of IFNB  and IFNG  levels in Kms27 MM  cells transiently transfected as in H. Values were normalized to Actin  expression. Error bars represent the standard error of three different biological experiments performed in duplicate (Two Tailed T test **P<0.01, ***P<0.005.)",
    "diseases": "MM"
  },
  {
    "caption": "C: Boxplot showing relative S9.6 nuclear  mean intensity in CD138+ plasma cells from 15 MM patients  (red) and 5 healthy (light blue). Dot plot representing each cell considered overlay the boxplot. Y-axis: S9.6 Nuclear  Mean Intensity (AU). The center line denotes the median value (50th percentile) while the boxes contain the 25th to 75th percentiles of data. The whiskers mark the 5th and 95th percentiles.",
    "diseases": "MM"
  },
  {
    "caption": "A: WB  analysis of total extracts from Kms27  and U266 human MM  cells with the indicated abs.",
    "diseases": "MM"
  },
  {
    "caption": "B: (Left) Kms27  and U266 MM  cells were subjected to immunostaining  with S9.6 antibody Scale bar 10 μm. (Right) Dot plot  showing relative S9.6 nuclear  mean intensity cell in the nucleus. 100 cells were counted in each replicate. Median scores per sample are written at the top of the median red line. P value: 3.3-13. T-test was performed to evaluate statistical significance.",
    "diseases": "MM"
  },
  {
    "caption": "C: Different expression   of IFNG  and IFNB  in Kms27  and U266 MM  cells was assessed by RT-qPCR. Values were normalized to Actin  expression. Error bars represent the standard error of three different biological experiments performed in duplicate (Two Tailed T test ***P<0.005).",
    "diseases": "MM"
  },
  {
    "caption": "D: WB  analysis with the indicated abs of total extracts from U266 MM  cells treated or not with Thapsigargin  (THAP) 0.5 μg/ml for 16 hours. G: WB  with indicated abs of total extracts from Kms27 MM  cells treated or not with ISRIB  1μM for 6 hours.",
    "diseases": "MM"
  },
  {
    "caption": "E: (Left) U266 MM  cells treated or not with THAP  as in D and immunostained  with  S9.6  antibody Scale bar 10 μm. (Right) Dot plot showing relative S9.6 nuclear  mean intensity per cell. 100 cells were counted in each replicate. Median scores per sample are written at the top of the median red line. P value: 1.1-20. T-test was performed to evaluate statistical significance. H: (Left) Immunostaining  with S9.6  antibody of Kms27 MM  cells treated or not with ISRIB  as in G Scale bar 10 μm. (Right)  Dot plot  showing relative S9.6 nuclear  mean intensity per cell. 100 cells were counted in each replicate Median scores per sample are written at the top of the median red line. P value: 4.7-23. T-test was performed to evaluate statistical significance.",
    "diseases": "MM"
  },
  {
    "caption": "F: RT-qPCR analysis of IFNG  and IFNB  in U266 MM  cells treated or not with THAP. Values were normalized to Actin  expression. Error bars represent the standard error of three different biological experiments performed in duplicate (Two Tailed T test ***P<0.005, ****P<0.001) I:  RT-qPCR  analysis of IFNG  and IFNB  levels in Kms27 MM  cells treated as in G. Values were normalized to Actin  expression. Error bars represent the standard error of three different biological experiments performed in duplicate (Two Tailed T test ****P<0.001).",
    "diseases": "MM"
  },
  {
    "caption": "D WB  of indicated proteins extracted from Wt and Cdk8 -/-/Cdk19 -/- organoids. Included are CFTR  positive and negative control cell line samples obtained from the Cystic Fibrosis  Foundation (CFF). Amidoblack  was used as loading control.",
    "diseases": "Cystic Fibrosis"
  },
  {
    "caption": "Tumor tissue (tumor) as well as corresponding non-tumorous adjacent tissue (control) were collected from colorectal cancer patients and prepared for histopathology. The expression of CD68 (red), CD206 (green) and ADRP (blue) indicate the lipid droplets in tumor infiltrating myeloid cells. Nuclei (white) were stained using DAPI. The absolute number of positive cells was quantified in 5 high-power fields (hpf) (scale bar = 20 µm).",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "A subplantar injection of 5% of formalin  (20 µl) was administered in the right  hind paw of Balb/c mice, and an equal volume of PBS  was injected in left hind paw. After induction of inflammation, Balb/c mice  were treated with PBS  or peptide  (8 mg/kg) via the intraperitoneal route. After 3 hours, paw  tissues were harvested and used for cDNA synthesis. B) (B) Next, Toluidine blue staining  was done to check the mast cell population. Photographs of representative sections were visualized at 20X magnification (scale bar = 100 µm).",
    "diseases": "inflammation"
  },
  {
    "caption": "A subplantar injection of 5% of formalin  (20 µl) was administered in the right hind paw  of Balb/c mice, and an equal volume of PBS  was injected in left  hind paw. After induction of inflammation, Balb/c mice  were treated with PBS  or peptide  (8 mg/kg) via the intraperitoneal route. After 3 hours, paw  tissues were harvested and used for cDNA synthesis. (C) Counting of  mast cells  was performed in Toluidine blue-stained  paw sections using ImageJ software and was normalized per unit area (mm2). Data information: Data shown are Mean ± SEM of 8 mice. unpaired t-test was applied to calculate p values.",
    "diseases": "inflammation"
  },
  {
    "caption": "Colitis was induced by oral administration of 3 % DSS for 5 d. Mice were treated daily (s.c.) with either PRN1126 (40 mg/kg), or ONX 0914 (10 mg/kg), or vehicle. Data points represent mean ± SEM of 15 mice pooled from three independent experiments.",
    "diseases": "Colitis"
  },
  {
    "caption": "Mice were immunized with MOG35-55 peptide and were monitored daily for clinical symptoms of EAE. Mice were treated three times a week (s.c.) with either PRN1126 (40 mg/kg), or ONX 0914 (10 mg/kg), or vehicle. All data were statistically compared to the vehicle treated group. *P < 0.05, **P < 0.01, ***P < 0.001. Two-way ANOVA. Shown are the means of the clinical scores ± SEM (n = 6 per group).",
    "diseases": "EAE"
  },
  {
    "caption": "Colitis was induced by oral administration of 3% DSS. Mice were treated daily (s.c.) with LU-001i (15 mg/kg), PRN1126 (40 mg/kg), PRN1126+ LU-001i (40 mg/kg+15 mg/kg), or vehicle starting from the begin of the experiment. Data points represent means ± SEM of 15 mice pooled from three independent experiments. (A) The body weight of individual mice was monitored daily and the percent weight loss (y-axis) was plotted versus time (x-axis). All data were statistically compared to the vehicle treated group. *",
    "diseases": "Colitis"
  },
  {
    "caption": "Colitis was induced by oral administration of 3% DSS. Mice were treated daily (s.c.) with LU-001i (15 mg/kg), PRN1126 (40 mg/kg), PRN1126+ LU-001i (40 mg/kg+15 mg/kg), or vehicle starting from the begin of the experiment. Data points represent means ± SEM of 15 mice pooled from three independent experiments. On day 9 after initiation of DSS treatment, colon lengths were measured (n=15). Naïve mice (n=5) were used as healthy controls. All data were statistically compared to the vehicle treated group.",
    "diseases": "Colitis"
  },
  {
    "caption": "Mice were immunized with MOG35-55 peptide and were monitored daily for clinical symptoms of EAE. Mice were treated intermittently with three times a week (s.c.) schedule with LU-001i (15 mg/kg), PRN1126 (40 mg/kg), PRN1126+ LU-001i (40 mg/kg+15 mg/kg), or vehicle starting from the start of the experiment. Data points represent the means of the clinical scores ± SEM of 12 mice pooled from two independent experiments. All data were statistically compared to the vehicle treated group.",
    "diseases": "EAE"
  },
  {
    "caption": "(B) Cell viability analysis of the indicated early-passage Eµ-Myc lymphoma cells treated with indicated compound(s) for 48 hours as determined by Beckman® Coulter counter.",
    "diseases": "lymphoma"
  },
  {
    "caption": "(G) Propidium iodide (PI) exclusion analysis of early-passage CX-5461-everolimus combination therapy-resistant (CMB), CX-5461-resistant (CX) and drug-naïve (CTRL) lymphoma cells treated with indicated concentrations of metformin for 48 hours.",
    "diseases": "lymphoma"
  },
  {
    "caption": "(E) PI exclusion analysis of early-passage drug-naïve (CTRL) lymphoma cells treated with CX-5461 and everolimus in the presence or absence of selective PKA activator 6-Bnz-cAMP for 48 hours.",
    "diseases": "lymphoma"
  },
  {
    "caption": "(B) Polysome profiles demonstrating increased ribosome abundance in CMB cells as compared to CTRL and CX-5461-resistant (CX) cells (representatives of n=3). (C) Quantitation of polysome:monosome ratio in the indicated early-passage Eµ-Myc lymphoma cells as determined by measuring the area under the curve using ImageJ software. Graph represents mean ± SEM of n=3. ",
    "diseases": "lymphoma"
  },
  {
    "caption": "(D) Kaplan-Meier curve of C57BL/6 mice transplanted with CX-5461-everolimus-resistant (CMB #8) early-passage Eµ-Myc lymphoma cells treated with vehicles (everolimus vehicle: 1% methylcellulose; CX-5461/metformin vehicle: 25 mM NaH2PO­­­4) (n=6); CX-5461 (35 mg/kg every twice weekly) and everolimus (5 mg/kg daily) (n=8), metformin (400 mg/kg twice daily) (n=6), or CX-5461, everolimus and metformin (35 mg/kg twice weekly, 5 mg/kg daily and 400 mg/kg twice daily, respectively) (n=8). Light grey: 5-day metformin pre-treatment period, dark grey: treatment period. Data were analyzed by a log-rank (Mantel-Cox) test. Vehicle vs. CX-5461-everolimus: P = 0.0006, Vehicle vs. CX-5461-everolimus-metformin: P = 0.0001. CX-5461-everolimus vs. CX-5461-everolimus-metformin: P = 0.0003.",
    "diseases": "lymphoma"
  },
  {
    "caption": "mRNA levels of TMX1 (A) and NFAT1 (B) in primary melanocytes, keratinocytes and melanoma cell lines. data are are normalized to the expression of TBP and are presented as mean ± SEM (n≥3).",
    "diseases": "melanoma"
  },
  {
    "caption": "Representative immunoblot (from 3) depicting protein abundance of TMX1 and NFAT1 in melanocytes and melanoma cell lines; actin was used as a loading control. Indicated band intensities were normalized to actin and background signal was subtracted.",
    "diseases": "melanoma"
  },
  {
    "caption": "Melan-A (brown), TMX1 (red-brown) and NFAT1 (deep red) staining (IHC) in a primary stage 4 high risk nodular melanoma patient I (out of four), the enlarged regions show healthy tissue (panels 2, 5 and 8) and tumor tissue (panels 3, 6 and 9). Arrows indicate Melan-A positive melanocytes.",
    "diseases": "melanoma"
  },
  {
    "caption": "TMX1 (red-brown) and NFAT1 (deep red) staining of healthy human skin and increasing melanoma stages; P1-P13 refer to the donor patient number.",
    "diseases": "melanoma"
  },
  {
    "caption": "Reduced nuclear translocation of NFAT1-GFP in TMX1 or TMX3 silenced (siRNA) melanoma cells. (C) Images show NFAT1-GFP fluorescence intensity before and after stimulation with thapsigargin (Tg; 1 µM) in WM3734 cells. (D) Corresponding time-dependent nuclear import of NFAT1 as a change of F/F0. (E) Normalized endpoint quantification. Same analysis was performed with Mel Juso cells with (F) images, (G) time-dependent nuclear import and (H) normalized endpoint quantification. data are presented as mean ± SEM (n values: WM3734, control=142, TMX1 kd=116, TMX3 kd=148; Mel Juso, control=75, TMX1 kd=47, TMX3 kd=67).",
    "diseases": "melanoma"
  },
  {
    "caption": "Cellular H2O2 (HyPer) was evaluated in two melanoma cell lines upon TMX1 kd and TMX3 kd. (F) Exemplary ratiometric images (F505 nm / F420 nm) are shown for WM3734 and Mel Juso. Quantification of basal cellular H2O2 in WM3734 (G) and Mel Juso (H) cells. In (G-H), data are presented as mean ± SEM (n values: WM3734: control=168, TMX1 kd=209, TMX3 kd=192; Mel Juso: control=297, TMX1 kd=343, TMX3 kd=440). In (F) scale bars: 10 µm; color code: WM3734: color code: blue=0, red=3; Mel Juso: color code: blue=0, red=1.5.",
    "diseases": "melanoma"
  },
  {
    "caption": "Proliferation (48 h) of melanoma cell lines measured after transient knockdown of TMX1 or TMX3.",
    "diseases": "melanoma"
  },
  {
    "caption": "Proliferation (48 h) of melanoma cell lines with stable TMX1 knockdown (two clones).",
    "diseases": "melanoma"
  },
  {
    "caption": "Proliferation (24 h) of melanoma cell lines after transient knockdown of NFAT1.",
    "diseases": "melanoma"
  },
  {
    "caption": "Transwell migration (48 h) of melanoma cell lines after preventing NFAT-calcineurin interaction with dipyridamole (40 µM) or inhibition of calcineurin with cyclosporine A (CsA, 2 µM).",
    "diseases": "melanoma"
  },
  {
    "caption": "Kaplan-Meier survival plots and log rank for the correlation between mRNA expression levels and survival probability of melanoma patients, separated in groups with high or low expression of any of the three genes of interest (GOI), TMX1, TMX3 and NFAT1.",
    "diseases": "melanoma"
  },
  {
    "caption": "mRNA expression levels of NFAT1, TMX1 and TMX3 in BRAF WT and BRAF V600E melanoma patients. In (B), expression levels are based on the FPKM values of the TCGA samples (center line: median; box: 25 % and 75 % percentile; whiskers: 1.5 times interquartile range).",
    "diseases": "melanoma"
  },
  {
    "caption": "Kaplan-Meier survival plots and log rank for the correlation between mRNA expression levels and survival probability of melanoma patients, separated in groups with (C) BRAF WT and (D) BRAF V600E and with high or low expression of NFAT1.",
    "diseases": "melanoma"
  },
  {
    "caption": "B Effects of myeloid-specific Lamtor1 deficiency in an acute gouty arthritis model. MSU crystals (0.5 mg) or the PBS control were injected intra-articularly into the tibia-tarsal joint of Lamtor1flox/flox and Lamtor1flox/flox LysM-Cre mice. Mice were assessed for joint swelling using electronic calipers. Images show photomicrographs (upper panel) and hematoxylin and eosin-stained sections (middle and lower panels) of ankle joints obtained at 24 h. Data are shown as the means ± SEM. *** indicates P < 0.001 by Student's t-test, n = 7 mice each.",
    "diseases": "joint swelling, acute gouty arthritis"
  },
  {
    "caption": "G Effects of DL-all-rac-α-tocopherol in an acute gouty arthritis model. MSU crystals (0.5 mg) suspended in 20 μL endotoxin-free PBS or PBS control were injected intra-articularly into the tibia-tarsal joint (ankle) of C57BL/6 WT mice with or without DL-all-rac-α-tocopherol. Ankle joint swelling at 24 h was assessed with electronic calipers and with photomicrographs and hematoxylin and eosin-stained sections of ankle joints.",
    "diseases": "swelling, acute gouty arthritis"
  },
  {
    "caption": "H Effects of DL-all-rac-α-tocopherol in an MSU-induced peritonitis model. Twelve hours after DL-all-rac-α-tocopherol pretreatment, 100 μL MSU solution (10 mg/mL) was intraperitoneally injected for 4 h. Peritoneal IL-1β production was then measured by ELISA, and CD11b+ Ly6G+ neutrophil recruitment was measured by FACS.",
    "diseases": "peritonitis"
  },
  {
    "caption": " The cell proliferation assay in HCT116 CRC cells shows growth advantage conferred by the SMARCB1 R377C mutation compared with the wild type SMARCB1 or the vector control. The error bars designate the standard deviation (SD) ",
    "diseases": "CRC"
  },
  {
    "caption": " The cell proliferation assay in HCT116 CRC cells shows growth advantage conferred by the expression of the wild type STK38L, whereas the R105W mutant only slightly increased the number of colonies. The error bars designate the standard deviation (SD) ",
    "diseases": "CRC"
  },
  {
    "caption": "(I) Double immunofluorescence labeling using antibodies against DYRK3 and FUS in  lumbar spinal cord α-MNs of healthy subjects (control) and fALS patients  carrying the p.521C mutation in the FUS  gene. Control (upper panel): α-MNs showing uniform cytoplasmic (white arrows) and speckled pattern of strong nuclear immunoreactivity (white arrowhead) of DYRK3, as well as diffuse  nuclear FUS immunoreactivity. fALS (p.R521C-FUS; lower panel): surviving α-MNs harboring large FUS aggregates (yellow arrows) showed markedly reduced  DYRK3 immunoreactivity both in the cytoplasm as well as in the  nucleus (red arrowheads). Instead, α-MNs devoid of  FUS  aggregates (white arrows) showed normal DYRK3 immunoreactivity similar to the one of α-MNs from normal controls. Asterix (*) represents non-specific lipofuscin granules in one of the α-MN in FUS-ALS. Paraffin sections; scale bars is 50 µm. (J) Quantification of α-MNs showing low or absent DYRK3 staining (upper graphic) and FUS aggregates (lower graphic) in lumbar spinal cord from five healthy subjects (control) and five  fALS patients carrying the p.521C mutation in the FUS gene. Total number  of α-MNs analyzed: 403 (control); 132 (fALS). n = 5, ± sem (Student's t-test). ",
    "diseases": "ALS, fALS"
  },
  {
    "caption": "(D) Analysis and quantification of a time dependent increase of ARSA activity in MSD primary fibroblasts (variant FGE Gly247Arg homozygous) simultaneously treated with 10 and 20 µM tazarotene and bexarotene, respectively, up to 21 days. Data represent mean ±SD of 3-6 independent experiments (biological replicates). One-way ANOVA followed by Tukey's test for multiple comparisons. Displayed are significance levels for the next significant difference between adjacent treatment times. #### p<0.0001. Difference against 0 days control: * p<0.05, **** p<0.0001.",
    "diseases": "MSD"
  },
  {
    "caption": "(E) Analysis and quantification of increased sulfatase activities different to ARSA, namely ARSB, GALNS, and STS in MSD primary fibroblasts (variant FGE Gly247Arg homozygous) after 6 days of simultaneous treatment with tazarotene/bexarotene 10/20 µM. Data represent mean ±SD of 3-6 independent experiments (biological replicates). One-way ANOVA followed by Tukey's test for multiple comparisons. *** p<0.001, **** p<0.0001.",
    "diseases": "MSD"
  },
  {
    "caption": "(F) Quantification of ARSA activities in MSD primary fibroblasts with different homozygous SUMF1 mutations (FGE Gly247Arg, FGE Gly263Val, FGE Ala279Val, FGE Arg349Trp) after 6 days of simultaneous treatment with tazarotene/bexarotene 10/20 µM. Data represent mean ±SD of 3 independent experiments (biological replicates). One-way ANOVA followed by Tukey's test for multiple comparisons. ****p<0.0001.",
    "diseases": "MSD"
  },
  {
    "caption": "(G) Quantification of ARSA activity in MSD patient-derived iPSCs differentiated into NPCs and unaffected control NPCs controls. Simultaneous treatment with 5 µM tazarotene and 5 µM bexarotene for 4 days. Data represent mean ±SD of 6 independent experiments (biological replicates). Unpaired t-test. **** p<0.0001. (H) Quantification of SGSH activity in MSD patient-derived iPSCs differentiated into NPCs and unaffected control NPCs controls. Simultaneous treatment with 5 µM tazarotene and 5 µM bexarotene for 4 days. Data represent mean ±SD of 3 independent experiments (biological replicates). Unpaired t-test. * p<0.05, *** p<0.001.",
    "diseases": "MSD"
  },
  {
    "caption": "(A) Representative confocal images of control and MSD fibroblasts with either tazarotene/bexarotene (10/20 µM, 6 days). Labelling with anti-LAMP1 antibody (green fluorescence) and DAPI (nuclei, blue). (B) Representative confocal images of control and MSD fibroblasts with either tazarotene/bexarotene (10/20 µM, 6 days). Labelling with anti-LAMP1 antibody (green fluorescence) and DAPI (nuclei, blue). (C) Quantification of total intensity of LAMP1- green fluorescence. N = 20 images and 13 z-series optical sections per condition with a step-size of 0.26 microns, displayed at maximum extension and automated equalization of brightness. Data represent mean ±SD of 3 independent experiments (biological replicates). One-way ANOVA followed by Tukey's test for multiple comparisons. *** p<0.001 (DMSO treated MSD cells compared to DMSO treated control cells), # p<0.05 (MSD DMSO vs MSD treated). RFU: relative fluorescence units. (D) Quantification of LAMP1- green fluorescence vesicle size (µm). N = 20 images and 13 z-series optical sections per condition with a step-size of 0.26 microns, displayed at maximum extension and automated equalization of brightness. Data represent mean ±SD of 3 independent experiments (biological replicates). One-way ANOVA followed by Tukey's test for multiple comparisons. *** p<0.001 (DMSO treated MSD cells compared to DMSO treated control cells), ## p<0.01 (MSD DMSO vs MSD treated).",
    "diseases": "MSD"
  },
  {
    "caption": "(A) ARSA protein amount quantification after treatment of MSD primary fibroblasts (variant FGE Gly247Arg homozygous) with tazarotene, bexarotene, and tazarotene/bexarotene in combination for 6 days referred to β- actin amounts and normalization of ARSA activity based on ARSA protein amount (specific ARSA activity). Data represent mean ±SD of 3 independent experiments (biological replicates). One-way ANOVA followed by Tukey's test for multiple comparisons. Displayed are significance levels for the next significant difference between adjacent concentrations. # p<0.05. Difference against 0/0 µM control: * p<0.05, *** p<0.001.",
    "diseases": "MSD"
  },
  {
    "caption": "(C) Quantification of ARSA activities in CRISPR/Cas9 generated ARPE19 SUMF1 -/- cells and appropriate controls (ARPE19 wild type, MSD primary fibroblasts (variant FGE Gly247Arg homozygous)) after 6 days of simultaneous treatment with tazarotene/bexarotene 10/20 µM for up to 21 days. Data represent mean ±SD of 3 independent experiments (biological replicates). One-way ANOVA followed by Tukey's test for multiple comparisons. Displayed are significance levels for the next significant difference between adjacent concentrations. ## p<0.01. Difference against 0 days control: **** p<0.0001.",
    "diseases": "MSD"
  },
  {
    "caption": "All data have been adjusted for age, gender and other latent covariates for downstream eigenvalue calculation. A. Eigen value showing the increased expression of the 3-microRNA signature in blood plasma samples of age matched MCI (n = 23) patients compared to controls (n = 27). B. Expression of 3-microRNA signature is increased in PAXgene blood samples of MCI patients (n=71) compared to controls (n=65) from the DELCODE cohort.",
    "diseases": "MCI"
  },
  {
    "caption": "E. Eigen value showing the expression the 3-microRNA signature in MCI patients for those the follow up diagnostics data assessed 2 years after were available. 15% of these MCI patients developed Alzheimer´s disease (AD), while the rest 85% patients remained with MCI (stable MCI). The boxplot depicts the increased expression levels of 3-miR signature in patients who converted to AD (n=8) compared to those that had stable MCI (n=47). F. Increased expression of 3-microRNA signature in cerebrospinal fluid (CSF) of MCI patients (n = 9) compared to controls (n = 26). Wilcoxon-rank test, P value is given on the corresponding panel. In the boxplots in (A, B, E, F), the center line indicates the median, while the upper and lower lines represent the 75th and 25th percentiles, respectively. The whiskers represent the smallest and largest values in the 1.5× interquartile range.",
    "diseases": "AD, Alzheimer´s disease, MCI"
  },
  {
    "caption": "cytokine profile of COVID-19 patients for IL-2, IL-4 (I)",
    "diseases": "COVID-19"
  },
  {
    "caption": "cytokine profile of COVID-19 patients for , IL-6, IL-10 (J) and TNF-α and IFN-γ (K).",
    "diseases": "COVID-19"
  },
  {
    "caption": "The baseline IL-6 level was 197.39 pg/mL in a 69-year-old female patient who showed high fever and dyspnea. IL-6 decreased to 9.47 pg/mL after treatment (day 8), while the symptoms were not relieved. The C-reactive protein (CRP) rebounded and procalcitonin (PCT) increased together with disease exacerbation. Follow-up chest computed tomography (CT) assessment was not performed due to poor general condition, whereas chest X-ray showed aggravated pneumonia. Follow-up sputum culture confirmed the exacerbation was caused by bacterial infection.",
    "diseases": "bacterial infection, dyspnea, fever, pneumonia"
  },
  {
    "caption": "A. Optical coherence tomography (OCT) horizontal B-scan and thickness map of neovascular age related macular degeneration (NV AMD) patient with active lesions (1), cystoid macular edema (2), subretinal fibrin deposits (3) and serous retinal detachment (4). B. Optical coherence tomography (OCT) horizontal B-scan and thickness map of control patient with a medium sized, stage 3, full thickness macular hole (5).",
    "diseases": "lesions, neovascular age related macular degeneration, NV AMD, cystoid macular edema, macular hole"
  },
  {
    "caption": "C-G. Vitreous humor analyzed by ELISA for VEGF-A (C); n = 7 (Ctrl), 9 (NV AMD), SEMA3A (D); n = 10 (Ctrl), 10 (NV AMD), TGFβ (E); n = 8 (Ctrl), 7 (NV AMD), PDGF-BB (F); n = 5 (Ctrl),6 (NV AMD), PGF (G): n = 5 (Ctrl), 5 (NV AMD). Dots represent concentrations of individual patient samples.",
    "diseases": "NV AMD"
  },
  {
    "caption": "K. Compilation of representative compressed Z-stack confocal images of FITC-dextran-labeled CNV and IB4-stained laser impact area from LysM-Cre/Nrp1+/+ and LysM-Cre/Nrp1fl/fl mice at D14. Scale bar: 20μm. L-N. Quantification of area of FITC-dextran-labeled CNV (L), isolectin B4 (IB4 )-stained laser impact area (M) and the ratio of FITC/IB4 per laser-burn (N) relative to LysM-Cre/Nrp1+/+ at D14; n = 23 burns (LysM-Cre/Nrp1+/+), n = 27 burns ( LysM-Cre/Nrp1fl/fl).",
    "diseases": "CNV"
  },
  {
    "caption": "E. Compilation of representative compressed Z-stack confocal images of FITC-dextran-labeled CNV and isolectin B4 (IB4)-stained laser impact area from Vehicle and NRP1-derived trap treated wildtype mice. Scale bar: 20μm. F-H. Quantification of area of FITC -dextran-labeled CNV (F), IB4-stained laser impact area (G) and the ratio of FITC/IB4 per laser-burn (H) relative to Vehicle at D14; n = 24 burns (Vehicle), n = 26 burns (NRP1-derived trap).",
    "diseases": "CNV"
  },
  {
    "caption": "J-L. Quantification of area of FITC-dextran-labeled CNV (J), isolectin B4 (IB4)-stained laser impact area (K) and the ratio of FITC/IB4 per laser-burn (L) relative to LysM-Cre/Nrp1+/+ + Vehicle in Vehicle and NRP1-derived trap treated LysM-Cre/Nrp1+/+ and LysM-Cre/Nrp1fl/fl mice at D14; n = 16 burns (LysM-Cre/Nrp1+/+ + Vehicle), n = 16 burns (LysM-Cre/Nrp1+/+ + Trap), n = 13 burns (LysM-null/Nrp1fl/fl + Vehicle) , n = 19 burns (LysM-Cre/Nrp1fl/fl + Trap).",
    "diseases": "CNV"
  },
  {
    "caption": "(A, B) (A) Representative  IHC images and (B) semi quantification of CRMP4  protein in human spinal cords (SC) cross sections from 2 control patients and 3 ALS patients. We analyzed total of 7 SC  sections of controls and 14 SC  sections of  ALS patients, Data presented as mean ±SE. DAB: labeled CRMP4. Scale bar: left images 20 µm, right insets 10 µm. Mann-Whitney test ***p = 0.0003.",
    "diseases": "ALS"
  },
  {
    "caption": "(A) Representative  images  of ALS patient or non-ALS human control  intra-muscular nerves. Red: denotes NFH, Green: denotes CRMP4, White: denotes  co-localization area using Imaris software. Scale bar: 20 μm. (B) Quantification of CRMP4 intensity levels in NFH  positive   intra-muscular distal  nerves from 5 non-ALS  controls and 4 sALS patients. We analyzed 40 terminal  axons from the healthy samples (~8 axons per sample) and 36 terminal  axons from sALS samples (~8 axons  per sample). Data presented as mean ±SE. Student's t-test, *p = 0.0475. ",
    "diseases": "ALS"
  },
  {
    "caption": "(B) Binding of dimeric sACE22-IgG1 proteins was compared to the binding of antibodies authorized for therapeutic use in COVID-19 patients. Binding to Expi293F cells expressing BA.1 omicron S was measured by flow cytometry.",
    "diseases": "COVID-19"
  },
  {
    "caption": " C, D. MR T2 weighted coronal slice of the chest at baseline demonstrating bilateral pleural effusions (arrow heads) and pulmonary interstitial edema (arrows) (C), and 3 months on trametinib therapy (D). ",
    "diseases": "pulmonary interstitial edema"
  },
  {
    "caption": "(I) Immunoblotting and quantification of Afadin S1718 phosphorylation in human Stromal vascular fractions (SVF) from lean, obese or Type 2 Diabetic (T2DM) subjects stimulated or not with insulin (n=6). Representative Western blots are shown. Data are presented as means + SEM; Student's unpaired t-test and ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "diseases": "obese, T2DM, Type 2 Diabetic"
  },
  {
    "caption": "(B) Representative immunoblot of DnaJA1 levels from the hippocampi of AD patients (AD) and aged non-demented controls (ctrl). PonceauS serves as a loading control. (C) Quantification by densitometry of DnaJA1 normalized to PonceauS from the hippocampi of AD patients (AD) and aged non-demented controls (ctrl). Representative immunoblot is shown in (B). Dot plots show all data points along with the mean (bar) ± s.d.. n = 4-5 independent patients. *, p < 0.05. Unpaired, two-tailed t-test.",
    "diseases": "AD"
  },
  {
    "caption": "(H-I) Two months after a single injection of rAAV, db/db mice showed similar body weight (H) and blood glucose levels (I) with the mice injected with PBS. n = 10 for each group. (J-K) Serum ALT (J) and AST (K) of mice in (H).",
    "diseases": "db"
  },
  {
    "caption": "(M) The hepatic p-MLKL protein level in normal and necrotic area from mice injected with PBS or rAAV in (H). Ncp, Necroptosis. n = 7 - 8 biological replicates.",
    "diseases": "necrotic"
  },
  {
    "caption": "(Q-R) Six months after a single injection of rAAV, db/db mice showed decreased body weight (Q) and similar blood glucose levels (R) compared to the mice injected with PBS. n = 8 - 12. (S-T) Serum ALT (S) and AST (T) activities of mice in (Q). n = 8 - 10.",
    "diseases": "db"
  },
  {
    "caption": "Two months after a single injection of rAAV, hyperglycemic mice induced by streptozotocin showed , blood glucose levels (F) compared with those mice injected with PBS. n = 9 (G-H) Serum ALT (G) and AST (H) activities of mice in (D).",
    "diseases": "hyperglycemic"
  },
  {
    "caption": "Body weight (L) of RHH (Resistance to HFD-induced Hyperglycemia) mice fed with HFD for 15 weeks. n = 6 - 12.",
    "diseases": "Hyperglycemia"
  },
  {
    "caption": "blood glucose levels (Q) of obese and euglycemic mice in (L) after a single injection of PBS or rAAV for 2 months. n = 6. Serum ALT (R) of mice in (O).",
    "diseases": "obese"
  },
  {
    "caption": "Two months after a single injection of PBS or rAAV blood glucose levels (G) of hyperglycemic and obese mice in (B) were not significantly changed. n = 10 - 11 for each group. (H-I) Serum ALT (H) and AST (I) activities of mice in (E).",
    "diseases": "hyperglycemic, obese"
  },
  {
    "caption": "(K) The hepatic p-MLKL protein level in normal or necrotic area from mice injected with PBS or rAAV in (E).",
    "diseases": "necrotic"
  },
  {
    "caption": "blood glucose levels (O) of hyperglycemic and obese mice after a single injection of PBS or rAAV for 6 months. n = 8. (P-Q) Serum ALT (P) and AST (Q) activities of mice in (M).",
    "diseases": "hyperglycemic, obese"
  },
  {
    "caption": "(R) Liver images, H&E staining and ki67 immunostaining of liver sections and HCC incidence of mice in (M).",
    "diseases": "HCC"
  },
  {
    "caption": "(A) The top 15 hepatic genes upregulated in 9-week-old db/db mice compared with wild type mice. n = 1, liver samples from 3 mice were mixed together in equal amounts for RNA extraction.",
    "diseases": "db"
  },
  {
    "caption": "Body weight (D) of db/db mice after a single injection of rAAV-si-NC/Cyp4a14/Pebp1/Tat for 2 months. n = 10 - 12. rAAV-si-NC was packaged as indicated in Fig. 1A",
    "diseases": "db"
  },
  {
    "caption": "Two months after a single injection of rAAV-si-Pebp1, HFD-induced hyperglycemic and obese mice showed blood glucose levels (C) with the mice injected with rAAV-si-NC. n = 10 - 11. (D-E) Serum ALT (D) and AST (E) activities from mice in (B). The colored dots indicate the mice with high ALT or AST activity, and the same color dot in (D) and (E) indicates the same mouse.",
    "diseases": "hyperglycemic, obese"
  },
  {
    "caption": "After a single injection of rAAV-si-Tbk1 for 11 weeks, the db/db mice showed blood glucose levels (M) with the mice injected with rAAV-si-NC. n = 11. (N-O) Serum ALT (N) and AST (O) activities of mice in (K).",
    "diseases": "db"
  },
  {
    "caption": "B Indicated MDA-MB-231-derived BC cells were injected into the mammary fat pad of female NSG mice to form tumors. Tumor-bearing and age-matched tumor-free mice were sacrificed for muscle collection at week 6. Western blots show protein levels in GA. Western blot signals are quantified and normalized to Gapdh.",
    "diseases": "BC"
  },
  {
    "caption": "H. BacB cells reduce melanoma  growth.  B16 F10 melanoma  cells (4 × 105) were injected s.c. in the mid-right flank of C57BL/6J (WT) host mice  (4 mice/group; treated with BacB or untreated). Once tumors were formed and visible (6 days after imlantation) mice  were treated with Listeria TRP2   BacB cells or with vehicle (PBS) (three consecutive injections in three days). Tumor growth were monitored every 1-3 days. It is shown the mean and the SD of the tumor volume  in each group at the indicated time points. Mice  with tumors ≥ 300 mm3 were sacrified. Data information: Bars in the figure represent the mean. Error bars indicate the SD. Statistical significant differences, analyzed by ANOVA are represented by asterisk; *P<0.05, ***P<0.0005, non-significant differences are marked as (ns). …",
    "diseases": "melanoma"
  },
  {
    "caption": "C. Quantification of LITATS1 expression levels by in situ hybridization in lung adenocarcinoma tissue microarrays. Representative images (bar=100 μm) and zoomed images (bar=20 μm) of in situ hybridization results in lung adenocarcinoma and matched adjacent normal tissues. The comparison of the LITATS1 staining index between the paired tissues is shown in the right panel. Tissue pairs with higher LITATS1 expression in the normal tissue (normal) than in the lung adenocarcinoma tissue (tumor) are highlighted in red, whereas tissue pairs with lower LITATS1 expression in the normal tissue than in the tumor tissue are highlighted in green.",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "D. Kaplan‒Meier survival curves of relapse-free survival in 175 breast cancer patients stratified by LITATS1 expression. LITATS1 expression was measured by in situ hybridization in breast cancer tissue microarrays.",
    "diseases": "breast cancer"
  },
  {
    "caption": "Kaplan‒Meier survival curves of overall survival (E) in breast cancer patients stratified by LITATS1 expression. The data were generated via Kaplan‒Meier Plotter",
    "diseases": "breast cancer"
  },
  {
    "caption": "Kaplan‒Meier survival curves of distant metastasis-free survival (F) and relapse-free survival (G) in breast cancer patients and overall survival (H) in non-small cell lung cancer patients stratified by LITATS1 expression. The data were generated via Kaplan‒Meier Plotter",
    "diseases": "breast cancer, non-small cell lung cancer"
  },
  {
    "caption": "F, G. In vivo zebrafish extravasation experiments with MDA-MB-231 cells upon ectopic LITATS1 expression (F) or LITATS1 knockdown (G). Representative zoomed images of the tail fin area are shown in the left panels. Extravasated breast cancer cell clusters are indicated with yellow arrows. Analysis of the extravasated cell cluster numbers in the indicated groups is shown in the right panel. Whole zebrafish image, bar=309.4 μm; zoomed image, bar=154.7 μm. Representative results from two independent experiments are shown.",
    "diseases": "breast cancer"
  },
  {
    "caption": "H. In vivo zebrafish extravasation experiments with MDA-MB-231 cells upon LITATS1 knockdown and blockage of TGF-β signaling. Representative zoomed images of the tail fin area are shown in the left panels. Extravasated breast cancer cell clusters are indicated with yellow arrows. Analysis of the extravasated cell cluster numbers in the indicated groups is shown in the right panel. Whole zebrafish image, bar=618.8 μm; zoomed image, scale bar=154.7 μm. Representative results from two independent experiments are shown.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(A-D) Relative growth  of (top) or western blot  analysis of YAP  in (bottom) the indicated prostate cancer  cell lines expressing control, YAP-WT, or YAP-5SA constructs through lentiviral  infection. Of note, LNCaP and C4-2 express full-length AR  while 22RV1 and R1-D567  express AR  splicing variants V7 and V567ES, respectively. Data information: Results are representatives of three independent experiments. Data are ± SD. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test).",
    "diseases": "prostate cancer"
  },
  {
    "caption": "(A-F) YAP  activation inhibited AR  positive  prostate cancer  growth in xenografts  bearing C4-2  or 22RV1 tumors  that stably express Tet-O-YAP-5SA. Male NOD scid gamma (NSG) mice  bearing C4-2 tumor  cells stably expressing a Tet-O-EGFP  construct were used as control. Male NOD scid gamma (NSG) mice  bearing the indicated tumors  were injected i.p. with PBS  containing Dox  (20mg/kg) or PBS  daily for the indicated time. Tumor growth  curve (A, D), photograph of tumor  samples (B, E), and quantification of  tumor weight  (C, F) at the end of treatment were shown. XMU-MP-1 inhibited AR  positive  prostate cancer  growth in xenografts  bearing C4-2  (G-I), tumors. Male NOD scid gamma (NSG) mice  bearing the indicated tumors  were treated daily with XUM-MP-1 at the indicated concentrations or with vehicle for the indicated periods of time. Tumor growth  curve (G, J, images of tumor samples (H, K, and quantification of tumor weight (I at the end of treatment were shown. Data information: Data are ± SD. **P<0.01, ***P<0.001 (Student's t-test). n=7 mice  for each group.",
    "diseases": "prostate cancer"
  },
  {
    "caption": "XMU-MP-1 inhibited AR  positive prostate cancer growth in xenografts  bearing 22RV1 tumors. Male NOD scid gamma (NSG) mice  bearing the indicated tumors  were treated daily with XUM-MP-1  or with vehicle for the indicated periods of time. Tumor growth curve J, Data information: Data are ± SD. **P<0.01, ***P<0.001 (Student's t-test). n=7 mice  for each group.",
    "diseases": "prostate cancer"
  },
  {
    "caption": "(C) Long-range PCR assay to detect mtDNA deletions in TOP3A patient muscle (lanes 2-5). Samples from unaffected individuals (lanes 6 and 7) and a single-deletion mitochondrial disease patient (lane 8) are used as negative and positive controls, respectively. 'M' indicates marker.",
    "diseases": "mitochondrial disease"
  },
  {
    "caption": "(A-B) Analysis of mtDNA structure in muscle from individuals with TOP3A-related mitochondrial disease using Southern blotting following restriction with BamHI (A) or PvuII (B). The black bar indicates the probe (nt. 16,262 - 128).",
    "diseases": "mitochondrial disease"
  },
  {
    "caption": "H: Immunoblots of human CJD brains (red: sampled region). Gt1Sc: prion-infected Gt1 cells. Loading controls: actin and calnexin (Cnx)",
    "diseases": "CJD"
  },
  {
    "caption": "G: Lysosomal enzymes, but not β-actin, were elevated in brains of terminally scrapie-sick mice. Panels show independent triplicates. Statistics: ANOVA.. **: p<0.01. Error bars represent s.e.m.",
    "diseases": "scrapie"
  },
  {
    "caption": "B: TFEB-controlled transcripts in brains of terminally scrapie-sick C57BL/6 mice were measured by qPCR. Prion infection led to upregulation of these genes, but not of STAT3. Control: NBH-inoculated mice. ANOVA on independent triplicates. ***: p<0.001. Error bars represent s.e.m.",
    "diseases": "scrapie"
  },
  {
    "caption": "Differential expression analysis for ACE2 expression changes in treated vs control samples was performed with the level 3 CMAP data of 24 hours response values using limma (Ritchie et al, 2015; Methods). (C) 672 clinically approved drugs that are each tested on four carcinoma cell lines from CMAP (Subramanian et al, 2017).",
    "diseases": "carcinoma"
  },
  {
    "caption": "Differential expression analysis for ACE2 expression changes in treated vs control samples was performed with the level 3 CMAP data of 24 hours response values using limma (Ritchie et al, 2015; Methods). The enrichment of positive/negative ACE2 expression regulators in different drug classes based on their mechanism of action (MOA) was tested with the GSEA method as implemented in the R package fgsea (Segushichev, 2016; Methods), and the enrichment significance (negative log10 P values) is shown in bar plots in (E), for the analysis on the 672 clinically approved drugs We further extended the analysis to a larger set of 989 clinically approved drugs tested on a total of 28 cell lines (16 cancer and 12 normal cells; this list is provided in Table EV2A with details including primary site, subtype and donor demographics) where each drug may have been tested on a different subset of cells (Methods). and performed enrichment analysis using the WHO ATC drug classification data (World Health Organization, 2006), and top enriched drug classes are shown in (F).",
    "diseases": "cancer"
  },
  {
    "caption": "(A-D) This Fig summarizes the differential expression analysis results for ACE2 upon treatment by clinically approved drugs in samples of lung and kidney datasets mined from the GEO database, spanning both cancer and non-cancer datasets (Methods). Volcano plots showing the log fold-change (X-axis) and uncorrected negative log10P value (Y-axis) of ACE2 expression changes are displayed in (A) for 74 datasets of cells or tissue samples from lung, involving 42 clinically approved drugs, and in (C) for 35 kidney datasets involving 29 clinically approved drugs. Among these, we focused on the top significant drugs that modulate ACE2 expression in non-cancerous cells or tissue samples from lung and kidney, which are shown in (B) and (D), respectively, where the ACE2 expression (Y-axis) difference between control and treated groups (X-axis) are shown with boxplots. In the title of each boxplot, the GEO identifier of the respective studies and the corresponding drug name and the sample type are provided. Different datasets involving experiments using the same drug were analyzed and presented separately, since the sample types can be different across datasets. All the P values are computed from differential expression analysis using limma (Ritchie et al, 2015) (Methods). In the boxplots of panels (B) and (D), the center line, box edges and whiskers denotes the median, interquartile range and the rest of the distribution in respective order, except for points that were determined to be outliers using a method that is a function of the interquartile range, as in standard box plots. Abbreviations: HBEC, human primary bronchial epithelial cells.",
    "diseases": "cancer"
  },
  {
    "caption": "A) Seeding efficiency was compared between control non-neurodegenerative and FTLD-TDP patient samples. Cells were transfected using Lipofectamine after mitotic arrest with AraC and were fixed 3 to 6 days post-transfection with SarkoSpin fractions (Laferrière et al, 2019). Surface masks generated with Imaris show DAPI (blue), nuclear TDP-43 (NuclTDP-43, cyan) and neoaggregates (NeoAgg, orange). All images are presented at the same scale, 20 μm as indicated in AraC panel Day 6. B) Higher magnification imaging of cells seeded for 6 days revealed presence of large cytoplasmic TDP-43-HA aggregates in cells seeded with FTLD-TDP-A and multiple cytoplasmic TDP-43-HA aggregates in cells seeded with FTLD-TDP-C. Surface representation generated with Imaris showing DAPI , TDP-43-HA (green), phosphorylated TDP-43 (pTDP-43, magenta) and neoaggregates (NeoAgg, orange). All images are presented at the same scale, 5 μm as indicated in FTLD-TDP-C top panel.",
    "diseases": "FTLD-TDP, FTLD-TDP-A, FTLD-TDP-C"
  },
  {
    "caption": "B) Bar graph showing the seeding effect at day 5 and day 6 post-seeding in untreated, temperature denaturation or autoclaving denaturation conditions. While seeding in untreated condition showed a significant increase in neoaggregates (One-way ANOVA, with post-hoc Fisher's LSD test, Day 5: F=(5,12)=6.713, p=0.0033, non-neurodegenerative control vs FTLD-TDP-A p=0.0016, Day 6: F(5,12)=4.271, p=0.0183, non-neurodegenerative control vs FTLD-TDP-A p=0.0397), this effect was abolished in denaturing conditions (N=3 biological replicates for non-neurodegenerative control, FTLD-TDP-A and FTLD-TDP-C, bar graph showing mean ± SEM).",
    "diseases": "FTLD-TDP-A, FTLD-TDP-C"
  },
  {
    "caption": "B) Bar graphs representing the number of NeoAggpS403 only (bars filled in light orange), NeoAggpS409 only (bars filled in light purple) and double phosphorylated NeoAggpS403-409 (unfilled bars) for each condition. Individual patients are labelled in different colored dots (n=3 biological replicates for each condition, graph bar showing mean ± SEM). Two-way ANOVA repeated measures, with post-hoc Fisher's LSD test, F(24.54)=3.799, p<0.0001, Day 4: non-neurodegenerative control pS403/404 vs pS409/410, p<0.0001, non-neurodegenerative control pS403/404 vs bi-phosphorylated, p<0.0001, FTLD-TDP-A pS403/404 vs pS409/410, p<0.0001, FTLD-TDP-A pS403/404 vs bi-phosphorylated, p<0.0001 FTLD-TDP-C pS403/404 vs pS409/410, p<0.0001, FTLD-TDP-C pS403/404 vs bi-phosphorylated, p<0.0001. Day 5: non-neurodegenerative control pS403/404 vs bi-phosphorylated, p=0.0219, FTLD-TDP-A pS403/404 vs double, p=0.0650, FTLD-TDP-C pS403/404 vs double, p=0.0157. Day 6: Control bi-phosphorylated vs FTLD-TDP-A bi-phosphorylated, p=0.5096, control bi-phosphorylated vs FTLD-TDP-C, p=0.1010. Non-neurodegenerative control pS403/404: day 3 vs 4, p=0.0559, day 3 vs 6, p=0.0369. FTLD-TDP-A pS404/404, day 3 vs 4, p=0.0075, day 4 vs 5, p=0.0714. FTLD-TDP-C pS403-404, day3 vs 4, P=0.0759, day 4 vs 6, 9=0.0305. FTLD-TDP-A bi-phosphorylated: day 3 vs 5, P=0.0577, day 3 vs 6, p=0.0609. FTLD-TDP-C bi-phosphorylatede: day 3 vs 4, p=0.0522.",
    "diseases": "FTLD-TDP-A, FTLD-TDP-C"
  },
  {
    "caption": "C) Bar graph representing the percentage of NeoAggpS403/404 bearing double phosphorylation (left side, bars filled in light orange) and percentage of NeoAggpS409 bearing double phosphorylation (right side, bars filled in light purple). Each individual patient is labelled in different colored dots. N=3 biological replicates per condition, graph bar showing mean ± SEM. Two-way ANOVA repeated measures, with post-hoc Fisher's LSD test, pS403/404 also double positive: F(3,6)=6.567, p=0.0253: FTLD-TDP-A: Day 3 vs 5, p=0.0491, day 4 vs 6, p=0.0321, FTLD-TDP-C: ay 4 vs 6, p=0.037. pS409/419 also double positive: F(3,6)=1.246, p=0.3731, FTLD-TDP-C: Day 4 vs 5, p=0.0144.",
    "diseases": "FTLD-TDP-A, FTLD-TDP-C"
  },
  {
    "caption": "A-C) dSTORM images of cells seeded for 6 days with non-neurodegenerative control (non-ND control), FTLD-TDP-A and FTLD-TDP-C seeds extracted from post-mortem brain tissue. Staining shows localization of TDP-43 (HA tag, cyan) along with LaminB1 (yellow, A), nucleopore complexes (nucleopores, yellow, B) and nucleolus (yellow, C). Cells seeded with FTLD-TDP seeds show coaggregation of nuclear membrane proteins upon neoaggregate formation. All images are presented at the same scale, 2 μm as indicated in the non-neurodegenerative control top panels. D) dSTORM images of cells containing aggregates after 6 days of seeding with SarkoSpin fractions of postmortem brain from patients with FTLD-TDP-A or FTLD-TDP-C. Red arrows point to cytoplasmic aggregates. Cells were labelled with TDP-43 (HA-tag, cyan) and phosphorylated TDP-43 pS403/404 (pTDP-43, magenta). All images are presented at the same scale, 2 μm as indicated in the FTLD-TDP-A top panel.",
    "diseases": "FTLD-TDP, FTLD-TDP-A, FTLD-TDP-C"
  },
  {
    "caption": "Light microscopy images (LM) showing the HA-immunoreactive inclusions (green color, black arrowheads) identified in ultrathin sections from resin-embedded cell monolayers. The LM images were overlaid with low magnification EM images (EM/LM overlay) to localize the same region within the cells for EM imaging at higher magnification (dotted black square, EM). A) HA-immunopositive regions within cells seeded with FTLD-TDPA patient material showed accumulated filaments (examples indicated with white arrowheads). B) HA-immunopositive regions within cells seeded with FTLD-TDP-C patient material showed aggregated amorphous material. Scale bars LM and EM/LM overlay, 10 µm; EM, 500 nm",
    "diseases": "FTLD-TDP-C, FTLD-TDPA"
  },
  {
    "caption": "A) 2D TEM (first column) shows an example of the overall morphology of neuronal cytoplasmic inclusions from FTLD-TDP-A localized in postmortem human brain by correlative light and electron microscopy (also shown in Fig. EV4D). 2D projections of the central slices of reconstructed 3D tomograms (middle column) taken at higher magnification within the aggregate show a dense accumulation of filaments seemingly enclosed by a boundary membrane (white arrowheads). The positions of filaments selected for subtomogram analysis are shown within a single orthoslice from the same tomogram (colored, dots last column). B) STED imaging of nuclear structures (left column) and neuronal cytoplasmic inclusions found in a postmortem tissue of a patient with FTLD-TDP-A. LaminB1 (green) was used as a nuclear membrane marker along with TDP-43 (cyan) and TDP-43pS403/404 (magenta).",
    "diseases": "FTLD-TDP-A"
  },
  {
    "caption": "C) Confocal imaging of dystrophic neurites found in a postmortem tissue of a patient with FTLD-TDP-C. Dystrophic neurites were identified using TDP-43 (cyan), and TDP-43pS403/404 (magenta). Neurite markers were used to visualize neuronal projections (MAP2 for dendrites, PNF for axons; yellow and orange, respectively). D) 2D TEM (first row) of dystrophic neurites from FTLD-TDP-C, localized in postmortem human brain by correlative light and electron microscopy (also shown in Fig. EV5D). 2D projections of the central slices of reconstructed 3D tomograms (middle row) taken at higher magnification from regions within each aggregate show a sparse arrangement of filaments which are interspersed with vesicles (white asterisk). A similar arrangement of sparse filaments and vesicles is seen in a cross-section of a dystrophic neurite from FTLD-TDP-C (cross-section, also shown in Fig. EV5G). The positions of filaments selected for subtomogram analysis are shown within a single orthoslice from the same tomogram (colored dots, last row).",
    "diseases": "dystrophic, Dystrophic, FTLD-TDP-C"
  },
  {
    "caption": "C, D. Immunoblot analysis of VGF protein in NB cells. (C) NB1 cells after 24h stimulation with ALKAL2 in the presence or absence of lorlatinib. (D) CLB-BAR and CLB-GE cells after 24h inhibition with lorlatinib.",
    "diseases": "NB"
  },
  {
    "caption": "Tumours harvested from Rosa26_Alkal2;Th-MYCN, Alk-F1178S;Th-MYCN and Th-MYCN mice express NB markers. Tumours from all three genotypes were large, in most cases filling the abdominal cavity (B).",
    "diseases": "NB"
  },
  {
    "caption": "H. Kaplan-Meier relapse free (RF) and event free (EF) survival probability curves from two different NB cohorts, the Versteeg 88 cohort (upper panel) and the Kocak 649 cohort (lower panel), as derived from the R2 platform. Patients with higher VGF expression are highlighted in blue, whereas patients with lower expression are highlighted in red. The log-rank test P values are indicated.",
    "diseases": "NB"
  },
  {
    "caption": "Murine NB cell lines were generated from tumours arising in Rosa26_Alkal2;Th-MYCN (#3540) and Alk-F1178S;Th-MYCN (#3456) mice. A. Alkal2 expression in cells derived from Rosa26_Alkal2;Th-MYCN (#3540) and Alk-F1178S;Th-MYCN (#3456) NB. Immunoblotting analysis for ALKAL2 and tubulin in the indicated mouse NB cell lines. Whole cell lysates (30μg) were analysed in each lane. ",
    "diseases": "NB"
  },
  {
    "caption": " I-K. Adeno-associated virus overexpression of NDIME in the dentate gyrus (DG) of the dorsal hippocampus of VPA-treated mice rescued autism-like social deficits. Open field test (I), three-chamber test (J), and elevated-plus maze (EPM) test (K). Data in (I-K) are represented as mean ± SEM; n = 9 per group. Asterisks indicate a difference between VPA+AAV-GFP and Saline+AAV-GFP, whereas hash tags indicate a difference between VPA+AAV-NDIME-GFP and VPA+AAV-GFP. #P < 0.05, **/##P < 0.01, ***P < 0.001 (one-way ANOVA with Bonferroni post-hoc test). NS-non‐significant. ",
    "diseases": "autism"
  },
  {
    "caption": "a) UnaG-based hypoxia sensing is applicable in vivo as shown here using the human Gli36 glioblastoma model. 500 Gli36 glioblastoma cells, constitutively expressing mCherry and stably transfected with the HRE-dUnaG sensor construct, were stereotactically transplanted into the cortex of a SCIDmouse. Shown is a 30 µm cryosection of a growing tumor 10 days after transplantation. Tumor cells are distinguished from the surrounding cortex by mCherry expression. Blood vessels were contrasted by immunostaining against PECAM-1. Expression of dUnaG was visualized by its green fluorescence and predominates in areas with reduced vascular density (outlined by white line in the composite panel (bottom right).b) Representative area from the tumor shown in a), which is located outside the viewfield in a) positioned more closely to the tumor border. Also at the tumor border UnaG-expressing cells are preferentially observed at a distance to PECAM-1+ vessels.",
    "diseases": "tumor, Tumor"
  },
  {
    "caption": "e) The dUnaG-based senor was efficiently applied in intravital microscopy. 500 Gli36 glioblastoma cells stably expressing mCherry and harboring the dUnaG-sensor construct were positioned at 200µm depth subcortically in a SCIDmouse and observed 4 days later through a cranial window using multiphoton microscopy. We noted two distinct areas of intense UnaG fluorescence (red lines). Shown is a MIP of a 60 µm z stack. The vasculature was contrasted by intravenous injection of non-functionalized Qdots.f) Depth color coding of the MIP shown in e) revealed the spatial relation between the vasculature, (contrasted by Qdots), areas of increased dUnaG expression (bordered by green lines) and tumor cells expressing residual levels of mCherry. The hypoxic areas were located towards the top of the imaged tissue cube and therefore at different levels compared to the large vessel at the lower left corner (red asterisk) and the smaller vessels with a more axial orientation (white arrows). Scale bars = 100µm",
    "diseases": "tumor"
  },
  {
    "caption": "a) Overview of a tumor induced by deep cortical deposition of approximately 500 Gli36 cells stably transfected with the dUnOHR sensor construct. The perimeter of the developing tumor (white line in the merged picture, lower right panel) was delineated by Hoechst 33342 staining. As observed for dUnaG the reoxygenation sensor was expressed in compact areas with low vascular density. Vascular endothelium was identified by PECAM-1 staining. 30 µm cryosection. Scale bar = 500µm.b) Details of the tumor shown in a). Sparse, distinct cells are characterized by intense green and orange fluorescence (shown as orange) and are located preferentially to the edge of the hypoxic phalanx (white arrows). A number of cells in close proximity of the nearest blood vessel display weak green and orange fluorescence (asterisks), indicative of previously hypoxic environment and subsequent reoxygenation. Scale bar = 50 µm.",
    "diseases": "tumor"
  },
  {
    "caption": "e) TUNEL staining of tumor sections revealed that the tissue areas rich in intense mOrange aggregates colocalized with areas of increased apoptosis. Scale bar = 50µm.",
    "diseases": "tumor"
  },
  {
    "caption": "AT-3-OVA breast cancer cells were injected into the fourth inguinal mammary fat pads of female Ptpn2fl/fl and Lck-Cre;Ptpn2fl/fl mice and (c) tumour growth monitored over 26 days.",
    "diseases": "breast cancer"
  },
  {
    "caption": "AT-3-OVA mammary tumour cells (1x106) were injected into the fourth inguinal mammary fat pads of female Ly5.1+ mice. Seven days after tumour injection FACS-purified 2x106 naïve CD8+CD44loCD62Lhi lymph node T cells from Ly5.2+;OT-1;Ptpn2fl/fl versus Ly5.2+;OT-1;Lck-Cre;Ptpn2fl/fl mice were adoptively transferred into tumour-bearing Ly5.1+ mice. Tumour-bearing Ly5.1+ mice were monitored for a) tumour growth over 21 days",
    "diseases": "mammary tumour"
  },
  {
    "caption": "AT-3-OVA mammary tumour cells (1x106) were injected into the fourth inguinal mammary fat pads of female Ly5.1+ mice. Seven days after tumour injection FACS-purified 2x106 naïve CD8+CD44loCD62Lhi lymph node T cells from Ly5.2+;OT-1;Ptpn2fl/fl versus Ly5.2+;OT-1;Lck-Cre;Ptpn2fl/fl mice were adoptively transferred into tumour-bearing Ly5.1+ mice. After 21 days TILs were processed for flow cytometry and donor T cell numbers (Ly5.1-Ly5.2+) determined.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "AT-3-OVA mammary tumour cells (1x106) were injected into the fourth inguinal mammary fat pads of female Ly5.1+ mice. Seven days after tumour injection FACS-purified 2x106 naïve CD8+CD44loCD62Lhi lymph node T cells from Ly5.2+;OT-1;Ptpn2fl/fl versus Ly5.2+;OT-1;Lck-Cre;Ptpn2fl/fl mice were adoptively transferred into tumour-bearing Ly5.1+ mice. After 9 days the proportion of Ly5.2+IFNγ+TNF+ versus Ly5.2+GrzB+ TILs was determined.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "AT-3-OVA mammary tumour cells (1x106) were injected into the fourth inguinal mammary fat pads of female Ly5.1+ mice. Seven days after tumour injection FACS-purified 2x106 naïve CD8+CD44loCD62Lhi lymph node T cells from Ly5.2+;OT-1;Ptpn2fl/fl versus Ly5.2+;OT-1;Lck-Cre;Ptpn2fl/fl mice were adoptively transferred into tumour-bearing Ly5.1+ mice. d) for survival over 86 days.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "B16.F10-OVA melanoma cells (1x105) were engrafted onto the abraded skin in the flanks of Ly5.1+ mice. 24 h after tumour cell engraftment naïve CD8+CD62LhiCD44lo lymph node T cells from Ly5.2+ OT-1;Ptpn2fl/fl versus Ly5.2+ OT-1;Lck-Cre;Ptpn2fl/fl mice were adoptively transferred and tumour incidence monitored.",
    "diseases": "melanoma"
  },
  {
    "caption": "Tumour sizes in B16.F10-OVA melanoma bearing mice were determined between day 21 and 23.",
    "diseases": "melanoma"
  },
  {
    "caption": "HER-2-specific Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl;Lck+/- CAR-T cells were incubated with HER-2 expressing 24JK sarcoma cells (24JK-HER-2) or HER-2 negative 24JK sarcoma cells and CD44, CD25, PD-1 and LAG-3 MFIs on CD8+ CAR-T cells were determined by flow cytometry.",
    "diseases": "sarcoma"
  },
  {
    "caption": "Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl, or Lck-Cre;Ptpn2fl/fl;Lck+/- HER-2 CAR-T cells were incubated with 24JK-HER-2 or 24JK sarcoma cells and the proportion of CD8+IFNγ+ versus CD8+IFNγ+TNF+ CAR-T cells determined by flow cytometry.",
    "diseases": "sarcoma"
  },
  {
    "caption": "Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl or Lck-Cre;Ptpn2fl/fl;Lck+/- HER-2 CAR-T cells were incubated with 5 μM CTV-labelled (CTVbright) 24JK-HER-2 and 0.5 μM CTV-labelled (CTVdim) 24JK sarcoma cells. Antigen-specific target cell lysis was monitored for the depletion of CTVbright 24JK-HER-2 cells by flow cytometry.",
    "diseases": "sarcoma"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD44hiCD62Lhi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl or Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl;Lck+/- splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer and monitored for tumour growth.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "TILs isolated from HER-2-E0771 mammary tumour versus lymphocytes isolated from the contralateral mammary fat pad were analysed for c) CD11b+ F4/80hiLy6ChiLy6Glo myeloid derived suppressor cells (MDSC) by flow cytometry.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "TILs isolated from HER-2-E0771 mammary tumour versus lymphocytes isolated from the contralateral mammary fat pad were analysed for CD4+CD25+FoxP3+ regulatory T cells (Tregs) by flow cytometry.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. f) 13 or g) six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD44hiCD62Lhi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with f) IL-2 (50,000 IU/day) or g) saline on days 0-4 after adoptive CAR-T cell transfer and monitored for tumour growth.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified Lck-Cre;Ptpn2fl/fl CD8+CD44hiCD62Lhi central memory HER-2 CAR-T cells. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer and monitored for survival.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "HER-2-E0771 versus HER-2 negative E0771 breast cancer cells (2x105) were injected into the contralateral fourth inguinal mammary fat pads of female HER-2 TG mice 50 days after adoptive CAR-T cell transfer and mice were monitored for tumour growth.",
    "diseases": "breast cancer"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer. Lymphocytes were isolated from the tumours and dLN at day 10 post adoptive transfer and mCherry+CD45+CD3+CD8+ CAR-T cell numbers were determined by flow cytometry.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer. CTV-labelled CD8+ HER-2 CAR-T cells were incubated with 24JK-HER-2 or 24JK sarcoma cells and CTV dilution assessed by flow cytometry to monitor proliferation.",
    "diseases": "mammary tumour, sarcoma"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer. CXCR3 MFIs on CD8+CD44hiCD62Lhi versus CD8+CD44hiCD62Llo CAR-T cells (c) and CXCR5, CCR7, CCR5 MFIs on CD8+CD44hiCD62Lhi CAR-T cells (d) were determined by flow cytometry.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer. Cxcl9 and Cxcl10 mRNA levels in HER-2-E0771 tumours were assessed by quantitative real time PCR.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer. Lymphocytes were isolated from HER-2-E0771 tumours at day 3 post adoptive CAR-T cell transfer and mCherry+CD45+CD3+CD8+ CAR-T cell numbers were determined by flow cytometry.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer. Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl;Lck+/- or Lck-Cre;Ptpn2fl/fl;Stat5fl/+ HER-2 CAR-T cells were incubated with plate-bound α-CD3 and CXCR3 MFIs on CD8+CD44hiCD62Llo CAR-T cells determined by flow cytometry.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer. Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl;Stat5fl/+ HER-2 CAR-T cells were incubated with plate-bound α-CD3 and stimulated with murine recombinant IL-2 and IL-15 for the indicated time points. Intracellular p(Y694)-STAT-5 MFIs in CD8+CD44hiCD62Llo were determined by flow cytometry.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "HER-2-E0771 mammary tumours cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl;Stat5fl/+ or Lck-Cre;Ptpn2fl/fl;Lck+/- splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer and monitored for tumour growth. Lymphocytes were isolated from the tumours on day 3 post adoptive transfer and mCherry+CD45+ CD8+ CAR-T cell numbers were determined by flow cytometry.",
    "diseases": "mammary tumours"
  },
  {
    "caption": "HER-2-E0771 mammary tumours cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl;Stat5fl/+ or Lck-Cre;Ptpn2fl/fl;Lck+/- splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer and monitored for tumour growth.",
    "diseases": "mammary tumours"
  },
  {
    "caption": "HER-2-E0771 mammary tumours cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl;Stat5fl/+ or Lck-Cre;Ptpn2fl/fl;Lck+/- splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer and monitored for tumour growth. Lymphocytes were isolated from the tumours on day 16 post adoptive transfer and mCherry+CD45+ CD8+ CAR-T cell numbers were determined by flow cytometry. In (c) TILs were stained for intracellular IFNγ and TNF after PMA/Ionomycin treatment.",
    "diseases": "mammary tumours"
  },
  {
    "caption": "E0771-HER-2-PTPN2hi mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Five days after tumour injection mice were administered vehicle or DOX in drinking water followed by irradiation (4 Gy) on day 6 and the adoptive transfer of 6x106 FACS-purified central memory Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl HER-2 CAR-T cells. Mice were then injected with IL-2 (50,000 IU/day) on days 0-4 post adoptive CAR-T cell transfer In (g) CD45+CD8+mCherry+ TILs were quantified by flow cytometry at day 4 post adoptive transfer.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "E0771-HER-2-PTPN2hi mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Five days after tumour injection mice were administered vehicle or DOX in drinking water followed by irradiation (4 Gy) on day 6 and the adoptive transfer of 6x106 FACS-purified central memory Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl HER-2 CAR-T cells. Mice were then injected with IL-2 (50,000 IU/day) on days 0-4 post adoptive CAR-T cell transfer and (h) tumour growth was monitored.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "c-d) HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 10x106 HER-2 CAR-T cells generated from C57BL/6 splenocytes transfected with GFP versus Ptpn2 siSTABLE™ FITC-conjugated siRNAs two days before adoptive CAR-T cell transfer. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer and tumour growth was monitored.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 10x106 HER-2 CAR-T cells generated from C57BL/6 splenocytes transfected with GFP versus Ptpn2 siSTABLE™ FITC-conjugated siRNAs two days before adoptive CAR-T cell transfer. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer and tumour growth was monitored. CD45+CD3+CD8+ mCherry+ CAR-T cells numbers were determined in HER-2-E0771 positive tumours and spleens by flow cytometry 21 days post adoptive transfer.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 10x106 control HER-2 CAR-T cells or those in which PTPN2 had been deleted by CRISPR RNP. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 post adoptive CAR-T cell transfer and tumour growth monitored.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 10x106 control HER-2 CAR-T cells or those in which PTPN2 had been deleted by CRISPR RNP. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 post adoptive CAR-T cell transfer and tumour growth monitored. g) CD45+ CD8+ mCherry+ CAR-T cells numbers were determined in HER-2-E0771 tumours by flow cytometry 19 days post adoptive transfer.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "Representative microphotographs of murine wound sections immunostained for Ly6G (neutrophils, green) and DNA-histone (displayed as expulsed streaks in red indicative of NETs). Wounds injected with LPS primed MSCs (upper row, outer right panel) depict enhanced NET formation (magnified inset) and increased expression of activation markers like neutrophil elastase (NE, lower panel, outer left panel) compared to wounds injected with non-primed MSC (middle panels) or PBS injected wounds (outer left panels). Murine skin wounds treated with PBS injections served as control. Scale bar: 10μm (upper row) and 50μm (lower row). To facilitate comparison, areas inside the rectangles are shown at 5x magnification in the insets.",
    "diseases": "wound, Wounds, wounds"
  },
  {
    "caption": "The upper scheme depicts the experimental design. Representative microphotographs show that injection of LPS primed MSCs into wounds increased the expression of CXCL6, IL-8 and IL-1β. Graphs display numbers of double positive cells for h-β2M + CXCL6, h-β2M + IL-8 and h-β2M + IL-1β, respectively. MSCs injected wounds served as controls. Statistical analysis was performed using unpaired t-test, values are represented as mean ± SEM, six biological replicates. To facilitate comparison, areas inside the rectangles are shown at 5x magnification in the insets. Es, eschar on wound margin; wm, wound margin; scale bars: 50µm.",
    "diseases": "wound, wounds"
  },
  {
    "caption": "Results show that LPS primed MSCs injected into wounds provoke increased expression of MIP/KC in endogenous neutrophils. MIP/KC represents functional homologues of IL-8 in mice and are known as neutrophil chemoattractant. Similar results were found for IL-1β, which is a strong chemoattractant for neutrophil recruitment and bacterial clearance. In addition, LIX which shares 63% amino acid sequence identity with human GCP-2/CXCL6, a chemoattractant for neutrophils. The graphs display numbers of double positive cells for Ly6G MIP/KC, IL-1β and LIX, respectively. PBS and non-primed MSCs injected wounds served as controls. To facilitate comparison, areas inside the rectangles are shown at 5x magnification in the insets. Statistical analysis was performed using one way ANOVA, values are represented as mean ± SEM, six biological replicates. Scale bars: 50µm.",
    "diseases": "wounds"
  },
  {
    "caption": "Representative clinical pictures of murine wounds at 0, 3, 5, 7 and 10 days after wounding. Enhanced wound healing in LPS primed MSCs group as opposed to all other groups. Statistical analysis of 20 wound areas per group at the indicated time points, expressed as percentage of the initial wound size (day 0), for PBS control, non-primed MSCs, LPS primed MSCs, non-primed scrambled siRNA-treated (Scr) MSCs, LPS primed Scr MSCs and LPS primed TLR4 silenced MSCs. Results are mean ± SD of five biological replicates representing 1 of 3 independent experiments. Statistical analysis was performed using one way ANOVA.",
    "diseases": "wounds"
  },
  {
    "caption": "Representative photomicrographs of confocal microscopy of sections from differently injected day 1 wounds stained for Ly6G+ neutrophils (green) and F4/80+ macrophages (red). Nuclei are stained with DAPI (blue). Double staining was performed for sections of day 1 wounds injected with PBS (control), non-primed MSCs, LPS primed MSCs and LPS primed TLR4-silenced MSCs Double stained cells indicate phagocytic engulfment of neutrophils by macrophages. To facilitate comparison, areas inside the rectangles are shown at 5x magnification in the insets. Scale bar: 100µm.",
    "diseases": "wounds"
  },
  {
    "caption": "Quantification of Ly6G and F4/80 double positive cells on sections of differently injected day 1 wounds. Wounds were injected as described in (a). Double positive cells were counted and statistical analysis was performed using one way ANOVA, values are represented as mean ± SEM, six biological replicates.",
    "diseases": "wounds, Wounds"
  },
  {
    "caption": "Quantification of Ly6G+ neutrophils and F4/80+ macrophages on sections of differently injected day 1 wounds. Wounds were injected as described in (a). Single positive cells were counted and statistical analysis was performed using one way ANOVA, values are represented as mean ± SEM, six biological replicates.",
    "diseases": "wounds, Wounds"
  },
  {
    "caption": "Representative photomicrographs of confocal microscopy of sections from differently injected day 3 wounds double-stained for TGFβ-1 (red) and for F4/80+ macrophages (green). Nuclei are stained with DAPI (blue). Double staining was performed for sections of day 5 wounds injected with PBS (control), non-primed MSCs, LPS primed MSCs and LPS primed TLR4-silenced MSCs. Scale bar: 50µm. Representative photomicrographs of sections of day 5 wounds immunostained for CD31 (indicative of endothelial cells and newly formed vessels) and for α-SMA (indicative of myofibroblasts differentiation) after injection of LPS primed MSCs, non-primed MSCs, LPS primed TLR4-silenced MSCs or PBS (middle and lower panel). To facilitate comparison, areas inside the rectangles are shown at 5x magnification in the insets. Scale bars: 50µm.",
    "diseases": "wounds"
  },
  {
    "caption": "Quantitative analysis of CD31 positive endothelial cells in sections of wounds injected with PBS, non-primed MSCs, LPS primed MSCs and LPS primed TLR4 silenced LPS Cell counting was performed on immunostained wound sections and statistical analysis was performed using one way ANOVA, values are represented as mean ± SEM, six biological replicates.",
    "diseases": "wound, wounds"
  },
  {
    "caption": "Western blot analysis of lysates from day 5 wounds (left panel) and the corresponding densitometric analysis (right panel) depicts enhanced α-SMA protein expression in wounds injected with LPS primed MSCs as opposed to the respective control groups. Actin served as loading control. Statistical analysis was performed using one way ANOVA, values are represented as mean ± SEM, three biological replicates.",
    "diseases": "wounds"
  },
  {
    "caption": " (I) In gastric cancer or normal tissues of both cohorts, there was a significant allele-differential expression between rs2978980G-allele carriers or T-allele carriers.",
    "diseases": "gastric cancer"
  },
  {
    "caption": " (F) Gastric cancer cells after lncPSCA-knockout or stably overexpressing lncPSCA and control cells were treated with cycloheximide (CHX) or vehicle for the indicated periods of time. DDX5 levels were analyzed by Western blot. ",
    "diseases": "Gastric cancer"
  },
  {
    "caption": " (I) Knockdown of DDX5 with siRNA (siD-1 and siD-2) substantially reduced the proliferation of gastric cancer cells. Data show one representative example of three biological replicates. (J) Silencing of DDX5 with shRNA (shD) significantly reduced the proliferation of gastric cancer cells. Data show one representative example of three biological replicates. ( ",
    "diseases": "gastric cancer"
  },
  {
    "caption": "Human derived GBM tumors were processed as in (A). Representative western blot were performed (F) and the percentage of ER-lumenal protein cytosolic localization (G) were quantified. Data are the average from six different tumors. N=6 Bars and error bars indicate mean",
    "diseases": "GBM"
  },
  {
    "caption": "C-E KRAS and TP53 alterations in the cancer genome atlas (TCGA) pan-cancer MPM dataset (n = 86 patients). Shown are clinical and molecular data plot with alteration frequencies (C) and patients reclassified as KRAS- or TP53-altered (asterisks), copy number variation data summary (D), and segments of the KRAS and TP53 loci (E).",
    "diseases": "MPM"
  },
  {
    "caption": "Molecular and clinical features of the cancer genome atlas (TCGA) pan-cancer MPM patients (n = 87) stratified by the presence of KRAS standalone (n = 10) and combined KRAS/TP53 (n = 7) alterations. Shown are unsupervised hierarchical clustering of n = 86 patients (gene expression data were not available for one patient) by 40 genes significantly overexpressed in KRAS/TP53-altered over KRAS-altered over KRAS/TP53-normal patients (A) and data summaries of mononucleotide change signatures (B), of indices of genomic instability and mutation burden (C), of clinical features",
    "diseases": "MPM"
  },
  {
    "caption": "Molecular and clinical features of the cancer genome atlas (TCGA) pan-cancer MPM patients (n = 87) stratified by the presence of KRAS standalone (n = 10) and combined KRAS/TP53 (n = 7) alterations. Shown are unsupervised hierarchical clustering of n = 86 patients (gene expression data were not available for one patient) by 40 genes significantly overexpressed in KRAS/TP53-altered over KRAS-altered over KRAS/TP53-normal patients overall survival (F).",
    "diseases": "MPM"
  },
  {
    "caption": "Pleural fluid cell pellets and supernatants from 10 patients (called CRCINA #) with pleural effusion and pleural tumor samples from 17 patients (called TR#) with MPM were subjected to digital droplet polymerase chain reaction (ddPCR) for the detection of mutant (MUT) copies of KRAS codon 12/13 (KRASG12/13) and KRAS codon 61 (KRASQ61), as well as copies of TP53 and TERT. Diagnoses were lung adenocarcinoma (LUAD; n = 4) and MPM (n = 23). The assays were designed for detection of down to 1:20000 copies using EKVX (KRASWTTP53G610T), A549 (KRASG12STP53WT), NCI-H460 (KRASQ61HTP53WT), NCI-H3122 (KRASWTTP53E285V), and NCI-H3255 (KRASWTTP53G560-1A) human LUAD cells as controls. Shown are individual patient (KRAS plot) and individual sample (TP53 plot) allelic frequencies with color code and limits of normal TP53 allelic frequency as vertical dashed lines in the TP53 plot (A) Any number of KRAS-mutant droplets detected in any sample (KRAS plot in A) and any patient that failed to achieve normal TP53 ploidy by any sample (TP53 plot in A) was deemed altered.",
    "diseases": "LUAD, lung adenocarcinoma, MPM"
  },
  {
    "caption": "Wild-type (Wt), KRASG12D, and Trp53f/f mice were intercrossed, and all possible offspring genotypes received 5 x 108 PFU intrapleural or intratracheal Ad-Cre and were sacrificed when moribund. In parallel, C57BL/6 mice received ten consecutive weekly intraperitoneal injections of 1 g/Kg urethane and were sacrificed after six months. Data summary (heatmap) and representative images of immunoreactivity of tissue sections of pleural and pulmonary tissues and tumors from these mice for different markers of human malignant pleural mesothelioma (MPM) and lung adenocarcinoma (LUAD). n = 10 mice/group were analyzed for each marker. Brown color indicates immunoreactivity and blue color nuclear hematoxylin counterstaining. Note the ubiquitous strong expression of Wilms' tumor 1 (WT1), patchy moderate expression of vimentin (VIM), ubiquitous moderate expression of mesothelin (MSLN), ubiquitous strong expression of calretinin (CALB2), podoplanin (PDPN), and osteopontin (SPP1), patchy moderate expression of cytokeratin 5/6 (CK5/6), and the absence of expression of surfactant protein C (SFTPC) in murine KRAS-driven mesotheliomas. Note also the ubiquitous strong expression of WT1, the patchy moderate expression of VIM, the ubiquitous low-level expression of MSLN, the ubiquitous strong expression of CALB2 and SPP1, the ubiquitous low-level expression of PDPN, the variable moderate expression of CK5/6, and the ubiquitous moderate expression of SFTPC in murine KRASG12D-driven and urethane-induced LUAD.",
    "diseases": "LUAD, lung adenocarcinoma, malignant pleural mesothelioma, mesotheliomas, MPM"
  },
  {
    "caption": "C KPM and PMC expression of classic mesothelioma markers (top) and top KPM versus PMC overexpressed genes (bottom).",
    "diseases": "mesothelioma"
  },
  {
    "caption": "  (A) ATG-5 staining in non-cancerous gastric tissues scored 285(×200); (B) ATG-5 staining in GC tumor tissues scored 50(×400); (C) ATG-5 staining in GC tumor tissues scored 270(×400); (D) ATG-5 staining in GC tumor tissues scored 400(×200). ",
    "diseases": "tumor"
  },
  {
    "caption": "A. Histology staining for IQGAP1 and GSDMD in naive and inflamed (3 days of DSS-challenge) colon tissues.",
    "diseases": "inflamed"
  },
  {
    "caption": "(F) Immunohistochemical analysis of Slf2-sgRNA lymphomas described in Figure 2E. Representative example of three analyzed Slf2-sgRNA lymphomas.",
    "diseases": "lymphomas"
  },
  {
    "caption": "(B, C) Kaplan-Meier overall survival curves of the indicated cohorts of DLBCL patients (Lenz, NEJM). DLBCL patients were classified according to SLF2 or SLF1 mRNA expression. P-value was determined by log-rank (Mantel-Cox) test.",
    "diseases": "DLBCL"
  },
  {
    "caption": "(B) Immunoblot analysis of a panel of human DLBCL cell lines with a specific SLF2 antibody and quantification of the SLF2 western blots (middle panel). Protein expression of SLF2 was normalized to β-Actin expression. The expression level of SLF2 in DB cells was set as 1. Data are presented as mean +/- SD of n=3 independent experiments.",
    "diseases": "DLBCL"
  },
  {
    "caption": "(G) Quantification of cell viability measured by celltiterGlo from primary murine Eµ-Myc lymphoma derived cells co-treated with indicated concentrations of SUMOi and Rabusertib for 72 hours. Bar plots represent cell viability relative to the DMSO treated control cells. Error bars represent SD from three independent experiments. P-value was determined by ANOVA test; Tukey's post hoc test.",
    "diseases": "lymphoma"
  },
  {
    "caption": "C, Quantification of telomeric allelic imbalances (TAI) in soft tissue and bone sarcoma.",
    "diseases": "bone sarcoma"
  },
  {
    "caption": "E-G, Ex vivo treatment of HRDhigh (NMFH-1, OH931, PM197, USZ-21_MFS2 and USZ-21_UPS1) sarcoma models compared with HRDlow (USZ-20_REA1, USZ-21_LG1, USZ-22_EMC2, USZ-20_SFT1 and USZ-21_CIC1) sarcoma models for 4 days with six doses of the chemotherapy agents oxaliplatin, doxorubicin and trabectedin.",
    "diseases": "sarcoma"
  },
  {
    "caption": "M-O, HRDhigh sarcoma cell models and UWB1.289 treated for 3 days with five doses olaparib alone and in combination with 1 nM trabectedin. Note that no sensitivity to olaparib in monotherapy was observed at 3 days",
    "diseases": "sarcoma"
  },
  {
    "caption": "Q-S, HRDhigh sarcoma cell models and UWB1.289 treated for 3 days with five doses adavosertib alone and in combination with 100 nM doxorubicin.",
    "diseases": "sarcoma"
  },
  {
    "caption": "A, Immunofluorescence showing nuclear expression of the DNA damage marker γH2A.X (magenta) upon 6 h treatment with 10 nM trabectedin and 100 nM olaparib in combination in HRDhigh and HRDlow sarcoma cell models as well as ovarian carcinoma UWB1.289 cells. B, Immunofluorescence showing RAD51 nuclear foci (magenta) upon 6 h treatment with 10 nM trabectedin and 100 nM olaparib in combination only in the HRDlow sarcoma cell model (USZ-21_LG1). C, D, Quantification of γH2A.X (C) or RAD51 (D) nuclear intensity per cell compared to untreated control cells. E,",
    "diseases": "ovarian carcinoma, sarcoma"
  },
  {
    "caption": "E, Immunohistochemistry (IHC) in human tissue sections showing RAD51 (brown) expression in HRDlow but not HRDhigh sarcoma patients. Small-nucleated lymphocytes and/or proliferating cells appeared RAD51-positive in HRDhigh models.",
    "diseases": "sarcoma"
  },
  {
    "caption": "F, Immunofluorescence in human tissue sections showing RAD51 (magenta) nuclear foci in an HRDlow but not an HRDhigh sarcoma patient.",
    "diseases": "sarcoma"
  },
  {
    "caption": "H, Magnetic resonance imaging (MRI) of LMS patient since primary diagnosis. Open arrowheads point at metastatic lesions.",
    "diseases": "LMS"
  },
  {
    "caption": "(C) Representative pictures of ZEB1 immunostaining in BRAFV600 tumors from patients, classified in ZEB1 high, int and low subgroups, based on the intensity of ZEB1 staining and on the percentage of cells positive for ZEB1. Scale bar = 80 µm. (D) Pie charts representing the distribution of ZEB1 alone (upper part), or ZEB1 and TWIST1 (lower part) immunohistochemistry staining in tumors according to their initial response to vemurafenib +/- cobimetinib treatment. ZEB1 +/- TWIST1 levels are higher in MAPKi primary resistant melanomas (initial non-responders) compared to tumors that initially respond to treatment (n=70, Fisher's exact test).",
    "diseases": "tumors"
  },
  {
    "caption": "(E) Representative pictures of ZEB1 and MITF immunostainings, before and after vemurafenib treatment, in the tumor from patient 1, exhibiting primary resistance to BRAFi. Scale bar = 80 µm. Right: Magnification of MITFhigh and MITFlow clones in the resistant tumor under treatment. Arrows indicate endothelial and stromal cells that also show positive staining for ZEB1, besides tumor cells.",
    "diseases": "tumor"
  },
  {
    "caption": "(D) Representative pictures of ZEB1 and MITF immunostainings in tumors from patients 2, 3 and 4, before and after vemurafenib treatment. Scale bar = 40 µm. For ZEB1 staining in patient 4, the inset shows a magnification. Arrows point at stromal cells (s). All other cells positive for ZEB1 are tumor cells.",
    "diseases": "tumors"
  },
  {
    "caption": "(H) Upper part: Western blot analyses of ZEB1 in shRNA-Control (1 to 4) or shRNA-ZEB1 (5 to 8) ESPxenografttumors, showing efficient ZEB1 knock-down directly in the tumors, after IPTG ±PLX4032 treatment in vivo. Lower part: Representative pictures of ZEB1 immunostaining in shRNA-Control or shRNA-ZEB1tumors, after IPTG treatment in vivo. Scale bar = 40µm.",
    "diseases": "tumors"
  },
  {
    "caption": "(E) Number of M1-like or  M2-like macrophages  based on TMA  data for lung cancer patients  with either high (above median) or low (below median) expression  of MRPL35.",
    "diseases": "lung cancer"
  },
  {
    "caption": "(C) Detection of sNrCAM and human serum albumin (hSA) in AD patients CSF that had been treated with acitretin (30 mg/d) or placebo for 30 days (n = 9) (Endres et al, 2014). (D) Densitometric quantification of the Western Blots in (C). sNrCAM/hSA ratios were calculated, and then the treatment to baseline ratios (t/b) for every patient were calculated. Two-sided student's t-test (n = 9). Given are mean +/- the standard error of them mean. Representative Western Blots are shown.",
    "diseases": "AD"
  },
  {
    "caption": "Volcano plot of the proteomic analysis of CSF from AD patients treated with acitretin or placebo for 30 days. Every circle represents one protein. The log10 transformed t-test p-values (again treatment/baseline for every patient) are plotted against the log2 transformed label-free quantification intensity ratios of acitretin and placebo CSF. ADAM10 substrates are indicated in bold writing. In total, more than 50 ADAM10 substrates were identified, but only the significantly altered substrates as well as NrCAM and APP are indicated.",
    "diseases": "AD"
  },
  {
    "caption": "A Flow cytometric quantification of lymphocytes, monocytes, B-cells, natural killer (NK) cells, dendritic cells (DCs) and granulocytes in peripheral venous blood samples from non-diabetic (ND) and type-2 diabetic (T2D) patients with COVID-19.",
    "diseases": "COVID-19, T2D, type-2 diabetic"
  },
  {
    "caption": "C Principle component analysis of lymphocyte and monocyte population frequencies in ND and T2D COVID-19 patients and in T2D patients without COVID-19.",
    "diseases": "COVID-19, T2D"
  },
  {
    "caption": "A Quantification of CD14 expression and size (FSC) in monocyte populations from non diabetic (ND) and type-2 diabetic (T2D) COVID-19 patients.",
    "diseases": "COVID-19, T2D, type-2 diabetic"
  },
  {
    "caption": "B Frequency of conventional (FSCLo) and large (FSCHi) monocytes in ND and T2D COVID-19 patients.",
    "diseases": "COVID-19, T2D"
  },
  {
    "caption": "C Expression of CD16, CD14 and HLA-DR in FSCLo and FSCHi monocytes from COVID-19 patients.",
    "diseases": "COVID-19"
  },
  {
    "caption": "D Proportions of classical, intermediate and non-classical monocytes within FSCLo and FSCHi monocytes from COVID-19 patients.",
    "diseases": "COVID-19"
  },
  {
    "caption": "F IL8, IL6 and CCL2 mRNA expression in PBMCs from ND and T2D COVID-19 patients.",
    "diseases": "COVID-19, T2D"
  },
  {
    "caption": "G Monocyte size quantified in ND and T2D COVID-19 patients treated in general wards (Gen) or in intensive care unit (ICU).",
    "diseases": "COVID-19, T2D"
  },
  {
    "caption": "A Quantification of IRF5 and IFNB1 mRNA expression in peripheral blood mononuclear cells of non-diabetic (ND) and type 2 diabetic (T2D) COVID-19 patients (A).",
    "diseases": "COVID-19, T2D, type 2 diabetic"
  },
  {
    "caption": "C IRF5 median fluorescence intensity (MFI) in monocytes of ND and T2D patients with COVID-19.",
    "diseases": "COVID-19, T2D"
  },
  {
    "caption": "E IRF5 expression (MFI) in monocyte subtypes from ND and T2D COVID-19 patients.",
    "diseases": "COVID-19, T2D"
  },
  {
    "caption": "F HLA-DR and IRF5 expression in monocytes from COVID-19 patients.",
    "diseases": "COVID-19"
  },
  {
    "caption": "G IRF5 expression in monocytes of ND or T2D COVID-19 patients admitted to intensive care unit (ICU) or treated exclusively in general wards (Gen) .",
    "diseases": "COVID-19, T2D"
  },
  {
    "caption": "H IRF5 expression in monocytes of ND or T2D COVID-19 patients admitted ICU or treated exclusively in Gen.",
    "diseases": "COVID-19, T2D"
  },
  {
    "caption": "B Proportions of lymphocytes and monocytes in peripheral venous blood from T2D patients with COVID-19 either treated in Gen or requiring ICU admission.",
    "diseases": "COVID-19, T2D"
  },
  {
    "caption": "C Phenotypic analysis of lymphocyte and monocyte subpopulations in peripheral venous blood from T2D COVID-19 patients treated in Gen or requiring ICU treatment.",
    "diseases": "COVID-19, T2D"
  },
  {
    "caption": "Liver tissue samples obtained from HBV-negative patients undergoing metastasis resection (Control), or patients with acute, self-limiting HBV infection or chronic hepatitis B, or chronic coinfection with HBV and hepatitis D virus (HDV) were stained for ISG20 by immunohistochemistry. For each clinical entity, tissue sections from three different patients are shown; scale bar: 50 µm. ISG20 positive area of each sample (n=3 biological replicates) was determined by Tissue IA image analysis software and is given in % of total tissue area scanned.",
    "diseases": "chronic hepatitis B"
  },
  {
    "caption": "A,B  NAD  and nicotinamide (NAM) levels in heart  of WT (n=5, n=6, respectively), mdx  (n=5, n=5, respectively) and mdx/CD38-/- mice (n=6, n=5, respectively). C,D NAD  and NAM levels in  diaphragm of WT (n=5, n=6, respectively), mdx (n=4, n=5, respectively) and mdx/CD38-/- mice (n=6, n=5, respectively). Data information: Each dot of the graphs represents a mouse and measured in duplicate After normality and variance comparison tests, significance was assessed using: ANOVA followed by Fisher's LSD test; B: Kruskal-Wallis followed by Dunn's test; D: Kruskal-Wallis followed by Mann-Whitney tests; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "E,F levels of ADP-ribose  (ADPR) (E),  cyclic ADP-ribose  (cADPR) (F) expressed as nmol/mg protein in heart of WT (n=6), mdx (n=5) and  mdx/CD38-/- mice (n=5, n=5, n=6 respectively). Data information: Each dot of the graphs represents a mouse and measured in duplicate After normality and variance comparison tests, significance was assessed using: : ANOVA followed by Fisher's LSD test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "(G) qPCR analysis of mRNA levels of Sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1) in  heart  of WT (n=6), mdx (n=5) and mdx/CD38-/- mice (n=5, n=5, n=6 respectively). Data information: Each dot of the graphs represents a mouse and measured in duplicate After normality and variance comparison tests, significance was assessed using: ANOVA followed by Fisher's LSD test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "H,I Levels of ADPR (H), cADPR (I) expressed as nmol/mg protein in  diaphragm  of WT (n=6), mdx (n=5) and  mdx/CD38-/- (n=5) mice. Data information: Each dot of the graphs represents a mouse and measured in duplicate After normality and variance comparison tests, significance was assessed using: ANOVA followed by Fisher's LSD test; ; I: Welch's ANOVA followed by Welch's t-tests Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "(J) qPCR  analysis mRNA levels of SARM1 in diaphragm of WT (n=6),  mdx (n=5) and mdx/CD38-/- (n=5) mice. Data information: Each dot of the graphs represents a mouse and measured in duplicate After normality and variance comparison tests, significance was assessed using: J: ANOVA Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "K, L Western blot  analysis of  CD38 protein expression in heart (K) and diaphragm (L) of WT (n=5, n=6, respectively) and mdx  (n=5) mice.  Vinculin is used as housekeeping protein control and the dot plots show the ratio of  CD38/vinculin. Data information: Each dot of the graphs represents a value/mouse. After normality and variance comparison tests, significance was assessed using: unpaired Student's t-test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "M, N qPCR analysis of  CD38  mRNA levels in  heart  (M) and  diaphragm (N) of WT (n=6) and  mdx  (n=5) mice. Data information: Each dot of the graphs represents a mouse and measured in duplicate After normality and variance comparison tests, significance was assessed using: M: unpaired Student's t-test; N: unpaired Welch's t-test. Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "A Cardiac  function evaluated by  echocardiography in  mdx/CD38-/- mice: the dot plots show the  left ventricular (LV)  diastolic (A1) and  systolic (A2) inner diameters and LV  ejection (A3) fraction in 7-month-old WT (n=5), mdx  (n=6) and  mdx/CD38-/- (n=10) mice. Data information: : Each dot of the graphs represents a mouse. in duplicate After normality and variance comparison tests, significance was assessed using:A1 ANOVA followed by Fisher's LSD test; A2,A3 Kruskal-Wallis followed by Dunn's test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "B Plasma levels of cardiac  stress biomarkers:  brain natriuretic peptide (BNP) (B1) and cardiac troponin I  (cTnI) (B2) in 7-month-old WT (n=7), mdx (n=6) and mdx/CD38-/- (n=11) mice. Data information: : Each dot of the graphs represents a mouse. After normality and variance comparison tests, significance was assessed using ANOVA followed by Fisher's LSD test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "C Cropped images revealed the    collagen (blue) stained by Masson's trichrome staining  in the  heart  of WT,  mdx, and  mdx/CD38-/- mice. Dot plot showing the quantification of heart collagen staining area (% total area) in 7-month-old WT, mdx, and mdx/CD38-/- mice (n=4 per group). Scale bars: 200 µm. Data information: : Each dot of the graphs represents a mouse. in triplicate After normality and variance comparison tests, significance was assessed using ANOVA followed by Fisher's LSD test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "D Isoproterenol-induced  heart failure in 3-month-old mice. The Kaplan-Meier  curve shows the survival rate of mdx mice  (NaCl, n=5); mdx  (n=19) and mdx/CD38-/- (n=9) mice following isoproterenol (subcutaneous injection) at 2.5 mg/kg/d for 10 days. Data information: one value/mouse. After normality and variance comparison tests, significance was assessed using D: Log-rank Mantel-Cox test and Log-rank test for trend and Gehan-Breslow-Wilcoxon test ; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx, heart failure"
  },
  {
    "caption": "E Histogram showing isoproterenol-induced heart hypertrophy in mdx NaCl (n=5) mice, surviving mdx  (n=9), mdx/CD38-/- NaCl  (n=9) and mdx/CD38-/- (n=9) mice, expressed as heart weight/body weight ratio (HW/BW). Data information: one value/mouse. After normality and variance comparison tests, significance was assessed using Kruskal-Wallis followed by Mann-Whitney tests Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx, heart hypertrophy"
  },
  {
    "caption": "F Plasma levels of cardiac  stress biomarkers: brain natriuretic peptide (BNP) (F1) and  cardiac troponin I (cTnI) (F2) following isoproterenol treatment in mdx NaCl  (n=5), surviving mdx  (n=8),  mdx/CD38-/- NaCl  (n=5) and mdx/CD38-/- (n=8) mice. Data information: in duplicate After normality and variance comparison tests, significance was assessed using F2 Kruskal-Wallis followed by Mann-Whitney tests; F1: ANOVA followed by Student's/ Welch's t-tests; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "G,H Time-lapse images recorded by confocal microscopy in \"line scanning mode\", showing Ca2+ sparks and waves in  cardiomyocytes at rest, extracted from  mdx and mdx/CD38-/- mice; scale bars: 10 µM (horizontal), 500 ms (vertical). Bar graphs showing the averaged Ca2+ sparks (G) and waves (H) frequencies in cardiomyocytes  isolated from WT (n=21 cells), mdx (n=28 cells) and mdx/CD38-/- (n=32 cells) mice. Data information: experiments performed in 3  mice of each group. After normality and variance comparison tests, significance was assessed using Kruskal-Wallis followed by Dunn's test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "I Bar graph showing the fractional release following caffeine application in  cardiomyocytes from WT (n=24 cells), mdx (n=33 cells) and mdx/CD38-/- (n=32 cells) mice. Data information: experiments performed in 3 mice of each group. After normality and variance comparison tests, significance was assessed using: ANOVA followed by Fisher's LSD test; ; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "J Bar graph showing the post-rest potentiation in cardiomyocytes from WT (n=24 cells), mdx (n=28 cells) and mdx/CD38-/- (n=32 cells)  mice. Data information: experiments performed in 3 mice of each group. After normality and variance comparison tests, significance was assessed using: Kruskal-Wallis followed by Dunn's test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "A Measurement of the ventilatory mechanic by barometric plethysmography: dot plots showing  inspiratory (A1) and expiratory times (A2), the relaxation time (A3) and the respiratory frequency (A4) in WT (n=8), mdx (n=11) and mdx/CD38-/- (n=9) mice. Data information: Each dot of the graphs represents a mouse. one value/mouse After normality and variance comparison tests, significance was assessed using: A1,A3 ANOVA followed by Fisher's LSD test; A2, A4 : Kruskal-Wallis followed by Dunn's test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "B Images showing muscle fiber typology revealed by immunostaining. Localization of the slow   MyHC (Type I) fiber and fast   MyHCs (Type IIa and IIb/X) fibers, along with laminin (red) on transverse cross-sections from  diaphragm of WT, mdx and mdx/CD38-/- mice. Scale bars: 100 µm. Histogram showing the percentage of I, IIa and IIb/X fiber type distribution in diaphragm of WT (n=7), mdx (n=6) and mdx/CD38-/- (n=7) mice. Data information: one value/mouse After normality and variance comparison tests, significance was assessed using: ; B: Chi-square test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "C Fiber size distribution in the  diaphragm of WT (n=7), mdx  (n=6) and  mdx/CD38-/- (n=7) mice. Data information: one value/mouse After normality and variance comparison tests, significance was assessed using: C: Kolmogorov-Smirnov test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "D Images revealing the collagen (blue) by Masson's trichrome staining in  diaphragm of WT, mdx, and mdx/CD38-/- mice. Quantification of collagen staining area (% total area) in the diaphragm of WT, mdx  and mdx/CD38-/- mice (n=4 per group). Scale bars: 200 µm. Data information: Each dot of the graphs represents a mouse. D in duplicate; After normality and variance comparison tests, significance was assessed using: : ANOVA followed by Fisher's LSD test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "E Embryonic myosin expression: immunostaining showing its localization along with laminin (green) on transverse cross-sections from diaphragm of WT,  mdx and mdx/CD38-/- mice. Scale bars: 50 µm. Histogram showing the relative proportion of embryonic myosin area (% total area) in diaphragm of WT (n=7), mdx  (n=8) and mdx/CD38-/- (n=8) mice. Data information: Each dot of the graphs represents a mouse. E one value/mouse. After normality and variance comparison tests, significance was assessed using: E: Welch's ANOVA followed by Welch's t-tests. Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "A Images showing immunostaining  of myeloid cells showing F4/80 (macrophage  marker), Ly-6G/6C (monocyte, granulocyte and neutrophil marker), CD8 (cytotoxic T lymphocyte  marker) and IL-6  positive cells in diaphragm of 7-month-old WT (n=8), mdx (n=8) and mdx/CD38-/- (n=7 or 8 ) mice. Lower panel: histograms quantifying the percentage of F4/80  (A1) mdx/CD38-/- (n=7), LY6 (A2) mdx/CD38-/- (n=8), CD8 (A3) mdx/CD38-/- (n=7), IL-6 (A4) mdx/CD38-/- (n=8) positive cells. Scale bars: 50 µm. Data information: Each dot of the graphs represents a mouse. A one value/mouse After normality and variance comparison tests, significance was assessed using: A1-4: Welch's ANOVA followed by Welch's t-tests; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "B qPCR  analysis of mRNA levels of  interleukin-1β (IL-1ß) (B1) and -6 (IL-6) (B2), cyclin-dependent kinase inhibitor 1 (p21) (B3) transforming growth factor-β  (TGF-β) (B4), and senescence markers (cell-cycle inhibitor p16, INK4a) (B5), Collagen Type I Alpha 1 Chain (Col1a1) (B6) in diaphragm of 20-month-old WT (n=6), mdx (n=5) and mdx/CD38-/- (n=5) mice. Data information: Each dot of the graphs represents a mouse. B in duplicate. After normality and variance comparison tests, significance was assessed using: B1-6: ANOVA followed by Fisher's LSD test. Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "A NAD+ levels in  limb muscles of 20-month-old WT (n=7), mdx  (n=5) and mdx/CD38-/- (n=6) mice. Data information: Each dot of the graphs represents a mouse. in duplicate; After normality and variance comparison tests, significance was assessed using: ANOVA followed by Fisher's LSD test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "B CD38 expression: western blot  analysis of CD38 (B1) protein in  limb of WT and mdx mice (n=6 per group). Vinculin  is used as housekeeping protein control and the dot plots show the ratio of  CD38/vinculin.  qPCR analysis of CD38 mRNA (B2) in  limb of 20-month-old WT and mdx mice  (n=4 per group). Data information: Each dot of the graphs represents a mouse. one value/mouse; After normality and variance comparison tests, significance was assessed using: B1: unpaired Welch's t-test; B2 : unpaired Student's t-test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "C Histograms showing the  grip duration (latency to fall) (C1) and the limb force (C2) measured by a  grip test in WT (n=89), mdx (n=52, 53 respectively) and mdx/CD38-/- (n=58)  mice (age: 9 to 26 months old). Data information: C1 one value/mouse; C2 in triplicate. After normality and variance comparison tests, significance was assessed using: : unpaired Student's t-test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "D Images showing  muscle fiber  typology revealed by  immunostaining. Localization  of the slow MyHC (Type I) fiber  and fast  MyHCs (Type IIa  and IIb/X) fibers, along with  laminin (red) on transverse cross-sections from soleus and tibialis (TA) of WT, mdx  and mdx/CD38-/- mice. Scale bars: 100 µm. Histogram showing the percentage of I, IIa and IIb/X fiber type distribution in soleus  and TA of WT, mdx  and mdx/CD38-/- mice. Experiments performed in WT (n=3), mdx  (n=5) and mdx/CD38-/- (n=7)  mice for soleus; WT (n=5), mdx  (n=6) and mdx/CD38-/- (n=6) mice for TA. Data information: one value/mouse; After normality and variance comparison tests, significance was assessed using: D: Chi-square test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "E Fiber  size distribution in soleus from WT, mdx  and  mdx/CD38-/- mice. Data information: one value/mouse After normality and variance comparison tests, significance was assessed using: E: Kolmogorov-Smirnov test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "F Images displaying the collagen (blue) revealed by Masson's  trichrome staining in limb  of WT, mdx, and mdx/CD38-/- mice. The dot plot shows the quantification of collagen staining area (% total area) in limb of WT (n=4), mdx  (n=5) and mdx/CD38-/- (n=5)  mice. Scale bars: 200 µm. Data information: Each dot of the graphs represents a mouse. in triplicate. After normality and variance comparison tests, significance was assessed using: : ANOVA followed by Fisher's LSD test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "G Embryonic myosin expression  revealed by  immunostaining along with laminin  (green) on transverse cross-sections from limb of WT (n=5), mdx  (n=8) and  mdx/CD38-/- (n=8) mice. Scale bars: 50 µm. Dot plot showing the relative proportion of  embryonic myosin area in limb of WT, mdx  and mdx/CD38-/- mice. Data information: Each dot of the graphs represents a mouse. one value/mouse; After normality and variance comparison tests, significance was assessed using: G: Welch's ANOVA followed by Welch's t-tests. Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "mdx"
  },
  {
    "caption": "A Young  mdx mice and treatment with an  CD38 inhibitor. 6-week-old mdx mice were treated for 5 weeks with K-rhein at 2.5 mg/kg/d by intraperitoneal injection. Dot plots showing measurement of the grip duration  (A1) and the force (A2) of WT (n=9), mdx (n=7) and  K-rhein-treated mdx (n=10) mice. Data information: Each dot of the graphs represents a mouse. A1 one value/mouse; A2, in triplicate. After normality and variance comparison tests, significance was assessed using: A1: Welch's ANOVA followed by Welch's t-tests; A2 ANOVA followed by Fisher's LSD test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001",
    "diseases": "mdx"
  },
  {
    "caption": "B, New-born double knockout utrophin-dystrophin (mdx/utr-/-) mice and treatment with an  CD38  inhibitor. Mdx/utr-/- mice were subcutaneously injected with  K-rhein (0.6 and 2.5 mg/kg/d) for 4 weeks. B: Dot plots showing the treadmill performances of K-rhein-treated  mdx/utr-/- mice: distance traveled (B1), maximum speed reached (B2) and maximum running time (B3) (WT (NaCl) and mdx/utr-/-+ K-rhein 2.5 mg/kg/d n=10 mice per group; mdx/utr-/-(NaCl) and mdx/utr-/-+ K-rhein 0.6 mg/kg/d, n=12 mice per group). Data information: Each dot of the graphs represents a mouse. one value/mouse; After normality and variance comparison tests, significance was assessed using: ANOVA followed by Fisher's LSD test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001, #: p<0.001 vs mdx/utr-/- .",
    "diseases": "mdx, Mdx"
  },
  {
    "caption": "C New-born double knockout utrophin-dystrophin  (mdx/utr-/-) mice and treatment with an CD38 inhibitor. Mdx/utr-/- mice were subcutaneously injected with K-rhein  (0.6 and 2.5 mg/kg/d) for 4 weeks. C: Measurement of the grip duration (grid test) in WT (n=10), mdx/utr-/- (n=8) and K-rhein-treated mdx/utr-/- mice (n=10, 6 mice, respectively for the 0.6 mg/kg/d and 2.5 mg/kg/d doses). Data information: Each dot of the graphs represents a mouse. in triplicate. After normality and variance comparison tests, significance was assessed using: : Kruskal-Wallis followed by Dunn's test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001, #: p<0.001 vs mdx/utr-/- .",
    "diseases": "mdx, Mdx"
  },
  {
    "caption": "D, Adult mdx mice and long-term treatment with an CD38 inhibitor. Mdx mice were evaluated after 6 months of intraperitoneal injection with the CD38 inhibitor 78c (10 mg/kg/d). D: Histogram showing  NAD+ levels in  limb of mdx (n=4) and 78c-treated mdx (n=5) mice. Data information: Each dot of the graphs represents a mouse. in duplicate; After normality and variance comparison tests, significance was assessed using: D: unpaired Student's t-test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001",
    "diseases": "mdx, Mdx"
  },
  {
    "caption": "E, Adult mdx mice and long-term treatment with an CD38 inhibitor. Mdx mice were evaluated after 6 months of intraperitoneal injection with the CD38 inhibitor 78c  (10 mg/kg/d). E: Histogram showing grip duration (E1) (n=8 mdx and n=11) in the inverted grid test and performances in chronic treadmill test  (E2) at days 1, 6 and 7 after treatment of mdx (n= 5 excepted for D7 n=4) and 78c-treated mdx  (n= 7) mice. Data information: Each dot of the graphs represents a mouse. in duplicate; After normality and variance comparison tests, significance was assessed using: E1: unpaired Mann-Whitney test; E2: two-way ANOVA; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001",
    "diseases": "mdx, Mdx"
  },
  {
    "caption": "F Adult mdx mice and long-term treatment with an CD38 inhibitor. Mdx mice were evaluated after 6 months of intraperitoneal injection with the CD38 inhibitor 78c (10 mg/kg/d). F: Dot plots showing barometric plethysmography measures of the tidal (F1) and minute (F2) volumes of mdx (n=4) and 78c-treated mdx (n=6) mice. Data information: Each dot of the graphs represents a mouse. in duplicate; After normality and variance comparison tests, significance was assessed using: F2, unpaired Mann-Whitney test ; F1 unpaired Welch's t-test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001",
    "diseases": "mdx, Mdx"
  },
  {
    "caption": "G Time-lapse confocal  imaging of calcium dynamics in  human healthy and DMD myotubes loaded with the  Ca2+-sensitive dye Fluo-4 (white arrows show the active cells) (G1). Traces illustrating recordings from region of interest (ROI) in an inactive healthy myotube (black line) and in a DMD myotube displaying Ca2+ spiking activity (red line) (G2). Histogram showing the percentage of myotubes displaying spontaneous  Ca2+  waves (G3): healthy myotubes (n=91 cells),  DMD myotubes  (n=186 cells). Scale bars: 200 µm. Data information: After normality and variance comparison tests, significance was assessed using: G3 Chi-square test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001",
    "diseases": "DMD"
  },
  {
    "caption": "H Human DMD myotubes treated by SAR650984  (isatuximab), a humanized anti-CD38  antibody. Fluorescence trace illustrating a recording of DMD myotubes treated with 10 µg/ml of  SAR650984 (blue). Histogram showing the percentage of spontaneous  Ca2+  waves in DMD myotubes untreated (n=740 cells) or treated with 10 µg/ml of SAR650984 (n=279 cells) (H1). Histogram showing the Ca2+ wave inter-spike duration (interval between spikes) in myotubes  treated with 10 µg/ml of SAR650984 (n=43 cells vs 91 for the untreated DMD myotubes) (H2). Data information: After normality and variance comparison tests, significance was assessed using: H2: unpaired Welch's t-test; H1: Chi-square test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001",
    "diseases": "DMD"
  },
  {
    "caption": "A-D. RNA blots were hybridized to AMV-specific probes to reveal accumulation of viral RNA in double (de) and triple (te) ect2/3/4 (A, B) or ect2/3/5 (C, D) mutants compared to WT plants. A and C show local infection at 3 days post-inoculation (dpi); B and D show systemic infection in aerial tissue at 7 dpi. Each panel shows a representative RNA blot displaying AMV RNAs 1-4 (left) and its quantification histogram (right). Dashed lines indicate non-contiguous samples analyzed on the same membrane. Ethidium bromide staining of ribosomal RNAs (EB) was used as RNA loading control. Error bars indicate standard deviations. Asterisks indicate significant differences from the WT (*: p < 0.05; **; p < 0.01) using the Student's t-test (n = 4). AU, arbitrary units.",
    "diseases": "local infection, systemic infection"
  },
  {
    "caption": "A, RNA-blot analysis of AMV systemic infection in plants expressing ECT2WT-mCherry (WT) or ECT2W464A-mCherry (W464A) in the de23 background (A) at 7 days post-inoculation. Each panel shows a representative RNA blot displaying AMV RNAs 1-4 (left) and its quantification histogram (right). Ethidium bromide staining of rRNAs (EB) was used as RNA loading control. Genotypes are indicated on the top of each northern blot. In A, upper and lower panels show independent complementation transgenic lines, and different letters indicate statistical differences according to Fisher's Least Significant Difference (LSD) (p < 0.05).",
    "diseases": "systemic infection"
  },
  {
    "caption": "B. RNA-blot analysis of AMV systemic infection in plants expressing in vir-1 plants (B) at 7 days post-inoculation. Each panel shows a representative RNA blot displaying AMV RNAs 1-4 (left) and its quantification histogram (right). Ethidium bromide staining of rRNAs (EB) was used as RNA loading control. Genotypes are indicated on the top of each northern blot. In B, dashed line indicates non-contiguous samples that are analyzed on the same membrane. Error bars indicate standard deviations. Asterisks indicate significant differences from the WT (**: p < 0.01) applying Student's t-test (n = 4). AU, arbitrary units.",
    "diseases": "systemic infection"
  },
  {
    "caption": "A, Systemic infection of rosettes at 7 days post-inoculation (dpi) (A) Each panel shows a representative RNA blot displaying AMV RNAs 1-4 (left) and its quantification histogram (right). Ethidium bromide staining of rRNAs (EB) was used as RNA loading control. Genotypes are indicated on the top of each northern blot. #1 and #2 correspond to the progeny of two different quadruple homozygous F2 siblings derived from the alkbh9b x te235 cross. Error bars show standard deviations. AU, arbitrary units. Different letters indicate statistical differences according to Fisher's Least Significant Difference (LSD) (p < 0.05).",
    "diseases": "Systemic infection"
  },
  {
    "caption": "B. Systemic infection of rosettes and floral stems at 20 dpi (B). Each panel shows a representative RNA blot displaying AMV RNAs 1-4 (left) and its quantification histogram (right). Ethidium bromide staining of rRNAs (EB) was used as RNA loading control. Genotypes are indicated on the top of each northern blot. #1 and #2 correspond to the progeny of two different quadruple homozygous F2 siblings derived from the alkbh9b x te235 cross. Error bars show standard deviations. AU, arbitrary units. Different letters indicate statistical differences according to Fisher's Least Significant Difference (LSD) (p < 0.05).",
    "diseases": "Systemic infection"
  },
  {
    "caption": "C-F (C) Quantitative analysis of liver steatosis (μm2) (N=6 per group; P<0.0001), (D) gastrocnemius muscle cross sectional area (μm2)(CTRL N=7, BAM15 N=8), (E) pancreatic insulin positive area (% of total area) (N=6 per group; P=0.0420), (F) and β-cell mass (N=4 per group; P=0.0005).",
    "diseases": "liver steatosis"
  },
  {
    "caption": "B. Survival curves of Bcs1l homozygotes without (GRAC) and with (GROX) alternative oxidase (AOX) expression (n=18-21/group). The median survival of GRAC mice was 210 days and of GROX mice 589 days with no gender difference Statistics: The survival data was analyzed using Log-rank (Mantel-Cox) test (p<0.0001)",
    "diseases": "GRAC"
  },
  {
    "caption": "Sirius Red staining (C) for fibrosis in liver, heart and kidney at P200",
    "diseases": "fibrosis"
  },
  {
    "caption": "(D) Quantification of fibrosis in myocardium, kidney cortex and liver (n=5-7) Bar graphs represent mean±SD Statistics: one-way ANOVA followed by Tukey"",
    "diseases": "fibrosis"
  },
  {
    "caption": "G. Expression of cardiac hypertrophy and fibrosis-associated genes in the pre-symptomatic (P150) heart (n=6/group) Bar graphs represent mean±SD Statistics: one-way ANOVA followed by Tukey"",
    "diseases": "cardiac hypertrophy, fibrosis"
  },
  {
    "caption": "A. Significantly altered metabolites (FDR<0.2; P<0.05, n=5/group) in presymptomatic (P150) heart tissue of GRAC (red) and GROX (green) mice Bar graph represent mean±S Statistics for graph one-way ANOVA followed by Tukey"s",
    "diseases": "GRAC"
  },
  {
    "caption": "B. Significantly altered metabolites (FDR<0.2; P<0.05, n=5/group) in liver tissue of GRAC (red) and GROX (green) mice Bar graph represent mean±S Statistics for graph one-way ANOVA followed by Tukey"s",
    "diseases": "GRAC"
  },
  {
    "caption": "Periodic acid-Schiff (PAS) staining of paraffin-embedded kidney sections of Prdm1ihCd2/+ and wild-type mice at 12 months of age. The mean score of kidney pathology was determined for each mouse by evaluating 40 individual glomeruli to assess the severity of glomerulonephritis as shown in Table EV2 and described in the Appendix Supplementary Methods. Representative pictures of glomeruli of Prdm1ihCd2/+ kidneys with different pathology scores are shown to the left, and dot plots with average scores for male and female mice (Table EV2) are shown to the right. Arrows denote intracapillary hyaline "thrombi", asterisks indicate mesangial sclerosis with obscured capillary loops, and the arrowhead points to an obsolescent glomerulus with collapse of the glomerular tuft architecture. Statistical data (A,C) are shown as mean value with SEM and were analyzed by the Mann-Whitney test (A) or the Student"s t-test (C); *P < 0.05, **P < 0.01, ***P < 0.001. Each dot correspon",
    "diseases": "mesangial sclerosis, glomerulonephritis"
  },
  {
    "caption": "IE were isolated and binding to HBMEC and HDMEC was determined under flow conditions. Number of IE bound per mm2 EC surface was calculated and shown is the mean ± 95% CI for 26 CM and 33 UM cases on HBMEC and 21 CM and 35 UM cases on HDMEC on a log scale. P-value was calculated by two-tailed unpaired t-test. The dotted line is 20 IE/mm2, the cut-off value for inclusion of the inhibition data.",
    "diseases": "CM, UM"
  },
  {
    "caption": "A. Representative images of brain  acute bleedings detected through hemoglobin IHC  in P30 Ctrl and Poly I:C MIA male offspring. Scale bar = 500 µm, enlargement scale bar = 50 µm. B. Representative images of brain  acute bleedings  detected through hemoglobin IHC  in P90 Ctrl and Poly I:C MIA male offspring. Scale bar = 500 µm, enlargement scale bar = 50 µm. C. Quantification of hemoglobin   (Hb) positive signal in the brain  of P30 and P90 male MIA offspring, expressed as percentage of the area. P30 Ctrl = 0.00 ± 0.00, P30  Poly I:C  = 0.01 ± 0.00, P90 Ctrl = 0.00 ± 0.00, P90  Poly I:C = 0.01 ± 0.00. Mann-Whitney U test, ***p < .001. Data information: Ctrl males = white bars with blu border. Poly I:C males = blu bars with blu border. Numbers in bars indicate the number of animals (N) and slices (n). Bars represent mean ± SEM.",
    "diseases": "bleedings"
  },
  {
    "caption": "A, Representative  immunofluorescence staining  of normal, tumor, and residual 3D  organoids grown from primary mammary cells  of a preclinical mouse model of breast cancer (Methods). Similar morphology of normal and residual organoids shown on the left with polarity markers ITGA6 (red), ZO-1 (green), GM-130  (magenta); DAPI (blue). Right: human MYC  oncoprotein (green) is expressed only in tumor cells,  CDH1 (red). Scale bar: 25 μm. Data information: Number of replicates corresponds to individual mice used to derive organoids.",
    "diseases": "breast cancer"
  },
  {
    "caption": "Validation of candidate gene expression in unique series of 39 RCC patients (GSE29609), where microvascular invasion (MVI) and renal vein involvement (RV) are specifically annotated. Progressive invasion relates to the three progressive degrees of invasion toward the vena cava in this series: 1st, no invasion; 2nd, microvascular invasion; and 3rd, renal vein involvement. The gene expression is shown for each variable and condition in box plots representing median, Q1/Q3 and max/min value whiskers, *p < 0.05 **p < 0.01 by Mann-Whitney test.",
    "diseases": "RCC"
  },
  {
    "caption": "F) Representation of ALDH1A3 score (0=absent, 1=low, 2=high expression) on pre-treatment samples of pro-aggressive and non-pro-aggressive ccRCC patients described above. n=15, Chi-square test for independence p=0.015, and Chi-square test for trend p=0.030 (*).",
    "diseases": "ccRCC"
  },
  {
    "caption": "Ala/Phe substitutions of aa 239-244 were introduced in the NCT ectodomain to evaluate the role of this region in the regulation of GSEC processivity. Aβ38, Aβ40, and Aβ42 levels present in the conditioned medium collected from KO NCT MEF cells rescued with WT or respective mutant NCT GSECs and transiently expressing with APPC99 were quantified by ELISA. Aβ(38+40)/42 ratio was calculated to determine GSEC processivity towards APPC99. DKO PSEN1/PSEN2 MEFs rescued with the indicated FAD PSEN1 mutant and transduced with APPC99 were used as references.",
    "diseases": "FAD"
  },
  {
    "caption": "(E) Schematic illustration of the hCST collateral into the cervical cord and confocal images of hCST collaterals (green), stained for vGlut (red) and vGAT (blue) 21 days following spinal cord injury. Insets represent 3D views generated in Imaris of the deconvolved confocal image. (F) Quantification of bouton density and characterization of bouton between control and FGF22 overexpressing mice (n = 4-5 mice per group). (",
    "diseases": "spinal cord injury"
  },
  {
    "caption": "(C) Schematic illustration of the hCST collateral exiting into the cervical cord and confocal images showing exiting hCST collaterals in control (left panel) and FGF22 treated (right panel) mice and quantification of the number of hCST collaterals that enter the cervical grey matter 3 weeks following spinal cord injury. (n = 6 mice per group).",
    "diseases": "spinal cord injury"
  },
  {
    "caption": "(E) Schematic illustration of the boutons on cervical hCST collateral and confocal images showing putative synaptic boutons (arrows) on newly formed cervical hCST collaterals at 3 weeks following spinal cord injury in a FGF22 (right) and a control (left) mice. Quantification of bouton density in control and FGF22 treated mice. (n = 6 mice per group",
    "diseases": "spinal cord injury"
  },
  {
    "caption": "(C) Timeline of the experiment with FGF22 injection right after the onset of the spinal cord lesion (top). Quantification of the functional recovery in the regular (middle) and irregular (bottom) ladder rung test in controls (grey) and FGF22 (orange) treated mice at baseline, at 3 days post injury ("3dpi"), 14dpi and 21dpi after spinal cord injury. (n = 9-10 mice per group). (D) Timeline of the experiment with FGF22 injection 24hrs after the onset of the spinal cord lesion (top). Quantification of the functional recovery in the regular (middle) and irregular (bottom) ladder rung test in control (grey) and FGF22 (orange) treated mice at baseline, at 3 days post injury ("3dpi" or 2 days "2dpi for the late treatment), 14dpi and 21dpi after spinal cord injury. (n = 9-10 per group). (E) Timeline of the experiment with FGF22 injection 5 days after the onset of the spinal cord lesion (top). Quantification of the functional recovery in the regular (middle) and irregular (bottom) ladder rung test in control (grey) and FGF22 (orange) treated mice at baseline, at 3 days post injury ("3dpi"), 14dpi and 21dpi after spinal cord injury. (n = 9-10 per group).). (F",
    "diseases": "spinal cord injury, spinal cord lesion"
  },
  {
    "caption": "A Ratio of toxicity and  viability  determined in pancreatic cancer-derived  organoids  from two  patients  ((left) PDO-42 and (right) PDO-48) treated as indicated for 3 (PDO-42) or 5 (PDO-48) days. Significant differences are shown for the comparison between single and combined drug treatments as indicated (NEN 1.2 µM or 2.5 µM, Amitriptyline (Ami, A), Imipramine  (Imi, I), Desipramine (Desi, D), each 30 µM, Clomipramine (Clomi, C) 20 µM). Data information: data are presented as mean (SD) (N=3) and were analyzed by a one-way ANOVA with Tukey post-hoc test.* p< 0.05; ** p< 0.01;*** p< 0.001; **** p < 0.0001.",
    "diseases": "pancreatic cancer"
  },
  {
    "caption": "B Ratio of  toxicity and viability determined in pancreatic cancer-derived   organoids  from two patients ((left) PDO-42 and (right) PDO-48) treated as indicated for 3 (PDO-42) or 5 (PDO-48) days. Significant differences are shown for the comparison between drug treatments as indicated to the control condition (NEN (N) 1.2 µM or 2.5 µM, Amitriptyline (A),  Imipramine (I) 20 µM, Paclitaxel  (Pacli), 2, 20 or 200nM). As references for sensitization effects to standard chemotherapy, the bars showing single Paclitaxel  treatments using the indicated concentrations are highlighted in blue. Bars for controls (Ctrl), Paclitaxel  (Pacli), NEN (N) alone and combined NEN+Paclitaxel treatment are identical in the individual graphs for comparison to combinations with the respective TCA drugs as indicated. Data information: data are presented as mean (SD) (N=3) and were analyzed by a one-way ANOVA with Tukey post-hoc test.* p< 0.05; ** p< 0.01;*** p< 0.001; **** p < 0.0001.",
    "diseases": "pancreatic cancer"
  },
  {
    "caption": "(A) Representative whole mount images of WT, Sas4cKO, Sas4cKO;Trp53bp1-/-, Sas4cKO;Usp28cKO animals at P14. Arrows indicate the cerebellar hypoplasia resulting from the lack of primary cilia. Scale bar = 0.2 cm. (B) Telencephalon area of P14 brains of the indicated genotypes. WT littermates N = 8, Sas4cKO N = 7, Sas4cKO;Trp53bp1-/- N = 6, Sas4cKO;Usp28cKO N = 10, Sas4cKO;Trp53-/- N = 5; one-way ANOVA with post-hoc analysis. WT and Sas4cKO data are from Figure 1D and shown alongside for comparison. Black circles represent Nestin-Cre+ animals. (C) Cortical thickness of P14 brains of the indicated genotypes. WT littermates N = 4, Sas4cKO N = 4, Sas4cKO;Trp53bp1-/- N = 4, Sas4cKO;Usp28cKO N = 4, Sas4cKO;Trp53-/- N = 4; one-way ANOVA with post-hoc analysis. WT and Sas4cKO data are from Figure EV1D and shown alongside for comparison. Black circles represent Nestin-Cre+ animals.",
    "diseases": "cerebellar hypoplasia"
  },
  {
    "caption": "(A) Plot from flow cytometry analysis of neutrophils in forepaw skin from 10-wk-old WT and RDEB mice. (B) Bar graph of flow cytometry analyses as in A of neutrophils in forepaw skin  of newborn, 4-wk-old and 10-wk-old WT and RDEB mice. Plotted as fold increase compared to mean of age-matched WT paws; replicates per age = 5-6. ( Data information: Individual data points, mean ± S.E.M are shown. The data were analyzed by one-way ANOVA with Tukey's correction P values < 0.05 are considered significant.",
    "diseases": "RDEB"
  },
  {
    "caption": "(C) Plot from flow cytometry analysis of CD38+ and Egr2+ macrophages in  forepaw skin from 10-wk-old WT and  RDEB mice. (D) Bar graph of flow cytometry analyses as in C of  inflammatory macrophages (CD38+Egr2-) or tissue-repair macrophages (CD38-Egr2+) macrophages in  forepaw skin of newborn, 4-wk-old and 10-wk-old WT and RDEB mice. Plotted as fold increase compared to mean of age-matched WT paws; replicates per age; n = 5-6 (CD38+Egr2-); n = 4-5 (CD38-Egr2+). ( Data information: Individual data points, mean ± S.E.M are shown. The data were analyzed by one-way ANOVA with Tukey's correction P values < 0.05 are considered significant.",
    "diseases": "RDEB"
  },
  {
    "caption": "(A-D)  Skin from healthy young (3-8 years old) and adult  donors ( > 25 years old) and from donors with RDEB with different stages of fibrosis - early  (0-3 years old), mild (6-10 years old) and advanced ( > 15 years old) - stained for CD68 (green), CD3ε (green), periostin (green) and tenascin-C (red). Nuclei were counterstained with DAPI (blue). A and B, scale bar = 50 μm; C and D, scale bar = 100 μm. The bar graphs at the right to the stained sections, represent for A and B quantification of the number positive cells per mm2 analyzed from 3 donors for each group and for C and D, the mean intensity of staining  from 3-6 donors per group. Individual data points, mean ± S.E.M are shown. The data were analyzed by one-way ANOVA with Tukey's correction. P values < 0.05 are considered significant.",
    "diseases": "fibrosis, RDEB"
  },
  {
    "caption": "(A)  Human dermal RDEBF treated daily with 10 μM LY2109761 (LY) (TGF-β Receptor I/II inhibitor‎), 10 μM 1D11 (neutralizing antibody to all TGF-βs) 100 nM Ang-(1-7), or 10 μM  losartan (AT1R antagonist). After five days of treatment cell and matrix lysates were extracted and analyzed by western blotting for the indicated proteins, THBS-1, thrombospondin-1, β-tubulin was used as loading control. (B) Densitometric  quantification of blots as in A. The abundance was normalized to  β-tubulin and then expressed as % of untreated (-). P values are shown; the data were analyzed with one-way ANOVA with Dunnett's correction (n = 5 biological replicates). ( Data information: P values < 0.05 are considered significant and shown, ns = not significant. individual data points, mean ± S.E.M are shown.",
    "diseases": "RDEBF"
  },
  {
    "caption": "(F)  Western blots of fibroblast lysates from co-cultures as described in E. The blots  were probed with antibodies detecting fibronectin, thrombospondin-1 (THBS-1) and pSMAD-2/3. β-tubulin was used as loading control. (G) Densitometric quantification of western blots of fibroblast  cell and matrix lysates as shown in F from multiple independent experiments, n = 4 -5 using cells from 4 donors with  RDEB. The abundance was normalized to  β-tubulin then and then expressed as % of both untreated. The data were analyzed by one-way ANOVA with Tukey's correction. Data information: P values < 0.05 are considered significant and shown, ns = not significant. For B, D and G individual data points, mean ± S.E.M are shown. ",
    "diseases": "RDEB"
  },
  {
    "caption": "(C) Photos of left and right  forepaws of RDEB mice before and after 7 weeks of daily injections with 0.1, 1.0 mg/kg Ang-(1-7)  or PBS. (D) Plot of numbers of toes  lost during the 7-week observation period, data tested with Kruskal-Wallis test, P values indicated, n= 20-24  paws as indicated in the figure. Median and range are shown. ( ",
    "diseases": "RDEB"
  },
  {
    "caption": "(A)  Haemotoxylin and Eosin (H&E) staining  of  toes from forepaws  from WT and  RDEB mice treated with daily injections of 0.1, 1.0 mg/kg  Ang-(1-7) or PBS for seven weeks. Inflammatory cells are elevated in the toes  from the PBS and the two Ang-(1-7) treated RDEB mice compared to the WT counterpart. Scale bar = 100 μm. Data information scale bar = 100 μm.",
    "diseases": "RDEB"
  },
  {
    "caption": "(B-D)  Flow cytometry analysis of the number  of CD45 positive cells (B), percentage of neutrophils (C) and of inflammatory macrophages (CD38+Egr2-) and tissue-repair macrophages (CD38-Egr2+) (D) in  forepaw skin  of RDEB mice treated as in A. Data information: individual data points, mean ± S.E.M are shown. The data were analyzed by one-way ANOVA with Tukey's correction, P values < 0.05 are considered significant and shown; n = 5-14 biological replicates.",
    "diseases": "RDEB"
  },
  {
    "caption": "(A) Picrosirius red staining  visualized under polarized light and Elastica van Gieson (EvG)  staining) of  forepaw toes from 12-wk-old WT or RDEB mice treated with daily injections of 0.1, 1.0 mg/kg Ang-(1-7) or PBS for seven weeks. Note the reduced signal for picrosirus red  in  RDEB mice treated with 0.1 mg/kg Ang-(1-7) indicating less parallel alignment of and/or thinner collagen fibrils, and additionally the more organized and less disrupted appearance of elastic fibers (black in the  EvG staining). (B) Quantification of picrosirius red stained forepaws visualized as in A. A digital threshold was applied to the red channel before quantification. The data were analyzed by one-way ANOVA with Tukey's correction, P values < 0.05 are considered significant; n = 10-15. Individual data points, mean ± S.E.M are shown. ( Data information scale bar = 100 μm",
    "diseases": "RDEB"
  },
  {
    "caption": "(C) Western blotting for the indicated proteins on tissue lysates from forepaws from RDEB mice treated as in A. α-SMA, α-smooth muscle actin; Thbs-1, thrombospondin-1. Data information: β- actin  or β-tubulin was used as loading control",
    "diseases": "RDEB"
  },
  {
    "caption": "(D) Dermal β-arrestin-1/2 (red) and NFκB (red) staining  in forepaws from WT and RDEB mice treated as in A. Nuclei counterstained  with DAPI (blue). Data information scale bar = 20 μm.",
    "diseases": "RDEB"
  },
  {
    "caption": "(A) Colocalization  of LacCer  and LysoTracker  (LyTr) in different CTR  and LSD patient fibroblasts. Mander´s coefficients were calculated using the Fiji JACoP plugin. Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells); one-way ANOVA, post hoc Bonferroni's (A, multiple comparisons test. *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "diseases": "LSD"
  },
  {
    "caption": "(B-C) Confocal  images (B) and statistical analysis (C) showing colocalization  of LacCer  and LyTr  in human  CTR and MLIV fibroblasts, treated with TPC2-A1-P  (30 µM, 16h). (D-E) Confocal  images (D) and statistical analysis (E) showing colocalization   of LacCer  and LyTr  in human  CTR and NPC1 fibroblasts, treated with TPC2-A1-P (30 µM, 48h). Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells); one-way ANOVA, post hoc Bonferroni's C, E, multiple comparisons test. *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "diseases": "MLIV, NPC1"
  },
  {
    "caption": "(F-G) Confocal  images and statistical analysis showing LacCer/LyTr colocalization  in MLIV patient fibroblasts  which were mock-electroporated and treated with DMSO  or electroporated with a gain-of-function hTPC2(M484L/G734E):mCherry  TOPO 3.1 vector and treated with either DMSO  or TPC2-A1-P (30 µM, 16h). Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells); one-way ANOVA, post hoc Bonferroni's G, multiple comparisons test. *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "diseases": "MLIV"
  },
  {
    "caption": "(J-K) Confocal  images (J) and statistical analysis (K) of NPC1 patient fibroblasts  treated with 50 nM mock siRNA (siSCR) or siRNA targeting TPCN2  (siTPC2) for 72 hours. Cells were then treated with DMSO  or  TPC2-A1-P (30 µM). Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells); one-way ANOVA, Tukey's (K) multiple comparisons test. *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "diseases": "NPC1"
  },
  {
    "caption": "(A-B) Confocal  images (A) and statistical analysis (B) of cholesterol  accumulation in human  CTR, MLIV, JNCL, and NPC1 fibroblasts. Cholesterol  accumulation was evident for NPC1  and MLIV fibroblasts, but not for JNCL fibroblasts. The images show filipin staining  to visualize cholesterol  accumulation and TO-PRO3 as nuclear staining. Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells); one-way ANOVA, post hoc Bonferroni's multiple comparisons test (B, *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "diseases": "MLIV, JNCL, NPC1"
  },
  {
    "caption": "(C-D) TPC2-A1-P (30 µM, 48h) rescued NPC1  and MLIV cholesterol  accumulation. Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells); one-way ANOVA, post hoc Bonferroni's multiple comparisons test D, *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "diseases": "MLIV, NPC1"
  },
  {
    "caption": "Confocal  images (E-F) of MLIV patient fibroblasts  mock-electroporated and treated with DMSO  or electroporated with a gain-of-function hTPC2(M484L/G734E):mCherry  TOPO 3.1 vector (white arrow heads) and treated with either DMSO  or TPC2-A1-P (30 µM, 48h).",
    "diseases": "MLIV"
  },
  {
    "caption": "statistical analysis (G) of MLIV patient fibroblasts  mock-electroporated and treated with DMSO  or electroporated with a gain-of-function hTPC2(M484L/G734E):mCherry  TOPO 3.1 vector (white arrow heads) and treated with either DMSO  or TPC2-A1-P  (30 µM, 48h). Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells); one-way ANOVA, post hoc Bonferroni's multiple comparisons test *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "diseases": "MLIV"
  },
  {
    "caption": "Confocal  images and statistical analysis of human NPC1 patient fibroblasts  treated with 50 nM mock siRNA (siSCR) or siRNA targeting TPCN2  (siTPC2) for 72 hours. Cells were then treated with DMSO  or TPC2-A1-P (30 µM). Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells); two-tailed Student's t-test K). *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "diseases": "NPC1"
  },
  {
    "caption": "Statistics (L) of human  CTR, MLIV, JNCL, and NPC1 fibroblasts. Effect of the treatment with TPC2  agonist (30 µM, 48h) was examined in NPC1  and MLIV  cells. Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells); one-way ANOVA, post hoc Bonferroni's multiple comparisons test , L) *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "diseases": "MLIV, JNCL, NPC1"
  },
  {
    "caption": "electron microscopy  images (M) of human  CTR, MLIV, JNCL, and NPC1 fibroblasts. Effect of the treatment with TPC2  agonist (30 µM, 48h) was examined in NPC1  and MLIV  cells.",
    "diseases": "MLIV, JNCL, NPC1"
  },
  {
    "caption": "(A) Confocal  images of CTR and JNCL fibroblasts. Images show LAMP1 staining  and autofluorescence at 405 and 488 nm excitation wavelength, respectively, corresponding to the lipofuscin  autofluorescence spectrum. Cells were treated with DMSO  or TPC2-A1-P  (30 µM) following cell cycle arrest (2h mitomycin C treatment). (B) Confocal  images showing no autofluorescence signal at 594 nm excitation wavelength (used for LAMP1 staining).",
    "diseases": "JNCL"
  },
  {
    "caption": "Mean intensity of shigatoxin   (STX) in CTR and JNCL fibroblasts. Cells were treated with DMSO  or TPC2-A1-P (30 µM) after cell cycle arrest. Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells; one-way ANOVA, post hoc Bonferroni's multiple comparisons test. **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "diseases": "JNCL"
  },
  {
    "caption": "Confocal  images of Gb3  accumulation stained  with shigatoxin   (STX) in CTR and JNCL fibroblasts. Cells were treated with DMSO  or TPC2-A1-P (30 µM) after cell cycle arrest.",
    "diseases": "JNCL"
  },
  {
    "caption": "Cortical neurons were differentiated from iPSCs, generating  lysosomal storage disease neurons  and isogenic controls. (C-D) Western blot  analysis of  cathepsin B (CtsB) in CTR and MCOLN1IVS3-2A>G neurons  treated with TPC2-A1-P (30 µM) or DMSO. Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells, obtained from at least three distinct neuronal  differentiations); two-tailed Student's t-test (C). **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "diseases": "lysosomal storage disease"
  },
  {
    "caption": "Cortical neurons  were differentiated from iPSCs, generating  lysosomal storage disease neurons  and isogenic controls. Cortical neurons were treated with compounds and acidic compartments stained  with LysoTracker (LyTr). Endolysosomal  expansion was observed in MCOLN1IVS3-2A>G, CLN3D416G and CLN3ΔEx4-7 neurons, which was ameliorated by TPC2-A1-P  (30 µM) treatment. Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells, obtained from at least three distinct neuronal  differentiations); one-way ANOVA, post hoc Tukey's multiple comparisons test **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "diseases": "lysosomal storage disease"
  },
  {
    "caption": "Cortical neurons were differentiated from iPSCs, generating lysosomal storage disease neurons  and isogenic controls. (H-I)  Electron microscopy analysis of neuronal rosettes (neuronal progenitor cells, NPC) treated with DMSO or TPC2-A1-P. TPC2-A1-P treatment significantly decreased the number of inclusion bodies (black arrow heads) in MCOLN1IVS3-2A>G. CLN3D416G and CLN3ΔEx4-7 lacked an appropriate assay window and showed no significant accumulation of  inclusion bodies. However, CLN3ΔEx4-7 NPC  showed significantly more mitochondria  with aberrant cristae  numbers (white arrow heads), a phenotype which was rescued by TPC2-A1-P (30 µM) treatment. Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells, obtained from at least three distinct neuronal  differentiations); one-way ANOVA, post hoc Tukey's multiple comparisons test **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "diseases": "lysosomal storage disease"
  },
  {
    "caption": "(A) Confocal  images of plasma membrane  (PM) LAMP1 immunofluorescence  in CTR fibroblasts. LAMP1  on the PM  is expressed as fold-change relative to DMSO-treated cells. (B) Statistical analysis of lysosomal exocytosis  data as shown in A. (C) Lysosomal exocytosis  in CTR, MLIV, NPC1  and JNCL human fibroblasts. PM-localized LAMP1  was measured by flow cytometry, expressed as % of CTR DMSO-treated cells. Ionomycin  in A-C (4 µM; 10 min treatment) was used as positive control. TPC2-A1-P  and ML-SA1  (30 µM, each; 90 min treatment in A-C). Statistics (B-C): Shown are mean values ± SEM. n > 3 for each tested condition (in B each dot represents an imaged frame containing several cells, in C each dot is the mean FITC  intensity value expressed as percentage obtained from at least 1*104 events); two-way ANOVA, post hoc Dunnett's (B) or Tukey's (C) multiple comparisons test, *p-value < 0.05; ***p-value < 0.001; ****p-value < 0.0001.",
    "diseases": "MLIV, JNCL, NPC1"
  },
  {
    "caption": "Immunoblot  analysis of endogenous LC3  (LC3I-II) following TPC2-A1-P or ML-SA1 (30 µM, each) treatment, alone or with BafA1, under fed  (complete media) or starvation  (HBSS) conditions in CTR, MLIV  and NPC1 patientfibroblasts.",
    "diseases": "MLIV, NPC1"
  },
  {
    "caption": "analysis of endogenous LC3 following  TPC2-A1-P  or ML-SA1  (30 µM, each) treatment, alone or with BafA1, under fed  (complete media) or starvation  (HBSS) conditions in CTR, MLIV and NPC1 patientfibroblasts. Graphs show densitometry  of LC3II  bands normalized to actin. Statistics (G, Shown are mean values ± SD. n = 3 lysates per condition pooled from 3 independent experiments; two-tailed Student's t-test. *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001.",
    "diseases": "MLIV, NPC1"
  },
  {
    "caption": "(H) Immunoblot  analysis of endogenous LC3 (LC3I-II) following  TPC2-A1-P (30 µM) or DMSO  treatment, under fed  (complete Neurobasal/B27) or starvation  (DMEM/F12 free) conditions in CTR and MLIV iPSC  derived cortical neurons. Graphs show densitometry  of LC3II  bands normalized to actin. Statistics H, Shown are mean values ± SD. n = 3 lysates per condition pooled from 3 independent experiments; two-tailed Student's t-test. *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001.",
    "diseases": "MLIV"
  },
  {
    "caption": "Immunoblot  analysis of endogenous SQSTM1  (P62) upon  TPC2-A1-P or ML-SA1  (30 µM, each) treatment, under fed  (complete media) or starvation  (HBSS) conditions in CTR, MLIV  and NPC1 patient fibroblasts. Statistics J): Shown are mean values ± SD. n = 3 lysates per condition pooled from 3 independent experiments; two-tailed Student's t-test. *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001.",
    "diseases": "MLIV, NPC1"
  },
  {
    "caption": "Human osteosarcoma U2OS cells were treated with dactinomycin (DACT) at 0.5 or 1 µM, or with mitoxantrone (MTX) between 1 and 6 µM as positive control Human osteosarcoma U2OS stably expressing CALR-GFP and H2B-RFP were treated as described above and images were acquired once per hour for 12 h (A). For one representative experiment among three, the mean ± SEM of the average area of high CALR dots (normalized to the control at each timepoint) of quadruplicates is shown (B). Values are depicted as the area under the curve ± SD of triplicates",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "Human osteosarcoma U2OS cells were treated with dactinomycin (DACT) at 0.5 or 1 µM, or with mitoxantrone (MTX) between 1 and 6 µM as positive control Treated U2OS cells stably expressing HMGB1-GFP and H2B-RFP images were acquired every hour for 24 h (D). For one representative experiment among three, the mean ± SEM of the green fluorescence intensity in the nucleus (normalized to the control at each timepoint) of quadruplicates is depicted (E). For each cell, the speed of nuclear release (difference of HMGB1 nuclear green fluorescence intensity between two time points) was calculated. Values are depicted as the average speed of the nuclear release ± SD of quadruplicates",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "Human osteosarcoma U2OS cells were treated with dactinomycin (DACT) at 0.5 or 1 µM, or with mitoxantrone (MTX) between 1 and 6 µM as positive control U2OS cells were treated for 6, 12 or 24 h and ATP was stained with quinacrine (G). The number of quinacrine negative cells was assessed based on the distribution of cellular green fluorescence intensity in MTX versus control conditions. For one representative experiment among three the mean ± SD of quadruplicate assessments is shown",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "Human osteosarcoma U2OS cells were treated with dactinomycin (DACT) at 0.5 or 1 µM, or with mitoxantrone (MTX) between 1 and 6 µM as positive control U2OS wild-type cells were treated with MTX or DACT as described above for 6 h. Then medium was refreshed and 24 h later, type I interferon response was assessed by transferring the supernatant on HT29 MX1-GFP reporter cells lines cells for additional 48 h. Human type 1α interferon (IFNα1) was also added on the cells as an additional positive control. Images were acquired by fluorescence microscopy and the number of positive cells was assessed based on the distribution of cellular green fluorescence intensity in IFNα1 versus control conditions (I). The percentage of MX1 positive cells was calculated and the mean ± SEM of five independent experiments is depicted",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "Human osteosarcoma U2OS cells were treated with dactinomycin (DACT) at 0.5 or 1 µM, or with mitoxantrone (MTX) between 1 and 6 µM as positive control U2OS wild-type cells were treated as mentioned above for 6 h and then medium was refreshed. Twenty-four hours later, cells were collected and surface-exposed calreticulin (CALR) was stained with an antibody specific for CALR. DAPI was used as an exclusion dye and cells were acquired by flow cytometry (K). The percentage of CALR+ cells among viable (DAPI-) ones are depicted. The mean ± SEM of six independent experiments is depicted",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "Human osteosarcoma U2OS cells were treated with dactinomycin (DACT) at 0.5 or 1 µM, or with mitoxantrone (MTX) between 1 and 6 µM as positive control U2OS cells were treated as described above for 24 h and the concentration of HMGB1 released in the supernatant was quantified with an ELISA kit, then normalized to control. The mean ± SEM of four independent experiments is shown.",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "Human osteosarcoma U2OS cells were treated with dactinomycin (DACT) at 0.5 or 1 µM, or with mitoxantrone (MTX) between 1 and 6 µM as positive control U2OS were treated as described above for 24 h. Concentration of secreted ATP in the supernatant was quantified with a luciferase-based bioluminescence kit. The mean ± SD of quadruplicates from one representative among three experiments is depicted.",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "Human osteosarcoma U2OS cells were treated with different concentrations of dactinomycin (DACT) (0.25, 0.5 or 1 µM) for 6 h. Thapsigargin (THAPS) at 3 µM was used as a positive control. After fixation, cells were stained with phospho-eIF2α (Ser51) specific antibody followed by an AlexaFluor-647 secondary antibody, nuclei were counterstained with Hoechst 33342 and phosphorylation was assessed by fluorescence microscopy. Images were segmented, analyzed and the red cytoplasmic fluorescence intensity was measured. Images are shown for untreated control cells (Ctr), THAPS and DACT at 1 µM",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "Mouse fibrosarcoma MCA205 cells were stained with CellTracker Orange (CMTMR) and treated for 24 h with 1 µM dactinomycin (DACT) or 500 µM oxaliplatin (OXA) as a positive control. Then, untreated or dying MCA205 were co-cultured with differentiated bone marrow-derived dendritic cells (BMDCs) for 4 h at 37 °C or at 4 °C. Cells were collected and dendritic cells were stained with CD11c specific antibody before analysis by flow cytometry The percentage of CMTMR and CD11c double positive cells among all CD11c+ cells are indicated",
    "diseases": "fibrosarcoma"
  },
  {
    "caption": "1 x 106 mouse fibrosarcoma MCA205 cells were treated in vitro with 1 µM dactinomycin (DACT). Next, tumor size was measured regularly and individual tumor growths of DACT-vaccinated versus Ctr mice are depicted",
    "diseases": "fibrosarcoma"
  },
  {
    "caption": "1 x 106 mouse fibrosarcoma MCA205 cells were treated in vitro with 1 µM dactinomycin (DACT). Overall survival is depicted and p-values (*** p<0.001.) were calculated with a Log-Rank test",
    "diseases": "fibrosarcoma"
  },
  {
    "caption": "3 x 105 mouse fibrosarcoma WEHI 164 cells were injected subcutaneously (s.c) into the flank of immunocompetent syngeneic Balb/c mice When tumors became palpable, the mice were injected intraperitoneally (i.p.) with injectable solution (Ctr) or with 0.5 mg/kg dactinomycin (DACT). A second injection of chemotherapy was performed four days later. Tumor size was assessed regularly and individual tumor growth curves of DACT versus Ctr",
    "diseases": "fibrosarcoma"
  },
  {
    "caption": "3 x 105 mouse fibrosarcoma WEHI 164 cells were injected subcutaneously (s.c) into the flank of immunocompetent syngeneic Balb/c mice When tumors became palpable, the mice were injected intraperitoneally (i.p.) with injectable solution (Ctr) or with 0.5 mg/kg dactinomycin (DACT). A second injection of chemotherapy was performed four days later. DACT + anti-CD4/CD8 versus anti-CD-4/anti-CD-8 Mean tumor area for each group was calculated and significances were tested using a type II ANOVA test Overall survival is depicted and p-values were calculated with a Log-Rank test Stars indicate the p-values of each treatment versus Ctr and hashes indicate the p-values of the DACT + anti-CD-4/anti-CD-8 versus DACT alone",
    "diseases": "fibrosarcoma"
  },
  {
    "caption": "3 x 105 mouse fibrosarcoma WEHI 164 cells were injected subcutaneously (s.c) into the flank of immunocompetent syngeneic Balb/c mice When tumors became palpable, the mice were injected intraperitoneally (i.p.) with injectable solution (Ctr) or with 0.5 mg/kg dactinomycin (DACT). A second injection of chemotherapy was performed four days later. DACT + anti-PD-1 versus anti-PD-1 are depicted. Overall survival is depicted and p-values were calculated with a Log-Rank test Stars indicate the p-values of each treatment versus Ctr and of DACT + anti-PD-1 versus anti-PD-1 alone",
    "diseases": "fibrosarcoma"
  },
  {
    "caption": "3 x 105 mouse fibrosarcoma WEHI 164 cells were injected subcutaneously (s.c) into the flank of immunocompetent syngeneic Balb/c mice When tumors became palpable, the mice were injected intraperitoneally (i.p.) with injectable solution (Ctr) or with 0.5 mg/kg dactinomycin (DACT). A second injection of chemotherapy was performed four days later. Five naïve mice or the eleven mice that were cured by treatment with DACT alone or in combination with PD-1 blockade were (re)challenged with WEHI 164 cells, and individual tumor growths (I, J), as well as overall survival (*** p<0.001, Log-Rank test) (K), were monitored.",
    "diseases": "fibrosarcoma"
  },
  {
    "caption": "Mice bearing WEHI 164 sarcomas were treated by systemic (intraperitoneal, i.p.) injections of DACT or PBS as a control (Ctr), and tumor were excised 9 days later for the quantitation of mRNA coding for IFNγ Two independent experiments were conducted with a total of 22 mice in the Ctr group and 23 mice in the DACT-treated group, with each data point indicating one tumor. The cycle threshold of the qRT-PCR of IFNγ was normalized to the one of the housekeeping gene peptidylpropyl isomerase A (Ppia) in each mouse and results are shown normalized with respect to controls as a dot plot depicting mean ± SD . The p-value (* p<0.05) was calculated by means of a Student's t test (B).",
    "diseases": "sarcomas"
  },
  {
    "caption": "Balb/c mice with palpable WEHI 164 sarcomas (n=7 mice in Ctr and anti-IFNγ groups; n=8 mice in DACT and DACT+anti-IFNγ groups) received two injections of DACT-based chemotherapy (0.5 mg/kg) as well as multiple injections (3 times per week) of neutralizing IFNγ-specific antibody (C). Tumor growth curves are shown for individual mice (D) and as means (E). Statistical difference between DACT-treated tumors and respective controls, which was calculated with a type II ANOVA (* p<0.05), is lost upon IFNγ neutralization (E). Overall survival of mice is also indicated with statistics to respective controls calculated with a Log-Rank test (* p<0.05) (F).",
    "diseases": "sarcomas"
  },
  {
    "caption": "Human osteosarcoma U2OS cells were pre-treated with dactinomycin (DACT), bortezomib (BTZ), daunorubicin (DAUN), docetaxel (DOC), doxorubicin (DOXO), epirubicin (EPI), mitoxantrone (MTX), paclitaxel (PACL), vinblastine (VB) and vincristine (VC) at 0.5, 1 and 5 µM ; with cisplatin (CDDP) at 75, 150 and 300 µM, with oxaliplatin (OXA) at 250, 500 and 1000 µM and with crizotinib (CRIZ) at 10, 20 and 40 µM for 1.5 to 2.5 h and followed by an additional hour of treatment in the presence of 100 mM 5-ethynyl uridine (EU). After fixation cells were permeabilized and EU was stained with an AlexaFluor-488-coupled azide. Representative images are shown for each treatment (A). The EU intensity in the nucleus of each condition was ranked between the untreated control (Ctr, 0 % transcription inhibition) and the control that was not incubated with EU (corresponding to 100 % transcription inhibition) (B). Representative images of DACT 1 µM, BTZ 1 µM, CDDP 150 µM, CRIZ 20 µM, DAUN 0.5 µM, DOC 1 µM, DOXO 1 µM, EPI 1 µM, MTX 1 µM, OXA 500 µM, PACL 1 µM, VB 1 µM, VC 1 µM are shown",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "Human osteosarcoma U2OS cells were pre-treated with dactinomycin (DACT), bortezomib (BTZ), daunorubicin (DAUN), docetaxel (DOC), doxorubicin (DOXO), epirubicin (EPI), mitoxantrone (MTX), paclitaxel (PACL), vinblastine (VB) and vincristine (VC) at 0.5, 1 and 5 µM ; with cisplatin (CDDP) at 75, 150 and 300 µM, with oxaliplatin (OXA) at 250, 500 and 1000 µM and with crizotinib (CRIZ) at 10, 20 and 40 µM for 1.5 to 2.5 h Cells were treated for 2.5 h and before fixation and permeabilization. Then, cells were stained with a rabbit anti-fibrillarin antibody followed by a staining with an anti-rabbit AlexaFluor-647- or AlexaFluor-546-coupled secondary antibody as well as with a mouse anti-nucleolin antibody followed by a staining with an anti-mouse AlexaFluor-488-coupled secondary antibody. Then images were acquired and colocalization between both signals was assessed (C). The surface overlap coefficient (SOC) was calculated and ranked between the untreated control (Ctr) and the positive control (DACT) Representative images of DACT 1 µM, BTZ 1 µM, CDDP 150 µM, CRIZ 20 µM, DAUN 0.5 µM, DOC 1 µM, DOXO 1 µM, EPI 1 µM, MTX 1 µM, OXA 500 µM, PACL 1 µM, VB 1 µM, VC 1 µM are shown",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "Human osteosarcoma U2OS cells were pre-treated with dactinomycin (DACT), bortezomib (BTZ), daunorubicin (DAUN), docetaxel (DOC), doxorubicin (DOXO), epirubicin (EPI), mitoxantrone (MTX), paclitaxel (PACL), vinblastine (VB) and vincristine (VC) at 0.5, 1 and 5 µM ; with cisplatin (CDDP) at 75, 150 and 300 µM, with oxaliplatin (OXA) at 250, 500 and 1000 µM and with crizotinib (CRIZ) at 10, 20 and 40 µM for 1.5 to 2.5 h Cells were pre-treated overnight with the aforementioned compounds in complete medium followed by washout and treatment pursued in methionine-free medium for 30 min. Afterwards, the treatments were continued in methionine-free medium supplemented with 25 µM L-azidohomoalanine (AHA) for additional 1.5 h. AHA incorporation was detected after fixation, permeabilization and blocking by the addition of an AlexaFluor-488-coupled azide. Then images were acquired (E) and AHA intensity in the cells was ranked between the untreated control (Ctr, 0 % translation inhibition) and the untreated control without AHA (corresponding to 100 % translation inhibition) (F). Representative images of DACT 1 µM, BTZ 1 µM, CDDP 150 µM, CRIZ 20 µM, DAUN 0.5 µM, DOC 1 µM, DOXO 1 µM, EPI 1 µM, MTX 1 µM, OXA 500 µM, PACL 1 µM, VB 1 µM, VC 1 µM are shown",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "Representative image of tumor cells transduced with GCaMP6 (Left). Yellow arrows (mesenchymal cells), red arrows (epithelial cells), scale bar = 50μm. GCaMP6 mean fluorescent intensity (MFI) in ECADHIGH or ECADLOW cells cultured in indicated medium (0 Ca2+ or 2 Ca2+) for 1h (Right). Representative of 3 independent murine PDA cell lines run in triplicate. Statistical analysis by Student's unpaired t-test (*, p<0.05; non-significant (NS); ±SD).",
    "diseases": "PDA"
  },
  {
    "caption": "Flow cytometry analysis of ECADHIGH or ECADLOW cells loaded with Indo-1 and cultured in indicated medium (0 Ca2+ or 2 Ca2+) for 1h. Representative of 2 independent cell lines (n indicates the number of cells analyzed in each group, ECADHIGH 0 Ca2+ n=4963, ECADLOW 0 Ca2+ n=14, ECADHIGH 2 Ca2+ n=6575, ECADLOW 2 Ca2+ n=29). Representative of 2 independent murine PDA cell lines run in triplicate. Statistical analysis by Student's unpaired t-test (****, p<0.0001; non-significant (NS); ±SD).",
    "diseases": "PDA"
  },
  {
    "caption": "Representative flow cytometry analysis of surface ECAD (Left), MFI of surface ECAD (Middle), and percentage of surface ECAD negative cells (Right) in murine PDA cells, after treatment with DMSO, 2.5μM Ionomycin (IONO), and 10ng/ml TGFβ for 72h. Representative of 3 independent murine PDA cell lines run in triplicate. Statistical analysis by ANOVA (****, p<0.0001; non-significant (NS); ±SD).",
    "diseases": "PDA"
  },
  {
    "caption": "Top: Relative mRNA expression of Ecad after treatment with 2.5μM ionomycin or 10ng/ml TGFβ for denoted time. Bottom: Western blot analysis of total E-cadherin and Vimentin protein for denoted time. Experiment was run in duplicate with three different murine PDA cell lines. Statistical analysis by ANOVA (***, p<0.001; non-significant (NS); ±SEM).",
    "diseases": "PDA"
  },
  {
    "caption": "Normalized MFI of surface E-cadherin in PDA cells treated with DMSO, 2.5μM Ionomycin (IONO), and 10ng/ml TGFβ for 7 days, followed by withdrawal of Ionomycin or TGFβ for 7 days as indicated on the x-axis. Treated cells were analyzed at day 2, 3, and 7. Withdrawn cells were analyzed on days 1, 2, and 7. Experiment was performed in duplicate in two different murine PDA cell lines. Error bars indicate SD.",
    "diseases": "PDA"
  },
  {
    "caption": "Quantification of live cellular migration over 4h after treatment with DMSO, 2.5μM Ionomycin (IONO), or 10ng/ml TGFβ for 48hrs. (n=16 cells per condition. Experiment was run in triplicate in two murine PDA different cell lines) (Right). Quantification of transwell migration after treatment with DMSO, 2.5μM Ionomycin (IONO), or 10ng/ml TGFβ for 72h (n= 2 cell lines, 3 replicates per cell line with 3 20X images taken per transwell) (Left). Statistical analysis by ANOVA (*, p<0.05; ****, p<0.0001; non-significant (NS); ±SD).",
    "diseases": "PDA"
  },
  {
    "caption": "Schematic for RNA sequencing after EMT induction for 48h. Heatmap illustration of EMT related genes in three independent murine PDA cell lines, sequenced in duplicate, treated with DMSO, 2.5μM Ionomycin, or 10ng/ml TGFβ. Scale indicates Z-score.",
    "diseases": "PDA"
  },
  {
    "caption": "Fura-2 Ca2+ measurements after addition of 5μM CNO (Top) or 10μM ATP (Bottom) in murine PDA cells expressing a Gαq-DREADD. Blue or red line indicates average of n=22 cells. ±SD. Tracings are representative of experiments performed twice in 2 independent cell lines.",
    "diseases": "PDA"
  },
  {
    "caption": "MFI of surface E-cadherin in CnB knockout lines after 48h treatment with DMSO, 2.5μM ionomycin, or 10ng/ml TGFβ. Experiment was repeated in two different murine PDA cell lines in triplicate. Statistical analysis by ANOVA (***, p<0.001; ****, p<0.00001; ±SD).",
    "diseases": "PDA"
  },
  {
    "caption": "MFI of surface E-cadherin of murine PDA cells pretreated with 20μM W7 for 24h and then DMSO, 2.5μM ionomycin, or 20μM W7 with 2.5μM ionomycin for 24h. Experiment was repeated in two different murine PDA cell lines in triplicate. Statistical analysis by ANOVA (**, p<0.01; ***, p<0.001; non-significant (NS); ±SD).",
    "diseases": "PDA"
  },
  {
    "caption": "MFI of surface E-cadherin of shRNA non-targeting (shNT) (Left) or shCAMK2B (Right) after 48h treatment with DMSO, 2.5μM ionomycin, or 10ng/ml TGFβ. Experiment was repeated in two different murine PDA cell lines. Statistical analysis by ANOVA (***, p<0.001; ****, p<0.00001; ±SD).",
    "diseases": "PDA"
  },
  {
    "caption": "F: Quantification of the glomerulosclerosis score at time of (M0), or 12 months after (M12)  kidney transplantation from elderly donors in  patients displaying a negative (PAI-1-, n = 17) or positive (PAI-1+, n = 13) glomerular PAI-1 staining  at time of transplantation (M0). Data information: Data are means ± SEM. Statistical analysis: ANOVA followed by the Tukey-Kramer test",
    "diseases": "glomerulosclerosis"
  },
  {
    "caption": "H: Urinary PAI-1 measured by ELISA in a cohort of elderly patients with (n = 48) or without (n = 48) chronic kidney disease. Data information: Data are means ± SEM. Statistical analysis: t-student test",
    "diseases": "chronic kidney disease"
  },
  {
    "caption": "C. The anti RIF  and VER  antibodies bound to immunoprecipitated  wild-type SLC44A2  in lysates of the UM-SCC-47 human squamous cancer  cell line (exposure time 5 min).",
    "diseases": "squamous cancer"
  },
  {
    "caption": "A. CT angiography of the giant unruptured  intracranial aneurysm  on the right  posterior cerebellar artery (PCA, blue arrow).",
    "diseases": "intracranial aneurysm"
  },
  {
    "caption": "B. 3D volume rendered of multiple cerebral  aneurysms   on the right PCA  (a), on  right  posterior communicating artery (b), and on  right middle cerebral artery (c).",
    "diseases": "multiple cerebral  aneurysms"
  },
  {
    "caption": "C and D. Angiograms  before and after embolization  of the PCA aneurysm, respectively.",
    "diseases": "aneurysm"
  },
  {
    "caption": "E Cardiac troponin I (cTnI) levels as a marker of cardiomyocyte necrosis in the perfusate of isolated WT and Nox4KO hearts subjected to ischemia-reperfusion (I/R). XeC was added at a final concentration of 2 µmol/L prior to ischemia. n=6-7/group.",
    "diseases": "necrosis, I/R, ischemia, ischemia-reperfusion"
  },
  {
    "caption": "F Immunoblotting for the phosphorylation levels of Akt and InsP3R in crude mitochondrial fractions from WT and Nox4KO hearts after I/R. InsP3R was first immunopreciptated and then the precipitate was immunoblotted for total InsP3R and for the phosphorylated Akt-substrate motif RXRXX(pS/T) (p-InsP3R). Mean data shown to the right. n=3/group.",
    "diseases": "I/R"
  },
  {
    "caption": "G Cardiac left ventricular contractile function in isolated Langendorff-perfused WT and Nox4KO hearts at baseline (Basal) and then after I/R. Hearts were treated with XeC (1 μmol/L) or vehicle control for 20 min prior to ischemia. RPP, heart rate x left ventricular pressure product; DEVP, left ventricular developed pressure. n=6-7/group.",
    "diseases": "I/R, ischemia"
  },
  {
    "caption": "(A, B) B-ALL progression measured as (A) absolute  number  or (B) percentage of OFP+ cells in  peripheral blood  of transplanted mice  (mean ± SD, each dot represents an individual mouse, CTRL = 6 mice, IFNγ   = 10  mice; **** p ≤ 0.001, Two-Way ANOVA; mice in blue and yellow (B) were also analyzed by single-cell RNA sequencing",
    "diseases": "B-ALL"
  },
  {
    "caption": "(F, G) Percentage of  CD4+ and CD8+ cells within OFP- BM cells (F) and maturation state (G) of  CD8+ lymphocytes (CD62L-CD44-  double negative, CD62L-CD44+ effector memory, CD62L+CD44-  naive and CD62L+CD44+  central memory) in the BM immune infiltrate at 12- and 17-days after B-ALL (mean ± SD, each dot represents an individual mouse; ** p = 0.005, **** p ≤ 0.001, Two-Way ANOVA).",
    "diseases": "B-ALL"
  },
  {
    "caption": "(C)  B-ALL progression measured as absolute  number of OFP+ cells in the  peripheral  blood (mean ± SD, each dot represents an individual  mouse; * p = 0.0286 at day 10; p = 0.0174 at day 12; *** p = 0.0002; **** p ≤ 0.0001; Ordinary Two-Way ANOVA).",
    "diseases": "B-ALL"
  },
  {
    "caption": "(B, C) Violin plots show the distribution of IFNγ (B) and  MHC-II gene (C) signatures for each experimental condition, within each custom cell-type. Wilcox Rank Sum Test for IFNγ  signature, condition IFNγ d12 vs. CTR d12: B-ALL p= 2.68x10-19, B cells p=0.5, plasma cells p= 0.78; Wilcox Rank Sum Test for MHC-II  signature, condition  IFNγ d12 vs. CTRL d12: B-ALL p= 4.26x10-46, B cells p=1x10-9, plasma cells p= 0.32.",
    "diseases": "B-ALL"
  },
  {
    "caption": "(F)  Expression of Mki67  transcripts in  B-ALL cells from CTRL d12 and IFNγ  d12 conditions, extracted from the scRNAseq   dataset (**** p ≤ 0.0001, Welch's test).",
    "diseases": "B-ALL"
  },
  {
    "caption": "(I) Loss of  IFNγ  response over  time in B-ALL  cells from the IFNγ  group, potentially facilitated by reduced expression of  Ifngr1, Ifngr2, Jak1, Stat1 and  Irf1 (data extracted from the scRNAseq  dataset statistical analysis by Two-Way ANOVA).",
    "diseases": "B-ALL"
  },
  {
    "caption": " A, B Western blots for total EB2, pS223 and tubulin using protein lysates obtained from neurons derived from three patients with CDD and their related control. 1 = p.D135_F154del, male; 2 = p.R59X, male; 3 = p.R59X, female. Quantification of EB2 phosphorylation is normalized for total protein level. Student's t-test: n = 3 patients/controls. * p < 0.05, error bars are SEM ",
    "diseases": "CDD"
  },
  {
    "caption": " C Representative images of human iPSC-derived neurons co-stained with the neuronal dendrite marker MAP2, EB2 and EB2 pS223. EB2 phosphorylation is present in dendrites of control neurons but not in CDD neurons. Enlarged images of the boxed areas are shown on the right panel. Scale bar is 20 μm ",
    "diseases": "CDD"
  },
  {
    "caption": "(F) Immunostaining of HSP27 (white) in motor neurons differentiated from CMT patient-derived iPSCs that harbor the heterozygous P182L mutation reveals large, cytoplasmic aggregates (center and right panels). The control motor neurons that contain WT HSP27 do not show evidence of any aggregates. The nucleus is stained with Hoechst (blue). Scale bar, 10 µm.",
    "diseases": "CMT"
  },
  {
    "caption": "(G) Effect of NAT on growth of HCT116 colon cancer cells in mice (BALB/cSlc-nu/nu, 6 wks old, female) (data are means ± SEM; n=5). *P<0.05, **P<0.01 vs. without NAT. Test mice began to freely drink 5 mg/ml NAT solution for 7 d before transplantation of the tumor cells on day 0: the average amount of NAT consumed by each mouse was about 8.8 mg/day (0.4 - 0.5 g/kg weight/day). HCT116 cells (5.0 x 106 cells) were transplanted into each test mouse using a 1 ml syringe with a 27G needle.",
    "diseases": "colon cancer"
  },
  {
    "caption": " (A) Heat map analysis of serum GM3 species in various pathological phases: control (n=24), VFA (n=38), lipidemia (n=28), glycemia (n=15), and lipidemia + glycemia (n=17). Colors indicate fold change average of each species relative to control (defined as 1), as shown in key at right. Order of pathological phases corresponds to increments of HOMA-IR and serum CRP. ",
    "diseases": "glycemia, IR, lipidemia, VFA"
  },
  {
    "caption": " (B-D) Properties of various GM3 species as a function of pathological phases: control (n=24), VFA (n=38), lipidemia (n=28), glycemia (n=15), and lipidemia + glycemia (n=17). Data shown are relative abundances of total LCFA species (16:0, 18:0, 20:0) (B), total VLCFA species (22:0, 23:0, 24:0, h24:0) (C), and total unsaturated VLCFA species (22:1, 24:1, h24:1) (D) relative to total of ten major GM3 species (defined as 1) in each subject. ",
    "diseases": "glycemia, lipidemia, VFA"
  },
  {
    "caption": " (E-H) Properties of various GM3 species as a function of BMI: LCFA-GM3 (E), VLCFA-GM3 (F), unsaturated VLCFA-GM3 (G), and α-hydroxyVLCFA-GM3 (h24:0) (H). Colors indicate disease severity: light blue, no abnormal scores (n=25); orange, early-phase obesity (n=74); purple, severe obesity (n=23). ",
    "diseases": "obesity"
  },
  {
    "caption": " (I, J) Spearman's correlations for GM3 h24:0 vs. ALT (I) and vs. HOMA-IR (J). ",
    "diseases": "IR"
  },
  {
    "caption": "A. Relative levels of OMA1 mRNA in colorectal cancer tissues (n=105) compared with adjacent normal tissues (n=43) from colorectal cancer patients were shown (using the GEO dataset GSE21510). The data are presented as mean ± SEM, and statistical significance was determined by a Mann-Whitney test. ***p < 0.001.",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "B. Kaplan-Meier curves were constructed to analyze and compare between patients with high and low levels of OMA1 in colorectal cancer samples from the GEO dataset GSE17537. \"Low\" indicates patients with OMA1 mRNA levels less than the median. \"High\" indicates patients with OMA1 mRNA levels greater than the median. Statistical analysis was performed using log-rank tests, n = 55, p=0.0180.",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "C. The lysates of tumors (T) and adjacent normal (N) tissues from colorectal cancer patients were analyzed by Western blotting with antibodies against OPA1 or Tubulin. The \"c, d and e\" bands of OPA1 indicate cleaved OPA1 bands. Tubulin was used as a loading control.",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "Western blotting analysis of MBP and Ser259-MYRF expression in the postmortem brain cortex tissues in 4 HD patients and 4 non-HD control individuals. Ratios of MBP to GAPDH, or Ser259 (pMYRF) to total MYRF are presented on the right. One-way ANNOVA with Tukey's test. MBP: ***P=0.0004; pMYRF: **P=0.0051. Data are mean ±SEM.",
    "diseases": "HD"
  },
  {
    "caption": "Western blotting analysis of the expression of Ser259 (pMYRF) and total MYRF (full-length: fMYRF and N-terminal: nMYRF) in 13-months-old HD-KI and WT mouse cortex. Ratios of pMYRF to total MYRF obtained from 3 independent experiments were presented beneath the blots. One-way ANNOVA with Tukey's test. ***P=0.00083. Data are mean ±SEM.",
    "diseases": "HD"
  },
  {
    "caption": "Expression of YAP1 in cytoplasmic (yellow) and nuclear (blue) fractions from SCP-1 cells transduced with FUS-DDIT3 or EV and liposarcoma cell lines. One of at least two independent experiments with similar results is shown. FUS‑DDIT3‑expressing cell types are indicated in red.",
    "diseases": "liposarcoma"
  },
  {
    "caption": "Strong nuclear expression of YAP1, FOXM1, and PLK1 in MLS patient samples (original magnification, x10 [inset, x20]).",
    "diseases": "MLS"
  },
  {
    "caption": "Intensity of nuclear YAP1 expression in liposarcoma patient samples. Immunoreactivity was assessed using a semi‑quantitative score (0, negative; 1, weak; 2, moderate; and 3, strong) defining the staining intensity in the positive control (hepatocellular carcinoma) as strong. Only tumors with at least moderate staining (semi‑quantitative score ≥2) and ≥30% YAP positive cells were considered positive for the purposes of the study.",
    "diseases": "hepatocellular carcinoma, tumors, liposarcoma"
  },
  {
    "caption": "Proportion of cells with nuclear YAP1 expression in liposarcoma patient samples. Boxes represent mean values and lower and upper quartiles. Whiskers represent minimum and maximum values.",
    "diseases": "liposarcoma"
  },
  {
    "caption": "Competition assays with liposarcoma cell lines transduced with RFP-labeled NTC or YAP1 shRNAs. Flow cytometric quantification of RFP-positive cells on day 17 relative to day 3 showed that YAP1 knockdown was preferentially toxic to MLS cells. Error bars represent the mean ± SD of two independent experiments.",
    "diseases": "MLS, liposarcoma"
  },
  {
    "caption": "Aggregate data from competition assays shown in (A). Statistical significance was assessed using an unpaired t-test. LS, non-myxoid liposarcoma.",
    "diseases": "myxoid liposarcoma"
  },
  {
    "caption": "Cell viability and expression of FOXM1 and PLK1 in MLS cell lines following siRNA-mediated YAP1 knockdown. Error bars represent the mean ± SD of three independent experiments, unpaired t-test. The blots represent one of at least three independent experiments with similar results.",
    "diseases": "MLS"
  },
  {
    "caption": "Flow cytometric cell cycle analysis of MLS cell lines following shRNA‑mediated YAP1 knockdown. Error bars represent the mean ± SD of three independent experiments, two-way ANOVA; ns, not significant.",
    "diseases": "MLS"
  },
  {
    "caption": "Senescence‑associated β‑galactosidase (SABG) staining intensity in MLS cell lines following shRNA-mediated YAP1 knockdown. Error bars represent the mean ± SD of ten random microscopic fields, two-way ANOVA).",
    "diseases": "MLS"
  },
  {
    "caption": "Expression of CDKN1A, CDKN2A, total and phosphorylated RB1, and TP53 in MLS cell lines following shRNA‑mediated YAP1 knockdown. One of at least two independent experiments with similar results is shown.",
    "diseases": "MLS"
  },
  {
    "caption": "Expression of cleaved PARP and cleaved caspase 3/8 in MLS cell lines following shRNA-mediated YAP1 knockdown. One of at least two independent experiments with similar results is shown.",
    "diseases": "MLS"
  },
  {
    "caption": "Flow cytometric analysis of apoptosis (cleaved PARP) and mitotic fraction (phosphorylated histone H3S10) in MLS cell lines cultured in the presence of 0.25 µM Verteporfin. One of two independent experiments with similar results is shown.",
    "diseases": "MLS"
  },
  {
    "caption": "Expression of total YAP1 and downstream effectors (FOXM1 and PLK1) in MLS cell lines treated with 0.5 or 1 µM verteporfin for 15 hours. One of at least three independent experiments with similar results is shown.",
    "diseases": "MLS"
  },
  {
    "caption": "YAP1-responsive luciferase activity in MLS cell lines transfected with a constitutively active YAP1S127A mutant and treated with 1 µM verteporfin. Relative luciferase activity is displayed relative to control. Error bars represent the mean ± SD of three independent experiments, unpaired t-test.",
    "diseases": "MLS"
  },
  {
    "caption": "Tumor formation on chicken CAM of MLS cell lines following shRNA-mediated YAP1 knockdown. The number of tumors is given above each bar, Fisher exact test; ns, not significant.",
    "diseases": "tumors, MLS"
  },
  {
    "caption": "Tumor growth on chicken CAM of MLS cell lines following treatment with 1 µM verteporfin. Shown are tumor volumes and representative photographs of tumors.",
    "diseases": "tumors, MLS"
  },
  {
    "caption": "Western blot analysis of lysates from cerebellum of control and FXS patients ''FXS'' (n = 4). Extract of pCI-hDGKk-transfected Hela cells (hDGKk) was used as antibody specificity control and size marker. Representative images of immunoblots probed with antibodies against the indicated proteins are shown. GAPDH was the loading control. Quantification of Western blots is shown on right. Protein amounts of DGKk are normalized to GAPDH and presented as fold change relative to control.",
    "diseases": "FXS"
  },
  {
    "caption": "A In vitro  viability  curves after 72hr exposure to mafosfamide or doxorubicin. Results are shown for three DX/REL neuroblastoma cell line pairs, two with attenuated   cytochrome c  release (CHLA15/CHLA20 and SKNBE1/SKNBE2C) and one without (CHLA122/CHLA136). Data information: data points are mean and SD from triplicate wells, experiments are representative of at least three biological replicates dotted-line represents 50% viability.",
    "diseases": "neuroblastoma"
  },
  {
    "caption": "A, B, C  Transmission electron microscopy image analysis was used to quantify mitochondrial size, circularity and roundness in DX/REL neuroblastoma  pairs (mean +/- SD shown). Data information: , n=137-241  mitochondria  per cell line statistical analyses were performed using a two-tailed Mann-Whitney U test, with significance p<0.05 (trend p<0.10).",
    "diseases": "neuroblastoma"
  },
  {
    "caption": "P. falciparum symptomatic  (n=30) and asymptomatic  (n=40) infected individuals, as well as light-microscopy and PCR parasite-negative healthy immune controls (n=31) were recruited for the study. G. Antibody titers specific for P. falciparum parasite lysate. Bars represent the mean ± SD of using 29 (symptomatic), 35 (asymptomatic) and 26 (healthy immune controls) biological replicates. The dotted line depicts the average antibody   background levels of malaria-naive healthy Melbourne controls. H. Mean antibody titers as determined by ELISA  to the P. falciparum  recombinant proteins EBA-175, EBA-140, PfRh2, PfRh4, PfRh5, and PfRipr.",
    "diseases": "malaria"
  },
  {
    "caption": "Gene expression  profiles of PBMCs  from  P. falciparum symptomatic  and healthy immune controls were compared. A. Unsupervised hierarchical clustering heat map of the 922 differentially expressed genes (DEGs) between symptomatic P. falciparum malaria   and healthy immune controls using the complete method and Euclidian measure of distance. B. Mean-difference plot displaying genes differentially expressed between symptomatic P. falciparum malaria  and healthy immune controls. Each gene is plotted as a single point determined by log-fold-change and average transcript abundance. Red genes are overrepresented, and blue genes are underrepresented in symptomatic  malaria.",
    "diseases": "P. falciparum malaria, malaria"
  },
  {
    "caption": "Gene expression profiles of PBMCs from P. falciparum symptomatic  and healthy immune controls were compared. F. Upstream regulator analysis of the 922 DEGs between  symptomatic P. falciparum malaria and healthy immune controls. The red lines represent a significant activation z-score of ±2.",
    "diseases": "P. falciparum malaria"
  },
  {
    "caption": "Gene expression  profiles of PBMCs  from  P. falciparum symptomatic  and healthy immune controls were compared. Hierarchical clustering heatmap (G) displaying DEGs in symptomatic P. falciparum malaria  and healthy immune controls predicted to be controlled by  IFN-γ and  IL-13  upstream regulators.",
    "diseases": "P. falciparum malaria"
  },
  {
    "caption": "Gene expression  profiles of PBMCs  from  P. falciparum symptomatic  and asymptomatic   infected participants were compared. C. Heat map of the 418 DEGs in  P. falciparum symptomatic  and asymptomatic  infected participants as well as in healthy immune controls. E. Volcano plot displaying selected genes clusters 1 and 2 from heatmap in C scaled by Log2-fold-change and -Log10(P-value) differentially expressed between P. falciparum symptomatic  and asymptomatic  infected individuals. Genes in red are overrepresented in symptomatic malaria   and genes in blue are overrepresented in asymptomatic malaria.",
    "diseases": "malaria"
  },
  {
    "caption": "Gene expression profiles of PBMCs  from P. falciparum symptomatic and asymptomatic  infected participants were compared. F. Mean RPKMs + SEM of selected genes in P. falciparum malaria symptomatic  (n=6) and asymptomatic  (n=5) individuals. Dotted red lines depict transcriptional levels  of healthy immune controls, Mann-Whitney test of biological replicates,*p<0.05.",
    "diseases": "P. falciparum malaria"
  },
  {
    "caption": "Gene expression profiles of bulk PBMCs  from P. falciparum-infected asymptomatic  individuals and healthy immune controls were compared. A. Hierarchical clustering heat map of the 171 differentially expressed genes (DEGs) in P. falciparum asymptomatic  and healthy immune control participants. C. Mean-difference plot displaying DEGs between asyptomatic P. falciparum malaria  and healthy immune controls. Each gene is plotted as a single point determined by log-fold-change and average transcript abundance. Red genes are overrepresented, and blue genes are underrepresented in asymptomatic malaria.",
    "diseases": "P. falciparum malaria, malaria"
  },
  {
    "caption": "Gene expression  profiles of bulk PBMCs  from  P. falciparum-infected asymptomatic  individuals and healthy immune controls were compared. E. Mean RPKMs + SEM of selected genes in P. falciparum malaria asymptomatic  individuals (n=5) and healthy immune controls (n=6). Dotted red lines depict transcriptional levels of  P. falciparum-infected symptomatic individuals, Mann-Whitney test of biological replicates, *p<0.05.",
    "diseases": "P. falciparum malaria"
  },
  {
    "caption": "Representative images of hematoxylin and eosin-stained testicular sections from the patient (V:3) and a man diagnosed with obstructive azoospermia, serving as the control. The magnified view of the boxed area is shown in the lower left corner of the image from the patient. The blue arrow indicates unaligned chromosomes in the representative metaphase cells. Scale bars, 50 μm.",
    "diseases": "obstructive azoospermia"
  },
  {
    "caption": "E. Effect of MTAP overexpression on lung cancer metastasis in vivo was demonstrated by orthotopic implantation assays. Top: representative photographs of lungs and H&E staining of the lung sections. The primary tumors are indicated by arrowheads and the metastatic nodules are indicated by arrows. Bottom: quantification of averaged primary tumor sizes, metastatic incidence and nodule number.",
    "diseases": "lung cancer"
  },
  {
    "caption": "F. Kaplan-Meier analyses of overall survival (top) and progression-free survival (bottom) for 101 patients with lung adenocarcinoma grouped into high- or low-MTAP mRNA expression measured by RT-qPCR. p values were obtained by log-rank test.",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "A-B. The correlation of MTAP and vimentin or PRMT5 and vimentin at protein (A) and mRNA (B) levels from 89 lung adenocarcinoma patients. r is the Spearman's rank correlation coefficient.",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "D. An association between MTAP and vimentin levels in 124 lung cancer patients was examined by Spearman's rank correlation.",
    "diseases": "lung cancer"
  },
  {
    "caption": "E. Kaplan-Meier analyses of overall survival for lung cancer patients grouped by MTAP and vimentin levels from IHC staining. p value was obtained by log-rank test.",
    "diseases": "lung cancer"
  },
  {
    "caption": "(A - D) Color fundus photographs and SW-AF examinations on four patients of β-thalassemia subject to chelation therapy by DFO for at least 16 years. Fundus phenotypes, including RPE mottling and depigmentation in the macula (Case Ⅰ) (Gelman et al, 2014), choroidal sclerosis in the perimacular areas (Case Ⅱ), peripapillary (Case Ⅲ and Ⅳ), and subretinal pigmentation (Case Ⅳ) were evaluated. RPE lesions including concentric distribution of stippled hyper-autofluorescence at the macula (Case Ⅰ), large areas of hypo-autofluorescent regions at parapapillary or perimacular area (Case Ⅱ and III), and extensive RPE loss in both eyes (Case Ⅳ) were observed by SW-AF.",
    "diseases": "β-thalassemia, choroidal sclerosis"
  },
  {
    "caption": "Effects of COUP-TFII inhibition and lactate treatment on tumor growth in vivo. (A) Growth curve in tumors derived from xenografted shScramble or shCOUP-TFII-HCT116 cells and treated with sodium chloride or sodium L-lactate (60 l x g-1 body weight; 150 mM).",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "(B) tumor volume at the experimental endpoint, in tumors derived from xenografted shScramble or shCOUP-TFII-HCT116 cells and treated with sodium chloride or sodium L-lactate (60 l x g-1 body weight; 150 mM).",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "Effects of COUP-TFII inhibition and lactate treatment on tumor growth in vivo. (C) Western blot analysis of the indicated proteins in tumors derived from xenografted shScramble or shCOUP-TFII-HCT116 cells and treated with sodium chloride or sodium L-lactate (60 l x g-1 body weight; 150 mM).",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "(D) Effects of trametinib treatment and overexpression of COUP-TFII on tumor growth in vivo. Tumors were derived from xenografted HCT116 expressing HA-COUP-TFII or carrying a control vector and treated with trametinib (3mg/kg).",
    "diseases": "tumor, Tumors"
  },
  {
    "caption": "(E) Western blot analysis of indicated proteins in tumors derived from xenografted HCT116 treated with trametinib with or without COUP-TFII overexpression. Asterisk indicates exogenous HA-COUP-TFII.",
    "diseases": "tumors"
  },
  {
    "caption": "B Lamin B1 distribution in human putamen was analysed by immunohistochemistry. Antibody against lamin B1 (red) was combined with DAPI-Fluoromount G (blue) to label nuclei. Representative images show the distribution of lamin B1 in the putamen of non-affected individuals (CTL) and HD patients at different stages of the disease (VS II-IV: Vonsattel grades). Yellow and white arrowheads indicate MSNs and glial cells, respectively. Scale bar 50 μm and 20 μm for low and high magnification, respectively.",
    "diseases": "HD"
  },
  {
    "caption": " C The distribution of lamin B1 in the putamen of HD patients was analysed by immunohistochemistry. Anti-lamin B1 antibody (red) was combined with anti-GFAP antibody (green) and nuclei were labelled with DAPI-Fluoromount G (blue). Representative images show the distribution of lamin B1 at Vonsattel grade III. Yellow arrowheads indicate MSNs and white arrowheads indicate GFAP-positive cells. Scale bar 10 μm. ",
    "diseases": "HD"
  },
  {
    "caption": " D Graphs showing lamin B1 intensity and circularity in MSNs nuclei from the putamen of HD patients at different stages of the disease (VS: Vonsattel grade) and corresponding controls (CTL: non-affected individuals). N = 6 for CTL, N = 3 for VS I-II and N = 4 for VS III-IV. An average of 50 nuclei was examined for each sample. Representative images (maximal Z-projections) are shown. Scale bar 7μm. ",
    "diseases": "HD"
  },
  {
    "caption": " C EAE clinical scores in mice immunized s.c. with MOG + RA, MOG + IL-2, MOG + RA + IL-2, or PBS + DMSO (Veh), 7 and 21 days before induction of EAE. Results are mean + SEM (n=12, except for MOG + IL-2, where n=6; combined from two experiments). *p<0.05, **p<0.01, ***p <0.001, MOG + IL-2 + RA vs Veh, #p<0.05, ##p<0.01, ###p<0.001, MOG + IL-2 + RA vs MOG + RA, †p<0.05, ††p<0.01, †††p <0.001, MOG + IL-2 + RA vs MOG + IL-2 by two-way ANOVA and Tukey post hoc test. ",
    "diseases": "EAE"
  },
  {
    "caption": " D Representative FACS plots of MOG dextramer+ CD4 T cells in LNs of naïve mice or 3 days after induction of EAE. Cells were gated as single live F4/80- CD8- B220- CD4+ CD44+. ",
    "diseases": "EAE"
  },
  {
    "caption": " E Mean percentages of MOG dextramer+ CD4 T cells in LNs 3 days after induction of EAE. Cells were gated as single live F4/80- CD8- B220- CD4+ CD44+. Bars are mean + SEM (n=5 or 6). *p <0.05 by unpaired two-tailed t test. ",
    "diseases": "EAE"
  },
  {
    "caption": "F Mean fluorescence intensity (MFI) of CD49b, ICOS and PD-1 by MOG-dextramer+ CD4 T cells in LNs 3 days after induction of EAE. Cells were gated as single live F4/80- CD8- B220- CD4+ CD44+ dextramer+. Bars are mean + SEM (n=5 or 6). *p <0.05, **p <0.01 by unpaired two-tailed t test.",
    "diseases": "EAE"
  },
  {
    "caption": " G MOG-specific IL-17 and IFN-γ production by spleen cells from day 7 of EAE, quantified in supernatants by ELISA after 5 d culture with increasing concentrations of MOG. Bars are mean + SEM (n=3 or 4). *p<0.05, **p<0.01 and ***p<0.001 by two-ANOVA and Tukey post hoc test. ",
    "diseases": "EAE"
  },
  {
    "caption": " A Representative FACS plots of CD11a+ CD4 T cells in the spleen on day 7 of EAE in mice immunized with MOG, RA and IL-2 or vehicle (Veh) only. Cells were gated as single live CD45+ CD3+ CD4+. B Mean absolute numbers of CD11a+ CD4 T cells in the spleen on day 7 of EAE in mice immunized with MOG, RA and IL-2. Bars are mean + SEM (n=4 or 5). *p<0.05 by unpaired two-tailed t test. ",
    "diseases": "EAE"
  },
  {
    "caption": " C Representative FACS plots of CD45+ CD4 T cells in the spinal cords of mice on day 12 of EAE. Cells were gated as single live CD45+. D Mean absolute numbers of infiltrating CD45+ cells in the spinal cords of mice on day 12 of EAE. Bars are mean + SEM (n=5 or 6). *p<0.05 by unpaired two-tailed t test. ",
    "diseases": "EAE"
  },
  {
    "caption": " E Representative FACS plots of infiltrating IL-17+ and IFN-γ+ CD4 T cells in the spinal cords on day 12 of EAE. Cells were gated as single live CD45+ CD3+ CD4+. F Mean absolute numbers of infiltrating IL-17+ and IFN-γ+ CD4 T cells in the spinal cords on day 12 of EAE. Bars are mean + SEM (n=5 or 6). *p<0.05 by unpaired two-tailed t test. ",
    "diseases": "EAE"
  },
  {
    "caption": " G Representative histogram of LAG-3 expression on CD4 T cells in the spinal cords on day 12 of EAE. Cells were gated as single live CD45+ CD3+ CD4+. ",
    "diseases": "EAE"
  },
  {
    "caption": " H Inverse correlation between LAG-3 and IL-17 and IFN-γ expression on CD4 T cells in the spinal cords on day 12 of EAE. *p<0.05 by unpaired two-tailed t test. ",
    "diseases": "EAE"
  },
  {
    "caption": " A IL-17 and IFN-γ production by ELISA on supernatants of spleen cells from mice with EAE (EAE) co-cultured for 3 days with MOG-specific Tr1 cells (from mice immunized twice with MOG, RA and IL-2 and amplified in vitro with MOG, RA and IL-2 for 8 days) or control T cells from LNs of mice injected with PBS + DMSO (Veh). Bars are mean + SD of one experiment. *p<0.05, **p<0.01 and ***p<0.001 by unpaired two-tailed t test. ",
    "diseases": "EAE"
  },
  {
    "caption": " B EAE clinical scores of mice transferred 1 day before induction of EAE with MOG-specific Tr1 cells amplified in vitro with MOG, RA and IL-2. Results are mean + SEM (n=4 or 6). *p<0.05 and **p<0.01 by two-way ANOVA with Bonferroni post hoc test. ",
    "diseases": "EAE"
  },
  {
    "caption": " C Representative FACS plots of IL-17+ CD4 T cells in the spinal cords on day 20 of EAE. Cells were gated as live single CD45.2+CD3+CD4+ cells. D Mean absolute numbers of IL-17+ CD4 T cells in the spinal cords on day 20 of EAE. Results are mean + SEM (n=6). *p<0.05 by unpaired two-tailed t test. ",
    "diseases": "EAE"
  },
  {
    "caption": " E Representative FACS plots of CTLA-4+ CD4 T cells in the spleens of mice with EAE. Cells were gated as live single CD45.1+CD3+CD4+. F Mean percentages of CTLA-4+ CD4 T cells in the spleens of mice with EAE. Results are mean + SEM (n=6). **p<0.01 by unpaired two-tailed t test. ",
    "diseases": "EAE"
  },
  {
    "caption": " G EAE clinical scores of WT and IL-10-/- mice immunized s.c. with MOG + RA + IL-2, or PBS + DMSO (Veh), 7 and 21 days before induction of EAE. Results are mean + SEM (n=6 or 7). ***p <0.001, WT MOG + IL-2 + RA vs WT Veh, ##p<0.01, ###p<0.001, IL-10-/- MOG + IL-2 + RA vs IL-10-/- Veh by two-way ANOVA and Tukey post hoc test. ",
    "diseases": "EAE"
  },
  {
    "caption": " Retinal inflammatory scores of mice immunized s.c. with PBS + DMSO (Veh), IRBP + DMSO (IRBP) or IRBP + RA + IL-2 21 and 7 days before induction of EAU by s.c. injection of IRBP emulsified in CFA. Bars are mean + SEM (n=6), *p<0.05 and ***p<0.001, IRBP + IL-2 + RA vs Veh, ###p<0.001 IRBP + IL-2 + RA vs IRBP by two-way ANOVA with Tukey post hoc test. ",
    "diseases": "EAU"
  },
  {
    "caption": " Representative fundus images of each group of mice 35 days after induction of EAU. Arrowheads indicate area with retinal vasculitis and the asterisk indicates a region of vitreous haze, where the image appears blurred. ",
    "diseases": "EAU, retinal vasculitis"
  },
  {
    "caption": " Representative photographs of each group of retinal fundus of HEL-TCR transgenic mice at pn 35. Arrowheads indicate representative areas with retinal vasculitis. ",
    "diseases": "retinal vasculitis"
  },
  {
    "caption": " F Mean absolute number of IL-17+ CD4 T cells in the retina (upper panels) or mean percentages of IL-10+ LAG-3+ Foxp3- CD4 T cells in the spleens of of HEL-TCR transgenic mice with vasculitis (lower panels). Results are mean + SEM (n=3, 4 or 5). **p <0.01 and ***p <0.001 by one way ANOVA with Bonferroni post hoc test. ",
    "diseases": "vasculitis"
  },
  {
    "caption": "A:  Kaplan-Meier plot was generated using the transcriptome data set of PDAC from TGCA and OncoLnc to visualize the survival of PDAC patients  with low or high PRMT1 transcript levels and short-term (<500 days, left plot) and long-term survival (>500 days, right plot).",
    "diseases": "PDAC"
  },
  {
    "caption": "B: Representative immunohistochemistry (IHC)  stainings of  PRMT1 (brown) are shown for normal human pancreatic tissue and three PDAC specimens deriving from the cohort of 75 patients. Based on the immunostaining intensity and the percentage of stained  tumor cells, all specimens were divided into three PRMT1 expression scores: not elevated, moderately elevated and highly elevated PRMT1 expression in tumor cells in comparison to normal pancreas. Right images are magnifications of the left images, as indicated by the black rectangles. Scale bars in the left images: 100 μm. Scale bars in the right images: 50 μm.",
    "diseases": "PDAC"
  },
  {
    "caption": "E: Immunofluorescence (IF) stainings of the 75  PDAC specimens were performed using α-p14ARF (red), α-CK8/18 (green, staining ductal cells in normal pancreas and neoplastic cells in PDAC) antibodies and DAPI (blue, nuclei/DNA). Representative  IF images are shown for normal human pancreatic tissue, two PDAC specimens displaying no  p14ARF expression  and three PDAC specimens displaying strong p14ARF expression  in tumor cells. Left and corresponding right images  show the same tissue section. Asterisks indicate nucleolar p14ARF localization in  neoplastic cells of PDAC. The last  image pair shows a magnification of the  image pair above (indicated by the rectangle). Scale bars: 35 μm.",
    "diseases": "PDAC"
  },
  {
    "caption": "A, B RT-qPCR quantification of SRSF3 (A) and CDKN1A (B) mRNA levels in colorectal tumours and their paired normal samples (*p<0.05, **p<0.01, two-tailed unpaired Student's t-test, data as mean ± SEM, n=25, biological replicates). N=normal, T=tumour.",
    "diseases": "colorectal"
  },
  {
    "caption": "(A) Stable RNAi screening of cancer-related genes was conducted to identify gene knockdowns that enhance reprogramming of MEFs into iPSCs. The graph shows the 10 shRNAs that were most strongly, positively selected in iPSCs compared to non-reprogrammed cells on day 14 of reprogramming (n=3 biological replicates).",
    "diseases": "cancer"
  },
  {
    "caption": "(A) AP radiograph demonstrates characteristic findings of ATD in the R05-365A proband. Note the shortened humeri (closed arrowhead) and elongated clavicles (arrow). (B) Radiographs of the Cmh001543-01 proband showing similar findings. ",
    "diseases": "ATD"
  },
  {
    "caption": "(D) Expression of GRK2 as measured by RT-PCR in three replicates each of control and R05-365A fibroblasts, demonstrating absence of GRK2 transcript in ATD cells. GAPDH served as a positive control.",
    "diseases": "ATD"
  },
  {
    "caption": "(E) Two control and ATD fibroblast samples were immunoblotted for GRK2. Note the absence of GRK2 protein in the ATD cells. Actin served as a loading control. The data shown are representative of three independent experiments.",
    "diseases": "ATD"
  },
  {
    "caption": "(B) Picrosirius red staining of the femoral growth plates of a control and the ATD R05-365A fetus. The control growth plate shows normal architecture with clearly distinguishable reserve (R), proliferating (P) and hypertrophic (H) zones. A profound disruption of growth plate architecture is obvious in the GRK2-/- growth plate, which shows irregularly-shaped reserve zone chondrocytes, a lack of discernable proliferating chondrocytes and a significantly under-developed hypertrophic zone. Scale bars, 100 μm.",
    "diseases": "ATD"
  },
  {
    "caption": "(D) Alcian blue staining of the femoral growth plates of a control and the ATD R05-365A fetus. Note the significantly lesser blue staining of the R05-365A growth plate stained by alcian blue pH 1.0, suggesting impaired sulfation of the extracellular matrix. Scale bars, 200 μm.",
    "diseases": "ATD"
  },
  {
    "caption": "F. Western blot analysis of total (RB) and phosphorylated (p-RB) retinoblastoma in growing (non-differentiated) versus differentiated podocytes. ß-actin was used as loading control.",
    "diseases": "retinoblastoma"
  },
  {
    "caption": "3 healthy controls (HC, #1 - #3), 3 mild  COVID-19 patients  (#1 - #3), and 6 severe COVID-19 patients  (#1 - #6) (B) from Cohort #1. Data were shown in UMAP. Single-cell  gene expression of MAP4K3  (GLK) in individual cells was shown in color scale.",
    "diseases": "COVID-19"
  },
  {
    "caption": "E, F GLK  mRNA levels in KRT18+ epithelial  (E) or KRT18+ TPPP3+ ciliated epithelial cells  (F) of Cohort #1. n (cell number) = 3, 14, 33 for HC; n = 65, 43, 74 for mild COVID-19 patients; n = 164, 62, 10, 4, 74, 66 for severe COVID-19 patients  (E). n = 25, 43, 36 for HC; n = 209, 244, 141 for mild COVID-19 patients; n = 189, 223, 330, 792, 80, 243 for severe COVID-19 patients  (F). Data information: In (E, F), *, P value < 0.05; **, P value < 0.01; ***, P value < 0.001; ****, P value < 0.0001 (Kruskal-Wallis test).",
    "diseases": "COVID-19"
  },
  {
    "caption": "C Immunoblotting  of ACE2  and CD63  proteins in serum exosomes  isolated from the sera of 4 healthy controls (HC) and 7 COVID-19 patients  from NHRI Biobank for COVID-19 patients  in Taiwan (Cohort #3). Serum  collection days from the onset are shown; treatment of oxygen  therapy on the patient  is also indicated. Exosomes  were isolated sequentially using ExoQuick kits and then ExoQuick ULTRA columns. Arrowhead denotes glycosylated ACE2  proteins; asterisk denotes non-glycosylated ACE2  proteins.",
    "diseases": "COVID-19"
  },
  {
    "caption": "D Mass spectrometry  analysis of the ACE2  peptides from the serum exosomes  of COVID-19 patients. The ACE2  protein peptide sequences containing phospho-Ser776 or phospho-Ser783 residue of ACE2  proteins detected in the serum exosomes  of COVID-19 patients  (Cohort #3) are shown. Exosomes  were isolated using ExoQuick kits, and soluble proteins were removed by ExoQuick ULTRA columns. Exosomes were further purified by immunoprecipitation  using a combination of anti-CD9, anti-CD63, and CD81  magnetic beads.",
    "diseases": "COVID-19"
  },
  {
    "caption": "Electron microscopy showing two adjacent mitochondria (one intact and one ruptured) in a DM platelet. a. Lower powered view of the single DM platelet. b. The enlarged inset highlights the ruptured mitochondria (with loss of cristae morphology) next to the intact mitochondria. c. Black dash line indicates mitochondria membrane and red dash line indicate phagophore formation. (M- mitochondria)",
    "diseases": "DM"
  },
  {
    "caption": "Immunoprecipitation (Meng et al) of MsrB2 in HC and DM human platelets followed by MsrB2 and LC3I/II western.",
    "diseases": "DM"
  },
  {
    "caption": " Confocal microscopy was used to corroborate the Western analysis using double staining for LC3 and MsrB2 in HC and DM platelets. Arrows indicate sites of colocalization of COXIV, LC3 and MsrB2 as determined by Volocity software (PerkinElmer, USA). Quantitation is presented for intensity of MsrB2 in HC vs DM and colocalization of COXIV, LC3 and MsrB2. (MsrB2 intensity; **p=0.0009, colocalization CoxIV and LC3; **p=0.0014 vs. HC, n=3).",
    "diseases": "DM"
  },
  {
    "caption": "LC3 and MsrB2 immuno-EM analysis of HC and DM platelets. 15 nm dots indicate immunogold-labeled LC3 clusters and 5nm dots indicate immunogold-labeled MsrB2 clusters. No significant clusters were found in HC (a) platelets. Representative areas of clusters of gold labeling in DM patients (b-d) are presented. The nonparametric t test was performed for comparisons of 2 groups. Analysis was performed with Prism software (GraphPad Software, Inc, La Jolla, CA). A difference of P<0.05 was considered significant.",
    "diseases": "DM"
  },
  {
    "caption": "Immunoprecipitation (Meng et al) of MsrB2 in HC and DM platelets, followed by western blot analysis of precipitated Parkin and modified Parkin.",
    "diseases": "DM"
  },
  {
    "caption": "Immunoprecipitation (Meng et al) of Parkin in HC and DM platelets, followed by Western blot analysis of precipitated Parkin and MsrB2.",
    "diseases": "DM"
  },
  {
    "caption": "Confocal microscopy was used to corroborate the Western analysis using triple staining for Parkin, LC3 and MsrB2 in HC and DM platelets. Arrows indicate sites of colocalization of Parkin, LC3 and MsrB2 as determined by Volocity software (PerkinElmer, USA). Graphical quantification of colocalization between Parkin, LC3 and MsrB2 signal.",
    "diseases": "DM"
  },
  {
    "caption": "Immunoprecipitation (Meng et al) of Parkin in HC and DM platelets. Western blot analysis of MetO Parkin using specific Parkin and MetO antibodies. The detection of MetO Parkin, was performed w/o β-mercaptoethanol (NonRe) SDS sample buffer.",
    "diseases": "DM"
  },
  {
    "caption": " ROS levels were measured in platelet with FACS using specific oxidative stress detection dyes (CellROX, Molecular Probes, USA) in HC (n=8) and DM (n=10) platelets. (ROS; **p<0.0001 vs. HC).",
    "diseases": "DM"
  },
  {
    "caption": "Western blot analysis of Methionine Sulfoxidation (MetO), Methionine sulfide reductase B2 (MsrB2) and Parkin in human Healthy Control (HC) and Diabetic Mellitus (DM) platelets. P.C. is a BSA-MetO positive control (Cayman Chemical Co.). Quantitation of western blot analysis shown in Fig 1C. Graphical representation and statistical analysis of HC (n=3) and DM (n=12) individuals. (MetO; **p=0.0003, MsrB2; *p=0.0186, Parkin; **p=0.0003 vs. HC).",
    "diseases": "Diabetic Mellitus, DM"
  },
  {
    "caption": "Western blot analysis of Parkin and Parkin aggregation in human Healthy Control (HC) (n=3) and Diabetic Mellitus (DM) (n=12) platelets. Graphical representation and statistical analysis of HC (n=3) and DM (n=12) individuals. (modified parkin *p=0.035 vs. HC). Actin served as the loading control.",
    "diseases": "Diabetic Mellitus, DM"
  },
  {
    "caption": "Parkin IP was performed in HC, HC plus H2O2, and DM patients.",
    "diseases": "DM"
  },
  {
    "caption": "Immunoprecipitation (Meng et al) of MsrB2 in HC and DM platelets. Western blot analysis of precipitated MsrB2, Parkin and ubiquitinated MsrB2 (UB).",
    "diseases": "DM"
  },
  {
    "caption": "Confocal microscopy in individual platelets in HC vs DM assessing for CoxIV (mitochondria marker), ubiquitin and MsrB2. Colocalization is demomstrated by arrows and quantitated. (colocalization ubiquitin, MsrB2; **p=0.0003 vs. HC).",
    "diseases": "DM"
  },
  {
    "caption": "Representative western blot analysis of MsrB2, LC3I/II and parkin using Parkinson's disease (PD) platelets. Quantification analysis of individual band intensity. (MsrB2; *p=0.0255, LC3II; *p=0.0101 vs. HC (n=5) and PD (n=12)). GAPDH served as the loading control.",
    "diseases": "Parkinson's disease, PD"
  },
  {
    "caption": "Platelet apoptosis (Annexin V) were measured by flow cytometry analysis in HC (n=9) and PD (n=13) platelets. (**p<0.01 vs. HC). The nonparametric t test was performed for comparisons of 2 groups. Analysis was performed with Prism software (GraphPad Software, Inc, La Jolla, CA). A difference of P<0.05 was considered significant.",
    "diseases": "PD"
  },
  {
    "caption": "A) oxLDL plasma concentration in ACM patients and HC (n=36; Mann-Whitney test). B) oxLDL plasma concentration in mutated ACM (n=7) and NON ACM relatives, carriers of the same causative mutation (n=9; Mann-Whitney test). C)  oxLDL plasma concentration in ACM patients carriers of a  PKP2 mutation and ACM patients carriers of other desmosomal or non desmosomal mutations, or gene elusive (n=10 vs. n=26; One-Way ANOVA). Data information: mean ± SEM. * p<0.05; ** p<0.01; *** p<0.001.",
    "diseases": "ACM"
  },
  {
    "caption": "D) Representative images of  MDA immunostaining (green) on ACM and HC ventricular  tissue sections and relative quantification (n=4 biological replicates; Two-tailed Student's t-test). Nuclei are counterstained with Hoechst33342 (blue). E) Representative images of CD36 immunostaining  on  ACM  and HC ventricular  tissue sections and relative quantification (n=4 biological replicates; Two-tailed Student's t-test). Nuclei are  counterstained  with Hoechst33342  (blue). Data information: mean ± SEM. * p<0.05; ** p<0.01; *** p<0.001. ",
    "diseases": "ACM"
  },
  {
    "caption": "B) Left panels: representative images of three cases of ACM in Steady State Free Procession sequences at cardiac MRI. On the left a case with RV dilation, regional bulging of the  RV  wall without fat infiltration, and  oxLDL levels below the cut-off; in the center and on the right, two cases with fat infiltration in the right or  left ventricle wall (white arrow), respectively, and oxLDL levels above the cut-off. Right panel: quantification of the myocardial fat mass  of the two  ACM subpopulations (above or below the cut-off) whose  MRI  was available for re-analysis (n=14 oxLDL<86ng/ml, n=25 oxLDL>86ng/ml; Two-tailed Student's t-test).",
    "diseases": "ACM"
  },
  {
    "caption": "G) Kaplan-Meier  analysis of actual MAE free  survival  of patient belonging to the two ACM  cohort subgroups in the first 5-year follow-up (n=26 oxLDL<86ng/ml vs. n=41oxLDL>86ng/ml; Log-Rank p<0.0001; HR=0.223[0.116-0.428]).",
    "diseases": "ACM"
  },
  {
    "caption": "B) Left panels: representative images of MDA immunostaining (green) on ACM  and HC C-MSC  in GM. Nuclei  are counterstained  with Hoechst33342 (blue). Right panel: image quantification (n=4 biological replicates ACM, n=5 biological replicates HC; Two-tailed Student's t-test). Data information: mean ± SEM. * p<0.05, ** p<0.01.",
    "diseases": "ACM"
  },
  {
    "caption": "D) Top panel: representative images of  Western Blot analysis of proteins extracted from ACM  and HC C-MSC cultured in GM, hybridized with anti-CD36 and anti-PPARγ antibodies. Immunostaining of the housekeeping GAPDH is shown for normalization. Bottom panel: d.a. of PPARγ (n=18 biological replicates) and CD36 (n=17 vs. n=16 biological replicates) levels, normalized on GAPDH (Mann-Whitney test). Data information: mean ± SEM. * p<0.05, ** p<0.01.",
    "diseases": "ACM"
  },
  {
    "caption": "F) Top panels: representative images of internalization of oxLDL (red) in HC and ACM cells, cultured either in GM or in AM, and subjected to 10μg/ml  DiI-oxLDL treatment. Nuclei are  counterstained with Hoechst33342 (blue). Bottom panel: quantification of the relative mean DiI fluorescence for each sample, measured by FACS analysis (n=3 biological replicates; Two-Way Anova). Data information: mean ± SEM. * p<0.05, ** p<0.01. ",
    "diseases": "ACM"
  },
  {
    "caption": "A) Left panels: representative images of ORO staining   on ACM and HC C-MSC in AM supplemented or not with 150µg/ml oxLDL. Middle panel: image quantification (n=11 biological replicates; Two-Way Anova). Right panels: representative images of Western Blot of CD36, PPARγ  and GAPDH protein expression  of ACM  and HC C-MSC protein extracts in  AM supplemented or not with 150µg/ml oxLDL (n=5 biological replicates) and d.a. normalized on the house-keeping GAPDH (Two-Way Anova). Data information: mean ± SEM. * p<0.05, ** p<0.01, *** p<0.001.",
    "diseases": "ACM"
  },
  {
    "caption": "B) Left panels: representative images of ORO staining on ACM and HC C-MSC in AM supplemented or not with 20μg/ml 13HODE, 5mmol/L NAC or both. Right panel: image quantification (n=13 biological replicates; Two-Way Anova). Data information: mean ± SEM. * p<0.05, ** p<0.01, *** p<0.001.",
    "diseases": "ACM"
  },
  {
    "caption": "C) Left panel: representative images of Western Blot of  CD36, PPARγ and GAPDH protein expression of ACM  and HC C-MSC protein extracts in AM supplemented or not with 20μg/ml 13HODE, 5mmol/L  NAC or both (n=8 biological replicates). Right panels: d.a. normalized on the house-keeping GAPDH (Two-Way Anova). Data information: mean ± SEM. * p<0.05, ** p<0.01, *** p<0.001. ",
    "diseases": "ACM"
  },
  {
    "caption": "D) Left panel: representative images of internalization  of  oxLDL (red) in ACM C-MSC  treated with scramble siRNA or CD36 siRNA, cultured in  AM  and subjected to 10μg/ml  DiI oxLDL treatment. Right panel: quantification of the  DiI fluorescence normalized on  nuclei number (n=3 biological replicates, arbitrary units; Two-tailed Student's t-test). Data information: mean ± SEM. * p<0.05; ** p<0.01.",
    "diseases": "ACM"
  },
  {
    "caption": "E) Left panel: representative images of internalization  of oxLDL (red) in ACM C-MSC cultured in AM or  AM+5μM GW9662 and subjected to 10μg/ml DiI oxLDL treatment.  Nuclei  are  counterstained with  Hoechst33342  (blue). Right panel: quantification of the DiI fluorescence  normalized on nuclei number for each sample (n=3 biological replicates, arbitrary units; Two-tailed Student's t-test). Data information: mean ± SEM. * p<0.05; ** p<0.01.",
    "diseases": "ACM"
  },
  {
    "caption": "F) Left panel: representative images of Western Blot of CD36  and GAPDH expression of protein extracts of ACM C-MSC   cultured in AM or  AM+5μM GW9662. Right panels: d.a. normalized on the house-keeping GAPDH  (n=7 biological replicates; Two-tailed Student's t-test). Data information: mean ± SEM. * p<0.05; ** p<0.01. ",
    "diseases": "ACM"
  },
  {
    "caption": "B) Bar graphic showing that human breast cancers with deletion of the miR-424/503 locus have higher protein levels of β-catenin (RPPA). P-value is calculated based on one-sided Wilcoxon rank-sum test. In the box-plots in B and C the relative expression of β-catenin in the RPPA data from TCGA is shown. The yellow line indicates the median and the bars indicate the 75th percentile (Q3)+1.5 interquartile range (IQR).",
    "diseases": "breast cancers"
  },
  {
    "caption": "C) The bar graph shows that human breast cancers with low expression levels of miR-424 and miR-503 have higher protein levels of β-catenin. P-value is calculated based on one-sided Wilcoxon rank-sum test.",
    "diseases": "breast cancers"
  },
  {
    "caption": "F-T. Representative images of 2 dpf zebrafish which displayed the rescue of the vascular integrity defects in the progeny of an outcross of veal2gib005Δ8/+ zebrafish upon complementing with the wild type (WT) veal2 RNA. (F-J) Control zebrafish embryos. (K-O) veal2gib005Δ8/+ embryos injected with vehicle control. (P-T) veal2gib005Δ8/+ embryos complemented with veal2 RNA. (F,K,P) bright field. (G,L,Q) mRFP. (H,M,R) Animals stained with O-dianisidine stain. (I,N,S) eGFP. (J,O,T) merged eGFP and mRFP filters. Arrowheads show the presence of hemorrhage due to the vascular integrity defects. (F-H,K-M,P-R) magnification-5X, scale bar-100μm (I-J,N-O,S-T) magnification-20X, Scale bar-50μm.",
    "diseases": "hemorrhage"
  },
  {
    "caption": "F-K. Enzastaurin treatment rescues hemorrhage phenotype in veal2gib005Δ8/+ zebrafish embryos indicated by rescue of the vascular integrity defects in veal2gib005Δ8/+. Arrowheads show the presence of hemorrhage due to the vascular integrity defects. Experiment was repeated in biological replicates and total no of embryos scored are mentioned on figure. (F-I) Magnification-5X, Scale bar-100μm, (J-K) Magnification-20X, Scale bars-50μm.",
    "diseases": "hemorrhage"
  },
  {
    "caption": "I-N. Complementation of VEAL2 in veal2gib005Δ8/+ embryos significantly rescued hemorrhage phenotype. Arrowheads show the presence of hemorrhage due to the vascular integrity defects. (I-L) Magnification-5X, Scale bar-100μm (M-N) Magnification-20X, Scale bars-50μm.",
    "diseases": "hemorrhage"
  },
  {
    "caption": "E-S. Modeling hyperglycemia in HUVEC resulted in dysregulation of junctional assembly of CDH5 and CTNNB1 proteins and increased membrane localization of PRKCB protein. Complementation of VEAL2 and veal2 in hyperglycemic conditions reverted junctional disassembly of CDH5 and CTNNB1 and also kept PRKCB in cytoplasm to mitigate pathological conditions associated with hyperglycemia. (E-H,Q) CDH5 protein, (I-L,R) CTNNB1 protein, (M-P,S) PRKCB protein. (E-P) Magnification-60X, Scale bar-15μm. Arrowheads indicate representation of signals of proteins in HUVECs. (Q-S) Data from cells of different fields of 3 technical replicates of 1 biological replicate is presented as representation. Data is shown as individual values; the middle bar represents the mean and the error bar represents ± standard deviation.",
    "diseases": "hyperglycemia, hyperglycemic"
  },
  {
    "caption": "Relative copy number estimation in 20 genes of interest, and 18 large genomic regions, determined by sWGS of CSF from 13 glioma patients. Genes are ordered by genomic position, and their chromosomal locations are indicated in parentheses. Amplifications are shown in dark blue, deletions in orange, and copy number neutral regions are in grey. The top green bar indicates the tumor largest length dimension (<42 mm vs >42 mm), and the top violet bar indicates the glioma subtype. SCNAs were more frequently detected in CSF from patients with large glioblastoma tumors",
    "diseases": "glioblastoma tumors, glioma, tumor"
  },
  {
    "caption": "SCNAs determined by sWGS in 4 tumor subparts (T1 - T4) and the CSF sample, collected from patient G1. Amplifications are shown in dark blue, deletions in orange, and copy number neutral regions are in dark grey. sWGS from plasma and urine samples collected at the same time as the CSF sample showed no SCNAs",
    "diseases": "tumor"
  },
  {
    "caption": "Heat map summarizing the SCNAs detected by sWGS of 28 genes of interest in tumor biopsies and CSF from patient G1 (4 tumor subparts and 1 CSF sample). Amplifications are shown in dark blue, deletions in orange, and copy number neutral regions are in light grey",
    "diseases": "tumor"
  },
  {
    "caption": "Heat map summarizing detection of EGFR and PTEN alterations in tumor tissue and in CSF samples. Shared detection in tissue and CSF is indicated in green, detection of the alteration only in tissue in orange, and non-detection in blue. The top bars indicate the cfDNA concentration (copies/mL; in a range of purples), the size of the tumors (in a range of browns), the type of glioma (in a range of blues), and whether the tumor was in direct contact with the CSF or not (based on MRI, green or red, respectively). Samples are ranked from the left to right by decreasing concentration of cfDNA (copies/mL)",
    "diseases": "glioma, tumor, tumors"
  },
  {
    "caption": "A) Fragment size distribution, determined by sWGS, in CSF (blue line), plasma (red dashed line) and urine (black dashed line) from patient G1. The 3 samples were collected simultaneously before initiation of treatment. B) Fragment size distribution of cfDNA, determined by sWGS, in CSF from 13 glioma patients. The samples contained a high fraction of reads from DNA fragments with lengths corresponding to ~145 bp and ~167 bp. The fragment size profile of cfDNA from the plasma sample from patient G1 is shown in red. All samples were collected simultaneously before initiation of treatment C) Cumulative frequency analysis of the average density of fragment size in CSF (blue) and plasma (red). The vertical dashed line represents 167 bp",
    "diseases": "glioma"
  },
  {
    "caption": "B VHIO179 PDTXs were grafted into CB17-SCID female mice. Pyridostatin was administered intravenously (7.5 mg/kg/day) over the indicated periods of time. Vertical dotted line indicates end of treatment. Tumour volume was measured at the timepoints shown on the graph and expressed relative to tumour volume at the beginning of treatment. Each experimental group included n = 7 mice. Error bars represent SEM. P values were calculated between treated and untreated tumours at day 24, using an unpaired two-tailed t-test. ****, P ≤ 0.0001.",
    "diseases": "SCID"
  },
  {
    "caption": "(D) Scatter plot shows the log fold change in editing levels of several candidates between ventricles of healthy donors and heart samples of cardiomyopathy patients. FLNA marked in the graph is one significant discriminator. Y axis is the -log 10 of the p value for the difference between healthy and sick. The colors (red vs green) reflect the threshold cutoffs randomly assigned to distinguish the sites, which demonstrate large, highly significant differences between the two groups. Fold change cutoff of 0.9 was used.",
    "diseases": "cardiomyopathy"
  },
  {
    "caption": "(C) Representative heart sections of a 5-6 months old mice stained with Masson Trichrome shows increased collagen (blue) around coronary vessels (marked by arrowheads) Scale bar: 50 μm. (D) Quantification shows a significant increase in perivascular fibrosis in FLNAΔECS hearts. Four sections from each heart were measured. Four mice analyzed for each genotype. P value <0.05 considered significant. (mixed model approach) ",
    "diseases": "perivascular fibrosis"
  },
  {
    "caption": "A. Representative micrographs of tissue sections derived from oral squamous cell carcinomas (OSCC) and esophageal squamous cell carcinomas (ESCC)  stained with the indicated antibodies by immunohistochemistry (IHC). Top panels show routine H&E staining. Black squares point to regions magnified in the adjacent panels to the right.",
    "diseases": "ESCC, esophageal squamous cell carcinomas, oral squamous cell carcinomas, OSCC"
  },
  {
    "caption": "C. Kaplan-Meier plots showing the correlation between HSPH1 mRNA expression level and the survival of  patients with  ESCC. The expression data was obtained from and visualized with KM Plotter (www.kmplot.com, (Nagy et al, 2018) using the Pan Cancer algorithm at default settings.",
    "diseases": "ESCC"
  },
  {
    "caption": "Expression of indicated miRNAs in purified spleen lymphocytes (B cells, CD4+ T cells and CD8+ T cells) from d0 naive (white) and day 28 L. donovani-infected (grey) mice. Expression of each miRNA normalized to levels in whole naïve spleen (dotted line). Data is mean + SEM of 2 experiments with cells purified from 3-5 pooled spleens.",
    "diseases": "infected"
  },
  {
    "caption": "Volcano plot of RNAseq gene expression in splenic WT and miR-132-/- CD4+ T cells from d28 L. donovani infected mice. Fold change determined as log2 mean FPKM (miR-132-/-/WT) from 4 WT and 5 miR-132-/- mice. Transcripts significantly different between WT and miR-132-/- (p<0.05) are shown in red. Dotted box indicates transcripts significantly up-regulated in miR-132-/- CD4+ T cells by more than 50%.",
    "diseases": "infected"
  },
  {
    "caption": "STRING network analysis of significantly up-regulated transcripts in CD4+ T cells from spleen of d28 L. donovani infected miR-132-/- mice compared to WT cells. Cluster of ribosomal proteins shown in green circle, with coding RP transcripts (black) and pseudogenes (red) indicated. Secondary clusters are shown in grey.",
    "diseases": "infected"
  },
  {
    "caption": "Volcano plot of all RP genes in splenic WT and miR-132-/- CD4+ T cells from d28 L. donovani infected mice. RPL genes are shown as circles, RPS genes as triangles, and pseudogenes as squares. Red symbols indicate significant difference between WT and miR-132-/- cells (p<0.05) whereas black non-significant.",
    "diseases": "infected"
  },
  {
    "caption": "Expression of RP transcripts determined by qPCR from L. donovani infected d28 WT (blue) and miR-132-/- mice (red). N=9 for each WT and miR-132-/- from 2 independent infection experiments. Box extends from 25-75th percentile, whiskers are minimum and maximum values, and horizontal lines indicate median. Significance determined by unpaired t-test. Data information: * p<0.05, ** p<0.01, *** p<0.001.",
    "diseases": "infected, infection"
  },
  {
    "caption": "E. Volcano plot of transcripts containing a conserved miR-212/132-3p target site in spleen CD4+ T cells from d28 L. donovani infected WT or miR-132-/- mice.",
    "diseases": "infected"
  },
  {
    "caption": "F. BTAF1 transcript levels determined by qRTPCR in WT (blue) or miR-132-/- (red) in naïve (d0) and Th1 polarised for 18h (d1) CD4+ T cells, and CD4+ T cells from d28 L. donovani infected WT or miR-132-/- mice. N=8-9 for each WT and miR-132-/ Data information: Significance in (F) determined by unpaired t-test. * p<0.05, ** p<0.01.",
    "diseases": "infected"
  },
  {
    "caption": "A. Percentage of IFNγ+ live TCRβ+ CD4+ cells from L. donovani infected WT (blue) or miR-132-/- (red) mice, determined by intracellular cytokine staining. Data representative of 3 independent experiments with 3-5 mice per group. Data information: statistical significance was determined by unpaired t-test. * p<0.05, ** p<0.01, *** p<0.001. NS: not significant.",
    "diseases": "infected"
  },
  {
    "caption": "B. Percentage of IFNγ+/IL-10+ live TCRβ+ CD4+ cells from L. donovani infected WT (blue) or miR-132-/- (red) mice, determined by intracellular cytokine staining. Data representative of 3 independent experiments with 3-5 mice per group. Data information: statistical significance was determined by unpaired t-test. * p<0.05, ** p<0.01, *** p<0.001. NS: not significant.",
    "diseases": "infected"
  },
  {
    "caption": "C. IL-10 mRNA levels, determined by RNA-sequencing, in TCRβ+ CD4+ cells purified from spleens of L. donovani infected WT (blue) or miR-132-/- (red) mice (n=5 per group).",
    "diseases": "infected"
  },
  {
    "caption": "Liver LDU (Leishman Donovan units) at day 28 in infected WT mice treated with anti-IL-10R antibody or isotype control antibody (left panel, n=5 mice per group), or at day 21 and day 28 from WT (blue), IL-10+/- (open green circles) and IL-10-/- (filled green circles) mice (right panel n= 3-6 mice per group) Data information: Significance determined by unpaired t-test * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.",
    "diseases": "infected"
  },
  {
    "caption": "Day 28 splenic parasite burdens expressed as LDU with each data point representing an individual mouse in WT (blue) and miR-132-/- (miR-132-/-; red) mice. Data from 4 independent infection experiments.   Mean WT and miR-132-/- spleen parasite burdens from the 4 independent experiments shown in (B). Lines link individual experiments.   Splenic parasite burdens relative to WT group (WT mean = 1) for each of the 4 experiments shown in (B), with each data point representing individual mouse.   Data information: Significance determined by unpaired t-test, and in (C) by paired t-test of mean values. * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.",
    "diseases": "infection"
  },
  {
    "caption": "Spleen size expressed as % body weight for d0 (naïve) or day 28 L. donovani infected WT (blue) and miR-132-/- (miR-132-/-; red) mice.   Liver size expressed as % body weight for d0 (naïve) or day 28 L. donovani infected WT (blue) and miR-132-/- (red) mice.   Data information: Significance determined by unpaired t-test * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.",
    "diseases": "infected"
  },
  {
    "caption": " (A) μCT images of the spine in PGIS model (2D and 3D reconstruction). Arrow head shows spinal ankylosis. n=5 per group. μCT images of new bone (red area) in hind paws (2D and 3D reconstruction) in DBA/1 model compared to baseline. ",
    "diseases": "spinal ankylosis"
  },
  {
    "caption": "  
(B) Incidence of spinal ankylosis in PGIS model. n=5 per cage of total 3 cages per group, Fisher's exact test. (C) Quantitative analysis of structural parameters of spinal ankylosis by μCT analysis. n=5 per group, one‐way ANOVA, Bonferroni post hoc. ",
    "diseases": "spinal ankylosis"
  },
  {
    "caption": " (A) μCT images of the spine in PGIS model (2D and 3D reconstruction). Arrow head shows spinal ankylosis. ",
    "diseases": "spinal ankylosis"
  },
  {
    "caption": " (C) Incidence of spinal ankylosis in PGIS model. n=5 per cage of total 6 cages per group, Fisher's exact test. 
(D) Quantitative analysis of structural parameters of new bone by μCT analysis. n=5, one‐way ANOVA, Bonferroni post hoc. ",
    "diseases": "spinal ankylosis"
  },
  {
    "caption": " (J) H&E and SOFG staining of Achilles tendon enthesis compartment in SMTS model. Data information: UF: Uncalcified fibrocartilage; CF: Calcified fibrocartilage; PCT: posterior calcaneal tuberosity. ",
    "diseases": "Achilles tendon"
  },
  {
    "caption": " (J) Immunofluorescence analysis of Achilles tendon enthesis compartment in SMTS model. Quantitative analysis of CaSR+, p-PLCγ+ and CaSR+ p-PLCγ+ cells number in Achilles tendon enthesis compartment. n=5, one‐way ANOVA, Bonferroni post hoc. Data information: UF: Uncalcified fibrocartilage; CF: Calcified fibrocartilage ",
    "diseases": "Achilles tendon"
  },
  {
    "caption": " (M) SOFG staining of Achilles tendon enthesis compartment in SMTS model. Data information: UF: Uncalcified fibrocartilage; CF: Calcified fibrocartilage; PCT: posterior calcaneal tuberosity. ",
    "diseases": "Achilles tendon"
  },
  {
    "caption": " (C) Immunofluorescence analysis of Achilles tendon enthesis compartment in SMTS model. Quantitative analysis of CaSR+ p-p65+ cells and CaSR+ p-stat3+ cells number in PCT. n=5, Student's t-test. UF: Uncalcified fibrocartilage; CF: Calcified fibrocartilage ",
    "diseases": "Achilles tendon"
  },
  {
    "caption": "Expression of TERT (D) in TERThigh and TERTlow cancer types (6 types in each). ACC (adrenocortical carcinoma), n = 79. KICH (kidney chromophobe), n = 66. KIRP (kidney renal papillary cell carcinoma), n = 291. LGG (brain lower grade glioma), n = 532. PRAD, n = 502. THCA, n = 513. BLCA (bladder urothelial carcinoma), n = 414. CESC (cervical squamous cell carcinoma and endocervical adenocarcinoma), n = 306. DLBC (lymphoid neoplasm diffuse large B-cell lymphoma), n = 48. LUSC (lung squamous cell carcinoma), n = 502. OV (ovarian serous cystadenocarcinoma), n = 430. All boxplots include the median line, box indicates the interquartile range (IQR) and whiskers denote the 1.5 × IQR. P-values were analysed using two-tailed Mann-Whitney U test.",
    "diseases": "ACC, adrenocortical carcinoma, bladder urothelial carcinoma, BLCA, brain lower grade glioma, LGG, cervical squamous cell carcinoma, CESC, KICH, kidney chromophobe, DLBC, lymphoid neoplasm diffuse large B-cell lymphoma, endocervical adenocarcinoma, THCA, lung squamous cell carcinoma, LUSC, OV, ovarian serous cystadenocarcinoma, kidney renal papillary cell carcinoma, KIRP, PRAD"
  },
  {
    "caption": "Expression of DDX58, IFIH1, CXCL10, IFI44, ISG15, and OASL (E) in TERThigh and TERTlow cancer types (6 types in each). ACC (adrenocortical carcinoma), n = 79. KICH (kidney chromophobe), n = 66. KIRP (kidney renal papillary cell carcinoma), n = 291. LGG (brain lower grade glioma), n = 532. PRAD, n = 502. THCA, n = 513. BLCA (bladder urothelial carcinoma), n = 414. CESC (cervical squamous cell carcinoma and endocervical adenocarcinoma), n = 306. DLBC (lymphoid neoplasm diffuse large B-cell lymphoma), n = 48. LUSC (lung squamous cell carcinoma), n = 502. OV (ovarian serous cystadenocarcinoma), n = 430. All boxplots include the median line, box indicates the interquartile range (IQR) and whiskers denote the 1.5 × IQR. P-values were analysed using two-tailed Mann-Whitney U test.",
    "diseases": "ACC, adrenocortical carcinoma, bladder urothelial carcinoma, BLCA, brain lower grade glioma, LGG, cervical squamous cell carcinoma, CESC, KICH, kidney chromophobe, DLBC, lymphoid neoplasm diffuse large B-cell lymphoma, endocervical adenocarcinoma, THCA, lung squamous cell carcinoma, LUSC, OV, ovarian serous cystadenocarcinoma, kidney renal papillary cell carcinoma, KIRP, PRAD"
  },
  {
    "caption": "G Representative sections of immunohistochemical staining of CD4 and FOXP3 in TERT-ERVshigh and TERT-ERVslow colon tumours. Red arrowheads indicate FOXP3+ cells. Scale bar = 100 μm.",
    "diseases": "colon tumours"
  },
  {
    "caption": "(A) MYB knockdown (MiaPaCa-shMYB and Panc1-shMYB) and forced MYB-overexpressing (BxPC3-MYB) PC cells along with their respective control cell lines (MiaPaCa-Scr, Panc1-Scr, and BxPC3-Neo) were subjected to hypoxia (1% O2) treatment for different time intervals (0-96 h). Their growth was measured by viable cell counting using a trypan blue exclusion assay.",
    "diseases": "PC"
  },
  {
    "caption": "(E, F) ECAR (E) and OCR (F) in control and MYB silenced MiaPaCa cells cultured under normoxia or treated with hypoxia mimetic CoCl2 (100 μM for 4 h). Thereafter, ECAR was measured in PC cells with sequential injection of glucose, oligomycin, and 2-DG, while OCR was measured with the serial addition of oligomycin, FCCP, and antimycin A/rotenone.",
    "diseases": "PC"
  },
  {
    "caption": "(A) MYB expression was analyzed by immunoblotting in pancreatic cancer cells cultured under hypoxia for different time intervals. HIF1α accumulation was examined as a positive control.",
    "diseases": "pancreatic cancer"
  },
  {
    "caption": "(E) Pancreatic cancer cells were transiently transfected either with non-targeted control siRNA (siCtrl) or HIF1α -targeting siRNA (siHIF1α) for 24 h and then incubated under hypoxia for 6 h. MYB expression was analyzed at protein and mRNA levels.",
    "diseases": "Pancreatic cancer"
  },
  {
    "caption": "(A) MYB-silenced (MiaPaCa-shMYB and Panc1-shMYB) and MYB-overexpressing (BxPC3-MYB) PC cells, along with their control cell lines (MiaPaCa-Scr, Panc1-Scr, and BxPC3-Neo) were exposed to hypoxia for 6 h. Protein lysates were made, and the expression of MYB and HIF1α was examined by immunoblotting. β-actin served as a loading control.",
    "diseases": "PC"
  },
  {
    "caption": "(C) The transcriptional activity of the HIF1α promoter was determined by performing the promoter-reporter assay. MYB-modulated PC cell lines were transfected with the reporter plasmid, and after 24 h of transfection, cells were cultured under hypoxia or normoxia for 24 h, and the supernatant was collected. HIF1α promoter-driven Gaussia luciferase activity was normalized with SEAP activity, and the data was presented as a bar diagram.",
    "diseases": "PC"
  },
  {
    "caption": "(E) MYB-silenced or -overexpressing PC cell lines were exposed to normoxia or hypoxia for 6 h and subjected to chromatin immunoprecipitation using anti-MYB antibodies or IgG control followed by qPCR analysis using site-specific primers.",
    "diseases": "PC"
  },
  {
    "caption": "(F) MYB-silenced and HIF1α overexpressing MYB knockdown PC cells and control cells were cultured under hypoxia for 48 h. Conditioned media was collected and analyzed to assess glucose consumption and lactate secretion by measuring their levels. The data was normalized with the number of cells and presented as relative fold changes.",
    "diseases": "PC"
  },
  {
    "caption": "(A, B) Interaction of MYB with HIF1α (A) and p300 (B) was examined by co-immunoprecipitation assays in the lysates of pancreatic cancer cells cultured under hypoxia for 6 h. Immunoprecipitation with IgG isotype antibody was used as a control. 10% of total cell lysate was used as input for western blot analysis.",
    "diseases": "pancreatic cancer"
  },
  {
    "caption": "(C, D) Co-localization of MYB with HIF1α (C) and p300 (D) was examined in pancreatic cancer cells grown under hypoxia for 6 h by immunofluorescence assays followed by confocal microscopy. Scale bar, 30 μm (lower left corner). Lower panels are digitally magnified views of the marked rectangles. For ease of visualization, a pseudo color (purple) was adopted for p300 staining.",
    "diseases": "pancreatic cancer"
  },
  {
    "caption": "A B16F10 melanoma cells with either mTRF2 overexpression or knockdown were inoculated into the backs of immunocompetent mice. The percentages of intratumoral CD11bHi GR1Hi MDSCs (n = 10 mice), CD25+ Foxp3+ regulatory T cells (Tregs), or CD25+ Foxp3− activated T cells (n = 5 mice per group) among CD45+ cells were analyzed by fluorescence-activated cell sorting (FACS) and represented as box plots Data information: data are presented by Box plots Min to Max showing all points with median. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001; Mann-Whitney test.",
    "diseases": "melanoma"
  },
  {
    "caption": "B16F10 melanoma cells with or without mTRF2 overexpression were inoculated into the backs of immunocompetent mice and treated with anti-GR1 antibody or isotypic control (200µg/IP). The tumor volume was determined every 2 days using hemi-ellipsoid formula (B). Tumor volume are presented in mm3 along the time in days. All experiments are performed with n = 8 mice per group; *p < 0.05, **p < 0.01, and ***p < 0.001; Mann-Whitney test.",
    "diseases": "melanoma, tumor, Tumor"
  },
  {
    "caption": "B16F10 melanoma cells with or without mTRF2 overexpression were inoculated into the backs of immunocompetent mice and treated with anti-GR1 antibody or isotypic control (200µg/IP). On day 19 of the tumor growth experiment, the percentages of GFP+ cells infiltrating the lungs were determined by FACS and presented as the number of GFP+ cells/mg lung tissue (C). Data information: data are presented by Box plots Min to Max showing all points with median corresponding to the percentages of each cell population among CD45+ cells or the indicated parent population or the number of lung nodules. All experiments are performed with n = 8 mice per group; *p < 0.05, **p < 0.01, and ***p < 0.001; Mann-Whitney test.",
    "diseases": "melanoma, tumor"
  },
  {
    "caption": "On day 21, lung metastasis was analyzed by counting macroscopic metastatic nodules (E scale bars = 500µM.",
    "diseases": "lung metastasis"
  },
  {
    "caption": "B16F10 melanoma cells with or without mTRF2 overexpression were inoculated into tail vein of immunocompetent mice and treated with anti-GR1 antibody or isotypic control (200µg/IP) every 3 days. On day 21, lung metastasis was analyzed by hematoxylin and eosin (H&E) staining F), scale bars = 500µM. Data information: data are presented by Box plots Min to Max showing all points with median corresponding to the percentages of each cell population among CD45+ cells or the indicated parent population or the number of lung nodules. All experiments are performed with n = 8 mice per group; *p < 0.05, **p < 0.01, and ***p < 0.001; Mann-Whitney test.",
    "diseases": "lung metastasis, melanoma"
  },
  {
    "caption": "Tumor-infiltrating immune cells from tumors were analyzed by FACS: MDSCs and CD25+ Foxp3+ Tregs (G) Data information: data are presented by Box plots Min to Max showing all points with median corresponding to the percentages of each cell population among CD45+ cells or the indicated parent population or the number of lung nodules. All experiments are performed with n = 8 mice per group; *p < 0.05, **p < 0.01, and ***p < 0.001; Mann-Whitney test.",
    "diseases": "Tumor, tumors"
  },
  {
    "caption": "Tumor-infiltrating immune cells from tumors were analyzed by FACS NK cells (H) Data information: data are presented by Box plots Min to Max showing all points with median corresponding to the percentages of each cell population among CD45+ cells or the indicated parent population or the number of lung nodules. All experiments are performed with n = 8 mice per group; *p < 0.05, **p < 0.01, and ***p < 0.001; Mann-Whitney test.",
    "diseases": "Tumor, tumors"
  },
  {
    "caption": "Tumor-infiltrating immune cells from tumors were analyzed by FACS: CD8+ T cells (I). Data information: data are presented by Box plots Min to Max showing all points with median corresponding to the percentages of each cell population among CD45+ cells or the indicated parent population or the number of lung nodules. All experiments are performed with n = 8 mice per group; *p < 0.05, **p < 0.01, and ***p < 0.001; Mann-Whitney test.",
    "diseases": "Tumor, tumors"
  },
  {
    "caption": "I Histograms of tumor weights on day 19 after implantation of subcutaneous xenografts containing BJcl2 cells overexpressing or knocked down for HS3ST4 or GPC6 Data information: data are represented as mean +/- SEM (n = 8 mice per group; *p < 0.05, and **p < 0.01; Mann-Whitney test).",
    "diseases": "tumor"
  },
  {
    "caption": "C AFM images showing the Modulus heatmap (stiffness) in GFP-expressing or TRF2-overexpressing cancer cells. At each of the 128x128 force curve points, corresponding to an area of 10 μm2, the AFM software automatically displays the Sneddon modulus analysis while scanning the sample. The color bar on the left of the images shows a qualitative representation of the elastic map.",
    "diseases": "cancer"
  },
  {
    "caption": "D Analysis of pSTAT3 levels in MDSCs after co-culture with GFP-expressing or TRF2-overexpressing cancer cells treated with or without sodium chlorate (NaClO3). Data information: In (D), data represents mean of n = 3 independent experiments +/- SEM (***p < 0.001; Student's t-test).",
    "diseases": "cancer"
  },
  {
    "caption": "Immunocompetent mice were subcutaneously engrafted with B16F10 cells with or without TRF2 overexpression and treated with three intraperitoneal injections of 50 mg/kg 5-FU. The tumor volume was determined every 2 days using a caliper, and growth curves over time (C) Data information: , data represent mean values +/- SEM (n = 8 mice per group; *p < 0.05 and **p < 0.01; Mann-Whitney test).",
    "diseases": "tumor"
  },
  {
    "caption": "Immunocompetent mice were subcutaneously engrafted with B16F10 cells with or without TRF2 overexpression and treated with three intraperitoneal injections of 50 mg/kg 5-FU. tumor volume were determined on day 19 and represented using Box plots Min to Max showing all points with median (D). Data information: (D), data are represented by Box plots Min to Max showing all points with median (n = 8 mice per group; *p < 0.05 and **p < 0.01; Mann-Whitney test)",
    "diseases": "tumor"
  },
  {
    "caption": "A Kaplan-Meier curves for overall survival of patients at all stages of cancers (breast, gastric, ovarian, and lung cancer) depending on TRF2 expression level. Data information: For all panels, the optimal cut-off is determined on KMplot. The p value (log Rank test), the Hazard Ratio and number of patients are indicated.",
    "diseases": "breast, cancers, lung cancer, ovarian, gastric"
  },
  {
    "caption": "The overall survival of gastric cancer patients (all stages) was analyzed depending on TRF2 and its targets genes expression level (HS3ST4, GPC6 and VCAN collectively named the HSPG genes) Data information: For all panels, the optimal cut-off is determined on KMplot. The p value (log Rank test), the Hazard Ratio and number of patients are indicated.",
    "diseases": "gastric cancer"
  },
  {
    "caption": "The overall survival of gastric cancer patients (all stages) was analyzed depending on TRF2 and with MDSC level (Lo or Hi), determine as the mean expression level of CD33 and C5AR, using KMplot Data information: For all panels, the optimal cut-off is determined on KMplot. The p value (log Rank test), the Hazard Ratio and number of patients are indicated.",
    "diseases": "gastric cancer"
  },
  {
    "caption": "E Repartition of number of gastric cancer patients depending on TRF2 and MDSC classification. Data information: For all panels, the optimal cut-off is determined on KMplot. The p value (log Rank test), the Hazard Ratio and number of patients are indicated.",
    "diseases": "gastric cancer"
  },
  {
    "caption": "F Overall survival of gastric cancer patients (all stages) analyzed depending on TRF2, HSPG genes (HS3ST4, GPC6 and VCAN) and MDSC level (Lo or Hi). Data information: For all panels, the optimal cut-off is determined on KMplot. The p value (log Rank test), the Hazard Ratio and number of patients are indicated.",
    "diseases": "gastric cancer"
  },
  {
    "caption": "(A) Western blot  analysis of CRIP1 protein expression in 16 paired HCC  tumor tissues (T) and adjacent nontumor tissues (N). The graph represents CRIP1 protein expression normalized to GAPDH  levels (right). Data information: Data represent the mean ± SD of at least three independent experiments. *P < 0.05, **P < 0.01, and ***P < 0.001. Differences were tested using a two-tailed, paired (A, Student's t-test",
    "diseases": "HCC"
  },
  {
    "caption": "(B) Representative IHC  images of CRIP1 protein expression  in 108 paired HCC  tumor tissues and adjacent nontumor tissues. Scale bars: 20 μm. Statistical analysis of immunohistochemical  score of CRIP1 expression  in HCC tumor tissues and paired adjacent tissues (right). Data information: Data represent the mean ± SD of at least three independent experiments. *P < 0.05, **P < 0.01, and ***P < 0.001. Differences were tested using a two-tailed, paired B) Student's t-test",
    "diseases": "HCC"
  },
  {
    "caption": "(C) CRIP1  mRNA expression  in the TCGA-LIHC  dataset. (D) mRNA levels of CRIP1  in the GSE36376 dataset from the GEO database. Data information: Data represent the mean ± SD of at least three independent experiments. *P < 0.05, **P < 0.01, and ***P < 0.001. Differences were tested using a two-tailed, unpaired Student's t-test",
    "diseases": "LIHC"
  },
  {
    "caption": "The protein (F) levels of CRIP1  in HCC  cell lines and normal LO2 hepatocytes. (G) Relative CRIP1 protein level compared to normal LO2 hepatocytes. Data information: Data represent the mean ± SD of at least three independent experiments. *P < 0.05, **P < 0.01, and ***P < 0.001. Differences were tested using a two-tailed, unpaired G) Student's t-test",
    "diseases": "HCC"
  },
  {
    "caption": "(H-I) Kaplan-Meier survival  analyses of OS (H) and PFS (I) based on CRIP1  expression levels in 108 HCC patients. Data information: Data represent the mean ± SD of at least three independent experiments. *P < 0.05, **P < 0.01, and ***P < 0.001. Differences were tested using log-rank test (H-I).",
    "diseases": "HCC"
  },
  {
    "caption": "(C)  Western blot  analysis of HCC  cancer  stem cell  markers in CRIP1-overexpressing Huh7  and Hep3B  cells.",
    "diseases": "HCC"
  },
  {
    "caption": "(I) Western blot analysis of HCC  cancer stem cell markers in CRIP1-knockdown MHCC-97H and HepG2  cells.",
    "diseases": "HCC"
  },
  {
    "caption": "protein levels  of HCC  cancer stem cell markers (G) in STUB1-overexpressing Huh7  and Hep3B cells transfected with BBOX1-WT or BBOX1  K240R mutant.",
    "diseases": "HCC"
  },
  {
    "caption": "(E) Western blot  analysis of HCC  cancer stem cell  markers in CRIP1-overexpressing Huh7  cells with or without iCRT3  (50 μM) for 24 h.",
    "diseases": "HCC"
  },
  {
    "caption": "(A) IHC  analysis of CRIP1, BBOX1, β-catenin, CD133, OCT4, and NANOG  using TAM (left). Scale bars: 20 μm. Correlation analysis of CRIP1 expression  with BBOX1, β-catenin, CD133, OCT4, and NANOG expression  in HCC  tissues (right). Data information: Data represent the mean ± SD of at least three independent experiments.. **P <0.01 and ***P < 0.001. Chi-square test was performed to determine the correlation (A).",
    "diseases": "HCC"
  },
  {
    "caption": "A,B. A breast cancer tissue array was analyzed for correlations among RagC, miR-105, and miR-204 in tumor stroma by IHC/ISH-determined scores. Representative IHC and ISH images (A) and correlations determined by Kendall's tau correlation tests (N=24 independent tumors; Kendall's tau and two-sided P value as indicated) (B) are shown. Bar=200 μm.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(G) Multiplex IF analyses revealed that transfection with the SEMA7A_WT or SEMA7A_R148W construct decreased the levels of canalicular membrane Bsep and Mrp2 expression in mouse primary hepatocytes in collagen sandwich cultures in a dose-dependent manner (0, 0.2, 1.0 μg per well of 6-well plate; 1.5 ml culture medium per well). Scale bar, 50 µm. Together, the Sema7aR145W mutation can reduce hepatic Bsep and Mrp2 protein expression and lead to intrahepatic BA accumulation and cholestasis (Appendix Table S16). Subsequently, cholestasis triggered an adaptive response in the liver by down-regulating the expression of BA synthetic enzymes of Cyp7a1 and Cyp8b1 and up-regulating the expression of BA efflux transporters Mrp3, Mrp4 and Ostα/β.",
    "diseases": "cholestasis"
  },
  {
    "caption": "Relative quantification of COASY mRNA in human PKAN primary cell lines. n= 5 for both genotypes and cell types",
    "diseases": "PKAN"
  },
  {
    "caption": "Relative quantification of COASY/Coasy in fresh, blood-derived lymphocytes from human and mouse compared by genotype. n=51,35 for human (control, PKAN, respectively) and n=5 for both mouse genotypes.",
    "diseases": "PKAN"
  },
  {
    "caption": "Calculation of active mitochondria using the JC-1 assay by genotype in control and PKAN lymphoblasts.",
    "diseases": "PKAN"
  },
  {
    "caption": "(F) Choroidal flat mounts of adult mice subjected two weeks prior to Laser-CNV injected with PBS, COCO or Flt1Fc stained with IB4 (green) and phalloidin (red). Scale bar, 100 μm. (G) Quantification of CNV surface area. *P=0.0210 (PBS vs COCO); *P=0.0113(PBS vs Flt1Fc); (n=12-14 burns from 5 animals/group).",
    "diseases": "CNV"
  },
  {
    "caption": "(b) Experimental validation of predicted synergistic SR-based combinational therapies in head and neck cancer: A table summarizing the experimentally observed synergism between primary drugs and their predicted rescuer-targeting treatments in 5 HNSC cell lines, based on drug treatment experiments. Synergism was estimated using standard Fa-CI analysis. The table displays the average combination index (CI; synergism CI < 1, additivity effect CI = 1, antagonism CI > 1, NAN indeterminate CI) at 50% growth inhibition (Fraction affected). Combinations that are synergistic are colored blue (black otherwise) for each cell lines tested. The inset shows an example of CI calculation for BYL719 and Dasatinib combination in HN12 cell lines based on the corresponding dose matrix (number indicates % cell viability at 48h, n = 3), and Fa-CI curve.",
    "diseases": "head and neck cancer"
  },
  {
    "caption": "(a) Experimental testing of the predicted SR (DU) rescuers of DNMT1 via drug combination experiments in 18 NSCLC cell lines insensitive to Decitabine. The matrix displays drug interactions between Decitabine, a DNMT1 inhibitor, and inhibitors of its predicted rescuer genes (X-axis) across 18 NSCLC cell lines (Y-axis) that are insensitive to Decitabine. Row labels present rescuer genes and their inhibitors. Colors in the matrix show whether the interactions found are significantly synergistic (red), antagonistic (green) or non-significant (in gray). Values in the matrix show average synergism (<1 synergism and >1 antagonism Thirteen predicted DU-SR rescuers (red lines), two predicted DD SR rescuers (green lines) of DNMT1 and one random control (JAK3i) were tested.",
    "diseases": "NSCLC"
  },
  {
    "caption": "The transcriptomic alterations of rescuer genes post PD1/PDL1 blockade in patient tumor biopsies: Their post (vs. pre) treatment expression changes of DU/DD rescuers after anti-PD1 (b) Each panel displays the expression fold change of each predicted rescuer gene (rows) for different tumor samples (columns) and the P-value of over-all paired Wilcoxon test of the expression changes observed in paired samples. Significantly altered up/down-regulated genes are marked by (*). Genes marked in red are those whose CRISPR knockdown enhances melanoma sensitivity to anti-PD1 blockade in mice models.",
    "diseases": "melanoma"
  },
  {
    "caption": "The transcriptomic alterations of rescuer genes post CTLA4 blockade in patient tumor biopsies: Their post (vs. pre) treatment expression changes of DU/DD rescuers after anti-CTLA4 (c) Each panel displays the expression fold change of each predicted rescuer gene (rows) for different tumor samples (columns) and the P-value of over-all paired Wilcoxon test of the expression changes observed in paired samples. Significantly altered up/down-regulated genes are marked by (*). Genes marked in red are those whose CRISPR knockdown enhances melanoma sensitivity to anti-PD1 blockade in mice models.",
    "diseases": "melanoma"
  },
  {
    "caption": "The transcriptomic alterations of rescuer genes post PD1/PDL1 and CTLA4 blockade in patient tumor biopsies: Their post (vs. pre) treatment expression changes of DU/DD rescuers after PD1 + CTLA4 combination therapies (d). Each panel displays the expression fold change of each predicted rescuer gene (rows) for different tumor samples (columns) and the P-value of over-all paired Wilcoxon test of the expression changes observed in paired samples. Significantly altered up/down-regulated genes are marked by (*). Genes marked in red are those whose CRISPR knockdown enhances melanoma sensitivity to anti-PD1 blockade in mice models.",
    "diseases": "melanoma"
  },
  {
    "caption": "(C) Representative pictures of Nlrp3A350V/wt MRP8-CreTg and Nlrp3A350V/wt MRP8-Cre- mice  on days 4 and 8 after birth. Left side in each picture: Nlrp3A350V/wt MRP8-Cre- mice; right side in each picture: Nlrp3A350V/wt MRP8-CreTg. Abscesses  (day 4) and  scaling erythema (day 8) are observed in Nlrp3A350V/wt MRP8-CreTg mice.",
    "diseases": "Abscesses, scaling erythema"
  },
  {
    "caption": "(C) Levels of mucosal vtRNA2-1, vtRNA1-1, vtRNA1-2, and vtRNA1-3 in the colon of patients with active ulcerative colitis (UC). Values are the means ± SEM (n = 6 per group). Unpaired, two-tailed Student's t test was used. * P < 0.05 compared with controls. (D) Levels of tissue vtRNAs in the ileal mucosa of patients with Crohn's disease (CD). Values are the means ± SEM (n = 6 per group). Unpaired, two-tailed Student's t test was used. * P < 0.05 compared with controls.",
    "diseases": "CD, Crohn's disease, UC, ulcerative colitis"
  },
  {
    "caption": "APP/PS1-21 mice  (5 m) treated with rhEPO (10000 IU/kg/d) or ARA290  (0.03 mg/kg/d) (i.p., once a day, for 14 days) (n=10), and Aβ plaques   in cortex  and hippocampus  (n = 5) were detected by IHC  (I). Data information: For multiple groups, one-way ANOVA was used. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance. ARA, ARA290; IHC, Immunohistochemical staining.",
    "diseases": "plaques"
  },
  {
    "caption": "11-month-old APP/PS-1-21+/+/Lyz2-Cre+/+/Eporloxp/loxp mice  (APP/PS1-21+EPOR-MKO) or APP/PS-1-21+/+/Lyz2-Cre+/+/Epor+/+ mice  (APP/PS1-21+EPOR-C), Aβ plaques  in the cortex  and hippocampus  of mice  of 11-month-old (M) (n = 5) were detected by IHC. Data information: Unpaired t-tests were used for the comparison of two groups. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance. IHC, Immunohistochemical staining.",
    "diseases": "plaques"
  },
  {
    "caption": "R Aβ plaques  in the cortex  and hippocampus  (n = 4) were detected by IHC. Data information: Unpaired t-tests were used for the comparison of two groups. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance. IHC, Immunohistochemical staining.",
    "diseases": "plaques"
  },
  {
    "caption": "E Aβ plaques   in the cortex  and hippocampus  (n = 5) were detected by IHC. Data information: vehicles were PBS. For multiple groups, one-way ANOVA was used. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance.",
    "diseases": "plaques"
  },
  {
    "caption": " A Pie chart depicting fine-mapping results (Huang et al, 2017) (posterior probabilities) for an IBD-associated locus on 21q21 (left panel). MPRA results in resting (centre panel) and stimulated CD4 T cells (right panel) showing that the putative causal variant has significant expression-modulating effect. ",
    "diseases": "IBD"
  },
  {
    "caption": " B Pie chart depicting Bayesian fine-mapping results for an AS-associated locus on 2p15 (left panel). MPRA results in stimulated T cells (right panel) showing that rs6759298 has a significant expression-modulating effect (the strongest of any variant at this locus) while the other candidate SNPs have negligible effects. ",
    "diseases": "AS"
  },
  {
    "caption": " C GWAS results (Liu et al, 2015) at a Crohn's disease and multiple sclerosis-associated locus on 6p23 (left panel). MPRA for candidate SNPs in stimulated T cells (right panel) identifying a SNP (rs34421390) with by far the greatest expression-modulating effect at this locus (blue, risk allele reduces expression; red, risk allele increases expression). Dotted horizontal line represents significance threshold (corrected for multiple-testing). ",
    "diseases": "Crohn's disease, multiple sclerosis"
  },
  {
    "caption": "D GWAS results at a Type 1 Diabetes-associated locus on 14q32 (Onengut-Gumuscu et al, 2015; left panel). MPRA for the candidate SNPs in stimulated T cells (right panel). The construct with the largest and most significant effect contains the risk alleles for 2 SNPs (rs1988588 and rs3902659), each of which has a smaller effect when tested individually (position indicated by vertical dotted line). Dotted horizontal line represents significance threshold (corrected for multiple-testing).",
    "diseases": "Type 1 Diabetes"
  },
  {
    "caption": " A IBD GWAS results (Liu et al, 2015) at a multi-disease-associated locus on chromosome 6q23. ",
    "diseases": "IBD"
  },
  {
    "caption": "I Expression of genes on 6q23 in CD4 T cells from 131 patients with active IBD, stratified by rs6927172 genotype (qPCR; one-way ANOVA). Error bars represent SD. Expression of IL20RA and IL22RAR2 not detected.",
    "diseases": "IBD"
  },
  {
    "caption": " A. Quantification of netrin-3 gene expression by q-RT-PCR in a panel of 181 human NB stages 1, 2, 3, 4 and 4S. Number of cases is indicated on the graph. Error bars indicate s.e.m. Statistical treatment of the data was performed using a two-sided Student t-test. ",
    "diseases": "NB"
  },
  {
    "caption": " B. Quantification of netrin-3 gene expression by q-RT-PCR in a panel of 181 human neuroblastoma patients, defined as low- and high-risk NB. The number of cases is indicated on the graph. Error bars indicate s.e.m. Statistical treatment of the data was performed using a two-sided Student t-test. ",
    "diseases": "NB, neuroblastoma"
  },
  {
    "caption": " C. Netrin-3 high expression is a marker of poor prognosis in NB. 280 months overall Kaplan-Meier survival curves in a panel of 181 patients of all NB stages. The cohort was dichotomized base on netrin-3 median expression (in green and red). Statistical treatment of the data: Mantel-Cox; p value is indicated below the graph. ",
    "diseases": "NB"
  },
  {
    "caption": " D. Netrin-3 high expression is a marker of poor prognosis in aggressive NB. 280 months overall Kaplan-Meier survival curves in a panel of 54 stage 4 patients. The cohort was dichotomized base on netrin-3 expression, as presented in panel C. Statistical treatment of the data: Mantel-Cox; p-value is indicated below the graph. E. Confirmation in 498 RNA-seq NB patients that netrin-3 high expression is a marker of poor prognosis in NB. 6,000 days overall Kaplan-Meier survival curves. The cohort was dichotomized based on netrin-3 median expression (in green and red). Statistical treatment of the data: Mantel-Cox; p-value is indicated below the graph.",
    "diseases": "NB"
  },
  {
    "caption": " A. Gene Set Enrichment Analysis (GSEA) in high netrin-3 NB patients. The cohort was dichotomized with the n=50 lowest vs 50 highest: amplification the MYCN pathway (p=0.039; fdqr=0.025). ",
    "diseases": "NB"
  },
  {
    "caption": " B. Netrin-3 expression is higher in MYCN amplified NB patients. The cohort was dichotomized based on mycn amplification and sorted for netrin-3 expression. Statistical treatment of the data: Welsh test; p-value is indicated on the graph. Error bars indicate s.e.m (boxes= 25th to 75th percentile; central band= mean; whiskers = min to max).",
    "diseases": "NB"
  },
  {
    "caption": " C. Q-RT-PCR analysis of netrin-3 gene expression in IMR32 (n=5) and IGRN91 (n=5) NB cell lines after MYCN silencing by siRNA (U-test). Error bars indicate s.e.m. ",
    "diseases": "NB"
  },
  {
    "caption": " D. ChIP-seq analysis of MYCN binding, active enhancer epigenetic marks H3K27ac, H3K4me1, and active promoter epigenetic mark H3K4me3, on netrin-3 locus (red line). An enrichment of MYCN, associated with active enhancer marks, was detected in three different neuroblastoma cell lines NB-1643, COGN415 and LAN5. ",
    "diseases": "neuroblastoma"
  },
  {
    "caption": " A. Deep analysis of netrin-3 gene expression in lung cancer cell lines (n=76; RNA-Seq). ",
    "diseases": "lung cancer"
  },
  {
    "caption": " B. Q-RT-PCR analysis of netrin-1 and -3 expression, in lung cancer cell Lines (Error bars indicate SD, n=3). ",
    "diseases": "lung cancer"
  },
  {
    "caption": "  C. Representative netrin-3 and -1 mRNA detection, using RNAscope on SCLC paraffin embedded tumor sections. Negative control DAPB, positive control PPiB. Each brown dot is a unique molecule of mRNA of each targeted gene (n=10, scale bars 20µm). D. Quantification of netrin-3 and -1 expression in human SCLC paraffin embedded tumor sections (High≥ 50% marked cells; Low≤ 5%).  ",
    "diseases": "SCLC"
  },
  {
    "caption": " B. ChIP-seq analysis of NeuroD1 and ASCL-1 chromatin enrichment, which was associated with broad H3K27ac-enriched regions at the netrin-3 locus (red line), indicating a transcriptionally active region in SCLC cell lines. (rep= experimental replicates). ",
    "diseases": "SCLC"
  },
  {
    "caption": " C. Q-RT-PCR analysis of netrin-3 gene expression in NCI-H82 (n=6) and NCI-H69 (n=4) SCLC cell lines after Neurod-1 and ASCL-1 silencing by siRNAs (U-test). Error bars indicate s.e.m. ",
    "diseases": "SCLC"
  },
  {
    "caption": " D. Netrin-3 silencing delays or inhibits SCLC engraftment in vivo. NMRI nude mice were subcutaneously engrafted with either NCI-H82-CRIPSR/cas9-NTN3 with three different guides RNAs (sG1 p=0.0022; sG2 p≤0.001; and sG3 p≤0.001) or control cells (sGc) n=6/group. Positive tumor engraftment was report when tumors reached 50 mm3 (Mantel Cox). ",
    "diseases": "SCLC"
  },
  {
    "caption": "Immunoblots with the indicated antibodies on lysates from A549 and NIH-H23 LAC cell lines treated with SB203580 for 24 hours.",
    "diseases": "LAC"
  },
  {
    "caption": "MTT viability assays of A549 and NCI-H23 LAC cells treated with SB203580.",
    "diseases": "LAC"
  },
  {
    "caption": "ATP proliferation (K) assays of A549 and NCI-H23 LAC cells treated with SB203580.",
    "diseases": "LAC"
  },
  {
    "caption": "Representative images of pADAM17-stained lung sections from normal (cancer-free) control and LAC patients. Scale bar, 100μm. Quantification of pADAM17-positive cells in (B) normal (cancer-free) control individuals (n = 8) and LAC patients (n = 18)",
    "diseases": "LAC"
  },
  {
    "caption": "Quantification of pADAM17-positive cells and pERK1/2 MAPK-positive cells in LAC patients either KRAS wild-type (WT, n = 13) or mutant (MUT, n = 5).",
    "diseases": "LAC"
  },
  {
    "caption": "Linear regression analyses of pADAM17 with pERK1/2 (D) and pp38 (E) MAPK staining in serial lung sections from LAC KRAS wild-type and mutant patients.",
    "diseases": "LAC"
  },
  {
    "caption": "Immunoblots of lysates from normal human bronchial epithelial cells (HBEC) and LAC cell lines A549, NIH-H23 and NIH-H2228 with the indicated antibodies. Shown are lysates from 2 separate passages per cell line. Pro, proADAM17; Mat, mature ADAM17. Densitometric semi-quantification of immunoblots showing the relative expression levels of pADAM17 (relative to Actin), pro and mature forms of ADAM17 (relative to Actin), and pERK1/2 and pp38 MAPK (relative to their total counterparts) protein levels.",
    "diseases": "LAC"
  },
  {
    "caption": "PC-1 signature is predictive of metastatic disease in mouse models of pancreatic cancer. Log-transformed expressions of signature transcripts from mouse tumor microarrays were mean-centered across samples and scaled to unit variance. These values were then multiplied by the matching loading values from the PC-1 signature and summarized for each sample across all transcripts to yield the risk score for that sample.",
    "diseases": "tumor"
  },
  {
    "caption": "D Kaplan-Meier (non-parametric) survival curve showing significantly extended tumor-free survival of KPC mice treated with LOX antibody (1 mg/kg i.p., twice weekly) + gemcitabine (100 mg/kg i.p., twice weekly) (green line, n = 17), compared with gemcitabine ± isotype control antibody-treated mice (blue line, n = 22, P = 0.014) or LOX antibody alone (red line, n = 9). Treatment was initiated when mice were 70 days old (randomization was not used when recruiting the mice) and the mice were treated twice weekly. Censored mice did not develop PDAC.",
    "diseases": "tumor"
  },
  {
    "caption": "A Outer left panels: Immunohistochemistry analysis of macrophage infiltration (by F4/80 staining) in tumors from isotype control + gemcitabine-treated KPC mice vs. LOX antibody + gemcitabine-treated KPC mice. Inner left panels: Immunohistochemistry analysis of neutrophil infiltration (by MPO staining) in tumors from isotype control + gemcitabine-treated KPC mice vs. LOX antibody + gemcitabine-treated KPC mice. Inner right panels: Immunohistochemistry analysis of tumorvasculature (by CD31 staining) in tumors from isotype control + gemcitabine-treated KPC mice vs. LOX antibody + gemcitabine-treated KPC mice. Outer right panels: Immunohistochemistry analysis of tenascin C expression in tumors from isotype control + gemcitabine-treated KPC mice vs. LOX antibody + gemcitabine-treated KPC mice.B-D Plots showing quantification of macrophage infiltration (B), neutrophil infiltration (C) and tumorvasculature (D) in tumors from KPC mice treated as indicated. At least 30 fields of view from at least four mice per cohort were scored, and scoring was conducted blind. P-values were calculated using Mann-Whitney U-test and median is indicated by horizontal lines.E Correlation of LOX protein with tenascin C expression in 47 cases of PDAC (Spearman's rho correlation coefficient = 0.61; P < 0.0001).",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "(B) Fold-change ± standard error in baseline IL-6 plasma levels at week 12 from RA patients treated with placebo (n=47), baricitinib 1-mg (n=23), 2-mg (n=24), 4-mg (n=23), and 8-mg (n=23) in the phase 2b randomized, placebo-controlled study NCT01469013. p values are for comparisons of baricitinib 1-mg, 2-mg, 4-mg, and 8-mg change from baseline compared to the placebo change from baseline. Treatment effects were estimated using a mixed effects repeated measures model (SAS Proc Mixed) using log10 transformed IL-6 levels with an unstructured covariance matrix.",
    "diseases": "RA"
  },
  {
    "caption": "(C) Chest CT scan for Patient C on day one and 19 from symptom onset showing clinical improvement over time. Day one CT scan shows ground glass opacity (arrows) sub-pleurally in the lower lobes bilaterally (early stage one according to Pan et al (Pan, Ye et al., 2020). Day 19 CT scan shows that consolidation was gradually absorbed with evident residual fibrosis and emphysema bubbles (arrows) in the site of the early lesions (absorption stage four according to Pan et al (Pan et al., 2020).",
    "diseases": "emphysema, fibrosis"
  },
  {
    "caption": "PEGSerp-1 treated mouse lung   sections from MA10   at day 2 follow up have significant reduction in uPAR  positive stained   areas (A) with reduced positively stained hemorrhagic  areas in lungs   at 2 days in MA10   infected BALB/c (B; p < 0.041) and reduced uPAR  + stained   cell counts at 4 days (C; p < 0.0202) and 7 days (C in alveoli   (p < 0.0148) in MA30   infected C57BL/6 mice. With delayed treatments uPAR  is reduced at 7 days follow up (D; ANOVA p< 0.0001, p < 0.0002 for PEGSerp-1 at 10µg/kg). FX staining   was reduced with prophylactic  PEGSerp-1 at day 7 but not at day 4 follow up (E; ANOVA p < 0.0008, p < 0.0001 for day 7 and p = 0.5148 for day 4). Data information: Mean ±SE. * p < 0.05, *** p < 0.001, **** p < 0.0001; ANOVA indicated by line at top with subgroup analyses in brackets below; back and blue circles Saline, red and green circles PEGSerp-1  treatments",
    "diseases": "hemorrhagic"
  },
  {
    "caption": "Representative en face Oil Red O staining  (A) of Oil Red O-positive plaque lesion   area in aortas. Plaque  area was defined as percentage of total surface area of the aorta  (n=10 biological replicates).",
    "diseases": "Plaque, plaque lesion"
  },
  {
    "caption": "Representative images (C) of plaque lesion  area in  aortic  arches (n=10 biological replicates).",
    "diseases": "plaque lesion"
  },
  {
    "caption": "(E-F) Representative images of Oil Red O staining  (E) and quantification (F) of  atherosclerotic lesion in aortic roots (scale bar=250 μm, n=10 biological replicates). Plaque  area was quantified by the proportion of plaque  area to aortic root area. Data information: Data were shown as mean ± SEM; *, P < 0.05; ns, not significant, two-tailed unpaired Student's t-test.",
    "diseases": "atherosclerotic lesion, Plaque, plaque"
  },
  {
    "caption": "(P-Q) Representative immunofluorescence staining  images (P) and quantification (Q) of p-p65  (red) in aortic roots. Tissues were counterstained  with DAPI  (blue). Scale bar=100 μm, n=10 biological replicates. p-p65  area was quantified by the proportion of p-p65  positive area to plaque  area. Data information: Data were shown as mean ± SEM; *, P < 0.05; ns, not significant, two-tailed unpaired Student's t-test.",
    "diseases": "plaque"
  },
  {
    "caption": "Representative images (C) of  plaque lesion area in aortic arches (n=10 biological replicates). The plaque  area was quantified by the proportion of plaque  area to aortic arches area.",
    "diseases": "plaque, plaque lesion"
  },
  {
    "caption": "E. ELISA  analysis shows increased αSMA levels in a TGFβ1 dose-dependent manner from MCs and IPF-MCs in the  co-culture  system. Note a stronger αSMA response in  IPF-MCs (mean + s.d., n = 3 biological replicates from 6 MCs and 6 IPF-MCs donors, **p = 0.0014, ****p < 0.0001, Nonlinear Regression followed by ANOVA/Sidak's).",
    "diseases": "IPF"
  },
  {
    "caption": "(J) Super-resolution microscopy of tumor tissues labelled as in (C).",
    "diseases": "tumor"
  },
  {
    "caption": "(K) Maximum Z-projection of a tumor section labelled with EpCAM antibodies (Red) and DNA in blue. The dashed line shows the absence of EpCAM staining, arrows show a disorganized region.",
    "diseases": "tumor"
  },
  {
    "caption": "(A) Images of EOC tumors labelled with antibodies against PCNT (red) and CDKRAP2 (green). Nuclei are shown in blue. The colored arrows reflect different centrosome number. The list of centrosome behaviors annotated it is not exhaustive to allow comprehension of the events. #TT72, shows a cyst-like arrangement of EOC nuclei where it is impossible to correspond centrosomes to individual nuclei. The white bars with arrows of different colors highlight possible interpretations of the same condition. In #TT79, regions without centrosomes can be identified. In the inset, a single centrosome localized in the lumen can be identified and it is not possible to know to which nucleus (white dashed lines) it corresponds to. #TT88 presents only very small clusters of centrosomes, few nuclei without centrosomes and many conditions with 2 centrosomes. In #TT61, regions without centrosomes can be distinguished, in addition to nuclei associated with single centrosomes. In #TT46, clusters containing large (inset 1) or small clusters (inset 3) can be identified. In cyst-like arrangements several centrosomes can be identified (inset 2), suggesting that all cells have at least one centrosome or, in contrast just one centrosome (inset 4), illustrating lack of centrosomes.",
    "diseases": "EOC"
  },
  {
    "caption": "(B-C) Plots showing the frequency of centrosome amplification events (B) and the frequency of nuclei without centrosomes (C) in tumor tissues. Note that in B and C, the order of the tumors is conserved between the two plots to allow for comparison. For each tumor, 10 random fields were chosen and analysed, with an average of 5248 nuclei counted per tumor.",
    "diseases": "tumor"
  },
  {
    "caption": "(D) Tumor sections labelled with CEP135 (green) and PCNT (red) on the left and CEP135 (green) and CEP192 (red) on the right. The white squares represent the regions shown in higher magnifications on the right.",
    "diseases": "Tumor"
  },
  {
    "caption": "Kaplan-Mayer curve evaluating the overall survival of HNSCC patients treated with RT+Cetuximab (CTX) combination included in the TCGA dataset, segregated on the expression of miR-9 in the primary tumor (Low expression <75819 reads n=8; High expression ≥75819 reads n=23). Number of evaluated samples (n) and p value are reported in the graph. Statistical significance was calculated with long-rank test.",
    "diseases": "HNSCC"
  },
  {
    "caption": "Kaplan-Mayer curve evaluating the progression free survival of HNSCC patients treated with RT+Cetuximab (CTX) combination at the CRO-Aviano National Cancer Institute and at the University Cattolica segregated based on miR-9 expression in primary tumors, defined as the expression in above (high expression n=18) or below (low expression n=17) the median expression, as defined by ddPCR. Hazard Ratio (HR) and statistical significance were calculated with long-rank (Mentel-Cox) test and are reported in the graph.",
    "diseases": "HNSCC"
  },
  {
    "caption": "A. Schematic diagram of sucrose  density gradient ultracentrifugation for  RNC isolation, and PCR  verification of the 12 screened lncRNA  in both RNC-RNA and total RNA from two groups of  CRC cells, among which the translation level of lnc-AP (marked with a green box) was the most notably dysregulated in both groups of drug-resistant cells (n = 3, biological replicates, mean±SEM, t test). Data information: * for P < 0.05; ** for P < 0.01; NS for no significance.",
    "diseases": "CRC"
  },
  {
    "caption": "B. PCR analysis of  lnc-AP in serum samples from  oxaliplatin-resistant (PD, n = 15) and -sensitive (PR, n = 9) CRC patients (mean±SEM, t test).",
    "diseases": "CRC"
  },
  {
    "caption": "C. In the public database lncCAR, high expression level of lnc-AP was correlated with long overall survival in CRC patients.",
    "diseases": "CRC"
  },
  {
    "caption": "B. CCK-8 assay of inhibition ratio by L-OHP in two groups of  CRC cells with down- or up-regulation of  lnc-AP  (n = 3, biological replicates, mean±SEM). Data information: * si-NC was the abbreviation of commercial normal control of siRNA.",
    "diseases": "CRC"
  },
  {
    "caption": "C.  IF detection of H2AFX for  DNA damage by L-OHP in two groups of CRC cells with down- or up-regulation of   lnc-AP, and nuclei were stained with DAPI (n = 3, biological replicates, mean±SEM, Dunnett-t test).",
    "diseases": "CRC"
  },
  {
    "caption": "A. WB analysis of  TALDO1 overexpression or knock down in two groups of  CRC cells, which was quantified by gray analysis on the right (n = 3, biological replicates, mean±SEM, t test). Data information: * for P < 0.05; ** for P < 0.01. Control referred to the corresponding plasmid vector and si-NC was the abbreviation of commercial normal control of siRNA.",
    "diseases": "CRC"
  },
  {
    "caption": "F. MMP detection with down- or up-regulation of   lnc-AP/pep-AP in two groups of  CRC cells. Scale bar, 10 µm.",
    "diseases": "CRC"
  },
  {
    "caption": "C. Flow cytometry of the cell apoptosis ratio under  L-OHP with down- or up-regulation of  lnc-AP/pep-AP in two groups of CRC cells, which was quantified in bar charts on the right (n = 3, biological replicates, mean±SEM, Dunnett-t test). Data information: * for P < 0.05; ** for P < 0.01; NS for no significance. Control referred to the corresponding plasmid vector and si-NC was the abbreviation of commercial normal control of siRNA.",
    "diseases": "CRC"
  },
  {
    "caption": "Representative composite immune-fluorescent images of whole hair follicle units from non-lesional and lesional scalp psoriasis patients. K15 (green), c-JUN (red A, C) and JUNB (red B, D) and DAPI (blue).",
    "diseases": "scalp psoriasis"
  },
  {
    "caption": "Confocal images of the bulge region of human psoriatic hair follicles from non-lesional and lesional regions of the scalp. K15 (green), c-JUN (red E, G) and JUNB (red F, H) and DAPI (blue).",
    "diseases": "psoriatic"
  },
  {
    "caption": "Percentage of HF-SCs (K15+) that express c-JUN (I) and JUNB (J) in the bulge region of human psoriatic hair follicles from non-lesional and lesional scalp in comparison with healthy scalp. n=2-6 hair follicles in anagen per group from five psoriatic patients and two healthy patients.",
    "diseases": "psoriatic"
  },
  {
    "caption": "Composite immunofluorescent images showing GFP expression of whole-ear sections from DKO*-mT/mG mice at day 5, 7, 15 and 30. Increased GFP expression is shown at day 7 followed by progressive decrease of GFP+ keratinocytes (white dotted line represents basal layer, and red dotted line represents outermost skin layer). n=3 per time point. Quantification analysis of GFP expression (top) and epidermal thickness (bottom) of DKO* mice at different time points during psoriasis-like disease progression. n=6 per time point. Statistical significance *p<0.05, **p<0.01, ***p<0.001 (t-student two tailed-test relative to control group).",
    "diseases": "psoriasis"
  },
  {
    "caption": "Quantification analysis of cleaved Caspase-3 (cCas3 top) and Ki67 (bottom) in ear skin of DKO* mice at different time points during psoriasis-like disease progression. n=3 per time point.",
    "diseases": "psoriasis"
  },
  {
    "caption": "Ear pictures of control, DKO*, and DKO*K15 mice after 15 days of induction show clear signs of inflammation and psoriatic-like scales in both models.",
    "diseases": "inflammation, psoriatic"
  },
  {
    "caption": "Ear thickness measurement at different time points during psoriasis-like development in control, DKO* and DKO*K15 mice. n > 5 per group. Statistical significance *p<0.05, **p<0.01, ***p<0.001 (t-student two tailed-test relative to control group).",
    "diseases": "psoriasis"
  },
  {
    "caption": "FACS quantification of CD45+ cells from ear skin of control, DKO* and DKO*K15 mice at different time points during psoriasis-like development. n > 5 per group. Statistical significance *p<0.05, **p<0.01, ***p<0.001 (t-student two tailed-test relative to controls).",
    "diseases": "psoriasis"
  },
  {
    "caption": "Quantification of IL-17A, IL-6 and LCN2 production in sera of control, DKO* and DKO*K15 mice at day 30 of psoriasis-like disease by ELISA. n > 4 per group. Statistical significance *p<0.05, **p<0.01, ***p<0.001 (t-student two tailed-test relative to controls).",
    "diseases": "psoriasis"
  },
  {
    "caption": "Quantification of total number of GFP+ epidermal cells by FACS analysis from DKO*-mT/mG and DKO*K15-mT/mG mice at different time points during psoriasis-like progression compared to Co-mT/mG mice. n = 3-6 per group and time point.",
    "diseases": "psoriasis"
  },
  {
    "caption": "Representative immunofluorescence images of ear sections from CoK15-mT/mG and DKO*K15-mT/mG mouse models after 15 days of induction. Red (Tomato), green (GFP) and blue (DAPI). Hyperplasia of Tomato+ keratinocytes in psoriatic-like DKO*K15-mT/mG mouse with clusters of GFP+ keratinocytes are derived from hair follicle K15+ GFP+ stem cells. n=3 per group. Dotted lines separate epidermis and dermis. Quantification analysis of cleaved Caspase-3 (cCas3) and Ki67 in ear skin of DKO*K15-mT/mG mice at different time points during psoriasis-like disease progression.",
    "diseases": "Hyperplasia, psoriasis, psoriatic"
  },
  {
    "caption": "Gene expression of TSLP in different epidermal cell subpopulations sorted at mid-term (D7) or late-term (D30) of psoriasis-like progression in DKO* mice.",
    "diseases": "psoriasis"
  },
  {
    "caption": "protein expression of TSLP in different epidermal cell subpopulations sorted at mid-term (D7) or late-term (D30) of psoriasis-like progression in DKO* mice. n=2-3.",
    "diseases": "psoriasis"
  },
  {
    "caption": "Quantification of TSLP production in sera of control, DKO* and DKO*K15 mice at day 30 of psoriasis-like disease by ELISA. n = 4 per group.",
    "diseases": "psoriasis"
  },
  {
    "caption": "Longitudinal analysis of ear thickness in DKO* mice at different time points during psoriasis-like disease progression",
    "diseases": "psoriasis"
  },
  {
    "caption": "Representative composite immune-fluorescent images of whole hair follicle units by confocal from non-lesional and lesional scalp psoriasis patients. c-JUN (purple), K-15 (green), TSLP (red) and DAPI (blue).",
    "diseases": "scalp psoriasis"
  },
  {
    "caption": "TSLP intensity measurement in hair follicle units and epidermis by ImageJ from healthy scalp, non-lesional and lesional scalp psoriasis patients. Representation of fold change relative to control healthy scalp. n= 3 samples.",
    "diseases": "scalp psoriasis"
  },
  {
    "caption": "Representative composite immune-fluorescent images of whole hair follicle units by confocal from non-lesional and lesional scalp psoriasis patients (D) and magnification images of specific regions from the HFs (E). CD200 (green), c-JUN (white), TSLP (red), DAPI (blue).",
    "diseases": "scalp psoriasis"
  },
  {
    "caption": "A. I.29µ+  B lymphoma  cells  were treated with  LPS to induce differentiation towards  IgM secretion. At the indicated  times, cells were lysed in TritonX114 to separate soluble and integral membrane proteins (aqueous and detergent phases, respectively). Aliquots from the two phases were resolved electrophoretically and the  blot was decorated by anti-µ antibodies. The blue arrow points at a band likely corresponding to  µs2L2C575OX, the intensity of which increases upon LPS stimulation.",
    "diseases": "B lymphoma"
  },
  {
    "caption": "FOXA1 and FOXA2 expression in human PDAC areas with distinct differentiation grade. Immunohistochemistry analysis of FOXA1 (top) and FOXA2 (bottom) in human PDAC. Representative G1, G2 and G3 areas from one patient are shown. Red dotted lines indicate the borders of poorly differentiated (G3) tumor areas.",
    "diseases": "PDAC"
  },
  {
    "caption": "Percent of FOXA1- and FOXA2-positive nuclei in PDAC cells from areas of different grade. Tissue microarrays were automatically acquired and quantified using QuPath. The number (n) of analyzed areas of each grade is indicated.",
    "diseases": "PDAC"
  },
  {
    "caption": "Expression of FOXA1 and FOXA2 in low-grade and high-grade PDAC cell lines. Vinculin is shown as loading control.",
    "diseases": "PDAC"
  },
  {
    "caption": "Representative areas from human PDAC tissue showing expression of HNF1β in G1, G2 and G3 areas. The red dotted line indicates the borders of a G3 area. The percentage of HNF1β-positive cells in areas of different grade from a PDAC tissue microarray is shown.",
    "diseases": "PDAC"
  },
  {
    "caption": "Colocalization of HNF1β and FOXA2 in human PDAC areas. PDAC sections from three different patients were stained with the anti-HNF1β antibody, stripped and re-stained with the anti-FOXA2 antibody. The red dotted areas on the left represent poorly differentiated (G3) tumor regions.",
    "diseases": "PDAC"
  },
  {
    "caption": "A. Arrest architecture of replicative stress. 2C  and 4C arrest  trajectories are shown, the regions that correspond to mitotic skipping and the senescent state are annotated and the arrest trajectory of 8C polyploid  cells is indicated. N = 4315 cells",
    "diseases": "polyploid"
  },
  {
    "caption": "E. Cyclin D1  abundance (left) and the proportion of polyploid  cells (right), as measured by immunofluorescence  and Hoechst staining, respectively, following siRNA-mediated knockdown of  cyclin D in control and etoposide-treated cells. Boxplots show data from four independent replicates (gray circles). Data information: Statistical significance in right panels was determined using a two-way analysis of variance (ANOVA) with Sidak's post hoc test (*** p < 0.001, * p = 0.02). boxes show the interquartile range, the whiskers indicate the full distribution of points and the central band represents the population.",
    "diseases": "polyploid"
  },
  {
    "caption": "F. Cyclin D1  abundance (left) and the proportion of polyploid  cells (right), as measured by immunofluorescence  and Hoechst staining, respectively, following doxycycline  (dox)-induced upregulation of  cyclin D1 in control and etoposide-treated cells. Boxplots show data from six independent replicates (gray circles). Data information: Statistical significance in right panels was determined using a two-way analysis of variance (ANOVA) with Sidak's post hoc test (*** p < 0.001, * p = 0.02). boxes show the interquartile range, the whiskers indicate the full distribution of points and the central band represents the population.",
    "diseases": "polyploid"
  },
  {
    "caption": "G. Cyclin A  abundance (left) and the proportion of polyploid  cells (right), as measured by immunofluorescence  and Hoechst staining, respectively, following doxycycline  (dox)-induced upregulation of cyclin A2  in control and etoposide-treated cells. Boxplots show data from six independent replicates (gray circles). Data information: Statistical significance in right panels was determined using a two-way analysis of variance (ANOVA) with Sidak's post hoc test (*** p < 0.001, * p = 0.02). boxes show the interquartile range, the whiskers indicate the full distribution of points and the central band represents the population.",
    "diseases": "polyploid"
  },
  {
    "caption": " A FAK phosphorylation of WT or interface mutant FAK in SCC cells. Whole cell lysates were subjected to western blot analysis with anti-pFAK Y397, anti-pFAK Y576/577, anti-pFAK Y861, anti-pFAK Y925 and anti-FAK. Anti-GAPDH served as a loading control. The graph shows densitometric analysis of relative pFAK/FAK ratios (mean) from three independent experiments. Student's t-test was carried out to calculate the statistical significance. Error bars: s.d. * = p < 0.01, # = p < 0.05. For full blots see source data. ",
    "diseases": "SCC"
  },
  {
    "caption": " B Downstream signaling in SCC cells expressing WT or interface mutant FAK. Whole cell lysates are analyzed by western blot analysis with the indicated antibodies. The graph shows densitometric analysis of relative phospho/total protein ratios (mean) from three independent experiments. Student's t-test was carried out to calculate the statistical significance. Error bars: s.d. * = p < 0.01, # = p < 0.05. For full blots see source data. ",
    "diseases": "SCC"
  },
  {
    "caption": " C Src phosphorylation and interactions between FAK and Src or pSrc Y416 in SCC cells . FAK, Src or pSrc Y416 were immunoprecipitated from whole cell SCC lysates using anti-pSrc Y416, anti-FAK, anti-Src or non-specific IgG-agarose, followed by western blot analysis with anti-FAK, anti-pSrc Y416 and anti-Src. Anti-GAPDH served as a loading control. For full blots see source data. ",
    "diseases": "SCC"
  },
  {
    "caption": "FAK-expressing SCC cells were grown on glass coverslips, fixed and stained with anti-FAK anti-Paxillin and DAPI Representative immunofluorescence images are shown. Scale bars, 20 μm.",
    "diseases": "SCC"
  },
  {
    "caption": " B FAK-expressing SCC cells were grown on glass coverslips, fixed and stained with anti-pSrc Y416 , anti-Paxillin and DAPI Representative immunofluorescence images are shown. Scale bars, 20 μm. The graph (B) shows the quantification of internalized active Src from three independent experiments. Student's t-test was carried out to calculate the statistical significance. Error bars, s.d. * = p < 0.01. ",
    "diseases": "SCC"
  },
  {
    "caption": " C Subcellular fractionation of SCC cells expressing FAK-WT or interface mutant FAK. Whole cell lysates (WCL) and subcellular fractions were subjected to western blot analysis with anti-FAK, anti-Tubulin (marker for cytoplasmic fraction; C), anti-RCAS (marker for perinuclear fraction; PN) and anti-H4 (marker for nuclear fraction; N). The graph shows densitometric analysis of relative FAK amount of the FAK mutants in the different fractions from three independent experiments. Student's t-test was carried out to calculate the statistical significance. Error bars: s.d. * = p < 0.01, # = p < 0.05. For full blots see source data. ",
    "diseases": "SCC"
  },
  {
    "caption": " A FAK-WT, interface mutant FAK or FAK -/- SCC cells were resuspended in methylcellulose solution in growth medium on a layer of agarose and observed for 3D sphere formation. Images were taken from 10 random fields after nine days (representative images are shown) and the relative colony size (top graph) as well as the number of colonies (bottom graph) were assessed from three independent experiments. Scale bars, 200 μm. Student's t-test was carried out to calculate the statistical significance. Error bars s.d. * = p < 0.01, # = p < 0.05. ",
    "diseases": "SCC"
  },
  {
    "caption": " B FAK-WT, interface mutant FAK or FAK -/- SCC cells were seeded on growth factor-reduced Matrigel in serum-free media. After 72 h, invasion towards a serum gradient was analyzed by staining the cells with calcein and taking images at 10 μm increments through the matrigel. Representative images of the invasion assay are shown. Scale bars, 200 μm. The graph shows relative invasion from five independent experiments. Student's t-test was carried out to calculate the statistical significance. Error bars, s.e.m. * = p < 0.01, # = p < 0.05. ",
    "diseases": "SCC"
  },
  {
    "caption": "B. Mid-sagittal (I), coronal  (II) and transversal  (III) MRI  scans of Patient  1 with newly identified ELP4  variants and Patient  2 and Patient  3 with ELP6  variants. Atrophy  of the cerebellum  with prominence of the cerebellar folia is marked by circles. Arrows indicate thin corpus callosum, red arrowheads point to enlarged extra-axial CSF  spaces and black arrowheads to cerebral sulci in keeping with cerebral  and cerebellar  volume loss.",
    "diseases": "Atrophy"
  },
  {
    "caption": "(B) Representative sequencing chromatograms  of PIK3CA  and TEK  mutant VM-derived ECs. Arrows show the detected point mutations.",
    "diseases": "VM"
  },
  {
    "caption": "D-F. Immunoblotting of DRG homogenates shows that nerve injury-dependent nuclear HDAC3 dephosphorylation is reduced by the calcium scavenger EGTA upon in vivo delivery on the injured sciatic nerve (Axo=Axotomy). Cytoplasmic pERK levels are used as control of axotomy-dependent signalling. (E-F). Data is expressed as mean fold change of band intensity levels ± s.e.m. N= 3 biological replicates. (**p<0.01, ***p<0.001) indicate a significant difference (ANOVA followed by Bonferroni test).",
    "diseases": "nerve injury, injured"
  },
  {
    "caption": "J-L. Immunofluorescence (J) in DRG tissue sections 24h after injury in vivo shows that the PP2a/PP4 inhibitor Fostriecin (F) inhibits the injury-induced decrease in pHDAC3 (K) and the increase in H3K9ac (L). Scale bar, 10 μm. (K-L). Data is expressed as mean fluorescence intensity in arbitrary units ± s.e.m. N= 3 (L) or 4 (K) biological replicates (*p<0.05; **p<0.01) indicate significant difference versus sham (ANOVA followed by Bonferroni test).",
    "diseases": "injury"
  },
  {
    "caption": "A, B. Co-immunofluorescence of anti-neuronal and anti-regeneration associated proteins in DRG following SCI and treatment with 966 or vehicle. Shown is increased protein expression for regeneration-associated targets in NF200 positive DRG neurons (arrows) after 966 treatment (5 weeks following SCI). Scale bar, 50 μm. (B) Data is expressed as fold change of fluorescence intensity in NF200+ cells, 966 versus vehicle ± s.e.m. N=4-7 biological replicates * p<0.05, ** p<0.01, *** p<0.005 indicate significant difference versus vehicle (Student's t-test).",
    "diseases": "SCI"
  },
  {
    "caption": "A-B. AAV-HDAC3 mutant (Y298H; dominant negative deacetylase inactive) promoted DRG regenerative growth after spinal cord injury vs AAV-V5 control (injected 5 weeks prior to SCI in the sciatic nerve bilaterally) as shown by dextran-red traced axons across and beyond the lesion site (GFAP, green) (dotted lines denote the rostral and caudal margins of the scar around the lesion). Scale bar, (A-B) 200 μm.",
    "diseases": "SCI, spinal cord injury"
  },
  {
    "caption": "A-B. Intrathecally administered RGFP966 (966) through osmotic minipump for 14 days promoted DRG regenerative axonal growth after spinal cord injury as shown by dextran-red traced axons across and beyond the lesion site (GFAP, green) (dotted lines denote the rostral and caudal margins of the scar around the lesion). Scale bar, 200 μm.",
    "diseases": "spinal cord injury"
  },
  {
    "caption": "(A) PAS staining for total glycogen in  skin  fibroblasts  from different APBD patients. Staining  fluorescence was quantified by InCell2200 (see Methods). Means (+/- SEM) are statistically different from each other (p<0.0001, One Way ANOVA). n=3 technical replicates from each patient  indicated at the x-axis were used.",
    "diseases": "APBD"
  },
  {
    "caption": "(B) PAS staining for total glycogen in APBD87 fibroblasts glucose-starved for 48 h (left), or glucose starved and then replenished for the last 24 h to induce  glycogen burden (right). Image acquisition performed by Nikon Eclipse Ti2 microscope using a 40x PlanFluor objective and CY3  filter. Scale bar, 100 µm.",
    "diseases": "APBD"
  },
  {
    "caption": "(D) Glycolytic (red) and mitochondrial  (blue)  ATP production determined by Agilent's Seahorse machine and real-time ATP rate assay kit. HC and APBD patient fibroblasts were serum/glucose-starved for 48 h and then full medium was replenished for 24 h without (untreated), or with (chronic) 50 µM 144DG11. Acute, 50 µM 144DG11  was added on assay for 20 min after 24 h of serum/glucose  replenishment. Readings were normalized to cell number as determined by Crystal Violet staining. Shown are mean and SEM values based on n=3-6 technical repeats. For all experiments (HC, p<0.01; APBD1, p<0.02; APBD2, p<0.09; APBD3, p<0.11; One Way ANOVA with Sidak's post-hoc correction for multiple comparisons) glycolytic ATP production was increased, as compared to untreated control, by acute, but not chronic, supplementation of 144DG11. Mitochondrial ATP  production was increased only by acute supplementation of 144DG11 to APBD2 fibroblasts (p<0.06).",
    "diseases": "APBD"
  },
  {
    "caption": "(E)  LAMP1-KD and 144DG11 treatment cause  lysosomal acidification. Upper panel, flow cytometry results showing that 144DG11 slightly increased acidification (yellow to blue median fluorescence ratio (Y/B)) in control, GFP-transduced, APBD fibroblasts (Y/B(GFP/144DG11)>Y/B(GFP), p<0.12), but significantly acidified  LAMP1-KD, GFP-shLAMP1-transduced, APBD fibroblasts (Y/B(LAMP1-KD/144DG11)>(Y/B(LAMP1-KD), p<0.03). LAMP1-KD itself led to the most significant acidification (Y/B (LAMP1-KD)>Y/B(GFP), p<0.007). n=3, two-tailed t-tests. Middle panel Lysosensor staining of the corresponding cells. Yellow fluorescence intensity correlates with acidification. Lower panel, PAS  (glycogen)  staining  of the corresponding cells. Scale bars, 50 µm.",
    "diseases": "APBD"
  },
  {
    "caption": "(B) Morphological  characterization of lysosomes based on  lysotracker staining  of n=4 HC and n=4 (biological replicates) APBD patient skin fibroblasts starved for 48 h and treated or not with 50 uM 144DG11 for 24 h. Values are deviations from untreated HC. 144DG11 has reduced lysotracker  mean intensity, integrated intensity (DXA), and area in both HC and APBD fibroblasts  (***p<0.0001, One-Way ANOVA with Sidak's multi-comparison post-hoc test).",
    "diseases": "APBD"
  },
  {
    "caption": "(C) Functional (mitochondrial membrane potential (TMRE parameters)) and biomass (mitotracker) characterization of mitochondria in HC and APBD  cells treated and analyzed as in (B). Mean (***, p<0.0001) and integrated (***, p<0.0006) TMRE  intensities, and mitochondrial  biomass (***, p<0.0001), were reduced in APBD v HC. 144DG11 increased TMRE mean (**, p<0.009, **, p<0.006) and integrated (*, p<0.01, **, p<0.001) intensities in APBD  and HC cells, respectively and  mitotracker  intensity in APBD cells only (***, p<0.0001). Data represent n=3 biological replicates. Statistical differences analyzed by One-way ANOVA with multiple comparisons.",
    "diseases": "APBD"
  },
  {
    "caption": "D CWR22 xenografts were grown in nude mice, and tumors were collected at different times after castration. mRNA was extracted from the tumors and used for qPCR analysis of STAMP2 expression. The results are presented as boxplots. Thick horizontal lines represent the median, with the box representing the upper and lower quartile. The whiskers represent the 5th and 95th percentiles, and the outlier is presented as an open circle. The statistical significance was determined by one-way ANOVA with a post hoc test. n = 3 in group week 0, 1, 2, and 4; n = 5 in refractory group. *P = 0.011; **P = 0.049. Error bars indicate SEM.",
    "diseases": "tumors"
  },
  {
    "caption": "E ATF4 expression in xenografted tumors of 22Rv1 cells stably expressing control shRNA or shRNA against STAMP2 was analyzed by qPCR. Student's t-test was used to analyze the statistical significance, n = 4. *P = 0.022; **P = 0.015; ***P = 0.044. Error bars indicate SEM.",
    "diseases": "tumors"
  },
  {
    "caption": "F CWR22 xenografts were grown in nude mice, and tumors were collected at different times after castration. The association between ATF4 and STAMP2 in the tumor samples was determined by Western blot analysis.",
    "diseases": "tumors"
  },
  {
    "caption": "b) Volcano plot of contrast MPX  vs healthy controls; α <= 0.015 and |logFC| >= 1.35 were used for selection of regulated proteins.",
    "diseases": "MPX"
  },
  {
    "caption": "d) Boxplots illustrating key proteins that differ between patients  with MPX  and controls (p-values and fdr for corresponding contrast MPX  vs Control are provided in brackets): TTR   (p-value = 9E-10, fdr = 2E-7), LBP   (p-value = 2E-4, fdr = 2E-3), APOC1  (p-value = 5E-8, fdr = 3E-6), and C9  (p-value = 2E-8, fdr = 2E-6). Here, as usual, the central bar marks the median (second quartile), the bottom edge of the box marks the first quartile, the top edge of the box marks the third quartile, and the bottom and top whiskers mark the minimum and maximum values that are not outliers. The specific values of the protein expressions  are also shown. Provided p-values are obtained from moderated statistics implemented in limma, dfrs were calculated according to Benjamini-Hochberg.",
    "diseases": "MPX"
  },
  {
    "caption": "e) Correlation between MPX  severity (NSkin lesions) and  protein expression (y-axis). One MPX patient  had an unclear additional skin  condition (not a pure case of MPX) and therefore was excluded from the regression analysis that compares the number of skin lesions with the proteome; however, the proteome of this patient  was largely in agreement with those of the other MPX  cases As a measure of MPX  severity, the log2(1 + NLesions / 15) was used. Here NLesions is the number of lesions. R2 shows squared correlation coefficient. MPX patients  are colored orange, control patients  green.",
    "diseases": "skin lesions, MPX"
  },
  {
    "caption": "a) Heatmap displaying hierarchical clustering using differentially regulated proteins between patients  with MPX, COVID-19, and controls.",
    "diseases": "COVID-19, MPX"
  },
  {
    "caption": "b) Scatterplot of log fold-change (logFC) for contrast MPX  vs control (C1, x-axis) and logFC for contrast  COVID-19 vs control (C2, y- axis). Only the central part of the cloud is shown here. Three truncated dots (APOC1, CRP, and SAA1) are shown in the lower left and upper right corner. Differentially abundant (Regulated; 'Reg') proteins are color coded, with the red color corresponding to 37 proteins differentially abundant in both MPX  vs control (C1) and COVID-19  vs control (C2), the orange color corresponding to proteins specifically changed in MPX  vs control (C1) only (16 proteins), and the green color corresponding to proteins responding to both MPX  vs control (C1) and MPX  vs COVID-19 (C3) (3 proteins). There are no intersections between COVID-19 vs control (C2) and MPX  vs COVID-19  (C3). The blue color corresponds to proteins responding to MPX  vs COVID-19 (C3), but not in MPX  vs control (C1) (11 proteins), and the pink color to proteins responding to COVID-19  vs control (C2) only (19 proteins). The red dotted line shows a linear regression through the red dots, i.e. proteins differentially abundant in MPX  vs control (C1) and COVID-19 vs control (C2). Note that orange and pink points have the same direction of regulation in both MPXV  vs control (C1) and COVID-19 vs control (C2). Only green and blue dots (except three proteins: ADIPOQ, GPLD1, and IGHV1-2) have opposite directions in C1 and in C2.",
    "diseases": "COVID-19, MPX, MPXV"
  },
  {
    "caption": "d) Differentially regulated proteins of patients  with MPX  and COVID-19 (Volcano Plot); α ≤ 0.015 and |logFC| >= 1.35 were used for selection of regulated proteins. The chosen significance level ensured that fdr for this contrast was below 22%.",
    "diseases": "COVID-19, MPX"
  },
  {
    "caption": "e) Key proteins that differ between patients  with MPX   and COVID-19  (Boxplots) (p-values and fdr for corresponding contrast MPX  vs COVID-19 are provided in brackets): LCP1   (p-value = 3E-4, fdr = 3E-2), LDHB   (p-value = 2E-3, fdr = 6E-2), CFHR1   (p-value = 2E-4, fdr = 3E-2). Here the central bar marks the median (second quartile), the bottom edge of the box marks the first quartile, the top edge of the box marks the third quartile, and the bottom and top whiskers mark the minimum and maximum values that are not outliers. The specific values of the protein expressions  are also shown. Provided p-values are obtained from moderated statistics implemented in limma, dfrs were calculated according to Benjamini-Hochberg.",
    "diseases": "COVID-19, MPX"
  },
  {
    "caption": "f) Top 8 proteins of an SVM-trained model discriminating between healthy controls (n=15) and MPX  cases (n=6) (top) or COVID-19  (n=10) and MPX  (n=6) cases (bottom). Means of the relative coefficients over a 5-fold cross-validation are shown. Error bars denote the standard deviations. Red denotes positive, blue denotes negative coefficients. The AUC was calculated based on withheld samples that were not used for training the model.",
    "diseases": "COVID-19, MPX"
  },
  {
    "caption": "b) Hierarchical clustering using differentially regulated proteins between patients  with MPX  and controls (Heatmap); p < 0.05 with Mann-Whitney U test with FDR-based multiple testing correction.",
    "diseases": "MPX"
  },
  {
    "caption": "c) Key proteins that differ between patients  with MPX  and controls, and COVID-19 (Boxplots). Dashed blue lines indicate the lowest detected peptide concentration from calibration curves. Statistics based on Mann-Whitney U test with multiple testing corrections. For boxplots, median is indicated by a solid line, hinges show the 25th and 75th percentiles, whiskers show values that, at maximum, are within 1.5 times the interquartile range.",
    "diseases": "COVID-19, MPX"
  },
  {
    "caption": "d) Top 15 peptides of an SVM-trained model discriminating between healthy controls (n=15) and MPX  cases (n=6). Means of the relative coefficients over a 5-fold cross-validation are shown. Error bars denote the standard deviations. Red denotes positive, blue denotes negative coefficients. The AUC was calculated based on withheld samples that were not used for training the model.",
    "diseases": "MPX"
  },
  {
    "caption": "A Up, Representative views of H2AXimmunostaining from 117 BC patients of Luminal-A (LumA, N=33), HER2 (N=37) and Triple-Negative (TN, N=47) subtypes. Scale bars = 100 μm. Down, representative views at high magnification of H2AXimmunostaining focused on the Fibroblasts (Left) or Epithelium (Right) cells. Scale bars = 25 μm.B Scatter plots of H2AX histological score (Hscore = staining intensity (0 to 4) x % of positive cells quantified from H2AXimmunostaining (as shown in A) in Fibroblasts (Left) or Epithelial (Right) cells from LumA, HER2 and TNbreasttumours.C Correlation plots between H2AX Hscores evaluated in fibroblasts and in epithelial cells (as shown in B), in HER2 (left) and TN (right) breasttumours.",
    "diseases": "tumours"
  },
  {
    "caption": "B Left, Representative views of H2AX and γ-H2AX immunostaining in TN tumours (N = 22) before and after successive cycles of chemotherapy. Scale bars = 100 μm. Zoom views are focused on the epithelial cells. Scale bars = 25 μm. Right, Scatter plots of H2AX, γ-H2AX histological scores (Hscores) and γ-H2AX/H2AX ratio evaluated from immunostaining in the epithelium, before and after chemotherapy.",
    "diseases": "tumours"
  },
  {
    "caption": "J Box plots showing expression levels of representative NRF2-target genes in TN tumours with minor- or major-H2AX decrease, as indicated. Lines indicate Means and whiskers show 10-90 percentiles. ACOT7: Acyl-CoA Thioesterase 7; PGD: Phosphogluconate Dehydrogenase. AHR: Aryl Hydrocarbon Receptor; JAG1: Jagged1. P-values are from t-test.",
    "diseases": "tumours"
  },
  {
    "caption": "(A) The ploidy index is inferred as 1/cell density of tumorous (T) and non-tumorous (NT) tissue of HCC patients with different liver diseases. ALD - alcoholic liver disease (n=65); HBV - hepatitis B virus infection (n=24); HCV - hepatitis C virus infection (n=85); NASH - non-alcoholic steatohepatitis (n=33). Statistical significance was determined by one-way ANOVA with multiplicity correction (Sidak-Holm); * p≤0.05, ** p≤0.01, *** p≤0.001. n-numbers refer to the number of patient samples analyzed.",
    "diseases": "alcoholic liver disease, ALD, hepatitis B virus infection, hepatitis C virus infection, HCC, NASH, non-alcoholic steatohepatitis"
  },
  {
    "caption": "(B) All patients were grouped according to HCC tumor cell density as surrogate for tumor ploidy. Data were divided at the median and exact patient numbers are shown in the graphs. Median recurrence-free survival (RFS) for a period of 10 years for patients with low tumor ploidy was 4.8 years. For patients with high tumor ploidy the median RFS could not be defined as more than 50% of the patients survived without relapse. Patient characteristics are shown in Appendix table S1. A Log-rank test was used to determine statistical significance.",
    "diseases": "HCC"
  },
  {
    "caption": "G Patients  suffering from  ulcerative colitis (UC) show reduced levels of both Elp1  and Elp3. The central band represents the mean value of relative expression  in the investigated cohort. Boxes represent 75th and 25th percentile. Whiskers represent maximum and minimum values before the upper and lower fence, respectively (**= p< 0.01, ***= p<0.001) (GSE9452-GEO DataSets, Definition of an ulcerative colitis  pre-inflammatory state).",
    "diseases": "UC, ulcerative colitis"
  },
  {
    "caption": "T2-weighed brain MRIs of patient A (D1-3) at 28 months of age and patient B at (D4-6) at 16 months of age, showing global brain atrophy as well as periventricular and deep white matter hyperintensities.",
    "diseases": "atrophy"
  },
  {
    "caption": "Identification of the ENU-induced hearing loss pedigree MPC169, subsequently named clarinet. ABR phenotyping of pedigree Muta-Ped-C3PDE-169 at 3-months of age identified 8 mice with elevated hearing thresholds (red triangles) compared to their normal hearing colony mates (n=61, black triangles). Indeed, all eight affected mice were found to not respond to the highest intensity stimulus (90 dB SPL) at the three frequencies tested, or the click stimulus, and so their thresholds are shown as 95 dB SPL.",
    "diseases": "hearing loss"
  },
  {
    "caption": "Auditory phenotyping of clarinet mice at P16 (C), P21 (D) ABR threshold measurements show that Clrn2clarinet/clarinet mice (red) exhibit a severe-to-profound hearing loss affecting all frequencies tested. At 16 kHz in Clrn2clarinet/clarinet mice, the mean ABR hearing thresholds vary from 55-65 dB SPL at P16, 60-90 dB SPL at P21, and to 80-100 dB SPL at P28 and P42. Age-matched Clrn2+/+ (black) and Clrn2clarinet/+ (grey) controls display thresholds within the expected range (15-45 dB SPL) at all frequencies and time-points tested. At P16, all eight Clrn2clarinet/clarinet mice exhibited recordable ABR responses for each frequency tested and the click stimulus. For the longitudinal ABR study, at P21 and P28 three of the seven Clrn2clarinet/clarinet mice were found to not respond at the highest intensity stimulus (90 dB SPL) for at least one frequency-specific/click stimulus. By P42, five of the Clrn2clarinet/clarinet mice were found to not respond at the highest intensity stimulus (90 dB SPL) for at least two frequency-specific/click stimuli. ABR data shown are mean ± s.d. ***p<0.001, one-way ANOVA.",
    "diseases": "hearing loss"
  },
  {
    "caption": "Auditory phenotyping of clarinet mice at P28 (E) and P42 (F). ABR threshold measurements show that Clrn2clarinet/clarinet mice (red) exhibit a severe-to-profound hearing loss affecting all frequencies tested. At 16 kHz in Clrn2clarinet/clarinet mice, the mean ABR hearing thresholds vary from 55-65 dB SPL at P16, 60-90 dB SPL at P21, and to 80-100 dB SPL at P28 and P42. Age-matched Clrn2+/+ (black) and Clrn2clarinet/+ (grey) controls display thresholds within the expected range (15-45 dB SPL) at all frequencies and time-points tested. At P16, all eight Clrn2clarinet/clarinet mice exhibited recordable ABR responses for each frequency tested and the click stimulus. For the longitudinal ABR study, at P21 and P28 three of the seven Clrn2clarinet/clarinet mice were found to not respond at the highest intensity stimulus (90 dB SPL) for at least one frequency-specific/click stimulus. By P42, five of the Clrn2clarinet/clarinet mice were found to not respond at the highest intensity stimulus (90 dB SPL) for at least two frequency-specific/click stimuli. ABR data shown are mean ± s.d. ***p<0.001, one-way ANOVA.",
    "diseases": "hearing loss"
  },
  {
    "caption": "Vestibular behavioural tests (swim tests, contact-righting, trunk-curl, and platform). The Clrn2clarinet/clarinet mice (red, P28, n=5, and P60, n=7) have no vestibular dysfunction, displaying similar performances to age-matched control Clrn2clarinet/+ mice (grey, P28, n=3, and P60, n=7). Being similar, the values at P28 and P60 were combined. Electroretinogram (ERG) measurements from control Clrn2clarinet/+ (grey) and mutant Clrn2clarinet/clarinet (red) mice. Each trace in B and C is representative of an ERG response from the eye of age-matched Clrn2clarinet/+ and Clrn2clarinet/clarinet mice, showing no significant difference in a- or b-wave amplitudes. (D-F) The lack of change in ERG amplitude responses in Clrn2clarinet/clarinet mice (aged 3 or 6-7 months), regardless of the test conditions: scotopic (D,E), or photopic (F), indicate normal photoreceptor kinetics and no change in the sensitivity of photoreceptor cells.",
    "diseases": "vestibular dysfunction"
  },
  {
    "caption": "Two human (SKMEL28 and 1205Lu) and a murine (B16BL6) melanoma cell lines were exposed, or not, to the indicated EV from primary murine adipocytes obtained from lean mice fed a normal diet (ND) or obese mice fed a high fat diet (HFD), then FAO was measured (n =5 for B16BL6, SKMEL28 HFD EV and 1205Lu ND EV and n=6 for other conditions).",
    "diseases": "melanoma, obese"
  },
  {
    "caption": "Volcano plot of mass spectrometry-based quantitative proteomics results showing relative abundance of proteins in primary murine adipocyte EV from obese mice (HFD), as compared to those from lean mice (ND). The dashed lines indicate cut-off values and points colored in grey indicate proteins that display non-significant fold-change by Welch t-test between both conditions (n=3 for ND, 4 for HFD). Proteins involved in FAO are indicated by yellow dots.",
    "diseases": "obese"
  },
  {
    "caption": "Western blot analysis of the indicated FAO enzymes in the EV secreted by primary adipocytes from lean (ND) and obese (HFD) mice (top panel) and from human individuals with varying BMI (normal weight, NW; overweight, OW and obese, OB) (bottom panel). For each blot, extracts from 3 independent batches of murine samples or 3 independent individuals for human samples (1-3) are shown. Flotillin 1 (FLOT1) is used as a loading control.",
    "diseases": "OB, obese, overweight, OW"
  },
  {
    "caption": "Western blot analysis of the indicated FAO enzymes in melanoma cells treated, or not, with EV from lean (ND) and obese (HFD) mice. Tubulin (TUB) is used as a loading control.",
    "diseases": "melanoma, obese"
  },
  {
    "caption": "RT-qPCR analysis of mRNAs for the indicated genes in 1205Lu cells treated or not with EV secreted by primary adipocytes from lean (ND) and obese (HFD) mice for 48 h. Results are expressed relative to the corresponding value for control cells (n=3).",
    "diseases": "obese"
  },
  {
    "caption": "Indicated melanoma cells were incubated with EV from 3T3-F442A adipocytes previously loaded with BODIPY FL C16 (3T3-FL C16-EV) and, 24h later, cells were fixed and nuclei were counterstained with DAPI before observation by confocal microscopy.",
    "diseases": "melanoma"
  },
  {
    "caption": "Lipids were extracted from EV secreted by adipocytes from lean (ND) and obese (HFD) mice (n=5) (left panel) or from human adipose tissue samples from patients with varying BMI (right panel) and fatty acid content was measured (n=15).",
    "diseases": "obese"
  },
  {
    "caption": "Indicated cells were exposed, or not, to adipocyte EV from primary adipocytes from lean mice fed a normal diet (ND) or obese mice fed a high fat diet (HFD) for 24h. Then, cells were fixed, stained with BODIPY and counterstained with DAPI. Left panel, confocal microscopy observation. Right panel, quantification of BODIPY staining area per cell (n=5 for SKMEL28 and n=6 for 1205Lu).",
    "diseases": "obese"
  },
  {
    "caption": "1205Lu cells were exposed, or not, to adipocyte EV from lean mice fed a normal diet (ND) or obese mice fed a high fat diet (HFD) with, or without, Lalistat 2 (Lal). Cells were then fixed, stained with BODIPY and counterstain with DAPI before observation by confocal microscopy. Quantification of BODIPY staining per cell is shown on the right (n=5).",
    "diseases": "obese"
  },
  {
    "caption": "Western blot analysis of the indicated mitochondrial fission proteins in melanoma cells treated, or not, with EV from 3T3-F442A adipocytes (3T3-EV). Tubulin (TUB) is used as a loading control.",
    "diseases": "melanoma"
  },
  {
    "caption": "1205Lu cells were exposed to adipocyte EV from lean mice fed a normal diet (ND) or obese mice fed a high fat diet (HFD) and immediately treated, or not, with Mdivi-1. Cell motility was then tracked by video microscopy (n = 40 cells per group).",
    "diseases": "obese"
  },
  {
    "caption": "Left panel, indicated melanoma cells exposed to 3T3-F442A EV were fixed, stained with BODIPY and Phalloidin before observation by confocal microscopy. Right panel, quantification of the percentage of cells presenting lipid droplets (LD) within membrane protrusions (n=6).",
    "diseases": "melanoma"
  },
  {
    "caption": "Left panel, melanoma cells exposed to EV secreted by adipocytes from lean mice fed a normal diet (ND) or obese mice fed a high fat diet (HFD) were fixed, stained with BODIPY and Phalloidin before observation by confocal microscopy. Right panel, quantification of the percentage of cells presenting lipid droplets (LD) within membrane protrusions (n=5 for SKMEL28 and n=6 for 1205Lu).",
    "diseases": "melanoma, obese"
  },
  {
    "caption": "Left panel, 1205Lu melanoma cells were exposed, or not, to 3T3-F442A EV. Then, live cells were stained with LysoTracker and BODIPY probes and observed by confocal microscopy. Right panel, quantification of the percentage of cells presenting lysosome within membrane protrusions (n=3).",
    "diseases": "melanoma"
  },
  {
    "caption": "TCGA data were analyzed to reveal the effect of high mRNA levels of key FAO enzymes on the overall survival of patients with melanoma. Statistical significance of survival was evaluated with a Log-rank (Mantel-Cox) Test (n=449, 450 and 459 for HADHA, HADHB and ECHS1 respectively).",
    "diseases": "melanoma"
  },
  {
    "caption": "BODIPY staining of neutral lipid stores in the indicated melanoma cell lines, which present increasing degrees of aggressiveness (from left to right). DAPI was used to counterstain nuclei. Scale bar: 20µm.",
    "diseases": "melanoma"
  },
  {
    "caption": "FAO in the indicated melanoma cell lines was measured. Bars and error bars represent means ± SEM (n=5); statistically significant by one-way ANOVA with post hoc Tukey's test, ***P < 0.001. If not indicated, non-significant.",
    "diseases": "melanoma"
  },
  {
    "caption": "TCGA data were analyzed to reveal the effect of high mRNA levels of key actors in mitochondrial dynamics on the overall survival of patients with melanoma. Statistical significance of survival was evaluated with a Log-rank (Mantel-Cox) Test (n=459).",
    "diseases": "melanoma"
  },
  {
    "caption": "G. Cell proliferation of SHSY5Y human neuroblastoma cells assessed by MTT assay post 12 h treatment with 5 µM ApoSOD12SH, I113T SOD12SH and G85R SOD12SH condensates and aggregates (fibrils). Cell culture medium (DMEM) was used as negative control and untreated SHSY5Y cells were used as positive control.",
    "diseases": "neuroblastoma"
  },
  {
    "caption": "H. Dot plots showing flow cytometric analysis of annexin V and propidium iodide (PI) staining of apoptotic SHSY5Y neuroblastoma cells following a 12 h treatment with 5 µM ApoSOD12SH condensates, I113T SOD12SH condensates, G85R SOD12SH condensates, ApoSOD12SH fibrils, I113T SOD12SH fibrils and G85R SOD12SH fibrils respectively (see Methods for details). High cytotoxicity was observed for SOD12SH condensates.",
    "diseases": "neuroblastoma"
  },
  {
    "caption": "In RSPO3 rescue experiment, each mouse was treated with 5 μg RSPO3 in 100μL PBS by retro-orbital injection 30 min before ischemia. PBS treated mice were used as vehicle control. (C) Representative images of crypts immunostained with OLFM4 and β-catenin in PBS/RSPO3 treated EC-Foxc-DKO mice 24h after I/R. The accumulation of β-catenin in the nuclei of ISCs (dotted circles) was found in RSPO3 rescued mice. Paraffin sections (4 µm), (D) Quantification of relative fluorescent intensity (FI) of β-catenin immunostaining within ISC and (E) quantification of the number of OLFM4+ ISCs were performed based on Figure 9C. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 4~6, *P<0.05.",
    "diseases": "ischemia"
  },
  {
    "caption": "In RSPO3 rescue experiment, each mouse was treated with 5 μg RSPO3 in 100μL PBS by retro-orbital injection 30 min before ischemia. PBS treated mice were used as vehicle control. (F) Representative images of immunostaining of CCND1 in intestines in PBS/RSPO3 treated EC-Foxc-DKO mice at I/R-24h. Scale bars = 100 µm. (G) Quantification of the number of CCND1+ epithelial cells per crypt at I/R-24h are based on Figure 9F. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 7, **P<0.01.",
    "diseases": "ischemia"
  },
  {
    "caption": "In RSPO3 rescue experiment, each mouse was treated with 5 μg RSPO3 in 100μL PBS by retro-orbital injection 30 min before ischemia. PBS treated mice were used as vehicle control. (H) Relative mRNA expression of Rspo3 in sorted LECs and Cxcl12 in sorted BECs from intestines of PBS/RSPO3 treated EC-Foxc-DKO mice at I/R-18.5h. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 4~6, *P<0.05.",
    "diseases": "ischemia"
  },
  {
    "caption": "In RSPO3 rescue experiment, each mouse was treated with 5 μg RSPO3 in 100μL PBS by retro-orbital injection 30 min before ischemia. PBS treated mice were used as vehicle control. Representative images of H&E staining show the rescue effects of RSPO3 in intestinal mucosa LEC-Foxc-DKO (I) mice as well as their control mice 24h after I/R. Red numbers indicate the Chiu scores. Quantification of Chiu Score for the intestines at I/R-24h are based H&E staining as shown in Figure 9A and 9I. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 6~13, **P<0.01.",
    "diseases": "ischemia"
  },
  {
    "caption": "In RSPO3 rescue experiment, each mouse was treated with 5 μg RSPO3 in 100μL PBS by retro-orbital injection 30 min before ischemia. PBS treated mice were used as vehicle control. (K) Representative images of CD31/LYVE1 immunostaining in the intestines of PBS/RSPO3 treated LEC-Foxc-DKO mice at I/R-24h. (L, M) Quantification of the vessel density (L) (= vessel area/total intestinal tissue area x 100%) for the blood (B) and/or lymphatic (L) vessels (markers listed below the graph were used to identify B and L) as well as the measurement of lacteal length (M) was performed based on Figure 9K. The Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 7, **P<0.01, n.s.=not significant.",
    "diseases": "ischemia"
  },
  {
    "caption": "In CXCL12 rescue experiments, mice were treated with 50μg/kg CXCL12 in PBS by retro-orbital injection 30 min before ischemia. Mice treated with PBS were used as control. (H) Representative confocal images of CD31 immunostaining of distal jejuna in PBS- and CXCL12- treated EC-Foxc-DKO mice after I/R at 24h. Paraffin sections (15 µm), scale bars = 100 μm. L represents the lacteal length measured in Figure 10J. (I, J) (I) Quantification of CD31+ vessel density (% = total CD31+ vessel area/total intestinal tissue area x 100%) and (J) quantification of lacteal length were performed based on Figure 10H. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 4~6, **P<0.01.",
    "diseases": "ischemia"
  },
  {
    "caption": "In CXCL12 rescue experiments, mice were treated with 50μg/kg CXCL12 in PBS by retro-orbital injection 30 min before ischemia. Mice treated with PBS were used as control. (K) Relative mRNA expression of Rspo3 in sorted intestinal LECs from PBS/CXCL12 treated EC-Foxc-DKO mice at I/R-18.5h. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 5~6, n.s.=not significant. The box-and-whisker plots in display the median value (central band in the box), second and third quartiles (bottom and top ends of the box, respectively) as well as minimum/maximum values (whiskers blow/above the box) of the data sets.",
    "diseases": "ischemia"
  },
  {
    "caption": "Volcano plot of differentially expressed brain mRNAs of 4.5-month-old mice (n = 3 biological replicates per genotype) detected by the Neuropathology panel of NanoString. Expression changes were only taken into consideration when the extent of change was above 20% as indicated by vertical lines for all volcano plots. Gliosis and Myelination related genes are highlighted if changes are above 20%. Fold changes are displayed after log2 transformation. (A) Comparison of differentially expressed brain mRNAs from Tmem106b-/- and wild type mice. From 680 detected genes 21 are significantly upregulated, while 10 are significantly reduced.",
    "diseases": "Gliosis"
  },
  {
    "caption": "Volcano plot of differentially expressed brain mRNAs of 4.5-month-old mice (n = 3 biological replicates per genotype) detected by the Neuropathology panel of NanoString. Expression changes were only taken into consideration when the extent of change was above 20% as indicated by vertical lines for all volcano plots. Gliosis and Myelination related genes are highlighted if changes are above 20%. Fold changes are displayed after log2 transformation. (B) Comparison of Grn-/- and wild type mice. From 680 detected genes 12 are significantly upregulated, while 6 are significantly reduced.",
    "diseases": "Gliosis"
  },
  {
    "caption": "Volcano plot of differentially expressed brain mRNAs of 4.5-month-old mice (n = 3 biological replicates per genotype) detected by the Neuropathology panel of NanoString. Expression changes were only taken into consideration when the extent of change was above 20% as indicated by vertical lines for all volcano plots. Gliosis and Myelination related genes are highlighted if changes are above 20%. Fold changes are displayed after log2 transformation. (C) Volcano plot for Grn-/-/Tmem106b-/- and wild type mice. From 680 detected genes 79 are significantly upregulated, while 24 are significantly reduced.",
    "diseases": "Gliosis"
  },
  {
    "caption": "Analysis of brain mRNA expression of 4.5-month-old mice (5 wild type 4 Tmem106b-/- mice) detected by the Neuroinflammation panel by NanoString. Expression changes were only taken into consideration when the extent of change was above 20% as indicated by vertical lines for in all volcano plots. Gliosis related genes are highlighted if changes are above 20%. Fold changes are displayed after log2 transformation. (A) Comparison of differentially expressed mRNA of Tmem106b-/- mice in comparison to wild type mice. From 622 detected genes 21 are significantly upregulated, while 12 are significantly reduced.",
    "diseases": "Gliosis"
  },
  {
    "caption": "Analysis of brain mRNA expression of 4.5-month-old mice (5 wild type, 4 Grn-/ mice) detected by the Neuroinflammation panel by NanoString. Expression changes were only taken into consideration when the extent of change was above 20% as indicated by vertical lines for in all volcano plots. Gliosis related genes are highlighted if changes are above 20%. Fold changes are displayed after log2 transformation. (B) Comparison of differentially expressed mRNA in Grn-/- and wild type mice. From 622 detected genes 32 are significantly upregulated, while only 1 is significantly reduced.",
    "diseases": "Gliosis"
  },
  {
    "caption": "Analysis of brain mRNA expression of 4.5-month-old mice (5 wild type 5 Grn-/-/Tmem106b-/- mice) detected by the Neuroinflammation panel by NanoString. Expression changes were only taken into consideration when the extent of change was above 20% as indicated by vertical lines for in all volcano plots. Gliosis related genes are highlighted if changes are above 20%. Fold changes are displayed after log2 transformation. (C) Volcano plot of differentially expressed brain mRNAs from Grn-/-/Tmem106b-/- mice in comparison to wild type mice. From 622 detected genes 110 are significantly upregulated, while 16 are significantly reduced.",
    "diseases": "Gliosis"
  },
  {
    "caption": "Representative confocal images of control (CTL-1, 2, 3) and DOA+ patient fibroblasts carrying indicated monoallelic mutations imaged as described in A. Scale bar=20μm. Passage number between P12-15. Mitochondrial morphology quantification of B. Data represent mean ± SD of two independent experiments, (195-2496 cells per cell line), One-way ANOVA; ** p < 0.01, ****p < 0.0001, ns; not significant",
    "diseases": "DOA"
  },
  {
    "caption": "A. Significantly recurrently mutated genes identified by MutSigCV analysis based on whole-exome sequencing data of 25 STAD patients' samples.",
    "diseases": "STAD"
  },
  {
    "caption": "B. Distribution of PWWP2B mutations identified in 25 STAD patients. Distribution of PWWP2B mutations identified in the TCGA PanCancer Atlas stomach adenocarcinoma dataset (Network, 2014). Distribution of PWWP2B mutations identified in a large-scale colorectal adenocarcinoma genomic study.",
    "diseases": "colorectal adenocarcinoma, STAD, stomach adenocarcinoma"
  },
  {
    "caption": "E. Overall survival curve of 25 gastric cancer patients with and without PWWP2B mutations.",
    "diseases": "gastric cancer"
  },
  {
    "caption": "(B) Violin plots displaying RNA-seq readings by FPKM (normalized Fragments Per Kilobase Million) of chaperones HSPA1A and HSPA1B of human hippocampus samples of demented patients and controls (n = 49,42; unpaired Kolmogorov-Smirnov test; continuous lines: median; dashed lines: quartiles).",
    "diseases": "demented"
  },
  {
    "caption": "A Normal human fibroblasts and HGPS fibroblasts were serum-starved for 48 h and stained for progerin (red), acetylated tubulin (green) and DNA (blue). The representative images show that the cell with high progerin (inset 2), but not low progerin (inset 1), displays defective cilia formation. Scale bars, 20 μm or 2 μm (in the magnified images).",
    "diseases": "HGPS"
  },
  {
    "caption": "F) In vitro tumor T cell co-culture competition assay in multiple melanoma  cell lines containing indicated sgRNAs. Statistics was done by Kruskal-Wallis test with Dunn's post hoc test. Error bars indicate SD of six biological replicates with different cell lines (n = 6). * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.",
    "diseases": "melanoma"
  },
  {
    "caption": "I) In vitro T cell co-culture competition assay of sgCtrl and sgTsc2-expressing lung cancer cell lines. Statistics was done by Mann-Whitney test. Error bars indicate SD of five biological replicates with different T cell  donors (n = 5). * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.",
    "diseases": "lung cancer"
  },
  {
    "caption": "A)  Western blot  analysis of baseline mTOR  signaling in sgCtrl- or sgTsc2-expressing melanoma  and lung cancer  cell lines. Representative plot of 2-6 independent experiments. All blots  shown in this panel were run in parallel.",
    "diseases": "lung cancer, melanoma"
  },
  {
    "caption": "E) Western blot  analysis of sgCtrl- or sgTSC2-expressing D10 melanoma  cells upon MART-1 T cell challenge for indicated time. Representative of three biological replicates with different T cell donors (n = 3).",
    "diseases": "melanoma"
  },
  {
    "caption": "A) Cell viability analysis by CellTiter-Blue assay of sgCtrl- or sgTSC2-expressing D10 melanoma  and A549 lung cancer  cells treated with TRAIL   at indicated concentrations for three days. Statistical analysis was performed by two-tailed unpaired Student t test. For D10, error bars represent SD from three independent experiments (n = 3). For A549, error bars represent SD of pooled data from two independent experiments with three technical replicates each (n = 2). * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.",
    "diseases": "lung cancer, melanoma"
  },
  {
    "caption": "C. WB  analysis of Splicing Factors levels in primary AML  samples with high (AML-H) or normal (AML-N) eIF4E  levels, as well as  bone marrow mononuclear cells from healthy volunteers (Norm for normal). Numbers refer to different individuals. β-actin was used as a loading control. (* = degraded sample).",
    "diseases": "AML"
  },
  {
    "caption": "(C, D) Representative western blots (C) and relative quantification (D) of protein levels for PUM1, PUM2, FMRP, AGO2, CNOT1, and MOV10 in PADDAS patient-derived and PRCA patient-derived cells compared to their respective controls. Data were normalized to GAPDH protein levels.",
    "diseases": "PADDAS, PRCA"
  },
  {
    "caption": "(A) Expression levels of CoV2-miR-O7a.1, CoV2-miR-O7a.2 and a 22 nt region from the ORF6 of the viral genome that does not produce detectable levels of small RNAs (Control ORF6) analyzed by stem-loop RT-qPCR from nasopharyngeal swabs of patients tested positive for COVID-19 or another seasonal human coronavirus (HCoV). Relative expression to hsa-miR-let-7a is shown. Ct values in parenthesis refer to the Ct value for the detection of viral genome in patient swab samples.",
    "diseases": "COVID-19"
  },
  {
    "caption": "(E) CHK2+/+ and CHK2-/- mice were subjected to MCAO for 1 hr and reperfusion for 12 h. Contralateral (C) and ipsilateral (I) tissues of the mouse brain were coronally sectioned and stained with 2 % TTC.",
    "diseases": "reperfusion"
  },
  {
    "caption": "(G-J) Immunoblots for p62, p-Beclin 1 Ser90, p-Beclin 1 Ser93 and Beclin 1 in the cortical extracts from ischemia and reperfusion-treated CHK2+/+ and CHK2-/- mice. Quantification of p62, p-Beclin 1 Ser90 and p-Beclin 1 Ser93 protein levels (n = 3 mice). Data are presented as mean ± s.e.m.; *P < 0.05, **P < 0.01 (Student's t-test).",
    "diseases": "ischemia, reperfusion"
  },
  {
    "caption": "C) Representative confocal microscopy images of calcein green labelled FIS organoids of a healthy individual and a CF patient, before and 60 min after stimulation with Fsk (5 uM). Scale bar, 200 μm.",
    "diseases": "CF"
  },
  {
    "caption": "IGF2R (green) and sarcomeric actin (magenta) expression in the VM muscles of two DMD patients. Scale bars=25μm. (b).",
    "diseases": "DMD"
  },
  {
    "caption": "(e) Representative WB analysis of IGF2R and GAPDH expression in total protein lysates of the human (healthy and DMD) and murine (C57Bl6/J and mdx) TA and VM muscles (n=2 per healthy and DMD; n=10 mice per group); quantifications are expressed as the IGF2R/GAPDH ratio in arbitrary units.",
    "diseases": "DMD"
  },
  {
    "caption": "(f) Representative WB analysis of IGF2R expression in sarcolemma protein lysates of the TA and VM muscles of healthy, DMD, C57Bl6/J and mdx (n=2 per healthy and DMD; n=10 mice per group). Densitometry analysis of IGF2R expression, results are shown as a fold increase, as indicated in the lower panel in arbitrary units. One-way ANOVA. *p<0.05; ****p<0.0001. All values are expressed as the mean±SEM.",
    "diseases": "DMD"
  },
  {
    "caption": "B SQLE gene expression in HCC and adjacent normal tissue was analyzed in TCGA Liver Hepatocellular Carcinoma (normal [n=50] versus tumors [n=371]). C SQLE gene expression in COAD and adjacent normal tissue was analyzed in TCGA Colon Cancer (normal [n=41] versus tumors [n=286]). ",
    "diseases": "COAD, Colon Cancer, HCC, Hepatocellular Carcinoma"
  },
  {
    "caption": "C) Percentages of E18.5 QKO foetuses exhibiting the indicated externally visible developmental defects (numbers above bars represent the number of animals examined). Age-matched TKO animals are included for comparison. An example of a QKO E18.5 pup presenting with an omphalocele (asterisk), exencephaly (arrow), and spina bifida (arrowhead) is shown alongside an age-matched WT control. Scale bar = 5 mm.",
    "diseases": "exencephaly, omphalocele, spina bifida"
  },
  {
    "caption": "B-D) Images depicting the hindlimbs (HL), tail (T), forelimbs (FL), and ventral view of the palate (P) in a wild-type foetus at E18.5 of development. E-G) Corresponding images of a representative age-matched QKO foetus. Panel G shows a cleft palate (indicated by arrowheads). H, I) Magnified images of panels E and F. Arrows indicate excess tissue at the anterior and posterior edges of the hindlimb and forelimb, respectively, of QKO foetuses.",
    "diseases": "cleft palate"
  },
  {
    "caption": "(A) Estimation of BID protein levels in TKO MEFs. DKO MEFs re-expressing human BAK, TKO MEFs, and two human leukaemia cell lines RS4;11 and MV4;11, were lysed and analysed by Western blot for BID levels, using a rat monoclonal antibody raised against human BID (anti-hBID clone 2D1) that also recognises mouse BID. Also present are samples of the human FL-BID protein added at the equivalent concentrations used in (B) and (C). On the right gel, duplicate samples of DKO and TKO cells and permeabilised DKO and TKO cells (from B and C) showing that endogenous mouse BID is cytosolic in these cells. Data shown are representative of 2 independent experiments.",
    "diseases": "leukaemia"
  },
  {
    "caption": "A. Representative  bright field micrographs  of netrin-1 immunohistochemistry  in formalin-fixed paraffin-embedded human ovarian, endometrial  and  hepatocellular carcinoma  (HCC) tumor sections. Scale bar 50 µm. B. Quantification by immunoblots  of netrin-1  in the ECM  of cancer cells of human  tumors(n=3, error bars are SD). The vertical line corresponds to the intercellular zone",
    "diseases": "HCC, hepatocellular carcinoma"
  },
  {
    "caption": "(A-C) qPCR  and western blot analysis indicated an upregulation of hepatic ZBTB22  in diabetic db/db mice, obese ob/ob mice  and high-fat diet  for 12 weeks mice  (n=6 mice). Data information: Data are means ± SEM. **p< 0.01, ***p< 0.001 by Student's t test.",
    "diseases": "db, diabetic, ob, obese"
  },
  {
    "caption": "(I) Hepatic ZBTB22   overexpression induces glucose   intolerance  and  insulin  resistance in ZBTB22  deficiency mice  fed on HFD (n=6 mice).",
    "diseases": "glucose   intolerance, insulin  resistance"
  },
  {
    "caption": "(A-B) Hepatic ZBTB22  silencing decreases the expression  of gene involved in gluconeogenesis, lipogenesis, and fatty acid oxidation in db/db mice  (n=6 mice). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "diseases": "db"
  },
  {
    "caption": "(D) Hepatic ZBTB22  silencing improved the  glucose  tolerance,  insulin  sensitivity  and pyruvate  tolerance in db/db mice  (n=6 mice). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "diseases": "pyruvate  tolerance, db, glucose  tolerance, insulin  sensitivity"
  },
  {
    "caption": "(C) Hepatic ZBTB22  overexpression significantly induced glucose intolerance and   insulin resistance in normal C57 mice  (n=6 mice). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "diseases": "glucose intolerance, insulin resistance"
  },
  {
    "caption": "Hepatic ZBTB22  overexpression failed to change  glucose tolerance,  insulin sensitivity  in PCK1-silencing C57 mice  (n=6 mice). Data information: Data are means ± SEM. *p < 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "diseases": "glucose tolerance, insulin sensitivity"
  },
  {
    "caption": "(b) Expression levels of FoxO1 and Atg7 conjugate in mice tumours were determined by western blotting.",
    "diseases": "tumours"
  },
  {
    "caption": "(e) Proteins were extracted from 16 paired samples from patients for western blotting with anti-FoxO1 or with anti-p62 antibody. Protein bands were scanned with a phosphorimager and relative band intensity was normalized to the β-actin band. FoxO1 of normal tissue, 0.37; FoxO1 of tumour tissue, 0.10; P = 0.001, two-sided t-test. p62 of normal tissue, 0.32; p62 of tumour tissue, 1.00; P = 0.009, two-sided t-test. Data in e are means ± s.d. (n = 16).",
    "diseases": "tumour"
  },
  {
    "caption": "i.t. administration (20µM) of Tat-P4-(C5)2 significantly reduced ipsilateral paw hypersensitivity of SNI mice in the initiation stage (2 days after injury) of the spared nerve injury model at time points 1 and 3 hours (n = 7)",
    "diseases": "spared nerve injury"
  },
  {
    "caption": "i.t. administration (20µM) of Tat-C5 did not affect ipsilateral paw hypersensitivity of SNI mice in the initiation stage (2 days after injury) of the spared nerve injury model (n = 8)",
    "diseases": "spared nerve injury"
  },
  {
    "caption": "Representative western blots (top) for GluA1 and GluA2 following surface biotinylation of spinal cord slices. Densitometric analysis (bottom) of immunoblots. We observed up-regulation of both GluA1 and GluA2 surface level following SNI surgery compared to non-operated animal CTL (unpaired t test GluA1: t(4)=3.372, GluA2: t(4)=3.991,#p≤0.05, n=3/group). Tat-P4-(C5)2 but not Tat-C5 significantly reduced the SNI-induced GluA2 surface expression and shows a strong tendency for GluA1 as well. Representative immunoblot shows unaltered PICK1 total level in the total lysate in the four conditions.",
    "diseases": "SNI"
  },
  {
    "caption": "Images of lumbar spinal cord sagittal sections showing the time course of TMR-Tat-P4-(C5)2 (magenta) after i.t. administration (20 µM) in SNI mice showing maximal accumulation in cells after 60 min. Scale bar 1000 µm and 100 µm in Zooms.",
    "diseases": "SNI"
  },
  {
    "caption": "Dose-dependent Von Frey test in the acute phase (2 days after injury) of the spared nerve injury model following i.t. administration of Tat-P4-(C5)2 (n=8/group) did not affect ipsilateral paw hypersensitivity of SNI mice and lasts up to 4h post injection.",
    "diseases": "SNI, spared nerve injury"
  },
  {
    "caption": "i.t. administration of Tat-P4-(C5)2 (20 µM) at day 14 and 28 after injury in the maintenance phase of SNI model in mice shows significant increase in pain withdrawal threshold up to 3 hours with equal efficacy in male and female mice (compared to time 0 pre-injection, D14 n=8/group/gender, D28 n=6 male, n=7 female).",
    "diseases": "SNI"
  },
  {
    "caption": "D 2a2iL-RH6 cells form teratomas that consist of three embryonic germ layer-derived tissues. (i) Rosette structures (ectoderm), (ii) cartilage (mesoderm), and (iii) primitive gut (endoderm; scale bar 50 µm).",
    "diseases": "teratomas"
  },
  {
    "caption": " D Chromatin accessibility as assessed by the number of ATAC peaks identified in the sorted populations of normal thymic T-cell precursors and in T-ALLs, respectively (n=10/19 patients have two biological replicates, n=9/19 patients have one replicate). Horizontal lines of the box plot indicate the median, lower and upper limits of each box correspond to the first and third quartiles (the 25th and 75th percentiles) and the lower and upper whiskers extend from min to max; pval=4.4e-08 (Kruskal-Wallis Test). ",
    "diseases": "T-ALLs"
  },
  {
    "caption": " E Heatmap representing the enrichment and depletion of binding motifs of top 50 TFs in OCRs of T-ALLs in comparison to healthy T-cell precursors. Patients on the x-axis; same order as in panel (C). Gray cells represent TFs having non-significant enrichment or depletion. ",
    "diseases": "T-ALLs"
  },
  {
    "caption": " C log2 fold changes of 292 genes which are differentially expressed (x-axis, RNA-Seq: non-sorted bulk thymi vs. T-ALLs) and differentially accessible (y-axis, ATAC-Seq: sorted T-cell populations vs. T-ALLs) in T-ALLs in comparison to healthy T-cell precursors. Dot size and color indicate the frequency (number of patients having dysregulation of the gene). Genes with ≥5/19 frequency are shown on the plot. Protein coding genes with ≥12/19 frequency are labelled. For plotting the average LFC values of ATAC and RNA are used per gene per quartile. Q1 - 4 stands for the quadrant 1 - 4. ",
    "diseases": "T-ALLs"
  },
  {
    "caption": "Kaplan-Meier analysis of overall survival in breast cancer patients with recurrent lethal disease, classified according to p-JNK expression. p-JNK was determined by immunostaining of breast cancer samples in a tissue microarray; p-JNK low, n = 31; p-JNK high, n = 10. P value and hazard ratio (HR) were calculated by log-rank test.",
    "diseases": "breast cancer"
  },
  {
    "caption": "Immunostaining of p-c-Jun (arrows) in patient-matched breast tumor and lung metastasis. Scale bar, 50 μm.",
    "diseases": "lung metastasis, breast tumor"
  },
  {
    "caption": "Quantification of p-c-Jun positive (p-c-Jun+) cells per tumor area in matched primary tumors and lung metastases. Boxes depict median from 12 patients with upper and lower quartiles.",
    "diseases": "primary tumors, lung metastases"
  },
  {
    "caption": "Quantification of p-c-Jun positive (p-c-Jun+) cancer cells within mammary tumors and matched metastases in mice injected with MDA231-LM2 cells.",
    "diseases": "cancer, metastases, mammary tumors"
  },
  {
    "caption": "Immunofluorescence analysis of p-c-Jun in micrometastatic (day 7) and macrometastatic (day 21) nodules in a xenograft mouse model injected intravenously with MDA231-LM2 cells. DAPI was used to stain cell nuclei, and cancer cells express GFP as a marker. Scale bar, 50 μm. Quantification of p-c-Jun+ cancer cells",
    "diseases": "cancer, macrometastatic, micrometastatic"
  },
  {
    "caption": "Mammary tumor growth curves from mice described in panel G. Each value represents the mean ± SEM. For MDA231-LM2, n = 12 tumors in 6 mice for each experimental group. For SUM159-LM1, n = 16 tumors in 8 mice for each experimental group.",
    "diseases": "tumors, Mammary tumor"
  },
  {
    "caption": "Lung metastatic burden in MDA231-LM2 or SUM159-LM1 tumor-bearing mice treated with JNKi. Quantification of lung metastases. FOV, field of view; LS, lung section. Each value represents the mean ± SEM. For metastatic foci per FOV, 8-10 fields were quantified per mouse. MDA231-LM2 tumor-bearing mice: n = 6 mice per group. SUM159-LM1 tumor-bearing mice, vehicle n = 8 mice; JNKi n = 7 mice.",
    "diseases": "tumor, lung metastases, metastatic"
  },
  {
    "caption": "Lung metastatic burden in MDA231-LM2 or SUM159-LM1 tumor-bearing mice treated with JNKi. Representative histology examples of metastasis in lungs, detected by expression of human vimentin. Scale bar, 100 μm.",
    "diseases": "tumor, metastasis"
  },
  {
    "caption": "Scatter plot elucidating fold change (FC) in gene expression between samples treated with JNKi compared to vehicle (Y-axis) and expression of constitutively active JNK (MKK7-JNK) versus vector control (X-axis) from biological triplicates. Representative examples of genes that are specifically induced by JNK in metastatic breast cancer cells are highlighted in red.",
    "diseases": "breast cancer, metastatic"
  },
  {
    "caption": "GSEA graphs showing (C) enrichment of a mammary stem cell signature (Pece et al, 2010) in MDA231-LM2 cancer cells expressing MKK7-JNK NES, normalized enrichment score.",
    "diseases": "cancer"
  },
  {
    "caption": "GSEA graphs showing under-representation of the same mammary stem cell signature in cancer cells treated with JNKi. NES, normalized enrichment score.",
    "diseases": "cancer"
  },
  {
    "caption": "Proportion of JNK signature-positive tumors in breast cancer patients from the METABRIC data set classified according to PAM50 intrinsic biological subtypes JNK-S, JNK signature as in panel F. Subtype patient numbers: Luminal, n = 1213; HER2, n = 240; Basal-like, n = 331.",
    "diseases": "Basal-like, breast cancer, tumors, HER2, Luminal"
  },
  {
    "caption": "GSEA graph showing enrichment of JNK signature in MDA231-LM2 cancer cells grown as oncospheres. NES, normalized enrichment score.",
    "diseases": "cancer"
  },
  {
    "caption": "GSEA of a basal-like breast cancer signature induced in MDA231-LM2 oncospheres.",
    "diseases": "basal-like breast cancer"
  },
  {
    "caption": "Oncosphere formation in JNKi-treated cancer cells from breast cancer patients (pleural effusions or ascites). (I) Quantification of oncospheres per well in 4 different patients. Values are mean from 10 wells ± SD. (J) Representative oncospheres from patient samples. Scale bar, 50 μm.",
    "diseases": "ascites, breast cancer, cancer, pleural effusions"
  },
  {
    "caption": "Matrigel invasion assay of MDA231-LM2 cells treated with JNKi. Left, examples of invading cancer cells stained with crystal violet (arrows). Scale bar, 50 μm. Right, quantification of invading cells per field of view (FOV) showing mean from 8 fields ± SEM.",
    "diseases": "cancer"
  },
  {
    "caption": "SPP1 and TNC expression in the indicated breast cancer cells treated with increasing concentrations of JNKi.",
    "diseases": "breast cancer"
  },
  {
    "caption": "SPP1 and TNC expression in pleural effusion (1 and 2) and ascites (3 and 4) samples from four different patients treated with JNKi (4 μM, 48h) in culture. Values are mean ± SD from triplicates. The results from all four patient samples were included to calculate significance of JNKi on gene expression. SPP1, P = 0.0079; TNC, P = 0.0002.",
    "diseases": "ascites, pleural effusion"
  },
  {
    "caption": "Correlation analysis of SPP1 and TNC with JUN expression in dissected metastatic nodules from breast cancer patients (GSE14020). N = 65 metastasis samples.",
    "diseases": "breast cancer, metastasis, metastatic"
  },
  {
    "caption": "Lung metastasis in Spp1+/- mice implanted with MDA231-LM2 cells expressing control shRNA (control), and Spp1-/- mice implanted with MDA231-LM2 cells independently expressing one of two different SPP1 shRNAs (SPP1-deficient). Ex vivo lung luminescence was analyzed, panel H. Boxes show the median value with upper and lower quartiles. Whiskers represent minimum and maximum values. Control n = 16 mice, SPP1 deficient (1) n = 14 mice and SPP1 deficient (2) n = 15 mice. P values were determined by a two-tailed Mann-Whitney test. (I) Representative histological images of metastatic foci (top) and ex vivo lung bioluminescence (bottom). In histological samples, immunohistochemistry was used to determine metastatic nodules based on expression of human vimentin (arrows). Scale bar, 100 µm.",
    "diseases": "Lung metastasis, metastatic"
  },
  {
    "caption": "SUM159-LM1 cells expressing either control shRNA (control), or one of two different TNC shRNAs (shTNC 1 and 2), were injected intravenously into NSG mice. (J) Metastatic colonization was quantified by lung bioluminescence. Control and shTNC (1) n = 8 mice per group, shTNC (2) n = 7 mice. P value was determined by a two-tailed Mann-Whitney test. (K) Representative images of metastatic foci (top) and ex vivo lung bioluminescence (bottom). Arrows denote vimentin-expressing cancer cells in metastases.",
    "diseases": "cancer, metastases, Metastatic, metastatic"
  },
  {
    "caption": "Kaplan-Meier analysis of breast cancer patients (combined GSE2603 and GSE5327 datasets) showing a link between high SPP1 and TNC expression and poor lung metastasis-free survival. Patient samples, SPP1 and TNC low n = 70; SPP1 and TNC high n = 70. HR, Hazard ratio.",
    "diseases": "lung metastasis, breast cancer"
  },
  {
    "caption": "Immunofluorescence analysis of p-c-Jun+ cancer cells in lung metastases from mice injected intravenously with MDA231-LM2 cells and treated with PAX at week 3 post injection. Lungs were harvested 72h after PAX treatment. Cancer cells express GFP as a marker. DAPI was used for nuclear staining. Scale bar, 50 µm.",
    "diseases": "cancer, Cancer, lung metastases"
  },
  {
    "caption": "Quantification of cancer cells expressing p-c-Jun in panel D. Values are mean from three mice ± SEM. Nine metastatic foci were analyzed per mouse.",
    "diseases": "cancer, metastatic"
  },
  {
    "caption": "Growth curves of mammary tumors in vehicle- or PAX-treated Spp1+/- mice implanted with the indicated cells expressing control shRNA, and Spp1-/- mice implanted with the indicated cells expressing SPP1 shRNA. MDA231-LM2: control, PAX and SPP1 def. + PAX n = 16 tumors per group, SPP1 def. n = 14 tumors. SUM159-LM1: control, PAX and SPP1 def. + PAX n = 16 tumors per group, SPP1 def. n = 15 tumors.",
    "diseases": "tumors, mammary tumors"
  },
  {
    "caption": "Quantification of lung metastasis from the animals described in panels A and B. The number of metastatic foci per field of view (FOV) or per lung section (LS) was determined. MDA231-LM2 tumor-bearing mice: control, PAX and SPP1 def. + PAX n = 8 mice per group, SPP1 def. n = 7 mice. SUM159-LM1 tumor-bearing mice: control, PAX and SPP1 def. + PAX n = 8 mice per group, SPP1 def. n = 7 mice.",
    "diseases": "lung metastasis, tumor, metastatic"
  },
  {
    "caption": "Tumor weight in mice at day 40 after implantation of MDA231-LM2 breast cancer cells in a control or SPP1 deficient setting undergoing combination treatment with doxorubicin (Adriamycin) and cyclophosphamide (AC regimen). Control, AC and SPP1 def. n = 16 tumors per group, SPP1 def. + AC n = 14 tumors.",
    "diseases": "breast cancer, Tumor, tumors"
  },
  {
    "caption": "Lung metastasis was quantified in mice that were implanted with MDA231-LM2 tumors and subjected to AC chemotherapy. Each value represents the mean ± SEM; n = 5 mice per group. Ten random fields per lung section were analyzed for percentage of metastatic area. Representative histological images of metastatic nodules in lungs of mice from the experiment described in panel E. Metastases were determined by expression of human vimentin (arrows). Scale bar, 100 µm.",
    "diseases": "Lung metastasis, tumors, Metastases, metastatic"
  },
  {
    "caption": "Mammary tumor growth curves in PAX-treated NSG mice bearing control or TNC knockdown MDA231-LM2 tumors. Values are means ± SEM, n = 16 tumors per group. **** P < 0.0001. Lung metastases quantified in tumor bearing mice",
    "diseases": "tumor, tumors, Lung metastases, Mammary tumor"
  },
  {
    "caption": "Representative histology of human vimentin-positive lung metastases (arrows)",
    "diseases": "lung metastases"
  },
  {
    "caption": "Mammary tumor growth curves in NSG mice implanted with MDA231-LM2 or SUM159-LM1 cells and treated with paclitaxel as single agent or in combination with JNKi. Each value represents the mean ± SEM. MDA231-LM2: n = 12 tumors per group. SUM159-LM1: vehicle, JNKi and PAX n = 12 tumors per group; PAX + JNKi n = 10 tumors. **P < 0.01, ***P < 0.001.",
    "diseases": "tumors, Mammary tumor"
  },
  {
    "caption": "Metastatic burden in lungs of MDA231-LM2 and SUM159-LM1 tumor-bearing mice treated with paclitaxel as single therapy or in combination with JNKi. Each value represents the mean ± SEM. MDA231-LM2 tumor-bearing mice: n = 6 mice per group. SUM159-LM1 tumor-bearing mice: vehicle, JNKi and PAX n = 6 mice per group; PAX+ JNKi n = 5. Ten fields were quantified per lung section. FOV, field of view, LS, lung section. PAX, paclitaxel. Representative histological images of metastatic foci (arrows) in lungs of the MDA231-LM2-implanted mice described in panel C, stained for human vimentin expression in differentially treated groups. Scale bar, 100 μm.",
    "diseases": "tumor, Metastatic, metastatic"
  },
  {
    "caption": "Apoptosis was determined by quantification of TUNEL-positive cells per field of view (FOV) in MDA231-LM2 tumors (from the animals described in (C)) treated with JNKi and/or PAX. Values are means from 6 mice per condition ± SEM.",
    "diseases": "tumors"
  },
  {
    "caption": "GSEA showing enrichment of the JNK signature in tumor samples from breast cancer patients from the TOP trial (GSE16446), stratified according to pathological response to neoadjuvant chemotherapy. NES, normalized enrichment score. pCR, pathological complete response.",
    "diseases": "breast cancer, tumor"
  },
  {
    "caption": "Kaplan-Meier analyses of chemotherapy-treated breast cancer patients associating JNK signature (JNK-S) with metastasis-free survival (TOP trial data set, JNK-S low n = 54 patients; JNK-S high n = 53 patients (G)) or overall survival (METABRIC data set, JNK-S low n = 135 patients; JNK-S high n = 135 patients (H)). HR, hazard ratio. P values were determined by log-rank test.",
    "diseases": "breast cancer, metastasis"
  },
  {
    "caption": "F, Histogram showing the in vivo GSC frequency measured by LDA in p3 tumors. GSC frequency (95% CI) was as follows: NS-ctrl, 1/258.2 (97.67-683.9); NS-IR 1/22.1 (8.05-62.6). *: 2 test, P=1.6×10-4.",
    "diseases": "tumors"
  },
  {
    "caption": "G, LDA (sphere forming) measuring the in vitro frequency of GSCs in cells derived from p3 tumors. *: 2 test, P=0.0006.",
    "diseases": "tumors"
  },
  {
    "caption": "H, LDA (sphere forming) measuring the in vitro frequency of GSCs in cells derived from intracranial tumors generated by BT463NS, and irradiated in vivo (2 Gy × 3 days) (n = 3). Ctrl: non-irradiated tumors. *: 2 test, P=2.04×10-11. Data are represented as mean ± CI or ± SEM in B.",
    "diseases": "tumors"
  },
  {
    "caption": "E, Representative immunofluorescence staining of MET (red) on tumors generated by subcutaneous injection of BT308NS, irradiated (2 Gy × 3) and explanted 72 h after the last irradiation. Nuclei are counterstained with DAPI (blue). Ctrl: non-irradiatedtumors. Scale bar, 10 µm (63× magnification). F left, Quantification of the percentage of MET-expressing cells in tumor sections represented in (E) (n = 12 HPF/group). HPF: high-power field. *: t-test, P=0.001. F right, Quantification of MET mean fluorescence intensity in tumor sections represented in (E) (n = 12 HPF/group, fold vs. non-irradiated cells, ctrl). *: t-test, P=0.00016.",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "G, representative METimmunohistochemistry staining of matched primary and recurrent tumors. Scale bar, 50 µm (40× magnification). H, Histogram representing the number of patient displaying different percentages of MET expressing cells in their primary or recurrent tumors: negative, 0-5%; low, 6-29%; moderate, 30-69%; high, 70-100% (see also Appendix Table 4). I, Dot plot representing the MET cumulative score (MET positive cell score + MET staining intensity score) in 19 primary and recurrent tumors (see Appendix Table 4). Wilcoxon, p<0.02. Data are represented as mean ± SEM or ± CI in B.",
    "diseases": "tumors"
  },
  {
    "caption": "Histology: all metastatic lesions are composed of poorly differentiated cells with an epithelial 'flavour'. The neoplastic population is mainly arranged in solid nests and sheets with focal rudimental gland formation. Scale bar: 50µm.",
    "diseases": "metastatic lesions"
  },
  {
    "caption": "Triplicate samples of L_03, L_04A, L_07A, L_09, L_10; L_12C are compared with the expression profiles deposited in the TCGA dataset of a spectrum of primary tumors or metastases (meta) from known origin. Two ovarian cancers analysed in house (CTR_OV1 and CTR_OV2) were used as controls and have expression profiles matching the profiles displayed by the ovarian cancers listed in TCGA (purple box). The acronyms are as follow: ACC: adrenocortical carcinoma; BLCA: bladder urothelial carcinoma; BRCA: breast invasive carcinoma; CESC: cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL: cholangiocarcinoma; COAD: colon adenocarcinoma; DLBC: lymphoid neoplasm diffuse large B-cell lymphoma; ESCA: oesophageal carcinoma; GBM: glioblastoma multiforme; HNSC: head and neck squamous cell carcinoma; KICH: kidney chromophobe; KIRC: kidney renal clear cell carcinoma; KIRP: kidney renal papillary cell carcinoma; LAML: acute myeloid leukaemia; LGG: brain lower grade glioma; LIHC: liver hepatocellular carcinoma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; MESO: mesothelioma; OV: ovarian serous cystadenocarcinoma; PAAD: pancreatic adenocarcinoma; PCPG: pheochromocytoma and paraganglioma; PRAD: prostate adenocarcinoma; READ: rectum adenocarcinoma; SARC: sarcoma; SKCM: skin cutaneous melanoma; STAD: stomach adenocarcinoma; TGCT: testicular germ cell tumors; THCA: thyroid carcinoma; THYM: thymoma; UCEC: uterine corpus endometrial carcinoma; UCS: uterine carcinosarcoma; UVM: uveal melanoma. ",
    "diseases": "bladder urothelial carcinoma, BRCA, acute myeloid leukaemia, LAML, ACC, adrenocortical carcinoma, MESO, mesothelioma, BLCA, brain lower grade glioma, LGG, breast invasive carcinoma, cervical squamous cell carcinoma, CHOL, cholangiocarcinoma, KICH, kidney chromophobe, kidney renal clear cell carcinoma, KIRC, COAD, colon adenocarcinoma, DLBC, lymphoid neoplasm diffuse large B-cell lymphoma, endocervical adenocarcinoma, CESC, ESCA, oesophageal carcinoma, GBM, glioblastoma multiforme, head and neck squamous cell carcinoma, HNSC, LIHC, liver hepatocellular carcinoma, LUAD, lung adenocarcinoma, lung squamous cell carcinoma, LUSC, STAD, stomach adenocarcinoma, meta, metastases, ovarian cancers, OV, ovarian serous cystadenocarcinoma, PAAD, pancreatic adenocarcinoma, kidney renal papillary cell carcinoma, KIRP, paraganglioma, PCPG, pheochromocytoma, PRAD, prostate adenocarcinoma, READ, rectum adenocarcinoma, SARC, sarcoma, SKCM, skin cutaneous melanoma, testicular germ cell tumors, TGCT, THYM, thymoma, THCA, thyroid carcinoma, UCS, uterine carcinosarcoma, UCEC, uterine corpus endometrial carcinoma, uveal melanoma, UVM"
  },
  {
    "caption": "Somatic mutations distribution: SNVs and InDels displayed by each metastasis (listed in the Y axis) were detected by Strelka2 tool (Kim et al., 2018). Brown traits represent single mutations. The number of fully shared (red), partially shared (orange) or private (yellow) mutations is indicated in the horizontal bar below. Five cancer-associated genes (TP53, ARID2, NTRK1, SMARCA4 and ZFHX3) mutated in all metastases are highlighted.",
    "diseases": "metastases, metastasis"
  },
  {
    "caption": "Genetic similarity among metastases: the heatmap has been drawn according to the Jaccard index. The similarity ranges from 58% to 82% among all pairs with the exception of L_08 due to the scarce number of mutations.",
    "diseases": "metastases"
  },
  {
    "caption": "Variant allele frequency of fully shared mutations present in copy neutral regions. The box plot represents the fluctuation of the VAF (in the Y axis) of single mutations (grey dots) in each metastasis; each box represents the upper and lower quartiles, while the central short black line within each box represents the median; whiskers indicate variability outside the upper and lower quartiles.",
    "diseases": "metastasis"
  },
  {
    "caption": "A) Infection susceptibility (top) to VSVG and Spike-typed lentiviruses of a panel of lung cancer cell lines with or without (Empty vector) overexpression of ACE2. ACE2 protein levels were determined by Western-blot (bottom).",
    "diseases": "lung cancer"
  },
  {
    "caption": "C) Western-blot analyses of SPNS1 and PLAC8 protein levels in the different lung cancer cell lines tested in Fig 1 with or without ACE2 overexpression. Note that PLAC8 and SPNS1 immunodetection was performed on the same blots than in Figure 1A, and that ACE2 and Actin panels from Figure 1A were included here to allow comparison.",
    "diseases": "lung cancer"
  },
  {
    "caption": "a. b. c. d. Chest computed tomographic scans of Patient 1 were obtained on the day of admission (day 6 after the onset of illness). Bilateral focal consolidation, lobar consolidation, and patchy consolidation were clearly observed, especially in the lower lung.",
    "diseases": "Bilateral focal consolidation, lobar consolidation, patchy consolidation"
  },
  {
    "caption": "C Droplet experiments showing that CHOPS syndrome patient missense mutations reinforced AFF4-ALF domain droplet formation. D Dotplot showing the droplet areas in Fig 7C. Fields per condition n = 5. Two-tailed, unpaired Student's t test was performed. T254S, T254A or R258W vs. WT, *p < 0.05, **p < 0.01, ***p < 0.001. E AFF4-ALF-mCherry condensed fraction as a function of AFF4-ALF-mCherry concentration for experiments in Fig 7C. Error bars represent standard deviations. Fields per condition n = 5. Two-tailed, unpaired Student's t test was performed. T254S, T254A or R258W vs. WT, *p < 0.05, **p < 0.01. F",
    "diseases": "CHOPS syndrome"
  },
  {
    "caption": " A-C Protein AD/non-AD fold changes plotted vs statistical significance for Sweden (A), Magdeburg/Kiel (B), and Berlin (C) cohort. Proteins associated with the GO annotation neuron projection labelled in orange. Proteins above the dashed green line are statistically significant (p < 0.05) and those above the black curves have a q-value below 0.05 ",
    "diseases": "AD"
  },
  {
    "caption": "Correlation of protein AD/non-AD fold changes in pairwise combinations of two cohorts each. Combinations are Sweden vs Magdeburg/Kiel Proteins included differ significantly (p < 0.05) and consistently in abundance by AD status in both cohorts each.",
    "diseases": "AD"
  },
  {
    "caption": " Correlation of protein AD/non-AD fold changes in pairwise combinations of two cohorts each. Combinations are Sweden vs Berlin (D), and Magdeburg/Kiel vs Berlin (E). Proteins included differ significantly (p < 0.05) and consistently in abundance by AD status in both cohorts each. ",
    "diseases": "AD"
  },
  {
    "caption": "Proteins that differ significantly (p-value < 0.05 in E; q-value < 0.05 in F) in abundance by AD status across all three cohorts. Z-scored abundances of proteins in the AD and non-AD groups of all cohorts shown by the heat map Hierarchical clustering separates AD from non-AD groups. Pyruvat kinase PKM (PKM) was quantified in two isoforms and UniProt IDs are given in parenthesis. Black frames highlight proteins with consistent AD/non-AD fold changes across cohorts.",
    "diseases": "AD"
  },
  {
    "caption": "Proteins that differ significantly (p-value < 0.05 in E; q-value < 0.05 in F) in abundance by AD status across all three cohorts. Z-scored abundances of proteins in the AD and non-AD groups of all cohorts shown by the heat map Hierarchical clustering separates AD from non-AD groups. Pyruvat kinase PKM (PKM) was quantified in two isoforms and UniProt IDs are given in parenthesis. Black frames highlight proteins with consistent AD/non-AD fold changes across cohorts.",
    "diseases": "AD"
  },
  {
    "caption": " A-C) Correlation of proteins with ELISA-measured t-tau concentration across samples within the Sweden (A), Magdeburg (B) and Berlin (C) cohorts. Proteins with a q-value below 0.05 are labeled in yellow. Proteins of the 40 protein signature are colored in red for those with higher abundance in AD CSF and in blue for those with higher abundance in non-AD CSF. ",
    "diseases": "AD"
  },
  {
    "caption": " Protein abundance distribution of CSF showing the abundances of AD-modulated CSF proteins. Proteins of our 40 protein signature are highlighted in red (elevated abundance in AD) and blue (elevated abundance in non-AD). Proteins linked to glucose metabolism are highlighted in purple and labelled. ",
    "diseases": "AD"
  },
  {
    "caption": " Protein abundance distribution of brain showing the abundances of AD-modulated CSF proteins. Proteins of our 40 protein signature are highlighted in red (elevated abundance in AD) and blue (elevated abundance in non-AD). Proteins linked to glucose metabolism are highlighted in purple and labelled. ",
    "diseases": "AD"
  },
  {
    "caption": "B, Time course of the changes in Vm evoked by 100-ms flash in 100KASW using caged cGMP (blue) and caged 8-Br-cGMP (black). The flashes released 260 nM cGMP or 2,600 nM 8-Br-cGMP.",
    "diseases": "100-ms flash"
  },
  {
    "caption": "Unsupervised hierarchical clustering heatmap of the gene expression (ratios of mutant/WT) categorized in "neurodegenerative disorders" ('Parkinson's disease', 'Alzheimer's disease', and 'Huntington's disease').",
    "diseases": "Alzheimer's disease, Huntington's disease, neurodegenerative disorders, Parkinson's disease"
  },
  {
    "caption": "C Immunohistochemistry of rat kidneys subjected to IRI and i.p. pCRP application revealed distinct staining by anti-pCRP*/mCRP-9C9 antibody (green, arrows). C10M reduces the deposition of total CRP in the impaired tissue. No deposits in the non-ischemic tissue (sham). Exemplary stainings out of at least three are shown.",
    "diseases": "IRI, ischemic"
  },
  {
    "caption": "D Tissue lysates of rat kidney were separated on SDS-PAGE and total CRP was identified with anti-CRP antibody. A band at the size of mCRP (~23 kDa) was detected in kidneys subjected to IRI and pCRP, but not in animals treated additionally with C10M. The household gene protein GAPDH served as a control for loading equal amounts of protein. 50 and 100 ng human pCRP, respectively, served as a positive control. Representative results are shown for replicated assays (n=3).",
    "diseases": "IRI"
  },
  {
    "caption": "F Immunohistochemical detection of transmigrated CD68+ cells in IRI kidneys. Quantification of immunohistochemical results is shown as mean ± SEM. pCRP (25 µg/ml) increased the number of CD68+ cells transmigrated into injured renal tissue significantly, while C10M abolished these effects. Presented are mean cell counts per ROI in each animal.",
    "diseases": "IRI"
  },
  {
    "caption": "G Periodic acid-Schiff (PAS) stained kidney sections show increased damage after renal IRI in rats when pCRP (25 µg/ml) was injected i.v. The tubulointerstitial injury was quantified by the loss of tubular brush border and by cast formation following an established protocol (Megyesi et al, 1998, 2001). Quantification of immunohistochemical results is shown as mean ± SEM.",
    "diseases": "tubulointerstitial injury, IRI"
  },
  {
    "caption": "H Representative results for the immunohistochemical detection of transmigrated CD68+ cells in IRI kidneys. CD68+ cells are stained with HistoGreen substrate (green). Scale bars indicate 100 µm.",
    "diseases": "IRI"
  },
  {
    "caption": "C Representative photographic examples of transplanted VCA hindlimb allografts. Shown are Lew hindlimb transplants in orthotopic situ on BN recipients three days after transplantation. Rats receiving i.p. pCRP presented VCA with massive edema (left). C10M treatment inhibits pCRP-aggravated early graft rejection (middle). The depicted C10M control without CRP shows no clinical signs of rejection after five days (right).",
    "diseases": "edema"
  },
  {
    "caption": "FFPE pancreatic sections from control, Tgif1KO, KC or KTC were stained with H&E or subjected to IHC analysis using antibodies to CK19 or α-SMA. Yellow arrows indicate PanINs in KC mice. Representative pictures at 20x are shown (n=30). Scale bars, 200 μM.",
    "diseases": "PanINs"
  },
  {
    "caption": "Expression of pTGIF1 and Twist1 in human tissue microarrays of human PDAC samples was analyzed by immunohistochemistry. Representative pictures at different stages (40x) are shown.",
    "diseases": "PDAC"
  },
  {
    "caption": "The percentages of samples with high versus low expression of pTGIF1 and Twist1 in normal tissues versus PDAC tissues are shown. Scale bars, 100 μM.",
    "diseases": "PDAC"
  },
  {
    "caption": "A) Representative specimen of colorectal (CRC) primary tumour stained with haematoxylin/eosin/saffron (HES), or antibodies against E-cadherin or Vimentin. i) The blue, orange and pink dotted lines highlight the normal mucosa, the submucosa and the muscularis propria respectively. Red dotted line highlights the neoplastic tissue. Black arrowheads indicate the direction of invasion. Boxed regions ii and iii show high magnification of normal colonic glands (ii) and the CRC invasive front (iii). Scale bar: 2 mm and 500 μm.",
    "diseases": "colorectal (CRC) primary tumour, CRC, neoplastic"
  },
  {
    "caption": "B) Representative images of histological sections of normal colon and primary CRC stained for EpCam and Villin. Boxed regions i, ii and iii are high magnifications of the luminal cavity of normal colonic gland (i) and colorectal carcinoma glands (ii and iii). Aarrowheads point to the apical pole enriched in villin. Scale bars: 50 μm.",
    "diseases": "colorectal carcinoma, primary CRC"
  },
  {
    "caption": "A) Representative confocal images of non-invasive or invasive human colorectal cancer explants collected from 8 patients with NOS adenocarcinoma The explants were fixed 4 days after recovery and stained for the lumen (Ezrin), F-actin (Phalloidin) and nuclei (DAPI). Boxed regions i, ii, iii and iv are displayed at high magnification. Arrowheads point to non-protruding cells, arrows point to protruding cells and white stars show off-centered nuclei. Scale bars: 20 μm.",
    "diseases": "adenocarcinoma, colorectal cancer"
  },
  {
    "caption": "Graphs representing the percentage of adenocarcinoma explants displaying lumens (B) from 8 patients. Evaluation performed from DIC observation of live tissues, at least 50 explants were analysed per patients. The error bar represents the Standard Error of the Mean (Means ± SEM). P values were calculated using unpaired t-test (ns: non significant).",
    "diseases": "adenocarcinoma"
  },
  {
    "caption": "Graphs representing the percentage of adenocarcinoma explants displaying protrusions (C) from 8 patients. Evaluation performed from DIC observation of live tissues, at least 50 explants were analysed per patients. The error bar represents the Standard Error of the Mean (Means ± SEM). P values were calculated using unpaired t-test (ns: non significant).",
    "diseases": "adenocarcinoma"
  },
  {
    "caption": "D) Time-lapse sequences of an adenocarcinoma explant undergoing collective invasion into collagen-I gel monitored by DIC microscopy over 2 days Arrowheads point to non-protruding cells, arrows point to protruding cells and white stars point to lumens. Scale bars: 50 μm.",
    "diseases": "adenocarcinoma"
  },
  {
    "caption": "E) Images of an invading gland of a colorectal NOS adenocarcinoma, at the light microscopic level (i, semithin section, 100x objective), and as seen by electron microscopy (ii, 1000x magnification; and iii, 4000x magnification). Note that the bulk of the invading neoplastic gland is in a state of glandular organization (regions denoted by arrowheads in the left panel): epithelia (E, middle panel) are polarized to form a lumen (L), and are attached to a basal membrane (asterisk) by hemidesmosomes; the gland is surrounded by fibroblasts (F). However, this organization is focally disrupted at the tubular invasion pole (arrows in the left panel) where neoplastic epithelial cells have lost polarization and directly contact the surrounding stroma as the basal membrane is missing (right panel).",
    "diseases": "colorectal NOS adenocarcinoma, neoplastic"
  },
  {
    "caption": "C) Representative images of human adenocarcinoma explants after 2 days in 3D collagen-I gel, in non-treated (NT) or ROCK inhibitors treated-conditions (+Y27632) and (+H1152) and stained for the apical pole (Ezrin), F-actin (Phalloidin) and nuclei (DAPI). Boxed regions of NT, +Y27632, and +H1152 explants are shown at high magnification. Arrowheads point to non-protruding cells. Arrows point to protruding cells. White stars show nuclei that engage in protrusions. Scale bars: 20μm. D Explants displaying (D) lumens from 10 patients were quantified and results presented as percentage of total explants. Over 50 explants were counted per condition (duplicate) and per patient(Means ± SEM). P values were calculated using unpaired t-test (****p<0.0001 , n.s : non significant).",
    "diseases": "adenocarcinoma"
  },
  {
    "caption": "F) Time-lapse sequences of an adenocarcinoma explant undergoing collective invasion into collagen-I gel in the presence of Y27632 monitored by DIC microscopy for 2 days Arrowheads point to non-protruding cells, arrows point to protruding cells and white stars point to lumens. Scale bars: 50 μm.",
    "diseases": "adenocarcinoma"
  },
  {
    "caption": "G) Overall Survival Prognostic value of ROCK2 expression in colon cancer patients of the GSE33582 data set (n=477 patients with survival annotation) using Kaplan-Meier survival analysis. The patient cohort was divided into tumours with or without a down-regulation of ROCK2 relatively to non-tumoural tissues (expression cut-off value corresponds to the 1st decile of ROCK2 expression in non-tumoural sample, i.e. 7.6). Log-rank test p-values for survival distribution difference are indicated at 3 and 5 years.",
    "diseases": "colon cancer"
  },
  {
    "caption": "Treatment of NPC fibroblasts and NPC null mice with thioperamide. Fibroblast lines obtained from patients with well-established heterozygote mutations in the NPC1 (GM17912 line: NPC1 P1007A / T1036M; GM17911 line: NPC1 I1061T / T1036M) or with a homozygote mutation in the NPC2 gene (GM17910 line: C93F / C93F) were treated or not for 72h with thioperamide 10µM, stained with filipin (cholesterol) and analysed by fluorescence automated microscopy.",
    "diseases": "NPC"
  },
  {
    "caption": "Quantification of cholesterol and LBPA staining in NPC fibroblasts. Cells as in (A) were treated or not with thioperamide for 48h or 72h, labelled with filipin (cholesterol) and anti-LBPA antibodies, and analysed by fluorescence automated microscopy. The panels show the integrated intensity of the filipin (left) and LBPA (right) signals were quantified after 48 (top) and 72h (bottom). The colour code of each fibroblast cell line is as in (A). (n=3 independent experiments with 144 images acquired and analysed automatically, >2000 cells per experiment, error bars = SD, one-way ANOVA, *=p<0.05; **=p<0.005;***=p<0.001).",
    "diseases": "NPC"
  },
  {
    "caption": "Quantification of cholesterol in NPC fibroblasts by mass spectrometry. NPC cell lines (A) were treated or not with thioperamide or 0.1% (2-Hydroxypropyl)-ß-cyclodextrin for 72h. After extraction, lipids were analysed and quantified by mass spectrometry. (n=3; error bars = SD, one-way ANOVA, *=p<0.05; **=p<0.005;***=p<0.001)",
    "diseases": "NPC"
  },
  {
    "caption": "Quantification of cell counts in the 3 NPC cell lines treated with thioperamide. The experiment was as in (A-C) except that nuclei were labelled with DAPI and quantified by automated microscopy. Data are normalized to DMSO control (n=2 independent experiments, 75 images per experiments)",
    "diseases": "NPC"
  },
  {
    "caption": "Plasma levels of IFNα were measured in a cohort of 36 patients with chronic HBV.",
    "diseases": "chronic HBV"
  },
  {
    "caption": "A. Hematoxylin and eosin (H&E)-stained cross section of adenocarcinoma of the prostate, lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and Ewing sarcoma (ES) of the abdomen tumor. Annotated regions are T-tumor, S-stroma, D/G-duct/glandular, and A-adipose tissue. Scale bar is representative of A and B. Images are also used in Fig. S4A, 5D and S6G. B. Spatial distribution and relative abundance of glycogen (represented by CL7) from an immediate adjacent resected tissue section shown in A. The image displays a heatmap gradient of intensity with white (least abundant) to red (most abundant). Images are also used in Fig. S4E, 5D, and S6G. C. Glycogen structure defined by distribution of released glucose polymers as representation of glycogen chain length (CL) distribution from tumor regions shown in A. Values are presented as mean +/- standard error (n=3 technical replicates per region).",
    "diseases": "ES, Ewing sarcoma, LUAD, lung adenocarcinoma, lung squamous cell carcinoma, LUSC, adenocarcinoma of the prostate"
  },
  {
    "caption": "A. (Left) Hematoxylin and eosin (H&E)-stained cross section of an Ewing sarcoma (ES) of the shoulder tumor. Annotated regions are annotated as T-tumor and M-muscle. (Right) Spatial distribution and relative abundance of glycogen (represented by CL7) from an immediate adjacent resected tissue section. The image displays a heatmap gradient of intensity from white (least abundant) to red (most abundant). Scale bar and intensity gradient below are representative of all images in A-E. B. (Left) H&E stained cross section of an ES of the chest wall tumor. Annotated regions are annotated as T-tumor and N-necrosis. (Right) Spatial distribution and relative abundance of glycogen (represented by CL7) from an immediate adjacent resected tissue section. C. (Left) H&E stained cross section of an ES of the rib tumor. Annotated regions are annotated as T-tumor and N-necrosis. (Right) Spatial distribution and relative abundance of glycogen (represented by CL7) from an immediate adjacent resected tissue section. D. (Left) H&E stained cross section of an ES of the abdomen tumor. Annotated regions are T-tumor, S-stroma, and A-adipose tissue. (Right) Spatial distribution and relative abundance of glycogen (represented by CL7) from an immediate adjacent resected tissue section. E. (Left) H&E stained cross section of an ES of the bladder tumor. Annotated regions are T-tumor and S-stroma. (Right) Spatial distribution and relative abundance of glycogen (represented by CL7) from an immediate adjacent resected tissue section. F. Magnified H&E cross section of (top, left) tumor, and (top, right) muscle tissue from ES rib with magnified image of CL7 (m/z=1175) of (bottom, left) tumor, and (bottom, right) muscle tissues. G. Magnified H&E cross section of (top, left) tumor, (top, middle) stroma, and (top, right) adipose tissues from ES abdomen with magnified image of CL7 (m/z=1175) of (bottom, left) tumor, (bottom, middle) stroma and (bottom, right) adipose tissues.",
    "diseases": "ES, Ewing sarcoma, necrosis"
  },
  {
    "caption": "A. (Left) Hematoxylin and eosin (H&E) stained cross section of a normal human tibia (Top) resected at the same time as the Ewing sarcoma (ES) of the tibia tumor (Bottom). Annotated regions are CT-connective tissue, B-decalcified bone, BM-bone marrow, T-tumor, and S-stroma. (Right) Spatial distribution and relative abundance of glycogen (represented by CL7) from an immediate adjacent resected tissue section shown in A. The image displays a heatmap gradient of intensity with white (least abundant) to red (most abundant). Scale bar and intensity gradient below are representative of all images in A. B. Glycogen structure defined by distribution of released glucose polymers as representation of glycogen chain length (CL) distribution from normal tibia in A. Values are presented as mean +/- standard error (n=3 technical replicates per region). #0.01 < P < 0.05; ****P<0.0001, analyzed by two-way ANOVA with Tukey's multiple comparison for each glycogen chain length.C. Glycogen structure defined by distribution of released glucose polymers as representation of glycogen chain length (CL) distribution from the ES of the tibia tumor in A. Values are presented as mean +/- standard error (n=3 technical replicates per region). **0.001 < P < 0.01; ****P<0.0001, analyzed by two-tailed t-test for each glycogen chain length.",
    "diseases": "ES, Ewing sarcoma"
  },
  {
    "caption": "J. Spatial distribution of phosphorylated CL5 of human tibia (top) and tibial ES tumor (bottom). The image displays a heatmap gradient of intensity with black (least abundant) to yellow (most abundant). K. Phosphorylated chain length distribution in normal human tibia and tibial ES tumor in J. Values are presented as mean +/- standard error (n=3 technical replicates per region). ****P<0.0001, analyzed by two-tailed t-test for each glycogen chain length.",
    "diseases": "ES"
  },
  {
    "caption": "N. Representatives image of immunohistochemical staining of laforin in ES patient samples with annotation between tumor (T) and stroma (S) tissues. Tissues were scanned digitally using the Axio Scan.Z1 side scanner. Scale bar is shown below the image. O. Quantification of immunohistochemical laforin staining between normal tissue (n=3 technical replicates per region), tibial ES tumor (n=7 technical replicates per region), and stroma of five ES tissues (n=7). Values are presented as mean +/- standard error. **0.001 < P < 0.0; ***P < 0.001; ****P<0.0001, analyzed by one-way ANOVA with Tukey's multiple comparison.",
    "diseases": "ES"
  },
  {
    "caption": "(A) analysis using transcriptomic data from the liver of sepsisBIM mice (16h after intraperitoneal injection of live E. coli).",
    "diseases": "sepsis"
  },
  {
    "caption": "(B-C) Enrichment plots from GSEA performed using LIVER-ID genes (B) or the response to ERS gene set (GO:0034976) (C) as the gene set and transcriptomic differences in sepsisBIM vs Control mouse liver as the ranked gene list.",
    "diseases": "sepsis"
  },
  {
    "caption": "(E) Box plots showing Log2 FC for ERS UP, DOWN or unchanged genes in sepsisBIM vs Control mouse liver (6 mice per group). Box plots are composed of a box from the 25th to the 75th percentile with the median as a line and min to max as whiskers. One-way ANOVA with Welch's correction and Dunnett's Modified Tukey-Kramer pairwise multiple comparison test was used to assess statistical significance, *P < 0.05.",
    "diseases": "sepsis"
  },
  {
    "caption": "(F) RT-qPCR analyses of selected ERS UP genes and LIVER-ID TFs monitoring expression changes in the liver of sepsisBIM vs Control mice (6 mice per group). The bar graph shows means ± SD (standard deviations). One-sample t-test with BH correction for multiple testing was used to determine if the mean Log2 FC sepsisBIM/Control is statistically different from 0, *P < 0.05.",
    "diseases": "sepsis"
  },
  {
    "caption": "(G) Nuclear extracts from livers of control or sepsisBIM mice were subjected to Western blot or Simple Western immunoassay with antibodies against HNF4A, NR1H4 or FOXA2. LMNA was used as loading control.",
    "diseases": "sepsis"
  },
  {
    "caption": "(H) Nuclear extracts from livers of sepsisBIM mice pre-treated for 4 consecutive days with vehicle or 500 mpk TUDCA were subjected to Western blot with antibodies against HNF4A, NR1H4, FOXA2 or XBP1S. TFIIB was used as loading control. (I) Densitometric quantification of the protein expression data from 6 mice precondition shown in panel (H) (3 mice per condition) The bar graph shows means ± SD (standard deviations). One-sample t-test with BH correction for multiple testing was used to determine if the mean Log2 FC TUDCA/Vehicle is statistically different from 0, *P < 0.05.",
    "diseases": "sepsis"
  },
  {
    "caption": "(J) Serum alanine aminotransferase (ALT) (left) and aspartate aminotransferase (AST) activities (right) from sepsisBIM mice pre-treated for 4 consecutive days with vehicle or 500 mpk TUDCA (10 mice per group). The bar graphs show means ± SD (standard deviations). Student's t-test was used to assess statistical significance, *P < 0.05.",
    "diseases": "sepsis"
  },
  {
    "caption": "(A) RT-qPCR analyses of selected ERS UP genes and LIVER-ID TFs in livers from sepsisCLP mice collected 10h, 30h or 3 days after CLP (15 mice per group) vs livers from healthy pair-fed mice (Control) (15 mice per group). The bar graph shows means ± SD (standard deviations). Wilcoxon test with BH correction for multiple testing was used to assess statistical significance, *P < 0.05.",
    "diseases": "sepsis"
  },
  {
    "caption": "(F) Expression of LIVER-ID TF encoding genes was analyzed in the livers of deceased critically-ill patients with sepsis displaying agonal bilirubin levels below (Bil<2; n=34) or above (Bil>2; n=28) 2mg/dL. Median fold-change expression level of each group for the different genes has been used to generate the box plots. Expression levels in the critically-ill groups are expressed relative to those in the control group (n=18). Box plots are composed of a box from the 25th to the 75th percentile with the median as a line and min to max as whiskers. One-tailed t-test was used to assess whether expression of LIVER-ID TF encoding genes in the Bil>2 group is significantly greater than in the Bil<2 group, *P < 0.05.",
    "diseases": "sepsis"
  },
  {
    "caption": "(G) RT-qPCR analyses of indicated LIVER-ID TF encoding genes monitoring expression in the livers of Bil<2 (n=34) or Bil>2 (n=28) groups of deceased critically-ill patients with sepsis vs control donors (n=18). Data are shown as box plots, with mRNA levels of the critically-ill groups expressed relative to those of the control group. Box plots are composed of a box from the 25th to the 75th percentile with the median as a line and min to max as whiskers. Wilcoxon test was used to assess statistically significant differences with the Bil>2 group, *P < 0.05.",
    "diseases": "sepsis"
  },
  {
    "caption": "scPEP or miPEP31 was injected intravenously every 3 days starting from day 8 post immunization. (D, E) H&E and Fast blue staining of paraffin sections of spinal cords derived from scPEP or miPEP31 treated mice on day 15 after immunization. Histopathology scores of inflammation and demyelination were shown in (E). Scale bars, 70 μm. Data in (C, E) are presented as mean ± SEM of three independent experiments with nine to ten mice per group in each. ****",
    "diseases": "inflammation"
  },
  {
    "caption": "B The neutralization curve of serum samples in COVID-19 convalescents and vaccinees against RshSTT182 and SARS-CoV-2 are shown. Bar represents the SD of two replicates.",
    "diseases": "COVID-19"
  },
  {
    "caption": "A. Immunohistochemical (IHC) staining of viral spike proteins in lung sections from K18-hACE2 mice (Winkler et al., 2020) at day 5 post-infection. Spike proteins were detected with anti-spike antibody and stained brown. Images of bronchial epithelium of vehicle control treated (i and ii) and C6G25S treated (iii and iv), alveoli of vehicle control treated (v and vi) and C6G25S treated (vii and viii), bronchiole and blood vessel of vehicle control treated (ix and x) and C6G25S treated (xi and xii) group were shown. Syncytial cell was indicated by green arrow in (xi) and thrombosis in (x).",
    "diseases": "thrombosis"
  },
  {
    "caption": " (B) Box plots show the MIG-6 (ERRFI1) gene expression in different breast tumor subtypes in the Servant dataset of 343 primary breast cancer carcinomas, analyzed using Illumina HumanWG-6_v3 Arrays. The gene expression levels are determined using the R2 Genomics Analysis and Visualization Platform (http://r2.amc.nl). In the box plot, error bars are the 95% confidence interval, the bottom and top of the box are the 25th and 75th percentiles, the line inside the box is the 50th percentile (median), and any outliers are shown as open circles. **p < 0.01, by Student's t-test. ",
    "diseases": "breast cancer"
  },
  {
    "caption": " (C) Immunoblotting analysis for MIG-6 protein expression in various human breast cancer cell lines. ",
    "diseases": "breast cancer"
  },
  {
    "caption": " (D) Representative images of histological analyses of MIG-6 in TNBC patients in low-grade (stage I) and high-grade (stage III) tumors. Scale bar, 200 µm. ",
    "diseases": "TNBC"
  },
  {
    "caption": "(E) Quantification analysis of MIG-6 expression in 85 cases of resected TNBCs. In the box plot, error bars are the 95% confidence interval, the bottom and top of the box are the 25th and 75th percentiles, the line inside the box is the 50th percentile (median). The p-value 0.011 is used for the comparison of all three groups, determined by the Kruskal-Wallis H test.",
    "diseases": "TNBCs"
  },
  {
    "caption": " (F) Kaplan-Meier plot analysis of the disease-specific survival of 85 TNBC breast cancer patients with low or high expression of MIG-6. ",
    "diseases": "breast cancer, TNBC"
  },
  {
    "caption": " (G) Kaplan-Meier plot analysis of the metastasis-specific survival of 85 TNBC patients with low or high expression of MIG-6. MIG-6 protein expression in the 85 TNBC specimens was determined by H-score and widely distributed. MIG-6 expression greater than or equal to the median is classified as \"high,\" while expression less than the median is classified as \"low.\" ",
    "diseases": "TNBC"
  },
  {
    "caption": " (A) Box plots show the GLUT1 (SLC2A1) gene expression in different breast tumor subtypes in the Servant dataset of 343 primary breast cancer carcinomas, analyzed using Illumina HumanWG-6_v3 Arrays. The gene expression levels are determined using the R2 platform. In the box plot, error bars are the 95% confidence interval, the bottom and top of the box are the 25th and 75th percentiles, the line inside the box is the 50th percentile (median), and any outliers are shown as open circles. **p < 0.01, by Student's t-test.. ",
    "diseases": "breast cancer"
  },
  {
    "caption": " (C) Representative images of histological analyses for GLUT1 and MIG-6 expressions in TNBC patients in low-grade (stage I) and high-grade (stage III) tumors Scale bar, 200 µm. ",
    "diseases": "TNBC"
  },
  {
    "caption": " (E) Representative images of the immunofluorescence multiplex assay for colocalization of MIG-6 and HIF1α protein expression in TNBC tumor specimens. The triangle indicates nuclear colocalization, and the star indicates cytoplasmic colocalization. ",
    "diseases": "TNBC"
  },
  {
    "caption": "(A) Correlation of ZEB1 mRNA expression with the expression of YAP, FOSL1 and JUN across all breast cancer cell lines included in the cancer cell line encyclopedia (CCLE). rs: Spearman's rank correlation coefficient.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(B) Heatmap of RNA-seq expression data of all CCLE breast cancer cell lines.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(A) Kaplan Meier plots from survival analyses of human ER-/PR- breast cancers showing distant metastasis free survival (DMFS) based on the expression of the indicated genes or gene combinations. HR: hazard ratio. p-value from log-rank test.",
    "diseases": "ER-/PR- breast cancers"
  },
  {
    "caption": "(B) Hypergeometric testing showed a significant association of nuclear ZEB1 and FOSL1 expression on the protein level as determined by immunohistochemistry on 81 human breast cancer samples. The upper panel shows staining of a serial section of a negative and a positive case. Note that stromal cells (asterisks) are negative for FOSL1, and partially positive for ZEB1 and YAP, and that expression of ZEB1 in tumour cells (arrows) of positive cases is weaker than in stromal cells. Odds ratio (OR): measure of association between categorical variables with OR > 1 indicating a positive association.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(C) Heatmap of mRNA expression data of ZEB1, YAP, JUN and 9 selected activated ZEB1/YAP/AP-1 target genes in breast cancer patient samples (GSE18229). Genes were selected for known roles in tumour promoting properties like cell migration. Tumours in which ≥ 6 out of 9 genes of the selected ZEB1/YAP/AP-1 target gene set were expressed higher than the 60th percentile of expression were defined as "tumour promoting gene set high"; when expression of ≥ 6 out of the 9 genes was below the 40th percentile, tumours were defined as "tumour promoting gene set low". Tumours were annotated according to their molecular subtype.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(E) Kaplan Meier plots from survival analyses of human breast cancers patient samples (GSE18229) showing relapse free survival (RFS) based on the combined expression of the 9 selected ZEB1/YAP/AP-1 activated targets HR: hazard ratio. p-value from log-rank test. (F) Kaplan Meier plots from survival analyses of human ER-/PR- breast cancers showing distant metastasis free survival (DMFS) based on the combined expression of the 9 selected ZEB1/YAP/AP-1 activated targets HR: hazard ratio. p-value from log-rank test.",
    "diseases": "ER-/PR- breast cancers, breast cancers"
  },
  {
    "caption": "(C) Immunofluorescence micrographs of VAMP8 (green) and Syntaxin-7 (STX7; red) show strong colocation around 3 µm silica bead phagosomes (white) in BMA macrophages. Nuclei are stained with Dapi. Scale bar is 5 µm. To account for people with red-green colour-blindness, (D) Colocation of VAMP8 (green) and STX7 (red) on individual phagosomes between WT and RNF115 KO cells represented by intersection, Manders' M1 and overlap coefficients. Data is represented as a box and whisker plot of total values across biological duplicate experiments, where the whiskers represent the minimum to maximum values and the central band indicates the median.",
    "diseases": "red-green colour-blindness"
  },
  {
    "caption": "(D) Box and whisker plot represents the quantification of the percentage (%) of the hepatic lesion area in the livers from six wild-type (WT) and six RNF115 KO (KO) mice after 48 h infection with S. aureus. Haematoxylin and eosin (H&E)-stained liver sections of one representative animal per genotype are shown on the right, dotted line depicts the damaged area.",
    "diseases": "hepatic lesion"
  },
  {
    "caption": "A Representative clinical picture of two patients with CAOP syndrome (14-year-old patient 1 and 5-year-old patient 2).",
    "diseases": "CAOP syndrome"
  },
  {
    "caption": "D Inflammatory lesions in CAOP syndrome were significantly improved by riboflavin supplementation. The representative head image of patient 1 before therapy is shown in Figure 1A (panel 1).",
    "diseases": "CAOP syndrome"
  },
  {
    "caption": "(C) Survival curves of p53-/-;MDMXSG/SG and p53-/-;MDMXwt/wt mice. Thymic lymphomas were the major cause of mortality in both genotypes.",
    "diseases": "Thymic lymphomas"
  },
  {
    "caption": "D) Protein expression of the ADAM17 variants in the mouse breast cancer cell line 4T1 Adam17-/-, determined by Western blot. GAPDH was used as an internal loading control.",
    "diseases": "breast cancer"
  },
  {
    "caption": "Representative immunofluorescence (IF) staining of Ki67 and TDP-43 in the regions of frontal cortices from 6-mon-old WT and FTLD-TDP Tg mice. Nuclei were stained with 4',6-diamidino-2-phenylindole (DAPI; upper panel in blue) or neural marker NeuN (lower panel in green). Scale bar: 50 μm. The circled area is emphasized for showing the distribution of immunoreactivity in cell subregions. Scale bar: 15 μm.",
    "diseases": "FTLD"
  },
  {
    "caption": "Representative data of reverse-transcription PCR (left panel) or Western blot (right panel) for cell cycle-related genes and semi-quantification of the expression levels in the frontal cortices and hippocampus from the 6-mon-old WT and FTLD-TDP Tg mice. N = 5 mice per group, data are presented as mean ± SEM (%), statistical analysis by multiple t-test with FDR correction, Q = 1%. *P < 0.05, **P ≤ 0.01; ***P ≤ 0.001 and ****P ≤ 0.0001",
    "diseases": "FTLD"
  },
  {
    "caption": "Representative image of comet assay for DNA fragmentation and the quantification of cells with comet tails in the regions of frontal cortices from 6-mon-old WT and FTLD-TDP Tg mice. Scale bar: 50 μm. n = 9 sections per mouse, N = 5 mice per group, data are presented as mean ± SEM, *p = 0.0114 by t-test.",
    "diseases": "FTLD"
  },
  {
    "caption": "Representative IF staining of γH2AX and TDP-43 in the regions of frontal cortices from 6-mon-old WT and FTLD-TDP Tg mice. Nuclei were stained with DAPI (upper panel in blue) or NeuN (middle panel in green). Scale bar: 50 μm. The circled area is emphasized for showing the distribution of immunoreactivity in cell subregions. Scale bar: 15 μm. Lower panel: quantification of cells or neurons with γH2AX immunoreactivity and TDP-43 proteinopathies from each view of microscope. n = 9 sections per mouse, N = 5 mice per group, data are presented as mean ± SEM, ***p = 0.0008 by t-test.",
    "diseases": "FTLD"
  },
  {
    "caption": "Representative IF staining of γH2AX and Ki67 in the regions of frontal cortices from WT and FTLD-TDP Tg mice. Nuclei were stained with DAPI (upper panel) or NeuN (middle panel). Scale bar: 50 μm. Subregions, scale bar: 15 μm. Lower panel: quantification of cells or neurons with γH2AX and Ki67 immunoreactivity from each view of microscope. n = 9 sections per mouse, N = 5 mice per group, data are presented as mean ± SEM, ***p = 0.0004 by t-test.",
    "diseases": "FTLD"
  },
  {
    "caption": "Top, representative western blot data of HDAC1 and TDP-43 in extracts obtained following RIPA fractional extraction in the frontal cortices and hippocampus from 6-mon-old of FTLD-TDP or WT mice. Bottom, semi-quantification of HDAC1 and TDP-43 expression levels. N = 5 mice per group, data are presented as mean ± SEM (%), **** p < 0.0001 by multiple t-tests.",
    "diseases": "FTLD"
  },
  {
    "caption": "IF staining of HDAC1 and SMI-32 in the regions of frontal cortices from WT and FTLD-TDP Tg mice. Scale bar: 150 μm. Blocked area in left bottom picture is showed in a magnified view in the right bottom picture. Scale bar: 50 μm.",
    "diseases": "FTLD"
  },
  {
    "caption": "Nuclear HDAC1 activity assay from frontal cortices and hippocampus in 6-mon-old of FTLD-TDP and WT mice. TSA: nuclear extracts that were treated with Trichostatin A (TSA, an HDAC inhibitor) as a negative control for HDAC1-transferred fluorescent activity during the HDAC1 activity assay. N = 5 mice per group, data are presented as mean ± SEM (%), *p = 0.0415 by t-test.",
    "diseases": "FTLD"
  },
  {
    "caption": "Left, representative western blot data of nuclear acetylated-histone H3 (Lys 9/14) and total-histone H3 in 6-mon-old of WT and FTLD-TDP Tg mice. Right, quantification of nuclear acetylated-histone H3/total-histone H3 ratio. N = 5 mice per group, data are presented as mean ± SEM (%), * p = 0.0147 by t-test.",
    "diseases": "FTLD"
  },
  {
    "caption": "Left graph: IF staining of TDP-43 and HDAC1 during progression of TDP-43 proteinopathies in the frontal cortices from the FTLD-TDP Tg and WT mice. Nuclei were stained with DAPI (in blue). Scale bar: 50 μm. The circled area is emphasized for showing the distribution of immunoreactivity in cell subregions. Scale bar: 15 μm. Right histogram: Quantification of co-localized TDP-43 and HDAC1 immunoreactivity in the cytosol or nucleus in the WT or 1-, 6-, and 12-month-old FTLD-TDP Tg mice. n = 9 sections per mouse, N = 5 mice per group, data are presented as mean ± SEM. *Nucleus: Tg 1m vs. Tg 6m or 12m; #Cytosol: Tg 1m vs. Tg 6m or 12m; @ Tg 6m vs Tg 12m. ****/####/@@@@ p < 0.0001 by multiple comparison.",
    "diseases": "FTLD"
  },
  {
    "caption": "Left graph: IF staining of γH2AX and HDAC1 in the frontal cortices from the 12-month-old FTLD-TDP Tg and WT mice. Nuclei were stained with DAPI (in blue). Arrow head: γH2AX+ nucleus; arrow: mislocalized HDAC1. Scale bar: 50 μm. Right histogram: Quantification of γH2AX+ and HDAC1 mislocalized cells in the WT or 1-, 6-, and 12-month-old FTLD-TDP Tg mice. n = 4 sections per mouse, N = 5 mice per group, data are presented as mean ± SEM. ** p = 0.0079, **** p < 0.0001 by multiple comparison.",
    "diseases": "FTLD"
  },
  {
    "caption": "Upper panel: Immunoprecipitation of cytosolic HDAC1 and immunoblotting of HDAC1 and TDP-43 in WT and FTLD-TDP Tg mice. Lower histogram: Quantification of immunoprecipitation results of HDAC1 and TDP-43 in WT and Tg mice. N = 5 mice per group, data are presented as mean ± SEM (%), * p =0.0149, *** p =0.0003 by t-test.",
    "diseases": "FTLD"
  },
  {
    "caption": "Representative IF staining of TDP-43 and HDAC1 in the frontal cortices from normal individuals and patients with FTLD-TDP. Scale bar: 50 μm. The circled area is emphasized for showing the distribution of immunoreactivity in cell subregions. Scale bar: 15 μm.",
    "diseases": "FTLD"
  },
  {
    "caption": "Representative IF staining of γH2AX and Ki67 in the frontal cortices from normal individuals and patients with FTLD-TDP from each view of microscope. Scale bar: 50 μm. The circled area is emphasized for showing the distribution of immunoreactivity in cell subregions. Scale bar: 15 μm.",
    "diseases": "FTLD"
  },
  {
    "caption": "Linear regression analysis of cells with DNA damage and aberrant cell cycle activity. Cell counts: 40 -113 (normal) and 418-887 (FTLD) per samples. p < 0.0001 by Pearson correlation analysis. Data information: All data represent mean ± SEM, **** p < 0.0001 by t-test.",
    "diseases": "FTLD"
  },
  {
    "caption": "Dot-blot of HDAC1 and TDP-43 in urea-soluble fractions from the frontal cortex of normal individuals and patients with FTLD-TDP.",
    "diseases": "FTLD"
  },
  {
    "caption": "A) 8-µm cross section of 15-week-old WT and Dup18-30 TA and triceps were analyzed for dystrophin localization by immunofluorescence. Asterisk indicates clusters of revertant fibers. Scale bars, 100 μm. B) The muscle architecture of the same muscles was investigated by H&E staining. A representative image is shown. Scale bars, 100 μm. Asterisk indicates areas with necrotic fibers and fibrosis. Arrows indicate fibers with central nuclei.",
    "diseases": "fibrosis"
  },
  {
    "caption": "A) Fibrosis was analyzed in the diaphragm via Masson Trichrome staining. Scale bars, 100 μm.",
    "diseases": "Fibrosis"
  },
  {
    "caption": "EAE disease course of RAG2-/- mice that received CD45.1+2D2CD4+ naive T cells alone or together with CD4+GFP/Foxp3+ iTreg cells from CD45.1-2D2CD4+GFP(Foxp3)+ naïve T cells transduced with either control retrovirus (MIN) or retrovirus encoding C/EBPβ, cultured in the presence of TGF-β, anti-IFN-γ and anti-IL-4 Abs and sorted based on GFP/Foxp3 expression. The recipients were immunized with myelin oligodendrocyte glycoprotein peptide (100 ug) 1 d after transfer. Data show mean ± s.e.m of the EAE clinical score of 9 (day 1 to day 11), 5 (day 12 to day 16) or 4 (day 17 to day 20) mice of each group",
    "diseases": "EAE"
  },
  {
    "caption": "(i) Representative images of  immuno-histochemical staining of SLC7A11 and YAP  proteins in HCC samples from patients. Scale bars, 50μm. (j) Quantification of the  immunohistochemical stainings shown in (i) revealed a positive correlation of YAP and SLC7A11 expression (N=10). Statistical significance was calculated using Pearson correlation analysis. ",
    "diseases": "HCC"
  },
  {
    "caption": "(f) Colony formation assay demonstrating that the ferroptosis  inhibitor Ferrostatin-1 (Fer) reversed Sorafenib-induced cell death in ATF4-deficient HCC cells. HLE cells transfected with siCtrl or siATF4 were treated with Sorafenib (8μM) or DMSO plus either DMSO or Ferrostatin-1 (Fer; 5μM) for 2 weeks. Results represent three independent experiments.",
    "diseases": "HCC"
  },
  {
    "caption": "(h) Immunohistochemical staining of ATF4 in HCC and adjacent non-neoplastic areas from patients. Tumor tissues showed a higher expression of ATF4. Scale bar, 100μm. (i) Quantification of ATF4-positive cells in tumor and non-tumor samples showed that HCC tumors present higher ATF4  levels. Data are shown as mean ± standard deviation (SD). Statistical significance was calculated using unpaired t-test. (j) Representative images of  immuno-histochemical staining  of ATF4 and SLC7A11 proteins in HCC samples from patients. Scale bars, 50μm. ",
    "diseases": "HCC"
  },
  {
    "caption": "(h) Representative images of immuno-histochemical staining  of ATF4 and YAP  proteins in HCC samples from patients. Scale bars, 50μm. (i) Quantification of the immunohistochemical staining in (j) showed a positive correlation of ATF4 and YAP expression (N=18). Statistical significance was calculated using Pearson correlation analysis. ",
    "diseases": "HCC"
  },
  {
    "caption": "Combination of  YAP/TAZ deficiency and Sorafenib treatment suppressed tumor growth in a HCC xenograft  model. SNU398-shLuc or SNU398-shYAP/TAZ (shY/T) cells were transplanted into the flanks of immunodeficient NSG mice. Once the tumors were palpable, mice were treated with 20mg/kg Sorafenib  or vehicle control, and tumor sizes were measured twice a week (b).  Tumor weights were also recorded after sacrifice of the mice Data are shown as mean ± standard deviation (SD). Statistical significance was calculated using two-way ANOVA analysis. Mouse numbers of shLuc + Vehicle, shY/T + Vechicle and shY/T + Srf  were 4 per cohort, mouse numbers of shLuc + Srf  were 3 per cohort.",
    "diseases": "HCC"
  },
  {
    "caption": "(e) Pharmacological inhibition of glutathione synthesis and function sensitizes  HCC tumors to Sorafenib therapy. SNU398 cells were transplanted into the flanks of immunodeficient NSG mice. Once the tumors were palpable, mice were treated with vehicle control or with 20mg/kg Sorafenib alone, or with 20mg/kg Sorafenib and 20mM BSO in the drinking water or 120mg/kg SSA per os. Tumor sizes were measured twice a week. Data are shown as mean ± standard deviation (SD). Statistical significance was calculated using two-way ANOVA analysis. Mouse numbers were 8 for the experimental cohorts Vehicle, Srf, and  Srf + SSA and 7 for  Srf + BSO.",
    "diseases": "HCC"
  },
  {
    "caption": "(C( Downregulation of USP1 markedly reduces muscle fiber atrophy. Cross-sectional areas of 500 fibers transfected with shUSP1 (that express GFP, green bars) vs. 500 nontransfected fibers (black bars) in the same muscle. n = 5 mice. A representative image is shown; Laminin staining is in red; Bar, 50μm.",
    "diseases": "atrophy"
  },
  {
    "caption": "(C) Downregulation of PHLPP1 markedly reduces muscle fiber atrophy. Cross-sectional areas of 500 fibers transfected with shPHLPP1 (that express GFP, green bars) vs. 500 nontransfected fibers (black bars) in the same muscle. n = 4 mice. A representative image is shown; Laminin staining is in red; Bar, 50μm.",
    "diseases": "atrophy"
  },
  {
    "caption": "D. Overall survival of ACC patients according to FATE1 expression in their tumours, as measured by quantitative immunohistochemistry (low, green curve; high, red curve) in mutivariate analysis. p=0.008.",
    "diseases": "tumours"
  },
  {
    "caption": "Immune cell contexture in healthy colon and colon tumors of Apcfl/fl-Cdx2CreERT2 mice. Relative TCRβ+ T cell content in colon (n=10) and tumor (n=22). relative content of individual cell types was determined in tissue-derived single cell suspension using cell type specific antibodies and FACS analysis.",
    "diseases": "colon tumors"
  },
  {
    "caption": "Immune cell contexture in healthy colon and colon tumors of Apcfl/fl-Cdx2CreERT2 mice. Anti-CD3 immunostaining on normal colon (left panel) and a representative colon tumor section derived from an Apcfl/fl-Cdx2CreERT2 mouse (right panel: higher magnification of area indicated in middle panel).",
    "diseases": "colon tumor, colon tumors"
  },
  {
    "caption": "Immune cell contexture in healthy colon and colon tumors of Apcfl/fl-Cdx2CreERT2 mice. Relative CD11b+ myeloid cell content in colon (n=16) and tumors (n=16). relative content of individual cell types was determined in tissue-derived single cell suspension using cell type specific antibodies and FACS analysis.",
    "diseases": "colon tumors"
  },
  {
    "caption": "Immune cell contexture in healthy colon and colon tumors of Apcfl/fl-Cdx2CreERT2 mice. Anti-Gr1 immunostaining on normal colon (left panel) and a representative colon tumor section derived from an Apcfl/fl-Cdx2CreERT2 mouse (right panel: higher magnification of area indicated in middle panel).",
    "diseases": "colon tumor, colon tumors"
  },
  {
    "caption": "Immune cell contexture in healthy colon and colon tumors of Apcfl/fl-Cdx2CreERT2 mice. Relative CD11b+ MHCII- Gr1hi neutrophil (E) and CD11b+ MHCII- Gr1lo monocyte (F) content in colon (n=13) and tumors (n=16). relative content of individual cell types was determined in tissue-derived single cell suspension using cell type specific antibodies and FACS analysis.",
    "diseases": "FACS, colon tumors"
  },
  {
    "caption": "Immune cell contexture in healthy colon and colon tumors of Apcfl/fl-Cdx2CreERT2 mice. , Correlation of tumor T cell numbers to sample-matched tumor-derived neutrophil (left panel) and monocyte (right panel) numbers (n=16). relative content of individual cell types was determined in tissue-derived single cell suspension using cell type specific antibodies and FACS analysis.",
    "diseases": "colon tumors"
  },
  {
    "caption": "Percentage of Tregs among total T cells (CD45+ TCRβ+) in normal colon (n=10) or colon tumors (n=11). relative content of individual cell types was determined in tissue-derived single cell suspension using cell type specific antibodies and FACS analysis.",
    "diseases": "colon tumors"
  },
  {
    "caption": "In vitro co-culture of activated T cells with increasing ratios of neutrophils, monocytes or macrophages. T cell proliferation index is numbers of proliferated T cells after three days of indicated co-culture condition relative to the number of proliferated T cells when cultured alone. CD4+ and CD8+ T cells were derived from lymph nodes of wild-type mice. Neutrophils, monocytes and macrophages were derived from colon tumors of Apcfl/fl-Cdx2CreERT2 mice. Each dot represents an individual neutrophil (n=4), monocyte (n=3) or macrophage (n=4) sample. Bars represent mean +/- SD.",
    "diseases": "colon tumors"
  },
  {
    "caption": "mRNA expression levels of Mmp9 (C) or Tgfb1, Tgfb2 and Tgfb3 (D) in indicated FACS sorted cell types isolated from mouse colon tumors (n=4). Data are derived from RNA-sequencing and are displayed as reads per kilo base per million mapped reads (rpkm).",
    "diseases": "colon tumors"
  },
  {
    "caption": "Evaluation of TGFβ signaling activity in mouse colon tumors after four consecutive daily injections of hosts with 40mg/kg of the MMP2/9-inhibitor SB3-CT (MMPi). , Co-immunostaining for pSMAD3 (green) and IGFBP7 (magenta) on representative tumor-containing colon sections derived from Apcfl/fl-Cdx2CreERT2 mice treated with vehicle (A) MMPi (B).",
    "diseases": "colon tumors"
  },
  {
    "caption": "Evaluation of TGFβ signaling activity in mouse colon tumors after four consecutive daily injections of hosts with 40mg/kg of the MMP2/9-inhibitor SB3-CT (MMPi). Quantification of pSMAD3+ cells (left panel) and pSMAD3 staining intensity per pSMAD3+ cell (right panel) on at least five arbitrarily selected tumor areas per section of MMPi (n=6) or vehicle (n=6) treated mice.",
    "diseases": "colon tumors"
  },
  {
    "caption": "effect of in vivo TGFBRi and MMPi treatment of mice for two weeks on colon tumor formation. Apcfl/fl-Cdx2CreERT2 mice were treated with Tamoxifen and, one day post treatment, injected with either MMPi (n=10) or the TGFBRi SB431542 (n=10) at 40mg/kg for two weeks with five injections per week. Vehicle treated mice: n=11. Average tumor size per mouse was assessed during colon resection one week after the end of treatments (E).",
    "diseases": "colon tumor"
  },
  {
    "caption": "evaluation of S100A9+ neutrophil and CD8+ T cell infiltration in histologic sections of human CRC tumors. , Anti-S100A9 immunostaining on a representative human CRC section. Arrowheads indicate neutrophil infiltration at the tumor boarder. Co-immunostaining for CD8 (brown) and S100A9 (gray-blue) in the same CRC sample as shown in A.",
    "diseases": "CRC"
  },
  {
    "caption": "evaluation of S100A9+ neutrophil and CD8+ T cell infiltration in histologic sections of human CRC tumors. Quantification of S100A9+ cells (upper panel) and CD8+ T cells in different areas on CRC tumor sections containing tumor border with adjacent benign mucosa as determined by a specialized pathologist: "Tumor center" was tissue within tumor >200μm from tumor border, "Tumor border" was tissue within tumor <100μm from tumor border and "Adjacent benign mucosa" was mucosa tissue outside tumor <100μm from tumor border. Per section, all identifiable tumor border and adjacent benign areas, as well as three arbitrary tumor center areas were scored. Sections were derived from 10 individual patients.",
    "diseases": "CRC"
  },
  {
    "caption": "Gene expression scores were generated as described in material and methods. Boxes are lower and upper quartiles with median as solid lines; horizontal lines define minimum and maximum; dots define outliers. Comparison of T cell gene expression scores in CMS4 tumors within two publicly available CRC gene expression datasets (median, lower and upper quartiles; horizontal lines define minimum and maximum; dots define outliers). Samples are categorized according to the medians (high = >median; low = neutrophil and TGFβ gene expression scores. Upper panel: TCGA dataset. Lower panel GSE39582 dataset.",
    "diseases": "CRC"
  },
  {
    "caption": "Proliferation of activated blood T cells in vitro in co-culture with increasing ratios of CRC patient-derived autologous blood neutrophils. CD3+ T cells and CD66b+ neutrophils were isolated and cultured individually for each patient. Bar graphs display relative numbers of proliferated T cells after three days of co-culture. Each dot per condition represents a neutrophil sample from an individual patient (n=13). Bars represent mean + SD.",
    "diseases": "CRC"
  },
  {
    "caption": "Proliferation of activated blood T cells in vitro in co-culture with autologous blood neutrophils. Cells were derived from both CRC patients (n=2) and healthy volunteers (n=5). T cells and neutrophils were cultured at a 1:1 ratio and treated with vehicle (T + Ne) or 10µm Galunisertib (T + Ne + TGFBRi). Each line represents a neutrophil sample from an individual healthy volunteer.",
    "diseases": "CRC"
  },
  {
    "caption": "(C) The stiff and soft tumor cells were isolated from 3 patients with breast cancer and stained with anti-BCL9L antibody. The expression of BCL9L was observed under confocal microscope. Scale bar, 10 μ Data information: Paired Student's t test (C) The data represent mean ± SD.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(E) The correlation between the expression of BCL9L from 18 melanoma patients and the grade of melanoma. Data information: Pearson's correlation test E) The data represent mean ± SD.",
    "diseases": "melanoma"
  },
  {
    "caption": "(F) Overall survival compared to the BCL9L level in breast cancer (BRCA, n = 536) or melanoma (n = 376) patients. Data information: Log-rank survival analysis (F). The data represent mean ± SD.",
    "diseases": "breast cancer, melanoma"
  },
  {
    "caption": "Primary skin fibroblasts from a normal individual, SLOS patient, ZS patients, X-ALD patient, and NPC patient incubated for 24 h without serum were immunostained with anti-pericentrin (red) and anti-acetylated tubulin (blue) antibodies. Cholesterol was stained with Filipin III (green). Arrows indicate primary cilia. Scale bar, 5 μm. The intensity of Filipin III signal at primary cilia from (a) was remarkably reduced in SLOS and ZS patient cells (**p<0.01: one-way ANOVA with Tukey's HSD, n=3: 45-50 cells per experiment). In the boxplot, medians, 25th/75th percentile and min/max were represented by the central lines, the box limits, and the whiskers/error bars, representatively.",
    "diseases": "X-ALD, NPC, SLOS, ZS"
  },
  {
    "caption": "Immunofluorescent staining of primary skin fibroblasts in quiescent G0 phase treated with 50 nM Shh-N for 24 h using anti-Smo (green), anti-acetylated-tubulin (blue), and anti-γ-tubulin (red) antibodies. Arrows indicate primary cilia. Scale bar, 2.5 μm. Quantification of proportion of Smo-positive ciliated cells upon Shh-N stimulation from (C). The populations of Smo-positive ciliated fibroblasts from the SLOS and ZS patients were significantly reduced (mean ± s.d.: ***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 100 cells per experiment). The Smo intensity at primary cilia in the fibroblasts from (C). The ciliary localization of Smo upon Shh-N stimulation was significantly impaired in fibroblasts from the SLOS and ZS patients (***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 90-100 cells per experiment). In the boxplot, medians, 25th/75th percentile and min/max were represented by the central lines, the box limits, and the whiskers/error bars, representatively.",
    "diseases": "SLOS, ZS"
  },
  {
    "caption": "Primary fibroblasts from a normal individual, and SLOS and ZS patients were treated with 1.5% methyl-β-cyclodextrin for 45 min to remove cellular cholesterol, and then incubated with or without cholesterol (cholesterol/methyl-β-cyclodextrin complex) for 1 h. After washing out the exogenous cholesterol, the fibroblasts were stimulated with 50 nM Shh-N for 24 h in the presence of pravastatin, and then immunostained with anti-Smo (green), anti-acetylated-tubulin (blue), and anti-pericentrin (red) antibodies. For the alternative cholesterol complementation, LDL (0.06 mg/ml) was co-incubated with Shh-N and pravastatin for 24 h after methyl-β-cyclodextrin-mediated cholesterol depletion. Scale bar, 2.5 μm. Quantification of the Smo intensity at primary cilia in the fibroblasts from (F). The ciliary accumulation of Smo upon the Shh-N stimulation of fibroblasts from an SLO patient was restored by the complementation of both exogenous cholesterol/methyl-β-cyclodextrin complex and LDL, while that of cells from ZS patients was efficiently rescued by not LDL but cholesterol/methyl-β-cyclodextrin complex (*p<0.05, **p<0.01, ***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 90-100 cells per experiment). In the boxplot, medians, 25th/75th percentile and min/max were represented by the central lines, the box limits, and the whiskers/error bars, representatively.",
    "diseases": "SLO, SLOS, ZS"
  },
  {
    "caption": "(A) Immunocytochemistry of patient-derived cystinotic tubuloids (CNTSPatient-1 and CTNSPatient-2) and healthy kidney tissue-derived control tubuloids (CNTSWT-1 and CTNSWT-2) for PAX8, TP63 and F-actin. Scale bar = 100 µm.",
    "diseases": "cystinotic"
  },
  {
    "caption": "(C, D) Quantification of cystine levels (nmol/mg protein) by HPLC-MS/MS in two different patient-derived cystinotic tubuloids in the absence of the drugs (NT) or upon treatment with cysteamine (100 μM), bicalutamide (35 μM) or cysteamine (100 μM)-bicalutamide (35 μM) combination treatment (n = 3). (E) αKG levels measured in patient-derived cystinotic tubuloids (CNTSPatient-1 and CTNSPatient-2) in the absence of the drugs (NT) or upon treatment with cysteamine, bicalutamide or cysteamine-bicalutamide combination treatment using metabolomics (n = 3). ",
    "diseases": "cystinotic"
  },
  {
    "caption": "(G) Representative  transmission electron microscopy  images from mesenteric adipose tissue 7 days post DSS-induced colitis  induction. Lower panel is showing magnification of selected area. White arrows show autophagosomal  structures.",
    "diseases": "colitis"
  },
  {
    "caption": "(J) Representative immunoblot  for  LC3-I/-II and ACTIN  protein expression and quantification of autophagic flux in creeping fat tissues (CrF) and adjacent mesenteric adipose tissues  (Ad. MAT) of   Crohn's disease patients  (n = 3/group). Additionally, autophagic flux was determined in the mesenteric adipose tissue (MAT) of a  colorectal cancer patient  as control (dotted line). Data are represented as mean ± s.e.m. (J) Paired Student's t-test.",
    "diseases": "colorectal cancer, Crohn's disease"
  },
  {
    "caption": "(G) Representative H&E staining  images (10x magnification) of colon  sections and quantification of histological  score at steady state  (n = 9/group) and DSS colitis  (n = 18-22/group). Data are represented as mean ± s.e.m. G, Unpaired Student's t-test.",
    "diseases": "colitis"
  },
  {
    "caption": "(B) Colitis  was induced in mice  for 7 days and adipose tissues  were extracted and cultured for 6 hours in serum-starved medium. Secretion of IL-10 and from mesenteric  (left panel) and gonadal adipose tissues (right panel) was measured by ELISA. Shapes identify individual experiments (n = 5-15/group). Data are represented as mean ± s.e.m. (B) Two-Way ANOVA with regression for experiment.",
    "diseases": "Colitis"
  },
  {
    "caption": "(F) Serum  cytokines upon DSS-induced colitis  at day 7 post-induction (n = 17-23/group). Data are represented as mean ± s.e.m. Two-Way ANOVA.",
    "diseases": "colitis"
  },
  {
    "caption": "(h)  TNF-α and  IL-6 levels in  faecal  samples from mice on the indicated diet demonstrated no colitis in all  mouse groups. IL-6 and  TNF-α protein production levels, as determined by performing enzyme-linked immunosorbent assays. Data information: All data shown are representative of at least three independent biological replicates.Error bars indicate SD (n=3). ****P-value < 0.0001 ***P-value < 0.001; **P-value < 0.01; *P-value < 0.05; NS: no significance (One-way ANOVA).",
    "diseases": "colitis"
  },
  {
    "caption": "Clustering of metabolome data in patients and controls; PLS-DA plots; VIP score plots of top 15 metabolites; volcano plots of all metabolites in blood of IOSCA (A) Data information Colours in VIP score and volcano plots indicate the same most relevant and/or significantly changed metabolites among all patients groups. C3, component 3 CDCA, chenodeoxycholic acid",
    "diseases": "IOSCA"
  },
  {
    "caption": "Clustering of metabolome data in patients and controls; PLS-DA plots; VIP score plots of top 15 metabolites; volcano plots of all metabolites in blood of MIRAS (B) Data information: a Significantly changed metabolites outside the FDR cut-off. b Metabolites not significantly changed between patients and controls. Colours in VIP score and volcano plots indicate the same most relevant and/or significantly changed metabolites among all patients groups. C3, component 3 CDCA, chenodeoxycholic acid",
    "diseases": "MIRAS"
  },
  {
    "caption": "Clustering of metabolome data in patients and controls; PLS-DA plots; VIP score plots of top 15 metabolites; volcano plots of all metabolites in blood of PEO (C) Data information: Colours in VIP score and volcano plots indicate the same most relevant and/or significantly changed metabolites among all patients groups. C3, component 3; CDCA, chenodeoxycholic acid; GABA, γ-aminobutyric acid; OH-Kyn, 3-hydroxy-DL-kynurenine",
    "diseases": "PEO"
  },
  {
    "caption": "A - D Clustering of metabolome data in patients and controls; PLS-DA plots; VIP score plots of top 15 metabolites; volcano plots of all metabolites in blood of MELAS/MIDD (D). Data information: Colours in VIP score and volcano plots indicate the same most relevant and/or significantly changed metabolites among all patients groups. C3, component 3 HIAA, 5-Hydroxyindole-3-acetic acid; SDMA, symmetric dimethylarginine; TCA, taurocholic acid.",
    "diseases": "MELAS, MIDD"
  },
  {
    "caption": "Clustering of metabolome data in patients and controls; PLS-DA plots; VIP score plots of top 15 metabolites; volcano plots of all metabolites in blood of IBM (A) Colours in VIP score and volcano plots indicate the same most relevant and/or significantly changed metabolites among all patients groups. C3, component 3; CDCA, chenodeoxycholic acid; OH-Kyn, 3-hydroxy-DL-kynurenine SDMA, symmetric dimethylarginine.",
    "diseases": "IBM"
  },
  {
    "caption": "Clustering of metabolome data in patients and controls; PLS-DA plots; VIP score plots of top 15 metabolites; volcano plots of all metabolites in blood of NMD patients (B) Data information: a Significantly changed metabolites outside the FDR cut-off. b Metabolites not significantly changed between patients and controls. Colours in VIP score and volcano plots indicate the same most relevant and/or significantly changed metabolites among all patients groups. C3, component 3; CDCA, chenodeoxycholic acid",
    "diseases": "NMD"
  },
  {
    "caption": "Clustering of metabolome data in patients and controls; PLS-DA plots; VIP score plots of top 15 metabolites; volcano plots of all metabolites in blood of MIRAS carriers (C). Data information Colours in VIP score and volcano plots indicate the same most relevant and/or significantly changed metabolites among all patients groups. cAMP, cyclic AMP; C3, component 3; GABA, γ-aminobutyric acid HIAA, 5-Hydroxyindole-3-acetic acid; IMP, inosine monophosphate; OH-Kyn, 3-hydroxy-DL-kynurenine; OH-Trp, hydroxytryptophan; SDMA, symmetric dimethylarginine.",
    "diseases": "MIRAS"
  },
  {
    "caption": "A Relative values of single metabolites and creatine/creatinine ratios in blood of primary MD, IBM and NMD patients, and MIRAS carriers compared to controls. Data information: All data represent mean ± SD. For individual metabolites: *P < 0.05, **P < 0.01, ***P < 0.001 (two sample T-test). For creatine/creatinine (cr/crn) ratio: *P = 0.022, **P = 0.005, ***P = 0.0001 (Kruskal-Wallis test with Dunn´s multiple comparisons test or Mann-Whitney test).",
    "diseases": "IBM, NMD, primary MD, MIRAS"
  },
  {
    "caption": "B Relative values of single metabolites in blood of adult IOSCA (marked "IOSCA") patients and one IOSCA child patient compared to controls. Data information: All data represent mean ± SD.",
    "diseases": "IOSCA"
  },
  {
    "caption": "Metabolomes of muscle of MIRAS (A) patients; PLS-DA plots; VIP score plots of top 15 metabolites; volcano plots of all metabolites. Data information: a Significantly changed metabolites outside the FDR cut-off. b Metabolites not significantly changed between patients and controls. AMP, adenosine monophosphate NAD, nicotinamide adenine dinucleotide TCA, taurocholic acid",
    "diseases": "MIRAS"
  },
  {
    "caption": "Metabolomes of muscle of PEO (B) patients; PLS-DA plots; VIP score plots of top 15 metabolites; volcano plots of all metabolites. Data information: a Significantly changed metabolites outside the FDR cut-off. b Metabolites not significantly changed between patients and controls. car., carnitine NAD, nicotinamide adenine dinucleotide",
    "diseases": "PEO"
  },
  {
    "caption": "D Relative values of metabolites in muscle of MIRAS, PEO and MELAS/MIDD patients compared to controls. All data represent mean ± SD. *P = 0.031, **P = 0.008 (two sample T-test). UDP, uridine diphosphate.",
    "diseases": "MELAS, MIDD, PEO, MIRAS"
  },
  {
    "caption": "A Separate specificity and sensitivity (ROC) of sorbitol, alanine, myoinositol and cystathionine (left) and conventional blood biomarkers lactate and pyruvate, and cytokine FGF21 (right) in blood of MIRAS, PEO and MELAS/MIDD patients (n = 20) compared to controls (n = 30). Data information: ROC analysis: AUC of sorbitol 0.81 (95% CI 0.68 - 0.94, P = 0.0003), alanine 0.81 (95% CI 0.66 - 0.94, P = 0.0003), myoinositol 0.79 (95% CI 0.66 - 0.91, P = 0.0007) and cystathionine 0.78 (95% CI 0.65 - 0.91, P = 0.001). AUC of conventional biomarkers: FGF21 0.87 (95% CI 0.74 - 0.99, P = 0.0001), lactate 0.86 (95% CI 0.76 - 0.97, P = 0.0001) and pyruvate 0.78 (95% CI 0.64 - 0.93, P = 0.0017).",
    "diseases": "MELAS, MIDD, PEO, MIRAS"
  },
  {
    "caption": "B Combined 'multi-biomarker' value of sorbitol/alanine/myoinositol/cystathionine; ROC-analysis (left); mean centroids MD, IBM and NMD patients, and MIRAS carriers compared to controls (right). Data information: ROC analysis AUC of 'multi-biomarker' 0.94 (95% CI 0.89 - 0.995, P = 0.0001). Mean centroid data represent mean ± SD. **P < 0.01, ***P < 0.001 (1-way ANOVA with Dunnett´s multiple comparison test).",
    "diseases": "IBM, NMD, MD, MIRAS"
  },
  {
    "caption": "B Forest plots display the hazard ratios of genes at the 17q12 amplicon according to the DFS (top right) and OS (bottom right) of breast cancer patients in the METABRIC dataset. Genes located at the HER2 amplicon were nominated according to hazard-ratio levels (all P-values < 0.01). The HER2 co-amplification percentage of the indicated genes is represented as bar graphs (left).",
    "diseases": "breast cancer"
  },
  {
    "caption": "C The frequency of CDK12 amplification in HER2-amplified- and HER2-nonamplified breast cancer. The bar graphs indicate the frequency of HER2 and CDK12 co-amplified cases among the patients with HER2 gene amplification (left). Tables show the percentage of CDK12 amplification in the indicated cohorts (right). Amp, amplification; non-amp, non-amplification.",
    "diseases": "breast cancer"
  },
  {
    "caption": "E Survival analysis of breast cancer patients according to the expression of CDK12 in METABRIC (top) and KM plotter (bottom) using the Kaplan-Meier method with the log-rank test.",
    "diseases": "breast cancer"
  },
  {
    "caption": "D Cell growth of the indicated stable cell lines treated with trastuzumab (Trz) or vehicle (veh) as measured by SRB assay. Trastuzumab-sensitive HER2+ breast cancer cell lines (S) and trastuzumab-insensitive HER2+ breast cancer cell lines (partial responsive, PR; resistant, R) were treated with 1 µg/mL or 100 µg/mL trastuzumab, respectively. Data represent the mean ± s.d. P-values were calculated using RM ANOVA with a post-hoc LSD test. cell line information was indicated as follows: a/a, CDK12-amplified/HER2-amplified cells; n/a, CDK12 non-amplified/HER2-amplified cells; R, trastuzumab-resistant; PR, trastuzumab-partial responsive; S, trastuzumab-sensitive.",
    "diseases": "breast cancer"
  },
  {
    "caption": "E Analysis of the effect of CDK12 deficiency on the in vivo trastuzumab response of HER2+ breast cancer. Mice were orthotopically xenografted with the indicated HER2+ breast cancer cells and treated with 20 mg/kg trastuzumab. The growth curve of each group was analysed twice weekly for 5 to 6 weeks (n = 8/group; mean ± s.e.m.). P-values were calculated using one-way ANOVA with a post-hoc LSD test for the last day of tumor measurement. cell line information was indicated as follows: a/a, CDK12-amplified/HER2-amplified cells R, trastuzumab-resistant S, trastuzumab-sensitive.",
    "diseases": "breast cancer"
  },
  {
    "caption": "H Tumor growth curves for mice xenografted with the indicated HER2+ breast cancer cells treated with 20 mg/kg trastuzumab and/or 20 mg/kg dinaciclib (n = 8/group; mean ± s.e.m.). P-values, one-way ANOVA with a post-hoc LSD (BT474) or Dunnett T3 (HCC-1954) test for the last day of tumor measurement. Cell line information: a/a, CDK12-amplified/HER2-amplified cells R, trastuzumab-resistant; S, trastuzumab-sensitive.",
    "diseases": "breast cancer"
  },
  {
    "caption": "B Immunoblots showing the levels of the indicated proteins in different types of HER2+ breast cancer stably expressing CDK12 or with CDK12 knocked down. Cell line information: a/a, CDK12-amplified/HER2-amplified cells; n/a, CDK12 non-amplified/HER2-amplified cells; R, trastuzumab-resistant; PR, trastuzumab-partial responsive; S, trastuzumab-sensitive.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(D) Number of  putative enhancer regions per cell line. Bar depicts the mean. Diamonds represent individual numbers in each cell line and are color-coded according to cancer  type",
    "diseases": "cancer"
  },
  {
    "caption": "(E) Heat maps of DNase I signal for  enhancer regions (rows). For intergenic enhancers (left) the signal is aligned at the upstream (relative to + strand) enhancer edge, shown from 4 kbp upstream to 5 kbp downstream, and ordered by increasing length of  enhancer regions. For  intragenic enhancers (right) the signal was aligned at the upstream and downstream enhancer edges and shown within ± 4 kbp. Exemplary data from LoVo colorectal cancer  cells. (F) Heat maps as in (E) showing composite  ChIP-seq peak coverage from 326 TFs ",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "(A) UCSC genome browser view of normalized TT-seq  coverage on the plus and minus strand at the TAL1 locus (hg38; chr1:47,194,268-47,242,880; (Kent et al., 2002)) in the leukemia cell lines Jurkat  and K562. For better visualization, TT-seq  coverage is cut at 200 (purple lines). eRNAs are shown between the  plus and minus strand. Red line indicates the short 12 bp insertion in Jurkat  cells, introducing novel binding sites for the transcription factor  MYB",
    "diseases": "leukemia"
  },
  {
    "caption": "(B) UCSC genome browser view of normalized  TT-seq  coverage on the  plus and minus strand at the 2.8 Mbp gene desert surrounding MYC (hg38; chr8:127,042,406-129,779,109; (Kent et al., 2002)) in fourteen cancer  cell lines. eRNAs represent the union from all cell lines. Genome-wide association studies (GWAS) risk loci contain GWAS  single nucleotide polymorphisms  (SNPs) for prostate cancer (PrCa), acute lymphocytic leukemia (ALL), breast cancer (BrCa),  colorectal cancer (CRC), and glioblastoma (GBM) including SNPs in linkage disequilibrium (r2 ≥ 0.8). TT-seq coverage is displayed between 8-250 to allow for better visualization of the eRNA signal surrounding MYC. Dashed rectangle is shown at full scale on the right. Note: TT-seq reads were mapped against the hg38 reference genome and we cannot rule out the existence of genomic rearrangements (e.g. translocations) affecting the shown region in the used cancer cell line clones.",
    "diseases": "acute lymphocytic leukemia, ALL, BrCa, breast cancer, cancer, colorectal cancer, CRC, GBM, glioblastoma, PrCa, prostate cancer"
  },
  {
    "caption": "(A)  Med1-defined enhancers ranked by  Med1 ChIP-seq  signal (Yan et al., 2013) in LoVo colorectal cancer cells. Super-enhancers (black rectangles) were determined as enhancer  regions lying above the inflection point of the curve",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "(E) UCSC genome browser view of normalized TT-seq coverage on the plus and minus  strand at the  PHLDA1  locus (hg38; chr12:75,612,350-76,042,552; in the  colorectal cancer cell line HCT 116. TT-seq coverage is cut at 250 (purple lines) to allow for better visualization.  eRNAs are shown between the plus and minus strand. Aggregated  transcription factor ChIP-seq peak regions (TF ChIP-seq) comprise ChIP-seq binding profiles of 19 TFs in HCT 116  cells from CISTROME The height of the signal indicates the number of different TFs binding at a particular region. Binding  regions for selected TFs (TCF7l2, YY1, SP1) are shown below together with p300 and RNA polymerase II (Pol II). TT-seq enhancer regions are shown at the bottom together with a  H3K27ac-defined super-enhancer  annotation, which was downloaded from SEdb 2019). At date of publication no Med1 ChIP-seq data was available for HCT 116.",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "(A) Unsupervised clustering of all pairwise Spearman correlations of normalized TT-seq signal for mRNAs (left) and eRNAs (right) for the union of transcripts over all fourteen cancer  cell lines Grey and colored bars on top indicate gender and cancer type, respectively.",
    "diseases": "cancer"
  },
  {
    "caption": "(B) Heatmaps showing mRNAs (left) and eRNAs (right) as being synthesized (red, normalized TT-seq signal FPK  ≥ 15) or not (blue, normalized TT-seq signal FPK < 15) for all fourteen cancer cell lines (columns). Heatmaps show only transcripts (rows) with normalized FPK ≥ 30 in at least one of the cell lines (mRNAs, n=14,040; eRNAs n=48,105). Heatmaps are ordered by increasing cell type specificity, as indicated by the grey bars to the right showing the number of cell lines a transcript is observed in.",
    "diseases": "cancer"
  },
  {
    "caption": "UCSC genome browser view of normalized TT-seq coverage on the plus and minus strand at the BMP4 locus (hg38; chr14:53,935,697-54,264,430; in LoVo colorectal cancer cells. TT-seq  coverage is cut at 500 (purple lines) to allow for better visualization.  eRNAs and enhancers are shown above and below the  minus  strand, respectively. Aggregated transcription factor ChIP-seq  peak regions (TF  ChIP-seq) include ChIP-seq binding profiles of 326 TFs in LoVo  cells The height of the signal indicates the number of different TFs  binding  at a particular region. Significant promoter capture  Hi-C (CHi-C)  interactions are shown in purple",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "Heatmap of the differentially expressed cholesterol-related genes between normal brain tissues (n = 28) and glioblastomas (n = 217) from the Rembrandt dataset. Gene expression values are z-transformed and colored red for high expression and blue for low expression, as indicated in the scale bar. Volcano plot showing the fold-change (log2) in cholesterol-related gene levels based on GBM vs normal brain tissue. Data were obtained from the Rembrandt dataset.",
    "diseases": "glioblastomas, GBM"
  },
  {
    "caption": "Representative images of IHC staining for CYP46A1 protein in normal brain and different pathological grades of gliomas (n = 64). Scale bar = 30 μm. Quantification of CYP46A1 IHC staining in normal brain (n = 6) and different pathological grades of gliomas (n = 58).",
    "diseases": "gliomas"
  },
  {
    "caption": "Representative images of CYP46A1 IHC staining in GBM and adjacent brain tissues from one specific case. Scale bar = 30 μm.",
    "diseases": "GBM"
  },
  {
    "caption": "CYP46A1 expression levels in different molecular subtypes from the Rembrandt GBM dataset. Shown are means and SEM (n = 245). ***P < 0.0001. Statistical significance was determined by one‐way ANOVA.",
    "diseases": "GBM"
  },
  {
    "caption": "Kaplan-Meier analysis for patient OS and PFS based on high vs low expression of CYP46A1 in LGG and GBM. Data were obtained from the CGGA dataset. P-values were obtained from the log-rank test.",
    "diseases": "GBM, LGG"
  },
  {
    "caption": "Western blot analysis to confirm CYP46A1 overexpression in GBM cells.",
    "diseases": "GBM"
  },
  {
    "caption": "Growth curves for GBM cells in vitro infected with lenti-Ctrl or lenti-CYP46A1 derived from trypan blue staining. Shown are means and SEM (n = 3). LN229: **P = 0.003; GBM#P3: **P = 0.002. Statistical significance was determined by two-sided Student's t‐test.",
    "diseases": "GBM"
  },
  {
    "caption": "Colony forming assay for GBM cells infected with lenti-Ctrl or lenti-CYP46A1. Shown are means and SEM (n = 3). LN229: *P = 0.013; GBM#P3: *P = 0.012. Statistical significance was determined by two-sided Student's t‐test.",
    "diseases": "GBM"
  },
  {
    "caption": "Representative H&E staining of orthotopic tumours derived from GBM cells infected with lenti-Ctrl or lenti-CYP46A1. Scale bar = 2 mm.",
    "diseases": "GBM"
  },
  {
    "caption": "Kaplan-Meier survival curve of tumour bearing mice injected with GBM cells infected with lenti-Ctrl or lenti-CYP46A1 (n = 5 per group). A log-rank test was used to assess statistical significance.",
    "diseases": "GBM"
  },
  {
    "caption": "IHC for CYP46A1, PCNA and cleaved caspase-3 protein levels in the intracranial tumours. Scale bar = 100 μm.",
    "diseases": "intracranial tumours"
  },
  {
    "caption": "Colony forming ability of GBM cell lines treated with 24OHC (0 - 20 μM) for 14 days.",
    "diseases": "GBM"
  },
  {
    "caption": "Western blot analysis of the apoptosis marker c-PARP, c-caspase 3 and PCNA in lysates (20 µg) from GBM cells treated with 24OHC (0 - 20 μM) for 72 h.",
    "diseases": "GBM"
  },
  {
    "caption": "Tumoursphere formation assays for GSCs treated with different concentrations of 24OHC (0 - 20 μM). Scale bar = 100 μm. Graphic representation of the quantification of tumoursphere formation. Data are shown as the mean ± SEM (n = 3). GBM#P3: *P = 0.0192, ***P = 0.0006, ***P = 0.0002; GBM#BG7: **P = 0.0017, ***P < 0.0001, ***P < 0.0001; GBM#BG5: **P = 0.0027, ***P = 0.0001, ***P < 0.0001.",
    "diseases": "GBM"
  },
  {
    "caption": "Intracellular levels of cholesterol in GBM cells treated with 20 μM of 24OHC or DMSO for 72 h quantified using the Invitrogen™ Amplex™ Red Cholesterol Assay Kit and normalized to total protein. Shown are means and SEM (n = 3). LN229: **P = 0.002; GBM#P3: **P = 0.011. Statistical significance was determined by two-sided Student's t‐test.",
    "diseases": "GBM"
  },
  {
    "caption": "Representative images of filipin staining in GBM cells treated with different concentrations of 24OHC (0 - 20 μM) for 72 h. Scale bar = 30 μm.",
    "diseases": "GBM"
  },
  {
    "caption": "Flow cytometry to detect annexin V-FITC and PI staining to determine the percentage of GBM cells undergoing apoptosis after exposure to DMSO or 10 μM 24OHC in the presence or absence of 0.5 μg/mL cholesterol for 72 h. Data are shown as the mean ± SEM (n = 3). LN229: **P = 0.0021, **P = 0.0046; GBM#P3: **P = 0.0012, *P = 0.0193.",
    "diseases": "GBM"
  },
  {
    "caption": "Western blot analysis of c-PARP in GBM cells treated with DMSO or 10 μM 24OHC in the presence or absence of 0.5 μg/mL cholesterol for 72 h.",
    "diseases": "GBM"
  },
  {
    "caption": "Colony forming ability of GBM cell lines treated with DMSO or 20 μM fatostatin for 14 days.",
    "diseases": "GBM"
  },
  {
    "caption": "Intracellular concentrations of cholesterol in GBM cells after treatment with 20 μM EFV or DMSO and normalized to total protein. Data are shown as the mean ± SEM (n = 3). LN229: *P = 0.013; GBM#P3: **P = 0.0023.",
    "diseases": "GBM"
  },
  {
    "caption": "Filipin staining of GBM cells after treatment with EFV (0 - 20 μM). Scale bar = 30 μm.",
    "diseases": "GBM"
  },
  {
    "caption": "IC50 curves for EFV in GBM cells determined using OD readings (450nm) from the CCK-8 assay.",
    "diseases": "GBM"
  },
  {
    "caption": "Images and quantification of colonies formed by GBM cell lines after treatment with different concentrations of EFV (0 - 20 μM). Data are shown as the mean ± SEM (n = 3). LN229: **P = 0.0056, ***P < 0.0001; LN18: ***P < 0.0001.",
    "diseases": "GBM"
  },
  {
    "caption": "Flow cytometry to detect annexin V-FITC and PI staining to determine the percentage of GBM cells undergoing apoptosis after treatment with EFV (0 - 20 μM) for 72 h. Data are shown as the mean ± SEM (n = 3). LN229: ***P = 0.0006, ***P < 0.0001; GBM#P3: ***P < 0.0001.",
    "diseases": "GBM"
  },
  {
    "caption": "Migration of colon cancer cells treated with an siRNA targeting CALIC. (n = 3)",
    "diseases": "colon cancer"
  },
  {
    "caption": "CALIC expression levels in cancer tissues. N, normal mucosa; T, tumor.",
    "diseases": "cancer"
  },
  {
    "caption": "Expression of CALIC in primary skin tumors (P) and their metastases (M). Expression of CALIC in primary skin tumors of patients without (w/o) or with (w) metastases.",
    "diseases": "skin tumors"
  },
  {
    "caption": "qRT-PCR analysis of CALIC expression in early (I/II) and late (III/IV) stage colon cancers. [Normal (N) n = 8, stage I/II n = 14, stage III/IV n = 26]",
    "diseases": "colon cancers"
  },
  {
    "caption": "Kaplan-Meier curves for disease-free survival of colon cancer patients whose primary tumors expressed low (blue, n = 113) or high (red, n = 250) levels of CALIC.",
    "diseases": "colon cancer"
  },
  {
    "caption": "Biotinylated full-length CALIC or antisense CALIC (negative control) generated in vitro were incubated with lysates from DLD-1 colon cancer cells and precipitated with streptavidin beads. Precipitated proteins were resolved by SDS-PAGE followed by silver staining. The protein band indicated by the arrow was excised and subjected to mass spectrometry.",
    "diseases": "colon cancer"
  },
  {
    "caption": "Heatmap showing the expression levels of genes positively regulated in common by both CALIC and hnRNP-L in colon and rectal cancers. Samples are ordered based on the expression levels of AXL.",
    "diseases": "colon and rectal cancers"
  },
  {
    "caption": "Representative images of gross specimens (top) and H&E stained sections (bottom) of lung metastatic lesions in mice injected with CALIC or AXL knockdown HCT116 cells. Tumors were marked with yellow arrows. The dashed lines depict the boundary between normal and tumor tissues. (Right) Percentage of mice with lung metastases.",
    "diseases": "lung metastases, lung metastatic lesions"
  },
  {
    "caption": "Representative images of gross specimens of primary cecal tumors (top) and liver metastatic lesions (bottom) in mice orthotopically (cecal) injected with CALIC knockdown HCT116 cells. Tumors are marked with yellow arrows. (Right) Percentage of mice with primary tumors and liver metastases.",
    "diseases": "cecal tumors, liver metastases, liver metastatic lesions"
  },
  {
    "caption": "A, B. A missense mutation in SPOP gene (Q165P, T >G) was identified in a PCa patient. Exome sequencing revealed that the primary tumor contained a heterozygous Q165P mutation (A) whereas the liver metastasis harbored a homozygous Q165P mutation (B).",
    "diseases": "liver metastasis, PCa"
  },
  {
    "caption": "D, E. IHC analysis of BRD4 protein expression in SPOP wild type (WT) and mutated (MUT) PCa patient samples. The representative images of BRD4 IHC staining in both SPOP WT and MUT PCa patients are shown in (D) and the quantified IHC data are shown in (E). Scale bars: 100 µm for 20 x fields; 50 µm for 40 x fields. The red dot in (E) indicates SPOP Q165P sample. All data shown are means ± SEM. The P value was calculated by the unpaired two-tailed Student's t-test; ** P < 0.01. See Appendix Table S4 for the detailed comparison, P values and sample number (n).",
    "diseases": "PCa"
  },
  {
    "caption": "F, G. IHC analysis of AR protein expression in SPOP WT and mutated PCa patient samples. The representative images of AR IHC staining in both SPOP WT and mutant PCa patients are shown in (F) and the quantified IHC data are shown in (G). Scale bars: 100 µm for 20 x fields; 50 µm for 40 x fields. The green dot indicates SPOP Q165P sample. All data shown are means ± SEM. The P value was calculated by the unpaired two-tailed Student's t-test; *** P < 0.01. See Appendix Table S4 for the detailed comparison, P values and sample number (n).",
    "diseases": "PCa"
  },
  {
    "caption": "A. DU145 PCa cells infected with virus expressing EV or SPOP Q165P were harvested for western blot analysis.",
    "diseases": "PCa"
  },
  {
    "caption": "B, C. SCID male mice with PDX tumors were treated with vehicle (40% polyethylene glycol), JQ1 (50 mg/kg), CPI-637 (30 mg/kg), combination of JQ1 (50 mg/kg) and CPI-637 (30 mg/kg) or NEO2734 (30 mg/kg) five days a week for three consecutive weeks. Tumors isolated from mice at day 21 of drug treatment were photographed (B) and tumor growth are shown in (C). All data shown are means ± SEM. The P value comparing the tumor volume at day 21 post- treatment was calculated by the unpaired two-tailed Student's t-test; *** P < 0.001.",
    "diseases": "SCID"
  },
  {
    "caption": "A. C4-2 PCa cells infected with virus expressing EV, SPOP Q165P or F133V were harvested for western blot analysis.",
    "diseases": "PCa"
  },
  {
    "caption": "J, K shHERC3 attenuates breast cancer lung metastasis. Mice were injected with control or HERC3-deficient MDA-MB-231 cells. J, Bright-field images (upper panel, scale bars, 2 mm) and H&E staining (lower panel, scale bars, 50 μm) of the lungs from mice. K, number of lung metastasis nodules. Data are shown as mean ±SEM; n = 5 biological replicates. Statistical analysis was performed using two-tailed Student t test. ***P < 0.001.",
    "diseases": "breast cancer"
  },
  {
    "caption": "HERC3 is highly expressed in breast cancer specimens. A, representative images of IHC staining of HERC3 in tumor samples of breast cancer specimens and their paired adjacent normal tissues. Scale bars, 50 µm.",
    "diseases": "breast cancer"
  },
  {
    "caption": "D HERC3 is correlated with poor prognosis in breast cancer patients. Kaplan-Meier curves for overall survival of breast cancer patients according to the HERC3 expression level (upper left panel) (http://kmplot.com/analysis/index.php?p=service&cancer=breast). HERC3 is negatively correlated with the overall survival (upper right panel), the distant metastasis free survival (lower left panel) and the relapse free survival (lower right panel) in breast cancer patients. Microarray analysis was performed to examine the prognostic potential of HERC3 in breast cancer using the PrognoScan database with one cohort (GSE7390) of 198 breast cancer specimens (http://www.prognoscan.org)",
    "diseases": "breast cancer"
  },
  {
    "caption": ". E HERC3 expression is positively correlated with TAZ or active YAP expression in breast cancer patients. Representative images of IHC staining of HERC3, TAZ and active YAP in tumor samples of breast cancer patients",
    "diseases": "breast cancer"
  },
  {
    "caption": "(B) Representative images of core, edge and adjacent non-tumour brain tissue for Iba1, p-S6 and DAPI staining in Pten-/-p53-/- (right) and GL261 (left) tumours. Percentage of Iba1+ cells co-expressing p-S6 in the three defined regions. Five high grade glioma models were analysed - GL261 (n=3), PDGFB (n=3), Ntv-a;PDGFB+shp53 (n=2), Pten-/-p53-/- (n=3), and Pten-/-p53-/-Idh1mut (n=3) (mean ±SEM; Two-Way ANOVA Tukey test).",
    "diseases": "glioma"
  },
  {
    "caption": "(A) Correlation between ssGSEA enrichment scores for the mTOR signature versus TAM-MG or TAM-BMDM signatures in TCGA GBM transcriptomic data. Comparison carried out on all IDH-wild-type samples, and in a subgroup specific manner according to Wang's classifier. Size of circle is indicative of Rsquare value and bold outline represents a p-value ≤0.05.",
    "diseases": "GBM"
  },
  {
    "caption": "(B) Separation of IDH-wildtype GBM samples between those displaying high mTOR and microglia enrichment (+ve correlation, group 1 in orange) and those without this signature (group 2 in green).",
    "diseases": "GBM"
  },
  {
    "caption": "(C) CIBERSORT cell fractions calculated from the TPM of TCGA IDH-wild type GBM samples from group 1 compared to those from group 2.",
    "diseases": "GBM"
  },
  {
    "caption": "A, Volcano plot of the differentially modulated proteins in 22rv1 (CRPC) versus CWR22res (HN) tumours. Red and blue dots represent the proteins that are significantly up- and down-regulated, respectively (p-value < 0.05, FC = 1.5). Data information: Data reproducibility: n = 3 tumours per group.",
    "diseases": "CRPC"
  },
  {
    "caption": "B, Western blot analysis of  THEM6 expression in CRPC (22rv1 and LNCaP   AI) and HN (CWR22res  and LNCaP) prostate orthografts. VCL was used as a sample loading control. Data information: Data reproducibility: : n = 1 gel loaded with three prostate orthografts per condition.",
    "diseases": "CRPC"
  },
  {
    "caption": "B-C, Changes in lipid content (total amount) observed in THEM6  KO CRPC cells when compared to CTL. Data information: Data are presented as mean values +/- SD. Statistical analysis : *p-value < 0.05 using a 1-way ANOVA with a Dunnett's multiple comparisons test. Data reproducibility: n = 3 independent biological experiments. DAG: diacylglycerol; TG: triglyceride;  PC: phosphatidylcholine; PE: phosphatidylethanolamine; PI: phosphatidylinositol; LysoPC: lysophosphatidylcholine; LysoPE: lysophosphatidylethanolamine;  Cer: Ceramide; SM: sphingomyelin; CE: Cholesteryl ester.",
    "diseases": "CRPC"
  },
  {
    "caption": "I, Western blot  analysis of THEM6,  AMFR, SEC61b and  XPO1 expression in CRPC cells following THEM6 immunoprecipitation  in CRPC  cells. Data information: Data reproducibility: representative image from 2 independent biological experiments.",
    "diseases": "CRPC"
  },
  {
    "caption": "J, Western blot  analysis of CALX and  CALR expression in PCa cells following THEM6 silencing. Data information: Data reproducibility: representative image from 3 independent biological experiments.",
    "diseases": "PCa"
  },
  {
    "caption": "C, Kaplan-Meier progression-free survival analysis of PCa patients  stratified according high and low THEM6 expression using the PRAD TCGA dataset. D, Kaplan-Meier recurrence-free survival analysis of  PCa patients  stratified according to median THEM6 expression using the GSE21034 dataset (n = 179). Data information: Statistical analysis: logrank test. Data reproducibility: C: n = 489 tumours. D: n = 179.",
    "diseases": "PCa"
  },
  {
    "caption": "E,  IHC staining of THEM6 expression  in treatment naïve, NHT-treated,  CRPC and NEPC tumours. Scale bar represents 100 µm. Data information: Data reproducibility: : n = 132; 90; 66; 137; 44; 30 tumours for Untreated; NHT  1-3; NHT4-6; NHT>7; CRPC; NEPC respectively.",
    "diseases": "NEPC, CRPC"
  },
  {
    "caption": "I-J, Kaplan-Meier recurrence-free (I) and overall (J) survival analysis of PCa patients  stratified according to median THEM6  expression. Data information: Statistical analysis: logrank test. Data reproducibility: n = 35 tumours for THEM6 low and n = 34 tumours for THEM6 high.",
    "diseases": "PCa"
  },
  {
    "caption": "K, Quantification of THEM6 expression in  PCa tissue samples according to Ki67 expression in the patients analysed in F. L, Quantification of THEM6 expression in PCa tissue samples according to  Ki67 expression in the patients analysed in I-J. Data information: Centre line corresponds to median of data, top and bottom of box correspond to 90th and 10th percentile, respectively. Whiskers extend to adjacent values (minimum and maximum data points not considered outliers). Statistical analysis: two-tailed Mann-Whitney U test. Data reproducibility: K: n = 269 tumours for Ki67 low and n = 270 tumours for Ki67 high. L: n = 35 tumours for  Ki67 low and n = 29 tumours for Ki67 high.",
    "diseases": "PCa"
  },
  {
    "caption": "M, Volcano plot of the differentially modulated genes in  PCa patients from the PRAD TCGA stratified according to THEM6 expression. Red dots represent the UPR-related genes extracted from the UPR-gene signature Data information: Data reproducibility: n = 489 tumours.",
    "diseases": "PCa"
  },
  {
    "caption": "A. Western blot of LC3B in lymphoblasts of OFD type I patients and controls, either untreated (-) or exposed to Baf-A1 (10nM, 2h)(+). Cells were cultured in complete medium (FM, top) or under serum starvation for 4h (STV, bottom). ACTIN and GAPDH were used as loading controls.",
    "diseases": "OFD type I"
  },
  {
    "caption": "C. Western blot of ATG13 and ATG101 proteins in serum starved lymphoblasts from controls and OFD type I patients. (Right) Protein levels relative to ACTIN (loading control) are expressed as fold change versus controls, represented by the dashed line, n=4 patients and 3 controls.",
    "diseases": "OFD type I"
  },
  {
    "caption": "Kaplan-Meier curves showing mammary tumor-specific survival for the different models. WB1P-BE3 females injected with Lenti-sgAkt1E17K-Myc (n=12) showed a reduced mammary tumor-specific survival compared to WB1P-BE3 female mice injected with Lenti-sgNT-Myc (n=11) vectors (58 days after injection vs 72 days after injection, P < 0.01 by Mantel-Cox test).",
    "diseases": "mammary tumor"
  },
  {
    "caption": "Kaplan-Meier curves showing mammary tumor-specific survival for the different models. WB1P-BE3 females injected with Lenti-sgPik3caE542K-Myc (n=10), Lenti-sgPik3caE545K-Myc (n=10) and Lenti-sgPik3caE453K-Myc (n=10) showed a reduced mammary tumor-specific survival compared to WB1P-BE3 female mice injected with Lenti-sgNT-Myc (n=11) vectors (respectively 47, 44 and 49 days after injection vs 72 days after injection, P < 0.0001 by Mantel-Cox test).",
    "diseases": "mammary tumor"
  },
  {
    "caption": "Kaplan-Meier curves showing mammary tumor-specific survival for the different models. WB1P-BE3 females injected with Lenti-sgPtenQ245*-Myc (n=11) showed a reduced mammary tumor-specific survival compared to WB1P-BE3 female mice injected with Lenti-sgNT-Myc (n=11) vectors (37 days after injection vs 72 days after injection, P < 0.0001 by Mantel-Cox test).",
    "diseases": "mammary tumor"
  },
  {
    "caption": "Kaplan-Meier curves showing mammary tumor-specific survival for the different models. WapCre;Brca1F/F;Trp53F/+;Col1a1invCAG-BE3/+ females injected with Lenti-sgPik3caE545K/sgTrp53Q97*-Myc (n=6) showed a reduced mammary tumor-specific survival compared to animals injected with Lenti-sgTrp53Q97*-Myc (n=5) vectors (76 days after injection vs 101 days after injection, P < 0.05 by Mantel-Cox test). Females injected with Lenti-sgNT-Myc (n=11) did not develop any palpable tumors during the 150 days observation period.",
    "diseases": "mammary tumor"
  },
  {
    "caption": "C. HDo-TRaMs were engineered with vectors relevant to treatment of Fabry, Gaucher, Farber and Pompe diseases. Intracellular lysosomal enzyme specific activities were measured in transduced T-Rapa and controls. Transductions varied across vectors/donors, as indicated. D, E. Enzyme activity was assessed in transduced T-Rapa supernatants compared to controls in activated/dividing (D) and quiescent/resting (E) states.",
    "diseases": "Fabry, Farber, Gaucher, Pompe diseases"
  },
  {
    "caption": "I. α-Gal A specific activity in Fabry patient-derived skin fibroblasts after 6 hours of exposure to conditioned media from TRaMs in the presence or absence of 1mM M6P.",
    "diseases": "Fabry"
  },
  {
    "caption": "C, D. α-Gal A activity in plasma, and specific activities in liver, spleen, heart and kidneys were measured after transplant of transduced healthy donor (HDo)-derived (C) or Fabry donor (FDo)-derived (D) TRaMs, non-transduced (NT) cells, or in sham-treated NOD/SCID (NS) and NSF mice.",
    "diseases": "Fabry, SCID"
  },
  {
    "caption": "A, B. Levels of globotriaosylceramide (Gb3) were measured by LC/MS in plasma and extracts of liver, spleen, heart, and kidneys of mice engrafted with healthy donor (HDo)-derived (A) or Fabry donor (FDo)-derived (B) TRaMs, non-transduced (NT) cells, or in sham-treated NOD/SCID (NS) and NSF mice.",
    "diseases": "Fabry, SCID"
  },
  {
    "caption": "A ATX gene expression from publicly available datasets in NASH patients (n=9) compared to healthy controls (n=7) (*P < 0.05); cirrhosis patients (n=40) compared to healthy controls (n=19) (***P < 0.001). Bars represent the mean ± SEM, statistical analysis was performed by two-tailed student's t-test. *P < 0.05, ***P < 0.001 denotes significance versus respective healthy controls.",
    "diseases": "cirrhosis, NASH"
  },
  {
    "caption": "C Representative images (scale=50μm) of ATX stained liver sections from human NASH  (n=5) compared to healthy controls (n=4); human cirrhosis  (n=5) compared to healthy controls (n=4).",
    "diseases": "cirrhosis, NASH"
  },
  {
    "caption": "D Representative images (scale=50μm) of ATX stained liver  sections (using AEC  chromogen denoted by red color staining  or DAB  chromogen denoted by brown color staining; nuclei  were stained  blue with hematoxylin) from MCD-diet-fed NASH  (n=9) and CCl4-induced  liver  fibrosis (n=8) mouse  models compared to respective controls (n=9 or n=5).",
    "diseases": "liver  fibrosis, NASH"
  },
  {
    "caption": "The increased total and Ace-β-cat (K49) levels positively correlated with increased phosphorylated Tau pS199 and AT8 as detected by Western blotting in the hippocampal extracts of AD patients compared with age-matched controls (n=10 each group, Pearson analysis was used for correlation analysis Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs Vec vs Ctrl (J) Data were analyzed by Student's t test",
    "diseases": "AD"
  },
  {
    "caption": "The increased total and Ace-β-cat (K49) levels positively correlated with increased phosphorylated Tau pS199 and AT8 as detected by Western blotting in the hippocampal extracts of AD patients compared with age-matched controls (n=10 each group Pearson analysis was used for correlation analysis",
    "diseases": "AD"
  },
  {
    "caption": "The increased mRNA levels of bcl2, survivin and dkk1 in the AD brains compared with the age-/sex-matched controls detected by Q-PCR (n=7 each group) Data information: Data are expressed as mean ± SEM, *, P<0.05; **, P<0.01, ***, P<0.001 vs Ctrl (I) Data were analyzed by Student's t test",
    "diseases": "AD"
  },
  {
    "caption": "The increased mRNA levels of bcl2, survivin and dkk1 in the AD brains compared with the age-/sex-matched controls detected by Q-PCR (n=7 each group), and the positive correlations with the increased K49-acetylated β-catenin (see Fig. 1I, J) analyzed by Pearson analysis.",
    "diseases": "AD"
  },
  {
    "caption": "Spearman correlation of relative SAMHD1 protein abundance and synergy delta scores for ara-C versus HU or dF-dC in a panel (n = 9) of haematological cancer cell lines. Error bars indicate s.e.m. Each data point corresponds to SAMHD1 protein levels determined by immunoblot analysis (n = 4 for each cell line, representative blot shown in Appendix Fig S2) and an average delta score from repeated dose-response matrix experiments each performed in triplicate: THP-1, n =4; HuT-78, n = 2; HL-60/iva, n = 1; KBM-7, n = 2 (HU) and 3 (dF-dC); K562, n = 3 (HU) and 4 (dF-dC); CCRF-CEM, n =3 (HU) and 4 (dF-dC); MV-4-11, n = 2 (HU) and 3 (dF-dC); Jurkat, n = 2 (HU) and 3 (dF-dC); MOLT-4, n = 2 (HU) an 3 (dF-dC).",
    "diseases": "haematological cancer"
  },
  {
    "caption": "Kaplan-Meier analysis of NOD/SCID mice injected i.v. with luciferase-expressing SAMHD1+/+ or -/- THP-1 cell clones (day 0) and treated with ara-C and/or HU as indicated (day 6). n = 6 per treatment group.",
    "diseases": "NOD, SCID"
  },
  {
    "caption": "Kaplan-Meier analysis of NOD/SCID mice injected i.v. with luciferase-expressing SAMHD1+/+ or -/- HL-60/iva cell clones (day 0) and treated with ara-C and/or HU as indicated (day 6). n = 6 per treatment group.",
    "diseases": "NOD, SCID"
  },
  {
    "caption": "Kaplan-Meier analysis of NOD/SCID mice injected i.v. with luciferase-expressing SAMHD1+/+ THP-1 cell clone (day 0) and treated with ara-C and/or dF-dC as indicated (day 6). n = 7 per treatment group.",
    "diseases": "NOD, SCID"
  },
  {
    "caption": "Kaplan-Meier analysis of CD45.2 C57BL/6J mice injected i.v. with murine MLL-AF9-transformed AML blasts (day 0) and treated with ara-C and/or HU days 20-24. n = 5 per treatment group, except for vehicle (n = 4).",
    "diseases": "AML"
  },
  {
    "caption": "Drug synergy plots for ara-C and HU or dF-dC in primary patient-derived AML blasts. Each data point indicates an average delta score from a single patient sample subjected to a dose-response matrix experiment performed in triplicate, n = 16 for HU and n = 9 for dF-dC. Zero, >0, or <0 corresponds to additive, synergy, or antagonism, respectively, whilst >5 indicates strong synergy. Median, upper and lower quartiles, and range of delta scores are indicated by box-and-whisker plots.",
    "diseases": "AML"
  },
  {
    "caption": "Pearson correlation of relative SAMHD1 protein abundance and synergy delta scores for ara-C and HU or dF-dC in primary patient-derived AML blasts (n = 23).",
    "diseases": "AML"
  },
  {
    "caption": "Immunoblot of primary patient-derived AML blasts treated with control (dX) or Vpx-containing (X) virus-like particles (VLPs): patient A2953 (C), ALG17_001 (E). Accompanying proliferation inhibition analysis of ara-C and indicated RNRi combination in these samples: patient A2953 (D), ALG17_001 (D). Error bars indicate s.d. of single experiment performed in triplicate.",
    "diseases": "AML"
  },
  {
    "caption": "Paired drug synergy plot for ara-C and RNRi (HU, n = 7; dF-dC, n = 5) in primary patient-derived AML blasts pre-treated with control (dX) or Vpx-containing (X) VLPs. Zero, >0, or <0 corresponds to additive, synergy, or antagonism, respectively, whilst >5 indicates strong synergy and <5 indicates strong antagonism. Each data point indicates an average delta score from a single patient sample subjected to a dose-response matrix experiment performed in triplicate. Statistical testing was performed using two-way ANOVA.",
    "diseases": "AML"
  },
  {
    "caption": "A) Severe onychomycosis in P2 (STIM1 p.L374P).",
    "diseases": "onychomycosis"
  },
  {
    "caption": "Tumor volume was monitored for control and Mettl3 or Mettl14-depleted tumors with treatment as indicated in CT26 colon cancer Data are mean ± s.e.m of the indicated number of mice in each group. n, the numbers of mice. * P < 0.05; * * * P < 0.001 by Student's t-tests.",
    "diseases": "colon cancer"
  },
  {
    "caption": "Tumor volume was monitored for control and Mettl3 or Mettl14-depleted tumors with treatment as indicated in B16 melanoma, respectively. Data are mean ± s.e.m of the indicated number of mice in each group. n, the numbers of mice. * P < 0.05; * * * P < 0.001 by Student's t-tests.",
    "diseases": "melanoma"
  },
  {
    "caption": "E, F. Survival analysis of control tumors and those with depleted genes were recorded as indicated in CT26 colon cancer and B16 melanoma, respectively. Data are mean ± s.e.m. of the indicated number of mice in each group. n, the numbers of mice. * P < 0.05; * * P < 0.01; * * * P < 0.001 by Student's t-tests.",
    "diseases": "colon cancer, melanoma"
  },
  {
    "caption": "A, B. The protein level of STAT1 was negatively correlated with METTL3 and METTL14 in human pMMR-MSI-L CRC colon tissue (r2=-3.2477 for METTL3, r2=-2.7491 for METTL14). Each dot represents one tumor tissue.",
    "diseases": "CRC"
  },
  {
    "caption": "(A) Human osteosarcoma U2OS GFP-LC3 cells were treated with a library of polyphenols and polyamines for 6 h And then GFP-LC3 dots were counted to measure autophagy activity. Top 20 hits were shown in the right frame.",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "Human osteosarcoma U2OS cells (B or neuroglioma H4 cells (D stably expressing GFP-LC3 were treated with a library of chalcones (30 µM) as indicated , or were left untreated for 6 h. The cells were then fixed and GFP-LC3 dots were counted as an indicator for autophagy. Data are means ± SD (* = p < 0.05; ** = p < 0.01;*** = p < 0.001). Representative images are shown in (B,D). Scale bar equals 10 µm. (C,E) Acetylation: U2OS and H4 cells were treated as described above, followed by incubation with specific antibodies to block acetylated tubulin; Thereafter immunofluorescence was conducted with antibodies against acetylated lysine residues and appropriate AlexaFluor conjugated secondary antibodies before the assessment of cytoplasmic fluorescence intensities. Representative images of acetylation are shown in (C,E). Scale bar equals 10 µm.",
    "diseases": "neuroglioma, osteosarcoma"
  },
  {
    "caption": "Human osteosarcoma U2OS cells F) or neuroglioma H4 cells H) stably expressing GFP-LC3 were treated with a library of chalcones (30 µM) as indicated or rapamycin (10 µM), or were left untreated for 6 h. The cells were then fixed and GFP-LC3 dots were counted as an indicator for autophagy. Data are means ± SD (* = p < 0.05; ** = p < 0.01;*** = p < 0.001). Viability: U2OS and H4 cells were treated with 30 µM of the indicated chalcones for 24 h and then nuclei were stained with Hoechst 33342 and the number of cells harboring normal nuclei (i.e. non pyknotic, "healthy cells") was determined. All chalcones were hierarchically clustered upon z-scoring the following phenotypes: autophagy (number of GFP-LC3 dots), viability (number of healthy cells) and acetylation (cytoplasmic fluorescence intensity of acetylated lysine residues) in U2OS and H4 cells. Results are reported as a heatmap (G, I).",
    "diseases": "neuroglioma, osteosarcoma"
  },
  {
    "caption": "Hepatoma HepG2 cells were treated with the indicated concentrations of 3,4-DC for 8 h (A,B) GAPDH was measured as a loading control. Band intensities of p62, GAPDH, LC3-I and LC3-II were measured and ratios of p62 or LC3-II versus GAPDH (LC3-II/GAPDH, p62/GAPDH) and LC3-II versus LC3-I (LC3-II/LC3-I) were calculated in (B Data are means ± SEM of at least three independent experiments (LC3-II/GAPDH: * = p < 0.05, ** = p < 0.01; p62/GAPDH: # = p < 0.05, ### = p < 0.001; LC3-II/LC3-I: $=p<0.05",
    "diseases": "Hepatoma"
  },
  {
    "caption": "Hepatoma HepG2 cells were treated with 30 µM 3,4-DC for the indicated time points (C,D). Then, cells were processed to measure LC3 and p62 protein levels by SDS-PAGE and immunoblot GAPDH was measured as a loading control. Band intensities of p62, GAPDH, LC3-I and LC3-II were measured and ratios of p62 or LC3-II versus GAPDH (LC3-II/GAPDH, p62/GAPDH) and LC3-II versus LC3-I (LC3-II/LC3-I) were calculated in D). Data are means ± SEM of at least three independent experiments (LC3-II/GAPDH: * = p < 0.05, ** = p < 0.01; p62/GAPDH: # = p < 0.05, ### = p < 0.001; LC3-II/LC3-I: $=p<0.05).",
    "diseases": "Hepatoma"
  },
  {
    "caption": "(A) Twelve weeks-old wild-type and cardiac specific Atg7 knockout (Atg7cKO) mice were injected with corn oil (vehicle control, Ctr) or 3,4-DC 24 h before surgery and subjected to 3 h prolonged ischemia. Representative images of left ventricular (LV) myocardial sections after alcian blue and triphenyltetrazolium chloride (TTC) staining are depicted. Scale bar equals 1 mm.",
    "diseases": "ischemia"
  },
  {
    "caption": "(B,C) The size of the infarction area (indicated by pale color) per area at risk (AAR) (B) and the global AAR per LV (C) were measured (mean value ±SEM, **p<0.01, #p<0.05 vs WT/Ctr).",
    "diseases": "infarction"
  },
  {
    "caption": "A. Induction of autophagy in murine MCA205 fibrosarcomas. Cells were treated with 3,4 DC alone or in combination with chloroquine, and were harvested 6 hours later for immunoblot detection of LC3 lipidation.",
    "diseases": "fibrosarcomas"
  },
  {
    "caption": "Growth kinetic of MCA205 fibrosarcomas that were wild type and were evolving in immunocompetent C57Bl/6 mice treated as indicated",
    "diseases": "fibrosarcomas"
  },
  {
    "caption": "Growth kinetic of MCA205 fibrosarcomas that were either wild type or Atg5KD (H-I) and were evolving in immunocompetent C57Bl/6 mice or immunodeficient nu/nu mice (G), treated as indicated",
    "diseases": "fibrosarcomas"
  },
  {
    "caption": "B16N melanoma cells stably expressing GFP-luciferase were injected into syngeneic WT and EGR4-/- mice by tail vein injection. (A) Luciferase expression was monitored by IVIS imaging at the indicated timepoints after luciferin injections. ",
    "diseases": "melanoma"
  },
  {
    "caption": "B16N melanoma cells stably expressing GFP-luciferase were injected into syngeneic WT and EGR4-/- mice by tail vein injection. (B-D) Mice were sacrificed on day 20 and tumors were counted. Data is presented as total/mouse (B), N=9 for each gender and genotype. Differences in luciferase activity measured by IVIS in Panel A were determined by two-way ANOVA. Changes in luciferase activity were significantly altered in EGR4 knockout mice (P < 0.0112).",
    "diseases": "melanoma"
  },
  {
    "caption": "B16N melanoma cells stably expressing GFP-luciferase were injected into syngeneic WT and EGR4-/- mice by tail vein injection. Mice were sacrificed on day 20 and tumors were counted. (B), lung tumors (C) and metastatic tumors (all tumors found outside of the lungs; D). N=9 for each gender and genotype. Differences in luciferase activity measured by IVIS in Panel A were determined by two-way ANOVA. Changes in luciferase activity were significantly altered in EGR4 knockout mice (P < 0.0112).",
    "diseases": "lung tumors, melanoma"
  },
  {
    "caption": "B16N melanoma cells stably expressing GFP-luciferase were injected into syngeneic WT and EGR4-/- mice by tail vein injection. All lung tumors were isolated from both WT and EGR4KO mice along with spleens and analysed for CD45+ cells. WT lung tumors were 5.407 ± 1.843% CD45+, while EGR4KO mice were 12.445 ± 2.239% CD45+. WT spleens were 83.92 ± 3.344% CD45+, while EGR4KO mice were 95.13 ± 1.856% CD45+. Relative distributions of T and myeloid cells within the CD45+ populations were determined by flow cytometric analysis. (E,F) Distributions of T and myeloid cells found within lung tumors (E) vs. the spleen (F).",
    "diseases": "lung tumors, melanoma"
  },
  {
    "caption": "B16N melanoma cells stably expressing GFP-luciferase were injected into syngeneic WT and EGR4-/- mice by tail vein injection. All lung tumors were isolated from both WT and EGR4KO mice along with spleens and analysed for CD45+ cells. (G) Representative FACS plots depicting gating strategies for defining Treg cell populations in Panels E and F",
    "diseases": "lung tumors, melanoma"
  },
  {
    "caption": "(A, B) Representative images of the expression  of NEDD4L in the skins from IMQ-treated mice (A) or psoriasis patients (B) as detected by  IHC on the left. The  NEDD4L expression level was calculated by multiplying the staining intensity score and the extent score and is shown on the right. (A, n=5, B, normal, n=15, psoriasis, n=36). Data information: Data are shown as the mean ± s.e.m., and are representative of three independent experiments Scale bar, 200 μm (100×) or 50 μm (400×). Significant differences were tested using a two-tailed Student's t test ** P＜0.01, *** P＜0.001. NS, no significance.",
    "diseases": "psoriasis"
  },
  {
    "caption": "(C, D) Representative images of the expression of EZH2 in the skin epidermis from the IMQ-treated  mice (C) and the  psoriasis patients (D). The number  of  EZH2-positive cells per HPF (high power field) in each mouse and patient is shown on the right. (C, control, n=3, IMQ, n=6. D, normal, n=13, psoriasis, n=27). Data information: Data are shown as the mean ± s.e.m., and are representative of three independent experiments Scale bar, 200 μm (100×) or 50 μm (400×). Significant differences were tested using a two-tailed Student's t test ** P＜0.01, *** P＜0.001. NS, no significance.",
    "diseases": "psoriasis"
  },
  {
    "caption": "(A) Representative pictures of the expression of NEDD4L, GP130 and p-STAT3 in the epidermis of a normal skin  section (same specimen) and sections from  psoriasis patients. Isotype are IgG  antibodies from same species served as negative control. (B) Semiquantitative scoring of NEDD4L, GP130 and p-STAT3 in the epidermis detected by IHC.  Data information: Each symbol represents one patient Scale bar, 200 μm (100×) or 50 μm (400×). All data are shown as the mean ± s.e.m., and significant differences were analyzed using two-tailed Student's t test (normal, n=15, psoriasis, n=36). * P＜0.05, ** P＜0.01, *** P＜0.001.",
    "diseases": "psoriasis"
  },
  {
    "caption": "Effects of overexpression of GFP-BBR-WT or -2E mutant on KYA1797K-induced growth and transformation of CRC cells. MT-HCT116 or SW48 cells were transfected with GFP-BBR-WT, -2E, or GFP-Mock for 24 hr and then treated with KYA1797K via indicated conditions MTT assays were performed for measurements of cell growth",
    "diseases": "CRC"
  },
  {
    "caption": "Effects of overexpression of GFP-BBR-WT or -2E mutant on KYA1797K-induced growth and transformation of CRC cells. MT-HCT116 or SW48 cells were transfected with GFP-BBR-WT, -2E, or GFP-Mock for 24 hr and then treated with KYA1797K via indicated conditions foci formation assay were performed to detect cellular transformation",
    "diseases": "CRC"
  },
  {
    "caption": "WCLs prepared from tumor tissues were immunoprecipitated with anti-β-catenin antibody. WCLs or co-IP samples were subjected to IB analyses",
    "diseases": "tumor"
  },
  {
    "caption": "(B) COUP-TFII expression (green) is increased in  human kidneys from patients with  thrombotic microangiopathy (TMA) and diabetic nephropathy (DN) (n=2). Quantification by  confocal micrographs in 400x hpf. ****p<0.0001 by one-way ANOVA; mean ± SD. The majority of these cells were localized in the interstitial region. More than 50% COUP-TFII (+) cells (green) are co-localized with expanded αSMA-positive (red) areas of fibrosis. Pearson correlation coefficient (PCC) = 0.56 ± 0.1 for patient#1 and 0.65 ± 0.13 for  patient#2.",
    "diseases": "fibrosis, diabetic nephropathy, DN, thrombotic microangiopathy, TMA"
  },
  {
    "caption": "(C) COUP-TFII expression  (green) is increased in lungs from  patients with  IPF (n=2) by immunofluorescence. Quantification by confocal micrographs in 400x hpf. **p<0.01; ****p<0.0001 by one-way ANOVA, mean ± SD.",
    "diseases": "IPF"
  },
  {
    "caption": "(A)  COUP-TFII expression  is significantly increased and co-localized with αSMA+ cells at day 10 of UUO  and day 14 of UIRI  in mice (n=3 animals per group). Quantification by  confocal micrographs in 200x hpf. *p<0.05 **p<0.01 by paired t test; mean ± SD.",
    "diseases": "UIRI, UUO"
  },
  {
    "caption": "(B) In a time course of UUO, COUP-TFII expression increased as early as day 2 and preceded the increased expression  of αSMA (n=2 animals per time point). Quantification by confocal micrographs in 200x hpf. *p<0.05; ***p<0.001 by two-way ANOVA test; mean ± SD.",
    "diseases": "UUO"
  },
  {
    "caption": "(E&F)  Gli1-tdTomato+ cells expanded primarily in the outer medullary region. In contrast, COUP-TFII+ cells are distributed both in cortex and medulla. A subset of COUP-TFII+ cells (green) overlap with genetically labeled Gli1+ pericyte/perivascular  cells (red) in  UUO injury model (n=3 animals per group). CTL:  contralateral kidney. Quantification by confocal micrographs in 200x hpf.",
    "diseases": "UUO"
  },
  {
    "caption": "(D) COUP-TFII+ cells decrease significantly in the UUO kidney in TAM-treated homozygous (F/F;Cre/+) mice (KO group, n=6) compared to wild-type littermates (WT group, n=4). Expression of αSMA (red) and collagen1 (yellow) are also markedly reduced. Masson Trichrome staining  shows less kidney fibrosis in KO compared to WT group. Quantification by confocal micrographs in 200x hpf. **p<0.01 by unpaired t test, mean ± SD.",
    "diseases": "fibrosis, UUO"
  },
  {
    "caption": "(A) Fluorescence microscopy of human fibroblast cell lines derived from ZSD patients-cWT, cWT+ATAD1, PEX3-/-, and PEX3-/-+ATAD1-expressing PEX13-GFP and stained with Mitotracker Deep Red FM. Representative images are shown, scale bar, 10 μm.",
    "diseases": "ZSD"
  },
  {
    "caption": "Kaplan Meier plots representing the survival difference between SKCM patients stratified according to the 40% highest or lowest BNIP3 expression.",
    "diseases": "SKCM"
  },
  {
    "caption": "Representative images of BNIP3 immunostaining in a benign nevus (n=5), primary melanoma and their paired metastasis (n=7). In the representative pictures, nevi or tumor tissue is circled in yellow and highlighted with a yellow asterisk (*). Histopathological scoring of BNIP3 protein levels in nevi and melanoma patients with paired primary and metastases harboring weak and in gradient (+/-), weak and homogeneous (+) or strong and homogeneous (++) BNIP3 protein levels based on histopathological staining intensity and distribution scoring. Scale bars represent 150µm.",
    "diseases": "benign nevus, nevi, melanoma, primary melanoma"
  },
  {
    "caption": "Representative images of BNIP3 immunohistochemistry in TMAs containing (n=158) melanoma metastases and related Kaplan Meier plot of survival difference comparing melanoma patients with different BNIP3 histopathological scores. Scale bars represent 50µm.",
    "diseases": "melanoma"
  },
  {
    "caption": "C. The arf7/arf19 mutant shows defective LR initiation. D. Formation of roots (arrows) close to the wound site of arf7/arf19 primary roots 6 days after excision (DAE). E. Blocking TOR-activity via exposure to 10µM AZD8055 (AZD) resulted in the loss of rooting capability on the wound site of arf7/arf19 primary roots at 6 DAE. S",
    "diseases": "wound"
  },
  {
    "caption": "F, G. Close-ups indicate root formation location or absence of root formation on ctrl media and AZD-containing media, respectively, in arf7/arf19 primary roots at 6 DAE. The proportion of root wound sites with the depicted phenotype is indicated.",
    "diseases": "wound"
  },
  {
    "caption": "(F) Quantification of Lucia reporter  gene expression following transduction of human  primary SEBTA003 glioblastoma  and G26 glioblastoma-derived  neural stem cells  with 1x106 TU/cell. Data are expressed as mean + SEM of n = 3 independent experiments. One-way ANOVA with Tukey's HSD test was used for data analysis.",
    "diseases": "glioblastoma"
  },
  {
    "caption": "Percentage of circulating highly differentiated CD4 T cells within CD4 cells (upper graph) in age-matched healthy donors or NSCLC patients before undergoing immunotherapies. G1 and G2, groups of patients classified according to high THD cells (G1, >40% CD4 THD cells) and low THD cells (G2, <40% CD4 THD cells). Relevant statistical comparisons are shown by the test of Mann-Whitney. In green, objective responders (OR). In red, no OR. Below the graph, correlation of objective responses to G1 and G2 groups by the Fisher´s exact test.",
    "diseases": "NSCLC"
  },
  {
    "caption": "The scatter plot shows PD-1 expression after co-culture of CD4 T cells from healthy donors or NSCLC patients, as indicated, with A459-SC3 lung cancer cells. Relevant statistical comparisons with the test of Mann-Whitney are indicated.",
    "diseases": "lung cancer, NSCLC"
  },
  {
    "caption": "Scatter plot graph with the percentage of lung cancer-specific systemic CD4 T cells quantified by an autologous DC-based antigen presentation assay (See Materials and Methods), in a sample of G1 and G2 patients as indicated. Objective responses (OR) are shown in green. In red, patients with no OR.",
    "diseases": "lung cancer"
  },
  {
    "caption": "The scatter plot graph on the left represents the percentage of CD4 THD cells within lung-cancer specific CD4 T cells in a sample of patients from the indicated G1/G2 groups. On the right, same as left but representing the percentage of CD28+ CD4 T cells within lung-cancer specific CD4 T cells. Objective responders (OR) are shown in green.",
    "diseases": "lung-cancer"
  },
  {
    "caption": "Column graphs representing the percentage of CD4 T cells from NSCLC patients or age-matched healthy donors as represented in the graph, expressing the indicated cytokines after T cell stimulation with anti-CD3/anti-CD28 antibodies. Data on total CD4 (left graph), CD28+ subsets (center graph) and CD28negative subsets (right graph) are shown. Error bars correspond to standard deviations and bars represent means from 5 independent biological replicates (patients).",
    "diseases": "NSCLC"
  },
  {
    "caption": "A-F Immunostaining of primary  HL with H2A.B (brown, indicated by black arrows) with a nuclear counterstain (blue). Human testis (positive control) (A), Human tonsils (negative control) (B), Nodular sclerosis classical cHL, double staining with CD15 (pink) to identify HRS cells and H2A.B  (brown) (C), Mixed cellularity cHL (D),  Lymphocyte rich cHL (E), Nodular sclerosis HL (F). Scale bar for panels A, B, D-F is 50 µm; scale bar for panel C is 15 µm.",
    "diseases": "HL, Lymphocyte rich cHL, Mixed cellularity cHL, Nodular sclerosis classical cHL, Nodular sclerosis HL"
  },
  {
    "caption": "A Relative  mRNA expression levels of  H2A.B in  L1236, L428, HDLM2 HL cell lines and Germinal centre B lymphocytes (GC) compared to the Ramos B lymphocyte cell line. The results are presented as the mean ± SD of three biological replicates.",
    "diseases": "HL"
  },
  {
    "caption": "E-G Following the subcutaneous inoculation of SK-Cha-1-NC (left) and SK-Cha-1-STUB1-FLAG (right) cells into the flanks of male NOD-SCID mice (E), overexpression of STUB1-FLAG inhibited malignant cell proliferation (F) and reduced subsequent tumor size and growth (G) in vivo. Data are means ± SEM. Statistical significance was analyzed by two-way ANOVA (F) or two-tailed unpaired t-test (G) (Five mice, *p < 0.05; **p < 0.01). H-J Following the subcutaneous inoculation of SK-Cha-1-sh-NC (left) and SK-Cha-1-sh-STUB1-1 (right) cells into the flanks of male nude mice (H), STUB1 knockdown promoted malignant cell proliferation (I) and increased subsequent tumor size and growth (J). Data are means ± SEM. Statistical significance was analyzed by two-way ANOVA (I) or two-tailed unpaired t-test (J). (Six mice, *p < 0.05; **p < 0.01; ***p < 0.001).",
    "diseases": "SCID"
  },
  {
    "caption": "B Immunoblot analysis showing STUB1 protein levels in eight pairs of CCA patient samples. N, adjacent non-tumor tissue; T, tumor tissue. β-actin was used as the loading control. The STUB1/β-actin densitometric ratio was recorded by ImageJ.",
    "diseases": "CCA"
  },
  {
    "caption": "C The 5-year disease-free survival of patients with high expression levels of METTL14 (p = 0.0366) and low expression levels of STUB1 (p = 0.0803) in the Fudan University intrahepatic cholangiocarcinoma (FU-iCCA) cohort among patient samples within the 5-95% ranges of STUB1 and METTL14 protein levels.",
    "diseases": "iCCA, intrahepatic cholangiocarcinoma"
  },
  {
    "caption": "(b) RNAscope analysis of Lgr5 mRNA in DSS colitis demonstrating loss of Lgr5 transcript (N=3 per condition). Data information: Nuclei are counterstained with Dapi (blue); white dashed lines indicate basement membrane. Scale bars =50µm",
    "diseases": "colitis"
  },
  {
    "caption": "(c) Hematoxylin and Eosin staining of the colonic epithelium following DSS induced damaged. Crypts are dramatically injured by d5. At d8 through d12, regenerating crypts are observed. Data information: Nuclei are counterstained with Dapi (blue); white dashed lines indicate basement membrane. Scale bars =50µm",
    "diseases": "injured"
  },
  {
    "caption": "(f) Effects of DSS colitis injury on RNA expression levels of stem (Lgr5 and Krt19) and progenitor (Atoh1 and Notch1) cell markers. Lgr5 mRNA expression is significantly decreased after exposure to DSS (N=6-7 per condition). Data are represented as mean ± SEM analyzed using Student's t-test. *P≤0.05, ** P≤0.01.",
    "diseases": "colitis, injury"
  },
  {
    "caption": "(b-c) Krt19+ cells lineage trace entire colonic crypts during both normal homeostasis and injury (N=3-4 per condition). Data information: Nuclei are counterstained with Dapi (blue); white dashed lines outline the basement membrane. Scale bars (b) =45µm Data are represented as mean ± SEM *P≤0.05, **P≤0.01.",
    "diseases": "injury"
  },
  {
    "caption": "(b-c) Notch1+ progenitors are able to generate Lgr5+ stem cells and contribute to epithelial renewal in homeostasis; however, do not contribute to regeneration after colitis (N=4 per condition). Data information: Nuclei are counterstained with Dapi (blue); white dashed lines indicate basement membrane. Scale bars=50μm. Data are represented as mean ± SD analyzed using two-way ANOVA with Sidak's multiple comparisons test. ****P≤0.0001.",
    "diseases": "colitis"
  },
  {
    "caption": "(j-k) Scattered labeling of Atoh1+ cells in control conditions, while DSS injury lead to Atoh1 lineage labeled crypts lacking Lgr5+ stem cells. Data information: Nuclei are counterstained with Dapi (blue); white dashed lines indicate basement membrane. Scale bars =50μm Data are represented as mean ± SD analyzed using Student's t-test with Welch's correction *P≤0.05, ***P≤0.001.",
    "diseases": "injury"
  },
  {
    "caption": "(i-j) Concurrent irradiation injury and Atoh1+ cell ablation results in significantly reduced organoid survival (N=3; n=3 technical replicates per condition). Data information: ; scale bars =100μm. Data are represented as mean ± SEM analyzed using Student's t-test. *P≤0.05.",
    "diseases": "injury"
  },
  {
    "caption": "(I)  IHC staining of GDH1  in primary KIRC tumors and adjacent normal tissues collected by us was performed (left). Quantitative analysis of the GDH1 protein levels was performed using unpaired t-test (right). ***p < 0.001. Scale bars: 50 μm.",
    "diseases": "KIRC"
  },
  {
    "caption": "(K) Overall survival of patients in different tumor stages in the TCGA-KIRC cohort. The R package \"survminer\"-based maximally selected log-rank statistic was used to determine the best cutoff. The log-rank test was used to determine the p value.",
    "diseases": "KIRC"
  },
  {
    "caption": "(I) IHCs of KIRC clinical samples were performed using antibodies against GDH1 or RNF213 (upper panel). The correlated IHC signal between GDH1 and RNF213  in  KIRC  samples was calculated (lower panel). The cor.test was used to determine the p-value. Scale bars: 50 μm.",
    "diseases": "KIRC"
  },
  {
    "caption": "(J) KIRC clinical samples were collected for  αKG  measurement, and we assessed overall survival (left panel) with log-rank test according to the dividing groups of high and low intracellular levels of   αKG with the best separation (right panel). Unpaired t-test was used in the right panel with ***p < 0.001.",
    "diseases": "KIRC"
  },
  {
    "caption": "I-K Schematic of experimental design (I), tumor growth curve (J), and summary of day 15 tumor weight (K) of B6.SJL mice inoculated with B16-OVA melanoma cells (2 x 105) and adoptively transferred on day 7 with in vitro activated and rapamycin- or DMSO-treated wildtype or Peli1-KO OT-I CD8 T cells (4 x 105).",
    "diseases": "melanoma"
  },
  {
    "caption": "HCT116 flank tumours produced by subcutaneous injection were established for 20 days before injection at three-day intervals with vehicle (PBS), or EVs isolated by UC from glutamine-replete or glutamine-depleted HCT116 cells. Tumours were excised 24 h after last of four injections for analysis. Panels show representative immunostained histological sections of tumour tissue quantified using the Visiopharm Integrator System. (C) Sections stained with haematoxylin and eosin, which highlights necrotic regions (pale staining). Proportion of tumour area that is necrotic is represented in bar chart.",
    "diseases": "necrotic"
  },
  {
    "caption": "(E) RT-qPCR measurement of  HERV-R-Env  transcript level in PBMCs  isolated from 19 healthy individuals and 16 COVID-19 patients. (F) RT-qPCR measurement of Exon1 region transcript level in PBMCs  isolated from 19 Healthy individuals and 16 COVID-19 patients. Data information: values were normalized to that of the GAPDH  and represented as mean±SD of samples from 19 healthy and 16 COVID-19 patients, assayed in duplicate.",
    "diseases": "COVID-19"
  },
  {
    "caption": "(G) Quantitation of HERV-R-Env  RNA level in transcriptome dataset of indicated human lung  tissues Data information: In G, HERV-R-Env  copy number in two biological replicates (Healthy lung) and two technical replicates (COVID-19 lung) of the transcriptome dataset are represented as mean±SD.",
    "diseases": "COVID-19"
  },
  {
    "caption": "C. Histopathological  analysis of the lung  tissues by hematoxylin  and eosin  (H&E) staining. The quantified  lung  injury  was depicted by defined clinical parameters in ALI score (n=6 mice/group). Scale bars: 50μm. Data information: P-values are shown, two-tailed Student's t-test Data are representative of three biological replicates with similar results. (mean ± SD",
    "diseases": "lung  injury"
  },
  {
    "caption": "(A) RNAscope fluorescence in-situ hybridization of Ch25h transcripts (red) in the spinal cord of non-immunized mice (NI) (left panels) and mice 17 days after EAE immunization (peak disease) (2 right panels) shown in endothelial cells (Isolectin B4 (IsoB4) green top panels) and activated macrophages/microglia (Ionized calcium biding adaptor molecule 1 (IBA1) green lower panels). Nuclei are shown in blue. (B) Quantitative analysis of Ch25h mRNA expression in the spinal cord of NI and EAE mice comparing expression in macrophages/microglia (MG) and endothelial cells (EC), n = 6 biological replicates/group.",
    "diseases": "EAE"
  },
  {
    "caption": "(E) Percentage of eGFP+ CNS ECs in the same condition as in (D). Symbols indicate individual mice and bars indicate mean ± SD. Ch25hfl/fl NI: n = 4 biological replicates, Ch25hfl/fl EAE: n = 5 biological replicates, Ch25hECKO NI: n = 4 biological replicates, Ch25hECKO EAE: n = 4 biological replicates. Representative results of 1 experiment.",
    "diseases": "EAE"
  },
  {
    "caption": "(A) EAE disease course in Ch25hECKO and Cre negative littermates (Ch25hfl/fl). Top panel: EAE clinical score. Bars indicate mean ± SEM. Bottom panel: Survival analysis of EAE, depicting disease incidence. Representative results of 2 experiments with a minimum of n = 5 biological replicates/group as indicated on the graph. (B) As in (A) except that Ch25h fl/fl- Pdgfb-iCreERT2 mice that express Cre recombinase in blood endothelial cells (Ch25hBECKO) are shown. Representative results of 2 experiments with a minimum of n = 5 biological replicates/group as indicated on the graph. (C) As in (A) except that Ch25hfl/fl- Prox1-CreERT2 mice that express Cre recombinase in lymphatic endothelial cells (Ch25hLECKO) are shown. Representative results of 2 experiments with a minimum of n = 5 biological replicates/group as indicated on the graph.",
    "diseases": "EAE"
  },
  {
    "caption": "(G) RT-qPCR of CNS endothelial cells sorted from Ch25hECKO and Ch25hfl/fl mice during EAE (day 10 after immunization). Ch25hECKO n = 3 biological replicates, Ch25hfl/fl n = 4 biological replicates. The experiment was performed once.",
    "diseases": "EAE"
  },
  {
    "caption": "(C) 25-OHC, 7-keto-25-OHC, and 24(S)-OHC concentration in the same conditions as in (B). Bars represent mean ± SD. n = 6 biological replicates/group except for Ch25fl/fl IL-1β were n = 5 biological replicates. The experiment was performed once. (D) 25-OHC, 7-keto-25-OHC, and 24(S)-OHC levels in spinal cord tissue extracted from Ch25hfl/fl (n = 8), Ch25hECKO (n = 3) and Ch25hBBBKO (n = 6) at the peak of EAE.",
    "diseases": "EAE"
  },
  {
    "caption": "(C) Impact of CNS PMN-MDSC and BM-PMN on CD4+ T cell proliferation assessed by CFSE dilution using flow cytometry. PMN-MDSC were FACS-sorted from the CNS (right panel) and BM (left panel) of WT mice at the peak of EAE. NS = non stimulated. n = 4 biological replicates/group. Bars indicate mean ± SD. CNS PMN-MDSC/CD4+ T cells: representative results of 2 independent experiments; BM-PMN: 1 experiment.",
    "diseases": "EAE"
  },
  {
    "caption": "(I) EAE disease course in Ch25hBBBKO mice (n = 11) where the Cre-recombinase is expressed in endothelial cells of the CNS and Cre negative littermates (Ch25hfl/fl: n = 7 and Ch25hfl/wt : n = 2). Bars indicate mean ± SEM. Representative results of 2 independent experiments.",
    "diseases": "EAE"
  },
  {
    "caption": "(C) Representative contour plots of PMN-MDSC in the CNS at day 22 of EAE assessed by flow cytometry in the same conditions as in (A). (D) As in (C) except that statistical analysis and percentage of PMN-MDSC in live cells are shown. Symbols depict individual mice and bars mean ± SD. Ch25hfl/fl Isotype n = 4, Ch25hECKO isotype n = 4, Ch25hfl/fl Combo, n = 3, Ch25hECKO Combo n = 4. (",
    "diseases": "EAE"
  },
  {
    "caption": "(E) Representative contour plots of CD101 and representative histograms of Ly6G expression in blood neutrophils at day 16 of EAE assessed by flow cytometry. Ch25hECKO and Ch25hfl/fl mice were treated with isotype or Combo treatment which was initiated at the first symptoms of EAE (day 14 after immunization). (F) As in (E) except that statistical analysis is shown. Symbols depict individual mice, bars mean ± SD. Ch25hfl/lfl isotype n = 7, Ch25hECKO isotype n = 5, Ch25hfl/lfl Combo n = 6, Ch25hECKO Combo n = 5. The experiment was performed once. (",
    "diseases": "EAE"
  },
  {
    "caption": "Representative H&E stainings of pancreata from KrasG12D and Hnf1apKO;KrasG12D mice. B-D. KrasG12D and Hnf1apKO;KrasG12D mice have normal morphology at 7 days. E-J. At 21 days Hnf1apKO;KrasG12D mice show acinar-to-ductal metaplasia (dashed encircled areas) and regions with desmoplastic reaction (asterisk), which are not observed in KrasG12D mice (E, H). K-P. At 8 weeks KrasG12D pancreas show occasional abnormal ductal structures (dashed encircled areas in N which is a magnification of squared dotted box in K) and Hnf1apKO;KrasG12D mice (L,M,O,P) present mucinous tubular complexes (black arrows), and more advanced PanINs with luminal budding (open arrows) including foci of spindle cell proliferation (asterisks) and incipient infiltrative growth (black dashed box area in O). Data information: Black dashed boxes in (E,F, K, L and O) indicate magnified areas in (H, G, N, M and P) respectively. Scale bars indicate 100 µm (C,E,F,K,L), 50 µm (O) and 20 µm (B,D,G,H-J,M,N,P).",
    "diseases": "PanINs"
  },
  {
    "caption": "H&E staining of pancreata from Kdm6apKO;KrasG12D and KrasG12D mice. A-C. 7 day-old KrasG12D and Kdm6apKO;KrasG12D mice showed normal morphology. D-I. At 21 days, KrasG12D mice showed normal pancreas morphology (dotted area at in D is shown at large magnification in G) whereas Kdm6apKO;KrasG12D mice already show acinar-to-ductal metaplasia (dashed encircled area in F), spindle cell proliferation (asterisks in E and H), sarcomatoid architecture (I) and desmoplastic reaction (black arrowhead in H). J-O. KrasG12D mice present occasional acinar-to-ductal metaplasia and low grade PanINs at 8 weeks (M is a magnification of squared dotted box in J and see Fig 1N) whereas at the same age pancreas from Kdm6apKO;KrasG12D mice show massive remodeling (K), extensive acinar-to-ductal metaplasia (L and dashed encircled area in N), cancer with prominent spindle/mesenchymal proliferation, infiltrative growth (black arrows and asterisk respectively in O) and abundant stroma (black arrowheads in N). Data information: Scale bars: 100 µm (B,D,E,J,K) or 20 µm (A,C,F-I, L-N). ",
    "diseases": "PanINs, sarcomatoid, cancer"
  },
  {
    "caption": "B Subcutaneous melanoma tumour growth in BL/6 WT mice (n=5) using B16F1 WT and XIAPKO (clone1 and 2).",
    "diseases": "melanoma"
  },
  {
    "caption": "A Intensities of CD177 and XIAP immunostainings in tumour sections from 55 patients were visually scored. The numbers of melanomas with different intensities were plotted into the table as a percentage of the total. Specific staining intensity for XIAP and CD177, corresponding to relative amounts of infiltrated neutrophils, was arbitrarily set as the following: -, not expressed; +, low; ++, moderate; and +++, strong expression. Representative IHC pictures (right panel).",
    "diseases": "melanomas"
  },
  {
    "caption": "B Representative IF (neutrophils staining) in B16F1 WT, XIAPKO, TAB1KO or RIPK2KO tumours (Scale bar 50 µm) and quantification of Ly6G+ cells. The sum of Ly6G-positive cells from 5 randomly selected areas of the tumour (5 mice per genotype) was represented. Dots represent individual mice (n=5). C B16F1 WT, XIAPKO (clone 2) subcutaneous melanoma tumour growth in BL/6 WT mice (n=5). Mice were intra-peritoneal injected with IgG antibody as a negative control or Ly6G antibody 1 day prior to the subcutaneous injection of the B16F1 WT or XIAPKO cells.",
    "diseases": "melanoma"
  },
  {
    "caption": "Representative H&E and immunohistochemical stainings on sequential sections of thymic lymphomas of the indicated genotypes. A picture with lower magnification of independent samples is included in Fig EV3B.",
    "diseases": "thymic lymphomas"
  },
  {
    "caption": "Kaplan-Meier curves of mice harboring thymocytes with indicated genotypes. An event was defined as death or sacrifice of a mouse caused by a thymic lymphoma. Mice that died due to other causes or were still alive and event-free at the end of the experiment were censored. Mice for which the cause of death could not be determined were removed from the data. Wild-type mice were the Cre- littermates of the mice that were used for the other curves.",
    "diseases": "thymic lymphoma"
  },
  {
    "caption": "Immunoblots showing HDAC1 status and H3K79me/H3K9ac levels in nuclear lysates of Hdac1-proficient (p53-null) and Hdac1-deficient thymic lymphoma cell lines. The top four and bottom two panels are from separate lysates of the same cell lines.",
    "diseases": "thymic lymphoma"
  },
  {
    "caption": "A Typical pictures of the immunohistochemical staining of LSD1 R838me2a, LSD1 and CARM1 in breast cancer samples. Scale bars, 100 μm.",
    "diseases": "breast cancer"
  },
  {
    "caption": "The percentage of samples with high level of LSD1 R838me2a (B) expression in different TNM stages of breast cancer (n = 70 breast tumor samples; B, P = 0.0095; C, P = 0.002; D, P = 0.0024; χ2 test).",
    "diseases": "breast tumor , breast cancer"
  },
  {
    "caption": "C, D The percentage of samples with high level of , LSD1 (C) and CARM1 (D) expression in different TNM stages of breast cancer (n = 70 breast tumor samples; B, P = 0.0095; C, P = 0.002; D, P = 0.0024; χ2 test).",
    "diseases": "breast cancer, breast tumor"
  },
  {
    "caption": "The correlation of LSD1 R838me2a with LSD1 (E) was statistically significant among breast cancer specimens (n = 70 breast tumor samples; E, R2 = 0.8835, P < 0.0001; F, R2 = 0.889, P < 0.0001; G, R2 = 0.8478, P < 0.0001; Pearson correlation test). Note that some samples have overlapping scores. IHC score was evaluated according to Feng et al.",
    "diseases": "breast cancer, breast tumor"
  },
  {
    "caption": "F, G The correlation of , CARM1 with LSD1 R838me2a (F) and CARM1 with LSD1 (G) was statistically significant among breast cancer specimens (n = 70 breast tumor samples; E, R2 = 0.8835, P < 0.0001; F, R2 = 0.889, P < 0.0001; G, R2 = 0.8478, P < 0.0001; Pearson correlation test). Note that some samples have overlapping scores. IHC score was evaluated according to Feng et al.",
    "diseases": "breast cancer, breast tumor"
  },
  {
    "caption": "A Bar graph and box-and-whisker plots are presented, which show the allelic proportions of WT FOXL2 mRNA and 402C>G FOXL2 mRNA in AGCT tissues from 46 patients analyzed by pyrosequencing. The box plot represents the minimum value, first quartile, median, third quartile and maximum value of a data set. X-axis indicates mRNAs of WT FOXL2 and 402C>G FOXL2. The whiskers extend to the most extreme data points not considered outliers, and the outliers are represented as dots. Comparisons between groups were performed using Student's t-test, and p values are presented.",
    "diseases": "AGCT"
  },
  {
    "caption": "G RNA-seq analysis was performed to determine AGO-expression levels (transcripts per million) from the individual tissues from 20 independent AGCT patients. X-axis represents mRNAs of AGO1 to 4. The box plot represents the minimum value, first quartile, median, third quartile and maximum value of a data set. The whiskers extend to the most extreme data points not considered outliers, and the outliers are represented as dots.",
    "diseases": "AGCT"
  },
  {
    "caption": "The effect of miR-1236 KO on AGCT metastasis was assessed, using an in vivo xenograft mice model. (A) Representative images of tumor nodules (white arrows) formed in the intestines of nude mice xenografted with control or miR-1236-/- KGN cells are shown (left and right; scale bar = 5 mm). Hematoxylin and eosin staining confirmed the pathological characteristics of the metastasized GCT nodules (middle, black arrows; scale bar = 50 µm). The black dashed circles are metastasized nodules of xenografted KGN cells found in mouse intestines. (B) The number of tumor nodules formed in the intestines was counted in control (n = 8) and miR-1236-/- (n = 8) mice.",
    "diseases": "AGCT, GCT"
  },
  {
    "caption": "D-F Box-and-whisker plots showing the relative expression of miR-1236 (D), variant FOXL2 mRNA (E), and WT FOXL2 mRNA (F), respectively, in 32 patients with non-metastasized AGCTs and 14 patients with metastasized AGCTs. X- axis indicates patient subgroups depending on whether they exhibit metastasized AGCTs (meta) or not (non-meta). The relative miR-1236 levels were measured using a TaqMan® microRNA RT-qPCR assay, with expression normalized to RNU6B. The levels of 402C>G or WT FOXL2 mRNA were determined by real-time RT-PCR, and the data were normalized to paired-gDNA levels. The relative levels of miR-1236 and FOXL2 mRNAs were quantified by setting the levels of AGCT #1 to 1. Real-time RT-PCR was performed in triplicate for each specimen. The box plot represents the minimum value, first quartile, median, third quartile and maximum value of a data set. The whiskers extend to the most extreme data points not considered outliers, and the outliers are represented as dots. Comparisons between groups were performed using Student's t-tests, and p values are presented.",
    "diseases": "AGCT, AGCTs"
  },
  {
    "caption": "G, H The estimated regression line superimposed on the scatter plot of miR-1236 levels with 402C>G FOXL2 mRNA (G) or WT FOXL2 mRNA (H) in AGCT samples (n = 46) is shown, along with correlation coefficient (r) and p values.",
    "diseases": "AGCT"
  },
  {
    "caption": "(E) H&E staining  of colon cancer tumours from GDH1IEC+/+ and GDH1IEC-/- mice  (scale bar, 200 μm). F F4/80 staining  in a noninflamed portion of the colon  after AMO/DSS  treatment (scale bar, 50 μm). G ZO-1 staining  in colon  sections of mice  treated with sequential AMO/DSS  treatment (scale bar, 200 μm).",
    "diseases": "colon cancer"
  },
  {
    "caption": "I Survival  percentages of  GDH1IEC+/+ mice  (n=11) and GDH1IEC-/- mice  (n=9) during progression of the inflammatory cancer  switch. Data information: Statistics: log-rank test (I).",
    "diseases": "cancer, inflammatory"
  },
  {
    "caption": "I Detection of AcK503/527-GDH1 expression  in CRC  grades I+Ⅱ and III+Ⅳ. (grade I+II, n=21; grade III+IV, n=12). J Detection of AcK503/527-GDH1 expression in patients  with (＋) or without (－) recurrence. (－, n=17; ＋, n=17). Data information: Data are mean ± SD from the biological replicates I, J Statistics: Mann-Whitney U-test (I, J)",
    "diseases": "CRC"
  },
  {
    "caption": "(B) Kaplan Meier plots of long-term overall survival of H/NSCC patients from the TCGA dataset divided on the basis of high versus low HSD17B7 expression levels relative to its median expression value among males (darkgreen and lightgreen lines) and females (red and orange lines), showing statistically significant association of elevated HSD17B7 expression with poorer patient survival. Statistical significance was calculated by the log-rank test between the groups. High_female: n=57patients. Low_female: n= 79 patients. High_male: n= 203 patients. Low_male: n= 181 patients.",
    "diseases": "H/NSCC"
  },
  {
    "caption": "(D) Colony forming assays of the indicated SCC cell lines plus/minus HSD17B7 silencing as in the previous panels. Cells plated in triplicate dishes 5 days after lentiviral vector infection and selection were tested for clonogenic capability as in (A). Data are represented as number of colonies +/- SD. n(dishes per condition)= 3 *p<0.05, **p<0.01; p****<0.0001, 2-tailed unpaired t-test.",
    "diseases": "SCC"
  },
  {
    "caption": "(C, D) SCC13 cells stably infected with an HSD17B7-expressing lentivirus (HSD-oe) versus empty vector control (Ctrl) (C) or two HSD17B7-silencing lentivirus (shHSD2, shHSD4) versus vector control (shCtrl) (D) were analyzed as in the previous panels. Shown are individual values for 3 parallel cultures per condition together with mean +/- SD. **p<0.005; ***p<0.0005; ****p<0.0001. 2-tailed unpaired t-test. Additional metabolic measurement experiments of SCC cells plus/minus HSD17B7 overexpression and silencing, in the context of additional manipulations are shown in Fig 9.",
    "diseases": "SCC"
  },
  {
    "caption": "Quantification of collagen content in lung sections from Bumetanide-treated control (CRTH2flox/flox) and F-CRTH2 KO mice. *P < 0.05 vs control, #P < 0.05 vs Vehicle (two-way ANOVA); n = 7 for all groups. Effect of Bumetanide treatment on pulmonary hydroxyproline levels in control and F-CRTH2 KO mice. *P < 0.05 vs control; #P < 0.05 vs Vehicle (two-way ANOVA); n = 7 for all groups.",
    "diseases": "pulmonary"
  },
  {
    "caption": "(E) 45S rDNA copy number analysis in patients' tumors compared to adjacent controls in the LUAD cohort. 67 tumor samples and 43 samples from adjacent tissue were analyzed. (F) 45S rDNA copy number analysis in the LUAD patient samples based on RASSF1A CpG promoter methylation. 67 samples were analysed.",
    "diseases": "LUAD"
  },
  {
    "caption": "qRT-PCR for mDia2/DIAPH3 relative to RPL27 using RNA from normal human skin (N=11), SCCs (N=9) and BCCs (N=7).",
    "diseases": "BCC, SCC"
  },
  {
    "caption": "Representative skin/tumor sections from normal human skin, SCC and BCC patients stained for mDia2/DIAPH3. Note the strong mDia2/DIAPH3-positivity in the tumor stroma. Scale bars: 100 μm. D: Dermis, E: Epidermis: T: Tumor.",
    "diseases": "BCC, SCC"
  },
  {
    "caption": "Expression levels of mDia2/DIAPH3 in tumor and normal tissues based on TCGA cancer data (TCGA data version 20141017, http://firebrowse.org/). Gene expression levels were presented as normalized log2 RSEM (RNA-Seq by Expectation-Maximization) index from the database. BLCA: Bladder Urothelial Carcinoma (N = 408 & 19 tumor and normal tissue samples, respectively), BRCA: Breast Invasive Carcinoma (N = 1100 & 112), CESC: Cervical SCC (N = 306 & 3), ESCA: Esophageal SCC (N = 185 & 11), HNSC: Head-Neck SCC (N = 522 & 44), LIHC: Liver Hepatocellular Carcinoma (N = 373 & 47), LUSC: Lung SCC (N = 501 & 51), PAAD: Pancreatic Adenocarcinoma (N = 179 & 4), PRAD: Prostate Adenocarcinoma (N = 496 & 50), READ: Rectum Adenocarcinoma (N = 167 & 10), STES: Stomach and Esophageal Carcinoma (N = 600 & 46), UCEC: Uterine Corpus Endometrial Carcinoma (N = 546 & 35). Box plot shows relative mDia2/DIAPH3 expression in human tumor (red) and normal (blue) tissue. Boxes indicate the interquartile range, whiskers indicate data points within 1.5 times interquartile range, dots outside the whiskers indicate outliers, and the central line indicates median.",
    "diseases": "Bladder Urothelial Carcinoma, BLCA, BRCA, Breast Invasive Carcinoma, Cervical SCC, CESC, STES, Stomach and Esophageal Carcinoma, ESCA, Esophageal SCC, Head-Neck SCC, HNSC, LIHC, Liver Hepatocellular Carcinoma, Lung SCC, LUSC, PAAD, Pancreatic Adenocarcinoma, PRAD, Prostate Adenocarcinoma, READ, Rectum Adenocarcinoma, UCEC, Uterine Corpus Endometrial Carcinoma"
  },
  {
    "caption": "Relative gene expression of mDia2/DIAPH3 and INHBA in the stroma of intrahepatic cholangiocarcinoma, breast and colorectal cancers vs. stroma of respective normal tissues based on datasets GSE45001 (D) (N = 10 normal tissue & 10 cancer samples, GSE9014 (E) (N = 4 & 13), and GSE35602 (F) (N = 6 & 53), and in CAFs from breast cancer samples vs. normal breast fibroblasts (GSE29270 dataset) (G) (N = 5 & 23). NS: Normal stroma, CS: Cancer stroma, NF: Normal fibroblasts, CAF: Cancer-associated fibroblasts). The expression values of the datasets were obtained using GEO2R tool in the GEO database.",
    "diseases": "breast cancer, colorectal cancers, intrahepatic cholangiocarcinoma"
  },
  {
    "caption": "Kaplan-Meier survival curves based on datasets from GEO, EGA and TCGA, demonstrating that high expression of both mDia2/DIAPH3 and INHBA in patients with liver, stomach and breast cancer correlates with poor overall survival. Data and statistical analyses were collected from KMPlotter.",
    "diseases": "breast cancer"
  },
  {
    "caption": "IFN-γ release (ELISA) in culture supernatants by PBMC from 6 celiac patients or 4 controls cultured in the lower compartment of a bidimensional co-culture model upon 24 h challenge of confluent CaCo-2 cells in the upper compartment with PT-gliadin (I) in presence or absence of VX-770. Mean ± SD of triplicates of independent pooled samples. ***p<0.001, PT-gliadin vs medium; °°°p<0.001, PT-gliadin vs PT-gliadin + VX-770 (n=4) (ANOVA, Bonferroni post hoc test).",
    "diseases": "celiac"
  },
  {
    "caption": "IFN-γ release (ELISA) in culture supernatants by PBMC from 6 celiac patients or 4 controls cultured in the lower compartment of a bidimensional co-culture model upon 24 h challenge of confluent CaCo-2 cells in the upper compartment with combination of P31-43 and P57-68 (J) in presence or absence of VX-770. Mean ± SD of triplicates of independent pooled samples. ; ***p<0.001, P57-68 or P31-43 vs P31-43/P57-68 combination (n=6); °°°p<0.001, P57-68/P31-43 combination vs VX-770 + P57-68/P31-43 (n=3), (ANOVA, Bonferroni post hoc test).",
    "diseases": "celiac"
  },
  {
    "caption": "(K) IL-10 release (ELISA) in culture supernatants by PBMC from 4 celiac patients cultured as in (J). Mean ± SD of triplicates of independent pooled samples. ****p<0.0001, P57-68/P31-43 combination vs P57-68/P31-43+VX-770 treatment (n=3) (ANOVA, Bonferroni post hoc test).",
    "diseases": "celiac"
  },
  {
    "caption": "(L) IFN-γ release (ELISA) into culture supernatants by PBMC from 3 celiac patients cultured in the lower compartment of a bidimensional co-culture model upon a 24 h challenge of confluent Caco-2CFTR-KO cells in the upper compartment with a combination of P31-43 and P57-68 in the presence or absence of VX-770, as in J and K. *p<0.05, medium vs P57-68/P31-43 combination (n=3) (ANOVA, Bonferroni post hoc test).",
    "diseases": "celiac"
  },
  {
    "caption": "Above: Representative funduscopic pictures from living healthy Cx3cr1CreERT2:Rosa26-tdTomato mice on d0. Funduscopy and red fluorescence visualize the fundus and regular distribution of tomato+ microglia before the laser-induced lesion formation. Below: Corresponding immunofluorescence pictures. Non-lesioned retina show a regular pattern of Iba1+ (green) tomato+ (red) retinal microglia while macrophages are absent on the retinal pigment epithelium (RPE) under native conditions. Pictures are representative for six mice analyzed in one experiment. Scale bars represents 50 µm. c) Above: In vivo funduscopy on d7 post lesion. Funduscopic and red fluorescence image depict the lesions (encircled with dashed white lines) and accumulation of tomato+ microglia in Cx3cr1CreERT2:Rosa26-tdTomato mice. Intraperitoneal fluorescein application was performed to label retinal vessels and areas of choroidal neovascularization. Below: Representative immunofluorescence for Iba1 (green) in Cx3cr1CreERT2:Rosa26-tdTomato mice. Resident retinal microglia are Iba1+tomato+ (asterisks) whereas blood-derived myeloid cells are Iba1+tomato- (arrows) and accumulate at sites of laser-induced CNV. Overlay is shown left. Typical pictures from six mice obtained from one independent experiment are shown. Scale bars represents 50 µm.",
    "diseases": "choroidal neovascularization, CNV"
  },
  {
    "caption": "c) HLA-DRA mRNA expression examined by RNA-Seq via Massive analysis of cDNA ends (MACE) analysis of human formalin-fixed and paraffin-embedded (FFPE) membranes of choroidal neovascularization (CNV). Bars represent means ± s.e.m. of four investigated human samples of age-related macular degeneration associated with choroidal neovascularization and four control tissues consisting of choroid and RPE. Level of significance was calculated using DESeq (p = 3.61x10-21).",
    "diseases": "age-related macular degeneration, choroidal neovascularization, CNV"
  },
  {
    "caption": "d) Immunohistochemistry for HLA-DR in the RPE/choroid of one control and the CNV membrane of one patient suffering from age-related macular degeneration associated with choroidal neovascularization.",
    "diseases": "age-related macular degeneration, choroidal neovascularization, CNV"
  },
  {
    "caption": "(H) 4T1 cells co-cultured with the indicated lymphocyte populations isolated from inguinal LN of 4T1 tumor-bearing mice by FACS sorting. After 5-day co-culture, 4T1 cells at lower well were analyzed for Il-17rb expression by RT-qPCR analysis. Gapdh was used as internal control.",
    "diseases": "tumor"
  },
  {
    "caption": "(B) Western blotting analysis of Il-17rb expression was performed in 4T1LN or 4T1PT cells collected from control IgG-, anti-CD4, or anti-CD25 antibody-treated 4T1 tumor-bearing mice.",
    "diseases": "tumor"
  },
  {
    "caption": "(E) NSG mice (n = 5 mice per group) were injected with 5x102 4T1LN or 4T1PT cells collected from control IgG-, anti-CD4, or anti-CD25 antibody-treated 4T1 tumor-bearing mice. Distant organ metastasis was examined by bioluminscent images on day 21. The bioluminescent signal (pseudocolor) was recorded as photons per second per centimeter squared per steradian (p/s/cm2/sr) and the luminescent image was overlaid on the photographic image.",
    "diseases": "tumor"
  },
  {
    "caption": "D) Loss of  C. elegans TDP-43 ortholog,  tdp-1, rescues  glutamatergic tail/phasmid neurodegeneration caused by hrpa-1HsLCD290V after 22 hours paraquat induced oxidative stress, but not  hrpa-1(∆). N=4-12 animals/genotype/trial, significance from  two tailed t-test; tdp-1∆=tdp-1(tgx58). E) Loss of C. elegans TDP-43 ortholog,  tdp-1, rescues glutamatergic tail/phasmid neurodegeneration caused by hrpa-1HsLCD290V after 22 hours paraquat induced oxidative stress, but not hrpa-1(∆). N=4-12 animals/genotype/trial, significance from two tailed t-test; tdp-1∆=tdp-1(ok803). ",
    "diseases": "phasmid neurodegeneration"
  },
  {
    "caption": "G) Expression of Fyn* in sensory glutamatergic neurons (osm-10 promoter, unc-54 3'UTR) reduces glutamatergic tail/phasmid neuron degeneration in hrpa-1HsLCD290V animals after 22 hours  paraquat induced oxidative stress. N=9-12 animals/genotype/trial, significance from two tailed t-test. H) Expression of an empty Fyn control (Fynempty) in sensory glutamatergic  neurons (osm-10  promoter, unc-54 3'UTR) does not alter glutamatergic phasmid  neuron degeneration in hrpa-1HsLCD290V animals  after 22 hours paraquat induced oxidative stress. N=9-12 animals/genotype/trial. ",
    "diseases": "phasmid  neuron degeneration, phasmid neuron degeneration"
  },
  {
    "caption": "(B) Depicted are phosphopeptides that responded to NCS treatment in A-T cells. No significant elevation was observed in these phosphorylations in A-T cells following continuous inhibition of DNA-PK. Box plots depict 71 phosphopeptides measured in two independent biological replicates. The box indicates the range from first to third quartiles, and the central band represents the median. Upper and lower whiskers extend from the box to the maximum and minimum values which are not farther than 1.5 time the interquartile range (IQR).",
    "diseases": "A-T"
  },
  {
    "caption": "(C) The first time points at which 'compensated sites' responded to NCS in WT and A-T cells are presented.",
    "diseases": "A-T"
  },
  {
    "caption": "(D) Temporal kinase dependencies of the 'compensated sites' in A-T cells. Shown are the numbers of 'compensated sites' in A-T cells, which depended on each kinase at the 20 and 240 min time points. The early ones depend mainly on DNA-PK, while the later ones - on ATR.",
    "diseases": "A-T"
  },
  {
    "caption": "(B) This group was enriched for sites that were compensated in an ATR-dependent manner in A-T cells. Box plots depict 9 phosphopeptides measured in two independent biological replicates. The box indicates the range from first to third quartiles, and the central band represents the median. Upper and lower whiskers extend from the box to the maximum and minimum values which are not farther than 1.5 times the interquartile range (IQR).",
    "diseases": "A-T"
  },
  {
    "caption": "G. Immunostain  for Ki67  in wildtype and lymphoma-bearing spleen. Representative images are shown at left. The proportion of nuclei  positive for Ki67  (proliferation index) is quantified at right for n=3 spleens(T-test p=0.00002331).",
    "diseases": "lymphoma"
  },
  {
    "caption": "F, G (F) PCR  for Cγ1-Cre and wildtype Cγ1 alleles and (G), wildtype, floxed or excised Blimp1 alleles in DNA from wildtype (wt) control C57bl/6J cells and purified  T-cells or CD45.2+ cells from  mouse with  lymphoma (T1, T2). PCR  data were confirmed in at least 3 independent tests. Lad. = ladder.",
    "diseases": "lymphoma"
  },
  {
    "caption": "F. Western blot  for c-MYC  in whole spleen  lysates from control C57bl/6J and mPTCL mice. Quantification of c-MYC expression  normalized to vinculin  housekeeper gene levels (n=6). T-test p=0.0007. Bars represent SEM.",
    "diseases": "PTCL"
  },
  {
    "caption": "B. Western blot  for phosphorylated and total ZAP70, AKT, S6  and GSK3β in lysates from three control (C) C57bl/6J and three mPTCL (T) spleens. Murine DLBCL  cell line A20  is a positive control for constitutively active AKT signaling.",
    "diseases": "DLBCL, PTCL"
  },
  {
    "caption": "H. Western blot for γH2AX, total H2AX, CHK1  and RPA32  in control C57bl/6J and mPTCL spleens. GAPDH  is a loading control. Three representative samples per group are shown in the blot  (left) and quantification was performed on n=6 at right. T-test p=0.0798 (CHK1; not statistically significant, ns), p=8.69E-05 (RPA32), p=2.11E-03 (γH2AX). ***p<0.001.",
    "diseases": "PTCL"
  },
  {
    "caption": "A. Sanger screen IC50  drug sensitivity data (IC50  values) for  DDR  inhibitors targeting ATR, CHK1/2 and  Wee1 in T-ALL, PTCL (DEL,  KARPAS-299, SUP-M2) and pan-cancer  cell lines. ANOVA p=0.413 (AZD6738, ATR  inhibitor), p=0.750 (AZD772, CHK1/2 inhibitor), p=0.119 (MK-8776, ATR  inhibitor) and 0.282 (AZD1775, Wee1  inhibitor). Bars represent SEM of biological replicates.",
    "diseases": "PTCL, T-ALL"
  },
  {
    "caption": "B.  PTCL (red) and T-ALL (yellow) human  cell lines were dosed in vitro with AZD6738  for 72h and  viable cell numbers assayed by luminescence  readout using Cell TiterGlo. Average IC50  values from three experiments are plotted. Bars represent SEM.",
    "diseases": "PTCL, T-ALL"
  },
  {
    "caption": "F. Western blot for γH2AX  relative to total H2AX levels of spleen lysates from mice  dosed for 71 days with AZD6738  (ATR; n=4) relative to untreated mPTCL spleens  taken at endpoint (n=6). T-test p=2.70E-06. PC9  cells dosed in vitro 24h with 1 µM aphidicolin  (Aph; an inhibitor of DNA replication) or with AZD6738  (ATR) are positive controls for DNA damage. Bars represent SEM. ***p<0.001",
    "diseases": "PTCL"
  },
  {
    "caption": "Histopathological (A-D) and virological (E) examinations of the lung tissues from an ill Malayan pangolin naturally infected with Pangolin-CoV (A and B, 200× and 400×, respectively) and an uninfected Malayan pangolin (C and D, 200× and 400×, respectively). Interstitial pneumonia with extensive infiltration of inflammatory cells is seen in the lung tissue from the infected pangolin. Viral particles are seen in double-membrane vesicles in the transmission electron microscopy image (small scale = 50 nm) taken from the Verno E6 cell culture inoculated with supernatant of homogenized lung (E), with morphology indicative of coronavirus (inserts at the upper right corner of E).",
    "diseases": "Interstitial pneumonia"
  },
  {
    "caption": "Normalized counts of processed fragments mapping to the right arm of Alu RNAs that are differentially processed (rows) between AD and no AD for each CBB patient (columns) (Dataset EV1). Red corresponds to higher normalized counts of processed Alu RNA fragments.",
    "diseases": "AD"
  },
  {
    "caption": "Boxplots depict differences in hippocampi of AD and no AD patients regarding SINE Alu RNA processing ratio (left panel) (a p value of 0.05 was considered as threshold for statistical significance with p=0.01 , n=24, unpaired non-directional t-test) and in total Alu RNA levels (right panel) (ns=not significant). In the boxplots, the central band (the line that divides the box into 2 parts) represents the median of the data, the ends of the box shows the upper (Q3) and lower (Q1) quartiles, the extreme line shows Q3+1.5xIQR to Q1-1.5xIQR (the highest and lowest value excluding potential outliers), while dots beyond the extreme line show potential outliers.",
    "diseases": "AD"
  },
  {
    "caption": "As in Figure 2B, normalized counts of processed fragments mapping to the right arm of Alu RNAs that are differentially processed (rows) between AD and no AD for each MAP patient (columns) (Dataset EV2). Red corresponds to higher normalized counts of processed Alu RNA fragments.",
    "diseases": "AD"
  },
  {
    "caption": "Boxplots depict differences in cortex of AD and no AD patients regarding SINE Alu RNA processing ratio (left panel) (a p value of 0.05 was considered as threshold for statistical significance with p<0.001, n=118, unpaired non-directional t-test) and in full length Alu RNAs (p=0.005). Boxplot representation as in subfigure 2D.",
    "diseases": "AD"
  },
  {
    "caption": "Boxplots depict full length Alu RNA levels in cortex of AD and no AD patients separated into three age groups. No significant difference observed between the different age groups of either AD or no AD patients or for the comparisons between no AD and AD of each age group (unpaired non-directional t-test, with p<0.05 considered the threshold for statistical significance, n for no AD=19 (below 85), 19 (between 85 to 90), 13 (above 90); n for AD=8 (below 85), 21 (between 85 to 90), 38 (above 90)). Boxplot representation as in subfigure 2D.",
    "diseases": "AD"
  },
  {
    "caption": "Boxplots depict differences in SINE Alu RNA processing ratio in cortex of AD and no AD patients separated into three age groups. No significant difference observed between the different age groups of either AD or no AD patients. A p value 0.05 was considered as threshold for statistical significance for the comparisons between no AD and AD of each age group (unpaired non-directional t-test, with p=0.003 for the comparison below 85, and p < 0.001 for the other two comparisons and n numbers as in (E)). Boxplot representation as in subfigure 2D.",
    "diseases": "AD"
  },
  {
    "caption": "Boxplots depict differences in SINE Alu RNA processing ratio in all MAP patients with regard to final clinical diagnosis (p < 0.01 for the comparison between NCI and MCI, between NCI and AD, and between MCI and AD, unpaired, non directional t-test). NCI=no cognitive impairment (n=71), MCI=mild cognitive impairment (n=67), AD=Alzheimer's disease (n=87). Boxplot representation as in subfigure 2D. Boxplots depict differences in SINE Alu RNA processing ratio in all MAP patients (n=241) with regard to Braak stage classified into three categories (p = 0.004 for the comparison between 0-2 and 3-4, and p < 0.001 for the comparisons between 3-4 and 5-6 and between 0-2 and 5-6, unpaired, non directional t-test, n=39[0-2],n=148[3-4] and n=54[5-6]). Boxplot representation as in subfigure 2D.",
    "diseases": "Alzheimer's disease, AD, MCI, mild cognitive impairment, NCI, no cognitive impairment"
  },
  {
    "caption": "Scatterplot depicting the positive correlation between TP53 expression values and Alu RNA processing ratio in AD patients (r=0.65, p < 0.001). Statistical test is based on Pearson's product moment correlation coefficient and follows a t distribution using the cor.test function in R package stats. Scatterplot depicting no correlation between TP53 expression values and full length Alu RNA levels in AD patients (r=0.06, no correlation, ns=non-significant). Statistical test as in subfigure 5C.",
    "diseases": "AD"
  },
  {
    "caption": "Association between SINE Alu RNA ratio (upper panel) and gene expression levels (lower panel) of genes up-regulated in AD (Dataset EV3, |log2FoldChange|> 0.5). Every column in both panels corresponds to the same MAP patient of either the no AD or AD group. Patients in each group are sorted from left to right in an ascending order with regard to Alu RNA processing ratio. Every row in the heatmap corresponds to one gene, with color density representing normalized FPKM values from RNA-seq for this gene for each patient (columns) (red represents high and blue low expression levels). Association between full length Alu RNA levels (upper panel) and gene expression levels (lower panel) of genes down-regulated in AD (Dataset EV4, |log2FoldChange|> 0.5). Every column in both panels corresponds to the same MAP patient of either the no AD or AD group. Patients in each group are sorted from left to right in an ascending order with regard to full length Alu RNA levels. Every row in the heatmap corresponds to one gene, with color density representing normalized FPKM values from RNA-seq for this gene for each patient (columns) (red represents high and blue low expression levels).",
    "diseases": "AD"
  },
  {
    "caption": "Scatterplot depicting the positive correlation between average gene expression values of upregulated genes in Figure 6B and Alu RNA processing ratio in AD patients (r = 0.88, p<0.001). Statistical test is based on Pearson's product moment correlation coefficient and follows a t distribution using the cor.test function in R package stats. Scatterplot depicting the negative correlation between average gene expression values of down-regulated genes in Figure 6C and full length Alu RNA levels in AD patients (r = -0.42, p<0.001). Statistical test as in subfigure 6D.",
    "diseases": "AD"
  },
  {
    "caption": "Correlation between gene expression and Alu RNA processing ratio for AD upregulated genes (Dataset EV3) (upper panel) and a random set of non-differentially expressed genes (Dataset EV5) (lower panel). For every gene a correlation coefficient was calculated (Pearson correlation) together with the respective p-value. Statistical test is based on Pearson's product moment correlation coefficient and follows a t distribution using the cor.test function in R package stats. Based on the r and p value genes were classified into four categories: i)NS, non-significant for p value > 0.05, ii) no correlation or weak correlation (r≤0.05), iii) significant (p < 0.05) and strong correlation (0.5",
    "diseases": "AD"
  },
  {
    "caption": "Scatterplot depicting the positive correlation between HSF1 mRNA expression values and Alu RNA processing ratio in MAP AD patients (r=0.72, p<0.001). Statistical test is based on Pearson's product moment correlation coefficient and follows a t distribution using the cor.test function in R package stats. Scatterplot depicting lack of correlation between HSF1 mRNA expression values and full length Alu RNA levels in MAP AD patients (ns=non-significant, with p value 0.05 as the significance threshold). Statistical test as in subfigure 8E.",
    "diseases": "AD"
  },
  {
    "caption": "F. Dopaminergic neuronal cultures from control lines and glucocerebrosidase (GBA) N370S PD patients were immunoblotted for the presence of LAG3. No band for LAG3 could be observed in neurons.",
    "diseases": "PD"
  },
  {
    "caption": "A. STING protein expression of 58 colon adenocarcinoma specimens within the TCGA COAD collection were obtained from the CPTAC project website. Samples were partitioned into STING-Low (non-detectable STING protein, N=15) and STING-Hi (detectable STING protein, N=43) groups. Kaplan Meier curve is shown with P value indicated.",
    "diseases": "colon adenocarcinoma"
  },
  {
    "caption": "D. From a published colorectal cancer chemotherapy response study, STING RNA expression in responders and non-responders were compared, with each dot representing a tumor.",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "Bioluminescence imaging and quantification of brain metastases (H) of BALB/c nude mice xenografted with control or IFITM1-knockout H1299 cells (populations of knockout cells) by intracardiac injection (1×106 cells). (The n-values denote the number of mice per group, and 4 independent Western blot experiments were performed.) (H, quantification of brain metastases",
    "diseases": "brain metastases"
  },
  {
    "caption": "(J) Bioluminescence imaging and quantification of brain metastases and overall survivals of BALB/c nude mice xenografted with control or IFITM1-overexpressing H460 cells by intracardiac injection (1×105 cells). (The n-values denote the number of mice per group, and 4 independent Western blot experiments were performed.) the log-rank test survival in J",
    "diseases": "brain metastases"
  },
  {
    "caption": "(N) Kaplan-Meier survival curves of lung cancer patients in the TCGA dataset (n=415) stratified by IFITM1 mRNA expression. HR, hazard ratio. the log-rank test survival in N)",
    "diseases": "lung cancer"
  },
  {
    "caption": "(A) Representative immunofluorescence images and quantification of microglial (TMEM119+) or macrophage (TMEM119-/F4/80+) density per microscopic field in the brain on day 1 or 7 after the intracardiac injection of control or IFITM1-overexpressing LLC-BrM cells (tdTomato, 1×106) into C57BL/6 mice (90, 90, and 120 fields for normal, day 1, and day 7, respectively; normal, 3 mice; day 1, 3 mice; day 7, 4 mice). Normal brain tissue was used as the control.",
    "diseases": "BrM"
  },
  {
    "caption": "(C) Flow cytometric analysis of violet-labeled LLC-BrM cells phagocytosed by microglia in the brains of LLC-BrM cell-allografted BALB/c nude mice on day 1 after intracardiac injection (1×106 control or IFITM1-knockout cells). Representative flow cytometry pseudocolor density plots and the gating strategy are shown, and the bar graph shows the percentage of violet+ microglia. (The n-values denote the number of mice per group.)",
    "diseases": "BrM"
  },
  {
    "caption": "(E) LLC-BrM cells (tdTomato) were surrounded by activated microglia (Iba1+, green) and IFNγ (white) in the brain on day 1 or 7 after intracardiac injection of control or IFITM1-overexpressing cells (1×106) into C57BL/6 mice. IFNγ intensities in the fields enclosed in the yellow dotted lines (ROIs) (90, 90, and 120 fields for normal, day 1, and day 7, respectively) are shown. The ROI was set as the entire area of the metastatic lesion for day 7 and as the area of single metastatic cell for day 1. ImageJ was used to quantify the immunofluorescence intensity in the ROI. Normal brain tissue was used as the control. ROI, region of interest.",
    "diseases": "BrM"
  },
  {
    "caption": "(G) Results of ELISA for mouse IFNγ in the brain on day 1 after the intracardiac injection of control or IFITM1-knockout LLC-BrM cells (1×106) into BALB/c nude mice. PLX5622 (1,200 PPM) was administered in chow from day -3 to day 1. BLZ945 (200 mg/kg) was administered by oral gavage from day -2 to day 1. Minocycline (33 mg/kg) was administered intraperitoneally on days -1, 0, and 1. Clodronate liposomes (100 μl/10 g) were administered intraperitoneally on day -1. Normal brain tissue was used as the control. (The n-values denote the number of mice per group.)",
    "diseases": "BrM"
  },
  {
    "caption": "(E) ELISA results of mouse IFNγ in the brain on day 1 after intracardiac injection of the indicated LLC-BrM cells (control, C3 knockout, IFITM1 overexpression, or IFITM1 overexpression in combination with C3 knockout, 1×106) into C57BL/6 mice. Normal brain tissue was used as the control. (The n-values denote the number of mice per group.)",
    "diseases": "BrM"
  },
  {
    "caption": "(G) Control and IFITM1-overexpressing LLC-BrM cells (1×106, tdTomato) were surrounded by activated microglia (left, green, Iba1+) and complement C3 (left, white) in the brain on day 1 after intracardiac injection into C57BL/6 mice (normal, 3 mice; day 1, 3 mice; day 7, 4 mice). Complement C3 intensities in the fields enclosed in the yellow dotted lines (ROIs) are shown (right; 90, 90, and 120 fields for normal, day 1, and day 7, respectively). The ROI was set as the area of a single metastatic cell. ImageJ was used to quantify the immunofluorescence intensity in the ROI. Normal brain tissue was used as the control. ROI, region of interest.",
    "diseases": "BrM"
  },
  {
    "caption": "We would like to point out that TNFα, instead of IFNγ, was used as a marker of microglial activation in vitro (H) Results of ELISA for mouse TNFα in the culture supernatant of primary mouse microglia (6×104, from 16 C57BL/6 mice), primary mouse BMDMs (6×104, from 3 C57BL/6 mice), or primary mouse BrM-BMDMs (6×104, from 37 C57BL/6 mice) stimulated with conditioned medium from control LLC-BrM cells (1×104) and IFITM1-knockout LLC-BrM cells (1×104). BMDMs, primary bone marrow-derived macrophages. BrM-BMDMs, primary bone marrow-derived macrophages from the brain metastatic lesions of LLC-BrM cell-isografted C57BL/6 mice on day 20 after the intracardiac injection of LLC-BrM cells (1×105 cells). CM, conditioned medium (3 independent experiments).",
    "diseases": "brain metastatic, BrM"
  },
  {
    "caption": "(L) Flow cytometric analysis of apoptotic LLC-BrM cells (6×104) in contact coculture with primary mouse microglia (6×104, from 16 C57BL/6 mice), which were activated by conditioned medium from control or C3-knockdown H460 cells (1×106). CM, conditioned medium (3 independent experiments).",
    "diseases": "BrM"
  },
  {
    "caption": "(A) Schematic of efficacy of adoptive CD8+ T cell immunotherapy in suppressing brain metastasis (top far left), representative western blots of IFITM1 expression in control or IFITM1-overexpressing LLC-BrM cells (bottom far left), bioluminescence imaging (middle left), quantification of brain metastases (middle right) and overall survivals (far right) of BALB/c nude mice allografted with control or IFITM1-overexpressing LLC-BrM cells by intracardiac injection (1×105 cells). Primary mouse naïve CD8+ T cells from 12 C57BL/6 mice or not were injected intravenously on days -1, 6, and 13 (1×104 cells at each time point). (The n-values denote the number of mice per group, and 4 independent Western blot experiments were performed.) (B) Schematic of efficacy of adoptive CD8+ or CD4+ T cell immunotherapy in suppressing brain metastasis (far left), bioluminescence imaging (middle left), quantification of brain metastases (middle right) and overall survivals (far right) of BALB/c nude mice allografted with control or IFITM1-overexpressing LLC-BrM cells by intracardiac injection (1×105 cells). Primary mouse naïve CD8+ or CD4+ T cells from 12 C57BL/6 mice were injected intravenously on days -1, 6, and 13 (1×104 cells at each time point). (The n-values denote the number of mice per group.) (quantification of brain metastases ANOVA with uncorrected Fisher's LSD test or the log-rank test (survival",
    "diseases": "brain metastasis, BrM, brain metastases"
  },
  {
    "caption": "(G) Bioluminescence imaging and quantification of brain metastases on day 20 in C57BL/6 mice isografted with control or IFITM1-overexpressing LLC-BrM cells by intracardiac injection (3×105 cells). Mice were systemically primed-boosted with homologous LLC-BrM cell lysates (1×106 cells for day -21 and 1×105 cells for day -7) before injection of cancer cells. Then, IgG or an anti-CD8α antibody (2 μg/mouse) was injected intravenously on day 3 alone or in combination with minocycline treatment (33 mg/kg) on day 1. Minocycline was administered intraperitoneally. (The n-values denote the number of mice per group.) one-way (G)",
    "diseases": "BrM, brain metastases"
  },
  {
    "caption": "(M) Cleaved caspase 3 (green)-positive LLC-BrM cells (tdTomato) were surrounded by CD8+ T cells (white) in the brain metastatic lesions of LLC-BrM cell-isografted C57BL/6 mice on day 20 after intracardiac injection of control or IFITM1-overexpressing LLC-BrM cells (1×106 cells). The positively stained areas of single CD8+ T cells, clustered CD8+ T cells, cleaved caspase 3+ cancer cells, and tdTomato+ cancer cells in the ROI were calculated by ImageJ. The ratios of the areas between the clustered and single CD8+ T cells are shown as the numbers of CD8+ T cells in the ROI, and the ratios of the areas between cleaved caspase 3+ cancer cells and tdTomato+ cancer cells are shown as the percentages of cleaved caspase 3+ cancer cells in the ROI (90 fields per group, 3 mice per group). Yellow dotted lines (ROIs), brain metastatic lesions; ROI, region of interest.",
    "diseases": "brain metastatic, BrM"
  },
  {
    "caption": "(O) Kaplan-Meier survival curves of lung cancer patients in the TCGA dataset stratified by IFITM1 and MHC-I mRNA expression. HR, hazard ratio. ANOVA with uncorrected Fisher's LSD test, or the log-rank test (O).",
    "diseases": "lung cancer"
  },
  {
    "caption": "(F) Bioluminescence imaging, quantification of brain metastases, and overall survival of C57BL/6 mice isografted with control or IFITM1-overexpressing LLC-BrM cells by intracardiac injection (3×105 cells). Mice were systemically primed-boosted with homologous LLC-BrM cell lysates (1×106 cells for day -21 and 1×105 cells for day -7) before injection of cancer cells, and IgG or an anti-PD-1 antibody (100 μg/mouse) was then injected intravenously on days 3, 6, and 9. (The n-values denote the number of mice per group.) unpaired two-way (quantification of brain metastases in F) ANOVA with uncorrected Fisher's LSD test, or the log-rank test (survival in F).",
    "diseases": "BrM, brain metastases"
  },
  {
    "caption": "(H) Bioluminescence imaging and quantification of brain metastases in C57BL/6 mice isografted with control or IFITM1-knockout LLC-BrM cells by intracardiac injection (3×105 cells). IgG (30 μg/mouse, days 3, 6, and 9), an anti-PD-1 antibody (30 μg/mouse, days 3, 6, and 9), or UV-irradiated oncolytic virus (106 pfu/mouse, days 0, 2, and 4) was injected intravenously alone or in combination as indicated. (The n-values denote the number of mice per group.) one-way (quantification of brain metastases in H)",
    "diseases": "BrM, brain metastases"
  },
  {
    "caption": "CSF p3-Alcβ37 values in subjects who were categorized along the AD continuum (n = 131). Cut-off values are 359.6 pg/mL for Aβ42 (A+ indicates <359.6 pg/mL), 30.6 pg/mL for p-tau (T+ indicates >30.6 pg/mL), and 105.3 pg/mL for t-tau (N+ indicates >105.3 pg/mL) respectively. Statistical significance was determined by a one-way ANOVA followed by Tukey's multiple comparisons test (means ± SEM; A-: n = 36, A+T-N-: n = 51, A+T+N-: n = 30, A+T+N+: n = 14), and significant p-values (p < 0.01, p < 0.0001) are indicated on the graph.",
    "diseases": "AD"
  },
  {
    "caption": "(K) Improvement of the inverse SUVR correlation between [18F]BCPP-EF and [11C]DPA713 in AD mice following administration of p3-Alcβ9-19. AD mice with (closed circle) or without (open circle) subcutaneous injection of p3-Alcβ9-19 peptide (1 mg/kg body weight) are also analyzed with [11C]DPA713. A solid linear line shows a significant inverse correlation (Pearson's correlation, r = 0.594, p < 0.05) in AD mice, whereas a dotted linear line shows a positive correlation tendency in AD mice in response to p3-Alcβ9-19 administration.",
    "diseases": "AD"
  },
  {
    "caption": "A-D Appearance of autophagic structures (marked with GFP-Atg8a) during wound closure in the epidermis of control third instar larvae and after epidermal knockdown of the autophagy pathway components Atg1, Atg5, Atg6, Atg7 or Atg12. All constructs are expressed in the epidermis under the control of the A58-Gal4 driver. (A) Time points from movies of wounded epidermis. The wounds have closed by 2 h in all cases. (B) Higher magnification of the areas marked by magenta boxes at t=120 min. (C) Quantification of the appearance of GFP-Atg8a puncta in the imaged area (10000 µm2) 3 control larvae, shown for each individual larva. (D) Quantification of number of GFP-Atg8a puncta in different genetic conditions measured in an area of 10000 µm2 at the time of wound closure; n=4-10 larvae each genotype, for the detail see Data analysis.",
    "diseases": "wound, wounded, wounds"
  },
  {
    "caption": "(D) After randomized, 4 weeks old and sex-matched Phb1F/F mice  and Phb1MyeKO mice  were administered with PBS  or LPS  (300 mg/kg) to induce septic  shock via intraperitoneal injection. The life span of  Phb1F/F mice  (n = 6) and Phb1MyeKO mice  (n = 7) was recorded.",
    "diseases": "septic  shock"
  },
  {
    "caption": "(E) PBMCs  were extracted from normal controls and patients  with sepsis  (n = 6 individuals). Intracellular mRNA levels were detected by  real-time quantitative PCR (RT-qPCR) assays (mean ± SEM). n.s., no significance, * p < 0.05, ** p < 0.01 (Student's t-test).",
    "diseases": "sepsis"
  },
  {
    "caption": "(F) PBMCs  were extracted from normal controls and infant patients  with sepsis. Protein levels in whole cell lysates were detected by WB  assays.",
    "diseases": "sepsis"
  },
  {
    "caption": "F Representative BLI  and histology  of organotypic cultures with H2030-BrM cancer  cells treated with  DMSO or decreasing concentrations of DEBIO-0932. Scale bar: 100 µm; high magnification: 50 µm. G Quantification of the bioluminescence signal emitted by each condition shown in (F) at day 3 normalized by the initial value obtained at day 0 and normalized to the organotypic cultures treated with  DMSO. Day 0 is considered 12-16h after the addition of cancer cells and treatment or DMSO. Values are shown in box-and-whisker plots where each dot is an organotypic culture and the line in the box corresponds to the median. The boxes go from the upper to the lower quartiles and the whiskers go from the minimum to the maximum value (n=8 DMSO, n=8 BKM120 and n=7 per concentration of DEBIO-0932-treated organotypic cultures, 2 independent experiments). P value was calculated using two-tailed t-test.",
    "diseases": "BrM"
  },
  {
    "caption": "B Representative images of organotypic cultures with established metastases with various glial  components of the microenvironment labelled. Scale bar: 75 µm. Each individual condition was evaluated in several organotypic cultures (3-6 slices).",
    "diseases": "metastases"
  },
  {
    "caption": "A-C Immunofluorescence against HSP90  in mouse brains  with established metastases. (A) HSP90 positive structures in areas not affected by the metastasis includes the  medial habenula, where  neurons co-localize with the chaperone. Scale bars: 100 µm (low magnification), 50 µm (medial habenula nucleus), 12 µm (high magnification neurons). (B) Established metastases from different primary origins and oncogenomic profiles stained  with HSP90. Dotted lines delineate the  metastasis  (cc: cancer cells). Scale bars: 75 µm. (C)  Iba1 colocalizes with HSP90 within areas affected by metastases. BB: bisbenzamide. Scale bar: 75 µm (low magnification), 12 µm (high magnification).",
    "diseases": "metastases, metastasis"
  },
  {
    "caption": "E Representative human brain metastases  showing different intensities or scores for HSP90. Scale bar: 50 µm. F Quantification of HSP90 in human brain metastases. 59 out of 60 (98%) showed positive staining of HSP90 in the tumor, 15 (25%) scored with 3 (strong), 36 (60%) with 2 (moderate) and 8 (13%) with 1 (weak) according to the signal intensity of HSP90 in the cytoplasm of cancer cells.",
    "diseases": "brain metastases"
  },
  {
    "caption": "Representative human brain metastases showing different percentages of nuclear HSP90. Scale bars: (J) 50 µm Black arrows point to cancer cells positive for HSP90 in the nucleus.",
    "diseases": "brain metastases"
  },
  {
    "caption": "Representative  human brain metastases  showing different percentages of nuclear HSP90. Scale bars: (K) low magnification: 100 µm; high magnification: 10 µm.",
    "diseases": "brain metastases"
  },
  {
    "caption": "L Quantification of nuclear HSP90 in human brain metastases. 54 out of 60 samples (90%) showed positive nuclear HSP90  in the tumor. 27 (45%) showed 1-5% (moderate) and 27 (45%) showed >5% (high) of  nuclear HSP90. M Quantification of nuclear HSP90 in human  primary tumors. 19 out of 30 (63%) showed positive nuclear HSP90 in the tumor. 9 (30%) showed 1-5% (moderate) and 10 (33%) showed >5% (high) of  nuclear HSP90.",
    "diseases": "brain metastases"
  },
  {
    "caption": "B Representative in vivo and ex vivo images of vehicle and  DEBIO-0932  treated mice  5 weeks (experimental endpoint) after intracardiac inoculation of H2030-BrM cells.",
    "diseases": "BrM"
  },
  {
    "caption": "E Representative sections of  brains from vehicle and DEBIO-0932 treated mice in (B-D). The dotted lines surround the metastases (GFP+). Representative field of view of metastasis stained  with  GFP  and cleaved caspase 3. Scale bars: slices,1mm; cleaved caspase 3, 50 µm. F Quantification of established metastases  found in vehicle and DEBIO-0932 treated brains  from panel (E). Values are shown in box-and-whisker plots where every dot represents a different  brain  and the line in the box corresponds to the median. The boxes go from the upper to the lower quartiles and the whiskers go from the minimum to the maximum value (vehicle: n=10 brains; DEBIO-0932: n=14 brains). P value was calculated using two-tailed t-test. G Quantification of number of cleaved caspase 3  (CC3+) in cancer cells found in vehicle and  DEBIO-0932 treated brains from panel (E). Values are shown in box-and-whisker plots where every dot is a metastatic lesion and the line in the box corresponds to the median. The boxes go from the upper to the lower quartiles and the whiskers go from the minimum to the maximum value (n=8 metastatic lesions from 4  brains per condition). P value was calculated using two-tailed t-test.",
    "diseases": "metastases, metastasis, metastatic"
  },
  {
    "caption": "I Representative BrM-PDOC stained with proliferation markers (BrdU) and markers of the microenvironment (GFAP for  astrocytes, Iba1 for microglia/  macrophages). Scale bar: 50 µm.",
    "diseases": "BrM"
  },
  {
    "caption": "F qRT-PCR  of H2030-BrM brain metastases obtained from animals during neurosurgery compared to relapsed  metastases  from the corresponding animals. A panel of five genes related to HSP90 pathway is evaluated. Values are shown in box-and-whisker plots where every dot represents a different animal and the line in the box corresponds to the median. The boxes go from the upper to the lower quartiles and the whiskers go from the minimum to the maximum value (n=5 mice per experimental condition). P value was calculated using two-tailed t-test.",
    "diseases": "brain metastases, BrM, metastases"
  },
  {
    "caption": "C Volcano plot with deregulated proteins (red: upregulated; green: downregulated) found in brain metastases treated with DEBIO-0932 compared to DMSO (n=3 biological replicates (mice) per condition, n≥12 brain metastases per mouse were pooled together). Proteins with a P value <0.05 and a log2 ratio >1 or <-1 were defined as deregulated. Gray dotted lines indicate P value and log2 ratio cut offs. The names of the top deregulated proteins are shown.",
    "diseases": "brain metastases"
  },
  {
    "caption": "G Kaplan-Meier curves showing significant correlation between worse survival post-brain metastasis and high expression levels of the HSP90 signature (AHR, DDA1, UBE4B, GPATCH8) in a cohort of 45  breast cancer brain metastasis patients.",
    "diseases": "brain metastasis, breast cancer"
  },
  {
    "caption": "H Representative images (selected cases obtained from Fig EV6M) and histological  score of  AHR, DDA1 and UBE4B in  human brain metastases (n=16) according to the signal intensity of the corresponding protein in cancer cells.",
    "diseases": "brain metastases"
  },
  {
    "caption": "N Representative images of primary tumors with high (red dot) or low (grey dot) UBE4B levels. A few cases of matched  primary-metastases allowed to evaluate the  HSP90-dependent protein. Scale bar: : 100 µm.",
    "diseases": "primary-metastases"
  },
  {
    "caption": "M Hemorrhagic P3 Jag1Ndr/Ndr brain (n= 2/83 Jag1Ndr/Ndr mice, sex n.d.).",
    "diseases": "Hemorrhagic"
  },
  {
    "caption": "N Hemorrhagic P15 Jag1Ndr/Ndr retina. Scale bar 20 µm. Sex n.d.",
    "diseases": "Hemorrhagic"
  },
  {
    "caption": "A-E αSMA coverage of (A) P10, (B) P15, (C) P30, (D) 3-6 month old and € 1-year-old retinal arterioles. Brackets in A, B denote perpendicular VSMCs around arteriole. Yellow arrows in A, B, C. indicate VSMCs with an orientation parallel to the blood vessel. Green arrowheads in D denote stenosis. White arrowheads in E label αSMA-negative gaps and white arrows an aneurysm. Cropped images were placed on black background for esthetic purposes.",
    "diseases": "stenosis, aneurysm"
  },
  {
    "caption": "® Retinal arteriolar αSMA coverage in vehicle or AngII-treated mice. Green arrowheads denote stenosis, blue arrowheads label αSMA-negative gap. (S) αSMA-negative gaps in arterioles per retina (Jag1+/+ ctrl n=4, Jag1+/+ AngII n=4, Jag1Ndr/Ndr ctrl n=3-5, Jag1Ndr/Ndr AngII n=5, two-way ANOVA, with Sidak's multiple comparison. Interaction P = 0.1054, treatment P=0.0815; Genotype P=0.0747. Ší'ák's multiple comparisons test: AngII treated Jag1+/+ vs AngII treated Jag1Ndr/Ndr *P= 0.0315).).",
    "diseases": "stenosis"
  },
  {
    "caption": "A Representative retinographs from a healthy adult, patient with CADASIL, healthy pediatric individual, patient with ALGS and patient with BA. Boxed regions and black arrowheads magnify arteriovenous crossing.",
    "diseases": "ALGS, BA, CADASIL"
  },
  {
    "caption": "G-K (G) Arteriovenous crossings per retina (CTRL n=5, ALGS n=3, BA n=4, one-way ANOVA, ns, P=0.0608, Sidak's multiple comparisons ALGS vs. CTRL *P=0.0492, ALGS vs. BA ns, P=0.0999). (H) Major arterioles (CTRL n=5, ALGS n=5, BA n=4, one-way ANOVA, **P=0.0026, Sidak's multiple comparisons ALGS vs. CTRL **P=0.0039, ALGS vs. BA ns, P=0.9799) and (I) venules (CTRL n=5, ALGS n=5, BA n=4, one-way ANOVA, ***P=0.0008, Sidak's multiple comparisons ALGS vs. CTRL **P=0.0011, ALGS vs. BA ns, P>0.9999). (J) Arterial (CTRL n=5, ALGS n=5, BA n=4, one-way ANOVA, *P=0.0486, Sidak's multiple comparisons ALGS vs. CTRL *P=0.0392, ALGS vs. BA ns, P=0.1204) and (K) venous tortuosity (CTRL n=5, ALGS n=5, BA n=4, one-way ANOVA, **P=0.009, Sidak's multiple comparisons ALGS vs. CTRL **P=0.0076, ALGS vs. BA *P=0.0327).",
    "diseases": "BA, ALGS"
  },
  {
    "caption": "A) Experiments shown for an exemplary group of 8 SLE patients and two healthy individuals. Dose-dependent reactivity of FcγRs IIIA and IIB/C was observed only for SLE patient sera and not for sera from healthy individuals. Each titration represents one donor measured in technical duplicates.",
    "diseases": "SLE"
  },
  {
    "caption": "C-D) Correlation of FcγR activation data from A with (C) patient SLEDAI or (D) conventional SLE disease markers (α-dsDNA levels indicated as IU/ml or C3d concentrations indicated as mg/L). Left panel: FcγRIIIA; right panel: FcγRIIB/C. FcγR activation from a dose-response curve as in A was calculated as area under curve (AUC) for each SLE patient represented by individual dots. AUC from SLE patients are expressed as fold change compared to the healthy control mean (n=4). SLE patients with α-dsDNA levels below 50 IU/ml and C3d values below 6 mg/L were excluded. One-tailed Spearman's. Dotted lines show 95% confidence bands.",
    "diseases": "SLE"
  },
  {
    "caption": "(B-B'). Cataract detection revealed abnormal lens reflection in psmc3 morpholino (MO)-mediated knockdown but not in controls (uninj, ctrl-mo). Similarly, abnormal lens reflection was also observed in embryos injected with sgRNA + Cas9 but not in sgRNA injected embryos without Cas9 (sgRNA2). Co-injection of wt psmc3 mRNA with either psmc3-mo or sgRNA2 + Cas9 reduced the number of embryos presenting abnormal lens reflection. Scale bar = 50 µm. (B') Quantification of embryos with abnormal lens reflection.",
    "diseases": "Cataract"
  },
  {
    "caption": "(A Bulk RNA-seq analysis of DE genes (DEG) significantly suppressed (FDR < 0.05; generalized linear model extraction (GLM) by edgeR) in proliferating RM1 bone-derived (BD) cells compared to parental RM1 and lung metastases. Tumor-intrinsic type I IFN signaling is suppressed in proliferating bone lesions (n = 1) compared to parental RM1 (n = 2) cells as shown by (A) camera analysis of Hallmark gene set responses associated with bone metastasis (bar length is the -log10FDR; false discovery rate). Color indicates mean log2fold change (FC) of all genes in gene set. Bar width is relative gene set size. Dashed line shows FDR = 0.05; (B) barcode plot showing enrichment of the Hallmark IFN-α response gene set in genes suppressed in bone metastases, using the signed log-likelihood ratio statistic (EdgeR). Bars indicate value of the statistic for each gene in the gene set;",
    "diseases": "bone lesions"
  },
  {
    "caption": "(A) Quantification of AURKB transcripts in non-IPF lung derived resident-fibroblasts treated with indicated mitogens for 16hrs. *P < 0.05, ***P < 0.0005, and ****P < 0.00005, 1-way ANOVA, (n=4).",
    "diseases": "IPF"
  },
  {
    "caption": "(B) Quantification of AURKB gene transcripts in isolated fibroblasts from non-IPF and IPF lung stromal cell cultures. **P < 0.005, unpaired t-test, (n=6).",
    "diseases": "IPF"
  },
  {
    "caption": "(C) IPF and non-IPF lung sections were immunostained using AURKB antibody (n=4). Representative images were obtained at 40X magnification. Scale bar: 40µm. Dotted area: black; myofibroblastic core, blue; active fibrotic front. Arrows indicate AURKB positive cells.",
    "diseases": "IPF"
  },
  {
    "caption": "(D) Immunoblots of Aurkb and Aurka in total lung lysates of normal (CCSP/-) and fibrotic (CCSP/TGFα) mice fed with Dox for 6wks. Quantification was performed using phosphor imager software and normalization was done using loading control GAPDH. *P < 0.05, unpaired t-test, (n=4).",
    "diseases": "fibrotic"
  },
  {
    "caption": "(A) Human IPF lung fibroblasts were transiently transfected with control or WT1 siRNA for 72hrs and AURKB transcripts were quantified. ****P < 0.00005, unpaired t-test, (n=4).",
    "diseases": "IPF"
  },
  {
    "caption": "(C) Immunoblot analysis of AURKB and WT1 in the lysates of non-IPF fibroblasts transduced with control or WT1-adenoviral particles for 72hrs. **P < 0.005, unpaired t-test, (n=3).",
    "diseases": "IPF"
  },
  {
    "caption": "(D) Quantification of AURKB transcripts in primary fibroblasts from IPF lung treated with either control or WT1 siRNA and stimulated with media or TGFα (100ng/mL) for 16hrs. ****P < 0.00005, unpaired t-test, (n=4).",
    "diseases": "IPF"
  },
  {
    "caption": "(E) Proliferation was measured in primary lung resident fibroblast isolated from either IPF lung or TGFα mice and treated with either control or AURKB siRNA. ****P < 0.00005, unpaired t-test, (n=9-11).",
    "diseases": "IPF"
  },
  {
    "caption": "(G) Quantification of CCNA2 and PLK1 transcripts in human IPF fibroblasts transiently transfected with control or AURKB siRNA for 72hrs. **P < 0.005, ***P < 0.0005, unpaired t-test, (n=3).",
    "diseases": "IPF"
  },
  {
    "caption": "(I) Quantification of apoptotic cells using Incucyte ZOOM (Caspase-3/7- positive cells) in lung-resident fibroblasts isolated from IPF and TGFα mice on Dox for 6 wks and treated with control or AURKB siRNA for 72h. **P < 0.005, ****P < 0.00005, 2-way ANOVA, (n=4).",
    "diseases": "IPF"
  },
  {
    "caption": "(J) Quantification of BAK, BAX and FAS gene transcripts in human IPF lung resident fibroblasts treated with either control or AURKB siRNA for 72hrs. **P < 0.005, ***P < 0.0005, unpaired t-test, (n=3).",
    "diseases": "IPF"
  },
  {
    "caption": "(A) Proliferation was assessed using BrdU incorporation assay in human IPF fibroblasts treated with indicated doses of barasertib for total of 48hrs. ****P < 0.00005, 1-way ANOVA, (n=9-11).",
    "diseases": "IPF"
  },
  {
    "caption": "(E) Quantification of apoptotic cells using Incucyte ZOOM (Caspase-3/7- positive cells) in resident fibroblasts isolated from IPF lung stromal cultures and treated with vehicle or 5µM Barasertib. ****P < 0.00005, 2-way ANOVA, (n=4).",
    "diseases": "IPF"
  },
  {
    "caption": "F. Representative pictures from tail wounds of 1-year-old Fbln7 WT and KO mice. G. Measurements of wound area over time in Fbln7 WT (N=5) and KO (N=7) mice.",
    "diseases": "wound, wounds"
  },
  {
    "caption": "H-J. Hematoxylin and eosin staining from tail sections of wounded Fbln7 WT vs. KO mice (H) and quantitation of the re-epithelialization length (I) and thickness at the healing front (J). Scale bar: 200 μm. N=3 WT and 5 KO mice.",
    "diseases": "wounded"
  },
  {
    "caption": "(C) Immunoblots  analysis of TOMM34  expression in parental and metformin  adaptive HCC   cells.",
    "diseases": "HCC"
  },
  {
    "caption": "The effects of TOMM34  on HCC lung metastasis   in the tail vein injection mouse  model (shTOM: shTOMM34, TOMM34  knockdown cells; Scale bars, (Left) 1000 μm, (Right) 25 μm. (n=5 mice  for each group, Student's t-test). Data information: Data are presented as means ± S.D.",
    "diseases": "HCC"
  },
  {
    "caption": "The effects of TOMM34  on HCC lung metastasis   in the  tail vein injection mouse  model OE-TOM: OE-TOMM34, TOMM34  overexpressed cells). Scale bars, (Left) 1000 μm, (Right) 25 μm. (n=5 mice  for each group, Student's t-test). Data information: Data are presented as means ± S.D.",
    "diseases": "HCC"
  },
  {
    "caption": "(L)  Western blot  analysis showing the effects of TOMM34  on the expression of EMT markers in HCC  cells (shTOM: shTOMM34, TOMM34  knockdown cells; OE-TOM: OE-TOMM34, TOMM34  overexpressed cells).",
    "diseases": "HCC"
  },
  {
    "caption": "(M) The protein expression of TOMM34  in clinical HCC  samples with or without metastasis. Scale bars, (Left) 100 μm, (Right) 25 μm. (n = 33 in metastasis  present group, n = 53 in metastasis  absent group, Student's t-test). Data information: Data are presented as means ± S.D.",
    "diseases": "HCC"
  },
  {
    "caption": "(C) Co-IP  assays indicate the interaction  between endogenous TOMM34  and ATP5B  in Huh7 HCC  cells.",
    "diseases": "HCC"
  },
  {
    "caption": "(H) Tissue immunofluorescence assay showing the co-localization of TOMM34  and ATP5B  at the invasive front of clinical HCC  tissues. Scale bars, 20 μm.",
    "diseases": "HCC"
  },
  {
    "caption": "(I) A positive correlation between TOMM34  and ATP5B  levels in human HCC  samples was shown by representative immunohistochemical  images Scale bars, 50 μm. (n=72).",
    "diseases": "HCC"
  },
  {
    "caption": "(B-C) Western blot showing the expression of indicated proteins in adaptive HCC  cells with or without ATP5B  silencing.",
    "diseases": "HCC"
  },
  {
    "caption": "(D-E) Transwell assays showing the migration  and invasion  of adaptive HCC  cells with or without the silence of ATP5B  (5×104 adaptive Huh7  cells, 1×105 adaptive PLC/PRF/5  cells), Scale bars, 100 μm. (n=3 biological replicates, Two-way ANOVA). Data information: Data are presented as means ± S.D.",
    "diseases": "HCC"
  },
  {
    "caption": "(C-D) Immunoblotting  of EMT markers of HCC  cells treated with or without 200 nM Gboxin  for 24 hours (shTOM: shTOMM34, TOMM34  knockdown cells; OE-TOM: OE-TOMM34, TOMM34  overexpressed cells).",
    "diseases": "HCC"
  },
  {
    "caption": "(E-F) Transwell assay  showing the migration  and invasion  of HCC  cells treated with or without 200 nM Gboxin  for 36 hours (5×104 cells; shTOM: shTOMM34, TOMM34  knockdown cells). Scale bars, 100 μm. (n=3 biological replicates, two-way ANOVA). Data information: Data are presented as means ± S.D.",
    "diseases": "HCC"
  },
  {
    "caption": "(A) Left quadriceps muscle biopsy performed at age 10 months (i-iii) demonstrating a dystrophic process with variation in fiber size (black arrow), increased connective tissue (blue arrow) and rare internalized nuclei (white arrow) on hematoxylin and eosin (H&E) staining (i) and Gömöritrichrome staining (ii) and type 1 fiber atrophy on nicotinamide adenine dinucleotide (NADH) staining (iii). Muscle biopsy in an unaffected (control) individual (iv-vi). Scale bar: 100μm.",
    "diseases": "dystrophic"
  },
  {
    "caption": "(B) Western blot data (n=1) with quantification demonstrated reduced α-Dystroglycan (α-DG) in P1's muscle compared to control. (C) Western blot data with quantification demonstrated reduced α-Dystroglycan in fibroblasts from P1 and P2 compared to control (c), although not to the extent of the reduction observed in fibroblasts from a patient with a confirmed α-dystroglycanopathy (α-DG pt) due to biallelic pathogenic variants in LARGE (n=1).",
    "diseases": "α-DG, α-dystroglycanopathy "
  },
  {
    "caption": "Relative levels of CIP2A-BP were determined by polysome profiling and qRT-PCR in MCF-10A and TNBC cells either mock treated or treated with TGF-β. Relative levels of LINC00665 were determined by qRT-PCR in MCF-10A and TNBC cells either mock treated or treated with TGF-β.",
    "diseases": "TNBC"
  },
  {
    "caption": "Micropeptide CIP2A-BP levels were determined by western blot with anti-CIP2A-BP antibody in MCF-10A and TNBC cells either mock treated or treated with TGF-β.",
    "diseases": "TNBC"
  },
  {
    "caption": "Micropeptide CIP2A-BP levels were detected by western blot with anti-CIP2A-BP antibody in the indicated non-metastatic TNBC tissues (non-metastasis) and metastatic TNBC tissues (metastasis). Micropeptide CIP2A-BP expression in MCF-10A cells was used as the positive control.",
    "diseases": "TNBC"
  },
  {
    "caption": "Kaplan-Meier overall survival curves for TNBC patients with high or low micropeptide CIP2A-BP expression in Suzhou cohort (discovery set, n = 112) and Guangzhou cohort (validation set, n = 105).",
    "diseases": "TNBC"
  },
  {
    "caption": "Migration and invasion of TNBC cells transfected with LINC00665 ORF and control lentiviruses for 48h. Right panel is the quantification of TNBC cells that migrated through the membrane without the Matrigel (upper) and invaded through Matrigel-coated membrane (lower).",
    "diseases": "TNBC"
  },
  {
    "caption": "Migration and invasion of wild-type and CIP2A-BP knockout TNBC cells and CIP2A-BP re-expressed Hs578TKO and MDA-MB-231KO cells. Right panel is the quantification of cells that migrated through the membrane without the Matrigel (upper) and invaded through Matrigel-coated membrane (lower).",
    "diseases": "TNBC"
  },
  {
    "caption": "Wild-type and CIP2A-BP knockout TNBC cells and CIP2A-BP re-expressed Hs578TKO and MDA-MB-231KO were seeded on cell culture inserts for wound-healing assay. The wound edges were photographed at the indicated time points after wounding. Right panel is the quantification of the relative wound healing area.",
    "diseases": "TNBC"
  },
  {
    "caption": "Macroscopic and histological analysis of the lungs of nude mice injected with the indicated Hs578T (G) and MDA-MB-231 cells (H) (1.0×105-106 cells/mouse) via tail vein; lung metastatic nodules were visualized 8 weeks post-transplantation (5 mice per group). Right panel is the quantification of pulmonary metastases.",
    "diseases": "pulmonary metastases"
  },
  {
    "caption": "Immunoblotting analysis of expression of the indicated proteins in TNBC cells cultured with or without TGF-β.",
    "diseases": "TNBC"
  },
  {
    "caption": "Chromatin immunoprecipitation showing Smad4 occupancy at the 4E-BP1 locus in TNBC cells. Co-precipitated DNA was analyzed for amplicons A-E by qPCR. Values represent the enrichment of bound protein fractions relative to input.",
    "diseases": "TNBC"
  },
  {
    "caption": "Regulation of 4E-BP1 expression and binding to eIF4E by TGF-β. TNBC cells were treated with TGF-β and equal amounts of proteins were subjected to immunoprecipitation and/or examined by immunoblotting analysis.",
    "diseases": "TNBC"
  },
  {
    "caption": "Immunoblotting analysis of expression of micropeptide CIP2A-BP and β-actin in TNBC cells cultured with or without TGF-β.",
    "diseases": "TNBC"
  },
  {
    "caption": "Smad4 siRNA and corresponding control transfected TNBC cells were cultured with or without TGF-β. The indicated proteins were determined by Immunoblotting analysis.",
    "diseases": "TNBC"
  },
  {
    "caption": "TNBC cells were pretreated with specific antagonist against Smad3 (SIS3, 3μM) for 1h and then cultured with or without TGF-β. The indicated proteins were determined by immunoblotting analysis.",
    "diseases": "TNBC"
  },
  {
    "caption": "4E-BP1 siRNA and corresponding control transfected TNBC cells were cultured with or without TGF-β. The indicated proteins were determined by immunoblotting analysis.",
    "diseases": "TNBC"
  },
  {
    "caption": "Co-immunoprecipitation assays showed that the interaction between CIP2A and B56γ in TNBC cells was affected by CIP2A-BP expression.",
    "diseases": "TNBC"
  },
  {
    "caption": "The expression levels of the indicated proteins were detected by immunoblotting analysis in CIP2A-BP KO, LINC00665 ORF overexpressed (OE) and respective controls of TNBC cells.",
    "diseases": "TNBC"
  },
  {
    "caption": "PP2A activity was measured using a protein phosphatase assay kit. PP2A activity assay was performed to evaluate PP2A activity in CIP2A-BP KO, LINC00665 ORF overexpressed (OE) and respective control TNBC cells.",
    "diseases": "TNBC"
  },
  {
    "caption": "Immunohistochemistry (IHC) staining of p-AKT from TNBC primary tumor (n = 20) with high or low micropeptide CIP2A-BP expression. Lower panels show higher-magnification images of insets in upper panels. Right panel is the quantification of IHC staining p-AKT.",
    "diseases": "TNBC"
  },
  {
    "caption": "Macroscopic and histological analysis of the lungs of 140 days old MMTV-PyMT mice; lung metastatic nodules were visualized 8 weeks post-transplantation (5 mice per group). Right panel is the quantification of pulmonary metastases.",
    "diseases": "pulmonary metastases"
  },
  {
    "caption": "Immunohistochemistry (IHC) staining of p-AKT of mammary tumors from MMTV-PyMT;CIP2A-BP+/+ or MMTV-PyMT;CIP2A-BP-/- mice. Lower panels show higher-magnification images of insets in upper panels. Right panel is the quantification of IHC staining p-AKT .",
    "diseases": "mammary tumors"
  },
  {
    "caption": "MMTV-PyMT mice were injected with CIP2A-BP or svCIP2A-BP via mammary fat pad. Macroscopic and histological analysis of the lungs of 140 days old MMTV-PyMT mice; lung metastatic nodules were visualized 8 weeks post-transplantation (5 mice per group). Right panel is the quantification of pulmonary metastases.",
    "diseases": "pulmonary metastases"
  },
  {
    "caption": "Representative IHC images of p-AKT of mammary tumors from MMTV-PyMT mice that were injected with CIP2A-BP or svCIP2A-BP via mammary fat pad; Lower panels show higher-magnification images of insets in upper panels. Right panel is the quantification of IHC staining p-AKT.",
    "diseases": "mammary tumors"
  },
  {
    "caption": "Macroscopic and histological analysis of the lungs of nude mice injected with MDA-MB-231 cells and CIP2A-BP or svCIP2A-BP via tail vein; lung metastatic nodules were visualized 8 weeks post-transplantation (5 mice per group). Right panel is the quantification of pulmonary metastases.",
    "diseases": "pulmonary metastases"
  },
  {
    "caption": "A-C.  Human patient samples demonstrate relative differences in the immunoexpression of AR, SDHA, p-CaMKK2/p-AMPK, p-p38, and p-Hsp27 in untreated (n=70), neoadjuvant-treated (NHT) (n=130) and CRPC (n=24) samples. Representative  images (A), dot plots (B), compiled bar graph (C) support the AR-SDH loop where inhibition of AR  axis in NHT samples reduced SDHA levels along with upregulation of p-CaMKK2/p-AMPK/p-p38/p-Hsp27 axis. AR-positive CRPC samples restored SDHA as well as the whole axis. Data information: Data shown as mean ± SEM. Statistical analysis was performed using one-way ANOVA followed by Tukey's test. **, p<0.01; ***, p<0.001 and ****, p<0.0001. Scale bar: 100µm. All the TMAs were constructed from minimum 2 cores per patient. ",
    "diseases": "CRPC"
  },
  {
    "caption": "(B) Fractional area occupied by Oil Red O-stained atheromas in aortic arch, brachiocephalic artery, at intercostal artery ostia, and away from ostia. Each dot is value for one mouse. Mean ± SEM, n = 13-18 mice/group.",
    "diseases": "atheromas"
  },
  {
    "caption": "(E) Fractional area occupied by Oil Red O-stained atheromas in aortic arch, brachiocephalic artery, at intercostal artery ostia, and away from ostia. Each dot is value for one mouse. Mean ± SEM, n = 17 mice/group.",
    "diseases": "atheromas"
  },
  {
    "caption": "Haematoxylin/eosin staining of paraffin sections of Ronin fl/del and ecto-Ronin teratomas.",
    "diseases": "teratomas"
  },
  {
    "caption": "Representative immunohistochemical stainings of serial sections showing reduced ZEB1 and increased E-cadherin in tumor tissues of mice treated with mocetinostat. Scale bar 40 μm, inserts for higher magnifications 10 μm. Squares indicate magnified regions.",
    "diseases": "tumor"
  },
  {
    "caption": "C Overabundance of MIAA  in  LAM plasma. Top panel shows each control and patient  group (number (n) of samples are indicated); bottom panel shows aggregation of related pulmonary  diseases. The asterisks indicate significant differences based on two-sided Mann-Whitney tests (*P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001; top panel, control-LAM P = 0.048, LAM-Langerhans P = 1x10-4, LAM-Sjögren P = 1x10-4, LAM-lupus P = 1x10-3,  LAM-emphysema P = 0.041; bottom panel,  LAM-Langerhans P = 7x10-6 and control-other P = 0.031). Average values are indicated with lilac-colored lines. Comparison of the three groups: Kruskal-Wallis test P = 6x10-4 (top panel) and P = 3x10-5 (bottom panel).",
    "diseases": "lupus, LAM, pulmonary  diseases, emphysema, Sjögren"
  },
  {
    "caption": "E Overabundance of MIAA in LAM patients not treated with rapamycin relative to rapamycin-treated (number (n) of samples are indicated). The asterisk indicates significant difference based on two-sided Mann-Whitney test (P = 0.043). Average values are indicated with lilac-colored lines.",
    "diseases": "LAM"
  },
  {
    "caption": "G Plasma  levels of three other metabolic products derived from monoamine  metabolism and showing significant differences from controls and/or between LAM  and related pulmonary diseases  (individual samples indicated in panel C). The asterisks indicate significant differences based on two-sided Mann-Whitney tests (*P < 0.05, **P < 0.01, and ****P < 0.0001; 4-HPA, control-LAM P = 0.024 and LAM-other P = 0.089; HVA, control-LAM P = 0.008 and LAM-other P = 0.013; and VMA, control-LAM P = 1x10-4 and LAM-other P = 0.10). Average values are indicated with lilac-colored lines. Comparison of the three groups: Kruskal-Wallis test; 4-HPA P = 0.095; HVA P = 0.013; and VMA P = 0.005.",
    "diseases": "LAM, pulmonary diseases"
  },
  {
    "caption": "A Overabundance of  MIAA  in LAM plasma  (UK cohort not treated with rapamycin) relative to healthy  women. The number (n) of individuals in each group is indicated; one of 20 healthy controls did not pass the quality controls for  LC-MS/MS. Asterisk indicates significance using two-sided Mann-Whitney test (P = 0.018). Average values are indicated with lilac-colored lines. B Overabundance of MIAA  in plasma of LAM patients with  AMLs. Asterisk indicates significance using two-sided Mann-Whitney test (P = 0.042). The number (n) of individuals in each group is indicated. Average values are indicated with lilac-colored lines. ",
    "diseases": "AMLs, LAM"
  },
  {
    "caption": "A Representative images of immunohistochemical  positivity of  MAO-A/B in LAM lung  lesions  (top panels, two patients) and lung  tissue from healthy (non-LAM) individuals (bottom panels). In total, seven LAM patients and three healthy controls were analyzed. Brown-stained cells, counter-stained with hematoxylin, are considered positive. Scale bars are shown.",
    "diseases": "LAM"
  },
  {
    "caption": "B Representative images of  immunofluorescence detection of MAO-A/B and αSMA in  LAM lung lesions, nuclei stained with DAPI (merged).",
    "diseases": "LAM"
  },
  {
    "caption": "G Representative images of  immunohistochemical  detection of acrolein in  LAM lung  lesions.",
    "diseases": "LAM"
  },
  {
    "caption": "E Representative images of immunohistochemical  detection of HRH1 in  LAM lung  lesions.",
    "diseases": "LAM"
  },
  {
    "caption": "E Representative images of  hematoxylin-eosin-stained Tsc2-deficient 105K tumors treated with vehicle or monotherapies. Tumors treated with rapamycin tend to have a fascicular growth pattern with bundles of spindle cells and foci of fibrosis, whereas most of the tumors of the other treatment groups showed extensive epithelioid morphology. Scale bars are shown.",
    "diseases": "fibrosis"
  },
  {
    "caption": "F Representative images of hematoxylin-eosin-stained Tsc2-deficient 105K tumors treated with rapamycin alone or rapamycin combinations. With the addition of a second drug to rapamycin, tumors more frequently tended to show glandular differentiation and less atypia. Scale bars are shown.",
    "diseases": "atypia"
  },
  {
    "caption": "AltFUS (arrow) endogenous expression in the motor cortex of three C9orf72 and three sporadic ALS patients (D) (representative image from n=3). The asterisk indicates a protein species detected with the anti-altFUS antibody specifically in the brain.",
    "diseases": "sporadic ALS"
  },
  {
    "caption": "AltFUS (arrow) endogenous expression in iPSC-derived motor neurons of three lines from controls and from ALS patients (E) (representative image from n=3). The asterisk indicates a protein species detected with the anti-altFUS antibody specifically in the brain.",
    "diseases": "ALS"
  },
  {
    "caption": "i3 cortical neurons from a C9orf72-ALS patient and the paired isogenic control were differentiated for 21 days, then were immunostained for neurofilament (red), and SV2 (green) (A) Shown are representative z-stack confocal images of neurites.",
    "diseases": "ALS"
  },
  {
    "caption": "B) i3 cortical neurons from a C9orf72-ALS patient and the paired isogenic control were differentiated for 21 days, then were immunostained for synaptophysin (green) (B). Shown are representative z-stack confocal images of neurites.",
    "diseases": "ALS"
  },
  {
    "caption": "E) mRNA was Trizol extracted from 3 independent wells of C9-ALS and isogenic i3 cortical neurons. RNA was converted to cDNA using the Superscript First-strand kit, and q-PCR was performed using PowerUp SYBR Green. Measurements were normalized to the housekeeping gene GAPDH and then to isogenic levels. Analysis was performed using the ΔΔCT method. 2ΔΔCT ± SE, is presented. Unpaired t-test, **p < 0.01.",
    "diseases": "ALS"
  },
  {
    "caption": "F) Whole cell lysates were generated from 3 independent wells of C9-ALS and isogenic i3 cortical neurons differentiated for 21 days. Lysates were immunoblotted for SV2, and normalized to total protein loading. Quantification band intensities revealed a significant decrease in SV2 protein levels in the C9orf72 lines compared with the isogenic. Data presented as mean ± SEM. Unpaired t-test, *p < 0.05.",
    "diseases": "ALS"
  },
  {
    "caption": "(a) Haematoxylin and eosin (H & E) staining of kidneys from control (Flcnflox/flox), Flcn KO, Flcn/Tfeb DKO, Flcn/Tfe3 DKO, Flcn/Tfe3 DKO; Tfeb-HET and Flcn KO; Tfeb-HET mice at p18 (replicated three times). Scale bars, 3 mm (upper panels). Boxed areas are magnified in the bottom panels. Arrowhead indicates tubular papillary atypical hyperplasia. Scale bars, 100 μm (lower panels).",
    "diseases": "tubular papillary atypical hyperplasia"
  },
  {
    "caption": "(a) Abdominal imaging, H&E staining and immunohistochemical staining for TFE3, TFEB, GPNMB and NPC1 in Hybrid RCC tumors from BHD patients 1 and 2, BHD Chromophobe RCC tumor (patient 3), BHD papillary/clear RCC (patients 4, 5 and 6), a BHD patient with clear/eosinophilic/papillary RCC (patient 7, origin of the BHD RCC cell line UOK257) and an area of normal kidney from the BHD patient 3. In the row 1-7, the arrows point to the tumor in the right or left kidney of BHD patients 1-7; in the bottom row, the arrow points to uninvolved, normal kidney in BHD patient 3.",
    "diseases": "BHD, clear, clear RCC, papillary RCC, RCC"
  },
  {
    "caption": "(d) Correlation between transcriptomic and proteomic analysis of BHD-associated kidney tumor samples (n=7 biological replicates) relative to control kidney tissues (n=5 biological replicates).",
    "diseases": "BHD"
  },
  {
    "caption": "IIA1.6 B lymphoma cells were stimulated with BCR-ligand- (IgM) or BCR-ligand+ (IgG) beads for 60 min, fixed and stained for F-actin (top) and α-tubulin (bottom). Scale bar: 3 µm.",
    "diseases": "B lymphoma"
  },
  {
    "caption": "IIA1.6 B lymphoma cells were fixed and immuno-stained for F-actin (red) and microtubules (green). Images show the projection of maximal intensity of three confocal slices spaced by 0.5 µm apart from the centrosome. Scale bars: 2 µm (0.5 µm in the zoomed insets).",
    "diseases": "B lymphoma"
  },
  {
    "caption": "IIA1.6 B lymphoma cells were treated 45 min with indicated inhibitors (CK666 at 25 µM, SMIFH2 at 25µM) or DMSO as control prior to being fixed and stained for α-tubulin (left column) and F-actin (right column). Scale bar: 3 µm.",
    "diseases": "B lymphoma"
  },
  {
    "caption": "IIA1.6 B lymphoma cells were transfected to transiently express centrin1-GFP (red) and EB3-mCherry (green) and video-recorded at the contact site with the glass coverslip (left) and at the centrosome (right). Scale bar: 3 µm.",
    "diseases": "B lymphoma"
  },
  {
    "caption": "IIA1.6 B lymphoma cells were transfected to transiently express centrin1-VCA-GFP (bottom) or centrin1-GFP (top) as control prior to be fixed and stained for α-tubulin (left column) and F-actin (middle column). The GFP signal of centrin1 or centrin1-VCA is shown in the right column to illustrate the proper centrosome targeting. Scale bar: 3 µm.",
    "diseases": "B lymphoma"
  },
  {
    "caption": "IIA1.6 B lymphoma cells were plated for 60 min on poly-L-lysine, fibronectin or ICAM-1 coated cover slides prior to be fixed and stained for F-actin (top line) and α-tubulin (bottom line). Scale bar: 3 µm.",
    "diseases": "B lymphoma"
  },
  {
    "caption": "Quantification of the area occupied by B lymphoma cells on the substrate (top left), F-actin content at the centrosome (top right) polymerized tubulin at the centrosome (bottom left) and in the entire cell (bottom right) for the three conditions of cell adhesion described in (D). Measurements came from 3 independent experiments with more than 80 analyzed cells in each. Errors bars represent standard deviations. F-actin and microtubule contents were compared using Mann-Whitney test, and variations of the cell area were compared using unpaired t-test.",
    "diseases": "B lymphoma"
  },
  {
    "caption": "A-C) A) Bilateral bowing deformity and short femora and tibiae with atypical growth plates, and B) short and bowed humerus at age 4.5 years, C) vertebral fractures (arrows) on lateral imaging at age 9 years.",
    "diseases": "Bilateral bowing deformity, vertebral fractures"
  },
  {
    "caption": "(A-H) Transiliac bone sample of the patient at age of 10 years viewed in the light microscope. A-E) Goldner stained sections, F-H): Giemsa stained sections. A) Overview of the entire sample shows scarcity of mineralized bone (stained in green). Black arrowheads point towards the very thin cortices (right side, only a fractured cortex is visible). B) Trabecular features are mostly small and isolated. C) Black arrows point toward three bone resorbing osteoclasts leading to the disconnection of two trabecular features. D) Cortical bone viewed under polarized light: white arrows point towards collagen fibers arranged in a parallel concentric way around osteon next to a region where collagen fibers are randomly arranged, as typical for woven bone (white asterisk). E) Detail from cortical bone showing roundish cells on the periosteal side surrounded by a mainly red, thus, poorly mineralized matrix (white stars). F), G) Details from the cortex in Giemsa stained section show areas with unmineralized cartilage (black arrows) and mineralized woven bone and or mineralized cartilage (dark purple, black asterisks), mineralized bone is stained pink. H) Trabecular feature with mineralized cartilage inclusion stained deep purple (arrowhead), surrounded by bone tissue stained pink. Note many osteoblasts on the trabecular surface (black arrows)",
    "diseases": "fractured"
  },
  {
    "caption": "D. CD4+ and  CD8+ T cells play a role in mediating   cancer-shrinking effect of Carfilzomib. Lung-cancer-bearing TD mice were treated by  saline, Carfilzomib, anti-mouse CD4  antibody (ip.), anti-mouse CD8 antibody (ip.), or Carfilzomib plus anti-mouse CD4/8 antibody. CT scanning was performed after two-week treatment. E. Representative images of H&E staining of the treated lung  tissues.  Expression of  Ki-67 in lung  tissues was detected by immunohistochemistry method. F. Carfilzomib synergized with PD1 antibody in shrinking lung cancers. Lung cancer bearing TD mice  were treated by  saline, anti-PD1 antibody (ip), Carfilzomib, or Carfilzomib plus anti-PD1 (ip). CT scanning  was performed after two-week treatment. G. Representative images of H&E staining of the lung tissues. Expression  of Ki-67 in lung tissue was detected by immunohistochemistry method.",
    "diseases": "Lung cancer, lung cancers, Lung-cancer"
  },
  {
    "caption": "(B) Analysis from the Mitelman database for the fraction of human solid tumors that have lost (top) or gained (bottom) individual chromosomes, that have modal chromosome number >2N or ~2N (top, p<0.0001 for chromosome 1-22, X and p<0.05 for chromosome Y; bottom, p<0.0001 for all chromosomes).",
    "diseases": "tumors"
  },
  {
    "caption": "(C) Analysis from the Mitelman database for the fraction of human solid tumors that have lost or gained any chromosome, that have modal chromosome number >2N or ~2N (p<0.0001 for both modal number >2N and ~2N).",
    "diseases": "tumors"
  },
  {
    "caption": "(C) Number of γH2AX positive cells in formalin fixed ICL and control tumor sections by immunofluorescence staining and quantification (Scale bars denote 20μm, p<0.0001 for Ch10 and p<0.05 for Ch14).",
    "diseases": "tumor"
  },
  {
    "caption": "A. Representative pictures of comet assays performed under alkaline conditions in DIS3  WT MM  cell lines  MM.1S  and RPMI-8226 (RPMI), and in DIS3  mutated MM  cell lines PCM6  and OPM2, untreated (UNTR) or treated with RNase H (RNase H). Tail  moments analysis was performed using Casplab software, error bars indicate s.e.m. Plots represent three biological replicates, with 150 cells for each cell line. **** = p < 0.0001 ns= not statistically significant, two-way ANOVA, scale bar is 20 µm.",
    "diseases": "MM"
  },
  {
    "caption": "(F) Violin plot of the number of non-synonymous (NS) mutation load comparison between DIS3  mutant versus DIS3 WT performed on the entire CoMMpass dataset, including 853 MM patients, 88 presenting DIS3  mutations (all samples) and on the CoMMpass dataset, stratified according to the intensity of the IFN   responsiveness (clusters C1, C2, C3). Wilcoxon rank-sum test was used for comparison between DIS3  mutant vs WT. **** = p <, ** = p < 0.01, * = p < 0.05. Black color dots represent the median in each group.",
    "diseases": "MM"
  },
  {
    "caption": " I and J H&E stained histological sections of bronchi (I) and lung parenchyma with alveolar epithelial cells (AEC, J). Arrowheads: areas of suppurative bronchitis/bronchiolitis; arrows: interstitial pneumonia, necrosis of AEC (bar: (I) 100 µm; (J) 50 µm). ",
    "diseases": "bronchiolitis, bronchitis, necrosis, interstitial pneumonia"
  },
  {
    "caption": "Confocal micrographs show CK7 (green) and vimentin (red) in patient-derived HGSC cells cultured in 3D collagen for 7 d. Scale bars: 50 μm.",
    "diseases": "HGSC"
  },
  {
    "caption": "Confocal micrographs of EphA2 (red) in HGSC cells cultured in 3D collagen for 7 d and treated for 72 h with 10 μM cisplatin (5 μM for OCKI_p01). The intensity of EphA2 is comparable only between mock and treatment conditions for each patient. Scale bars: 20 μm.",
    "diseases": "HGSC"
  },
  {
    "caption": "Quantitative assessment of EphA2 (total and phosphorylated) and pS897/pY588 ratio in early passage patient-derived HGSC cultures treated with 0-20 μM cisplatin for 72 h (see immunoblots in Appendix Fig S2A). N = 6 patients, pooled.",
    "diseases": "HGSC"
  },
  {
    "caption": "Charts show OC cell viability after 72 h treatment with 0-20 μM cisplatin and 10 μM BI-D1870",
    "diseases": "OC"
  },
  {
    "caption": "Charts show OC cell viability after 72 h treatment with 0-20 μM cisplatin and 50 μM LJH685",
    "diseases": "OC"
  },
  {
    "caption": "RSK and EphA2 (total and phosphorylated) in OC cells treated with 10 µM cisplatin and 25 µM LJH685 as indicated for 72 h.",
    "diseases": "OC"
  },
  {
    "caption": "Immunoblot images (A) and quantification (B) show GPRC5A 46/41 kDa ratios in OC cells treated with 0-10 µM cisplatin and with 25 µM LJH685 alone or as a combination for 72 h. The ratio in mock cells was set to 1. N = 4.",
    "diseases": "OC"
  },
  {
    "caption": "Representative confocal micrographs show EphA2 (red), RSK (green: top) and GPRC5A (green: bottom) in frozen sections of HGSC patient tumors. S indicates the stroma. Scale bars: 50 μm.",
    "diseases": "HGSC"
  },
  {
    "caption": "GPRC5A in earlier (top) and later passage (bottom) HGSC cells. See normalized GPRC5A relative to OCKI_p01 below the immunoblot images.",
    "diseases": "HGSC"
  },
  {
    "caption": "Charts illustrate EphA2-pS897 inhibition (circles) and EphA2-pY588 increase (squares) by 10 µM BI-D1870 alone (unbroken line) or in combination with 0-10 µM cisplatin (dotted line) in the GPRC5Ahigh HGSC cells. See Appendix S7B for immunoblots.",
    "diseases": "HGSC"
  },
  {
    "caption": "Representative immunostainings for GPRC5A scoring in HGSC primary and metastatic tumors. For maximum intensity scores an optical 4-point scale (0: negative, 1: mild, 2: moderate, 3: high) was used. For survival analyses a 2-point scale (low: scores 0-2, high: score 3) was used. Scale bars: 200 μm.",
    "diseases": "HGSC"
  },
  {
    "caption": "XBP-1S expression was determined by IHC in two different cohorts of human prostatectomy samples.Representative pictures of benign and tumor samples.",
    "diseases": "tumor"
  },
  {
    "caption": "Tissue microarrays (Wang et al, 2010) containing 25 benign and 283 tumor samples were stained with a XBP-1S specific antiserum and scored by a pathologist. The P-value indicates the difference between XBP-1S staining (strong and moderate) in normal vs cancer cells using Mann-Whitney test.",
    "diseases": "tumor"
  },
  {
    "caption": " (C) Histological analysis of H&E-stained sections of the kidneys of age-matched healthy control mice or sick Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras as indicated, showing from left to right, shrunken scarred kidney, segmental chronic tubulo-interstitial disease, accumulation of cellular debris and amorphous material within the collecting ducts of the papilla. The higher magnification shows tubular epithelial degeneration, apoptosis and segmental secondary glomerular sclerosis. Pictures are representative of at least 5 mice for each genotype and treatment. ",
    "diseases": "chronic tubulo-interstitial disease, glomerular sclerosis"
  },
  {
    "caption": "(S) BM12/SJL mice  (recipient, R) were adoptively transferred with CD4+ T cells from WT and Cpt1a-KO lean  or obese mice  (donors, D) to induce inflammation. The anti-nuclear  antibody (ANA) in serum  (top, scale bar: 50 μm) and the kidney IgG  deposition (bottom, scale bar: 50 μm) were visualized using immunofluorescence  (n = 4 or 5, biological replicates). Data are presented as Immunofluorescent  images (left) and quantification bar graphs (right). Data information: All data are representative of at least 3 individual experiments. Statistics, two-tailed Student's t test; ns: not significant, *p < 0.5, **p < 0.01, ***p < 0.001. Error bars represent SD.",
    "diseases": "inflammation"
  },
  {
    "caption": "(J-L) BM12/SJL mice  (recipient, R) were adoptively transferred with  CD4+ T cells from WT and Goliath-KO lean  or obese mice  (donors, D) to induce inflammation. The anti-dsDNA, anti-ssDNA  and anti-histone IgG  or IgM  in serum  were examined by ELISA (J). ANA in serum  (top, scale bar: 50 μm) and the kidney IgG  deposition (bottom, scale bar: 50 μm) were visualized using immunofluorescence  (n = 3, biological replicates). Data are presented as Immunofluorescent  images (K) and quantification bar graphs (L). Data information: All data are representative of at least 3 individual experiments. Statistics, two-tailed Student's t test; ns: not significant, *p < 0.5, **p < 0.01, ***p < 0.001. Error bars represent SD.",
    "diseases": "inflammation"
  },
  {
    "caption": "Human FXS-patient derived fibroblasts (FXS-1, FXS-2) and control human fibroblasts were synchronized in early G1 by Monastrol release and analysed by Western blot (A)",
    "diseases": "FXS"
  },
  {
    "caption": "Human FXS-patient derived fibroblasts (FXS-1, FXS-2) and control human fibroblasts were synchronized in early G1 by Monastrol release and analysed by immunofluorescence microscopy Examples of Nup localization defects are shown in (B)",
    "diseases": "FXS"
  },
  {
    "caption": "Human FXS-patient derived fibroblasts (FXS-1, FXS-2) and control human fibroblasts were synchronized in early G1 by Monastrol release and analysed by immunofluorescence microscopy The percentage of cells with cytoplasmic Nup granules was quantified in (C), 283 cells were analysed (mean ±SD, ***P < 0.001; N = 3).",
    "diseases": "FXS"
  },
  {
    "caption": "Human FXS-patient derived fibroblasts (FXS-1, FXS-2) and control human fibroblasts were synchronized in early G1 by Monastrol release and analysed by immunofluorescence microscopy examples of nuclear architecture defects are shown in (D).",
    "diseases": "FXS"
  },
  {
    "caption": "Human induced pluripotent stem cells (iPSCs) derived from a FXS patient (FXS-iPSC) and the isogenic rescue cells (C1_2-iPSC) were analysed by immunofluorescence microscopy",
    "diseases": "FXS"
  },
  {
    "caption": "Human induced pluripotent stem cells (iPSCs) derived from a FXS patient (FXS-iPSC) and the isogenic rescue cells (C1_2-iPSC) were analysed by immunofluorescence microscopy The percentage of cells with cytoplasmic Nup133 granules was quantified in (F), 5500 cells were analysed (mean ±SD, **P < 0.01; N = 3).",
    "diseases": "FXS"
  },
  {
    "caption": "Human induced pluripotent stem cells (iPSCs) derived from a FXS patient (FXS-iPSC) and the isogenic rescue cells (C1_2-iPSC) were analysed by immunofluorescence microscopy Examples of co-localization events of re-expressed FMRP and Nup133 are shown in (G).",
    "diseases": "FXS"
  },
  {
    "caption": "Mouse YUMM1.7 melanoma  cells were subcutaneously inoculated into C57BL/6  mice and when tumors reached 100 mm3 mice  were treated with vehicle (Ctrl), Nintedanib/BIBF1120 (BIBF), MAPKi (BRAFi, Vemurafenib  and MEKi, Trametinib) or BRAFi/MEKi plus  BIBF  (n=6). (C) Kaplan-Meier survival  curves of  mice treated with the indicated therapies (n = 6). Log rank (Mantel-Cox) statistical test was used for MAPKi vs MAPKi/BIBF1120. ****P≤0.0001.",
    "diseases": "melanoma"
  },
  {
    "caption": "Mouse YUMM1.7 melanoma  cells were subcutaneously inoculated into C57BL/6 mice and when tumors reached 100 mm3 mice  were treated with vehicle (Ctrl), Nintedanib/BIBF1120 (BIBF), MAPKi (BRAFi, Vemurafenib  and MEKi, Trametinib) or BRAFi/MEKi plus BIBF  (n=6). (F) Quantification of collagen fibers thickness (n = 6 for control, BIBF and  BRAFi/MEKi groups and n = 5 for  BRAFi/MEKi + BIBF group). Two-way ANOVA statistical test was used for statistical analysis of mature collagen fibers thickness quantification. **P≤0.01, ***P≤0.001, ****P≤0.0001. Significance was calculated against the control group. Statistical significance of BIBF vs BIBF + BRAFi/MEKi was also calculated.",
    "diseases": "melanoma"
  },
  {
    "caption": "Mouse YUMM1.7 melanoma  cells were subcutaneously inoculated into C57BL/6  mice  and when tumors reached 100 mm3 mice were treated with vehicle (Ctrl), Nintedanib/BIBF1120 (BIBF), MAPKi (BRAFi, Vemurafenib  and  MEKi,  Trametinib) or  BRAFi/MEKi plus BIBF (n=6). (G) Heatmap showing the differential expression of  ECM  and myofibroblast/CAF  genes in  mice treated with MAPK-targeted therapies with or without  BIBF  compared to control mice (log2 ratio, n = 5).",
    "diseases": "melanoma"
  },
  {
    "caption": "A. Serum  levels of 15-keto-dihydro-PGF2α in  type 2 diabetic patients  without  diabetic retinopathy  (no DR), with non-proliferative diabetic retinopathy (NPDR), and with  proliferative diabetic retinopathy  (PDR) (n=20-24). Data information: n.s. stands for \"not significant.\" Data were analyzed by Kruskal-Wallis test with Dunn's multiple comparisons test (A), Data are represented as mean ± SEM.",
    "diseases": "diabetic retinopathy, DR, PDR, proliferative diabetic retinopathy, non-proliferative diabetic retinopathy, NPDR, type 2 diabetic"
  },
  {
    "caption": "C. Representative images of OIR retinas  from CKO-T and control mice  on postnatal day 17. The green color shows the isolectin B4-stained vessels. The second-row panels are the enlarged images of white boxes from the first-row panels. The third-row images show  neovascular tufts (NV, white) and the fourth-row images show the vaso-obliteration  (VO, white) area. D. Quantitation of oxygen-induced   retinal neovascularization in CKO-T and control mice  (n=12). E. Quantitation of retinal vaso-obliteration in CKO-T and control mice  (n=12). Data information: n.s. stands for \"not significant.\" Data were analyzed by Mann-Whitney test D, E). Scale bars: 500 μm (unmagnified image), 150 μm (magnified image). Data are represented as mean ± SEM.",
    "diseases": "vaso-obliteration, retinal neovascularization"
  },
  {
    "caption": "D-G. Relative expression  levels of enriched ELR+ CXC chemokines in retinal microvascular ECs from patients  with PDR  (n=4) compared with those from normal subjects (n=7) (Gene Expression  Omnibus Database dataset GSE94019). TPM stands for \"Transcripts per kilobase million.\" Data information: n.s. stands for \"not significant.\" Data were analyzed by Mann-Whitney test (D, E, F, G), Data are presented as the mean + SD.",
    "diseases": "PDR"
  },
  {
    "caption": "H. Representative images of oxygen-induced retinal angiogenesis   in Cxcl1-expressing lentivirus-injected CKO mice  on postnatal day 17. Green represents the isolectin B4-stained vessels, the second-row panels display the enlarged images of white boxes in the first-row panels, the third-row images show  neovascular tufts (NV, white), and the fourth-row images show the vaso-obliteration (VO, white) area. I. Quantitation of oxygen-induced retinal neovascularization  in H (n=8). J. Quantitation of retinal vaso-obliteration  in H (n=8). Data information: n.s. stands for \"not significant.\" Data were analyzed by two-way ANOVA with Tukey's multiple comparisons test , I, J). Scale bar: 500 μm (H, unmagnified image), 150 μm (H, magnified image).Data are represented as mean ± SEM.",
    "diseases": "vaso-obliteration, retinal neovascularization"
  },
  {
    "caption": "B. Relative expression  levels of FOS  in  retinal microvascular ECs from patients  with PDR  (n=4) compared with the corresponding expression  levels from normal subjects (n=7) (Gene Expression Omnibus Database dataset GSE94019). TPM stands for \"Transcripts per kilobase million.\" Data information: n.s. stands for \"not significant.\" Data were analyzed by Mann-Whitney test (B, Data in B are expressed as the mean + SD.",
    "diseases": "PDR"
  },
  {
    "caption": "B. Representative images of OIR retinas  in WT and Cxcr2-/- mice  with or without AL8810  treatment. The green color shows the  isolectin B4-stained vessels, the second-row panels display the enlarged images of white boxes in the first-row panels, the third-row images show  neovascular tufts (NV, white), and the fourth-row images show the  vaso-obliteration (VO, white) area. C. Quantitation of oxygen-induced retinal neovascularization  in WT and Cxcr2-/- mice  with or without AL8810  treatment (n=12). D. Quantitation of retinal vaso-obliteration in WT and Cxcr2-/- mice  with or without AL8810  treatment (n=12). Data information: n.s. stands for \"not significant.\" Data were analyzed by two-way ANOVA with Tukey's multiple comparisons test (C, D) Scale bar: 500 μm (unmagnified image), 150 μm (magnified image). Data are represented as mean ± SEM.",
    "diseases": "vaso-obliteration, retinal neovascularization"
  },
  {
    "caption": "A. Overrepresentation of Aβ APRs in amyloid plaques of AD brains (statistics: hypergeometric test with Bonferroni correction) * P ≤0.05, *** P≤0.001, **** P≤0.0001. The original data was taken from Xiong et al and included three biological replicates.",
    "diseases": "AD"
  },
  {
    "caption": "G. Overrepresentation of Aβ APRs in amyloid plaques of nonAD brains.(statistics: hypergeometric test with Bonferroni correction). * P ≤0.05, ** P≤0.01 The original data was taken from Xiong et al and included three biological replicates.",
    "diseases": "AD"
  },
  {
    "caption": "(A) Representative morphologies of smyhc1+/+, smyhc1R673H/+, and smyhc1R673H/R673H larvae at 2 dpf after 24 hour treatment with 0.25% DMSO (control) or 25 μM para-aminoblebbistatin. All larvae treated with para-aminoblebbistatin develop a slight dorsal tail curve and pericardial edema regardless of genotype. All para-aminoblebbistatin-treated smyhc1R673H/+ (n=9) and smyhc1R673H/R673H (n=3) larvae are indistinguishable from smyhc1+/+ unlike the untreated larvae which have markedly curved or distorted body axis. (B) Representative images of smyhc1+/+, smyhc1R673H/+, and smyhc1R673H/R673H larvae at 3dpf after 48 hour treatment with 0.25% DMSO (control) or 25 μM para-aminoblebbistatin. All larvae treated with para-aminoblebbistatin develop a slight dorsal tail curve and pericardial edema regardless of genotype. Para-aminoblebbistatin-treated smyhc1R673H/+ (n=9) and smyhc1R673H/R673H (n=3) larvae are indistinguishable from smyhc1+/+ unlike the untreated larvae which have markedly curved or distorted body axis. ",
    "diseases": "pericardial edema"
  },
  {
    "caption": "G. Bar graph showing the efficiency of attachment to the feeder cells (left) and si6B-mdx-ntES derivation (right). The mdx sick mice tail-tip fibroblasts as nuclear donors. N, total number of embryos analyzed for each condition. Results are from four replicate experiments",
    "diseases": "mdx"
  },
  {
    "caption": "H. Immunostaining images of si6B-mdx-ntES expressed pluripotency markers. Scale bar, 50 μm",
    "diseases": "mdx"
  },
  {
    "caption": "I. The si6B-mdx-ntES possessed multiple-differentiation potential, as shown in embryoid body.\u2028 Scale bar, 100 μm.",
    "diseases": "mdx"
  },
  {
    "caption": "J. An image of a chimeric mouse derived from si6B-mdx-ntES",
    "diseases": "mdx"
  },
  {
    "caption": "Four-week-old male WT (Prom1+/+) and KO (Prom1-/-) mice were fed a high-fat diet for 8 weeks (Diet-Induced Obesity; DIO), and fasted for 4 hours before experiments. (C) DIO WT (Prom1+/+) and KO (Prom1-/-) mice were intraperitoneally injected with glucagon. Blood glucose levels (mg/dL) were measured 0, 15, 30, 60 and 120 minutes after glucagon (100 µg/kg body weight) stimulation (n = 10 mice/ group).",
    "diseases": "Diet-Induced Obesity, DIO"
  },
  {
    "caption": "Four-week-old male WT (Prom1+/+) and KO (Prom1-/-) mice were fed a high-fat diet for 8 weeks (Diet-Induced Obesity; DIO), and fasted for 4 hours before experiments. (D) Levels of p-PKA substrates, p-CREB, CREB, Prom1 and GAPDH were determined by immunoblotting 10 minutes after glucagon (2 mg/kg body weight) stimulation (n = 3 mice/group).",
    "diseases": "Diet-Induced Obesity, DIO"
  },
  {
    "caption": "Four-week-old male WT (Prom1+/+) and KO (Prom1-/-) mice were fed a high-fat diet for 8 weeks (Diet-Induced Obesity; DIO), and fasted for 4 hours before experiments. (E) Glucose disposal rates in DIO WT (Prom1+/+) and KO (Prom1-/-) mice were measured using glucose and insulin tolerance tests (n = 10 mice/group).",
    "diseases": "Diet-Induced Obesity, DIO"
  },
  {
    "caption": "Four-week-old male WT (Prom1+/+) and KO (Prom1-/-) mice were fed a high-fat diet for 8 weeks (Diet-Induced Obesity; DIO), and fasted for 4 hours before experiments. (F) DIO KO (Prom1-/-) mice were infected with an adenovirus harboring LacZ or Prom1 for 24 hours, fasted for 4 hours and intraperitoneally injected with glucagon (100 µg/kg body weight). Blood glucose levels (mg/dL) were measured 0, 15, 30, 60 and 120 minutes after glucagon stimulation (GST). Glucose disposal rates were measured using the pyruvate tolerance test (PTT) (n = 10 mice/group).",
    "diseases": "Diet-Induced Obesity, DIO"
  },
  {
    "caption": "A Histological analysis of RFP+ cells in Siglechdtr/dtr:Ccr2RFP/+ mice. Lumber spinal cord after EAE induction, and hippocampal CA1 2 or 4 days after PBS or DT injection were analyzed. Iba1 immunoreactivity (green) and RFP fluorescence (red) are shown. Images were acquired using the same laser power and sensitivity, and image processing was the same for all RFP signals (red). Scale bar, 50 µm.",
    "diseases": "EAE"
  },
  {
    "caption": "Heat-induced paralysis. Indicated worm strains maintained in compounds at indicated concentrations were exposed to 37 °C over a period of 120 min, and paralysis was scored at indicated time points. Data are means ± SEM (n = 3-4 independent experiments on ten worms per experiment; exact n and p values are shown in Appendix Table S1). (B, D, F, H, J, L) Quantification of paralysis at 20 minutes. Data are means ± SEM (*,#p < 0.05, **,##p < 0.01, ***,###p < 0.001, # as compared to WT, * as compared to mutant by two-way ANOVA and Dunnett's multiple comparison test; n = 3-4 independent experiments on ten worms per experiment; exact n and p values are shown in Appendix Table S1).",
    "diseases": "paralysis"
  },
  {
    "caption": "Quantification of aggregated and total muHTT in the infused striatum of HD mice after 4-week cholesterol infusion by TR-FRET analysis using different antibody pairs. Preliminary assessment of the sustainability of the assay in wt and R6/2 striata (N=5/group) using 4C9-4C9 and 2B7-MW1 antibodies in combination to detect, respectively, muHTT aggregates (J) and total muHTT (K). Quantification of muHTT aggregates (L) and soluble and other muHTT species (M) in the infused striata of R6/2 ACSF and R6/2 chol-high mice. Data in (J-M) are shown as scatterplots with means±standard error. Each dot corresponds to the value obtained from one striatum. Statistics: student's t-test (*p<0.05).",
    "diseases": "HD"
  },
  {
    "caption": "Tumour diameter before and after doxycycline withdrawal in 4 K and 5 KM breast tumours with cMet amplification. 0 indicates when doxycycline was removed. Each colour represents one tumour. Blue and green squares indicate the timeframe between doxycycline withdrawal and the moment in which tumours resumed growth.",
    "diseases": "breast tumours"
  },
  {
    "caption": "D Loss of DNA methylation of the NTN1 and DAPK1 promoters in decitabine treated tumors, compared with PBS treated tumors. >1700 sequences were analyzed per group in 2 independent experiments. **** P< 0.0001, two-way ANOVA and post-hoc Tukey-test.",
    "diseases": "tumors"
  },
  {
    "caption": "E, F After one week of treatment, tumors from xenografted mice were fixed in formalin, embedded in paraffin, and sliced into 4 μm sections. (E) Levels of DAPK1, UNC5B, and netrin-1 were measured in 4 independent tumors per treatment group by immunohistochemistry staining, and expressed as a percentage of total tumor surface normalized against the control PBS-group. Data represented as means ± s.e.m. **** P<0.0001, two-way ANOVA and post-hoc Tukey-test. (F) Representative tumor sections corresponding to MDA-MB-231xenografts, scale bars = 50 μm.",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "A Loss of DNA methylation of the NTN1 and DAPK1 promoters in decitabine treated PDX tumors, compared with the control PBS-group. The percentage of mean DNA methylation of the 11 DAPK1-CpGs was 94% (550 amplicons analyzed), while that of the 7 NTN1-CpGs was 64% (213 amplicons analyzed). Two-way ANOVA and post-hoc Tukey-test.",
    "diseases": "tumors"
  },
  {
    "caption": "B Expression of DAPK1, UNC5B, and NTN1 was measured by Q-RT-PCR in PDX tumors after 7 days of in vivo DAC treatment (0.4 mg/kg). The level of PBGD expression was used as an internal control. Data are expressed as mean ± s.e.m. for at least 3 grafts per group. **** P<0.0001,, two-way ANOVA and post-hoc Tukey-test.",
    "diseases": "tumors"
  },
  {
    "caption": "C Levels of DAPK1, UNC5B, and netrin-1 were measured in at least 3 independent paraffin embedded xenografts per treatment group by immunohistochemistry. Data are expressed as the percentage of the total tumor surface normalized against the median tumor surface of the PBS-group. **** P<0.0001, one-way ANOVA. Error bars = s.e.m.",
    "diseases": "tumor"
  },
  {
    "caption": "B, C) Logarithm of the odds (LOD) scores of cancer associated gene KOs in NCI-N87 and NCI-H358 cells derived from screens with gRNAs (B) and RNPs (C). Bottom panels show distribution of positive (POLR2A) and negative (scrambled) controls for each experiment. LOD score of 3 is highlighted with a dashed line, indicating statistical significance.",
    "diseases": "cancer"
  },
  {
    "caption": "A) Solid phase transfection of nontargeting (scrambled) or PLK1 targeting RNP complexes into human primary lung fibroblasts (HLF-1), primary lung adenocarcinoma cells (LAD-1) or RPE-1TP53 -/- cells. 72 hours post transfection cells were stained with Hoechst and imaged. Boxplots represent values from 3 independent experiments containing 3 technical replicates. For all cell lines, P values (scrambled vs Plk1) < 0.05. In the right panels, representative images for each cell line is shown after RNP transfection targeting PLK1. Arrowheads indicate the cells that are arrested in prometaphase due to Plk1 downregulation. Scale bars indicate 20μm.",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "B) Two human primary lung fibroblasts (HLF) and three primary tumor cell lines derived from patients suffering from either lung squamous carcinoma (LSC) or lung adenocarcinoma (LAD) were transfected with RNP complexes with scrambled or POLR2A targeting gRNA. 5 days post transfection, cell viability in each well was measured. Results are from at least 3 independent experiments containing 3 technical replicates. For all cell lines, P values (scrambled vs POLR2A) < 0.005.",
    "diseases": "LAD, lung adenocarcinoma, LSC, lung squamous carcinoma"
  },
  {
    "caption": "(I) Representative image showing changes in  colon morphology and  length following  DSS-induced colitis with concurrent treatment with  MBELNs. (J) Column graph showing changes in colon length. Data are mean ± SEM from seven biological replicates, **P<0.01 using one-way ANOVA. (",
    "diseases": "colitis"
  },
  {
    "caption": "Mice  were treated by 2% dextran sodium sulfate  (DSS) in drinking water for 7 days. (F) Representative  hematoxylin and eosin (HE)  stained sections of colon  and cecum from COPS8fl/fl and COPS8ΔIEC mice after DSS-indcued colitis (day 9). Scale bar 100μm, representative data from five biological replicates per genotype. (G) Histopathologically scored sections of distal colon; cecum and colon length were analyzed from COPS8fl/fl and COPS8ΔIEC mice after  DSS-indcued colitis (day 7). Data are represented as mean ± SEM from five biological replicates per genotype. **P<0.01 using Student's t-test. (",
    "diseases": "colitis"
  },
  {
    "caption": "Mice  were treated by 2% dextran sodium sulfate (DSS) in drinking water for 7 days. (H) Cytokine levels (interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α)) in the  colon  collected on day 7 in colitis induced COPS8fl/fl and COPS8ΔIEC mice. Data are represented as mean ± SEM from five biological replicates per genotype. *P<0.05, **P<0.01, NS- non-significant using Student's t-test.",
    "diseases": "colitis"
  },
  {
    "caption": "Mice were treated by 2% dextran sodium sulfate (DSS) in drinking water for 7 days. (I) The frequency of CD11b+Ly6C+ and CD11b+Ly6G+ cells in colonic lamina propria  (cLP) of COPS8fl/fl and or COPS8ΔIEC mice  with DSS-induced colitis. The column graph represents percentage of Ly6C+ and Ly6G+ cells, presented as mean ± SEM from three biological replicates per genotype. *P<0.05, NS- non-significant using Student's t-test. (J) Representative  FACS plots and percentage of intracellular staining of  Forkhead box protein P3 (FOXP3), Interferon gamma (IFN-γ) and IL-17A in CD3+CD4+  T cells from  colonic lamina propria  of COPS8fl/fl or COPS8ΔIEC mice with DSS-induced  colitis. The column graph represents percentage of Treg+ and ratio of Th1/Th17 cells, represented as mean ± SEM from three biological replicates per genotype. *P<0.05 using Student's t-test.",
    "diseases": "colitis"
  },
  {
    "caption": "(B) Representative image showing changes in  colon morphology and length following DSS-induced  colitis  with concurrent treatment with MBELNs COPS8fl/fl and COPS8ΔIEC mice. Representative data from seven biological replicates per genotype.",
    "diseases": "colitis"
  },
  {
    "caption": "C57BL/6J mice  were intraarticularly infected with MRSA  (4 × 106 CFU; n = 3-4 per group) and left untreated for 24 hours. K. Paraffin-embedded tissues were sectioned and used to measure inflammation  score and synovial hyperplasia. GLUT1  and MCT4 expression was detected, and the percentage of positively staining  cells were determined (Scale bar: 1,000 μm). Data information: Error bars show means ± SD with individual data points. Two-tailed unpaired t-test analysis was conducted to determine statistical significance (*p<0.05 or **p <0.01; N.D. = not detected).",
    "diseases": "hyperplasia, inflammation"
  },
  {
    "caption": "D and E. Infiltrating  immune cell counts within  synovial fluid  and MRSA synovial fluid  bioburden were quantified. MRSA  bioburden in synovial tissue was quantified. F. Paraffin-embedded tissues were sectioned and measured at 7 and 14 days with respect to inflammation  score, synovial hyperplasia, synovial  cellularity, OARSI score, proteoglycan  depletion, osteophyte   formation, bone  erosion, and bone  formation (Scale bar: 1,000 μm). G and H. Lactate  level in synovial fluid was measured at 14 days and expression  of GLUT1, MCT4, cleaved-IL-1β, and NLRP3  in synovial tissue  was measured with GAPDH  as a loading control. Data information: In vivo experiments were repeated in at least two independent experiments. Error bars show means ± SD with individual data points. One-way ANOVA with Tukey's post hoc analysis was conducted to determine statistical significance (*p<0.05 or **p<0.01; N.D. = not detected; N.S. = not significant).",
    "diseases": "osteophyte, hyperplasia, inflammation"
  },
  {
    "caption": "F. Blood  was collected, and  complete blood counts (CBC) were measured. G. Paraffin-embedded tissues were sectioned and measured with respect to inflammation  score, synovial hyperplasia, OARSI  score, proteoglycan  depletion, osteophyte  formation, bone  erosion, and bone  formation (Scale bar: 1,000 μm). The expression  of GLUT1  was detected and the percentage of positively staining  cells was determined. Data information: In vivo experiments were repeated in at least two independent experiments. Error bars show means ± SD with individual data points. One-way ANOVA with Tukey's post hoc analysis was conducted to determine statistical significance (*p<0.05 or **p<0.01; N.D. = not detected).",
    "diseases": "osteophyte, hyperplasia, inflammation"
  },
  {
    "caption": "C57BL/6J mice  were subcutaneously treated with vancomycin  (30 mg/kg) and rifampin  (20 mg/kg) for 3 days following MRSA  (8 × 106 CFU) infection, followed by systemic  (14 mg/kg) or local  (70 μg/joint) DMF  treatment at 3 days interval for a total of 3 times (n = 6 per group). D. Paraffin-embedded tissues were sectioned and measured with respect to inflammation  score, synovial hyperplasia, synovial  cellularity, proteoglycan  depletion, osteophyte   formation, bone  erosion, and bone  formation (Scale bar: 2,000 or 500 μm). Bone  resorption by osteoclasts  was measured by  tartrate-resistant acid phosphatase  (TRAP) staining  (Scale bar: 2,000 μm). Lameness score was also measured. E. Illustrated summary of DMF's  effect on MRSA-induced septic arthritis. Data information: In vivo experiments were repeated in at least two independent experiments. Error bars show means ± SD with individual data points. One-way ANOVA with Tukey's post hoc analysis was conducted to determine statistical significance (*p < 0.05 or ** p < 0.01 or *** p < 0.001 or **** p < 0.0001; N.D. = not detected).",
    "diseases": "osteophyte, hyperplasia, inflammation, septic arthritis"
  },
  {
    "caption": "C-D: Immunohistochemical  analysis (C) and quantification (D) of STAT5  activation in sections representing normal myocardia  or pathological  cardiac hypertrophy  (n = 3, aortic stenosis; n = 2, idiopathic cardiomyopathy). Phospho-STAT5b staining  intensity was quantified. One dot in the boxplot corresponds to one subject (normal: n = 6, hypertrophic  n = 13; biological replicates). In the boxplot the central band represents the median, the box the interquartile range and whiskers the whole range of values. Unpaired two-tailed T-test was used for statistics. Scale bar 50µm.",
    "diseases": "aortic stenosis, hypertrophic, cardiac hypertrophy, idiopathic cardiomyopathy"
  },
  {
    "caption": "C Unsupervised hierarchical clustering of 12 healthy, 20 AK  and 35 cSCC epidermal  samples based on the methylation  status at undifferentiated and differentiated keratinocyte-specific peaks. Each row represents the average methylation  value of all CpGs  contained in a particular peak.",
    "diseases": "AK, cSCC"
  },
  {
    "caption": "B, C Average  DNA methylation in the 15 chromatin  states defined by ChromHMM in NHEK  for (B) both EpSC  and Keratinocytes  from the sci-MET  single-cell dataset, or for (C) EpSC-like and keratinocyte-like AK/cSCC  from the EPIC dataset. ChromHMM state 1: active promoter; state 2: weak promoter; state 3: inactive/poised promoter; state 4: strong enhancer; state 5: strong enhancer; state 6: weak/poised enhancer; state 7: weak/poised enhancer; state 8: insulator; state 9: transcriptional transition; state 10: transcriptional elongation; state 11:  weak transcription; state 12: polycomb-repressed; state 13: heterochromatin/low signal; state 14: repetitive/copy number variation; state 15: repetitive/copy number variation. AK: actinic keratosis, cSCC:  cutaneous squamous cell carcinoma. Data information: Statistical analyses in B and C were performed using a Wilcoxon Rank Sum test comparing the average methylation values in genomic states 4 and 5 between EpSC  (n= 6) and keratinocytes  (n= 548) (B) or EpSC-like (n= 22) and keratinocyte-like (n= 33) AK/cSCC  samples (C). *P <0.05, **P <0.01, ***P <0.001, ****P<0.0001.",
    "diseases": "cutaneous squamous cell carcinoma, actinic keratosis, AK, cSCC"
  },
  {
    "caption": "C Upper: Heatmaps displaying the unsupervised clustering of 67 AK/cSCC  and healthy controls based on the methylation  patterns of the MIR200C/141 cluster and the MIR205  gene. Lower: Bar plots showing the quantification of the methylation  values at CpGs  located at promoter regions in each cell-of-origin-based subclass. For the MIR200C/141 cluster, probes located at the regulatory CpG  island are depicted with green arrows. For the MIR205  gene, all probes shown in the heatmap are part of the promoter region and were used for quantification. Data information: AK:  actinic keratosis, cSCC: cutaneous squamous cell carcinoma.",
    "diseases": "cutaneous squamous cell carcinoma, actinic keratosis, AK, cSCC"
  },
  {
    "caption": "D Left: Representative images of EpSC-like (n=5) and Keratinocyte-like (n=5) cSCC  tumors stained  for the EMT-marker ZEB2  (green) and the keratinocyte  marker TP63  (red). Nuclei  were counterstained  with DAPI. Images are shown at 40x original magnification. Scale bar, 50 µm. Right: Quantification of ZEB2-positive tumor cells (TP63-positive) in three independent regions per sample. Each dot represents a region with at least 500 tumor cells (TP63-positive) counted. Data information: Statistical analysis in D was performed using an unpaired two-sided t-test (EpSC-like: n= 5 samples, 15 technical replicates; keratinocyte-like: n= 5 samples, 15 technical replicates). Central bar represents the mean and error bars represent the standard deviation. *P <0.05, **P <0.01, ***P <0.001, ****P<0.0001.",
    "diseases": "cSCC"
  },
  {
    "caption": "Optic nerve parameters are unaltered in early EAE (9 days after injection). (A,B) Cryostat sections of the optic nerve from MOG/CFA-injected mice (own lab-made suspension; for comparison with commercial MOG/CFA suspensions, see Appendix Fig. S12) and CFA-injected control mice were stained with anti-Nav antibody (1:50 dilution) to label the node of Ranvier and with anti-CASPR1 antibody (1:500 dilution) to stain the paranodal region. Length of the node of Ranvier and length of the paranodal region were quantified in C) D)",
    "diseases": "EAE"
  },
  {
    "caption": "The amount of CASPR1 protein in the synapse is also altered in the PLP mouse model of multiple sclerosis. Semi-thin sections of PLP/CFA and CFA-injected mice were probed with the indicated antibodies (A, B; see also Appendix Fig. S13)",
    "diseases": "multiple sclerosis"
  },
  {
    "caption": "HSF1 was measured in the mitochondria-enriched fractions of the HD transgenic YAC128 mice (9 months old) or age-matched littermates. (n=5 biological replicates).",
    "diseases": "HD"
  },
  {
    "caption": "mtHSF1 was analyzed in HD patient fibroblasts (GM04208, GM04222, and GM21756) and fibroblasts from healthy individuals. (n = 5 for Con1/ GM04208 and Con2/ GM04222 groups; n = 3 for Con3/ GM21756 group).",
    "diseases": "HD"
  },
  {
    "caption": "Representative images and scatterplot confirming the increased HSF1 (green) translocation to mitochondria (Tom20, red). The data were obtained from 3 independent biological experiments. Con: n=15 organoids; HD: n=14 organoids. Two-tailed unpaired t-test; Means ± SEMs. Images were taken using Structured Illumination Microscopy (SIM).",
    "diseases": "HD"
  },
  {
    "caption": "The subcellular localization of HSF1 in HD striatal organoids was observed by immunoelectron microscopy. The arrows (red) mark HSF1 in mitochondria. The negative control lacked the HSF1 antibody. The scale bar represents 200 nm.",
    "diseases": "HD"
  },
  {
    "caption": "F 1205Lu human melanoma cells or 1205Lu melanoma cells over-expressing Bcl-XL were treated with ABT-737. Concentrations of IL-6 in the supernatants were measured after 48 h (n=5).",
    "diseases": "melanoma"
  },
  {
    "caption": "G 1205Lu human melanoma cells or 1205Lu melanoma cells over-expressing mouse Bcl-XL were treated with various concentrations of ABT-737. To some aliquots the caspase-inhibitor zVAD-fmk (50 μM) was added. Relative numbers of apoptotic cells were determined as in EV 1B after 48 h. Data are means/SEM of at least three independent experiments. (1205Lu, n=4; 1205Lu 5 µM ABT-737, n=3; 1205Lu/Bcl-XL and 1205Lu + zVAD, n=3).",
    "diseases": "melanoma"
  },
  {
    "caption": "qRT-PCR  was performed at 3 days post-tamoxifen  to analyze Fancd2  expression in human SETD1A-expressing Setd1afl/fl;CreER MLL-AF9 leukemia   cells. qRT-PCR  with 3 biological replicates was performed. Data information: data are presented as mean ± SD. **P ≤ 0.01, *P ≤ 0.05 (Student's t-test).",
    "diseases": "leukemia"
  },
  {
    "caption": "Relative expression of Mlh1  in SETD1A  rescued MLL-AF9 leukemia  cells. qRT-PCR with 3 biological replicates was performed. Data information: data are presented as mean ± SD. **P ≤ 0.01, *P ≤ 0.05 (Student's t-test for (D)",
    "diseases": "leukemia"
  },
  {
    "caption": "Survival  of recipient mice  harboring SETD1A  mutant-expressing  leukemia  cells  after transplantation  (TX) was plotted (n = 5 / group). Data information: **P ≤ 0.01, *P ≤ 0.05  Kaplan-Meier for (F)).",
    "diseases": "leukemia"
  },
  {
    "caption": "F. MOLM-13 leukemia  cells were examined by  ChIP-seq  analyses against HA-tagged SETD1A, BuGZ, BUB3, H3K4me3 and H3K4me1. Heatmaps of SETD1A(+)/BuGZ(+) regions (upper) and SETD1A(-)/BuGZ(+) regions (lower) are shown.",
    "diseases": "leukemia"
  },
  {
    "caption": "Relative expression  levels of Bugz  were analyzed in Bugz  shRNA-expressing mouse MLL-AF9 leukemia  cells at day 3 post-treatment, respectively. Data from 3 biological replicates are shown. Data information: data are presented as mean ± SD. **P ≤ 0.01 (Student's t-test",
    "diseases": "leukemia"
  },
  {
    "caption": "Survival  of recipient mice  harboring dox-inducible shRNA-expressing leukemia  cells was plotted (n = 8-10 / group). Data information: **P ≤ 0.01  Kaplan-Meier  for (H)).",
    "diseases": "leukemia"
  },
  {
    "caption": "Images are shown of representative karyotypes  in control, Bugz  and Bub3  shRNA-expressing leukemia  cells. Asterisks in images indicate the trisomy 15 in all cells analyzed. Red arrows indicate chromosomal aneuploidies. Representative images of sister-chromatid  separation or aneuploidy  in Bub3  shRNAs are shown in lower panels.",
    "diseases": "trisomy 15, aneuploidies, aneuploidy, leukemia"
  },
  {
    "caption": "SGC-expressing Setd1afl/fl;CreER MLL-AF9 leukemia  cells were treated with tamoxifen, and RNA-seq  analysis was performed with sorted cells. Data are shown as log2 fold change over tamoxifen  non-treated GFP-expressing control.",
    "diseases": "leukemia"
  },
  {
    "caption": "A, B Intracellular NAD levels and NAD/NADH ratio in DC and age-matched healthy control fibroblasts. All values are presented as mean ± SD of four and eight replicates in A and B, respectively. Student's t test was performed on DC cells vs controls.",
    "diseases": "DC"
  },
  {
    "caption": "Immunoblots of the expression of NAD synthesis and consuming proteins, and their activities in DC and control cells. Protein levels are normalized to GAPDH.",
    "diseases": "DC"
  },
  {
    "caption": "E Immunoblots of the expression of NAD synthesis and consuming proteins Quantification values are presented as mean ± SD of four controls versus five DC samples as shown in D. Student's t test was performed on DC cells vs controls. Con: control fibroblasts.",
    "diseases": "DC"
  },
  {
    "caption": "F Effects of NR and NAM supplementation (24 hours) on the NAD levels in DC fibroblasts. All values are presented as mean ± SD of four replicates. One-Way ANOVA was performed on DC cells in indicated conditions.",
    "diseases": "DC"
  },
  {
    "caption": "Quantitative RT-PCR and immunoblots of the expression of CD38 and SARM1 in DC and age-matched health control fibroblasts. All values are presented as mean ± SD of three replicates in quantitative RT-PCR. Protein levels are normalized to GAPDH, and mean (± SD) quantification values of 4 controls vs 5 DC samples are shown. Student's t test was performed on DC cells vs controls. Irrelevant intervening lanes have been removed for clarity (full blots are available online as Source Data).",
    "diseases": "DC"
  },
  {
    "caption": "Immunoblots and quantification of indicated proteins in DC fibroblasts treated with DMSO and with 2 μM ATM inhibitor, KU-55933 for 48 hours. Mean (± SD) quantification values of three DC lines with and without ATMi treatment are shown. P values on the basis of Student's t test.",
    "diseases": "DC"
  },
  {
    "caption": "The efficacy of CD38 shRNA (sh-1 and sh-2) was verified by quantitative RT-PCR in DC fibroblasts and by RT-PCR and immunoblots in A549 cells. The relative CD38 mRNA values in the CD38 knockdown cells were normalized to the scrambled shRNA. All values are presented as mean ± SD of three replicates. Student's t test was performed on DC and A549 cells in indicated conditions.",
    "diseases": "DC"
  },
  {
    "caption": "Intracellular NAD levels in the scramble and CD38 knockdown DC fibroblasts. The CD38 knockdown DC fibroblasts were treated with the PARP1 inhibitor Olaparib (400nM) and the SIRT1 inhibitor EX 527 (1 μM) for 24 hours. Data are representative four replicates. All values are presented as mean ± SD of four replicates. One-way ANOVA was performed on DC cells in indicated conditions.",
    "diseases": "DC"
  },
  {
    "caption": "immunoblots of the expression of indicated proteins in the scramble and CD38 knockdown DC fibroblasts. The CD38 knockdown DC fibroblasts were treated with the PARP1 inhibitor Olaparib (400nM) and the SIRT1 inhibitor EX 527 (1 μM) for 24 hours. Data are representative four replicates. All values are presented as mean ± SD of four replicates. One-way ANOVA was performed on DC cells in indicated conditions.",
    "diseases": "DC"
  },
  {
    "caption": "A Representative immunoblots of the expression of PGC1-1α in DC cells treated with vehicle or 3 mM NR. Quantification of the indicated proteins is from three immunoblots.",
    "diseases": "DC"
  },
  {
    "caption": "B-D Cellular and mitochondrial ROS in DC and age-matched healthy control cells supplemented with vehicle and NR were measured by flow cytometry from three replicates.",
    "diseases": "DC"
  },
  {
    "caption": "Cellular and mitochondrial ROS in DC and age-matched healthy control cells in the scramble and CD38 knockdown DC cells (D) were measured by flow cytometry from three replicates.",
    "diseases": "DC"
  },
  {
    "caption": "E Representative images captured by transmission electron microscopy of DC1 cells treated with vehicle or NR. White arrows: mitochondria. Yellow arrow: autophagosome-like structures with engulfed mitochondria. Enlarged image within white frame is shown. F-H Quantifications of percentage of damaged mitochondria per cell (F), mitochondrial length (G), and mitochondrial diameter (H). A minimum of 200 mitochondria counted per group.",
    "diseases": "DC"
  },
  {
    "caption": "Representative images of mitophagy showing co-localization between the mitophagy dye (red) and the lysosome dye (green) in DC and control fibroblasts treated with vehicle or 3 mM NR. White arrows: mitophagy. B The mean value of fluorescence intensity/cells in each image was scored. At least 15 images (~ 200 cells) were counted per group. The relative values in each group was normalized to Con1. ",
    "diseases": "DC"
  },
  {
    "caption": "C Representative immunoblots of the expression of PINK1 and PARKIN in DC cells treated with vehicle or 3 mM NR. Quantification of immunoblots from the indicated proteins is from three replicates.",
    "diseases": "DC"
  },
  {
    "caption": "A PCR amplification efficiency at the telomere in the mock- and FPG-treated DC and age-matched healthy control fibroblasts supplemented with vehicle or 3 mM NR. All values are presented as mean ± SD of three replicates. The relative telomere PCR amplification in each sample was normalized to the 36B4 reference gene.",
    "diseases": "DC"
  },
  {
    "caption": "B Telomere restriction fragment analysis in DC and control fibroblasts treated with vehicle or 3 mM NR. Genomic DNA was isolated from the indicated cell lines at 0 d or 14 d, with or without 3 mM NR treatment. At left, DNA molecular mass markers, in kilobase pairs (Kb).",
    "diseases": "DC"
  },
  {
    "caption": "C, D Representative images of γH2AX (green), telomere immuno-FISH (red) in DC cells treated with vehicle or 3 mM NR. White arrows: co-localization of γH2AX foci and telomeric DNA (or TIF). Enlarged views of co-localizing foci are shown at the right panel and in Figure EV1. Percentage of DC and control cells with indicated TIFs per nuclei. ~ 100 cells per condition were scored.",
    "diseases": "DC"
  },
  {
    "caption": "A Cumulative population doubling analysis of the proliferation of representative scramble and CD38 knockdown DC fibroblasts or DC fibroblasts treated with vehicle or 3 mM NR. Each data point is represented as mean ± SD of three replicates.",
    "diseases": "DC"
  },
  {
    "caption": "B, C Representative images of BrdU (red) and DAPI (blue) staining of DC and age-matched healthy control fibroblasts treated with vehicle or NR. Percentage of BrdU -positive cells per condition. Each dot represents the percentage of cells with BrdU staining per image. ~400 cells were counted per condition. All values are presented as mean ± SD.",
    "diseases": "DC"
  },
  {
    "caption": "D, E Representative images of SPiDER-β-gal (green) and DAPI (blue) staining of DC and age-matched healthy control cells treated with vehicle or 3 mM NR. Percentage of SA-β-gal-positive cells per condition. Each dot represents the percentage of cells with SA-β-gal staining per image. ~400 cells were counted per condition. All values are presented as mean ± SD.",
    "diseases": "DC"
  },
  {
    "caption": "F The levels of IL-6, IL-8, and MCP-1 in both supernatant and cell lysate of indicated DC fibroblasts treated with vehicle or 3 mM NR. All values are represented as mean ± SD of three replicates.",
    "diseases": "DC"
  },
  {
    "caption": "G, H Representative immunoblots of p21 and p16 in DC fibroblasts treated with vehicle or 3 mM NR. Quantification of the indicated proteins are presented as mean ± SD from three immunoblots.",
    "diseases": "DC"
  },
  {
    "caption": "(A) Kaplan Meier plot for survival in NeuT;Apln+/+ (n=11) and NeuT;Apln-/- (n=10) mice with mammary cancer after tumor onset. *P=0.0185; Log rank test.",
    "diseases": "mammary cancer"
  },
  {
    "caption": "(B) Tumor volumes, followed over time, of control mammary tumor E0771 cells (shRenilla) and Apelin-depleted (shApln) E0771 cells orthotopically-injected into both syngeneic C57BL/6J Apln+/+ and Apln-/- mice (5x105 cells/mouse), respectively. Tumor volumes were determined using calipers and are shown as mean tumor volumes ± S.E.M. Data shown is pooled from 2 independent experiments. Apln+/+;shRenilla (n=18), Apln+/+;shApln (n=17), Apln-/-;shRenilla (n=14), Apln-/-;shApln (n=15); ** P<0.01, *** P<0.001; two-way ANOVA.",
    "diseases": "mammary tumor"
  },
  {
    "caption": "(C) Mean percentages (± S.E.M.) of CD31+ area in E0771 shRenilla (n=3) or shApln (n=3) mammary tumors, assessed on day 23 post-orthotopic injection into C57BL/6J Apln+/+ or Apln-/- mice, respectively. **P<0.01; t test. (D) Mean percentages (± S.E.M.) of extravasated Dextran in E0771 shRenilla (n=9) or shApln (n=12) mammary tumors, assessed on day 19 post-orthotopic injection into C57BL/6J Apln+/+ or Apln-/- mice, respectively. **P<0.01; t test. Right panel shows representative immunofluorescence of Dextran (red), CD31+ vessels (green), and DAPI (blue). The white arrows indicate regions of Dextran extravasation. Scale bars = 100 μm",
    "diseases": "mammary tumors"
  },
  {
    "caption": "(A) Experimental set up and (right) Kaplan Meier survival plot of NeuT;Apln+/+ and NeuT;Apln-/- mice with mammary cancer, left untreated (control) or treated with the indicate dose of the broad VEGFR blocker sunitinib. NeuT;Apln+/+ Control (n=8), NeuT;Apln-/- Control (n=11), NeuT;Apln+/+ Sunitinib (n=11), NeuT;Apln-/- Sunitinib (n=12); *P<0.05; Log rank test. Mice were sacrificed when the tumor size reached 1cm3, following ethical guidelines. The dotted line indicates 50% of survival.",
    "diseases": "mammary cancer"
  },
  {
    "caption": "(C) Tumor volumes of untreated (control) and sunitinib-treated NeuT;Apln+/+ and NeuT;Apln-/- mammary tumors, size-matched at 20-70mm3 and followed over time by MRI analysis; NeuT;Apln+/+ Control (n=7), NeuT;Apln-/- Control (n=5), NeuT;Apln+/+ Sunitinib (n=5), NeuT;Apln-/- Sunitinib (n=6) mice per group; Lines represent nonlinear fit of tumor growth. Box and arrow indicate the time point used for analysis in panel D. (D) Mitotic counts (mean ± S.E.M.) and representative H&E images of mammary tumors in untreated (control) ­and sunitinib-treated NeuT;Apln+/+ and NeuT;Apln-/- mice, assessed 6 weeks after tumor onset.; NeuT;Apln+/+ Control (n=7), NeuT;Apln-/- Control (n=6), NeuT;Apln+/+ Sunitinib (n=9), NeuT;Apln-/- Sunitinib (n=4) tumors per group; *P<0.05; one-way ANOVA to sunitinib-treated NeuT;Apln-/-. White arrows indicate mitotic figures. Scale bars = 50 μm",
    "diseases": "mammary tumors"
  },
  {
    "caption": "(B) Representative MRI images; Scale bar = 5mm and (C) quantification (mean ± S.E.M.) of relative tumor blood volume (rTBV) over time after NeuT+ mammary tumors were size-matched at 20-70mm3 (0 weeks). Treatments and genotypes are indicated. NeuT;Apln+/+ Control (n=4), NeuT;Apln-/- Control (n=4), NeuT;Apln+/+ Sunitinib (n=5), NeuT;Apln-/- Sunitinib (n=5); **P<0.01, and ***P<0.001 compared to untreated NeuT;Apln+/+ mice and #P<0.05 compared to untreated control NeuT;Apln-/- mice; two-way ANOVA. Of note, in NeuT;Apln+/+ mice, only 2 tumors could be analyzed after 6 weeks as some mice had to be sacrificed due to the large tumor sizes following ethical guidelines. Thus, we did not perform any statistical analysis on the 6 weeks timepoints.",
    "diseases": "mammary tumors"
  },
  {
    "caption": "(D) Analysis (mean values ± S.E.M.) of CD31+ area (x104 μm2)/field, number of dilated tumor vessels and percentage of alphaSMA+ area per CD31+ blood vessels in mammary tumors of untreated (control) and sunitinib-treated NeuT;Apln+/+ and NeuT;Apln-/- mice, assessed 6 weeks after mammary tumors were size-matched. NeuT;Apln+/+ Control (n=4), NeuT;Apln-/- Control (n=4), NeuT;Apln+/+ Sunitinib (n=5), NeuT;Apln-/- Sunitinib (n=4); *P<0.05; **P<0.01; ***P<0.001; one-way ANOVA and Kruskal-Wallis test. (E) Representative immunofluorescence and immunohistochemistry images from Fig. 5D quantification. Dilated blood vessels are marked by a red asterisk. DAPI (blue) is shown as a counterstain to visualize nuclei. Scale bars = 100 μm (upper panels), 50 μm (middel panels) and 20 μm (lower panels).",
    "diseases": "mammary tumors"
  },
  {
    "caption": "(A) Percentages of CA9+ cells adjacent to CD31+ tumor blood vessels in untreated (control) and sunitinib-treated NeuT;Apln+/+ and NeuT;Apln-/- mice, 6 weeks after mammary tumors were size-matched. NeuT;Apln+/+ Control (n=4), NeuT;Apln-/- Control (n=4), NeuT;Apln+/+ Sunitinib (n=4), NeuT;Apln-/- Sunitinib (n=4); 100-200 peri-vascular intra-tumoral regions per group were counted. ***P<0.001; one-way ANOVA. Right panels show representative immunofluorescent images. Areas limited by dotted white lines indicate CA9+ areas. Scale bars = 50 μm.",
    "diseases": "mammary tumors"
  },
  {
    "caption": "(B) Representative MRI images; Scale bar = 5mm and (C) quantification (mean ± S.E.M.) of vessel permeability (K2) in NeuT+ mammary tumors followed over time. Treatments and genotypes are indicated. NeuT;Apln+/+ Control (n=4), NeuT;Apln-/- Control (n=5), NeuT;Apln+/+ Sunitinib (n=4), NeuT;Apln-/- Sunitinib (n=5); ***P<0.001, compared to untreated control NeuT;Apln+/+ mice and §P<0.05 compared to sunitinib-treated NeuT;Apln+/+ mice; two-way ANOVA. Of note, in NeuT;Apln+/+ mice, only 2 tumors could be analysed after 6 weeks as some mice had to be sacrificed due to the large tumor sizes following ethical guidelines. Thus we did not perform any statistical analysis on the 6 weeks timepoints.",
    "diseases": "mammary tumors"
  },
  {
    "caption": "(A) Number of metastatic lung foci in untreated (control) and sunitinib-treated (60mg/kg, three times a week from tumor initiation) NeuT;Apln+/+ or NeuT;Apln-/- mice, assessed 6 weeks after mammary tumors were size-matched. Data of individual lung sections and means (black bars) are shown. Right panels show representative H&E images, where black arrows and insets indicate metastatic foci. Scale bars = 1000 μm (large panels) and 50 μm (insets). *P<0.05, **P<0.01; ***P<0.001; Kruskal-Wallis test; n=3 mice per cohort and three sections per lung were analysed.",
    "diseases": "mammary tumors"
  },
  {
    "caption": "(B) Kaplan Meier survival plot for distant metastasis free survival from the KM-plotter database (Data Ref: Győrffy et al, 2013) for high and low Apelin (APLN)-expressing groups in human breast cancer. Patients were split by the median. Affymetrix Apelin ID 222856_at.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(C) Kaplan-Meier plot for progression-free survival stratifying RCC patients with high and low APELIN serum levels 3-5 months after the start date of sunitinib treatment. *P=0.0367; Log rank test.",
    "diseases": "RCC"
  },
  {
    "caption": "(D) Kaplan Meier plots for progression-free survival in RCC patients stratified into groups of high or low levels of APELIN and VEGF. Cut-off levels were set by the median. Serum was analysed 3-5 months after the start date of sunitinib treatment. *P<0.05, **P<0.01; Log rank test.",
    "diseases": "RCC"
  },
  {
    "caption": "A Concentrations of amylase, lipase, CRP, and ANGPTL4 in the sera of patients (n = 90) diagnosed with pancreatitis. The box plots show a typical display consisting of a median value depicted by the line in the center of the box; an interquartile range (IQR; 25th to the 75th percentile) depicted by the box; and the maximum (Q3+1.5*IQR) and minimum (Q1-1.5*IQR) values depicted by the whisker. Statistical significance of Mann-Whitney U-tests is indicated (** P < 0.01 and *** P < 0.001). Exact P values are shown in Appendix Table S2. ANGPTL4 and CRP concentration from pancreatitis patients were determined by sandwich ELISA. The correlation between ANGPTL4 and CRP is depicted with Pearson correlation coefficient (R). Each dot represents the levels of ANGPTL4 and CRP from an individual patient (n = 90).",
    "diseases": "pancreatitis"
  },
  {
    "caption": "B Pancreatitis and adjacent normal regions (n = 6) were stained by immunofluorescence for amylase and ANGPTL4. Scale bar represents 30 µm",
    "diseases": "Pancreatitis"
  },
  {
    "caption": "C H&E staining, ANGPTL4 and amylase expression by immunofluorescence analysis after the induction of mild (AP) and severe acute pancreatitis (SAP) for 2 h (n = 15, each group). Scale bar represents 50 µm.",
    "diseases": "AP, SAP, severe acute pancreatitis"
  },
  {
    "caption": "D Amylase, lipase, and ANGPTL4 were assessed in the serum from AP and SAP animal models and ANGPTL4 protein expression were determined in the blood and pancreas (n = 15, each group).",
    "diseases": "AP, SAP"
  },
  {
    "caption": "A AP was induced by 5 injections (IP) of cerulein at a dosage of 50 μg/kg. SAP was induced by AP and one injection of lipopolysaccharide (LPS, IP) at a dosage of 20 mg/kg. AP+ANGPTL4 (2 mg/kg) was induced by AP and one injection of ANGPTL4 (IP) at a dosage of 2 mg/kg. ANGPTL4 (4 mg/kg) was induced by two injections of ANGPTL4 (IP) at a dosage of 2 mg/kg. Mice were sacrificed 6 h after pancreatitis induction. (H&E and immunofluorescent staining for IL-1β (red) and amylase (green) was performed along with immunohistochemistry for ANGPTL4 in pancreas tissues (n = 10, each group). Scale bar represents 50 µm",
    "diseases": "AP, SAP, pancreatitis"
  },
  {
    "caption": "D T.E.M. ANGPTL4 immunogold labelling were performed in pancreas tissues from the AP, SAP and ANGPTL4-treated models (n = 5, each group).",
    "diseases": "AP, SAP"
  },
  {
    "caption": "A AP and SAP were induced in wild type (WT) and ANGPTL4 -/- mice (n = 15, each group), as described in the material and methods. H&E staining, TUNEL staining for apoptosis, and immunofluorescence staining for ANGPTL4 (red) and amylase (green) were performed in the pancreatic tissues. ANGPTL4 and IL-6 protein expressions were also determined in pancreatic tissues from ANGPTL4 WT and -/- mice by Western blotting. Scale bar represents 100 µm.",
    "diseases": "AP, SAP"
  },
  {
    "caption": "A For macrophage depletion models, mice (six weeks) were injected with GdCl3 (15 mg/kg). After the induction of macrophage depletion in the mice, pancreatitis was induced by cerulein, LPS, and ANGPTL4 for 24 h (n = 10, each group). H&E staining of pancreatic tissue, and levels of amylase and lipase in the serum. Scale bar represents 100 µm",
    "diseases": "pancreatitis"
  },
  {
    "caption": "B Immunohistochemistry for the macrophage marker CD11b and ANGPTL4 in pancreas tissues. Levels of ANGPTL4 in the serum were measured in the AP, SAP, and ANGPTL4 (4 mg/kg) groups of macrophage WT or depletion mice h (n = 10, each group). Scale bar represents 100 µm",
    "diseases": "AP, SAP"
  },
  {
    "caption": "C Immunofluorescent staining of the F4/80 macrophage marker and quantification of macrophage-positive cells in the AP and SAP groups from the ANGPTL4 -/-and WT mice (n = 10). Scale bar represents 150 µm",
    "diseases": "AP, SAP"
  },
  {
    "caption": "B ANGPTL4 and C5a expression levels were measured in bone marrow-derived macrophages from pancreatitis-induced ANGPTL4-/- and WT mice.",
    "diseases": "pancreatitis"
  },
  {
    "caption": "A Concentrations of C5a in the sera from pancreatitis patients, and correlation between ANGPTL4 and C5a in the sera from pancreatitis patients (n = 90). The box plots show a typical display consisting of a median value depicted by the line in the center of the box; an interquartile range (IQR; 25th to the 75th percentile) depicted by the box; and the maximum (Q3+1.5*IQR) and minimum (Q1-1.5*IQR) values depicted by the whisker. Statistical significance of Mann-Whitney U-tests is indicated (*** P < 0.001). Exact P values are shown in Appendix Table S2. The correlation between C5a and ANGPTL4 is depicted with Pearson correlation coefficient (R). Each dot represents the levels of C5a and ANGPTL4 from an individual patient (n = 90). The immunofluorescent expression of C5a and amylase was observed in pancreatitis and adjacent normal regions in patient tissues. Scale bar represents 50 µm",
    "diseases": "pancreatitis"
  },
  {
    "caption": "B Immunofluorescence staining of C5a in pancreas tissues from ANGPTL4 -/- and WT animals and macrophage depletion/WT models with pancreatitis. Scale bar represents 150 µm. Levels of C5a were measured in serum (n = 7).",
    "diseases": "pancreatitis"
  },
  {
    "caption": "D The neutralizing ANGPTL4 antibody (10 mg/kg) was injected twice (IP) into the AP and SAP models. H&E staining of pancreatic tissues and the concentrations of ANGPTL4, C5a, TNF-α, and amylase in the serum (n = 10, each group). Scale bar represents 50 µm",
    "diseases": "AP, SAP"
  },
  {
    "caption": "A. RNA-seq of whole blood from symptomatic (n=26; median 8 days PIO) and asymptomatic (n=30; median 3 days post-hospital admission) COVID-19 patients at the acute phase of infection (SARS-CoV-2 PCR-positive) was performed. Only samples with RNA integrity number >6 were sent for sequencing and included in the analysis. Volcano plot indicating DEGs between asymptomatic and symptomatic COVID-19 patients, with thresholds of FDR < 0.05 and |FC| > 2. Numbers of over-expressed and under-expressed genes are indicated.",
    "diseases": "COVID-19"
  },
  {
    "caption": "B. Network analysis of significant immune mediators between symptomatic and asymptomatic COVID-19 patients. Interactive relationships between the cytokines or chemokines were determined by STRING (Search Tool for the Retrieval of Interacting Genes/ Proteins) analysis, with a confidence threshold of 0.5.",
    "diseases": "COVID-19"
  },
  {
    "caption": "C. SARS-CoV-2 specific CD4+ non T follicular helper (TFH) cells from symptomatic (n=5) and asymptomatic COVID-19 (n=5) patients were characterized with flow cytometry based on the expression of IL-17a, IFN-γ, TNF-⍺, IL-4 and IL-10 upon SARS-CoV-2 peptide stimulation. Representative plot overlay of unstimulated (black) on peptide stimulated (red) was performed on asymptomatic patient. Data are presented as Mean ± SD **P<0.01 (Mann-Whitney U test).",
    "diseases": "COVID-19"
  },
  {
    "caption": "A, B. (A) IgG and (B) IgM responses were analysed by screening plasma samples of asymptomatic (n=39, median study day 29) and symptomatic (n=57, median study day 31) COVID-19 patients. Data are presented as Mean ± SD ***P<0.001 (Mann-Whitney U test).",
    "diseases": "COVID-19"
  },
  {
    "caption": "A. Flow cytometry acquisition of patient whole blood was performed and number of mature and immature neutrophils were compared between asymptomatic (n=16) and symptomatic (n=52) COVID-19 patients and healthy controls (n=17). Data are presented as Mean ± SD *P<0.05; **P<0.01; ***P<0.001 (Kruskal-Wallis test with Dunn's multiple comparison).",
    "diseases": "COVID-19"
  },
  {
    "caption": "B. Mass cytometry was performed on PBMCs obtained from acute asymptomatic (n=19) and acute symptomatic (n=37) COVID-19 patients and healthy donors (n=10). Monocytes were characterized based on their CD14 and CD16 expression. Data are presented as Mean ± SD **P<0.01; ***P<0.001 (Kruskal-Wallis test with Dunn's multiple comparison). C. Classical, intermediate and non-classical monocytes were further defined in acute asymptomatic (n=19) and acute symptomatic (n=37) COVID-19 patients and healthy donors (n=10) with inflammatory marker CD169. Data are presented as Mean ± SD **P<0.01; ***P<0.001 (Kruskal-Wallis test with Dunn's multiple comparison).",
    "diseases": "COVID-19"
  },
  {
    "caption": "D. Expression data of genes associated with inflammatory monocytes, activated neutrophils and pro-inflammatory cytokines were compared between acute asymptomatic (n=30) and asymptomatic (n=26) COVID-19 patients and were represented by ratio with respect to expression in asymptomatic patients. Bar graphs show DEGs with FDR adjusted P value < 0.05 and fold change values are represented in the log2 scale.",
    "diseases": "COVID-19"
  },
  {
    "caption": "E. Pro-inflammatory associated immune mediator levels in plasma fraction samples from first collection timepoint during hospital admission were quantified with 45-plex microbead-based immunoassay. Immune mediator levels were compared between asymptomatic patients (n=48) and symptomatic patients stratified by COVID-19 severity (mild, n=61; moderate, n=43; severe, n=68). Immune mediator levels for healthy controls (HC) (n=23) are indicated by the black dotted line. Patient samples with concentrations out of measurement range are presented as the value of Limit of Quantification (LOQ). Data are presented as Mean ± SD *P<0.05; **P<0.01; ***P<0.001 (One-way ANOVA with post hoc t test).",
    "diseases": "COVID-19"
  },
  {
    "caption": "a, representative  histopathology photomicrographies of lungs according to the different groups: mock_saline, CoV_saline and CoV_ivermectin. Top panels: whole lung  sections. Bottom panels: high magnification. CoV_saline section exhibits important congestion (*), edema associated with few mononuclear cells (white arrowheads). Note the thickening of the  alveolar walls. CoV_ivermectin section exhibits important amounts of mononuclear cells (black arrowheads) and less marked signs of congestion  or edema. Hematoxylin and Eosin. Scale bars = 1 mm (top panels) and 20 μm (bottom panels).",
    "diseases": "edema, congestion"
  },
  {
    "caption": "Tumour volume on re-challenge with BN175 sarcoma on contralateral limb of long-term survivors following ILP-TNF/Mel or ILP-TNF/Mel/SM (n=3 animals per TNF/Mel cohort and n=5 per TNF/Mel/SM cohort). Unless otherwise stated, SM represents Birinapant. Error bars represent S.D.",
    "diseases": "sarcoma"
  },
  {
    "caption": "A Representative confocal images of microvessels in transversal tumor sections from HBCx-14 (TP53mutant) tumors treated with either DMSO, CDDP or a combination of CDDP and PFT-α. The sections were immunolabeled for CD31 (red) and viewed with a 20x objective. The basal-like breast cancer cells were immunolabeled in green with an antibody against cytokeratin 5 and 8. Upper right panel is a 2D projection from the white boxed area in upper left panel. The red area corresponds to CD31 labeled endothelial area and the white area represents the lumen area. The white line shows the vessel perimeter. Scale bars: left panel=50 µm, right panels=35 µm. The tumor samples were collected at day 21.B Histograms representing the percentage of vascular area calculated using 2D reconstruction image analysis and the formula: vessel/vascular area = area of CD31-positive objects + lumen area per field area × 100 %. The both HBCx-14 (TP53mutant) and HBCx-90 (TP53wt) tumors from the different treated groups were collected at day 21 (n=4 sections/tumor and 3-4 tumors/group). Data are expressed as mean ± SEM. Kruskal-Wallis test followed by post hoc Dunn's test (***P ≤0.0004, CDDPvs. DMSO or CDDPvs. CDDP+PFT-α).",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "C Representative confocal images of cleaved caspase 3 positive cells (red) in the transversal tumor sections and viewed with a 20x objective. The stromal compartments were immunolabeled in green with an antibody against vimentin. HBCx-14 (TP53mutant) tumors from the different treated groups were collected at day 18. Scale bar=50 µm. c-cas-3: cleaved caspase 3.",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "D Representative western blot analysis using antibodies against β-actin, p53 and p21 in tumor extracts from HBCx-14 (TP53mutant) and HBCx-90 (TP53 wt) tumors treated with either DMSO or CDDP and collected at day 18. Note the higher CDDP-induced increase of p53 and p21 expression in TP53wt HBCx-90tumors.",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "E, F Representative western blot analysis using antibodies against β-actin, p-Chk1, Beclin 1, LC3-I/II and Rab7 in tumor extracts from HBCx-14 (TP53mutant) and HBCx-90 (TP53 wt) tumors treated with either DMSO, PFT-α, CDDP or a combination of CDDP and PFT-α. The tumor samples were collected at day 18.G, H, I Histograms representing the levels of Beclin 1, LC3-II and Rab7 in HBCx-14 and HBCx-90tumors treated with the different regimens (n=3-4 tumors per group, all experiments were performed in triplicate). Actin served as a loading control. Data are expressed as mean ± SEM. One-way ANOVA test followed by post hoc Tukey's test (G: *P = 0.03, **P =0.006 , ***P ≤ 0.0004 ; H: *P =0.02, ***P = 0.0005 ; I: *P =0.03, ***P ≤ 0.0006 , CDDPvs. DMSO or CDDPvs. CDDP+PFT-α).",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "C, D Evidence of lymphoproliferative disease in Traf6fl/flFoxp3Cre+ mice. (C) Spleens and lymph nodes were recovered from Traf6fl/flFoxp3Cre+ mice and Traf6fl/fl littermates at 8 weeks of age (Scale bars: 5 mm). (D) The cellularity of the lymphoid tissues of Traf6fl/flFoxp3Cre+ mice and their Traf6fl/fl Foxp3Cre- littermates was determined (8 mice/group).",
    "diseases": "lymphoproliferative disease"
  },
  {
    "caption": "B Implanted B16 melanoma growth in Traf6fl/flFoxp3Cre+ and wild type (Traf6fl/flFoxp3Cre-) mice. 1x105 B16F10 cells were injected subcutaneously (s.c.) into the shaved flanks of the indicated mice (n= 5/group). Tumor volumes were monitored every 3 days.",
    "diseases": "Tumor"
  },
  {
    "caption": "C, D Proinflammatory cytokine production in tumor-bearing mice with and without Treg-specific TRAF6 expression. Cell suspensions of the tumor-draining lymph node and tumor-infiltrating leukocytes (TILs) were recovered after 21 days of tumor growth. Ex vivo stimulation with PMA and ionomycin in the presence of Golgistop for 5 hour preceded intracellular staining for IFNγ and IL-17 and flow cytometry analysis.",
    "diseases": "tumor"
  },
  {
    "caption": "E, F FOXP3 expression by CD4+ T cells in tumor bearing Traf6fl/flFoxp3Cre+ and wild type (Traf6fl/flFoxp3Cre-) mice. The frequency of FOXP3+ cells in the CD4+ cells of tumor-draining lymph nodes (dLN), peripheral, non-tumor draining lymph nodes (pLN), spleens, and TILs were determined by flow cytometry.",
    "diseases": "tumor"
  },
  {
    "caption": "C In vivo suppression of colitis by wild type- and K262R mutant-Foxp3 expressing T cells. 2x105 naïve CD4+ transductants from A were mixed with 1x106 colitogenic naïve CD4+ T cells from wild type mice and transferred i.v. into Rag2-/- mice. Rag2-/- mice receiving no cell transfers, naïve CD4+ T cells alone, or purified wild type Tregs served as controls (n= 6/group). Recipient mouse body weights were monitored weekly for each group.",
    "diseases": "colitis"
  },
  {
    "caption": "Pearson correlation between log fold change (LFC) Ppara expression levels and body temperature 24h post-sepsis (n= 38, r = 0.6875, combined data of 4 independent experiments).",
    "diseases": "sepsis"
  },
  {
    "caption": "Liver Hmgcs2 mRNA expression at different timepoints post-sepsis, expression is shown as relative expression, normalized to housekeeping genes Hprt and Rpl. P-values were calculated using 1-way ANOVA analysis (n = 4/group, data are representative of 2 experiments).",
    "diseases": "sepsis"
  },
  {
    "caption": "Apoptosis in liver paraffin-fixated sections 24h after sepsis, measured by TUNEL staining, and presented as % PI positive cells/µm² tissue area. (n= 6/7 mice/group, combined data of 2 independent experiments). P-values were calculated with 1-way ANOVA tests.",
    "diseases": "sepsis"
  },
  {
    "caption": "Mice were pre-treated with Pemafibrate (1mg/kg) or vehicle (0,9% NaCl) for 1 week before being subjected to CLP. Plasma was isolated 24h after sepsis and FFA concentration and (D) glycerol concentration were determined as described in the method section. P-values were calculated with 2-way ANOVA tests. n = 5-7/group, combined data of 2 independent experiments. Arrows represent the % of decrease caused by pemafibrate treatment during sepsis.",
    "diseases": "sepsis"
  },
  {
    "caption": "Mice were pre-treated with Pemafibrate (1mg/kg) or vehicle (0,9% NaCl) for 1 week before being subjected to CLP. Quantification of lipid peroxidation by determination of MDA concentration in liver homogenates 24h post-surgery in CLP mice (n= 6-7/group, combined data of 2 independent experiments ), as described in methods. P-values were calculated with 2-way ANOVA tests. Arrows represent the % of decrease caused by pemafibrate treatment during sepsis.",
    "diseases": "sepsis"
  },
  {
    "caption": "Mice were pre-treated with Pemafibrate (1mg/kg) or vehicle (0,9% NaCl) for 1 week before being subjected to CLP. Quantification of lipid peroxidation by determination of MDA concentration in kidney homogenates 24h post-surgery in CLP mice (n= 6-7/group, combined data of 2 independent experiments ), as described in methods. P-values were calculated with 2-way ANOVA tests. Arrows represent the % of decrease caused by pemafibrate treatment during sepsis.",
    "diseases": "sepsis"
  },
  {
    "caption": "Mice were pre-treated with pemafibrate (1mg/kg) or vehicle (0,9% NaCl) for 1 week before being subjected to CLP. Apoptosis in liver paraffin-fixated sections 24h after sepsis, measured with TUNEL staining and depicted as % of PI positive cells/µm² tissue area. P-values were calculated with 2-way ANOVA tests. n = 6-7/group, combined data of 2 independent experiments.",
    "diseases": "sepsis"
  },
  {
    "caption": "Mice were pre-treated with pemafibrate (1mg/kg) or vehicle (0,9% NaCl) for 1 week before being subjected to CLP. Apoptosis in kidney paraffin-fixated sections 24h after sepsis, measured with TUNEL staining and depicted as % of PI positive cells/µm² tissue area. P-values were calculated with 2-way ANOVA tests. n = 6-7/group, combined data of 2 independent experiments.",
    "diseases": "sepsis"
  },
  {
    "caption": "Mice were pre-treated with pemafibrate (1mg/kg) or vehicle (0,9% NaCl) for 1 week before being subjected to CLP. Systemic bacterial load (CFU/ml blood) 24h post-sepsis in vehicle or pemafibrate treated mice. P-values were calculated with 2-way Student's t-test.",
    "diseases": "sepsis"
  },
  {
    "caption": "Pemafibrate (1 mg/kg) or vehicle (0,9% NaCl) was administered at different timepoints before and after the induction of sepsis and survival was monitored during 9 days, after which no further deaths occurred. Survival curve was analyzed via Log rank tests",
    "diseases": "sepsis"
  },
  {
    "caption": "Blood samples were collected from healthy volunteers and septic patients (n= 13 septic patients, = 15 healthy controls). Plasma was prepared and (A) FFA and (B) glycerol concentrations were determined as described in the methods. P-values were calculated with two-way Student t-tests.",
    "diseases": "septic"
  },
  {
    "caption": "Display of differentially expressed genes in NeuNT tumors (WT, TNCKO) as volcano plot representing all associated genes in WT tumors. N = 3 tumors per genotype. (A) Log2 Fold Change (X-axis) and the negative log10 (P.Value) (Y-axis) is displayed, the blue line indicating p = 0.05 (Y-axis), points above the line, p < 0.05. The dashed red lines indicate the log 2 Fold Change cutoff of -0.25 and 0.25, respectively (X-axis). Green dots represent genes that display both statistical significance (p < 0.05) and fold changes -0.25 and 0.25, respectively. Selected genes regulated by TNC are marked in red (type I interferon response) or pink (Cxcl12) dot.",
    "diseases": "NeuNT"
  },
  {
    "caption": "(I, J) Detection (I) and quantification (J) of CD8 TIL in lung metastasis of NeuNT WT and TNCKO mice (N = 3 mice, n = 7 and 12 lung metastases, respectively). Scale bar, 100 µm. ** p = 0.0097, Mann Whitney test. Mean ± SEM.",
    "diseases": "lung metastases, lung metastasis, NeuNT"
  },
  {
    "caption": "(A-C) Adjacent human breast cancer tissue microarray  (TMA) sections were stained with the indicated antibodies, scale bar, 50 μm, arrows point at CD8 TIL (A) and,  CD8 TIL were counted  per field (B), or in the stroma and nest, respectively (C), N = 103 TNC+ tumors, N = 116 TNC- tumors.. (B) ** p = 0.0055, Fisher's exact test. The central band represents the median, the ends of the box the first and the third quartiles, and the whiskers reach from each quartile to the minimum or maximum. (C) ** p = 0,0055, Mann-Whitney test.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(D-G)  Kaplan Meier  analysis to address correlation of TNC expression (D), total  numbers of CD8 TIL (E), combined high (above median) CD8 TIL and high or low (above/below median) TNC (F) and stromal CD8  cells (G) with metastasis-free survival (MFS) of breast cancer patients. Stromal CD8- or CD8+ is defined as below or above median  stromal CD8 TIL per area. Log-rank test.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(H, I) Correlation of TNC  and CD8a levels with overall survival  (OS) using survival analysis on breast cancer patient cohort GSE 19783-GPL6580. Hazard ratio (HR) and p values are indicated in Appendix Fig. S5N. Log-rank test.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(D) Kaplan Meier survival analysis of breast cancer patients upon stratification into tumors with a CXCL12 Hscore below or above the median, p = 0.002. Mann-Whitney test. (E) Survival analysis of  breast cancer patients in the GSE 19783-GPL6580 cohort upon stratification into tumors with high or low expression of TNC and CXCL12. Log-rank test. HR and p values are indicated, ",
    "diseases": "breast cancer"
  },
  {
    "caption": "A. STAT3 immunohistochemistry- staining of low STAT3 and high STAT3 PCa samples. Red arrows indicate transformed PCa glands, black arrows indicate pre-transformed normal prostate glands. Scale bar = 100µm. # = sample-IDs.",
    "diseases": "PCa"
  },
  {
    "caption": "B. Representative IHC- staining of SDHB in normal prostate glands and Gleason grade (GL) 3 - 5 PCa glands. Scale bar = 100µm.",
    "diseases": "PCa"
  },
  {
    "caption": "D. Representative IHC staining of IDH2 in normal prostate glands and GL 3 - 5 PCa glands. Scale bar = 100µm.",
    "diseases": "PCa"
  },
  {
    "caption": "C.- D. Kaplan-Meier plots showing time to biochemical recurrence in months for PDK4 in primary tumors (C) and in primary and metastatic tumors combined (D) in the MSKCC PCa GSE21032 data set. Groups were generated by a median split. P-values were estimated by Log-rank test (C-D) and adjusted with Benjamini-Hochberg method (D). + = censored.",
    "diseases": "PCa"
  },
  {
    "caption": "A. STAT3 and PDK4 stratified subgroups were generated by median splits in MSKCC PCa GSE21032 data set. Pearson correlation between STAT3 and PDK4 is shown. Kaplan-Meier plot shows stratified subgroups. P-values were estimated by Log-rank test and adjusted with Benjamini-Hochberg method. Hi = high, lo = low.",
    "diseases": "PCa"
  },
  {
    "caption": "D. Correlation of STAT3, c-MYC and HIF-1α with PDK1-4, PDC- genes (PDHA1, PDHB, PDHX, DLAT, DLD) and TCA/OXPHOS genes (CS, IDH2, IDH3A, SDHB, SDHC, ATP5A1, NDUFS1) in MSKCC PCa (GSE21032). Dot colors represent Pearson correlation (1 = red, -1 = blue), dot sizes represent adj. p-values ≤ 0.05. Only significant correlations are shown. P-values were adjusted with Benjamini-Hochberg method.",
    "diseases": "PCa"
  },
  {
    "caption": "F. Quantification of soft agar colony formation assay of LNCaP and DU145 prostatic cancer cell lines treated with increasing concentrations of siRNA targeting GOLPH3 or LCS (data are means ± SEM of at least 3 independent experiments; ***p <0.001 [Student's t-test]).",
    "diseases": "prostatic cancer"
  },
  {
    "caption": "D. Representative images of NSCLC sections stained for GOLPH3 and LCS. Scale bar, 100 µm.",
    "diseases": "NSCLC"
  },
  {
    "caption": "Event-free survival (EFS) and percentage of human CD45+ leukocytes in peripheral blood in acute lymphoblastic leukemia (ALL) orthotopic models.",
    "diseases": "acute lymphoblastic leukemia, ALL"
  },
  {
    "caption": "Event-free survival (EFS) and percentage of human CD45+ leukocytes in peripheral blood in acute lymphoblastic leukemia (ALL) orthotopic models.",
    "diseases": "acute lymphoblastic leukemia, ALL"
  },
  {
    "caption": "A Lung function data of COPD (II-IV) and no COPD (ex-smoker controls) donors used in this study. The lung function between the two groups is significantly different. In (A), data points represent each donor values and horizontal bars the group median. An unpaired non-parametric t test (Mann-Whitney test, GraphPad Prism software, version 8.0.1) was employed to compare the lung function (FEV1 and FEV1/FVC values) between control (no COPD, n=3) and COPD II-IV donors (n=5), *p-value<0.05. Exact p-values are: FEV1, p-value= 0.0357; FEV1/FVC, p-value= 0.0357. FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity;",
    "diseases": "COPD"
  },
  {
    "caption": "T-WGBS data of primary fibroblasts from no COPD and COPD (II-IV) patients was analyzed DMRs E Detailed view of a representative hypo- (top) and hypermethylated (bottom) DMR (grey box). CpG methylation levels of each individual donor (dots) and the group average (lines) methylation profile of three no COPD (blue) and five COPD (II-IV) (dark green) donors are displayed. RefSeq annotated genes and CpG islands are indicated.",
    "diseases": "COPD"
  },
  {
    "caption": "D Genome browser view of an example DMR at a putative enhancer region. Group median CpG methylation is shown for no COPD (blue), COPD (I) (light green) and COPD (II-IV) (dark green). At the bottom the level of enhancer marks is depicted as fold-change over control: H3K4me1 (ENCODE accession: ENCFF102BGI) and H3K27ac (ENCODE accession: ENCFF386FDQ).",
    "diseases": "COPD"
  },
  {
    "caption": "D Selected examples of DEG across disease stages from clusters 2-5 defined in (C). In (D) each donor is represented by an individual point (no COPD n=3, COPD I n=3, COPD II-IV n=5), the group mean is shown as black dot and the error bar represents the standard deviation. In (D) FDRs and log2(fold-changes) (in A) were calculated using DESeq2, which uses a negative binominal GLM (generalized linear model) and Wald statistics. *: FDR <0.05; **: FDR <0.01; ***: FDR <0.001. The specific statistically significant FDR values are the following: RAD18 in COPD II-IV= 0.000434; ADAMTSL1 in COPD II-IV=0.02771; STEPA3 in COPD I= 0.04219 and in COPD II-IV= 0.001272; BMP4 in COPD II-IV= 0.0000535. ",
    "diseases": "COPD"
  },
  {
    "caption": "C Heatmap showing the effect of the KD of each candidate gene on the three measured readouts (αSMA, col1 and proliferation) in primary normal (NHLF) or COPD (DHLF) human lung fibroblasts, red: readout higher than NTC, blue: readout lower than NTC. |SSMD values| ≥ 2 are shown in lighter shade and |SSMD values| ≥ 3 in stronger shade. ; αSMA, alpha smooth-muscle actin; col1, collagen 1 SSMD, strictly standardized mean difference.",
    "diseases": "COPD"
  },
  {
    "caption": "(E) In situ hybridization for ISLR with RNAscope probe in human mucosa, inflamed mucosa from CD and UC patients. Scale bar: 25 μm.",
    "diseases": "CD, UC"
  },
  {
    "caption": "(H) The cancer genome atlas (TCGA) RNA-seq analysis showing that ISLR is upregulated in human rectal adenocarcinoma relative to normal rectal tissues. The horizontal lines between the box limits represent the median, the box limits indicate the interquartile ranges and the whiskers indicate limit superior and limit inferior respectively. n = 65.",
    "diseases": "rectal adenocarcinoma"
  },
  {
    "caption": "(I) Kaplan-Meier survival curve of 270 CRC cases. P = 0.02 (log-rank test).",
    "diseases": "CRC"
  },
  {
    "caption": "(J) ISLR level increased with nodal metastasis in colorectal cancer patients. N0, no regional lymph node metastasis; N1, metastases in 1 to 3 axillary lymph nodes; N2, metastases in 4 to 9 axillary lymph nodes; N3, metastases in 10 or more axillary lymph nodes. The solid horizontal lines represent the median, the box limits indicate the interquartile ranges and the whiskers indicate limit superior and limit inferior respectively.",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "(K In situ hybridization for ISLR/Islr with RNAscope probes in normal human colon, human malignant adenocarcinoma, metastatic adenocarcinoma (K), t indicating tumor; a indicating adjacent tissues of tumor. Scale bar: 50 μm.",
    "diseases": "adenocarcinoma"
  },
  {
    "caption": "(C) Double immunofluorescence for ETS1 and β-catenin in intestinal biopsies of healthy controls and inflamed mucosa from UC patients. Scale bar: 50 μm.",
    "diseases": "UC"
  },
  {
    "caption": "(F) Pearson correlation analysis on ETS1 and ISLR in colorectal adenocarcinoma TCGA RNA-seq (P < 0.001; R = 0.68).",
    "diseases": "colorectal adenocarcinoma"
  },
  {
    "caption": "(I) The growth curve of HT29 CRC cells cultured in the supernatant with or without ISLR-HA. The supernatant were collected for HT29 CRC cells 24 hours after transfected with pcDNA3.1 empty vector or pcDNA3.1-ISLR-HA vector. n=5 at each timepoint.",
    "diseases": "CRC"
  },
  {
    "caption": "(H) The growth curve of HCT116 colorectal cancer cells cultured in the supernatant from WT or cKO IMCs, concomitantly transfected with PCDH empty vector or PCDH-YAP1-5SA vector. n = 4 technical replicates.",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "(I) Pearson correlation analysis of ISLR and CTGF (P < 0.001; R = 0.69), ISLR and FSTL1 (P < 0.001; R = 0.81), as well as ISLR and CYR61 (P < 0.001; R = 0.65) in human colorectal cancer based on TCGA RNA-seq database.",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "(E) Western blotting for HA and ISLR in the supernatant from NCM460 colonic epithelial cells with pcDNA3.1 empty vector or pcDNA3.1-hISLR-HA plasmids. Western blotting for pMST1/2, MST1, pMOB1 and MOB1, pYAP1 and YAP1 in lysates from NCM460 CRC cells cultured in the supernatants with or without hISLR-HA. β-actin was used as a loading control.",
    "diseases": "CRC"
  },
  {
    "caption": "(F) ATPase assay of recombinant NSF  upon incubation with tau coimmunoprecipitates  (tau5) from brain  lysates of healthy controls (HC), mild cognitive impairment  (MCI), and  Alzheimer's disease (AD) (n = 3-4 biological replicates). IgG, control immunoprecipitate. Data information: Values are mean ± 95% confidence intervals. Adjusted p-values: ***p < 0.001, **p < 0.01, *p < 0.05, ns, not significant, ANOVA with Sidak's test.",
    "diseases": "MCI, mild cognitive impairment, AD, Alzheimer's disease"
  },
  {
    "caption": "E. Representative images of IHC  analysis of the indicated markers on tumor samples from mice  bearing MDA-MB-231 human breast cancer xenografts. Scale bar: 50μm. F. The histograms show: the expression of TRF2, calculated as immunoreactivity score (IRS) by IHC, and the count of positive cells to  γH2AX, Tunel  or CD31 staining. The analyses were performed on 3 mice  per group, the points represent the number of field analysed for each condition. Data information: For F, data are shown as mean ± SD. (F), P values are determined by Mann-Whitney test.",
    "diseases": "breast cancer"
  },
  {
    "caption": "G, H. Luminescent MDA-MB-436 cells were injected into the brain  and monitored by IVIS imaging system. After one week from implant, treatment with LNPs-miR-Control and LNPs-miR-182-3p was performed as indicated in A and B. Representative images from in vivo (upper panel) or ex-vivo (bottom panel) brain tumors are shown in G. Boxplots (H) show the measurement of photons for each  brain tumor (n=5 per group) acquired at the indicated times. Data information: For H, the line in the middle of the box plot denote a median value, the limits of box represent the interquartile range (25th to 75th percentiles), while, the whiskers denote the minimum to maximum values. For H, P values are determined by unpaired two-tailed t test;",
    "diseases": "brain tumor, brain tumors"
  },
  {
    "caption": "Representative Ca2+ signals in sperm from a patient with deafness-infertility syndrome lacking functional CatSper channels (CATSPER2-/-) (red) and a healthy donor (black), evoked by progesterone, PGE1, NH4Cl, or ionomycin. NH4Cl increases the intracellular pH. Bar graph: Amplitudes (n = 4; mean ± SD) of Ca2+ signals in CATSPER2-/- sperm",
    "diseases": "deafness-infertility syndrome"
  },
  {
    "caption": "Representative immunocytochemical staining of control sperm from healthy donors and CATSPER2-/- sperm form DIS patients using antibodies directed against CatSper 3 (D) or CatSper 4 (E); DNA was labelled with DAPI (blue). Scale bars represent 10 µm.",
    "diseases": "DIS"
  },
  {
    "caption": "Representative immunostaining of IDH2, CAIX (surrogate marker of Hif-1α), TIGAR, TKT, and CTPS1 in surgical specimens from upper tract urothelial carcinoma (UTUC) patients. The upper panel represents the immunostaining of metabolic enzymes of early-stage UTUC tumors, whereas the lower panel represents the images of invasive UTUC tumors. The power field",
    "diseases": "upper tract urothelial carcinoma, UTUC"
  },
  {
    "caption": "Kaplan-Meier curves showing the cancer-specific survival (CSS) of 74 UTUC patients treated with GC adjuvant chemotherapy. Metabolic enzymes were classified according to the results of receiver operating curve (ROC) analysis. Data were compared with the log-rank test.",
    "diseases": "UTUC"
  },
  {
    "caption": "Kaplan-Meier method showing the CSS of 32 MIBC patients treated with GC chemotherapy. The cutoffs for metabolic enzyme levels were determined according to the results of ROC analysis. Data were compared with the log-rank test.",
    "diseases": "MIBC"
  },
  {
    "caption": "(A) Waterfall plot showing the percentage of tumor volume change in olaparib-treated tumors compared to the tumor volume on day 1. +20% and -30% are marked by doted lines to indicate the range of PR, SD and PD. The box underneath summarizes different characteristics of each model and the clinical context at the moment of PDX implantation. TNBC, Triple Negative Breast Cancer; ER+BC, Estrogen Receptor positive Breast Cancer; P, primary; M, metastasis. Error bars indicate SEM from independent tumors (n ≥ 3).",
    "diseases": "ER+BC, Estrogen Receptor positive Breast Cancer, TNBC, Triple Negative Breast Cancer"
  },
  {
    "caption": "(B) Percentage of geminin-positive, RAD51 or γH2AX nuclear foci-containing cells in FFPE tumor samples from patients with HBOC syndrome. The box underneath summarizes the patient's young onset (<35y: <35 years), her family history (FH, purple box for PALB2-related tumors) and the presence of BRCA1 nuclear foci in the analyzed tumor samples.",
    "diseases": "HBOC syndrome"
  },
  {
    "caption": "(E) The DFS and OS assays of HCC patients (n=201) stratified by WDR6 expression.",
    "diseases": "HCC"
  },
  {
    "caption": "(F) Analysis of WDR6 using TCGA LIHC data. Fi and Fiii were plotted with GEPIA analyzing tool, and Fii were analyzed by UALCAN analyzing tool.",
    "diseases": "LIHC"
  },
  {
    "caption": "(A) Western blots confirmed WDR6 knockdown in HCC cells transduced with shWDR6 or shcontrol lentiviral vector.",
    "diseases": "HCC"
  },
  {
    "caption": "(B) The effects of WDR6 silencing on the invasive and proliferative ability of HCC cells, respectively. Left panel: HCC-LM3: P=0.912 shControl vs shWDR6-#1, P=0.889 shControl vs shWDR6-#2; HepG2: P=0.826 shControl vs shWDR6-#1, P=0.796 shControl vs shWDR6-#2; right panel: HCC-LM3: P=0.856 shControl vs shWDR6-#1, P=0.814 shControl vs shWDR6-#2; HepG2: P=0.726 shControl vs shWDR6-#1, P=0.745 shControl vs shWDR6-#2.",
    "diseases": "HCC"
  },
  {
    "caption": "(C) The survival plot of Albumin-Cre/+; Wdr6f/f mice with DEN-induced HCC.",
    "diseases": "HCC"
  },
  {
    "caption": "(B) The effects of WDR6 knockdown on the protein levels of p65, RelB, c-Rel, p52, and p50 in HCC cells.",
    "diseases": "HCC"
  },
  {
    "caption": "(Di-ii) The effects of autophagic deficiency using 3-MA on the levels of p65 protein and TNFα secretion in HCC cells with WDR6 knockdown.",
    "diseases": "HCC"
  },
  {
    "caption": "(Ei) WDR6 mRNA levels in Hep3B and MHCC-97L cells treated with or without TNFα in culture media. (Eii) Schematic diagram showing three candidate NF‐κB-binding sites in WDR6 promoter. (Eiii) The impact of IMD0354 on the luciferase reporter of WDR6 proximal promoter in HCC cells. (Eiv-v) ChIP assays using HCC cells or HCC tissues from patients (P#36 and P#54). Da",
    "diseases": "HCC"
  },
  {
    "caption": "(A) WDR6 or its mutant (Ai) or WDR6 shRNAs (Aii) or WDR6 with CUL4A siRNA (Aiii) affected the levels of endogenous UVRAG in HCC cell lines.",
    "diseases": "HCC"
  },
  {
    "caption": "(C) BALB/c mice introduced with H22-WDR6 overexpression cells were administered with Pep2-WDxR or Pep2-con with or without anti-PD-L1 antibody. The images and sizes of HCC (Ci), hematoxylin-eosin (H&E) staining and metastasis nodules of lung were presented (Cii). The survival analysis of the mouse after treatment was performed (n = 9/group) (Ciii). In the BALB/c mice from (C), Flow cytometry was performed to analyze PMN-MDSC, M-MDSC, and IFN-γ+ CD8+ T cells in tumors (Civ).",
    "diseases": "HCC"
  },
  {
    "caption": "(D) The survival test of DEN- and CCl4-induced HCC using WDR6-knockout and WT mice. At twenty-six weeks, mice were administered with or without anti-PD-L1 antibody (n = 6/group).",
    "diseases": "HCC"
  },
  {
    "caption": "F. 3D views (light-sheet imaging) of HH25 chick embryos engrafted with different melanoma patient samples, showing different patterns of tumor cell localization 50 hours post-engraftment.",
    "diseases": "melanoma"
  },
  {
    "caption": "(A) Immunofluorescence staining against Iba-1 in cortex (Cx), hippocampus (Hip) and cerebellum (Cb) of NPA affected and control 3 year-old children. Scale bars, 50 μm. (B) Magnified image showing ramified (left) versus amoeboid (right) morphology in control and NPA microglia. Scale bars, 10 μm. (C) Mean ± SEM area of Iba-1 positive cells in different brain regions from a NPA affected and a control child (n = 20 cells, Student´s t-test). ",
    "diseases": "NPA"
  },
  {
    "caption": "(D) Immunofluorescence staining against Iba-1 in the Cb of a NPC affected and a control child. Scale bars, 50 μm. Graph shows mean ± SEM area of Iba-1 positive cells (n = 30 cells, Student´s t-test).",
    "diseases": "NPC"
  },
  {
    "caption": "(I) Immunofluorescence staining against Iba-1 and CathB in Cb of a NPC patient. DAPI shows cell nuclei. Scale bar, 50 μm. A merged magnified image of the selected area is shown in the right down panel, scale bar 10 μm. Table shows mean ± SEM percentage of microglia presenting CathB staining in NPC and control children.",
    "diseases": "NPC"
  },
  {
    "caption": "A. FGF21SS and FGF21 improve insulin resistance by countering the inflammation in 3T3-L1 adipocytes. Cells were cultured in RAW-CM to induce inflammation and insulin resistance, while vehicle, FGF21 or FGF21SS were added simultaneously. The insulin sensitivity was indicated by insulin-induced AKT phosphorylation using western blotting analysis. Error bars show the SEM of four independent experiments. *p < 0.05, **p < 0.01 (Student's t-test) vs RAW-CM treated only group.",
    "diseases": "insulin resistance"
  },
  {
    "caption": "Anti-diabetic effect evaluation in ob/ob mice. Mice were injected subcutaneously with vehicle, FGF21 or FGF21SS at indicated doses every day. Body weight (B) was measured Error bars show the SEM of ten independent experiments. *p < 0.05, **p < 0.01 and ***p < 0.001 (Student's t-test) vs vehicle.",
    "diseases": "diabetic"
  },
  {
    "caption": "Anti-diabetic effect evaluation in ob/ob mice. Mice were injected subcutaneously with vehicle, FGF21 or FGF21SS at indicated doses every day. plasma glucose (D) was measured every day. Plasma insulin (C) was analyzed at day 7 using insulin ELISA kit. Error bars show the SEM of ten independent experiments. *p < 0.05, **p < 0.01 and ***p < 0.001 (Student's t-test) vs vehicle.",
    "diseases": "diabetic"
  },
  {
    "caption": "Expression levels of EMX2 and HOXB9 in 62 glioma cell lines. Data sourced from CCLE. Every dot represents a cell line. RPKM: reads per kilobase of transcript per million. In the boxplot, the top, middle and bottom box delimiters represent the 75th, 50th and 25th percentiles of the data, respectively. Top and bottom whiskers show the 75th percentile + 1.5*interquartile range and 25th percentile - 1.5*interquartile range, respectively.",
    "diseases": "glioma"
  },
  {
    "caption": "Quantification of EZH2 binding at EMX2, HOXB9 and GAPDH (negative control) promoters by ChIP-qPCR in M059K GBM cells. Values from two biological replicates are shown. Three asterisks indicate p-value < 0.001 of EZH2 samples relative to the negative control GAPDH (two-way ANOVA followed by pairwise comparisons using Holm-Sidak method). Ns: non-significant.",
    "diseases": "GBM"
  },
  {
    "caption": "Quantification of EMX2 levels by qRT-PCR in five different GBM cell lines upon treatment with 1μM, 3μM or 10μM of EZH2i for eight days, or a DMSO control. Values represent mean ± SEM from three technical replicates. The SEM is indicated to show reliability of the RT-PCR values, due to the low endogenous levels of EMX2. Two asterisks indicate p-value <0.01 comparing EZH2i- and DMSO-treated cells (Two-way ANOVA).",
    "diseases": "GBM"
  },
  {
    "caption": "Relationship between the extent of EMX2 upregulation induced by EZH2i and the DNA methylation level at the EMX2 promoter in GBM cell lines. Values for EMX2 upregulation are the fold-change in mRNA expression induced upon treatment with 10μM EZH2i (see: panel G), and are expressed relative to a DMSO control. Values represent mean ± SEM from three technical replicates. The SEM is indicated to show reliability of the RT-PCR values, due to the low endogenous levels of EMX2. Methylation values are averages of DNA methylation at CpGs across the promoter of EMX2 in GBM cell lines. All data sourced from the CCLE. The significance of the anti-correlation between mRNA levels and DNA methylation levels across cell lines is indicated (Spearman rank correlation).",
    "diseases": "GBM"
  },
  {
    "caption": "Expression of EMX2 in normal brain and GBM patient samples. Data sourced from the Repository of Molecular Brain Neoplasia Data (REMBRANDT). Four asterisks indicate p-value < 0.0001 (two-tailed Mann Whitney U test). Bars represent median ± interquartile range. Values are expressed relative to the mean of normal brain samples. N: 21 for normal brain, 214 for GBM. Note that the extent of EMX2 repression in GBM patients is likely underestimated due to the possible presence of normal adjacent tissue in the analysed samples, and due to the intrinsic background noise of microarrays, which limits detection of truly silenced genes.",
    "diseases": "GBM, Brain Neoplasia"
  },
  {
    "caption": "Relative expression of HOX genes in normal brain and GBM patient samples as detected by microarray analysis. Data sourced from REMBRANDT. Values are expressed relative to the median of normal brain samples. In the boxplots, the top, middle and bottom box delimiters represent the 75th, 50th and 25th percentiles of the data, respectively. Top and bottom whiskers show the 75th percentile + 1.5*interquartile range and 25th percentile - 1.5*interquartile range, respectively. One asterisk indicates p-value <0.05 (two-tailed Mann Whitney U test corrected for multiple comparison using Holm's method). N: 21 for normal brain, 214 for GBM. Data was not available for HOXD8.",
    "diseases": "GBM"
  },
  {
    "caption": "Covariance between EMX2 and EZH2 expression levels in GBM patient samples, as detected by microarray analysis. Data sourced from REMBRANDT. P-value and correlation coefficient (r) of the covariance are shown (Spearman rank correlation). Every dot is a patient. N: 214.",
    "diseases": "GBM"
  },
  {
    "caption": "Expression levels of EMX2 (top) and EZH2 (bottom) in tumour or adjacent normal regions laser microdissected from human GBM tumours as detected by RNA-seq. Data sourced from the Ivy Glioblastoma Atlas. FPKM: fragments per kilobase of transcript per million. The significance of the differential expression in normal and tumour regions across patients is indicated (two-way ANOVA). Bars represent mean ± SEM. N: 3 regions sampled for each GBM tumour, 2, 3, 2, 3, 2, 3, 3 and 1 regions for normal tissue of patients 1-8, respectively.",
    "diseases": "GBM, Glioblastoma"
  },
  {
    "caption": "Hematoxylin and eosin (H&E) staining of a human GBM tumour. The black square represents the approximate location of the field shown in G (left image). Serial sections were used for H&E and RNA-FISH. Scale bar: 300 µm.",
    "diseases": "GBM"
  },
  {
    "caption": "Visualisation of EZH2 (green) and EMX2 mRNA (red) in a human GBM tumour by RNA FISH. Nuclei were counterstained with DAPI. Scale bar: 20 µm.",
    "diseases": "GBM"
  },
  {
    "caption": "Expression of EMX2 (left) and EZH2 (right) in glioma patient samples, grouped according to tumour grade, as detected by RNA-seq. Data sourced from the Chinese Glioma Genome Atlas. Four asterisks indicate p-value < 0.0001 (Kruskal-Wallis test). Bars represent median ± interquartile range. N: 109 for grade II -, 72 for grade III, 144 for grade IV. RPKM: Reads per kilobase of transcript per million.",
    "diseases": "glioma, Glioma"
  },
  {
    "caption": "Proliferation assay examining the effect of EMX2 ectopic expression in U-87 MG and DBTRG-05MG GBM cells, RFP is used as a control. Values represent mean ± SEM from three biological replicates. The fold change in cell number after eight days of proliferation whilst expressing the exogenous protein is shown relative to an uninduced control. Two asterisks indicate p-value < 0.01 (one-tailed unpaired Student's t-test). Similar results were reported in [103] using other GBM cell lines.",
    "diseases": "GBM"
  },
  {
    "caption": "MRI scans showing representative brain tumours six weeks post-injection of DBTRG-05MG cells expressing EMX2 or RFP. Axial anatomical scan and coronal signal intensity map indicate location of tumour in RFP control (yellow arrow). Contrast enhancement in post-contrast images indicates tumour blood brain barrier breakdown. Signal was not present in pre-contrast images. Images show the same MRI slice position between mice. Scale bar: 2mm. Quantification of brain tumour size in mice injected with EMX2- or RFP- expressing DBTRG-05MG cells. Values represent mean ± SEM from four control and three EMX2 tumours. Five mice per conditions were injected but three (one for RFP, and two for EMX2) had to be excluded from the study due to complications from the procedure.",
    "diseases": "brain tumours"
  },
  {
    "caption": "B Representative pictures of different CTCs from the initial CellSearch® analysis of the metastatic breast cancer patient who gave rise to the breast CTC line. The detected tumor cells display clear keratin and DAPI staining, CD45-negativity as well as lack of, or very weak (4, 8), ERBB2 expression. Cells of small (about 5 µm in diameter, 1, 2) and large size (larger than 10µm in diameter, 2,3) were detected. While some CTCs displayed dot-like perinuclear keratin signals (1, 2), the majority showed diffuse keratin staining. Additionally, CTC clusters of 4-8 cells were present (5, 6). Some CTCs showed multiple/lobed nuclei (4, 7, 8).",
    "diseases": "breast cancer"
  },
  {
    "caption": "A Western blot analysis of selected protein markers, including ERα, EGFR, ERBB2, EpCAM, K18, K19, K8, E-cadherin, N-cadherin, vimentin, CD44, CD24, SNAIL, SLUG, TWIST and α-tubulin (as a loading control) (n=3 replicates). CTC-ITB-01 was compared to more mesenchymal ER- Hs578t and epithelial ER+ MCF-7 breast cancer cell lines.",
    "diseases": "breast cancer"
  },
  {
    "caption": "C PAM50 classifier results showing probabilities of pooled CTC-ITB-01 cells matching specific molecular breast cancer subtypes. Starting from lowest probability, CTC-ITB-01 was classified as 1.02% (s=2.5%) normal-like, 3.11% (s=6.6%) Basal-like, 13.11% (s=9.3%) ERBB2-positive, 16.77% (s=23.7%) luminal A, and 65.22% (s=16.6%) luminal B breast cancer subtype. Data was generated from n=3 replicates.",
    "diseases": "breast cancer"
  },
  {
    "caption": "D PAM50 classifier results showing probabilities of the non-adherent and adherent CTC-ITB-01 fractions matching molecular subtypes. Selected bars are not visible due to extremely low probability (close to zero). Both fractions show greatest alignment with a luminal B subtype. Starting from lowest probability, the adherent fraction of CTC-ITB-01 was classified as 0% (±0%) normal-like, 6.22% (±9.0%) Basal-like, 17.85% (±8.6%) ERBB2-positive, 0% (s=0%) luminal A, and 75.92% (s=0.7%) luminal B breast cancer subtype. The suspension cell fraction of CTC-ITB-01 was classified as 2.04% (s=3.5%) normal-like, 0% (s=0%) Basal-like, 17.32% (s=9.7%) ERBB2-positive, 33.5% (s=23.8%) luminal A, and 68.67% (s=18.6%) luminal B breast cancer subtype, respectively. Data was generated from n=3 replicates.",
    "diseases": "breast cancer"
  },
  {
    "caption": "E Representative images of the wound closure process were captured during the twenty-one-day in vivo experiments (scale bar: 500 μm; n=8, biological replicates).",
    "diseases": "wound"
  },
  {
    "caption": "G H&E (day 7 and 14) and Masson's  (day 14) staining  for full-thickness skin  samples containing the entire wound  area (scale bar: 500 μm; n=8), the under images are the higher magnification images that indicates an area in the red boxed region in day 7 and day 14 (scale bar: 100 μm; n=8, biological replicates), (gt: granulation tissue, he:  hyperproliferative epithelium, black arrow: wound  edges).",
    "diseases": "wound"
  },
  {
    "caption": "H- J Quantitative analysis of  regenerated granulation  (H) on day 7 and Re-epithelialization of wound  bed (I) and Masson's trichrome-stained  tissue (J) on day 14 (blue for collagen) (***P < 0.001, ****P < 0.0001, and ns: not significant (P > 0.05) vs. the blank control group; n=8, biological replicates). Data information: Data represent means ± SD. The differences between groups were analyzed using ordinary one-way ANOVA with Tukey's multiple comparison test in (H, I, J, in Graph Pad Prism 8.",
    "diseases": "wound"
  },
  {
    "caption": "E IF staining  for CD31  (red; endothelial  marker, for new capillary  formation) at day 7 and  α-SMA (green; smooth muscle marker, for vascular  maturation) at day 14, with both the entire wound  region and magnified yellow-box zone (scale bar: 100 μm; n=8, biological replicates) (gt:  granulation tissue, he: hyperproliferative epithelium).",
    "diseases": "wound"
  },
  {
    "caption": "G Representative  multiphoton projection images   of  blood vessels  (lectin) in healed skin wound  tissue after the administration of different treatments at day 21 post-injury, uninjured skin   was analyzed as positive control. Up: the images of the entire sampling area (yellow circled) containing the healed wound  (green circled); Down: magnified zone (blue boxed in the upper images; scale bar: 100 μm; n=3, biological replicates).",
    "diseases": "wound"
  },
  {
    "caption": "B Gross view of the wound    closure process was captured during the twenty-one-day in vivo experiments (scale bar: 500 μm; n=8, biological replicates). C The percentage of wound  closure determined at each time point (****P < 0.0001 and ns: not significant (P > 0.05) vs. the blank control group; n=8, biological replicates). Data information: Data represent means ± SD. The differences between groups were analyzed using two-way ANOVA with Tukey's multiple comparison test in (C) in Graph Pad Prism 8.",
    "diseases": "wound"
  },
  {
    "caption": "D Full-thickness skin  samples containing entire wound  sites were stained  with H&E (day 7 and day 14) and Masson (day 14) (scale bar: 500 μm, n=8, biological replicates), the under images are the higher magnification images that indicates an area in the red boxed region in day 7 and day 14 (scale bar: 100 μm; n=8, biological replicates) (gt: granulation tissue, he: hyperproliferative epithelium, black arrow: wound  edges).",
    "diseases": "wound"
  },
  {
    "caption": "F Representative  multiphoton projection images  of  blood vessels (lectin) in healed skin wound  tissue after the administration of different treatments at day 21 postinjury, uninjured skin  was analyzed as positive control (Up: the images of entire sampling sites (the yellow circular region) containing healed wound  sites (the green circular region); Down: the images of higher magnification that indicates an area in the blue boxed region in the upper images; scale bar: 100 μm; n=3, biological replicates).",
    "diseases": "wound"
  },
  {
    "caption": "(c) Immunohistochemistry to detect LC3I, p62 and Atg5 in tumours from KRas;Atg5fl/+ and KRas;Atg5fl/fl mice 18 weeks after AdCre inhalation. Note highly elevated levels of LC3I and p62, both indicative of defective autophagy, in KRas;Atg5fl/fl tumours. Scale bars, 50 μm. (d,e) Impaired formation of autophagosomes (arrows) in KRas;Atg5fl/fl tumour cells.",
    "diseases": "tumours"
  },
  {
    "caption": "(d,e) Impaired formation of autophagosomes (arrows) in KRas;Atg5fl/fl tumour cells. (d) Representative electron microscopy images are shown for KRas;Atg5fl/+ and KRas;Atg5fl/fl tumours18 weeks after AdCre inhalation. Scale bars, 5 μm for upper and 2 μm for lower panels. M, mitochondria; *, lamellar bodies (Corpuscula lamellariae), rare cell organelles containing surfactant lipoproteins characteristic for type II pneumocytes. (e) Mean percentages (±s.e.m.) of tumour cells with detectable autophagosomes or autolysosomes, counted on electron microscopy images. n≥8 mice per genotype and at least 20 intact cells for each electron microscopy section were counted. ***P0.001 (χ2-test of a generalized linear model with logit link assessing the genotype effect).",
    "diseases": "tumours"
  },
  {
    "caption": "(a) Representative electron microscopy images of autolysosomes (left panels), autophagosomes (middle panels) and mitophagy (right panels), all indicated by arrows, in lungtumour cells from control KRas;Atg5fl/+ mice18 weeks after AdCre inhalation. Note the near-to-complete absence of such structures in the lungtumour cells from KRas;Atg5fl/fl littermates. Very rarely, we found cells with one autolysosome (left panels) or one single autophagosome (middle panels; arrows) in KRas;Atg5fl/fl tumours, whereas such structures can frequently be seen within single KRas;Atg5fl/+ tumour cells. Of note, the presence of a single autophagosome or a single autolysosome was scored as a positive event in Fig. 1e. Also note aberrant mitochondrial morphologies and increased mitochondrial numbers in KRas;Atg5fl/fl tumour cells. * indicates lamellar bodies. Scale bars, 2 μm. (b) Mean numbers (±s.e.m.) of mitochondria per lungtumour cell from KRas;Atg5fl/+ and KRas;Atg5fl/fl mice18 weeks after tumour induction. Numbers of mitochondria were determined by electron microscopy. n≥8 mice per genotype and a minimum of 20 intact cells were counted per sample. ***P0.001 (χ2-test assessing the genotype effect in a generalized linear model with log link).",
    "diseases": "tumours"
  },
  {
    "caption": "(c) Mitochondria (arrows) in KRas;Atg5fl/+ and KRas;Atg5fl/fl lung tumour cells 18 weeks after AdCre inhalation. Note markedly altered mitochondrial morphology, that is, disorganized matrix structures, rounding and enlargement in the autophagy-defective KRas;Atg5fl/fl cells. Au, autophagosomes; Au-L, autolysosome; *, lamellar bodies. Scale bars, 2 μm.",
    "diseases": "tumour"
  },
  {
    "caption": "(d-g) Bioenergetics profiling of purified tumour cells from KRas;Atg5fl/+ and KRas;Atg5fl/fl mice (e) 6 weeks and (g) 18 weeks after tumour induction. Representative experimental data are shown. Oxygen consumption rates (OCR) were used to detect the bioenergetics profiles of purified tumour cells using a Seahorse Bioscience 24XF extracellular flux analyser. OCR±s.e.m. were recorded to construct bioenergetics profiles for basal respiration (BR), ATP turnover (AT), respiratory capacity (RC), spare respiratory capacity (SRC) and proton leakage (PL). A minimum of seven different samples were analysed for each group. *P0.05; **P0.01(unpaired, two-sided t-test).",
    "diseases": "tumour"
  },
  {
    "caption": "(b) Atg5 mRNA expression was determined by quantitative PCR. Data are shown as mean relative mRNA expression±s.e.m. in KRas;Atg5fl/fl tumours as compared with tumours from KRas;Atg5fl/+ mice (set to 1). Values were normalized to β-actin mRNA expression. n=3 per group.",
    "diseases": "tumours"
  },
  {
    "caption": "A) Selective enrichment of AGR2 modulators in colonic Crohn's disease (CD). Percentage of tested genes with altered expression in colonic biopsies from patients with Ulcerative Colitis (UC, n=8) and colonic CD (CC, n=15) and in ileal biopsies from patients with ileo-colonic CD (IC, n=9).",
    "diseases": "CD, Crohn's disease, UC, Ulcerative Colitis"
  },
  {
    "caption": "B) Hierarchical clustering of the AGR2 modulator genes significantly deregulated in non-inflamed colonic mucosa from patients with Crohn's Disease (CD) versus healthy controls (C) (dChip software t-Test)",
    "diseases": "Crohn's Disease"
  },
  {
    "caption": "C) TMED2 mRNA expression in healthy controls (CT), colonic Crohn's disease (CC) and ulcerative colitis (UC).",
    "diseases": "Crohn's disease, UC, ulcerative colitis"
  },
  {
    "caption": "D) Representative immunohistological analysis of TMED2 in non-inflamed colonic biopsies from healthy controls and patients with active CD.",
    "diseases": "CD"
  },
  {
    "caption": "E) Representative immunohistological analysis of CD163 (scavenger receptor present in macrophages), AGR2, and TMED2 in non-inflamed colonic biopsies from healthy controls and patients with active or quiescent CD.",
    "diseases": "CD"
  },
  {
    "caption": "F) Semi-quantitative analysis of CD163, AGR2, and TMED2 immunostaining in colonic mucosa from healthy controls (C) and patients with quiescent (Q) or active (A) CD. Three random sections from each patient of the four groups were scored. Final IHC scores (AxB range to 0-9) combine the percentage of positively labelled cells. A: % of IHC positive labeled cells - 0 (0%), 1 (<30%), 2 (30 to 60%), 3 (>60%)) and the intensity of the reaction product. B: 0 (no reaction), 1 (weak), 2 (mild), 3 (strong) in most of the examined fields. All values are mean ± S.E.M.",
    "diseases": "CD"
  },
  {
    "caption": "b. Heatmap depicting mean  expression of the top 20 upregulated genes of fibroblast  isolated from wound-induced tumours (Pap) compared to fibroblasts from wild-type (WT) and inflamed (InvEE)   back  skin (n=3 per condition).  PRSS35 is indicated in red as a top upregulated gene in  CAFs.",
    "diseases": "Pap"
  },
  {
    "caption": "a.  Immunofluorescent images  of skin sections from  PDGFRα-eGFP reporter mice with normal (WT, n=4), inflamed (InvEE, n=4), wounded (d14 post-wounding;  wound, n=4), or tumour-associated (Papilloma, Pap d17 and d30 post-wounding, n=4 per condition) skin. Nuclei  were  stained  with Dapi  (4', 6-diamidino- 2- phenylindole; blue). Dotted line represents  epidermal-dermal   boundary. Scale bars: 50 μm. b. Quantification of the  number of fibroblasts present in different skin conditions (n=4 mice per condition; ** p<0.01; *** p<0.001; **** p<0.0001; One-way ANOVA testing). Data represent means of multiple microscopic fields ± S.E.M. ",
    "diseases": "Pap, Papilloma, wound"
  },
  {
    "caption": "c.   Herovici staining  of sections of normal (WT), inflamed (InvEE), wound, or tumour-associated (Papilloma) skin. Scale bars: 100 μm.",
    "diseases": "Papilloma, wound"
  },
  {
    "caption": "c. Relative mRNA levels of PRSS35 in lysates from normal skin (WT, n=4  mice), inflamed skin (InvEE, n=4 mice), wounds  (d14pw, n=4 mice) and wound-induced  papillomas (Pap, n=5  mice). (* p=0.0159; Mann-Whitney test). Data represent means of three technical replicates ± S.E.M.",
    "diseases": "Pap, papillomas, wound, wounds"
  },
  {
    "caption": "c, d. Incidence of  papilloma  formation (ns: non-significant; Gehan-Breslow-Wilcoxon test) (c) and number of tumours per mouse (d) in wild-type (WT, n=17) and PRSS35-/- (n=22) mice treated with DMBA-TPA (*p=0.0171; Wilcoxon matched-paired rank test). Data represent means ± S.E.M.",
    "diseases": "papilloma"
  },
  {
    "caption": "d.  Picrosirius red staining of normal  skin, day 14 post-wounding (d14pw) skin or wound-induced papillomas from WT and PRSS35 KO mice. Red colouring indicates thick  fibres, green colouring indicates thin fibres. Scale bars: 200 µm. e. Quantification of picrosirius red staining as total collagen  density (upper panel) and ratio of red versus green picrosirius staining (lower panel). Using QuPath Bioimage analysis software pixels colouring red or green were determined per area. (n≥4 technical replicates per condition) (* p<0.05, ** p<0.01, **** p<0.0001.; Two-way ANOVA with multiple comparisons). Data represent means ± S.E.M. ",
    "diseases": "papillomas, wound"
  },
  {
    "caption": "(a) Plasma levels of TNF and IL8 from patients with uncomplicated (black circles, n=14) or cerebral (red circles, n=9) malaria correlate with levels of XO-produced ROS detected in each sample. ROS is expressed as fold change over plasma from healthy controls. Uncomplicated malaria, gray circles, cerebral malaria, red circles. Linear regression (a) were performed to determine statistical significance (*p<0.05, **p<0.01).",
    "diseases": "cerebral, cerebral malaria, malaria, uncomplicated, Uncomplicated malaria"
  },
  {
    "caption": "(b) Levels of XO activity in malaria patients correlate with disease severity UM (uncomplicated malaria), CM (cerebral malaria). Mann-Whitney test (b) were performed to determine statistical significance (*p<0.05, **p<0.01).",
    "diseases": "cerebral malaria, CM, malaria, UM, uncomplicated malaria"
  },
  {
    "caption": "(c) Plasma from malaria patients induce macrophages to secrete cytokines, which are inhibited by a XO specific inhibitor. Plasma from a healthy control (HP) and from three patients: P1 (with cerebral malaria), P2 and P3 (both with uncomplicated malaria) was pre-incubated for 30 min with febuxostat (Feb) or alone at 37ºC before addition to macrophages at 1:2 dilution in media for 30 min. Cells were washed and cytokine secretion measured in triplicates after 24 h of incubation. unpaired t-tests (c) were performed to determine statistical significance (*p<0.05, **p<0.01).",
    "diseases": "cerebral malaria, malaria, uncomplicated malaria"
  },
  {
    "caption": "C. Dissected flatmount of zebrafish embryos injected with Alx1DN, after Alcian blue staining. The embryos developed an absence of the frontonasal derived median portion of the anterior neurocranium (ANC) and a profound hypoplasia of the Meckel's and ventral cartilages. In the most severely affected zebrafish, a nearly abrogated ANC was observed. Scale bar: 200 µm.",
    "diseases": "hypoplasia"
  },
  {
    "caption": "D Survival analysis of HRD positive patients according to quartile of RAD51NES. Log-rank test, shading denotes 95% confidence intervals. E, Survival analysis of HRD negative patients. Log-rank test, shading denotes 95% confidence intervals. ",
    "diseases": "HRD"
  },
  {
    "caption": "A In-vitro cell survival assay of HGSOC cell lines upon stable RAD51 overexpression. Mean with standard deviation is shown of at least three biological replicates per point. Extra-sum-of-squares F test.",
    "diseases": "HGSOC"
  },
  {
    "caption": "B In-vitro colony forming assays comparing RAD51-overexpressing and control HGSOC cell line, Caov-3, after treatment with increasing doses of carboplatin. Mean and SD of four biological replicates (left) a representative experiment (right). P-value for a comparison between cell lines for each drug treatment condition is indicated above the bars. T-test.",
    "diseases": "HGSOC"
  },
  {
    "caption": "F Immune genes enriched in RAD51- High and RAD51-Low tumours across four EOC mRNA cohorts (TCGA, AOCS, MGH, Duke).",
    "diseases": "EOC"
  },
  {
    "caption": "Representative images (left) and percentage (right) of cells presenting 1 or more γH2AX and RAP1 colocalizing foci (TIFs) upon treatment of CHA9-3 lung cancer cells with the indicated compounds. White arrowheads point to colocalization of γH2AX and RAP1. Scale bars, 5μm. Data are representative of n=6 (DMSO) and n=3 (mTORi, PI3Ki, RTKi, MEKi, ERKi, HSPO90i, CDKi, Docetaxel) biological replicates",
    "diseases": "lung cancer"
  },
  {
    "caption": "Effect of trastuzumab (50 nM, 5 days) in HER2 positive breast cancer cell lines (SKBR3, BT474, BTRH, MDA-MB-361, HCC1419, HCC1569 and HCC1954). The blue line indicates the threshold (established from BTRH) used to consider a cell line resistant to trastuzumab.",
    "diseases": "breast cancer"
  },
  {
    "caption": "Fibroblast activation during wound repair. Immunofluorescence staining for α−sma (red) of PDGFRαH2BEGFP (green) wound sites at indicated post wounding (PW) times Nuclei were labelled with DAPI (blue)",
    "diseases": "wound, wounding"
  },
  {
    "caption": "Fibroblast activation during wound repair. quantification of α−sma fluorescence intensity in pixel per area inside the upper and lower wound bed (n= 4 PW0, PW2, PW7, PW21; n= 3 PW10, PW14; n= 2 PW4 biological replicates)",
    "diseases": "wound"
  },
  {
    "caption": "Changes in fibroblast density, proliferation and collagen deposition during wound repair. Quantification of fibroblast proliferation in the upper and lower dermis inside the wound bed over time (n= 4 PW0, PW2, PW21; n= 3 PW4, PW10; n= 2 PW7, PW14 biological replicates).",
    "diseases": "wound"
  },
  {
    "caption": "Quantification of fibroblast density during wound repair inside and outside the wound bed (n= 4 PW0, PW2, PW21; n= 3 PW4, PW10; n= 2 PW7, PW14 biological replicates).",
    "diseases": "wound"
  },
  {
    "caption": "Polarised light image of Picrosirius red stained back skin section shown as binary image at indicated time points after wounding.",
    "diseases": "wounding"
  },
  {
    "caption": "Quantification of fibroblast proliferation (left; n= 4 PW0, PW2, PW21; n= 3 PW4, PW10; n= 2 PW7, PW14 biological replicates) and collagen density (right; n= 4 PW0, PW2; n= 3 PW4, PW7, PW10, PW14; n= 2 PW21 biological replicates) inside (A) and outside (B) the wound bed over time.",
    "diseases": "wound"
  },
  {
    "caption": "Live imaging of adult PDGFRαH2BEGFP back skin during wound healing. Representative wound bed Z-stack stitched maximum projections of the entire wound bed (upper panel) showing fibroblasts (green) and collagen with second harmonic generation (SHG) in purple at indicated time points after wounding and before live imaging. Dotted line indicates wound edge and boxed area indicates the position of the magnified area below.",
    "diseases": "wound, wounding"
  },
  {
    "caption": "Live imaging of adult PDGFRαH2BEGFP back skin during wound healing. Representative time-lapse images of adult wound bed at PW4, where Z-directional movement is visualized by pseudo colouring the fibroblast nuclei (red, movement towards the basement membrane; blue, movement away from the basement membrane).",
    "diseases": "wound"
  },
  {
    "caption": "In vivo lineage tracing of upper (Blimp1Cre) and lower (Dlk1CreER) dermal fibroblasts during wound healing. Immunofluorescence image of Blimp1Cre x Confetti (upper panels) and Dlk1CreER x Confetti (lower panel) back skin inside and outside the wound bed at 10 days post wounding. Colours show YFP (green), RFP (red) and CFP (blue) with bright field image overlaid. (G) Clone size quantification of Blimp1Cre labelled fibroblasts inside and outside the wound bed at 10 days post wounding (n= 400 clones of 4 biological replicates). (H) Clone size quantification of Blimp1Cre labelled fibroblasts inside and outside the wound bed at 10 days post wounding (n=300 clones of 2 biological replicates).",
    "diseases": "wound, wounding"
  },
  {
    "caption": "A. Immunoblotting of c-MYC and ATF4 in melanoma cells treated with NT-siRNA (-) or siASNS (#1 or #2) for 72 hr.",
    "diseases": "melanoma"
  },
  {
    "caption": "Reverse transcription with quantitative PCR (RT-qPCR) of the indicated transcripts in melanoma cells 36 hr after treatment with siASNS (#1 or #2) (B)",
    "diseases": "melanoma"
  },
  {
    "caption": "C. Reverse transcription with quantitative PCR (RT-qPCR) of the indicated transcripts in melanoma cells 36 hr after treatment with siASNS, siATF4, or both (C).",
    "diseases": "melanoma"
  },
  {
    "caption": "D. Immunoblotting of ATF4 and ASNS in melanoma cells 72 hr after treatment with siASNS, siATF4, or both.",
    "diseases": "melanoma"
  },
  {
    "caption": "E. Proliferation of melanoma cells over indicated times after treatment with siASNS, siATF4, or both.",
    "diseases": "melanoma"
  },
  {
    "caption": "F. RT-qPCR analysis of indicated transcripts in melanoma cells 36 hr after treatment with siASNS (#1 or #2).",
    "diseases": "melanoma"
  },
  {
    "caption": "Immunoblotting of c-MYC in melanoma cells treated for 72 hr with siASNS, L-Asn, or both (G)",
    "diseases": "melanoma"
  },
  {
    "caption": "Immunoblotting of indicated proteins in melanoma cells 72 hr after treatment with NT-siRNA (-) or siASNS (#1 or #2) (B and C)",
    "diseases": "melanoma"
  },
  {
    "caption": "Immunoblotting of indicated proteins in melanoma cells 72 hr after treatment with siASNS, PLX-4032, or both (D).",
    "diseases": "melanoma"
  },
  {
    "caption": "H. RT-qPCR analysis of indicated transcripts in melanoma cells 36 hr after treatment with siASNS, HA-GSK3-β (S9A), or both.",
    "diseases": "melanoma"
  },
  {
    "caption": "A. Immunoblotting of indicated proteins in melanoma cells treated with siASNS, sicMYC (#1 or #2), or a combination of siASNS and sicMYC (#1 or #2) for 72 hr.",
    "diseases": "melanoma"
  },
  {
    "caption": "B. RT-qPCR analysis of indicated transcripts in melanoma cells 36 hr after treatment with siASNS, sicMYC, or both.",
    "diseases": "melanoma"
  },
  {
    "caption": "C. Immunoblotting of indicated proteins in melanoma cells 72 hr after treatment with siASNS, sicMYC, PLX-4032, or a combination of siASNS and sicMYC, or siASNS and PLX-4032.",
    "diseases": "melanoma"
  },
  {
    "caption": "E. RT-qPCR analysis of indicated transcripts in melanoma cells after 36 hr treatment with siASNS, HA-GSK3-β (S9A), or both.",
    "diseases": "melanoma"
  },
  {
    "caption": "Proliferation of melanoma cells over indicated times after treatment with siASNS, sicMYC, or both (G),",
    "diseases": "melanoma"
  },
  {
    "caption": "Proliferation of melanoma cells over indicated times after treatment with siASNS, HA-GSK3-β (S9A), or both (H).",
    "diseases": "melanoma"
  },
  {
    "caption": "B. RT-qPCR analysis of indicated transcripts in melanoma cells after 36 hr treatment with siASNS, siSLC7A5, or both.",
    "diseases": "melanoma"
  },
  {
    "caption": "C. Proliferation of melanoma cells over indicated times after treatment with siASNS, siSLC7A5, or both.",
    "diseases": "melanoma"
  },
  {
    "caption": "L. RT-qPCR analysis of indicated transcripts in melanoma cells after 36 hr treatment with siASNS, siSLC3A2, or both.",
    "diseases": "melanoma"
  },
  {
    "caption": "M. Proliferation of melanoma cells over indicated times after treatment with siASNS, siSLC3A2, or both.",
    "diseases": "melanoma"
  },
  {
    "caption": "(A) Representative images showing the myogenic differentiation, as assessed by immunostaining for MyHC (green), of human MuSCs (hMuSCs) isolated from muscle biopsies of DMD patients, either before the beginning of the clinical trial (hMuSCs (-)) or after 1 year of treatment with Givinostat (hMuSCs Giv (-)). Cells were cultured alone or (only for hMuSCs -) in transwell co-culture with FAPs isolated from the same patients and exposed in vitro to Giv (+ehFAPs Giv Vitro) or control vehicle (+ehFAPs). The upper panels represent myogenic differentiation of DMD-1 patient; bottom panels represent myogenic differentiation of DMD-2 patient. Dose and timing of Giv treatment as described in Bettica et al., 2016 (23). Scale bar = 50 μm. (B) Graph showing the differentiation index of hMuSCs described in (A). Two technical replicates are shown. Data information: Nuclei were counterstained with DAPI (blue). All data correspond to the average ± SEM.",
    "diseases": "DMD"
  },
  {
    "caption": "(E) Representative images of miR-206-3p (violet) immunohistochemistry in vastus medialis bioptic samples of Control and DMD patients at different ages: 1 year (n=2), 4 years (n=3) and 9 years old (n=2). (F) Graph representing miR-206-3p violet area quantification relative to (E). ",
    "diseases": "DMD"
  },
  {
    "caption": "(D) Representative images of CD90 (green), Dapi (blue) and miR-206-3p (violet) immunohistochemistry in brachial biceps bioptic samples of DMD patient before (CTR) and after Givinostat treatment (GIV). Scale bar = 50 μm. (E) Graph showing the quantifications of miR-206-3p violet area measured as pixel^2/field relative to the experimental points indicated in (D) (n=18, biological replicates). Star (*) indicates t-test analysis. **p<0.01. Data information: Nuclei were counterstained with DAPI (blue).",
    "diseases": "DMD"
  },
  {
    "caption": "(F) Graph showing the relative expression of miR-206-3p in EVs isolated from a human population of muscle resident cells enriched in FAPs (ehFAPs) isolated from biopsies of two DMD patients (DMD-1 and DMD-2) before (CTR) and after (GIV) Givinostat treatment, Two technical replicates are shown.",
    "diseases": "DMD"
  },
  {
    "caption": "Stainings and relative measurements on Tibialis Anterior muscle transversal sections of 1.5 months old mdx mice treated daily for 21 days with intra-peritoneal injection of vehicle (CTR) or TSA, or once a week with intramuscular injections (Tibialis Anterior) of EVs derived from FAPs (EVs-FAPs) exposed or not to TSA in vivo (EVs-FAPs CTR -, EVs-FAPs TSA -) EVs derived from FAPs control transfected with the antagomiR-206 (EVs-FAPs CTR A-206) and of EVs-FAPs TSA transfected with antagomiR-206 and antagomiR-145 (EVs-FAPs TSA A-206, EVs-FAPs TSA A-145). EVs were injected every seven days and sacrificed after 21 days of treatment (n=5 for CTR, TSA EVs-FAPs CTR and EVs-FAPs TSA while for AntagomiRs n=3, biological replicates). (L) Representative images of myeloperoxidase staining (MPO-red). Scale bar = 50 μm. (M) Graph showing the quantifications of inflammation (MPO). Data information: Nuclei were counterstained with DAPI (blue).",
    "diseases": "inflammation"
  },
  {
    "caption": "Representative sections of WT and MPSIIIA brains at 9 months of age stained for astrocytes (GFAP) or microglia (isolectin B4, ILB4). Images correspond to high power views covering cortical layers II-V. Scale bar, 100 μm. (n=4 mice per group).",
    "diseases": "MPSIIIA"
  },
  {
    "caption": "Quantitative PCR for various inflammatory cytokines in whole brains from 9 month old WT and MPSIIIA mice. Symbols above bars are versus WT. (n=6 mice per group). Data are expressed as mean ± STDEV, data for each cytokine were tested by unpaired t-test; *P<0.05, **P<0.01, ***P<0.001. Symbols above bars are versus WT.",
    "diseases": "MPSIIIA"
  },
  {
    "caption": "Quantification of IL-1β and IL-1Ra levels in plasma from human healthy control and MPSIII patients (n=6 control participants and n=21 MPSIII patients). Data are expressed as mean ± STDEV and were tested by unpaired t-test. C. IL-1β, control vs. MPSIII P=0.0407; D. IL-1Ra, control vs. MPSIII P=0.0001. Quantification of IL-1β and IL-1Ra levels in cerebrospinal fluid (CSF) from control and MPSIII patients (n=3 control participants and n=21 MPSIII patients). Data are expressed as mean ± STDEV and were tested by unpaired t-test; *P<0.05. F. IL-1Ra, control vs. MPSIII P=0.0167.",
    "diseases": "MPSIII"
  },
  {
    "caption": "Multi-heparinase (HepM) and/or chondroitinase ABC (cABC) digests were performed on MPSIIIA GAG, and the resulting oligosaccharides applied to a WT mixed glial culture for 24 hours alongside heparin, bovine HS (bHS), porcine DS (pDS) and WT GAG. The intracellular production of IL-1β was measured (n=3 independent experiments each with 3 inter-experimental replicates). Data are expressed as mean ± STDEV and were tested by one-way ANOVA with Tukey's post-test; *P<0.05, ***P<0.001. Symbols above bars are versus MPSIIIA GAG alone.",
    "diseases": "MPSIIIA"
  },
  {
    "caption": "Representative sections from 9 month old WT and MPSIIIA brains showing secondary storage of GM2 ganglioside, cholesterol, protein aggregates and amyloid beta peptide 1-40 and 1-42 within cortical layers II to V/VI, x20, scale bar: 50 μm. Inserts, 100x, scale bar: 10μm. (n=4 mice per group)",
    "diseases": "MPSIIIA"
  },
  {
    "caption": "ATP levels in whole brain homogenate from 9 month old WT and MPSIIIA mice (n=6 mice per group). Data are expressed as mean ± STDEV and were tested by unpaired t-test. WT vs. MPSIIIA P<0.02",
    "diseases": "MPSIIIA"
  },
  {
    "caption": "Caspase 1 activity levels in whole brain homogenate from WT and MPSIIIA mice (n=6 mice per group). Data are expressed as mean ± STDEV and were tested by unpaired t-test. WT vs. MPSIIIA P<0.0001",
    "diseases": "MPSIIIA"
  },
  {
    "caption": "Human IL-1Ra expression was quantified in the plasma of mice at 6 months of age (4 months post-transplant) (n=10 mice per group). Data are expressed as mean ± STDEV and were tested by one-way ANOVA with Tukey's post-test; WT vs. LV.IL1RN P<0.0001; MPSIIIA vs. LV.IL1RN P<0.0001. Symbols above bars are versus WT.",
    "diseases": "MPSIIIA"
  },
  {
    "caption": "Quantification of human IL-1Ra levels in the brain of transplanted MPSIIIA mice (n=10 mice per group). Data are expressed as mean ± STDEV and were tested by one-way ANOVA with Tukey's post-test; WT vs. LV.IL1RN P<0.0001; MPSIIIA vs. LV.IL1RN P<0.0001. Symbols above bars are versus WT.",
    "diseases": "MPSIIIA"
  },
  {
    "caption": "Representative sections from 6-month old MPSIIIA and LV.IL1RN transplanted MPSIIIA mice. Sections show the CA3 region of the hippocampus. Cells expressing high levels of human IL-1Ra are indicated with black arrows. 40x, scale bar, 50 μm (n=4 mice per group).",
    "diseases": "MPSIIIA"
  },
  {
    "caption": "(Left) Representative images of Sirius red staining and (right) % of fibrosis area in 24 month-old mice treated or not with navitoclax.",
    "diseases": "fibrosis"
  },
  {
    "caption": "J Swing Duration CV (CV%) (Left panel) and Ataxia  Coefficient in  Gait tests 7 days post-MPTP. Data information: The data are presented as the mean ± SEM. Statistical significance was analyzed with two-sided student's t-tests, and is indicated with NS for not significant (p > 0.05), * for p < 0.05, ** for p < 0.01, and *** for p < 0.001. n value means the number of biological replicates made for each data point.",
    "diseases": "Ataxia"
  },
  {
    "caption": "Relative mRNA levels of KDM6A, nephrin and WT-1, normalized to β-actin, expressed in kidney glomeruli of normal and diabetic mice at 4, 8 and 12 weeks after diabetic induction. *Significant differences (P < 0.05) compared with normal controls (Wilcoxon two-sample test; n =8 each).",
    "diseases": "diabetic"
  },
  {
    "caption": "B Western blot analysis of nephrin, KDM6A and H3K27me3 in kidney glomeruli of normal and diabetic mice at different time points. *P < 0.05 versus normal controls for the indicated time points (Wilcoxon two-sample test; n = 3).",
    "diseases": "diabetic"
  },
  {
    "caption": "C Changes in body weights and levels of blood glucose in normal, diabetic and GSK-J4-treated diabetic mice. As noted, GSK-J4 treatment did not significantly affect body weights or blood glucose levels in diabetic mice during the experimental period of 12 weeks (Wilcoxon two-sample test; n = 8).",
    "diseases": "diabetic"
  },
  {
    "caption": "D Levels of urinary protein excretion, weights of kidney, and levels of HbA1c in normal, diabetic and GSK-J4-treated diabetic mice. Urinary total protein excretion, kidney weight and levels of HbA1c were measured at 12 weeks after diabetic induction. The mean relative kidney weight (%) shown in the study is determined as the percent of kidneys out of total body weight, and the HbA1c level is defined as the ratio of HbA1c to the total hemoglobin (% HbA1c; DCCT unit). *P < 0.05 versus normal controls, #P < 0.05 versus untreated diabetic mice (Parametric ANOVA and a Bonferroni post hoc test; n = 8).",
    "diseases": "diabetic"
  },
  {
    "caption": "E Western blot analysis of KDM6A, nephrin, WT-1 and H3K27me3 expressed in kidney glomeruli of normal, diabetic and GSK-J4-treated diabetic mice at 12 weeks after diabetic induction. *P < 0.05 versus normal controls, #P < 0.05 versus untreated diabetic mice (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "diseases": "diabetic"
  },
  {
    "caption": "F Immunofluorescence analysis of KDM6A, nephrin and WT-1 in kidney sections from normal, diabetic, and GSK-J4-treated diabetic mice. Green: nephrin or WT-1; Red: KDM6A; Blue: DAPI. Scale bars, 20 μm. *P < 0.05 versus normal controls, #P < 0.05 versus untreated diabetic mice (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "diseases": "diabetic"
  },
  {
    "caption": "G Immunofluorescence staining of F-actin and KDM6A in primary podocytes isolated from normal, diabetic, and GST-J4-treated diabetic mice. Green: F-actin; Red: KDM6A; Blue: DAPI. Scale bars, 20 μm. Presented experiments were performed at least three times independently.",
    "diseases": "diabetic"
  },
  {
    "caption": "C Changes in body weights and levels of blood glucose in wild-type or KDM6A-KO mice with or without STZ treatment. No significant differences in body weights or blood glucose levels between wild-type and KDM6A-KO mice with diabetes were observed during the 8-week experimental period (Wilcoxon two-sample test; n = 8).",
    "diseases": "diabetes"
  },
  {
    "caption": "D Levels of urinary protein excretion, weights of kidney and levels of HbA1c in wild-type and KDM6A-KO mice with or without STZ treatment (at 8 weeks after the onset of diabetes). The mean relative kidney weight (%) shown in the study is determined as the percent of kidneys out of total body weight, and the HbA1c level is defined as the ratio of HbA1c to the total hemoglobin (% HbA1c; DCCT unit). *P < 0.05 versus untreated wild-type controls, #P < 0.05 versus STZ-treated wild-type mice (Parametric ANOVA and a Bonferroni post hoc test; n = 8).",
    "diseases": "diabetes"
  },
  {
    "caption": "E Immunofluorescence analysis of KLF10 and nephrin in renal sections of normal, diabetic, and GSK-J4-treated diabetic mice. Scale bars, 20 μm. *P < 0.05 versus the normal control group, #P < 0.05 versus the untreated diabetic group (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "diseases": "diabetic"
  },
  {
    "caption": "G Western blot analysis of KDM6A, KFL10 and nephrin expression in primary podocytes isolated from normal, diabetic, and GSK-J4-treated diabetic mice. *P < 0.05 versus normal controls, #P < 0.05 versus the untreated diabetic group (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "diseases": "diabetic"
  },
  {
    "caption": "B Western blot analysis of KLF10 expression in kidney samples of wild-type or KLF10-KO mice treated with or without STZ at 8 weeks after the onset of diabetes.",
    "diseases": "diabetes"
  },
  {
    "caption": "C Changes in body weight and blood glucose levels in wild-type or KLF10-KO mice with or without STZ treatment. No significant differences in body weights or blood glucose levels between diabetic wild-type mice and diabetic KLF10-KO mice were detected (Wilcoxon two-sample test; n = 8).",
    "diseases": "diabetic"
  },
  {
    "caption": "A Immunofluorescence analysis of kidney sections from diabetic nephropathy subjects and non-diabetic controls stained with KDM6A, KLF10, nephrin and WT-1. Scale bars, 50 μm. *P < 0.05 by Wilcoxon two-sample test (n = 6 for each group).",
    "diseases": "diabetic nephropathy"
  },
  {
    "caption": "B Western blot analysis of kidney tissues from non-diabetic controls and diabetic nephropathy subjects. Expression levels of KDM6A, KLF10, nephrin and WT-1 in kidney tissues were determined by immunoblotting using the indicated antibodies. Relative protein levels in kidney tissues were normalized to actin. *P < 0.05 by Wilcoxon two-sample test (n = 6 for each group).",
    "diseases": "diabetic nephropathy"
  },
  {
    "caption": "C Levels of KDM6A and KLF10, nephrin mRNAs in urine exosomes of diabetic nephropathy patients and non-diabetic controls. Relative mRNA levels in human urinary exosomes were normalized to 18S rRNA. Horizontal lines are medians. *P < 0.05, **P < 0.01, and ***P < 0.001 by Wilcoxon two-sample test (n = 12 for each group).",
    "diseases": "diabetic nephropathy"
  },
  {
    "caption": "B, C. Cryosections of samples from patients with prostate carcinoma and SCC of the lung. Samples were processed as described in the methods section. Ve=vessel, Tu=tumor. Scale 50µm. See also Fig 1D for comparative semi-quantitative analysis of a panel of samples from patients with prostate carcinoma, lung SCC and non-lung SCC.",
    "diseases": "prostate carcinoma, SCC"
  },
  {
    "caption": "(d) Differential gene expression between end stage lung disease patients and controls across cohorts was compared for the indicated cell type identities. The color code demonstrates similarities of gene expression changes calculated by Pearson correlation of the t-value coefficient, which represents differences in the likelihood of detection for any gene between health and disease.",
    "diseases": "lung disease"
  },
  {
    "caption": "(f-h) The box plots illustrate differences in mRNA detection for the indicated genes between tissues from end stage lung fibrosis patients in (f) alveolar epithelial cells, (g) fibroblasts, and (h) macrophages when compared to control tissue. The boxes represent the interquartile range, the horizontal line in the box is the median, and the whiskers represent 1.5 times the interquartile range (Chicago cohort: ILD n = 9, controls n = 8; Nashville cohort: ILD n = 20, controls n = 10; Munich cohort: ILD n = 3, controls n = 11).",
    "diseases": "ILD, lung fibrosis"
  },
  {
    "caption": "(e) The heatmap shows changes of the indicated cell type signatures in published bulk RNA-seq data (GEO GSE124685) across different histopathological stages that represent increasing extent of fibrosis from stage 1-3, as determined by quantitative micro-CT imaging and tissue histology Samples used in this study were 10 IPF and 6 control patients.",
    "diseases": "fibrosis, IPF"
  },
  {
    "caption": "(f) The heatmaps show z-scores for the individual marker genes of the indicated cell types across IPF stages and controls.",
    "diseases": "IPF"
  },
  {
    "caption": "(b) The boxplots show the number of proteins quantified (y-axis) across various diagnoses (x-axis). The mean and 10-90 percentiles are shown; the dotted line marks 1000 proteins (IPF n=16, HP/EAA n=8, COP n=11, NSIP n=10, RB-IL, n=3, Sarcoidosis n=22, other ILDs n=25, non-IL, n=29).",
    "diseases": "RB-IL, COP, HP/EAA, IPF, ILDs, NSIP, Sarcoidosis"
  },
  {
    "caption": "(e) Barplot displays coefficients derived from correlating lung function associations at the protein level with cell type specific ILD associations at the RNA level.",
    "diseases": "ILD"
  },
  {
    "caption": "(f) The heatmap illustrates gene expression changes associated with lung fibrosis across indicated cell types (columns) for selected BALF protein biomarkers (rows). The dotplot visualizes the frequency changes of the indicated cell types inferred from the deconvolution of bulk mRNA data of ILD samples compared to controls (GSE47460). Samples used in this study from the LTRC n = 254 ILD patients and n = 108 controls.",
    "diseases": "ILD, lung fibrosis"
  },
  {
    "caption": "(a, b) Scatter plots stratify genes based on the protein lung function associations (y-axis) and cell type specific ILD associations (x-axis). The size of the dots represents the detection level of each gene in the corresponding cell type. Colors highlight genes with marginal associations at the protein and RNA levels.",
    "diseases": "ILD"
  },
  {
    "caption": "(c, d) The box plots illustrate differences in mRNA detection for the indicated genes between tissues from end stage lung fibrosis patients in (c) basal cells, and (d) alveolar epithelial cells when compared to controls. The boxes represent the interquartile range, the horizontal line in the box is the median, and the whiskers represent 1.5 times the interquartile range (Chicago cohort: ILD n = 9, controls n = 8; Nashville cohort: ILD n = 20, controls n = 10; Munich cohort: ILD n = 3, controls n = 11).",
    "diseases": "ILD, lung fibrosis"
  },
  {
    "caption": "(g-j) Immunofluorescence analysis of the indicated proteins and cell type markers in IPF (n=3) and control samples (n=3).",
    "diseases": "IPF"
  },
  {
    "caption": "(c) The volcano plot depicts the fold changes (x-axis) and the -log10 p-values (y-axis) derived from the differential gene expression analysis using diffxpy between ILD and controls within the subset of PDGFRB+ pericytes (outlier values truncated).",
    "diseases": "ILD"
  },
  {
    "caption": "(f) Immunofluorescence analysis of SSTR2, the pericyte cell type marker PDGFRB and a marker for smooth muscle cells DESMIN in IPF (n=3) and control samples (n=3).",
    "diseases": "IPF"
  },
  {
    "caption": "(g) Representative images of immunohistochemistry analysis of SSTR2 protein expression in tissue regions (n = 474) from ILD patients (n = 53) and control patients (n = 26).",
    "diseases": "ILD"
  },
  {
    "caption": "(d) The box plots illustrate differences in mRNA detection for CRTAC1 in alveolar epithelial cells from fibrosis patients compared to control samples across the three indicated patient cohorts (Chicago cohort: ILD n = 9, controls n = 8; Nashville cohort: ILD n = 20, controls n = 10; Munich cohort: ILD n = 3, controls n = 11).",
    "diseases": "fibrosis, ILD"
  },
  {
    "caption": "(e) Relative gene expression levels of CRTAC1 in GSE47460. Dots represent average expression in the tissue of individual patients. The line represents the mean, error bars show SD. CRTAC1 is significantly downregulated in ILD but not COPD patients",
    "diseases": "COPD, ILD"
  },
  {
    "caption": "(n) Immunofluorescence analysis of SPRR1A, KRT8 as well as SFTPC in IPF (n=3) and control samples (n=2).",
    "diseases": "IPF"
  },
  {
    "caption": "(o) A high throughput experimental workflow for plasma proteomics(Niu allowed for profiling of two independent cohorts of ILD patients (Munich, n=30 and Hannover, n=81; healthy age matched controls, n=30). All proteins quantified in plasma are shown, ranked by their abundance measured by mass spectrometry (MS-intensity).",
    "diseases": "ILD"
  },
  {
    "caption": " (B) Two-stage DMBA (initiation) plus TPA (promotion) skin carcinogenesis. The number and size of skin papillomas are plotted against time for each genotype: SEPARASE+/+ (n=8) versus SEPARASE+/- (n= 11) ",
    "diseases": "skin carcinogenesis, skin papillomas"
  },
  {
    "caption": " (C) Representative hematoxylin- and eosin-stained sections from SEPARASE+/- biopsies. (i) glandular hyperplasia; (ii) benign papilloma; (iii) squamous cell carcinoma. Scale bars are 200 µm in (i) and 500 µm in (ii) and (iii). (D) Quantitative histological assessment of the DMBA-TPA skin cancerogenesis assay. Given are numbers of total, and corresponding percentage in brackets ",
    "diseases": "benign papilloma, glandular hyperplasia, squamous cell carcinoma"
  },
  {
    "caption": "C) Antibody staining for TEAD4 reveals a gradient of expression along the crypt-villus axis in both the small and large intestine, with uniformly high expression in colorectal adenomas, similar to SOX9.",
    "diseases": "colorectal adenomas"
  },
  {
    "caption": "Quantification of ventral hair loss area 21 days post-IR   (15Gy) in WT and IL-6-/- mice, (n=11). Photographic images showing hair  loss  (area demarked by yellow dashed line) 21 days post-IR   (15 Gy) in wild type (WT) and IL-6-/- mice. Data information: Data represent mean ± SD C, *P<0.05, **P<0.01, **P<0.01, ****P<0.001 by , two-tailed Mann-Whitney test (C, ; five independent experiments.",
    "diseases": "hair  loss"
  },
  {
    "caption": "Photographic images showing hair  loss in mice  at 14 days post-IR   (15 Gy) following treatment by daily topical application of acquosum  (carrier control) or JAK  inhibitors, ruxolitinib  or tofacitinib. Chest  and neck hairs  of mice  in all groups were clipped prior to irradiation   to enhance drug absorption. Quantification of the area of  ventral hair  loss (in pixels) in mice  in (D), (n = 4). Data information: Data represent mean ± SD. *P<0.05, **P<0.01, by two-tailed Student's t test; two independent experiments.",
    "diseases": "hair  loss"
  },
  {
    "caption": "Photographic images showing hair  loss 14 days post-IR   (15 Gy) in WT and IL-1R-/- mice. Quantification of ventral hair loss area 14 days post-IR   (15Gy) in WT and IL-1R-/- mice, (n = 4). Data information: Data represent mean ± SD. *P<0.05, by two-tailed Mann-Whitney test (C) five independent experiments.",
    "diseases": "hair  loss"
  },
  {
    "caption": "Photographic images showing the development of radiodermatitis  and alopecia in irradiated  (15 Gy) WT and CCR6-/- mice at indicated times  post-IR. Escalating radiodermatitis, which manifests on day 7-10 as serous exudates  on the chin  and neck, is visible in both strains and progresses in WT mice  to alopecia  by day 14 post-IR  but resolves spontaneously in the CCR6-/- mice. Quantification (lower right) of the area of hair  loss at 14 days post-IR, (n = 6). Data information: Data represent mean ± SD. *P < 0.05, **P < 0.01 by Mann-Whitney test Two independent experiments.",
    "diseases": "alopecia, hair  loss, radiodermatitis"
  },
  {
    "caption": "Photographic images showing hair  loss in control (PBS) and cyclosporine  (CsA) treated WT mice  at 14 days post-IR  (15 Gy). Quantification of the area of ventral hair loss in mice  in (A), (n = 6). Data information: Data represent mean ± SD. *P < 0.05, **P < 0.01 by two-tailed Mann-Whitney test; two independent experiments.",
    "diseases": "hair  loss"
  },
  {
    "caption": "cTAZ repressed the antiviral activity of ectopic STAT1/2. HEK293A were transfected with indicated plasmids, infected with gVSV (MOI = 0.01) for 12 hours, fixed, and subjected to microscopy (Left). Viral infection and replication were marked by green fluorescence. Scale bar, 100 μm. (Right) Quantification of GFP positive cells. About 300 cells (from 3 different fields) were analyzed. Error bars indicate SD. **P<0.01; ***P<0.001; Student's t-test.",
    "diseases": "infected, Viral infection"
  },
  {
    "caption": "cTAZ effectively repressed antiviral activity of IFN-α. Transfection and infection were performed Top: GFP intensity of cell lysates was measured by a fluorometer. Bottom: viral GFP and ectopic cTAZ protein levels were detected by IB.",
    "diseases": "infection"
  },
  {
    "caption": "Depletion of cTAZ repressed viral replication. RKO cell lines (WT and two independent cTAZ -/- clones) were infected with gVSV (MOI = 0.1) for 12 hours. Scale bar, 100 μm. The ratio of GFP positive cells were calculated About 300 cells (from 3 different fields) were analyzed. Error bars indicate SD. ***P<0.001; Student's t-test.",
    "diseases": "infected"
  },
  {
    "caption": "Overexpression of cTAZ promotes virus infection. DOX-inducible cTAZ-overexpressing RKO cell lines were pre-treated with DOX for 48 hours (1 μg/ml). gVSV infection and GFP Fluorescence intensity quantification were performed Error bars indicate SD, n = 3. **P<0.01; ***P<0.001; Student's t-test.",
    "diseases": "infection"
  },
  {
    "caption": "gVSV induced expression of cTAZ. RKO cells were infected with gVSV (MOI = 0, 0.001, 0.01, 0.01, 1) for 8 hours. Protein expression was determined by IB (Left) and quantified (Right). Error bars indicate SD, n = 3. ***P<0.001; two-way ANOVA test was used for statistical analysis.",
    "diseases": "infected"
  },
  {
    "caption": "The proportion of GABA+ cells of TUJ1+ neurons from both CTRL and sMDD iPSCs derived GINs at day 35. (CTRL, n=120 fields were counted from 5 cell lines; sMDD, n=134 fields were counted from 6 cell lines).",
    "diseases": "sMDD"
  },
  {
    "caption": "Representative images and schematic morphometric Sholl analysis from CTRL and sMDD GINs at day 35. Sholl intersection number of CTRL and sMDD GINs at day 35 (Each red box is from 5 CTRL cell lines, n=25 independently differentiations from 5 cell lines, each point represents mean value of neurons from five independent experiments, n=226 neurons from CTRL groups. Each blue box is from 6 sMDD cell lines, n=30 differentiations independently from 6 cell lines, each point represents mean value of neurons from five independent experiments, n=260 neurons from sMDD groups). Two-way ANOVA for different distance from soma, ****p＜0.0001 for 10, 30 and 50 μm.",
    "diseases": "sMDD"
  },
  {
    "caption": "Representative images of GINs from CTRL and sMDD at day 65.",
    "diseases": "sMDD"
  },
  {
    "caption": "Quantification of primary branch numbers of GINs shown in 5 CTRL cell lines and 6 sMDD cell lines at day 65, n≥11, Nested t-test, **p=0.0016 for CTRL versus sMDD. Quantification of longest neurite length of GINs shown in 5 CTRL cell lines and 6 sMDD cell lines at day 65, n≥11, Nested t-test, **p=0.0075 for CTRL versus sMDD.",
    "diseases": "sMDD"
  },
  {
    "caption": "Representative images of GINs subtype calretinin (CR) expression. The proportion of CR+ cells of TUJ1+ neurons from both CTRL and sMDD iPSCs derived GINs at days 35, 40 and 50, respectively. (Red bar from 5 CTRL cell lines, blue bar from 6 sMDD cell lines). n=5 in each cell line. Two-way ANOVA for timepoints,",
    "diseases": "sMDD"
  },
  {
    "caption": "Representative images of GINs subtype somatostatin (SST) expression co-staining with mature neuron marker MAP2 in CTRL and sMDD GINs at day 65. The proportion of SST+ neurons of MAP2+ cells from CTRL and sMDD iPSCs derived GINs at day 65. n=43 in CTRL groups and n=37 in sMDD groups.",
    "diseases": "sMDD"
  },
  {
    "caption": "Representative electrophysiological traces of AP at a holding potential of -70 mV from GINs in sMDD (blue) and CTRL (red) groups. Average number of APs evoked during 500ms stepwise depolarization (CTRL, n=35 neurons from 3 lines; sMDD, n=55 neurons from 3 lines).",
    "diseases": "sMDD"
  },
  {
    "caption": "D-F. Amplitude and half width of the first AP generated in response to a 10-pA injection (CTRL, n=35 neurons from 3 lines; sMDD, n=55 neurons from 3 lines). Nested t-test, **p＜0.01; ***p＜0.001. Mean ratio ± SEM.",
    "diseases": "sMDD"
  },
  {
    "caption": "G. Traces of Na+/K+ currents recorded from GINs in sMDD and CTRL groups. Quantification showed average of peak values of Na+ currents (CTRL, n=46 neurons from 3 lines; sMDD, n=38 neurons from 3 lines). Nested t-test, **p＜0.01. H. Average fast potassium currents of GINs in sMDD and CTRL groups (CTRL, n=43 neurons from 3 lines; sMDD, n=36 neurons from 3 lines).",
    "diseases": "sMDD"
  },
  {
    "caption": "Representative images of calcium imaging in CTRL and sMDD GINs at each timepoint. Scale bar = 20 μm.",
    "diseases": "sMDD"
  },
  {
    "caption": "The representative trajectory of average intensity changes over time from CTRL (red line) and sMDD (blue line) neurons in response to 67 mM KCL. CTRL, n=6 neurons; sMDD, n=6 neurons. Traces are from a representative experiment (the whole quantification result is shown in D). Quantification of peak [Ca2+] (Fmax-F0)/F0 shown per cell line (n=155 neurons derived from 5 CTRL cell lines, n=198 neurons derived from 6 sMDD cell lines). Nested t-test, **p=0.0022 for CTRL versus sMDD.",
    "diseases": "sMDD"
  },
  {
    "caption": "Immunostaining for the GABA interneuron marker GAD67, neural progenitor marker SOX2 and ventral prosencephalic progenitor marker NKX2.1 at day 30 in CTRL and sMDD ventral forebrain organoids.",
    "diseases": "sMDD"
  },
  {
    "caption": "Representative images of calcium imaging in CTRL and sMDD ventral forebrain organoids at different states.",
    "diseases": "sMDD"
  },
  {
    "caption": "Quantification of peak [Ca2+] (Fmax-F0)/F0 shown per cell line (n=156 neurons derived from 4 CTRL cell lines, n=88 neurons derived from 4 sMDD cell lines). Nested t-test, ***p=0.0005 for CTRL versus sMDD.",
    "diseases": "sMDD"
  },
  {
    "caption": "Bar plot showing the number of genes associated with known mental illnesses, based on PsyGeNET. \"Total\" presents all of the genes related to a given disease. \"100% association\" presents the genes only positively correlated with the disease. \"100% no association\" presents the genes only negatively correlated with the disease. \"Both\" means genes that both positive and negative results were found. AUD, BD, CUD, MDD and SCZ represent alcohol use disorder, bipolar disorder, cocaine use disorder, major depressive disorder and schizophrenia, respectively.",
    "diseases": "cocaine use disorder, CUD, alcohol use disorder, AUD, BD, bipolar disorder, major depressive disorder, MDD, schizophrenia, SCZ"
  },
  {
    "caption": "The representative trajectory of average intensity changes over time in Vehicle virus and KD virus groups. CTRL, n=10 neurons; sMDD, n=10 neurons. Traces are from a representative experiment (the whole quantification result is shown in I). Quantification of peak [Ca2+] (Fmax-F0)/F0 shown per virus group. n=89 for Vehicle virus, n=118 for KD virus, respectively from 4 batches. T-test, ****p<0.0001.",
    "diseases": "sMDD"
  },
  {
    "caption": "The representative trajectory of average intensity changes over time in Vehicle virus and OE virus groups. CTRL, n=10 neurons; sMDD, n=10 neurons. Traces are from a representative experiment (the whole quantification result is shown in D). Quantification of peak [Ca2+] (Fmax-F0)/F0 shown per virus group. n=166 for Vehicle virus, n=81 for OE virus, respectively from 3 batches.",
    "diseases": "sMDD"
  },
  {
    "caption": "Representative images of calcium imaging in CTRL (from RC01001-C) and sMDD (from SA004) GINs at resting and stimulus state with different treatments.",
    "diseases": "sMDD"
  },
  {
    "caption": "Quantification of peak [Ca2+] (Fmax-F0)/F0 shown with different treatments including BDNF, Trzd, PNU, Ro at concentrations of 1 μM and 10 μM. T-test, **p=0.0042 for sMDD+BDNF versus sMDD; one-way ANOVA, ****p＜0.0001 for sMDD+10 μM Trzd versus sMDD. n≥7 neurons from each group.",
    "diseases": "sMDD"
  },
  {
    "caption": "Dot plots showing the expression level and percentage of genes selected from functional gene sets across CTRL, sMDD and sMDD with Trzd GINs clusters.",
    "diseases": "sMDD"
  },
  {
    "caption": "Top: Violin plots showing the expression level of CAMK2N1 and CAMK2N2 in three groups. Bottom: Scatter plot showing the correlations of foldchanges according to the expression of genes encoding CaMK family proteins between CTRL GINs and sMDD GINs and between sMDD with Trzd GINs and sMDD GINs. A linear regression line is added to the plot based on these two variables. sMDD+Trzd vs. sMDD, n=14 genes; CTRL vs. sMDD, n=14 genes.",
    "diseases": "sMDD"
  },
  {
    "caption": "Representative images of single neuron from CTRL, CTRL+Trzd, sMDD and sMDD+Trzd GINs.",
    "diseases": "sMDD"
  },
  {
    "caption": "Representative line chart of Sholl intersection number over distance from soma in CTRL, CTRL+Trzd, sMDD and sMDD+Trzd GINs at day 45. CTRL, n=81 neurons from 5 cell lines; CTRL+Trzd, n=81 neurons from 5 cell lines; sMDD, n=73 neurons from 6 cell lines; sMDD+Trzd, n=71 neurons from 6 cell lines. Quantification of maximum intersections from CTRL, CTRL+Trzd, sMDD and sMDD+Trzd GINs via Sholl analysis. CTRL, n=81 neurons from 5 cell lines; CTRL+Trzd, n=81 neurons from 5 cell lines; sMDD, n=73 neurons from 6 cell lines; sMDD+Trzd, n=71 neurons from 6 cell lines.",
    "diseases": "sMDD"
  },
  {
    "caption": "Quantification of sum of intersections from CTRL, CTRL+Trzd, sMDD and sMDD+Trzd GINs via Sholl analysis. CTRL, n=81 neurons from 5 cell lines; CTRL+Trzd, n=81 neurons from 5 cell lines; sMDD, n=73 neurons from 6 cell lines; sMDD+Trzd, n=71 neurons from 6 cell lines. One-way ANONA, ****p＜0.0001 for CTRL versus sMDD; ***p=0.0002 for sMDD versus sMDD+Trzd. The representative trajectory of average intensity changes over time from CTRL, CTRL+Trzd, sMDD and sMDD+Trzd GINs in response to 67 mM KCL. CTRL, n=20 neurons; CTRL+Trzd, n=20 neurons; sMDD, n=20 neurons; sMDD+Trzd, n=21 neurons. Tracs are from a representative experiment (the whole quantification result is shown in Fig EV5E).",
    "diseases": "sMDD"
  },
  {
    "caption": "Quantification of peak [Ca2+] (Fmax-F0)/F0 shown per group, CTRL, CTRL+Trzd, sMDD and sMDD+Trzd all from 3 cell lines. T-test, *p=0.0495 for CTRL versus sMDD, **p=0.0075 for sMDD versus sMDD+Trzd.",
    "diseases": "sMDD"
  },
  {
    "caption": "Representative images of calcium imaging in sMDD and sMDD+Trzd ventral forebrain organoids at different states.",
    "diseases": "sMDD"
  },
  {
    "caption": "Quantification of the effect of Trzd on peak [Ca2+] (Fmax-F0)/F0 in ventral forebrain organoids (CTRL from IMR90-4, n=40 cells; CTRL+Trzd from IMR90-4, n=58 cells; sMDD from SA007, n=49 cells; sMDD+Trzd from SA007, n=64 cells). Two-tailed test, ****p＜0.0001 for CTRL versus sMDD; ***p=0.0007 for sMDD versus sMDD+Trzd.",
    "diseases": "sMDD"
  },
  {
    "caption": "Representative electrophysiological traces of AP at a holding potential of -70 mV from GINs in sMDD and sMDD+Trzd groups. Average number of APs evoked during 500ms stepwise depolarization (CTRL, n=35 neurons from 3 lines; CTRL+Trzd, n=30 neurons from 3 lines; sMDD, n=55 neurons from 3 lines; sMDD+Trzd, n=44 neurons from 3 lines).",
    "diseases": "sMDD"
  },
  {
    "caption": "Traces of Na+/K+ currents were recorded from GINs in sMDD and sMDD+Trzd groups. Average peak values of Na+ currents (CTRL, n=46 neurons from 3 lines; CTRL+Trzd, n=32 neurons; sMDD, n=38 neurons from 3 lines; sMDD+Trzd, n=36 neurons from 3 lines).",
    "diseases": "sMDD"
  },
  {
    "caption": "Flow cytometric analysis of γδ T cells in RORγtCRE-STAT3F/F (Cre+) and littermate control mice (Cre−). In graphs, each symbol represents a mouse and line the median. *p < 0.05, **p < 0.01, ***p < 0.001 using Mann-Whitney test. Numbers of γδT17 cells in the LN (A) and skin (B) before (steady-state) and after (IMQ) IMQ-induced psoriasis. Steady-state: n = 8; 4 experiments, IMQ: n = 11-12; 4 experiments.",
    "diseases": "psoriasis"
  },
  {
    "caption": "Representative micrographs indicating ear skin sections stained for H&E before and after IMQ-induced psoriasis (scale bar = 100μm). Quantification of epidermal thickening from H&E stained sections. Steady-state: n = 8; 4 experiments, IMQ: n = 11-12; 4 experiments. Each symbol is the average thickening from 5 micrographs measured in μm.",
    "diseases": "psoriasis"
  },
  {
    "caption": "Flow cytometric analysis of γδ T cells in STAT4−/− (−/−) and littermate control mice (+/−). In graphs, each symbol represents a mouse and line the median. Numbers of γδT17 cells in the LN and skin (staining as in Fig EV1) before (steady-state) and after (IMQ) IMQ-induced psoriasis. Steady-state: n = 6; 3 experiments, IMQ: n = 11; 4 experiments.",
    "diseases": "psoriasis"
  },
  {
    "caption": "Representative micrographs indicating ear skin sections stained for H&E before and after IMQ-induced psoriasis (scale bar = 100μm). Quantification of epidermal thickening from H&E stained sections. Steady-state: n = 6; 3 experiments, IMQ: n = 8; 3 experiments. Each symbol is the average thickening from 5 micrographs measured in μm.",
    "diseases": "psoriasis"
  },
  {
    "caption": "Flow cytometric analysis of lymph node γδ T cells in RORγtCRE-STAT3F/F (Cre+) and littermate control mice (Cre−). In graphs, each symbol represents a mouse or experiment and line the median. Representative dot plots showing IL-17A (A) or IL-17F (D) and IFNγ production in γδ T cells before (steady-state) and after IMQ-induced psoriasis. Numbers in gate indicate % positive cells; numbers outside the gate indicate mean fluorescence intensity of IL-17A or IL-17F. (B, E) Frequency of IL-17A+ (B) and IL-17F+ (E) γδ T cells before (steady-state) and after (IMQ) IMQ-induced psoriasis. (C, F) Quantification of mean fluorescence intensity (MFI) of IL-17A (C) and IL-17F (F) staining in γδ T cells after IMQ-induced psoriasis (each color represents a different experiment).",
    "diseases": "psoriasis"
  },
  {
    "caption": "Flow cytometric analysis of lymph node γδ T cells in RORγtCRE-STAT3F/F (Cre+) and littermate control mice (Cre−). In graphs, each symbol represents a mouse or experiment and line the median. Representative dot plots showing IL-22 and IL-17A production in γδ T cells (A) and frequency of IL-22+ γδ T cells (B) before (steady-state) and after (IMQ) IMQ-induced psoriasis. Steady-state: n = 6; 3 experiments, IMQ: n = 8-9; 3 experiments.",
    "diseases": "psoriasis"
  },
  {
    "caption": "Flow cytometric analysis of lymph node γδ T cells in STAT4−/− (−/−) and littermate control mice (+/−). (A, ) Frequency of IL-17A+ (A) γδ T cells before (steady-state) and after (IMQ) IMQ-induced psoriasis. (B) Frequency of IL-17F+ γδ T cells before (steady-state) and after (IMQ) IMQ-induced psoriasis. (C) Quantification of mean fluorescence intensity (MFI) of IL-17A staining in γδ T cells after IMQ-induced psoriasis (D) Quantification of mean fluorescence intensity (MFI) of IL-17F staining in γδ T cells after IMQ-induced psoriasis.",
    "diseases": "psoriasis"
  },
  {
    "caption": "Flow cytometric analysis of lymph node γδ T cells in STAT4−/− (−/−) and littermate control mice (+/−). Frequency of IL-22+ γδ T cells before (steady-state) and after (IMQ) IMQ-induced psoriasis.",
    "diseases": "psoriasis"
  },
  {
    "caption": "Total PD-L1, PARP from triple negative breast cancer cell (MDA-MB-436) lysates treated with indicated DR5 agonist antibodies named Lexa (lexatumumab), KMTR2, BaCa, GAPDH is loading control",
    "diseases": "triple negative breast cancer"
  },
  {
    "caption": "(L) KMTR2 treated (50μg, 4 doses) UCD52 TNBC PDX tumors were stained for PD-L1 using immunohistochemistry (IHC).",
    "diseases": "TNBC"
  },
  {
    "caption": "(O) TNBC WT and DR5-KO (MDA-MB-436) cells were treated with either DR5 agonist or TNFα as indicated. Lysates were analyzed for PD-L1, S5a and DR5. GAPDH is loading control.",
    "diseases": "TNBC"
  },
  {
    "caption": "a, b. The amount of FDP-lysine, which was major protein-bound acrolein, in the sera of healthy controls and PD patients was determined by an ELISA (a. all patients, (control n= 22; PD n=94) b. staged by the H&Y scale, a five-steps index of PD severity. Larger number indicates more severe condition. n=94; H&Y stage I (n=18), stage II (n=42) stage III (n=23), stage IV (n=7), and stage V (n=4).",
    "diseases": "PD"
  },
  {
    "caption": "C Analyzing the number of HCIPs with RNA expression changes identified by single-cell RNA sequencing using cells from COVID-19 patients.",
    "diseases": "COVID-19"
  },
  {
    "caption": "(L)Immunohistochemical staining showing that high expression of circLMP2A in EBVaGC tissues resulted in significant increases in CD44+ CD24- cells and significant decreases in p53+ cells.",
    "diseases": "EBVaGC"
  },
  {
    "caption": "B, C  Cell death measured by lactase dehydrogenase (LDH) (B) and cell viability  measured by 3-(4,5- dimethyl-thiazol-. 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) (C) in T98 cells 42 hrs post-transfection of pure and interrupted   SCA8  repeat tracts; LDH n=8, MTT n=12, n=independent experiments, * p < 0.05, NT not transfected, EV: empty vector; unpaired t test; mean ± SEM.",
    "diseases": "SCA8"
  },
  {
    "caption": " (A) Relative mRNA levels of FX in CD45+ leukocytes in the peripheral blood of E0771 (abbreviated to E) or LLC tumour-bearing mice. The mean sizes of E0771 and LLC tumours were 9.8 mm and 9.5 mm, respectively. Shown are averages (N = 8 mice/group) with SEM and one-way ANOVA ",
    "diseases": "tumour"
  },
  {
    "caption": " (B) Relative mRNA levels of FX in CD45+ leukocytes in various organs such as lung (Lu), Liver (Li), spleen (Sp), bone marrow (BM) and lymph node (Lymph) derived from no tumour-bearing or E0771-bearing mice. "Tumour" stands for mRNA levels of FX in E0771 tumours. Shown are averages (N = 6: organs from no tumour-bearing mice, N = 6: organs from E0771-bearing mice) with SEM and one-way ANOVA",
    "diseases": "tumour, Tumour, tumours"
  },
  {
    "caption": " (C) Immunohistochemical quantifications of FX expression in CD45+ leukocytes in the liver and lungs of no tumour-bearing or E0771-bearing mice. Shown are averages (N = 6) with SEM and Welch"s t-test ",
    "diseases": "tumour"
  },
  {
    "caption": " (D) Immunohistochemical quantifications of fibrinogen deposition in no tumour-bearing- and tumour-bearing- mouse lungs. Shown are averages (N = 7/ group, 14 random fields) with SEM. Welch"s t-test ",
    "diseases": "tumour"
  },
  {
    "caption": " (E) Representative photos of immunohistochemical co-localisation of FX+CD45+ cells and fibrinogen deposition in tumour-bearing mouse lungs. Circles show high fibrinogen deposition areas (scale bar, 50 μm) ",
    "diseases": "tumour"
  },
  {
    "caption": " (E) Representative immunostaining images of FX expression in NK1.1+, CD11c+, B220+ and CD4+ cells in tumour-bearing lungs (scale bar, 10 μm) ",
    "diseases": "tumour"
  },
  {
    "caption": " (A) Representative photos of IFNγ expression in B220+CD11c+NK1.1+cells derived from TCM-stimulating mouse liver. These cells were cultured with LiCM or LuCM that had been prepared by culture with tumour-bearing- liver or lungs, respectively. NoCM stands for CM without tissues, and it was used as control (scale bar,10 μm) ",
    "diseases": "tumour"
  },
  {
    "caption": " (C) Flow cytometric analysis of living Zombie- tumour cells with B220+CD11c+NK1.1+ cells that were primed by NoCM or LuCM. NoCM: N=3, LuCM: N=4. Shown are averages with SEM. Welch"s t-test. Rhodamin+ tumour cells were counted as viable cells ",
    "diseases": "tumour"
  },
  {
    "caption": " (D) Representative immunohistochemical stainings of rhodamin+ (red) Zombie+ (green) tumour cells (scale bar, 10 μm) ",
    "diseases": "tumour"
  },
  {
    "caption": " (E) Ratios of living tumour cells after co-culture with B220+CD11c+NK1.1+cells that had been primed with lung- or liver-CM. Shown are averages (N = 6/group) with SEM and one-way ANOVA ",
    "diseases": "tumour"
  },
  {
    "caption": " (A) Western blotting of fibrinogen in tumour-bearing and no tumour-bearing livers ",
    "diseases": "tumour"
  },
  {
    "caption": " (D) Quantification of fibrinogen deposition areas after injection of CD45+ cells derived from the liver in tumour-bearing mice. Shown are averages (N = 7/ group) with SEM. 1-way ANOVA ",
    "diseases": "tumour"
  },
  {
    "caption": " (F) Separation of Vtn+/ CD45+ HepELs from tumour-bearing FX+/- and FX-/- mouse livers by a cell sorter (Moflo Astrios). Sorted Vtn+CD45+HepELs cells obtained from a littermate (3 animals each) were pooled, and 8 x 103 Vtn+CD45+HepELs cells were i.v. injected into a tumour-bearing mouse. Right graph shows fibrinogen depositions in the lung. Shown are averages (N = 3/ group, 9 fields/ sample) with SEM. 1-way ANOVA",
    "diseases": "tumour"
  },
  {
    "caption": " (A) Representative immunostaining of fibrinogen depositions in tumour-bearing mouse lungs received an injection of rhodamine-labelled B220+CD11c+NK1.1+HepELs derived from tumour-bearing- FX+/− or FX−/− mice (scale bar, 20 μm) ",
    "diseases": "tumour"
  },
  {
    "caption": " (B) Immunohistochemical quantifications of fibrinogen depositions in tumour-bearing mouse lung after an injection of B220+CD11c+NK1.1+cells derived from tumour-bearing- FX+/− or FX−/− mouse liver. Sorted B220+CD11c+NK1.1+cells were prepared from three mice per each genotype, and were i.v. injected. Shown are averages (N = 6/group, 4 sections/mouse) with SEM and Welch"s t-test ",
    "diseases": "tumour"
  },
  {
    "caption": " (B) Tumour cell homing in the lungs pre-treated with LiCM-primed B220+CD11c+NK1.1+cells from tumour-bearing WT or FX−/− mouse liver. Representative photos of homing of rhodamine-labelled tumour cells (upper, scale bar, 20 μm). Number of homing tumour cells are shown (lower). Shown are averages (N = 60 sections, 5/group, all field count/section, 12 sections/sample) with SEM and Welch"s t-test ",
    "diseases": "Tumour, tumour"
  },
  {
    "caption": " (C) Tumour cell homing in the lungs pre-treated with activated FX-overexpressed B220+CD11c+NK1.1+cells (FX-OE-HepELs) from tumour-bearing lungs. Number of homing tumour cells after an injection of lung HepELs or FX-OE-HepELs are shown. Shown here are averages (N = 24 sections, 4/group, all field count/section, 6 sections/sample) SEM and one-way ANOVA ",
    "diseases": "Tumour, tumour"
  },
  {
    "caption": "G.  Western blot  of TREM2 in lysates  and media of cultured  human macrophages isolated from GRN-FTLD #1 and HC #1 upon treatment with Ab1  and Ab2. An isotype antibody was used as a negative control. ADAM protease inhibition (GM) does not further increase mTREM2 levels in GRN-FTLD patients. Equal amounts of protein were loaded. GAPDH was used as loading control.",
    "diseases": "GRN-FTLD"
  },
  {
    "caption": "(A) TCGA cohort of pancreatic cancer patients were divided into two groups according to the median level of ARFGAP1 mRNA expression. Overall survival and disease-free survival were compared between these two groups, as shown in Kaplan-Meier curves. Median survivals (in months), log-rank P values, and hazard ratios (HR) with 95% confidence intervals are indicated.",
    "diseases": "pancreatic cancer"
  },
  {
    "caption": "WT and Nlrc3-/- mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Mean clinical scores of EAE in immunized WT (n= 10) and Nlrc3-/- mice (n= 10).",
    "diseases": "EAE"
  },
  {
    "caption": "Representative flow cytometry data showing intracellular production of IFN-γ and IL-17A by CD4+ T cells from the spinal cord and brain of WT or Nlrc3-/- mice 26 d after EAE induction after restimulation with MOG(35-55) peptide. Pooled data are presented in the right panel.",
    "diseases": "EAE"
  },
  {
    "caption": "Representative flow cytometry data showing surface phenotypes of DCs from spleens of WT or Nlrc3-/- mice 26 d after EAE induction.",
    "diseases": "EAE"
  },
  {
    "caption": "Expression of Nlrc3, Il12, Il6, Il23 and Il27 mRNA in DCs sorted from WT and Nlrc3-/- mice 26 d after EAE induction, presented relative to that of Gapdh.",
    "diseases": "EAE"
  },
  {
    "caption": "DC(WT) and DC(NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Mean clinical scores of EAE in immunized DC(WT) (n= 5) and DC(NLRC3-KO) mice (n= 5).",
    "diseases": "EAE"
  },
  {
    "caption": "DC(WT) and DC(NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Representative flow cytometry data showing intracellular production of IFN-γ and IL-17A by CD4+ T cells in the spinal cord and brain from DC(WT) and DC(NLRC3-KO) mice 26 d after EAE induction after restimulation with MOG(35-55) peptide.",
    "diseases": "EAE"
  },
  {
    "caption": "DC(WT) and DC(NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Recall response to MOG(35-55) by splenocytes isolated from DC(WT) and DC(NLRC3-KO) mice 26 d after EAE induction.",
    "diseases": "EAE"
  },
  {
    "caption": "DC(WT) and DC(NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Expression of Il12, Il6, Il23 and Il27 mRNA in DCs sorted from DC(WT) and DC(NLRC3-KO) mice 26 d after EAE induction, presented relative to that of Gapdh.",
    "diseases": "EAE"
  },
  {
    "caption": "DC(WT) and DC(NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. CFSE proliferation assay of naive 2D2 CD4+ T cells stimulated with MOG(35-55) plus DCs sorted from DC(WT) and DC(NLRC3-KO) mice 26 d after EAE induction.",
    "diseases": "EAE"
  },
  {
    "caption": "DC(WT) and DC(NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. cytokine secretion of naive 2D2 CD4+ T cells stimulated with MOG(35-55) plus DCs sorted from DC(WT) and DC(NLRC3-KO) mice 26 d after EAE induction.",
    "diseases": "EAE"
  },
  {
    "caption": "Activity phosphorylation of p38 were detected in DCs in the spleens from DC(WT) and DC(NLRC3-KO) mice 26 d after EAE induction. Pooled data are presented in the right panel.",
    "diseases": "EAE"
  },
  {
    "caption": "DC(p38-KO) and DC(p38+NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Mean clinical scores of EAE in immunized DC(WT) (n= 5) and DC(NLRC3-KO) mice (n= 5).",
    "diseases": "EAE"
  },
  {
    "caption": "DC(p38-KO) and DC(p38+NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Frequencies of CD4+ T cells that express IFN-γ and IL-17A in the spinal cord and brain from DC(WT) and DC(NLRC3-KO) mice 26 d after EAE induction after restimulation with MOG(35-55) peptide. Pooled data are presented in the right panel.",
    "diseases": "EAE"
  },
  {
    "caption": "DC(p38-KO) and DC(p38+NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Expression of Il12, Il6 and Il23 mRNA in DCs sorted from spleens of DC(WT), DC(NLRC3-KO), DC(p38-KO) and DC(p38+NLRC3-KO) mice 26 d after EAE induction, presented relative to that of Gapdh.",
    "diseases": "EAE"
  },
  {
    "caption": "EAE was induced by immunization of naive B6 mice with MOG (35-55), and the mice were randomly divided into five groups. BMDCs transduced with either lentiviral vector encoding GFP and NLRC3 (LV-NLRC3) or only GFP (LV-Ctrl) were administered i.v. 4 times, once every 4 days, starting at day 10 after EAE induction. Mean clinical scores of EAE (n= 5 mice per group ). Arrows indicate DC vaccine administration.",
    "diseases": "EAE"
  },
  {
    "caption": "EAE was induced by immunization of naive B6 mice with MOG (35-55), and the mice were randomly divided into five groups. BMDCs transduced with either lentiviral vector encoding GFP and NLRC3 (LV-NLRC3) or only GFP (LV-Ctrl) were administered i.v. 4 times, once every 4 days, starting at day 10 after EAE induction. Recall proliferative to MOG (35-55) in splenocytes taken from DCs-treated mice 26 days after EAE induction.",
    "diseases": "EAE"
  },
  {
    "caption": "EAE was induced by immunization of naive B6 mice with MOG (35-55), and the mice were randomly divided into five groups. BMDCs transduced with either lentiviral vector encoding GFP and NLRC3 (LV-NLRC3) or only GFP (LV-Ctrl) were administered i.v. 4 times, once every 4 days, starting at day 10 after EAE induction. cytokine response (D) to MOG (35-55) in splenocytes taken from DCs-treated mice 26 days after EAE induction.",
    "diseases": "EAE"
  },
  {
    "caption": "(A) Representative images of H&E staining  of colon  from 3m C57Bl (n=4) and mdx  (n=4) mice. High magnification (scale bar: 20 μm) and low magnification (scale bar: 200 μm).",
    "diseases": "mdx"
  },
  {
    "caption": "(D) SCFA faecal  quantification of 3m C57Bl (n=3) and mdx  (n=4-5) mice. Data information: Data are presented as mean ± SD (*p<0.05; **p<0.01, ***p<0.001, ****p<0.0001; Student t-test).",
    "diseases": "mdx"
  },
  {
    "caption": "(E) Colon  images captured with the iMScope TRIO described altered pattern of expression of different Phosphatidylcholines  (PC) and Lysophosphatidylcholines  (LysoPC) (as indicated by m/z values) in 3m mdx mice  (n=3). Scale bar: 50 μm. For each lipid, the mean intensities measured at 12 positions throughout colon  images are shown on the right side where bars are mean ± SEM (n = 3). Data information: Data are presented as mean ± SD (*p<0.05; **p<0.01, ***p<0.001, ****p<0.0001; Student t-test).",
    "diseases": "mdx"
  },
  {
    "caption": "(F) Cropped images of representative WB  showing the expression of proteins involved in inflammation  and fibrosis  in colon  tissues of 3m C57Bl (n=3) and 3m mdx  (n=5). Densitometric analyses of protein expression was shown as ratio to actin. Data information: Data are presented as mean ± SD (*p<0.05; **p<0.01, ***p<0.001, ****p<0.0001; Student t-test).",
    "diseases": "mdx, fibrosis, inflammation"
  },
  {
    "caption": "(E) Faecal  content quantification of SCFAs  in 3m mdx  and 3m mdx+ABX mice  (n=5 per group). Data equal to 0. Data are presented as mean ± SD (**p< 0.01, ***p< 0.001; Student t-test).",
    "diseases": "mdx"
  },
  {
    "caption": "(A-D) FACS  analysis of spleen  and muscle  homogenates from 3m C57Bl (n=4), mdx  (n=5) and mdx+ABX (n=7) mice  demonstrates no significant alteration of CD45+CD11b+CD4-CD8-  myeloid cells (A and C) and few differences in CD4+ or CD8+ naïve  (CD62L+ CD44-), central memory (CD62L+ CD44+) and effector  (CD62L- CD44+) T cells  (B and D). Data information: Data are presented as mean ± SD. *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001 ordinary one-way ANOVA, Tukey's multiple comparison test.",
    "diseases": "mdx"
  },
  {
    "caption": "(E) FACS  analysis of spleen  of 3m C57Bl (n=7), mdx  (n=9) and GFmdx  (n=5) mice  revealed similar proportions of CD4+ and CD8+ T cells but reduced activated CD44+ T cells  in GFmdx mice. Representative plots are depicted. Data information: Data are presented as mean ± SD. *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001 ordinary one-way ANOVA, Tukey's multiple comparison test.",
    "diseases": "mdx"
  },
  {
    "caption": "(F) Graphs show cumulative frequencies of CD4+ and CD8+  T cells on live cells of 3m C57Bl (n=7), mdx   (n=4) and GFmdx  (n=5) mice. Representative dot plots and cumulative frequencies of splenic CD4+GITR+CD25+ Treg. Frequencies of effector CD44+ T cells  were significantly decreased in spleen  of GFmdx mice. Data information: Data are presented as mean ± SD. *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001 ordinary one-way ANOVA, Tukey's multiple comparison test.",
    "diseases": "mdx"
  },
  {
    "caption": "(G) Representative dot-plots showing the proportion of muscle-infiltrating CD45+ cells of 3m C57Bl (n=6), mdx  (n=6) and GFmdx  (n=5) mice. Cumulative frequencies of muscle-infiltrating CD45+ cells are shown. Data information: Data are presented as mean ± SD. *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001 ordinary one-way ANOVA, Tukey's multiple comparison test.",
    "diseases": "mdx"
  },
  {
    "caption": "(H) Representative images of TA muscles  from 3m mdx  and GFmdx mice stained  for CD45  (in green), isolectin  (in red) and phalloidin  (in purple). Nuclei  were counterstained  with DAPI  (in blue). Scale bar: 10 μm.",
    "diseases": "mdx"
  },
  {
    "caption": "(I) Absolute number of CD3+  inflammatory cells  (white arrows) were quantified in n=12 images of TA  of 3m C57Bl, 3m mdx  and 3m GFmdx mice  (n=6 each). CD3 staining  is shown in green and DAPI  in blue. Scale bars: 50 μm. Data information: Data are presented as mean ± SD. *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001 The comparisons among the averages of CD3+ cells were evaluated using unpaired t-test.",
    "diseases": "mdx"
  },
  {
    "caption": "(D) RT-qPCR analysis of TA muscles  of two independent experiments with 3m mdx  (n=4), mdx+ABX (n=4) and GFmdx  (n=5) mice  determined the expression of myogenic markers. Data information: Data are presented as mean ± SD (*p<0.05, **p<0.01, ***p<0.001; ****p<0.0001, ordinary one-way ANOVA and non-parametric test followed by Kruskal-Wallis test for RT-qPCR).",
    "diseases": "mdx"
  },
  {
    "caption": "(E) Representative Gomori modified staining  and quantification of myofiber   area and relative frequency of the myofiber   cross-sectional area (CSA) expressed as the frequency distribution of the TA muscles  of 3m C57Bl (n=4), 3m mdx  (n=4), mdx+ABX (n=4) and  GFmdx mice  (n=5). Pooled samples for each group with n=6240 for 3m C57Bl; n=6001 for 3m mdx; n=10556 for 3m mdx+ABX; n=23059 for  GFmdx. For morphometric  analysis, images were quantified with Image J software for each mouse. Scale bars: 50 μm. Data information: Data are presented as mean ± SD (*p<0.05, **p<0.01, ***p<0.001; ****p<0.0001, ordinary one-way ANOVA",
    "diseases": "mdx"
  },
  {
    "caption": "(G) Representative images of skeletal muscle showed the distribution and composition of the myosin heavy chain (MyHC) isoforms (Type IIa, Type IIx  and Type IIb). (H, I) Graph portrays (H) the percentage of myofibers  expressing different MyHC isoforms and (I) myofibers  area per type of MyHC in TAs  of 3m mdx  (n=4), mdx+ABX (n=4) and GFmdx  (n=5) mice  (n=12 images per animal). Data information: Data are presented as mean ± SD (*p<0.05, **p<0.01, ***p<0.001; ****p<0.0001, ordinary one-way ANOVA",
    "diseases": "mdx"
  },
  {
    "caption": "(J) Representative SDH staining  and quantification of percentage of SDH+ myofibers  of TAs  from 3m mdx (n=4), mdx+ABX (n=4) and GFmdx mice  (n=5) (n=12 images per animal). Scale bars: 50 μm.",
    "diseases": "mdx"
  },
  {
    "caption": "(D, E) Representative H&E staining (D) and quantification of myofiber  area with Image J software (E) of TA muscles  from 3m C57Bl (n=5), mdx  (n=5) and ABX-mdxFMT_C57Bl (n=6). Scale bars for H&E: 200 μm. Data information: Data for staining  quantification are presented as mean ± SD (*p<0.05, **p<0.01, ***p<0.001; ****p<0.0001, one-way ANOVA, Tukey's multiple comparison test).",
    "diseases": "mdx"
  },
  {
    "caption": "(J-K) Representative SDH staining  and quantification of percentage of SDH+ myofibers  of TA muscles  from mdx  (n=5) and ABX-mdxFMT_C57Bl (n=6) (n=12 images per mouse). Scale bar: 200 μm. Data information: Data for staining  quantification are presented as mean ± SD (*p<0.05, **p<0.01, ***p<0.001; ****p<0.0001, one-way ANOVA, Tukey's multiple comparison test).",
    "diseases": "mdx"
  },
  {
    "caption": "(L-M) Representative image of CD31  (in cyan), α-SMA (in green) and isolectin  (in red) staining  and their quantification in TA muscles  from mdx  (n=5) and ABX-mdxFMT_C57Bl (n=6) mice. Scale bar: 500 μm. Data information: Data for staining  quantification are presented as mean ± SD (*p<0.05, **p<0.01, ***p<0.001; ****p<0.0001, one-way ANOVA, Tukey's multiple comparison test).",
    "diseases": "mdx"
  },
  {
    "caption": "(D) Western blotting was used to visualise ASS1 protein levels in untreated or imatinib treated (2µM, 48 hours) CML CD34+ samples, normal CD34+ samples and indicated cell lines following 16 hours arginine starvation.",
    "diseases": "CML"
  },
  {
    "caption": "(A) CTV analysis of CML CD34+ patient samples after 72 hours arginine starvation (n=3). Data are shown with mean and SEM. Data information: For statistical analysis, multiple unpaired tests with Benjamini, Krieger, and Yekutieli Benjamini two-stage step up correction was performed out on log-transformed data in A",
    "diseases": "CML"
  },
  {
    "caption": "(B) Viability data from CML CD34+ patient samples recorded after 72 hours starvation of indicated amino acid. Data are shown are from 3 biological replicates with mean and SEM plotted. Mean and SEM are shown. Data information for B-E Mann-Whitney tests were performed.",
    "diseases": "CML"
  },
  {
    "caption": "(D) CFCs from CML CD34+ patient samples generated after 72 hours starvation of indicated amino acid. The upper panel shows representative image of colonies, counts are plotted in the lower panel. Data are shown are from 4 (-arginine) or two (-ornithine or -citrulline) biological replicates. Mean and SEM are shown. (E) CFCs from Normal CD34+ samples generated after 72 hours starvation of indicated amino acid. Upper panel shows representative image of colonies, counts are plotted in lower panel. Data are shown are from 3 biological replicates. Mean and SEM are shown. Data information: Mann-Whitney tests were performed.",
    "diseases": "CML"
  },
  {
    "caption": "(E) Viability data from CML CD34+ patient samples (5 biological replicates) recorded after 72 hours of treatment as in D, Mean and SEM are shown. Data information: For statistical analysis, ordinary one-way ANOVA with Tukey's correction for multiple comparisons was performed",
    "diseases": "CML"
  },
  {
    "caption": "(G) CFCs from CML CD34+ samples are shown. Cells were treated as in D before seeding for CFCs. The left panel shows representative image of colonies, counts are plotted in the right panel. Data are shown are from 7 biological replicates. Mean and SEM are shown. Data information: For statistical analysis, ordinary one-way ANOVA with Tukey's correction for multiple comparisons was performed",
    "diseases": "CML"
  },
  {
    "caption": "(B) Volcano plot showing differentially expressed (DE) genes between CML CD34+ vehicle and BCT-100 treated cells, red denotes q-value <0.1. Data information: , DESEQ2 and GSEA were used as described in methods.",
    "diseases": "CML"
  },
  {
    "caption": "Western blot analysis of MICU1 and MICU2 levels in lung cancer cells with low or high Akt activity",
    "diseases": "lung cancer"
  },
  {
    "caption": "Lung cancer cells were transfected with the GFP-tagged WT MICU1. MICU1-GFP immunocomplexes were precipitated with a GFP antibody and analyzed with a PAS (phospho-Akt substrate) antibody by western blotting",
    "diseases": "Lung cancer"
  },
  {
    "caption": "Western blot analysis of MICU1 and MICU2 levels in melanoma cells with low or high Akt activity",
    "diseases": "melanoma"
  },
  {
    "caption": "Melanoma cells were transfected with the GFP-tagged WT MICU1. MICU1-GFP immunocomplexes were precipitated with a GFP antibody and analyzed with PAS (phospho-Akt substrate) antibody by western blotting",
    "diseases": "Melanoma"
  },
  {
    "caption": "Western blot analysis of MICU1 and MICU2 levels in glioblastoma cells with low or high Akt activity",
    "diseases": "glioblastoma"
  },
  {
    "caption": "Glioblastoma cells were transfected with the GFP-tagged WT MICU1. MICU1-GFP immunocomplexes were precipitated with GFP antibody and analyzed with PAS (phospho-Akt substrate) antibody by western blotting",
    "diseases": "Glioblastoma"
  },
  {
    "caption": "The graph depicts the standardised differences of CSF PGRN between MCs and NCs as a function of EYO, in the context of other biomarker and cognitive changes. The curves were generated by the linear model that best fit each marker (see statistics section and Appendix Table S2). CSF PGRN is significantly increased in MC compared to NC 10 years before the expected symptom onset (shadowed area) after brain amyloidosis and brain injury (as measured by CSF T-tau) have started, and shortly before CSF sTREM2 starts to increase. Abbreviations: Aβ1-42: amyloid-β 42; CSF, cerebrospinal fluid; MC, mutation carriers; MMSE, Mini-Mental State Examination; NC, non-carriers; T-tau, total tau.",
    "diseases": "amyloidosis, brain injury"
  },
  {
    "caption": "Scatter plot representing the levels of CSF PGRN in healthy controls (depicted in blue) and the different stages of the Alzheimer's continuum (depicted in red). The analysis and graphs were performed excluding CSF PGRN outliers (1 'healthy control', 1 'Preclinical AD A+/TN-', 4 'AD CDR = 0.5' and 1 'AD CDR = 1'). Including them yielded a similar result and CSF PGRN was still significantly higher in the 'AD CDR = 1' group compared to the 'healthy controls' (P = 0.001) and 'Preclinical AD A+/TN-' (P = 0.0001) groups. Abbreviations: A: amyloid-β biomarker status; AD: Alzheimer's disease; CDR: clinical dementia rating; CSF, cerebrospinal fluid; N: neurodegeneration biomarker status; T: tau pathology biomarker status.",
    "diseases": "AD, Alzheimer's, Alzheimer's disease"
  },
  {
    "caption": "Scatter plots representing the association of CSF PGRN with different cognitive tests. Only the subjects of the Alzheimer's continuum group (n = 474) were included. In all tests studied, higher levels of CSF PGRN were associated with worse cognitive performance (namely, lower scores in ADNI-Mem, ADNI-EF and MMSE and higher scores in ADAS-Cog11, ADAS-Cog13 and CDR-SB). The analysis and the graphs are excluding PGRN outliers; including them rendered similar results (Appendix Table S6). Abbreviations: ADAS-Cog, Alzheimer's disease Assessment Scale - cognitive subscale; ADNI-Mem: ADNI memory composite score; ADNI-EF: ADNI executive function composite score; CDR-SB: clinical dementia rating Sum of Boxes; MMSE, Mini-Mental State Examination.",
    "diseases": "Alzheimer's, Alzheimer's disease"
  },
  {
    "caption": "Scatter plots representing the association of CSF PGRN with temporo-parietal FDG-PET uptake within the subjects of the Alzheimer's continuum group (n = 474). Abbreviations: FDG-PET: Fludeoxyglucose positron emission tomography",
    "diseases": "Alzheimer's"
  },
  {
    "caption": "Scatter plots representing the association of CSF PGRN with total hippocampal volume (B) within the subjects of the Alzheimer's continuum group (n = 474).",
    "diseases": "Alzheimer's"
  },
  {
    "caption": "Scatter plots representing the associations of CSF PGRN with CSF sTREM2 and each of the AD CSF core biomarkers (T-tau, P-tau181P and Aβ1−42) in non-carriers (NC, blue; A, C, E and G) and in mutation carriers (MC, red; B, D, F and H). Each point depicts the value of CSF PGRN and the corresponding biomarker of a subject and the solid lines indicate the regression line and the 95% confidence interval (CI) for each of the groups. The standardized regression coefficients (β) and the P-values are shown and were computed using a linear model adjusting for age, gender and APOE ε4. The sample contained some outliers (defined as 3 SDs below or above the group mean) of the CSF core markers of AD. Abbreviations: Aβ1-42: amyloid-β 42; T-tau: total tau; P-tau: tau phosphorylated at Threonine 181.",
    "diseases": "AD"
  },
  {
    "caption": "Scatter plots representing the associations of CSF PGRN with CSF sTREM2 and each of the AD CSF core biomarkers (T-tau, P-tau181P and Aβ1−42) in healthy controls (blue; A, D, G and J), Alzheimer's continuum (red; B, E, H and K) and 'suspected non-Alzheimer's pathophysiology (SNAP)' groups (green; C, F, I and L). Each point depicts the value of CSF PGRN and the corresponding biomarker of a subject and the solid lines indicate the regression line and the 95% confidence interval (CI) for each of the groups. The standardized regression coefficients (β) and the P-values are shown and were computed using a linear model adjusting for age, gender and APOE ε4. The sample contained some outliers (defined as 3 SDs below or above the group mean) of the CSF core markers of AD, the analysis including these outliers yielded similar results (Appendix Table S8). The Aβ1-42 values used for the associations test are those based on an extrapolation curve since the upper technical limit is 1700pg/ml. We also tested the associations with Aβ1-42 values truncated at the upper technical limit and the result was similar. Abbreviations: Aβ1-42: amyloid-β 42; T-tau: total tau; P-tau: tau phosphorylated at Threonine 181; SNAP: suspected non-Alzheimer's pathophysiology.",
    "diseases": "AD, Alzheimer's"
  },
  {
    "caption": "(A) Serum levels of miR-483-3p/-5p in IPAH patients (n = 139) and HC (n = 95) measured by qPCR. The data are fold change normalized to the averaged level of HC. Data information: Values are expressed as median ± interquartile range. Statistical test: Mann Whitney U test (A)",
    "diseases": "IPAH"
  },
  {
    "caption": "(B) ROC curve with sensitivity and specificity of serum levels of miR-483-3p/-5p for differentiating IPAH patients from HCs at diagnosis (IPAH, n = 139; HC, n = 95). Data information: Values are expressed as median ± interquartile range.",
    "diseases": "IPAH"
  },
  {
    "caption": "(C) Levels of miR-483-3p/-5p associated with PAH risk in 3 groups. IPAH patients were divided into a low risk group (Low) and an intermediate plus high risk group (Inter&high) according to the World Symposium on Pulmonary Hypertension 2018 [14]. Data information: Values are expressed as median ± interquartile range. Statistical test: Kruskal-Wallis U test (C).",
    "diseases": "IPAH, PAH, Pulmonary Hypertension"
  },
  {
    "caption": "(D) Levels of miR-483-3p were inversely correlated with serum levels of ET-1 (IPAH, n = 118; HC, n = 95) and IL-6 (IPAH, n = 112; HC, n = 93). Data information: Values are expressed as median ± interquartile range.",
    "diseases": "IPAH"
  },
  {
    "caption": "(A) CD144-enriched EVs were isolated from serum of IPAH patients (n = 37) and HCs (n = 34). The levels of miR-483-3p/-5p were measured by qPCR. Data information: Values are expressed as median ± interquartile range. Statistical test: Mann Whitney U test.",
    "diseases": "IPAH"
  },
  {
    "caption": "qPCR analysis of miR-483-3p/-5p in serum from PH (MCT-treated) rats. Data information: Values are expressed as mean ± SEM. Statistical test: t-test (*P < 0.05 vs. respective controls or between the indicated groups",
    "diseases": "PH"
  },
  {
    "caption": "qPCR analysis of miR-483-3p/-5p in lung tissue from PH (MCT-treated) rats. Data information: Values are expressed as mean ± SEM. Statistical test: t-test (*P < 0.05 vs. respective controls or between the indicated groups",
    "diseases": "PH"
  },
  {
    "caption": "B-D. Mice were analyzed by Kaplan-Meier survival plot (B), the percentage of body weight (C), and the clinical scores (D) of WT and GPx8-/- mice with colitis induced by 4% DSS for 6 days (n = 10 per group). Data information: Data are presented as the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's two‐tailed t‐test).",
    "diseases": "colitis"
  },
  {
    "caption": "After undergoing macrophage depletion, C57BL/6 mice received macrophages derived from WT (WT BMDMs) or GPx8-/- mice (GPx8-/- BMDMs) were under DSS-induced colitis (n = 6-9 per group). (C) The percentage of body weight. (D) The clinical scores of mice. Data information: Data are presented as the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's one‐tailed t‐test).",
    "diseases": "colitis"
  },
  {
    "caption": "After undergoing macrophage depletion, C57BL/6 mice received macrophages derived from WT (WT BMDMs) or GPx8-/- mice (GPx8-/- BMDMs) were under DSS-induced colitis (n = 6-9 per group). Colon samples from BMDMs transplanted mice were collected on day 7 under colitis model. (E) Statistical analysis of colon length. Data information: Data are presented as the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's one‐tailed t‐test).",
    "diseases": "colitis"
  },
  {
    "caption": "After undergoing macrophage depletion, C57BL/6 mice received macrophages derived from WT (WT BMDMs) or GPx8-/- mice (GPx8-/- BMDMs) were under DSS-induced colitis (n = 6-9 per group). Colon samples from BMDMs transplanted mice were collected on day 7 under colitis model. (F) Images and semiquantitative scoring of hematoxylin and eosin staining colon sections. Data information: Data are presented as the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's one‐tailed t‐test).",
    "diseases": "colitis"
  },
  {
    "caption": "After undergoing macrophage depletion, C57BL/6 mice received macrophages derived from WT (WT BMDMs) or GPx8-/- mice (GPx8-/- BMDMs) were under DSS-induced colitis (n = 6-9 per group). Colon samples from BMDMs transplanted mice were collected on day 7 under colitis model. (G) Colon sections stained with anti-F4/80. Data information: Data are presented as the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's one‐tailed t‐test).",
    "diseases": "colitis"
  },
  {
    "caption": "After undergoing macrophage depletion, C57BL/6 mice received macrophages derived from WT (WT BMDMs) or GPx8-/- mice (GPx8-/- BMDMs) were under DSS-induced colitis (n = 6-9 per group). D) Colon samples from BMDMs transplanted mice were collected on day 7 under colitis model. (H) Production of IL-1β, IL-6 and IL-18 in colon tissue lysates. Data information: Data are presented as the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's one‐tailed t‐test). ",
    "diseases": "colitis"
  },
  {
    "caption": "Mice were injected intraperitoneally with VX-765 (20 mg/kg) under colitis model and analyzed by a Kaplan-Meier survival plot (B) of mice with colitis induced by 4% DSS for 6 days (n = 10-11 per group). Data information: , data are presented as the mean ± SEM. NS: not significant (P > 0.05). *P < 0.05; **P < 0.01; ***P < 0.001 (Student's two‐tailed t‐test).",
    "diseases": "colitis"
  },
  {
    "caption": "Mice were injected intraperitoneally with VX-765 (20 mg/kg) under colitis model and the percentage of body weight (C) and clinical scores (D) of mice with colitis induced by 4% DSS for 6 days (n = 10-11 per group). data are presented as the mean ± SEM. NS: not significant (P > 0.05). *P < 0.05; **P < 0.01; ***P < 0.001 (Student's two‐tailed t‐test).",
    "diseases": "colitis"
  },
  {
    "caption": "Mice were injected intraperitoneally with VX-765 (20 mg/kg) under colitis model Colon samples from mice treated with 4% DSS for 5 days (n = 6-10 per group). Full-length and cleavage forms of caspase-11, caspase-1, and GSDMD (E) in colon tissue lysates were analyzed by immunoblots on day 7 after DSS treatment. data are presented as the mean ± SEM. NS: not significant (P > 0.05). *P < 0.05; **P < 0.01; ***P < 0.001 (Student's two‐tailed t‐test).",
    "diseases": "colitis"
  },
  {
    "caption": "Mice were injected intraperitoneally with VX-765 (20 mg/kg) under colitis model Colon samples from mice treated with 4% DSS for 5 days (n = 6-10 per group). Production of IL-1β and IL-6 (F) in colon tissue lysates was assessed on day 14 after treatment. data are presented as the mean ± SEM. NS: not significant (P > 0.05). *P < 0.05; **P < 0.01; ***P < 0.001 (Student's two‐tailed t‐test).",
    "diseases": "colitis"
  },
  {
    "caption": "A. GPx8 was predominantly expressed in macrophages of UC patients. Colon biopsies of non-inflamed regions from UC patients were stained with the pan-macrophage marker, CD68, or the monocyte/macrophage activating marker, CD163, combined with anti-GPx8. Quantification of double-positive cells was calculated from 3 individual patients and is presented as the mean ± SEM of the percentage of double-positive cells. The total cell numbers are the sum of double- and single-positive cells.",
    "diseases": "UC"
  },
  {
    "caption": "B. Relative expression levels of GPx8, GPx7 and caspase-4 in non-inflamed biopsy specimens from healthy controls (Ctrl) (n = 14) and UC patients (n = 25) are demonstrated by immunoblots. C. Data are normalized to the mean of healthy controls and presented as the mean ± SEM. Mann Whitney test for GPx8 and Student's two‐tailed t‐test for GPx7 and caspase-4 expression analysis. Data information: NS: not significant (P > 0.05). *P < 0.05; **P < 0.01; ***P < 0.001.",
    "diseases": "UC"
  },
  {
    "caption": "A. Immunofluorescence of SATB2 (green) and the GSC marker SOX2 or OLIG2 (red) on frozen tissue sections of human GBM surgical specimens. SATB2 is preferentially expressed by GSCs in human GBMs. Scale bar, 25 μm. B. Quantification of the fraction of SATB2+ cells in SOX2+ or OLIG2+ cells in human GBMs. More than 90% SOX2+ or OLIG2+ cells showed SATB2 staining. n=3 GBMs. ",
    "diseases": "GBM, GBMs"
  },
  {
    "caption": " A. Bioluminescent images of the GBM xenografts derived from the luciferase-labeled T3359 GSCs expressing NT or SATB2 shRNA. Representative images on day 21 posttransplantation are shown (n=5 mice per group). Silencing SATB2 significantly delayed GBM growth . B. Quantification of the bioluminescence of xenografts derived from the luciferase-labeled T3359 GSCs expressing shNT or shSATB2 on day 21 posttransplantation (n=5 mice per group).",
    "diseases": "GBM"
  },
  {
    "caption": " In vivo bioluminescent images of the tumor xenografts derived from luciferase-labeled T3359 GSCs transduced with FOXM1 or vector control in combination with shNT or shSATB2 (shNT: n=5 mice; shNT+FOXM1: n=4 mice; shSATB2: n=5 mice; shSATB2+ FOXM1: n=5 mice). Representative images on day 21 posttransplantation are shown. Ectopic expression of FOXM1 in GSCs expressing shSATB2 markedly restored GBM tumor growth. ",
    "diseases": "GBM"
  },
  {
    "caption": " E. In vivo bioluminescent images or quantification of the tumor xenografts derived from luciferase-labeled T3359 GSCs transduced with FOXM1 or vector control in combination with shNT or shSATB2 (shNT: n=5 mice; shNT+FOXM1: n=4 mice; shSATB2: n=5 mice; shSATB2+ FOXM1: n=5 mice). Representative images on day 21 posttransplantation are shown. Ectopic expression of FOXM1 in GSCs expressing shSATB2 markedly restored GBM tumor growth. ",
    "diseases": "GBM"
  },
  {
    "caption": " F. Kaplan-Meier survival curves of mice intracranially implanted with T3359 GSCs transduced with FOXM1 or vector control in combination with shNT or shSATB2 (shNT: n=8 mice; shNT+FOXM1: n=7 mice; shSATB2: n=6 mice; shSATB2+ FOXM1: n=8 mice). Median survival: shNT, 30 days; shNT+FOXM1, 28 days; shSATB2, 50.5 Days; shSATB2+FOXM1, 34 days. Ectopic expression of FOXM1 in GSCs expressing shSATB2 markedly attenuated the increased survival of mice bearing the GSC-derived GBMs. ",
    "diseases": "GBMs"
  },
  {
    "caption": "Kinetic analyses of EC migration in an ex vivo aortic ring angiogenesis model. Upper panels are snapshots of time-lapse imaging in which EC nuclei are labeled by SYTO dye (green). In analyzed regions framed by dotted lines, the centroids of the first five EC nuclei from the tip at 0 min are pseudocolored in magenta and those of the remaining EC nuclei are shown in cyan. Initial discrete labeling becomes intermixed over time (see also Movie EV1). Lower panels show trajectory analyses representing normalized positional changes of individual ECs during vessel elongation. Scale bar, 100 µ",
    "diseases": "aortic ring angiogenesis"
  },
  {
    "caption": "Labeling for GFP (green) and CD31 (red) in retina of P18 OIR-RhojGFP/WT mouse. Scale bar, 200 µ",
    "diseases": "OIR"
  },
  {
    "caption": "Labeling for CD31 in retinas of P18 OIR-Rhojflox/flox and OIR-Rhoji∆EC mice after daily i.p. injection of 200 µg of 4OHT from P12. Scale bar, 500 µm. Quantification of areas of neovascular tufts in P18 OIR-Rhojflox/flox and OIR-Rhoji∆EC mice. n = 6 per group.",
    "diseases": "OIR"
  },
  {
    "caption": "Immunoblot detection and its quantification of PDGFR-β in kidney cortex lysates of healthy and diseased human kidneys shows twice as much PDGFR-β abundance in diseased tissue. A stronger signal for phosphorylated PDGFR-β indicates the active status of the receptor. The high α-SMA content in the diseased kidneys shows that they are affected by fibrosis. Bar graphs show means ± SD, healthy n = 5, diseased n = 6",
    "diseases": "fibrosis"
  },
  {
    "caption": "PDGFR-β staining is detectable in mesangium of healthy (a) and diseased (b-d) glomeruli of human kidneys. PDGFR-β positive mesangial cells expand in mesangioproliferating and scarring glomerular changes. Similarly, the population of PDGFR-β positive interstitial cells is discrete in healthy kidney cortex (e) but expands in fibrosis (f-h). Arrows point to selected areas of positive PDGFR-β staining. Scale bar = 50 µm",
    "diseases": "fibrosis"
  },
  {
    "caption": "Tissue clearing with Scale and 3D reconstruction of Pdgfrb-GFP reporter mice in a healthy and fibrotic kidney (UUO day 5) shows the expansion of Pdgfrb expressing cells in fibrosis.",
    "diseases": "fibrosis, fibrotic kidney"
  },
  {
    "caption": "Collagen I staining and its histomorphometric quantification (D) show the progression of interstitial fibrosis in the time course.",
    "diseases": "fibrosis"
  },
  {
    "caption": "The tubular stress marker Lipocalin-2 (LCN2) is not expressed in early time points but increases in time course in late stages when fibrosis is more prominent, as seen on histological staining",
    "diseases": "fibrosis"
  },
  {
    "caption": "The tubular stress marker Lipocalin-2 (LCN2) is not expressed in early time points but increases in time course in late stages when fibrosis is more prominent and mRNA level",
    "diseases": "fibrosis"
  },
  {
    "caption": "After induction of anemia by blood taking, the erythrocyte numbers recovered after one week in wt mice, whereas Foxd1Cre::Pdgfrb+/J mice were not able to recover their erythrocytes numbers at all. Data are means ± SD of n = 5 per group.",
    "diseases": "anemia"
  },
  {
    "caption": "Five days after the induction of unilateral ureteral obstruction (UUO), a model of obstructive nephropathy and interstitial fibrosis, we assessed fibrosis (collagen I, α-SMA) and inflammation (F4/80), the classical read-out parameters in this model. Compared to wt mice with UUO, Foxd1Cre::Pdgfrb+/J mice developed significantly stronger fibrosis and inflammation (A). Representative pictures of the histological stainings are shown in (B). Scale bar = 50 µm All data in A and B show means ±SD, wt n = 4, Foxd1Cre::Pdgfrb+/J n = 3. *: p≤0.05 compared to wt",
    "diseases": "inflammation, obstructive nephropathy, fibrosis, interstitial fibrosis, unilateral ureteral obstruction, UUO"
  },
  {
    "caption": "Angiotensin II infusion via an osmotic pump induced hypertension similarly in wt and Foxd1Cre::Pdgfrb+/J mice (C).",
    "diseases": "hypertension"
  },
  {
    "caption": "In this model of hypertensive injury, the kidney function and even the histopathology was largely unaffected in wt mice, whereas the Foxd1Cre::Pdgfrb+/J mice showed a significantly increased BUN values and prominent glomerulopathy after 28 days compared to the starting values (day 0), to wt animals after 28 days and to age-matched Foxd1Cre::Pdgfrb+/J mice without Angiotensin II infusion (D).",
    "diseases": "glomerulopathy, hypertensive"
  },
  {
    "caption": "Consistently the creatinine clearance per g bodyweight decreased in the hypertensive Foxd1Cre::Pdgfrb+/J mice (E).",
    "diseases": "hypertensive"
  },
  {
    "caption": "PAS staining showed more prominent mesangial expansion and intratubular protein casts indicative of proteinuria only in hypertensive Foxd1Cre::Pdgfrb+/J mice.",
    "diseases": "hypertensive, proteinuria"
  },
  {
    "caption": "Hypertension did not induce mesangial expansion and activation in wt mice, but led to a significant increase in hypertensive Foxd1Cre::Pdgfrb+/J mice as visualized by α-SMA staining. (H) Histomorphometric analysis of α-SMA positive percentage of the glomerular tuft area.",
    "diseases": "Hypertension, hypertensive"
  },
  {
    "caption": "22 weeks old Foxd1Cre::Pdgfrb+/J mice were treated with imatinib (daily gavage, 50mg/kg bodyweight for 21 days; Foxd1Cre::Pdgfrb+/J + imatinib) and were compared to control Foxd1Cre::Pdgfrb+/J mice receiving vehicle (water; Foxd1Cre::Pdgfrb+/J + water). Aged-matched wt mice are indicated as dashed lines. Histomorphometric quantifications of collagen I showed no effect of imatinib treatment on mesangial sclerosis in the glomeruli (K), whereas reduced interstitial fibrosis in imatinib treated Foxd1Cre::Pdgfrb+/J mice compared to controls was found (L).",
    "diseases": "mesangial sclerosis, interstitial fibrosis"
  },
  {
    "caption": "Gene expression arrays were performed in 6 week old Foxd1Cre::Pdgfrb+/J mice compared to wt mice. Listed are genes with log2 fold changes higher or lower than 0.6. Out of these 46 genes, 17 are IFN-regulated genes, 5 are involved in autophagy and 5 in matrix remodeling and fibrosis. Same genes were analysed in microdissected glomeruli (G) and tubulointerstitium (T) of patients with diabetic (DN, G: n=14, T: n=18), hypertensive (HT, G: n=15, T: n=21) nephropathy and living donors (LD, G: n=42, T: n=42) as controls, revealing a similar expression profile.",
    "diseases": "diabetic, DN, HT, hypertensive, nephropathy, fibrosis"
  },
  {
    "caption": "Heatmap depicting pathway activities in Foxd1Cre::Pdgfrb+/J mice and human CKD patients according to PROGENy.",
    "diseases": "CKD"
  },
  {
    "caption": "Based on the gene array datasets transcription factor activities were estimated by using DoRothEA. Depicted are the most regulated ones regulated both in Foxd1Cre::Pdgfrb+/J mice and in human CKD patients.",
    "diseases": "CKD"
  },
  {
    "caption": "Representative [68Ga]Pentixafor PET images of three mice bearing MM.1S (right shoulder) and OPM-2 (left shoulder) tumors.",
    "diseases": "tumors"
  },
  {
    "caption": "Flow cytometric quantification of CXCR4 cell surface expression on resected MM.1S and OPM-2 tumors. Data are the mean ± SEM, n = 4. *P = 0.0286; Mann-Whitney U-test.",
    "diseases": "tumors"
  },
  {
    "caption": "Correlation of [68Ga]Pentixafor PET mean TBR and CXCR4 cell surface expression assessed by flow cytometry. n = 8 tumors were analyzed.",
    "diseases": "tumors"
  },
  {
    "caption": "(G) H&E staining was performed on the injured TA muscles collected from the designated times post-CTX injection to visualize the degree of regeneration. Scale bar = 100 µm.",
    "diseases": "injured"
  },
  {
    "caption": "(H) IF staining for eMyHC on the TA muscles 5 days post-CTX injury. Quantifications of the number of eMyHC+ fibers are shown on the right (n=3, each). Scale bar = 50 µm.",
    "diseases": "injury"
  },
  {
    "caption": "(I) Left: representative images of TA muscles isolated from Ctrl or YY1iKO mice 60 days post-CTX injury. Right: Masson's Trichrome staining of the above muscles to visualize the degree of fibrosis. Scale bar = 100 µm.",
    "diseases": "fibrosis, injury"
  },
  {
    "caption": "(J) Cross-section area (CSA) of individual myofibers in TA muscles 4 weeks after injury was measured. The distribution for CSA was calculated (n=3 mice).",
    "diseases": "injury"
  },
  {
    "caption": "(K) Representative FACS plots showing the percentage of SCs sorted from TA muscles 3 days after CTX injury of Ctrl and YY1iKO mice.",
    "diseases": "injury"
  },
  {
    "caption": "Immunostaining for Pax7 together with Laminin was performed on the TA muscles 3 days post-CTX injury. Scale bar = 100 µm. Quantifications of the numbers of Pax7+ SCs per area are shown on the right (n=3 mice, each).",
    "diseases": "injury"
  },
  {
    "caption": "Immunostaining for MyoD together with Laminin was performed on the TA muscles 3 days post-CTX injury. Scale bar = 100 µm. Quantifications of the numbers of MyoD+ SCs per area are shown on the right (n=3 mice, each).",
    "diseases": "injury"
  },
  {
    "caption": "(N) IF staining for Pax7 and Laminin on TA muscles 4 weeks after CTX injury of Ctrl or YY1iKO mice. Quantifications of the numbers of Pax7+ SCs per 100 fibers are shown on the right (n=3 mice, each). Scale bar = 100 μm.",
    "diseases": "injury"
  },
  {
    "caption": "(P) H&E staining was performed on TA muscles of Ctrl or YY1iKO mice 7 day after second CTX injury. Scale bar = 400 μm (left) or 100 μm (right).",
    "diseases": "injury"
  },
  {
    "caption": "(Q) Representative images of above TA muscles 7 days after second injury.",
    "diseases": "injury"
  },
  {
    "caption": "(S) IF staining for eMyHC and Laminin on TA muscles 7 days after the second CTX injury of Ctrl or YY1iKO mice. Quantifications of the number of eMyHC+ fibers per area are shown on the right (n=3 mice, each). Scale bar = 100 μm.",
    "diseases": "injury"
  },
  {
    "caption": "(G) SCs expansion in vivo was determined by EdU labeling for 12 hrs 2.5 days after CTX injury. Quantifications of the numbers of EdU+ cells are shown on the right (n=3 mice, each). Scale bar = 100 µm.",
    "diseases": "injury"
  },
  {
    "caption": "B, Representative images (left panel) and quantifications (right panel) of NNMT immunostaining  in tissue sections from primary tumors (T) and metastases   (M) in different breast cancer models, scale bar: 100 µm. n = 5 tissue sections per model. **P < 0.01; n.s., not significant, n.a., not available; Mann-Whitney U-test. All data are means ± SD.",
    "diseases": "breast cancer"
  },
  {
    "caption": "C, Kaplan-Meier overall survival  analysis of breast cancer patients  stratified according to NNMT  protein levels (negative or weak, n = 541; intermediate, n = 108; strong, n = 44) in primary  (n = 517) and metastatic  (n =176) tumor tissue. Estimated 5-year overall survival  rates for subjects with strong, intermediate, and negative/weak NNMT  levels were 43.0 ± 10.0%, 69.0 ± 6.0% and 73.0 ± 2.0%, respectively. **P < 0.01; Log-rank test.",
    "diseases": "breast cancer"
  },
  {
    "caption": "D, Graphic quantification (pie charts) and representative images of immunostaining  from 625 primary breast cancer specimens classified according to NNMT  protein abundance [negative (neg)/weak, intermediate or strong]. NNMT  levels are significantly higher (P = 0, Student's T-test) in ERα  negative (neg) than in ERα  positive (pos) breast cancers (side table). Scale bar: 100 µm.",
    "diseases": "breast cancer, breast cancers"
  },
  {
    "caption": "E, Kaplan-Meier  plot depicting metastasis   onset after tumor removal in mice  injected orthotopically with SUM159PT  WT (n = 10), KO (KOd: n = 5; KOs: n = 5) or KO-NNMT  (KOd-NNMT: n= 5; KOs-NNMT: n= 5) cells. *P < 0.05; Log-rank test.",
    "diseases": "metastasis"
  },
  {
    "caption": "C HPO1 and HPO2 inactivation results in rapid iCCA. H&E and CK19 staining for Nf2-/- (8-month-old), Nf2-/-;Sav1-/- (1-week-old) and Nf2-/-;Wwc1-/-;Wwc2+/- (1-week-old) livers. Nf2-/- liver displayed bile duct hyperplasia at 8 months, while Nf2-/-;Sav1-/- and Nf2-/-;Wwc1-/-;Wwc2+/- livers at 1 week exhibited massive expansion of cholangiocytes with enlarged nuclei, irregular shape, and invasive behaviors. Nf2-/-;Sav1-/- also exhibited cholestasis, as indicated by asterisk. Scale bar: 20 μm (H&E and IHC).",
    "diseases": "cholestasis, bile duct hyperplasia"
  },
  {
    "caption": "A Tumor formation in mouse livers with long term HPO1 or HPO2 inactivation. Gross images (black arrow heads indicate HCC lesions), H&E staining and IF images of livers with HPO1 or HPO2 inactivation at indicated ages. IF: green for CK19, red for YAP/TAZ, Ki67 or HNF4α, blue for nuclei. Scale bars: 1 cm (gross liver image), 50 μm (H&E), 50 μm (IF).",
    "diseases": "HCC"
  },
  {
    "caption": "G Immunofluorescent staining  of spinal cord sections from mice  at EAE  peak and control mice  with anti-F4/80 (green), TOP1  (magenta), and nuclei  with Hoechst  (blue). For the left panels, bar = 400 μm; for the magnified panels, bar = 100 μm. The yellow arrowhead indicates a representative F4/80+ cell with high TOP1 expression.",
    "diseases": "EAE"
  },
  {
    "caption": "K TOP1 expression  in the spinal cord homogenates of EAE mice  dissected at disease peak (scored 3) or control mice  were examined by Western blotting. L The quantification of TOP1 protein expression  of Western blot bands in (K) with normalization to GAPDH  and β-actin  (n = 3 biological samples). Data information: Data are presented as the mean ± s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001 Statistical analyses were performed using the student's unpaired two-tailed t-test.",
    "diseases": "EAE"
  },
  {
    "caption": "P Brain  sections from healthy control and MS brain  tissues, including the active MS  lesion, chronic active lesion, and the normal-appearing white matter (NAWM), were stained  with anti-HLA-DR, anti-TOP1, and co-stained  with Hoechst  (bar = 50 μm).",
    "diseases": "MS"
  },
  {
    "caption": "K Spinal cord  sections dissected from Day 30 from the EAE  batch in (H) were stained  with CD11b  (red), Fluoromyelin   (green), and Hoechst  (blue) (bar = 200 μm). L The CD11b immunofluorescent  intensity in (K) was graphed (n = 2 mice  for the control group; n = 4 mice  for the EAE-PBS  and EAE-TPT  groups). M The percentage of demyelinated area in the white matter of the spinal cord  was graphed (n = 2 mice  for the control group, n = 4 mice  for the EAE-PBS  and EAE-TPT  groups). Data information: Data are presented as the mean ± s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001; the Student's unpaired two-tailed t-test was used for comparing the EAE-PBS  group with the EAE-TPT  group in L, and M.",
    "diseases": "EAE"
  },
  {
    "caption": "A) Citrate synthase activity in spinal cord homogenates at disease end stage. Results are expressed as mean ± SEM; n= 8 (4 males and 4 females) mice per group; *p= 0.024, by paired Student's t test. Activities are expressed as nmoles of substrate oxidized per minute per mg of protein.",
    "diseases": "disease"
  },
  {
    "caption": "E, F) Representative Western blots (E) and quantification (F) of PARIS at disease end stage. Protein levels are normalized by β-actin and results are expressed as mean ± SEM and as percent of Non Tg; n= 8 (4 males and 4 females). No statistically significant differences were found between G93A and PKO/G93A by paired Wilcoxon's test (p= 0.99). PARIS levels are unchanged in SOD1-G93A mice relative to Non Tg at disease end stage.",
    "diseases": "disease"
  },
  {
    "caption": "A, B) Western blots (A) and quantification (B) of Miro1 in spinal cord homogenates at disease end stage. β-actin is used as loading reference. Results are expressed as mean ± SEM and as percent of Non Tg; n = 8 (4 males and 4 females) mice per group; *p= 0.011 by paired Student's t test (for comparison G93A vs. PKO/G93A) and **p= 0.003 by paired Friedman's test with Dunn's correction (for Non Tg vs. G93A). Parkin knockout increases the levels of Miro1 in SOD1-G93A mice at disease end stage.",
    "diseases": "disease"
  },
  {
    "caption": "C, D) Western blots (C) and quantification (D) of Mfn2 in spinal cord homogenates at disease end stage. Protein levels are normalized by β-actin. Results are expressed as mean ± SEM and as percent of Non Tg; n= 8 (4 males and 4 females) mice per group; No statistically significant differences were found between G93A and PKO/G93A (p=0.078 by paired Wilcoxon's test); ***p= 0.0007 by paired Friedman's test with Dunn's correction (for Non Tg vs. G93A) and *p= 0.037 by paired Friedman's test with Dunn's correction (for PKO vs. PKO/G93A). Parkin knockout increases the levels of Mfn2 in SOD1-G93A mice at disease end stage.",
    "diseases": "disease"
  },
  {
    "caption": "E) Western blots of spinal cord mitochondria at disease end stage, probed for lysine 48 (left panel) and lysine 63 (right panel) ubiquitin chains. Citrate synthase is used as loading control. Asterisks indicate ubiquitinated proteins with different abundance in SOD1-G93A samples.",
    "diseases": "disease"
  },
  {
    "caption": "I) Quantification of March5 at disease end stage. Results are expressed as mean ± SEM and percent of Non Tg; n= 8 (4 males and 4 females) mice per group. No statistically significant differences were found between G93A and PKO/G93A by paired Wilcoxon's test (p= 0.742). Protein levels are normalized by Complex V. March5 levels are unaffected by Parkin knockout.",
    "diseases": "disease"
  },
  {
    "caption": "J) Quantification of Mul1 at disease end stage. Results are expressed as mean ± SEM and percent of Non Tg; n= 8 (4 males and 4 females) mice per group. No statistically significant differences were found between G93A and PKO/G93A by paired Wilcoxon's test (p= 0.94). Protein levels are normalized by Complex V. Mul1 levels are unaffected by Parkin knockout.",
    "diseases": "disease"
  },
  {
    "caption": "IHC of ALSP patient post mortem tissue for amyloid-β (green) and CLD5 (red), (B) human IgG (green) and PDGFRβ (red), (C) GFAP (green) and CLD5 (red). ΔA781_N783 and P824R indicate the CSF-1R variant present.",
    "diseases": "ALSP"
  },
  {
    "caption": "(D) Iba1 (green) and GFAP (red), (E) amyloid-β (green) and CD68 (red), (f) CD163 (green) and CLD5 (red), imaging of an ALSP patient with the ΔA781_N783 CSF-1R variant. ΔA781_N783 and P824R indicate the CSF-1R variant present.",
    "diseases": "ALSP"
  },
  {
    "caption": "(G) Fibrinogen (green) and CLD5 (red) and (H) FLAIR imaging of an ALSP patient with the ΔA781_N783 CSF-1R variant. ΔA781_N783 and P824R indicate the CSF-1R variant present.",
    "diseases": "ALSP"
  },
  {
    "caption": "(A) Heat map showing a subset of mRNAs of genes immunoprecipitated by anti-EZH2 antibody in LNCaP and C4-2 prostate cancer cell lines, which was generated based on the distinct RIP-seq reads on specific gene exons. The units of the heatmap values were reads per kilobase million (RPKM).",
    "diseases": "prostate cancer"
  },
  {
    "caption": "(A) IHC analysis of Pten, Ezh2 and p53 proteins in prostatic tissues of 4-month-old mice with different genotypes: Ptenpc-/- (n=11); Ezh2pc-/- (n=8); Ptenpc-/-;Ezh2pc-/- (n=10) and 'wild-type' littermate controls (n=10). Scale bars, 50",
    "diseases": "prostatic"
  },
  {
    "caption": "(G) Quantification of nonmalignant, low-grade PIN (LGPIN) and high-grade PIN (HGPIN) or cancerous acini in the prostates (including anterior prostate (AP), ventral prostate (VP) and dorsolateral prostate (DLP)) of mice with the indicated genotypes and number as in (A).",
    "diseases": "cancerous acini, HGPIN, high-grade PIN, LGPIN, low-grade PIN, nonmalignant"
  },
  {
    "caption": "(A) Correlation analysis of EZH2 and p53 mRNA expression measured by RT-qPCR in primary and metastatic prostate cancer specimens of a cohort of patients from University of Washington.",
    "diseases": "metastatic prostate cancer, primary"
  },
  {
    "caption": "(B) IHC analysis of EZH2 and p53 protein expression in human prostate cancer tissues of a cohort of patients from Mayo Clinic. Case 1 and 2 show low and high expression in primary tissues, respectively; case 3 shows high expression in lymph node metastasis. Scale bar, 50 µm. Scale bars in insets, 10 µm.",
    "diseases": "lymph node metastasis, primary, prostate cancer"
  },
  {
    "caption": "(C) Correlation analysis of EZH2 and p53 protein expression in primary and metastatic prostate cancer specimens of the Mayo Clinic cohort.",
    "diseases": "metastatic prostate cancer, primary"
  },
  {
    "caption": "(D) IHC analysis of EZH2 and p53 protein expression in commercially purchased TMA with patient specimens of brain, colorectal, pancreatic cancer and sarcoma. Scale bars in low magnification images, 200 µm; Scale bars in high magnification images, 50 µm. Arrows, indicated the zoom out-box. (E) IHC data as shown in (D) were quantified and used for correlation analysis of EZH2 and p53 protein expression in patient specimens of brain, colorectal, pancreatic cancer and sarcoma. Pearson correlation r and P values in each cancer type are indicated. ",
    "diseases": "brain, colorectal, pancreatic cancer, sarcoma"
  },
  {
    "caption": "(C, D) VCaP cells (1x107) infected with lentivirus were injected subcutaneously into NSG mice (n = 8/group). Tumors were measured by caliper twice a week. Tumors at the end point of measurement were isolated and photographed (C), and data are shown as means ± SD (D). Statistical significance was determined by two-tailed Student's t-test for tumors at day 56. *** P < 0.001.",
    "diseases": "Tumors, tumors"
  },
  {
    "caption": "(E-G) Luciferase-expressing MIA PaCa-2 cells (2×106) infected with lentivirus were injected via tail vein into NSG mice (n = 6/group). At 12 weeks after injection, mice were subjected to bioluminescent imaging, and images were recorded (E) and bioluminescent signals were quantified (F). Bioluminescent flux (photons s-1 sr-1 cm-2) was determined for lesions in lung, the ends of the box are the upper and lower quartiles and the box spans the interquartile range; the median is marked by a vertical line inside the box; the whiskers are the two lines outside the box that extend to the highest and lowest observations. Lungs were isolated from mice, stained with Bouin's solution, and photographed (G). The white spots on lungs (stained in yellow) are metastatic tumors. * P < 0.05; NS, no significance.",
    "diseases": "lesions, metastatic tumors"
  },
  {
    "caption": "(B) Kaplan-Meier plots showing the association of EZH2 overexpression with biochemical recurrence of prostate cancer in patients from the TCGA cohort. Tumors were separated into two groups according to EZH2 expression levels (high or low) and three groups based on the mutation status of p53 (WT, loss or mutated).",
    "diseases": "Tumors, prostate cancer"
  },
  {
    "caption": "(E, F) Effect of Ezh2 ASOs on growth of murine prostate cancer allografts. Mice (n=10) bearing the Ptenpc-/-;Trp53pc-/- (E) and Ptenpc-/-;Trp53pc-/R172H allografts (F) were treated with control ASOs (50 mg kg-1) or Ezh2 ASOs at different doses (25 mg kg-1 and 50 mg kg-1). Tumor growth was measured twice a week for 3 weeks and the data are shown in the bottom panels. Each allograft was isolated by the end of ASO treatment and photographed (top panels). Data shown as means±SD (n=10). Statistical significance was determined by two-tailed Student's t-test. *** P < 0.001.",
    "diseases": "Tumor, prostate cancer"
  },
  {
    "caption": "F Whole-mount visualization of mitochondria  in injured hypoglossal motor axon at 5 days after injury. G Immunostaining  of injured hypoglossal nerves for GFP  and cytochrome c (Cytc) at 5 days after injury. H Number of mitochondria  in injured axons  of Atf3:BAC2 Tg and Rpt3  CKO mice  at 5 days after injury  (n= 5 mice  per group). I Total number of GFP-positive injured motor neurons  in Atf3:BAC2 Tg and Rpt3  CKO mice  at 5 days after injury  (n= 4 mice  per group). J Number of GFP-positive mitochondria  in soma  at 5 days after injury. Data are shown as the mean ± s.e.m. (n= 3 mice). Data information: Data are shown as the mean ± s.e.m., ** P = 0.0005 in (H), no significant difference (P = 0.8915) in (I) and * P = 0.0068 in (J), determined by unpaired t-test. Dashed lines reveal hypoglossal nucleus  in axon  in (F and G). Scale bars, 5 μm in (F) and 2.5 μm in (G).",
    "diseases": "injury"
  },
  {
    "caption": "C Hypoglossal motor neurons of Atf3:BAC2 Tg and Rpt3  CKO mice  before and at 5 days (5d) and 28 days (28d) after injury, immunostained  by AnkG  and GFP. Arrows indicate the AIS stained  by AnkG. Scale bars, 20 μm. D Quantification of the number of the AIS  in control (Cont) and injured  (Inj) hypoglossal motor neurons of Atf3:BAC2 and Rpt3  CKO mice. Data are expressed as mean ± s.e.m. * P = 0.043, ** P = 0.0162, *** P = 0.008, **** P < 0.0001, determined by one-way ANOVA followed by Tukey post hoc analysis, n.d., not detected, n = 5 mice  for each group. E Quantification of the AIS  length in control (Cont) and injured  (Inj) hypoglossal motor neurons of Atf3:BAC2 and Rpt3  CKO mice. Data are expressed as mean ± s.e.m. * P = 0.0087, ** P = 0.0024, *** P = 0.0007, determined by one-way ANOVA followed by Tukey post hoc analysis, n.d., not detected, n = 5 mice  for each group.",
    "diseases": "injury"
  },
  {
    "caption": "C  Western blot  of hypoglossal nuclei  (left) and nerves  (right) at 5 days after injury  with anti-AnkG, RPT3  and GAPDH  antibodies. AnkG  products of 190/ 270/ 480 kDa are indicated by arrowheads. The positions of the degraded products by calpain  are shown by asterisks at ~95 kDa and 72 kDa.",
    "diseases": "injury"
  },
  {
    "caption": "I Altered localization  of the GFP-labeled mitochondria  in the AIS  of injured motor neurons  of AnkG  shRNA AAV-infected Rpt3  CKO mice  at 5 days after injury. J Fluorescent intensity scans of GFP  and AnkG  corresponding to (I). K Graph represents the percentage (%) of GFP  intensity in the AIS, compared with that in the AIS  of Atf3:BAC2 Tg mouse  treated with AnkG  shRNA (n = 5 mice  per group). Data information: For data are shown as the mean ± s.e.m. , ** P = 0.0064 in (K) determined by one-way ANOVA followed by Tukey post-hoc test, n.d., not detected. In I), closed arrowheads denote the presence of the AIS, while open arrowheads show disappeared AIS. Scale bars, 5 μm in I)",
    "diseases": "injury"
  },
  {
    "caption": "L Thionine-stained hypoglossal motor neurons of Rpt3  CKO mice  at 10 days after injury. Rpt3  CKO mice  are infected by AnkG  shRNA or scramble shRNA AAVs. Dashed lines outline hypoglossal nucleus. XII, hypoglossal nucleus; cc,  central canal. M The percentage of surviving motor neurons on the injured  side compared with that on the control side in Rpt3  CKO mice  after infection of AnkG  shRNA or scramble shRNA AAVs  (n= 4 mice  per group). Data information: For M), data are shown as the mean ± s.e.m. , * P = 0.0405, ** P = 0.003 in (M), determined by one-way ANOVA followed by Tukey post-hoc test, n.d., not detected. Scale bars, 100 μm in (L).",
    "diseases": "injury"
  },
  {
    "caption": "A. HAT1 levels were assessed by  immunohistochemical staining  in clinical tissues of liver cancer patients, pancreatic cancer patients, and cholangiocarcinoma patients. Scale bar = 100 μm",
    "diseases": "cholangiocarcinoma, liver cancer, pancreatic cancer"
  },
  {
    "caption": "Mononuclear cells from bone marrow aspirates of newly diagnosed (#2, #5, #9 and #13) or relapsed (#7 and #12) MM patients  were treated with mycolactone and/or  BZ  at the indicated concentrations, or vehicle as control, for 18 h. Then, MM  cells were identified by  staining  with anti-CD38  and anti-CD138 antibodies A Following treatment, induction of apoptosis/necrosis was measured by exposure of annexin V  and PI incorporation. Data are Mean % of live cells from technical duplicates, relative to controls.",
    "diseases": "MM, necrosis"
  },
  {
    "caption": "Mononuclear cells from  bone marrow aspirates of newly diagnosed (#2, #5, #9 and #13) or relapsed (#7 and #12) MM patients were treated with mycolactone and/or  BZ at the indicated concentrations, or vehicle as control, for 18 h. B Synergy between  mycolactone and BZ in treated tumors. Data are Mean Loewe scores from technical duplicates, shown as heatmaps.",
    "diseases": "MM"
  },
  {
    "caption": "D, Scoring of the PI3Kα activation transcriptomic signature was used to cluster patients with high, medium (both groups were combined, high+medium: red) and low (black) scoring levels in the primary tumours of confirmed PDAC patients from PAAD (TCGA) or PACA-AU (BH corrected p-values). The survival curves of each cluster were then plotted, and the statistical significance was calculated using the logrank test.",
    "diseases": "PDAC"
  },
  {
    "caption": "A, Representative images of PI3K activation (as shown by positive pAkt substrate staining) on the primary tumours of PDAC patients, with values of quantification of cfDNA and mutated KRAS allele frequency.",
    "diseases": "PDAC"
  },
  {
    "caption": "(E) MDA-MB-231 breast cancer cells were transfected with vector, wild type PPM1G or catalytically inactive PPM1G D496A (D/A) mutant. Levels of phosphorylated α-catenin were detected by using phospho-specific antibodies.",
    "diseases": "breast cancer"
  },
  {
    "caption": "OVX mice and 18-month-old male mice  serve as the model of  osteoporosis, AAV-MYDGF or AAV-GFP were injected into bone marrow cavity every 3 weeks for 12 weeks (n=10, there were 10 mice in each group, and 6 mice in each group were selected for detection at the end of the experiment). Micro-CT  reconstruction, H&E staining of trabecular bone from distal femurs in Sham +GFP, OVX  +GFP and OVX + MYDGF groups (n=6). Representative images of micro-CT reconstruction, scale bar, 2mm (A). Representative images of H&E staining in distal  femora, scale bar, 500μm for upper panel,100μm for lower panel (D).",
    "diseases": "osteoporosis"
  },
  {
    "caption": "OVX mice and 18-month-old male mice  serve as the model of osteoporosis, AAV-MYDGF or AAV-GFP  were injected into bone marrow cavity every 3 weeks for 12 weeks (n=10, there were 10 mice in each group, and 6 mice in each group were selected for detection at the end of the experiment). H&E staining  of  trabecular bone from distal femurs  in aged mice with AAV-GFP or AAV-MYDGF  (n=6). Representative images of H&E staining in distal femora, scale bar, 500μm for upper panel,100μm for lower panel (J).",
    "diseases": "osteoporosis"
  },
  {
    "caption": "(F) PTEN immunohistochemistry analysis of MCF-7-miR-10b-OE or control MCF-7-miR-Scr-OE tumorxenografts.",
    "diseases": "tumor"
  },
  {
    "caption": "Spearman correlations between protein expression and sensitivity to Plk1 inhibitors (BI2536 GSK461364 AUC values for two Plk1 inhibitors are compared with expression of selected proteins (cMet, E-cadherin, β-catenin, and Snail); each data point represents an individual non-small cell lung cancer cell line. E-cadherin, β catenin, and cMet protein expression correlated with drug resistance.",
    "diseases": "non-small cell lung cancer"
  },
  {
    "caption": "Three epithelial/resistant non-small cell lung cancer cell lines were treated with 5 ng/ml TGF-β for 14 days to induce a mesenchymal phenotype, which was confirmed with Western blot (left) and qPCR (right) analysis of epithelial-to-mesenchymal transition (EMT) markers (A).",
    "diseases": "epithelial/resistant non-small cell lung cancer"
  },
  {
    "caption": "Thirty-three proteins were differentially regulated between epithelial and mesenchymal NSCLC cell lines after treatment with volasertib, including those involved in the cMet/FAK/Src signaling axis (blue text) and those involved in the PI3K/Akt signaling axis (orange text).",
    "diseases": "NSCLC"
  },
  {
    "caption": "Epithelial (red text) and mesenchymal (blue text) NSCLC cell lines transfected with 10nM siRNA as indicated for 48 hours. NT, non-targeting control and subjected to Western blotting with the indicated antibodies. Data are means ± standard error of the mean from three independent experiments. Significant differences using two-sided Student t test are indicated by *p < 0.05.",
    "diseases": "NSCLC"
  },
  {
    "caption": "Cell viability was measured using CellTiter-Glo in NSCLC cell lines treated with volasertib, tepotinib, or a 1:2 ratio of both for 72 hours. Left: representative cell viability graph of cells treated with the indicated drugs. Right: heatmap depicting the calculated combination indices at Fa = 0.25 and Fa = 0.5.",
    "diseases": "NSCLC"
  },
  {
    "caption": "Immunoblots from cells transfected with siRNA as indicated for 48 hours (left) with densitometric quantification normalized with β-actin (right). Data are means ± standard error of the mean from three independent experiments. Significant differences using two-way analysis of variance with Bonferroni or Benjamini-Hochberg (BH) correction for multiple comparison are indicated (*p < 0.01). Mesenchymal and epithelial NSCLC cell lines are indicated in blue and red text, respectively.",
    "diseases": "NSCLC"
  },
  {
    "caption": "Mice bearing epithelial (red text) and mesenchymal (blue text) non-small cell lung cancer tumors were treated with vehicle control, volasertib (30 mg/kg per week intravenously), tepotinib (25 mg/kg per day orally), or the combination for 5 weeks to generate tumor growth curves of patient-derived xenografts (PDX; A) and cell line xenografts The percent change in tumor volume at the end of treatment (normalized to day zero) was calculated with each data point representing an individual mouse, and the bar is the mean value ± standard error of 10 mice for each group",
    "diseases": "non-small cell lung cancer tumors"
  },
  {
    "caption": "Kaplan-Meier survival curves for mesenchymal PDX TC424 (top) and cell line xenograft Calu6 (bottom) with death due to excessive tumor burden as the endpoint.",
    "diseases": "tumor"
  },
  {
    "caption": "Mesenchymal NSCLC cell lines with the noted MET alterations were incubated with 50nM volasertib for four hours and subjected to immunoblotting with the indicated antibodies. *p < 0.05. **p < 0.01.",
    "diseases": "NSCLC"
  },
  {
    "caption": "Epithelial and mesenchymal non-small cell lung cancer (NSCLC) cell lines after treatment with 50nM volasertib for 24 hours. Cells were then harvested, and lysates were immunoblotted for the indicated proteins.",
    "diseases": "non-small cell lung cancer, NSCLC"
  },
  {
    "caption": "Epithelial and mesenchymal NSCLC cell lines after Plk1 silencing with siRNA for 48 hours. Cells were then harvested, and lysates were immunoblotted for the indicated proteins.",
    "diseases": "NSCLC"
  },
  {
    "caption": "Calu6 and H1792 mesenchymal NSCLC cell lines after VIM silencing with siRNA for 48 hours. Cells were then harvested, and lysates were immunoblotted for the indicated proteins.",
    "diseases": "NSCLC"
  },
  {
    "caption": "Calu6 (mesenchymal) and H1975 (epithelial) NSCLC cell lines after Plk1 and INTB1 silencing with siRNA for 48 hours. Cells were then harvested, and lysates were immunoblotted for the indicated proteins.",
    "diseases": "NSCLC"
  },
  {
    "caption": "Calu6 (mesenchymal) and H1975 (epithelial) NSCLC cell lines after treatment with fibronectin for 24 hours. Cells were then harvested, and lysates were immunoblotted for the indicated proteins.",
    "diseases": "NSCLC"
  },
  {
    "caption": "Calu6 and H1975 NSCLC cell lines after treatment with 50nM volasertib for 24 hours. Cells were then harvested, and lysates were immunoprecipitated (IP) using β1-integrin, vimentin, and Plk1 antibodies, then immunoblotted for the indicated proteins.",
    "diseases": "NSCLC"
  },
  {
    "caption": "A Representative G9A immunostaining (left) and semi-quantitative results (right) of human kidney samples. AKI (acute kidney injury), n = 3; Con (control), n = 6.",
    "diseases": "acute kidney injury, AKI"
  },
  {
    "caption": "C Representative renal H&E images (left) with quantitative pathological scores (right) of WT (n = 8) and Ehmt2Ksp mice (n = 7) at day three after renal I/R injury (I/R 3D).",
    "diseases": "I/R, I/R injury"
  },
  {
    "caption": "G, H Representative immunoblots (G) and quantitative results (H) of p-Rip3 and p-Mlkl of WT (n = 3) and Ehmt2Ksp mice (n = 3) under I/R 3D injury.",
    "diseases": "I/R 3D injury"
  },
  {
    "caption": "I Representative Sirius Red staining (left) with quantitative results (right) on the kidney sections of WT (n = 7) and Ehmt2Ksp (n = 4) mice at day seven after renal I/R injury (I/R 7D).",
    "diseases": "I/R, I/R injury"
  },
  {
    "caption": "K Representative TUNEL staining (left) with quantitative results (right) of WT (n = 8) and Ehmt2Ksp mice (n = 4) under I/R 7D injury.",
    "diseases": "I/R"
  },
  {
    "caption": "qPCR validation (C) of indicated genes related to fatty acid metabolism of WT+NI (n = 6), Ehmt2Ksp+NI (n = 6), WT+I/R 3D (n = 6) and Ehmt2Ksp+I/R 3D (n = 6) groups.",
    "diseases": "I/R"
  },
  {
    "caption": "qPCR validation (E) of indicated genes related to fatty acid beta-oxidation of WT+NI (n = 6), Ehmt2Ksp+NI (n = 6), WT+I/R 3D (n = 6) and Ehmt2Ksp+I/R 3D (n = 6) groups.",
    "diseases": "I/R"
  },
  {
    "caption": "G Representative CES1 immunostaining (left) with semi-quantitative analysis (right) of human kidneys. AKI (acute kidney injury), n = 3; Con (control), n = 6.",
    "diseases": "acute kidney injury, AKI"
  },
  {
    "caption": "H Representative immunoblots (left) with quantitative results (right) of Ces1 level in the kidneys of WT (n = 3) and Ehmt2Ksp (n = 3) mice at I/R 3D.",
    "diseases": "I/R"
  },
  {
    "caption": "C mRNA levels of Kim1 and Ngal of PBS+NI (n = 6), A366+NI (n = 5), PBS+I/R 3D (n = 6) and A366+I/R 3D (n = 5) groups.",
    "diseases": "I/R"
  },
  {
    "caption": "Representative renal TG (triglyceride) and TC (cholesterol) levels (E) of PBS+I/R 3D (n = 12) and A366+I/R 3D (n = 12) groups.",
    "diseases": "I/R"
  },
  {
    "caption": "F mRNA levels of fatty acid oxidation related genes of PBS+I/R 3D (n = 6) and A366+I/R 3D (n = 5) groups.",
    "diseases": "I/R"
  },
  {
    "caption": "K Representative immunostaining for CD3, Ly6G, and F4/80 and quantitative results of PBS+I/R 3D (n = 6) and A366+I/R 3D (n = 5) groups.",
    "diseases": "I/R"
  },
  {
    "caption": "Representative immunoblots (left) with quantitative results (right) of p-Rip3 for PBS+I/R 3D (n = 3) and A366+I/R 3D (n = 3) groups.",
    "diseases": "I/R"
  },
  {
    "caption": "A Representative H&E staining (left) and pathological scores (right) of injured kidneys from mice received intervention treatment of saline (n = 4) or atorvastatin (20 mg/kg, i.g., first dose at 6-hours after ischemia, n = 5, or 14-hours after ischemia, n = 5).",
    "diseases": "ischemia"
  },
  {
    "caption": "E. 3D7 or PfCDPK7-KO parasites were cultured in the presence or absence of 200 μM choline in culture medium. After 3 days,  parasitemia was determined by counting parasites on thin blood  smears (mean± SEM, n=6; biological replicates, *p< 0.05, ***p<0.001, ANOVA).",
    "diseases": "parasitemia"
  },
  {
    "caption": "A. Parasites overexpressing  EK-GFP or its S37A mutant were synchronized and parasitemia was determined at the end of first (48 h.p.i) and second cycle (96 h.p.i). Fold change in  parasitemia of EK_S37A parasites with respect to WT EK overexpressing parasites was compared, which was significantly reduced (mean± SEM, n=3; biological replicates, *p<0.05, ANOVA).",
    "diseases": "parasitemia"
  },
  {
    "caption": "B, Colon adenocarcinoma cell lines HCT116 (circles), LoVo (squares), LS174 (triangles), or RKO (inversed triangles) were treated with the vehicle alone (-), 1 µM MPA or 10 µM MPA for 24 hrs and subjected to propidium iodide staining and FACS analysis. Data are shown as the fold induction of the cell number in G0/G1 phases (blue), S phase (red), and G2/M phases upon treatment with 1 µM MPA (dark) or 10 µM MPA (clear) over vehicle treated cells.",
    "diseases": "Colon adenocarcinoma"
  },
  {
    "caption": "Top-left - tSNE plot of the Seurat clusters, boxes demarcate compared clusters. Dashed boxes and labels indicate the cell clusters that are compared in panels A-C. (A) Volcano plot of differential gene expression (DGE) between liver vascular endothelial cells in the tumor and non-tumor samples. (B) Volcano plot of DGE between mononuclear phagocytes in the malignant and non-malignant samples. (C) Volcano plot of DGE between T cells in the tumor and non-tumor samples. (D) DGE analysis between tumor mononuclear phagocytes classified by cancer type (cholangiocarcinoma in dark purple and metastasis in light purple). Wilcoxon rank-sum tests were used to generate p-values, Benjamini-Hochberg multiple hypotheses correction was used to compute q-values. Labeled dots in all panels are gene names of selected differentially expressed genes between the compared two clusters.",
    "diseases": "cholangiocarcinoma"
  },
  {
    "caption": "A Representative image of tumor-bearing mice and tumors after subcutaneous injection of Hepa1-6 hepatoma cells into WT and Tet2-/- (KO) mice.",
    "diseases": "hepatoma"
  },
  {
    "caption": "F Representative images of tumors from WT and KO mice subcutaneously injected with Py8119 breast cancer cells, as well as quantification of tumor weights (n=5).",
    "diseases": "breast cancer"
  },
  {
    "caption": "A, B Immunohistochemistry analysis of CD8a, CD4 (A), PCNA, and Foxp3 (B) in tumors from WT and Tet2-/- (KO) mice subcutaneously injected with Hepa1-6 hepatoma cells. Corresponding bar charts display positive staining, quantified using Image Pro Plus 6.0 software (n=3). Pictures were captured at 400X magnification. Scale bar = 50 μm.",
    "diseases": "hepatoma"
  },
  {
    "caption": "A BreastMark microarray platform; Kaplan-Meier curves of overall survival (OS), demonstrating that high expression of ESRP1 (red line) is associated with poor prognosis in ER+ breast cancer. A log rank test was used to calculate P=2.8 e-07 (n= 934, number of events= 216).",
    "diseases": "ER+ breast cance"
  },
  {
    "caption": "B BreastMark microarray platform; Kaplan-Meier curves of overall survival (OS) of ER- breast cancer. A log rank test was used to calculate P=0.4481 (n= 322, number of events= 130).",
    "diseases": "ER- breast cancer"
  },
  {
    "caption": "E The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) RNA-seq dataset; Kaplan-Meier curves of overall survival (OS) in ER+ breast cancer, demonstrating that high expression of ESRP1 (red line) is associated with poor prognosis in ER+. A log rank test was used to calculate P=0.00011 (n= 656, number of events= 62).",
    "diseases": "BRCA, Breast Invasive Carcinoma, ER+ breast cancer"
  },
  {
    "caption": "F The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) RNA-seq dataset; Kaplan-Meier curves of overall survival (OS) in ER- breast cancer. Red-high ESRP1 expression; Black-low ESRP1 expression. A log rank test was used to calculate P=0.19 (n=100, number of events=17).",
    "diseases": "BRCA, Breast Invasive Carcinoma, ER- breast cancer"
  },
  {
    "caption": "E Impact of ESRP1 knockdown on in vivo tumor growth. Five million cells (2-control, 2C3, 9-control and 9C2) were implanted into mammary fat pads of athymic mice (five mice per group) in the presence of supplemental estrogen. Tumors were measured weekly using calipers for external measurements. Tumor volume was calculated as L x W2/2, where L is length and W is width (note the different scale for tumor volumes). Data (mean ± SD) were calculated using two-way ANOVA (n= 5 mice per group).",
    "diseases": "Tumor, Tumors"
  },
  {
    "caption": "B TCGA Splicegraphs for the EMT signature genes in ESRP1high versus ESRP1low tumors. A splice graph of the gene's exons is shaded based on expression level and shows the selected splice event outlined in red.",
    "diseases": "tumors"
  },
  {
    "caption": "A t-SNE map of combined  scRNA-seq profiles of total cells isolated from pathologically normal preneoplastic tissue from BRCA1 mutation carriers (BRCA1; n=4) and non-BRCA premenopausal  women (n=8) with no family history of breast cancer. Cell colors represent individual samples. B Same t-SNE map as in (A) but colored by cluster (cluster resolution 0.12). C Epithelial clusters were identified by EPCAM expression  and the  non-epithelial cells  were re-clustered to reveal  immune and  stromal cell populations (cluster resolution 0.08). Lineage identity was determined by hierarchical clustering according to top marker genes",
    "diseases": "breast cancer"
  },
  {
    "caption": "D t-SNE plot showing the combined single-cell transcriptomes of total tissue cells from  BRCA1 preneoplastic tissue and TNBCs  (n=4 for each), colored according to individual patients (B1 = preneoplastic BRCA1+/- tissue; TN-B1= BRCA1-associated TNBCs). E Same t-SNE map as (D) but colored by cluster (cluster resolution 0.15). F Expression  of epithelial  markers indicated on the combined t-SNE plot as in (D, E) for BRCA1  preneoplastic and BRCA1-associated tumor cells. G Epithelial  clusters were identified by EPCAM expression  and  non-epithelial cells  are indicated by the dotted line. H Same t-SNE map as in (D, E) but colored according to cancerous state: preneoplastic tissue (blue) and BRCA1-associated TNBCs (yellow). I Box plots of signature expression  scores for the 13 cell clusters in (D, E) according to human breast epithelial  and stromal  gene signatures. Cluster 1 corresponds to tumor cells, while clusters 6, 9 and 10 represent adjacent normal LP, basal  and ML cells, respectively. Box plots show quartiles, minimum and maximum.",
    "diseases": "TNBCs"
  },
  {
    "caption": "A Reclustered EPCAM-negative cells (excluding clusters 1, 6, 9 and 10 revealed immune/stromal cells in the microenvironment, identified using lineage markers. B Combined t-SNE plot as in (A) of the single-cell transcriptomes of immune  and stromal cells from preneoplastic tissue of BRCA1  mutation carriers (blue; preneo) and BRCA1-associated TNBCs (yellow; tumor). C t-SNE plots showing expression  profiles of cardinal markers of immune  and stromal cells. D Bar plots showing the percentage of cells expressing typical immune cell (including Treg) genes for clusters in (A) by preneoplastic vs tumor. E Left panel, same t-SNE map as in (A) but separated into cells from preneoplastic (blue) and tumor specimens (yellow). Endothelial cell (endo), fibroblast cell (fibro) and pericytes (peri) clusters are marked. Right panel, proportion of clusters as in (A) according to tissue type. F Relative cluster sizes as in (E) but by individual patient.",
    "diseases": "TNBCs"
  },
  {
    "caption": "A-C t-SNE plots of combined scRNA-seq  profiles of total cells from 8 TNBC  tumors, 6 HER2+ tumors and 13 ER+ tumors respectively. Integration and cluster sizes for the same cells Cells colored by cluster (top left panels), EPCAM expression  (top right), cancer subtype marker (bottom left) or MKI67 expression  (bottom right). Dotted lines delineate epithelial cells  (top panels) and cycling epithelial cells (bottom panels). Normal epithelial  subsets (normal) are also demarcated by dotted lines in the upper-right panels of B and C. D InferCNV plots to map inferred copy number variation (CNV) for the combined tumor scRNA-seq expression  data for the epithelial  clusters indicated in panels A-C. scRNA-seq data from normal  breast epithelial cells  (N-1105-epi) served as a reference for normalization. Each row represents a gene and each column cells from a cluster in a single tumor. The tumor clusters are color-coded as in A-C. Amplifications (red) and deletions (blue) are inferred from the  gene expression. Tumor cells were distinguished from normal (N) cells by abundance of CNV.",
    "diseases": "TNBC"
  },
  {
    "caption": "A, B Image quantification showing number of CD8+Ki67+ cells (A) or CD68+Ki67+ cells (B) per mm2 of tissue from TNBC, HER2+ and ER+ tumors, either within the tumor region (K8/18+) or the stroma  (defined as >5 μm from tumor border). Error bars represent s.e.m. CD8/Ki67: n=11 for TNBC, n=12 for ER+, n=5 for HER2+. CD68/Ki67: n=6 for TNBC, n=8 for ER+, n=5 for HER2+.",
    "diseases": "TNBC"
  },
  {
    "caption": "C-F Representative confocal  images of ER+ (ER-0032) and  triple negative tumors  ( TN-0066) immunolabeled  for K8/18 (yellow), CD68  (green) and Ki67  (red) (C, E) or K8/18 (yellow), CD8 (green) and  Ki67 (red) (D, F). DAPI  is shown in blue. Arrows depict proliferative T cells  (CD8+Ki67+) or macrophages  (CD68+Ki67+). Enlargements on shown in the right-hand panels. Scale bars, 200 µm for large tilescans; 50 µm for enlargements and smaller tilescans.",
    "diseases": "triple negative tumors"
  },
  {
    "caption": "(A) NPM1 expression in CD34+Lin- cells from myelodysplastic syndrome (MDS) patients compared to healthy volunteers (n = 29).",
    "diseases": "MDS, myelodysplastic syndrome"
  },
  {
    "caption": "(B) Representative staining of NPM1 protein levels in bone marrow samples of MDS or acute myeloid leukemia (AML) with multi-lineage dysplasia (MLD). Insets show representative staining in blasts [B] and in differentiated myeloid cells [e.g., neutrophil, M] with a high magnification.",
    "diseases": "MLD, multi-lineage dysplasia, acute myeloid leukemia, AML, MDS"
  },
  {
    "caption": "(C) Percentages of patient samples with NPM1-low and NPM1-normal in healthy, MDS and MLD in AML groups.",
    "diseases": "MLD, AML, MDS"
  },
  {
    "caption": "(F) Representative peripheral blood (PB) smears. Insets show the differentiated granulocytes (a, b) in control mice, and anisocytosis (c), dysplastic myeloid cells (d-g) in Npm1 cKO mice (Npm1F/FVav1Cre+). Npm1 cKO mice show dysplastic erythroid cells (polychromatophilic, blue arrowhead; schistocyte, blue-outlined arrowhead; tear drop, Howell-Jolly bodies, black arrowhead; black-outlined arrowhead), dysplastic monocytes (black arrow), and dysplastic neutrophils (d-f). Scale bars, 10 μm.",
    "diseases": "anisocytosis"
  },
  {
    "caption": "(F) Representative PB smears of DKO mice. Insets show anisocytosis (a), poikilocytosis (b) and dysplastic myeloid cell (c). DKO mice show dysplastic erythroid cells (polychromatophilic, blue arrowhead), Howell-Jolly bodies, (black arrowhead in insert a), dysplastic monocytes (black arrow, and i-v), dysplastic neutrophils (vi), a pseudo-Pelger-Huet anomaly (ii), and dysplastic platelets (giant platelet, iv and vii). Scale bars, 10μm.",
    "diseases": "anisocytosis, poikilocytosis, pseudo-Pelger-Huet anomaly"
  },
  {
    "caption": "(I) Representative H&E staining of sections of the spleen of 2-month-old DKO mice with myeloid disorders. Arrowheads (right) indicate the infiltrating myeloid blasts. Scale bars, 250 μm (left) and 10μm (right), respectively.",
    "diseases": "myeloid disorders"
  },
  {
    "caption": "Immunoblot of expression levels of MYC, TSC1, TSC2, and β-actin loading control in high MYC Burkitt's lymphoma (BL) cells compared to low MYC Hodgkin lymphoma (HL) cells.",
    "diseases": "BL, Burkitt's lymphoma, HL, Hodgkin lymphoma"
  },
  {
    "caption": "Elevated TSC1 and MYC expression in BL (cohort 1). Example of immune staining of TSC1, MYC, the B-cell marker CD20, and DAPI nuclear DNA-staining in germinal centers of control lymph nodes (upper rows) and samples from BL patients (lower rows). Boxplots at the right show quantification of TSC1 or MYC staining from control germinal centers and BL samples (see materials and methods) (the horizontal line shows the median, whiskers show maximum and minimum data points and the box represents the first to the third quartiles, n=56 fields for tumor samples and n=21 fields for control germinal centers; scale bar = 100 μm).",
    "diseases": "BL"
  },
  {
    "caption": "Quantification of immunoblot analysis of TSC expression in BL (cohort 2) (n=13) compared to healthy tonsils (n=3) or reactive lymph nodes (n=3) (mean ± st. dev.) shown in Fig EV2B.",
    "diseases": "BL"
  },
  {
    "caption": "Survival rate of different BL cell lines upon TSC1 knockdown. Graphs show numbers of viable cells expressing either a scrambled control sh-RNA or a TSC1-specific sh-RNA 3 days after seeding of equal number of viable cells (determined by trypan blue exclusion; mean ± st.dev., n=3 biological replicates).",
    "diseases": "BL"
  },
  {
    "caption": "Ramos cells expressing either a TSC1-specific or a control shRNA were inoculated into NOD/SCID mice and tumor volume was measured regularly. The immunoblot shows the level of knockdown of TSC1 (sh-TSC1b) compared to control (sh-contr), and levels of TSC2 and phosphorylated mTORC1 target proteins before inoculation. Tumor growth curves show mean ± SEM (n=8/group). Pictures of xenotransplanted human Ramos lymphoma tumors 35 days after inoculation. The top panels show tumors derived from Ramos cells stably expressing control sh-RNA (sh-contr); the lower panels show tumors derived from Ramos cells stably expressing TSC1-specific sh-RNA (sh-TSC1b).",
    "diseases": "lymphoma"
  },
  {
    "caption": "Impaired wound closure in αSMA-TK mice. (A) IHC for αSMA+ cells in wound tissue sections at day 6 post-wounding. Representative images are shown. Scale bar, 50 µm. Black boxes denote zoomed regions displayed in bottom panels. (B) Quantification of αSMA+ cells at day 6 post-wounding. WT, N=6; TK, N=5 biological replicates. Two-tailed non-parametric Mann-Whitney test performed.",
    "diseases": "wound, wounding"
  },
  {
    "caption": "(F) Expression levels of ACTA2 in normal and diabetic human wound tissue. RNA-seq reads are derived from (Davis et al., 2020, Data ref: Davis et al, 2020). Normal, N=3; diabetic, N=4 biological replicates. Data are presented as a box and whisker plot of min to max values. Unpaired t-test performed.",
    "diseases": "diabetic, wound"
  },
  {
    "caption": "(J-O) Impaired granulation tissue formation and angiogenesis in αSMA-TK mice. (J) Representative H&E images of wound tissue sections at day 17 post-wounding. Granulation areas are marked by black lines, triangles (open: incomplete closure, filled: closed wounds) denote the epithelial tongues. Epi, epidermis; derm, dermis regions denoted. Scale bar: 200 μm. (K) Granulation tissue thickness measured on digital images and normalized to the average values in the WT control (set to 100%). NA (not assessed) reflects the lack of granulation in αSMA-TK mice. WT, N=5; TK, N=4 biological replicates. (L) Immunofluorescent staining for CD31 (red) and nuclei (blue) on wound tissue sections at day 17 post-wounding. White boxes denote zoomed regions depicted in right panels. Scale bar, 100 μm. (M) Quantification of CD31+ cells per visual field normalized to WT mice. WT, N=3; TK, N=5 biological replicates. (N) IHC for hypoxyprobe (brown) on wound tissue sections at day 17 post-wounding. Black boxes denote zoomed regions depicted in right panels. Scale bar, 100 μm. (O) Quantification of hypoxyprobe area per visual field normalized to WT mice. WT, N=5; TK, N=6 biological replicates.",
    "diseases": "wound, wounding, wounds"
  },
  {
    "caption": "(D) Representative FACS plots of digested skin from bone marrow (BM) transplanted αSMA-RFP mice 17 days post-wounding. (E) FACS quantification of αSMA-RFP+ cells in wounds of BM transplanted mice. αSMA-RFP with αSMA-RFP BM, N=2; WT with αSMA -RFP BM, N=3; αSMA-RFP with WT BM, N=4 biological replicates. One-way ANOVA with Tukey's multiple comparison test performed comparing WT with αSMA-RFP BM and αSMA-RFP with WT BM to αSMA-RFP with αSMA-RFP BM. (",
    "diseases": "wounding, wounds"
  },
  {
    "caption": "(H-J) Multispectral imaging of changes in fibroblast subsets during wound repair. (H) Representative images (20x magnification) of orthogonal wound tissue sections at day 6 post-wounding displaying αSMA, FAP, and FSP1 overlaid with DAPI in the wound bed. Subcutaneous (subq), dermis (derm), epidermis (epi), and scar regions are denoted. Individual αSMA, FAP, and FSP1 channel images overlaid with DAPI. Scale bar, 50 µm. (I) Analysis of multiplex immunostaining of full thickness skin wounds performed at indicated time points. Data are presented as the fractional area of each image positive for the indicated markers and negative for CD31. Day 0, N=2; Day 6, N=4; Day 9, N=3; Day 14, N=3; Day 21, N=3; Day 32, N=4 biological replicates. One-way ANOVA with Dunnett's multiple comparison test performed. (J) Percent overlap of αSMA with FAP and FSP1 throughout wound healing. αSMA+ denotes cells positive for αSMA but not FAP or FSP1. Day 0, N=2; Day 6, N=4; Day 9, N=3; Day 14, N=3; Day 21, N=3; Day 32, N=4 biological replicates.",
    "diseases": "wound, wounds"
  },
  {
    "caption": "(L) Representative H&E images of wound tissue sections at day 17 post-wounding. Granulation areas are marked by black lines. Scale bar, 200 μm. (M) Granulation tissue thickness measured on digital images and normalized to the average values in the WT control. WT, N=3; FAP-TK, N=3; WT, N=17, FSP1-TK, N=9 biological replicates. (N) Immunofluorescent staining for CD31 (red) and nuclei on wound tissue sections at day 17 post-wounding. White boxes denote zoomed regions depicted in right panels. Scale bar, 100 μm. (O) Quantification of CD31+ cells per visual field normalized to WT mice. WT, N=4; FAP-TK, N=4; WT, N=3; FSP1-TK, N=3 biological replicates. (P) IHC for hypoxyprobe (brown) on wound tissue sections at day 17 post-wounding. Black boxes denote zoomed regions depicted in right panels. Scale bar, 100 μm. (Q) Quantification of hypoxyprobe area per visual field normalized to WT mice. WT, N=3; FAP-TK, N=3; WT, N=3; FSP1-TK, N=4 biological replicates. (R) W",
    "diseases": "wound, wounding"
  },
  {
    "caption": "(A) IHC for collagen I on wound tissue sections at day 17 post-wounding (brown stain). Black boxes denote zoomed regions depicted in bottom panels. Scale bar: 50 μm. (B) Quantification of collagen I positive area normalized to the average area in WT controls. WT, N=5; TK, N=5 biological replicates. (C) Polarized light images of picrosirius red stained wound tissues at day 17 post-wounding. Red: collagen fibers. White boxes denote zoomed regions depicted in bottom panels. Scale bar, 50 µm. (D) Quantification of collagen fiber (picrosirius red) percent area normalized to the average area in WT controls. WT, N=3; TK, N=3 biological replicates. (E-",
    "diseases": "wound, wounding"
  },
  {
    "caption": "(E-H) Reduced collagen deposition in Col1α1cKO wounds. (E) IHC for collagen I on wound tissue sections at day 14 post-wounding (brown stain). Black boxes denote zoomed regions depicted in bottom panels. Scale bar: 25 μm. (F) Quantification of collagen I positive area normalized to the average area in WT controls. WT, N=7; Col1α1cKO, N=4 biological replicates. (G) Polarized light images of picrosirius red stained wound tissues at day 14 post-wounding. Red: collagen fibers. White boxes denote zoomed regions depicted in bottom panels. Scale bar, 50 µm. (H) Quantification of collagen fiber percent area and fiber width normalized to the average area and width, respectively, in WT controls. WT, N=4; Col1α1cKO, N=5 biological replicates.",
    "diseases": "wound, wounding, wounds"
  },
  {
    "caption": "(J-M) Reepithelization and vascularization in WT and Col1α1cKO mice. (J) Representative images of keratin 5 (Krt5, red) stained wounds at day 14 post-wounding. White boxes denote zoomed regions depicted in right panels. Scale bar, 500 µm. (K) Quantification of epidermal thickness. WT, N=6; Col1α1cKO, N=5 biological replicates. (L) Immunofluorescent staining for CD31 (red) and nuclei (blue) on wound tissue sections at day 14 post-wounding. White boxes denote zoomed regions depicted in right panels. Scale bar, 20 μm. (M) Quantification of CD31+ area per visual field normalized to WT mice. WT, N=6; Col1α1cKO, N=5 biological replicates.",
    "diseases": "wound, wounding, wounds"
  },
  {
    "caption": "(C) IF for β1 integrin (red) and αSMA (green) on wound tissue sections at day 17 post-wounding. White boxes denote zoomed regions depicted in right panels. Scale bar: 20 μm.",
    "diseases": "wound, wounding"
  },
  {
    "caption": "(F-K) Reepithelization, granulation tissue formation, and vascularization in WT and Itgb1cKO mice. (F) Representative images of keratin 5 (Krt5, red) stained wounds at day 14 post-wounding. White boxes denote zoomed regions depicted in right panels. Scale bar, 500 µm. (G) Quantification of epidermal thickness. WT, N=4; Itgb1cKO, N=6 biological replicates. (H) Immunofluorescent staining for CD31 (red) and nuclei (blue) on wound tissue sections at day 14 post-wounding. White boxes denote zoomed regions depicted in right panels. Scale bar, 20 μm. (I) Quantification of CD31+ area per visual field normalized to WT mice. WT, N=6; Itgb1cKO, N=6 biological replicates. (J) Polarized light images of picrosirius red stained wound tissues at day 14 post-wounding. Red: collagen fibers. White boxes denote zoomed regions depicted in right panels. Scale bar, 50 µm. (K) Quantification of collagen fiber percent area normalized to the average area in WT controls. WT, N=6; Itgb1cKO, N=6 biological replicates. (L) Quantification of collagen fiber width normalized to the average width in WT controls. WT, N=6; Itgb1cKO, N=6 biological replicates. D",
    "diseases": "wound, wounding, wounds"
  },
  {
    "caption": "Representative H&E and immunohistochemical stainings of CK5/6 and p63 in pulmonary and head-and-neck squamous-cell carcinomas. Scale bar: 500 µm.",
    "diseases": "pulmonary, head-and-neck squamous-cell carcinomas"
  },
  {
    "caption": "Heatmap showing somatic mutations in defined pathways and HPV status for all HNSCC and SQCLC cases analysed. (Blue, no mutation/ no HPV detected; red, mutation/HPV detected; white, no data available)",
    "diseases": "SQCLC, HNSCC"
  },
  {
    "caption": "Comparison of mutation rates in HNSCC (n=279) and SQCLC (n=178) cases from TCGA. Genes exhibiting a mutation rate >0.25 in both cancer types are labelled.",
    "diseases": "cancer, SQCLC, HNSCC"
  },
  {
    "caption": "Representative histogram showing the SILAC ratio distribution between the Super-SILAC standard and SQCLC (left) and HNSCC (right) samples.",
    "diseases": "SQCLC, HNSCC"
  },
  {
    "caption": "Boxplot showing the numbers of quantified proteins, derived from 44 SQCLC and 30 HNSCC tissue samples. The central line in the boxes represents the median number of proteins over all samples, upper and lower borders of boxes correspond to 25% and 75% quantiles. Whiskers indicate minimum and maximum.",
    "diseases": "SQCLC, HNSCC"
  },
  {
    "caption": "Principal-component analysis of SQCLC (n=44; blue) and HNSCC (n=30; red) protein expression. Shown are the first two principal components, accounting for 8.51% and 8.03% of the total variance in the data, respectively.",
    "diseases": "SQCLC, HNSCC"
  },
  {
    "caption": "Volcano plot adjusted p values for differential protein expression to averaged normalised SILAC ratios of two replicates. Red (higher expression in HNSCC) and blue (higher expression in SQCLC) dots indicate significantly regulated proteins (p < 0.05).",
    "diseases": "SQCLC, HNSCC"
  },
  {
    "caption": "Two-class comparison of genetic dependencies from a publically available genome-scale CRISPR-Cas9 screen of HNSCC (12 cell line) versus SQCLC (10 cell lines) identified a subset of differentially expressed proteins that were also differential dependencies in these tumor types. The x-axis represents the effect size of the mean difference of dependency scores in HNSCC compared to SQCLC cell lines. Positive effect size indicates a greater mean dependency in HNSCC; negative effect size indicates a greater mean dependency in SQCLC. The y-axis represents the statistical significance of differential enrichment calculated as -log10(p-value) from a two-sided t-test. The p-values used for this plot are uncorrected for multiple hypothesis testing. Highlighted in green are genetic dependencies that were also identified as differentially expressed proteins in our study.",
    "diseases": "tumor, SQCLC, HNSCC"
  },
  {
    "caption": "Immunohistochemical analysis of the expression of HMGCS-1 (p=0.0014),FTL (p=0.0001) (C),LGALS7 (p=0.0001) and FAM83H (p=0.0001)(D) in an independent cohort of 212 SQCLC and 343 HNSCC cases. Scale bar indicates 100µm. Shown are mean values and standard deviation. Statistical significance was assessed using Wilcoxon-Mann-Whitney test.",
    "diseases": "SQCLC, HNSCC"
  },
  {
    "caption": "Boxplot showing the number of quantified proteins derived from 19 SQCLC, 19 HNSCC and 51 squamous-cell lung tumours of unknown origin derived from HNSCC patients. The central line in the boxes represents the median number of proteins over all samples, upper and lower borders of boxes correspond to 25% and 75% quantiles. Whiskers indicate minimum and maximum.",
    "diseases": "SQCLC, squamous-cell lung tumours, HNSCC"
  },
  {
    "caption": "Representative H&E and immunohistochemical stainings of CK5/6 and p63 in squamous-cell lung tumours of unknown origin derived from HNSCC patients. Scale bar: 500 µm.",
    "diseases": "squamous-cell lung tumours, HNSCC"
  },
  {
    "caption": "Kaplan-Meier analysis of overall survival (OS) in which all patients with lung tumours were grouped according to the clinical classification (left, median survival SQCLC: 55 months; metHNSCC: 31 months) or proteomic classification (right, median survival SQCLC: 55 months; metHNSCC: 8 months) of the tumour as metHNSCC or SQCLC. The p value is from a log-rank test. Kaplan-Meier analysis of overall survival (OS) in which only the patients that were independent from the training cohort were grouped according to the clinical classification (left, median survival SQCLC: 84 months; metHNSCC: 35 months) or proteomic classification (right, median survival SQCLC: 84 months; metHNSCC: 5 months) of the tumour as metHNSCC or SQCLC. The p value is from a log-rank test.",
    "diseases": "tumour, lung tumours, SQCLC, HNSCC"
  },
  {
    "caption": "K-L: Percentage of pDCs grouped by COVID-19  severity, as determined by  oxygen  supplementation (no oxygen n=43, nasal oxygen n=65 and high flow oxygen n=5). Percentage of pDCs (K) was correlated to COVID-19 disease severity (L) using simple linear regression. Data information: Each dot represents a patient, lines with error bars show the median values with interquartile ranges mean values with the standard error of the mean Statistical significance was determined using the Kruskal-Wallis test and simple linear regression *<p0.05, **<p0.01 ***<p0.001, ns= not significant.",
    "diseases": "COVID-19"
  },
  {
    "caption": "(D) Histologic  H&E sections of ileum  and hind paw indicate severe ileitis  and arthritis  in 20-30 w/o SPF TNFemARE/ARE mice  (Scale bars upper panel: 100 μm, scale bars lower panel: 500 μm).",
    "diseases": "arthritis, ileitis"
  },
  {
    "caption": "(F) Comparing SPF  versus GF  H&E sections of the ileum  shows complete rescue of gut inflammation  under axenic conditions in 20-30 w/o TNFemARE/ARE mice  (Scale bars: 100 μm).",
    "diseases": "gut inflammation"
  },
  {
    "caption": "(C) 20-30 w/o SPF TNFemARE/ARE mice  clearly suffer from inflammation  in the synovio-entheseal complex, which is not rescued in age-matched GF mice. (Scale bars: 200 μm)",
    "diseases": "inflammation"
  },
  {
    "caption": "(C) H&E sections of the  calcaneo-cuboid joint of 5-15 w/o A20myel-KO mice  indicate immune cell  infiltrates in the synovium  and the fat pad and severe bone marrow edema. (Scale bars: 100 μm)",
    "diseases": "bone marrow edema"
  },
  {
    "caption": "(E) Histologic  images of  hind paws of old (44 w/o) GF wild-type (left) versus A20myel-KO (right) mice. The morphology  of the paw  is completely lost in the transgenic mouse  due to severe inflammation. (Scale bars: 200 μm)",
    "diseases": "inflammation"
  },
  {
    "caption": "(F) Splenomegaly  in GF A20myel-KO mice  of 15 w/o indicates  systemic inflammation in this mouse  model (wild-type n=7, A20myel-KO n=8). Data information: For panels F), data are represented as Mean +/- SEM, n=biological replicates. For graph (F), two-tailed unpaired t-test was used. ns= p-value > 0.05, * = p-value ≤ 0.05, ** = p-value ≤ 0.01, *** = p-value ≤ 0.001, **** = p-value ≤ 0.0001.",
    "diseases": "systemic inflammation, Splenomegaly"
  },
  {
    "caption": "A, Correlation between MYC   and OTUD6B  expression in MM patient  samples at diagnosis. mRNA expression in primary CD138+ MM  cells was quantified by  real-time qPCR  (n = 89 patients). Data are fit by linear regression (black line); Pearson r, Pearson correlation coefficient; P < 0.0001; by linear regression and Pearson correlation.",
    "diseases": "MM"
  },
  {
    "caption": "NRP1-expressing cells amongst CD4+CD3+ Th cells were measured by  flow cytometry in PBMC  from 18 healthy volunteers (healthy controls, HC) and 10 SLE patients. Representative staining  is shown for CD4+CD3+ Th cells (B), and summary data for CD3+CD4+ Th cells (C) Plots show individual subjects, HC, n=18; SLE, n=10; with mean ± SD indicated by error bars; ***p<0.001, ****p<0.0001 Unpaired Student's T test.",
    "diseases": "SLE"
  },
  {
    "caption": "NRP1-expressing cells amongst CD4+CD3+ Th cells were measured by flow cytometry  in PBMC  from 18 healthy volunteers (healthy controls, HC) and 10 SLE patients. summary data for CD3+CD4+CD127hi conventional cells (D). Plots show individual subjects, HC, n=18; SLE, n=10; with mean ± SD indicated by error bars; ***p<0.001, ****p<0.0001 Unpaired Student's T test.",
    "diseases": "SLE"
  },
  {
    "caption": "(E) Individuals were divided into NRP1-high subjects (NRP1+ cells >1.3% in  Th cells) and NRP1-low subjects (NRP1+ cells≤1.35% in Th cells). Numbers of HC and SLE  falling into each group are shown. *** p<0.001 Chi squared test with Yates' correction.",
    "diseases": "SLE"
  },
  {
    "caption": "(F, G) NRP1-expressing cells amongst CD3+CD4+CD45RO- cells were measured, representative staining  (F) and summary data (G). The plot shows individual subjects, HC, n=18; SLE, n=10; with mean ± SD indicated by error bars; ****p<0.0001 Unpaired Student's T test.",
    "diseases": "SLE"
  },
  {
    "caption": "(B) SH-SY5Y neuroblastoma cells expressing Cas9 together with a sgRNA targeting PRKN (sgPRKN) or a non-targeting control (sgCon) were assessed for Parkin expression by immunoblotting of cytosolic fractions.",
    "diseases": "neuroblastoma"
  },
  {
    "caption": "(D) Domain architecture of human Parkin with positions of selected PD-associated mutations. Ubl, ubiquitin-like; IBR, in-between-RING HeLa cells expressing wild-type Parkin or the indicated PD-associated Parkin mutants were treated with antimycin A and oligomycin (AO) for 2h. Immunoblots are representative of three independent experiments. Graph shows densitometric analysis of non-ubiquitinated proteins in AO-treated samples relative to untreated control from three independent experiments. Error bars represent mean +/- SD. All Parkin constructs were N-terminally FLAG-tagged except R104W.",
    "diseases": "PD"
  },
  {
    "caption": "(A) Western blot analysis with representative blot including lamin A/C, NLRP3, caspase 1, and actin levels in skin fibroblats from patients with HGPS, n = 2 controls and 2 patients. Positive control correspond to THP1 cells stimulated with LPS+ATP.",
    "diseases": "HGPS"
  },
  {
    "caption": "(A) Cell growthn (lower subpanel left patient 1 and right patient 2) and morphological aspect (upper subpanel) with MCC950 determined in healthy and representative HGPS fibroblasts. **P < 0.01, *P < 0.05 patient cells no treatment vs treatment. Results are presented as the mean ± SD of three independent experiments.",
    "diseases": "HGPS"
  },
  {
    "caption": "(B) Western blot analysis with representative blots including lamin A/C, NLRP3, IL-1β and actin levels in skin fibroblats from control and HGPS patient after 48 hr of vehicle and MCC950 treatment.",
    "diseases": "HGPS"
  },
  {
    "caption": "(C-E) Representative fluorescence images of HGPS and control fibroblasts to evaluate the effect of the MCC950 in the nuclear morphology (D) and NLRP3 expression (E). Scale bar: 30µm. Results are presented as the mean ± SD of three independent experiments. ***P < 0.01 patient vs control cells, aaaP < 0.01 patient cells no treatment vs treatment. One-way ANOVA test was used for statistical analysis.",
    "diseases": "HGPS"
  },
  {
    "caption": "WT and C2βD1212A/D1212A mice were subjected to tMCAO followed by 24h of reperfusion. (B) Protein expression of TNFα, IL-1β and IL-6. Data represent mean ± SEM (n=4 mice per group; *p=0.05; Mann-Whitney test). Data represent mean ± SEM (n=5-7 mice per group; **p<0.01; Mann-Whitney test).",
    "diseases": "tMCAO, reperfusion"
  },
  {
    "caption": "A Gene expression of TNFα (n=8-10 mice for WT and n=6 mice  for  C2βD1212A/D1212A), IL-1β (n=8 mice for WT and n=10-12  mice for C2βD1212A/D1212A), IL-6 (n=8 mice for WT and n=10-12 mice for C2βD1212A/D1212A) and VCAM-1  (n=8-10 mice for WT and n=10 mice for C2βD1212A/D1212A) after 1 hour of ischemia without reperfusion (right panel). Gene expression of IL-6 (n=10-12 mice for WT and n=8 mice for C2βD1212A/D1212A) and  VCAM-1 (n=12 mice for WT and n=10mice for C2βD1212A/D1212A) after 1 hour of ischemia followed by 4 hours of reperfusion (bottom, left panel) on WT and C2βD1212A/D1212A mice. The mRNA levels are given as the fold increase normalized to PGK1  relative to the healthy contralateral hemisphere of WT mice. Data represent mean ± SEM (***p<0.001, **p<0.01, *p<0.05, Mann-Whitney test or unpaired t-test, as accordance).",
    "diseases": "ischemia, reperfusion"
  },
  {
    "caption": "Representative photographs of coronal brain sections and graph quantification of  infarct volume (dashed white line) measurements in bone marrow  (BM) chimeric mice 24 hours after tMCAO. WT>WT: transplantation  of WT BM into WT hosts; C2βD1212A>WT: transplantation  of C2βD1212A/D1212A BM into WT hosts;  C2βD1212A>C2βD1212A: transplantation of C2βD1212A/D1212A BM into C2βD1212A/D1212A hosts; WT> C2βD1212A transplantation of WT BM into kinase-dead hosts. Data represent mean ± SEM; n=13-16 mice per group; *p<0.05 **p<0.01; ***p<0.001 vs WT>WT, Mann-Whitney test or unpaired t-test, as accordance.",
    "diseases": "tMCAO"
  },
  {
    "caption": "A. Four representative images of RHOB immunostaining in human non-small-cell lung cancers. Figures correspond to the percentage of tumor analyzed.",
    "diseases": "tumor"
  },
  {
    "caption": "D. Progression-free survival of erlotinib-treated patients with EGFR-mutated lung tumors, according to RHOB expression, assessed by immunohistochemistry (low RHOB group = negative + weak staining; high RHOB group = moderate + high staining).",
    "diseases": "tumors"
  },
  {
    "caption": "G. RHOB immunostaining score evolution in EGFR-mutated lung tumors before treatment and after EGFR-TKI relapse.",
    "diseases": "tumors"
  },
  {
    "caption": "E. Immunostaining of cleaved caspase-3 in lung tumors from EGFRL858R/Rhob+/+ or EGFRL858R/Rhob-/- mice treated for 24 h with erlotinib at 12.5 mg/kg. Scale bar: 50 µm. (**: p<0.001 vs. placebo; ***: p<0.0001 vs. placebo).",
    "diseases": "tumors"
  },
  {
    "caption": "B. Representative immunostaining of phospho-AKT (Ser473), phospho ERK1/2 and their total protein amounts in lung tumors from EGFRL858R/Rhob-/- or EGFRL858R/Rhob+/+ mice treated or not with erlotinib (12.5 mg/kg/day) for four days. The remaining hyperplastic areas were selected in erlotinib-treated mice to efficiently characterize the effect of erlotinib on ERK and AKT pathways in both Rhob genotypes. Scale bar: 100 µm.",
    "diseases": "tumors"
  },
  {
    "caption": "C. Representative Ki67 immunostaining of lung tumors from EGFRL858R/Rhob-/-, EGFRL858R/Rhob+/- and EGFRL858R/Rhob+/+ mice treated or not with erlotinib alone (12.5 mg/kg/day) or in combination with the AKT inhibitor G594 (25 mg/kg/day) for four days (scale bar: 50 µm), and the corresponding quantification (D).",
    "diseases": "tumors"
  },
  {
    "caption": "F Western blot analysis of YAP protein levels in the tumor xenografts derived from ME180-MXIV, ME180-YAP, and ME180-YAPS127A cells.",
    "diseases": "tumor"
  },
  {
    "caption": "G Expression of Ki67 in the tumor xenografts of ME180-MXIV, ME180-YAP, and ME180-YAPS127A cells implanted in athymic nude mice. Ki67 was visualized using an Alexa-488 (green)-conjugated secondary antibody. Actin was visualized using an Alexa-594 (red)-conjugated secondary antibody. Nuclei were stained with DAPI. Scale bar: 20 μm. Note the significant increase in the Ki67-positive cells in the ME180-YAP and ME180-YAPS127A tumor xenografts.",
    "diseases": "tumor"
  },
  {
    "caption": "A-F Representative images showing expression of YAP (in red) in wild-type mousecervical tissues (n = 5) (A), HPV16E6-induced (C) and HPV16E6/E7-induced (E) mousecervicaltumor tissue (n = 4 each). Scale bars for (A), (C), and (E): 100 μm. High-resolution images showing the expression and cellular location of YAP in normal cervical tissues (B), HPV16E6-induced (D) and HPV16E6/E7-induced (F) mousecervicaltumor tissue. Scale bars for (B), (D), and (F): 25 μm.",
    "diseases": "tumor"
  },
  {
    "caption": "Integrative Genome Viewer (IGV) snapshot showing  ATAC-seq peaks along and upstream of the  VWF  gene in GPR56high vs. low samples (top, average peak size of 10 GPR56high (turquoise) and 15 GPR56low samples (violet)), RNA-seq  reads of the same location in  AML samples with high (n=9) versus low (n=11)  GPR56 expression (two middle tracks), and RNA-seq reads of shLuc  versus GPR56 knockdown CD34+ cells (3 bottom tracks, one of two replicates shown for each condition). Track height was group-scaled. Dashed vertical lines indicate  binding sites for the annotated TFs. TFBS: transcription factor  binding site derived from the HOCOMOCO v10 database; TSS: transcription start site. TFs in blue  bind to differentially accessible chromatin  regions.",
    "diseases": "AML"
  },
  {
    "caption": "Jacob expression in human AD. The ratio of normalized levels of pJacob/Jacob is significantly reduced in the temporal cortex of AD patients as compared to the age-matched control group. All samples are normalized to Histone3 (H3). N=11-12 different subjects.",
    "diseases": "AD"
  },
  {
    "caption": "(K, L) Nitarsone reduces number of varicosities in SLM of CA1 of TBA2.1 mice. (K) Representative, confocal images of dendrites filled with biocytin stained from 13 weeks old mice. Arrows indicate varicosities. Scale bar: 1 μm. (L) Number of dendritic swellings per 10 μm. N=19-22 dendrites from 2 animals per genotype.",
    "diseases": "varicosities"
  },
  {
    "caption": "A. Glucose transporter1 (Glut1) immunohistochemistry on sections of 5 weeks growth glioma in ROSAmT/mG::Pdgfb-iCre mouse (50 µm depth stack). Hypoxic tumor cells upregulate Glut1.",
    "diseases": "glioma"
  },
  {
    "caption": "B. Still image of two-photon live imaging on 2 weeks growth glioma implanted in ROSAmT/mG::Pdgfb-iCre mouse demonstrating tip cell filopodia extension indicative of sprouting. See Supplementary movie 1.",
    "diseases": "glioma"
  },
  {
    "caption": "C. Representative images of two-photon live imaging of the same glioma area of the same mouse on 2 and 5 weeks growth glioma (BFP positive) implanted in ROSAmT/mG::Pdgfb-iCre mouse (350µm depth stack). Note differences in network complexity and vessel diameter.",
    "diseases": "glioma"
  },
  {
    "caption": "E. Branchpoint quantification during glioma growth (n=8 mice).",
    "diseases": "glioma"
  },
  {
    "caption": "G. Quantification of unperfused vessel segments (asterisk) shows increase during glioma growth (n=5 mice).",
    "diseases": "glioma"
  },
  {
    "caption": "I. Late stage glioma growthvessels are leaky compared to early tumor growth (n=5 mice per group). Statistical analysis: D.E.G.I. one-way ANOVA followed by multiple comparisons Tukey's test. Error bars: meanSD. Scale bars: A: 250µm; B: 50µm; C-F: 150µm; G: 0,5cm.",
    "diseases": "glioma"
  },
  {
    "caption": "A. F4/80 immunohistochemistry on a section of 5 weeks growth glioma implanted in ROSAmT/mG::Pdgfb-iCre mouse (50µm depth stack).",
    "diseases": "glioma"
  },
  {
    "caption": "B. Two-photon live imaging of LifeAct-GFP bone marrow transplantation in 5 weeks implanted glioma in ROSAmT/mG mice (100µm depth stack).B lower panels: 280µm;",
    "diseases": "glioma"
  },
  {
    "caption": "C. Two-photon live imaging of LifeAct-GFP bone marrow transplantation in 3 and 5 weeks implanted glioma in ROSAmT/mG. Macrophages relocate close to blood vessels during glioma growth (50µm depth stack) (n=4 mice). Statistical analysis: C: t-test. Error bars: meanSD. Scale bar:C: 100µm.",
    "diseases": "glioma"
  },
  {
    "caption": "A. MHCII and MRC1 immunohistochemistry on a section of 3-5 weeks growth glioma implanted in ROSAmT/mG::Pdgfb-iCre mouse. M1 macrophages, preferentially located in hypoxic area, are abundant at 3 weeks and their number decreases at 5 weeks. M2 macrophages, preferentially located around blood vessels, are present at a low level at 3 weeks and their number increases at 5 weeks.Scale bars: A: 200µm;",
    "diseases": "glioma"
  },
  {
    "caption": "B. Macrophage quantification during glioma growth (n=5 mice per group). Statistical analysis: B. one-way ANOVA followed by multiple comparisons Tukey's test;",
    "diseases": "glioma"
  },
  {
    "caption": "C. MHCII and MRC1 macrophage population FACs analysis in 2, 3, 4 and 5 weeks glioma (subsets in gated CD11b+ cells) (n=3 mice per group).",
    "diseases": "glioma"
  },
  {
    "caption": "D. Correlation analysis of M2 like macrophages accumulation (MRC1 positive) with vessel dysmorphia over glioma growth (n=12 mice). Statistical analysis: D. Spearman correlation test;Scale bars: D: 70µm;",
    "diseases": "glioma"
  },
  {
    "caption": "E. MRC1 immunohistochemistry on 3 weeks growth glioma in ROSAmTmG::Pdgfb-iCre mouse following MHCII-FITC labeled IV injection at 6 or 24h (5µm depth stack). Note the segregation of MRC1 and MHCII cell labeling at 6 hours and the overlapping of these two markers at 24 hours (n=5 mice per group). Statistical analysis: E. t-test. Error bars: E: 50µm.",
    "diseases": "glioma"
  },
  {
    "caption": "A. Glut1immunohistochemistry on human grade II and grade IV glioma samples (50µm depth stack). Blood vessel diameter increases and network complexity decreases with increasing grade. Statistical analysis: A.C.D. one-way ANOVA followed by multiple comparisons Tukey's test; Scale bars: A-B: 100µm.",
    "diseases": "glioma"
  },
  {
    "caption": "B. CD68, MHCII and MRC1 immunohistochemistry on human grade II and grade IV glioma samples (50µm depth stack). Statistical analysis: A.C.D. one-way ANOVA followed by multiple comparisons Tukey's test; Scale bars: A-B: 100µm.",
    "diseases": "glioma"
  },
  {
    "caption": "
C. Macrophage polarization quantification. Low-grade glioma is characterized by high number of M1 polarized macrophages. High-grade glioma is characterized by high number of M2 polarized macrophages. Statistical analysis: A.C.D. one-way ANOVA followed by multiple comparisons Tukey's test;
",
    "diseases": "glioma"
  },
  {
    "caption": "D. Correlation analysis of M2 like tumor accumulation (MRC1 positive) with vessel dysmorphia depending on the tumor grade. Statistical analysis: A.C.D. one-way ANOVA followed by multiple comparisons Tukey's test;",
    "diseases": "tumor"
  },
  {
    "caption": "E. Quantification of macrophage distance to the nearest blood vessel. Macrophages relocate close to blood vessels in late stage gliomas. For n of patients per group refer to TableEV1. Statistical analysis: E. Spearman correlation test. Error bars: meanSD. Scale bars: A-B: 100µm.",
    "diseases": "gliomas"
  },
  {
    "caption": "A. Glut1 immunohistochemistry on sections of 4 weeks growth glioma in ROSAmT/mG mice treated with anti-CSF1 or control antibodies. Anti-CSF1 antibody treatment induces a two-fold decrease in vessel caliber compared to control antibody (n=6 mice per group) (50µm depth stack). Statistical analysis: A.F. t-test; Error bars: A-C-F: meanSD; Scale bars: A-B-E: 150µm.",
    "diseases": "glioma"
  },
  {
    "caption": "B. Glut1 and MRC1 immunohistochemistry on 4 weeks growth glioma in ROSAmT/mG mice treated with anti-CSF1 or control antibodies. Anti-CSF1 antibody induces a decrease in macrophage recruitment in the tumor microenvironment associated with an improved blood brain barrier functionality assessed by a better Glut1 blood vessel coverage compared to control antibody treated mice (50µm depth stack). Scale bars: A-B-E: 150µm.",
    "diseases": "glioma, tumor"
  },
  {
    "caption": "E. Two-photon live imaging of vessel perfusion in 4 weeks implanted glioma growth using FITC-dextran IV injection in ROSAmT/mG mice treated with anti-CSF1 or control antibodies. Scale bars: A-B-E: 150µm.",
    "diseases": "glioma"
  },
  {
    "caption": "A. MRC1 immunohistochemistry on sections of 3 weeks growth glioma in ROSAmT/mG mice treated with recombinant CSF1 or carrier. Recombinant CSF1 treatment induces blood vessel enlargement in early tumors (50µm depth stack).",
    "diseases": "glioma, tumors"
  },
  {
    "caption": "D. Tumor volume quantification in 3 weeks glioma implanted mice treated with recombinant CSF1, anti-CSF1 antibody or control antibody. Recombinant CSF1 treatment reduces tumor growth compared to control (n=6 mice per group). Statistical analysis: B.D. one-way ANOVA followed by multiple comparisons Tukey's test; Error bars: D: median interquartile. Scale bar: 100µm.",
    "diseases": "glioma"
  },
  {
    "caption": "A. qPCR analysis of CCR7, IL12, CCL19, CXCL10, MRC1, TGFβ, CD209 and VEGF on RNA samples from MHCII or MRC1 tumor extracted macrophages (n=5 isolation per group).Statistical analysis: A. G. Mann-Whitney u-test. Error bars: A-D-E-F: meanSD",
    "diseases": "tumor"
  },
  {
    "caption": "B. sFlt1 binding assay on 5 weeks growth glioma section implanted in ROSAmT/mG::Pdgfb-iCre mouse. At late stage tumor growth, M2 macrophages surrounding blood vessels present very high amount of VEGF (binding sFlt1) to the neighboring endothelial cells (5µm depth stack).",
    "diseases": "glioma, tumor"
  },
  {
    "caption": "C. F4/80 immunohistochemistry and sFlt1 binding on sections of 4 weeks growth glioma in Vegfafl/fl::LysMCre+ or Vegfafl/fl ::LysMCre- mice (50µm depth stack).",
    "diseases": "glioma"
  },
  {
    "caption": "E. Quantification of F4/80 positive macrophages binding sFlt1. VEGF depletion is effective in 61% of the macrophages invading the tumor (n=7 mice per group). Statistical analysis: D.E.F. t-test; Error bars: A-D-E-F: meanSD;",
    "diseases": "tumor"
  },
  {
    "caption": "G. Tumor volume quantification in 4 weeks growth glioma in Vegfafl/fl::LysMCre+or Vegfafl/fl::LysMCre- mice (n=7 mice per group). Statistical analysis: G. Mann-Whitney u-test. Error bars: G: median interquartile. Scale bars: 100µm.",
    "diseases": "glioma"
  },
  {
    "caption": "C. phospho-H2AX and Glut1 immunohistochemistry on 3 weeks growth glioma in wild-type mice treated as described in A.",
    "diseases": "glioma"
  },
  {
    "caption": "Anti-CSF1 antibody in combination with temozolomide chemotherapeutic agent induces a wider tumor cell death efficiency with a significant decrease of blood vessel caliber (D.) (50µm depth stack) (n=6 mice per group). Statistical analysis: D.E. one-way ANOVA followed by multiple comparisons Tukey's test. Error bars: meanSD. Scale bars: 300µm",
    "diseases": "tumor"
  },
  {
    "caption": "Action of the CP1-WT peptide in treatment of S. Typhimurium oral infection. F-J Histopathology  analyses with representative H&E-stained liver  sections at different magnifications are shown for S. Typhimurium infected liver  treated with various agents. K Mean pathological scoring from the tissue sections used in histopathology  analyses in panels F-J. Data information: For all the three infection models stated above, n = 2 biological replicates with 7 mice  per cohort were used. In panels K to assign histopathological  scores, data are collected from five mice  in each cohort, and the representative data for only one biological replicate are presented as mean ± SD values. Mann-Whitney rank sum test was used (ns P > 0.05, * P < 0.05, ** P < 0.01, *** P < 0.001). The notations, namely, N.T denote no treatment; Pep and Cip  denote CP1-WT and ciprofloxacin  treatments respectively. For histopathology  analyses in panels (F-J) except for uninfected and peptide-treated mice, pathology sections from infected or treated (DMSO  or ciprofloxacin) mice  showed aggregation of multiple  inflammatory cells  (INF) and edema  (E) in liver parenchyma, central vein congestion (C), distortion of hepatic portal vein  (HPV), hemorrhage  (H), necrosis  (N) and pyknotic nuclei  (arrows in panels H, Scale bar: 50µm in panels (F-J)",
    "diseases": "edema, hemorrhage, necrosis"
  },
  {
    "caption": "Bone tumor number per mouse at 5-6 months of age (n=23 wa/+, 15 wa/wa)",
    "diseases": "tumor"
  },
  {
    "caption": "Quantification of tumor size in tibiae at 5-6 months of age (n=23 wa/+, 15 wa/wa)",
    "diseases": "tumor"
  },
  {
    "caption": "Quantification of tumor number during treatment (n=6 Vehicle, 5 Erlotinib)",
    "diseases": "tumor"
  },
  {
    "caption": "Tumor size during treatment (n=6 Vehicle, 5 Erlotinib)",
    "diseases": "Tumor"
  },
  {
    "caption": "PET summation images (0-90 min) in horizontal (upper panel) and coronal view (lower panel) depicting [11C]Erlotinib distribution in one H2-c-fosLTR/Egfrwt mouse (M125). Anatomical structures are labelled with arrows (T, tumor; L, liver; H, heart; B, brain). Scale bars: 1cm Concentration-time curves of [11C]Erlotinib in bone tumors in right scapula of three H2-c-fosLTR/Egfrwt mice measured with PET. Broken line indicates threshold for in vitro effect of Erlotinib (1 µM)",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "Bone tumor number per mouse at 6-7 months of age (n=22 wt, 11 ∆Ob) Quantification of tumor size in tibiae (n=22 wt, 11 ∆Ob)",
    "diseases": "tumor"
  },
  {
    "caption": "µPET/CT analysis of 7-months-old H2-c-fosLTR/Egfrwt and H2-c-fosLTR/Egfr∆Ob littermates Standardized uptake values (SUV) of the µPET-tracer Na[18F]F in the pelvic osteosarcoma of 4- and 7-months-old H2-c-fosLTR/Egfrwt and H2-c-fosLTR/Egfr∆Ob mice. n=6 wt, 4 ∆Ob for 4 month time-point, n=6 wt, 3 ∆Ob for 7 month time-point",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "PCNA and cleaved Caspase 3 IHC staining and quantification shown as % positive cells (for PCNA) and as positive cells per mm² (for cleaved Caspase 3) in OS from H2-c-fosLTR/Egfrwt (n=6) and H2-c-fosLTR/Egfr∆Ob (n=5) mice. Scale bars: 100µm",
    "diseases": "OS"
  },
  {
    "caption": "Egfr, Ccnd1, c-fos and transgenic c-fos (c-fostg) mRNA expression levels in tumors of H2-c-fosLTR/Egfrwt and H2-c-fosLTR/Egfr∆Ob mice normalized to Tbp. n=17 wt, 14 ∆Ob (Egfr, Ccnd1), n=16 wt, 13 ∆Ob (c-fos), n=16 wt, 14 ∆Ob (c-fostg",
    "diseases": "tumors"
  },
  {
    "caption": "IHC staining and quantification showing pRSK2 (n=4), pCREB (n=7 wt, 6∆Ob) and c-Fos (n=5) positive cells (%) in OS from H2-c-fosLTR/Egfrwt and H2-c-fosLTR/Egfr∆Ob littermates. Scale bars: 100µm",
    "diseases": "OS"
  },
  {
    "caption": "Western Blot analysis of primary OS cells isolated from H2‑c‑fosLTR/Egfrwt and H2-c-fosLTR/Egfr∆Ob mice",
    "diseases": "OS"
  },
  {
    "caption": "c-fos and transgenic c-fos (c fostg) mRNA expression levels in primary H2-c-fosLTR OS cells after 4x in vitro passages, cultured under standard conditions (n=3 independent cell lines)",
    "diseases": "OS"
  },
  {
    "caption": "Western Blot analysis of H2-c-fosLTR/Egfrwt OS cells treated for 24h with Erlotinib",
    "diseases": "OS"
  },
  {
    "caption": "c-fos and c-fostg mRNA expression levels in H2-c-fosLTR/Egfrwt OS cells treated for 24h with Erlotinib (10µM) or DMSO as control (n=4 independent cell lines)",
    "diseases": "OS"
  },
  {
    "caption": "Western Blot analysis of starved H2-c-fosLTR/Egfrwt OS cells, pre-treated with DMSO (1:1000), Afatinib (5µM), GSK2233470 (10µM), Rapamycin (10nM) or U0126 (10µM) for 30 minutes and stimulated with EGF (50ng/ml) as indicated",
    "diseases": "OS"
  },
  {
    "caption": "Western Blot analysis of primary OS cells isolated from a p53f/f Rb1f/f Osx-Cre mouse after 24h Erlotinib treatment",
    "diseases": "OS"
  },
  {
    "caption": "c-fos mRNA expression levels in p53f/f Rb1f/f Osx-Cre OS cells treated for 24h with Erlotinib (10µM) (n=3)",
    "diseases": "OS"
  },
  {
    "caption": "Western Blot analysis of starved p53f/f Rb1f/f Osx-Cre OS cells, pre-treated with DMSO (1:1000) or Afatinib (5µM) for 30 minutes and stimulated with EGF (50ng/ml) as indicated",
    "diseases": "OS"
  },
  {
    "caption": "Bone tumor number per mouse at 5-6 months of age (n=22 wt, 13 ColAREG)",
    "diseases": "tumor"
  },
  {
    "caption": "Quantification of tumor size in tibiae at 5-6 months of age (n=22 wt, 13 ColAREG)",
    "diseases": "tumor"
  },
  {
    "caption": "c-fos mRNA expression levels in osteosarcomas of H2-c-fosLTR (n=11) and H2-c-fosLTR/ColAREG mice (n=14)",
    "diseases": "osteosarcomas"
  },
  {
    "caption": "Western Blot analysis of bone tumor protein lysates from H2-c-fosLTR and H2-c-fosLTR/ColAREG mice",
    "diseases": "tumor"
  },
  {
    "caption": "Representative images of OS biopsies stained with antibodies against EGFR and c‑Fos. Scale bars: 50µm",
    "diseases": "OS"
  },
  {
    "caption": "Kaplan-Meier survival curve comparing the survival of patients with EGFR and c-Fos double positive osteosarcomas against patients without co-expression of both proteins. (n=52)",
    "diseases": "osteosarcomas"
  },
  {
    "caption": "Western Blot analysis showing EGFR and c-Fos protein levels in human OS cell lines cultured under standard conditions",
    "diseases": "OS"
  },
  {
    "caption": "143b xenograft growth curve during therapeutic regime (n=8 vehicle, 6 Erlotinib; two independent experiments) 143b tumor weight at endpoint (n=8 Vehicle, 6 Erlotinib; two independent experiments)",
    "diseases": "tumor"
  },
  {
    "caption": "LM7 xenograft growth curve during therapeutic regime (n=7 Vehicle, 5 Erlotinib; two independent experiments) LM7 tumor weight at endpoint. n=7 vehicle, 5 Erlotinib, two independent experiment",
    "diseases": "tumor"
  },
  {
    "caption": "IHC analysis of PCNA and cleaved Caspase 3 in 143b-derived tumors (n=4). Scale bars: 50µm IHC analysis of pCREB and c-Fos in 143b-derived tumors. (n=5 for pCREB and n=4 for c-Fos analysis). Scale bars: 50µm",
    "diseases": "tumors"
  },
  {
    "caption": "D The mRNA expression level of METTL3 in sorafenib-sensitive (n=3) and sorafenib-resistant (n=3) human liver tumors. Data information: In all relevant panels, ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "diseases": "liver tumors"
  },
  {
    "caption": "E Expression of METTL3 was significantly down-regulated in advanced stage of liver cancer from TCGA.",
    "diseases": "liver cancer"
  },
  {
    "caption": "K Capillary-like structures in HUVECs treated with the tumor-conditioned medium (TCM) from control HCCs and METTL3-knockdown HCCs cultured under hypoxic conditions for 48 h. Quantification of the number of tubes with image J in K-1. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "diseases": "HCCs"
  },
  {
    "caption": "N The protein levels of VEGF-A in METTL3-knockdown HCCs. O The protein levels of PDGF-B in METTL3-knockdown HCCs. ",
    "diseases": "HCCs"
  },
  {
    "caption": "C Protein level of FOXO3 in METTL3-knockdown HCCs under hypoxia for 48h.",
    "diseases": "HCCs"
  },
  {
    "caption": "O Correlation analysis of the RNA expression levels of METTL3 and FOXO3 in liver tumor cohort (Kim-90) by Pearson.",
    "diseases": "liver tumor"
  },
  {
    "caption": "P Correlation analysis of the RNA expression levels of YTHDF1 and FOXO3 in liver tumor cohort (Kim-90) by Pearson.",
    "diseases": "liver tumor"
  },
  {
    "caption": "D Knockdown of METTL3 slightly increased liver tumor growth treated with sorafenib in orthotopic xenograft mouse model. Stable METTL3-knockdown Bel-7402 cells and control cells were injected into the liver of each NOD/SCID mouse. 3 weeks after injection, livers were separated for pathological analysis. Red circle indicates tumors in the livers.",
    "diseases": "NOD, SCID"
  },
  {
    "caption": "In vivo analyses of tumor (B) in mice that were subcutaneously implanted with tumor tissues from two human liver cancer patients and divided into four groups.",
    "diseases": "liver cancer"
  },
  {
    "caption": "In vivo analyses of tumor growth (C) in mice that were subcutaneously implanted with tumor tissues from two human liver cancer patients and divided into four groups.",
    "diseases": "liver cancer"
  },
  {
    "caption": "In vivo analyses of tumor weight (D) in mice that were subcutaneously implanted with tumor tissues from two human liver cancer patients and divided into four groups. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD.",
    "diseases": "liver cancer"
  },
  {
    "caption": "E H&E and immunohistochemical images of Ki67, LC3-B, VEGF-A in randomly selected PDX#1 and PDX#2 tumors.",
    "diseases": "tumors"
  },
  {
    "caption": "Quantification of Ki67 (F) expression in immunohistochemical images from PDX tumors by Image Pro Plus (IPP) analysis. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD.",
    "diseases": "tumors"
  },
  {
    "caption": "Quantification of LC3-B (G), and VEGF-A (H) expression in immunohistochemical images from PDX tumors by Image Pro Plus (IPP) analysis. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD.",
    "diseases": "tumors"
  },
  {
    "caption": "A-C. PTEN  mRNA levels in LCM normal ovarian  surface epithelium   versus high-grade serous ovarian cancer  (HGSOC) epithelium  or normal  ovarian  stroma   versus ovarian cancer-associated stroma. Datasets; (A) GSE40595, (B) GSE38666, (C) Epithelium  only, GSE14407. Sample size (n) and p-values, (Mann-Whitney) annotated, whiskers Min-Max, line at median.",
    "diseases": "HGSOC, high-grade serous ovarian cancer, ovarian cancer"
  },
  {
    "caption": "F. Overall survival (% patients, months) of OC patients. Highest quartile (Q4) versus combination of quartiles 1-3 (Q1+2+3), PTEN  mRNA (TCGA, OV). Median survival  (40 and 44 months), sample size (n) and p-value, Log-rank test (Mantel-Cox) annotated. G.  Overall survival  (% patients, months) of OC patients. Highest quartile (Q4) versus combination of quartiles 1-3 (Q1+2+3), PTEN  protein. Reverse Phase Protein Array Data, TCGA OV. Median survival  (46 and 57 months), sample size (n) and p-value, Log-rank test (Mantel-Cox).",
    "diseases": "OC, OV"
  },
  {
    "caption": "H. Differential abundance (x, Log Ratio between conditions; y, -Log10 q-values) of Reverse Phase Protein Array data (TCGA, OV) in patient  grouped by PTEN  mRNA, High (Q4) vs Low (Q1). Significant, blue (-Log10 q-values >1.3); AKT  signalling pathway, labelled. I. Differential abundance (x, Log Ratio between conditions; y, -Log10 q-values) of proteins in PTEN  High (Q4) vs PTEN  Low (Q1) protein samples. Reverse Phase Protein Array Data, TCGA OV. Significantly altered components in AKT  signalling pathway labelled (-Log10 q-value> 1.3).",
    "diseases": "OV"
  },
  {
    "caption": "ARF6  and AGAP1   mRNA levels in LCM normal ovarian surface epithelium versus HGSOC epithelium  or normal ovarian stroma   versus OC-associated stroma. Specific datasets, sample size (n) and p-values (Mann-Whitney) annotated, whiskers Min-Max, line at median.",
    "diseases": "HGSOC, OC"
  },
  {
    "caption": "K-O. Overall survival (% patients, months; TCGA OV  dataset), of patients  grouped by low (M1) versus high (M2) levels, based on a median split, of (K) ARF6  mRNA, (L) AGAP1  mRNA, (M) AGAP1  Exon 14 percentage spliced in ratio (PSI), (N) combination of ARF6  and AGAP1  mRNA, or (O) combination of ARF6  mRNA and AGAP1  Ex14 PSI. Median survival, sample size (n) and p-value, Log-rank test (Mantel-Cox) annotated.",
    "diseases": "OV"
  },
  {
    "caption": "I-K. Overall survival  (% patients, months; TCGA OV  dataset) of patients  grouped into combined expression based on median mRNA split. (I) Low (red line, M1) or high (blue line, M2) expression for all mRNA, control, remaining patients  (green line), (J), same as (I), but CYTH2  Ex9 PSI, rather than total CYTH2. (K), as for (I), but PTEN  protein levels split by quantiles (red and blue, Q1+Q2,Q3, low PTEN, green Q4, high PTEN). Median survival, sample size (n) and p-value, Log-rank test (Mantel-Cox) annotated.",
    "diseases": "OV"
  },
  {
    "caption": "Expression of TCHP, p62, IL-1β, IL-8, and IL-6 in ECs from vessels wall from patients with CAD (n=8 patients per group, unpaired t-test; TCHP **p <0.0001; p62 **p = 0.0007; IL-1β **p <0.0001; IL-8 **p <0.0001; and IL-6 **p <0.0001 vs. Healthy subject).",
    "diseases": "CAD"
  },
  {
    "caption": "(C) Wound healing assay: HeLa cells were incubated with nt or IRF2BP1 siRNA for 2 days, grown to 90% confluency and analysed for wound closure with or without addition of 100 ng/ml EGF. Data show means of the relative wound density +/- SEM from 4 biological replicates.",
    "diseases": "wound"
  },
  {
    "caption": "D UNC13D knock-out (KO) HeLa cells, UNC13D knock-out HeLa cells stably expressing FLAG-tagged wild-type UNC13D (UNC13D RE) and FHL3 mutation (FHL3 mut), and control cells were stimulated with cGAMP (100 nM) (or left unstimulated) for 30 min. Cell lysates were separated by native (top) or SDS (bottom) PAGE and analyzed by immunoblotting (IB) with anti-UNC13D, -Flag, -p-IRF3, -STING or -tubulin antibody.",
    "diseases": "FHL3"
  },
  {
    "caption": "A) TDP-43 ALS-linked amino acid substitutions K181E, A315T/E, A321G, Q331K, M337V, and A382T. Boxed in the C-terminal domain is the α-helical structure within the conserved region (a.a. 320-343). Droplets formed by TDP-43 wild-type (WT) and the different mutants (4 μM) observed by brightfield microscopy in the presence of no RNA control or A(GU)18 RNA (3.9 μM) at 250 mM NaCl. Mutations A321G and M337V, showing decreased liquidity of the condensates in the presence of A(GU)18, are boxed in red. Representative images for 3 biological replicates using 3 different protein preparations of WT and M337V, 2 preparations of A321G, Q331K, K181E and one preparation of A315T/E and A382T. Scale bars, 10 μm.",
    "diseases": "ALS"
  },
  {
    "caption": "(E)  mtATP content measured in control and human mitochondrial  disease fibroblasts  treated for 30min with increasing concentrations of EPI  as indicated. Analysis shows the mean intensity of mtATP probe in MTG  area normalized per % of correspondent untreated cells (n=3). In all cases, for each biological replicate, technical replicates were averaged. Data represent average ± SEM. Two-way ANOVA followed by Šídák's multiple comparisons test shows statistical differences depicted by p-value.",
    "diseases": "mitochondrial  disease"
  },
  {
    "caption": "D2.mdx mice, harboring the mdx   mutation in a DBA/2J genetic background (D2.mdx) were subjected to exercise induced gastrocnemius injury  by stimulating muscle contraction (eccentric injury). Levels of CV, ATPIF1  and maximal CV ATP  hydrolytic capacity were measured. (A) Representative western blot image (left) and quantification (right) showing CV  (ATP5A1) and CII  (SDHA) levels in gastrocnemius   homogenate in WT and mdx mice  after 24hrs of eccentric injury (inj). Vinculin  was used as loading control. Note that only in mdx mice eccentric injury  results in reduced CV  content. n=4. For each biological replicate, technical replicates were averaged. Data represent average ± SEM. Two-way ANOVA followed by Šídák's multiple comparisons test shows statistical differences depicted by p-value.",
    "diseases": "mdx, eccentric injury, injury"
  },
  {
    "caption": "D2.mdx mice, harboring the mdx   mutation in a DBA/2J genetic background (D2.mdx) were subjected to exercise induced gastrocnemius   injury by stimulating muscle contraction (eccentric injury). Levels of CV, ATPIF1  and maximal CV ATP  hydrolytic capacity were measured. (C) Analysis of levels of the cleaved OPA1  in gastrocnemius   homogenate in WT and mdx mice  24hrs after  eccentric injury. n=4. For each biological replicate, technical replicates were averaged. Data represent average ± SEM. Two-way ANOVA followed by Šídák's multiple comparisons test shows statistical differences depicted by p-value.",
    "diseases": "mdx, eccentric injury"
  },
  {
    "caption": "D2.mdx mice  were treated with EPI  orally twice daily, with doses ranging from 0.5 to 15 mg/kg/day. After 13 days of treatment, mice  were subjected to exercise induced gastrocnemius injury  by stimulating muscle  contraction and the effect of EPI  on muscle  force were measured. (A) Plantarflexor force quantification after  eccentric injury. n=8. For each biological replicate, technical replicates were averaged. Data represent average ± SEM. unpaired t-tests (A, shows statistical differences depicted by p-value.",
    "diseases": "mdx, eccentric injury, injury"
  },
  {
    "caption": "D2.mdx mice  were treated with EPI  orally After 13 days of treatment, mice  were subjected to exercise induced gastrocnemius injury by stimulating muscle  contraction and OPA1  cleavage were measured. (E) Levels of cleaved OPA1  in gastrocnemius   homogenate from mdx mice  subjected to the indicated combinations of injury   and EPI  treatment. n=8. For each biological replicate, technical replicates were averaged. Data represent average ± SEM. Two-way ANOVA followed by Šídák's multiple comparisons test",
    "diseases": "mdx, injury"
  },
  {
    "caption": "D2.mdx mice  were treated with EPI  (G) Detection and quantification of myofiber  membrane integrity or damage following injury  using Evans Blue dye (EBD) in gastrocnemius  muscle  from vehicle and EPI  treated mdx mice. Damaged fiber membranes allow dye entry that appears as red color. Yellow asterisks indicate damage fibers  (n≥4). unpaired t-tests G) shows statistical differences depicted by p-value.",
    "diseases": "mdx, injury"
  },
  {
    "caption": "A. Heatmap of IC50 values for cell viability. Human dermal fibroblasts (HDFB) controls and 4 MCC cell lines (PeTa, MKL-1, WaGa, MS-1) were treated with the 43 indicated small molecules targeting epigenetic modifiers. IC50 values are depicted as log10(IC50) in [mM]. n/a, IC50 values could not be calculated. n = 4 technical replicates.",
    "diseases": "MCC"
  },
  {
    "caption": "B. Dose-response curves of PeTa cells and control HDFB cells after 6 days of treatment with GSK-LSD1 or ORY-1001. Dose-response curves of 3 other MCC cell lines are displayed in Fig EV1A. n = 4 technical replicates. Data are represented as means ± SD.",
    "diseases": "MCC"
  },
  {
    "caption": "D. In vitro competition assay of the 3 MCC cell lines MKL-2, PeTa, and WaGa transduced with either shLSD1.1, shLSD1.2, shRenilla (negative control), or shRPS15 (positive control). Individual graphs are displayed in Fig EV1E.",
    "diseases": "MCC"
  },
  {
    "caption": "E. Dependency plot depicting the mean dependency of the 3 MCC cell lines PeTa, MKL-1, MKL-2 of the genes targeted by the compound library in Fig 1A. A score of 0 indicates that a gene is not essential; correspondingly -1 is comparable to the median of all pan-essential genes. Data obtained from DepMap; dependencies for the individual cell lines are displayed in Fig EV1F.",
    "diseases": "MCC"
  },
  {
    "caption": "F. Violin plot depicting the LSD1 dependency score in MCC compared to cancer types from 23 tissues, ordered according to mean dependency score. Red horizontal line depicts the median. Data obtained from DepMap RNAi screen. Blood, hematopoietic and lymphoid tissue; U. aerodigestive, upper aerodigestive tract; A. ganglia, autonomic ganglia; CNS, central nervous system.",
    "diseases": "MCC"
  },
  {
    "caption": "A. Photomicrographs of the MCC cell line PeTa after 6 days of 100 nM GSK-LSD1 or DMSO treatment. Scale bar, 100 μm.",
    "diseases": "MCC"
  },
  {
    "caption": "E. Violin plot depicting the HMG20B dependency in MCC compared to cancer types from 23 tissues, ordered according to mean. Red horizontal line depicts the median. Data obtained from DepMap RNAi screen. Blood, hematopoietic and lymphoid tissue; U. aerodigestive, upper aerodigestive tract; A. ganglia, autonomic ganglia; CNS, central nervous system.",
    "diseases": "MCC"
  },
  {
    "caption": "ELISA  assay of fecal IgA1  (A), IgA2  (B), total IgA  (C), levels from non-IBD  (n= 7), CD  (n=18), and UC  (n=12) patients' stool. Data were analyzed using Kruskall-Wallis multiple comparisons with Dunn's correction, when possible, or a Mann-Whitney test. P-values are as follows: (A)** : p= 0,0098; (B) *: p=0,0406; (C) Non-IBD   v. UC  *: p=0,0479, CD  vs. UC  *: p=0,0166;",
    "diseases": "CD, IBD, UC"
  },
  {
    "caption": "ELISA  assay of secretory component (D) levels from non-IBD  (n= 7), CD  (n=18), and UC  (n=12) patients' stool.",
    "diseases": "CD, IBD, UC"
  },
  {
    "caption": "In vitro assay of purified IgA1  (G) and IgA2  (H) reverse-transcytosis abilities on an inverted model of FAE   from Caco2  and Raji  cells co-culture. Data were analyzed using Kruskall-Wallis multiple comparisons with Dunn's correction, when possible, or a Mann-Whitney test. P-values are as follows: (G) *: p=0,0441; (H) *: p=0,423 ; For some patients, antibody purification did not yield a high enough concentration, so samples had to be excluded. N are thus as follows: IgA1: Non-IBD: n= 7; CD: n= 8; UC  : n=4; IgA2  : Non-IBD: n=7; CD  : n= 8; UC: n=5. All patient  samples (biological replicates) have been tested in technical duplicates meaning nx2.",
    "diseases": "CD, IBD, UC"
  },
  {
    "caption": "(I) ELISA  assay of IgA1-Dectin-1 binding, at a rate of one receptor per 10 IgA; (J) ELISA  assay of IgA2-Dectin-1 binding, at a rate of one receptor per 10 IgA. Data were analyzed using Kruskall-Wallis multiple comparisons with Dunn's correction, when possible, or a Mann-Whitney test. P-values are as follows: (J) Non-IBD  vs. UC  *: p=0,0199 , CD  vs. UC  *: p= 0,0243; For some patients, antibody purification did not yield a high enough concentration, so samples had to be excluded. N are thus as follows: IgA1: Non-IBD: n= 7; CD: n= 8; UC  : n=4; IgA2  : Non-IBD: n=7; CD  : n= 8; UC: n=5. All patient  samples (biological replicates) have been tested in technical duplicates meaning nx2.",
    "diseases": "CD, IBD, UC"
  },
  {
    "caption": "Percent of IgA1  (K, L) and IgA2  (M, N) reverse-transcytosis  for weak (K, M) and strong (L, N) Dectin-1 binding. Data were analyzed using Kruskall-Wallis multiple comparisons with Dunn's correction, when possible, or a Mann-Whitney test. P-values are as follows: (K) *: p=0,0221 ; (L) *: p=0,0486 . For some patients, antibody purification did not yield a high enough concentration, so samples had to be excluded. N are thus as follows: IgA1: Non-IBD: n= 7; CD: n= 8; UC  : n=4; IgA2  : Non-IBD: n=7; CD  : n= 8; UC: n=5. All patient  samples (biological replicates) have been tested in technical duplicates meaning nx2.",
    "diseases": "CD, IBD, UC"
  },
  {
    "caption": "Heatmaps displaying standardized log2-transformed signal intensities per glycan  for IgA1   (A) and IgA2   (B) in non-IBD, CD  and UC  groups, plotted by hierarchical clustering of Euclidean distance.",
    "diseases": "CD, IBD, UC"
  },
  {
    "caption": "Flow cytometry analysis of total IgA1-bound (A) and IgA2-bound (B) fecal microbiota. (C) Flow cytometry analysis of stool IgA1+ IgA2- bacteria  (grey dots), IgA1- IgA2+ bacteria  (black dots) and IgA1+ IgA2+ bacteria  (empty dots). (A-C) Data were analysed with a Kruskall-Wallis multiple comparison test. In (C) *: p= 0,0226. Non-IBD: n= 7, CD: n=18, and UC: n=12.",
    "diseases": "CD, IBD, UC"
  },
  {
    "caption": "(A-E) Optical density (600nm) variations during in vitro growth assay of Salmonella enterica Typhimurium (SL1344)  co-cultured with stool-purified IgA1  (A) or IgA2  (B) from non-IBD  (n=4), CD  (n=6) and UC  (n=3). Comparison between IgA1  and IgA2 co-culture in non-IBD  (C), CD  (D), and UC  (E). Two-way ANOVA with Holm-Sidak correction after D'Agostino-Pearson nomality test, p-values are as follows: (A) UC  curve: 2h - p=0,0024, 3h - p=0,003; CD  curve: 2h and 3h p<0,0001 (B) UC  curve: 4h - p=0,0186, 5h - p=0,0393, 6h - p=0,039, 8h - p<0,0001; CD  curve: 4h - p=0,0001, 5h - p=0,0028, 6h - p=0,0024, 8h - p<0,0001. (C) 3h - p=0,0422, 4h - p=0,0422, 6h - p=0,0012, 8h - p<0,0001.",
    "diseases": "CD, IBD, UC"
  },
  {
    "caption": "(F-I) Optical density (600nm) during in vitro growth assay of   Escherichia coli  (25922  strain from ATCC) co-cultured with stool-purified IgA1  (F) or IgA2  (G) from non-IBD  (n=2) and CD  (n=2). All patient  samples (biological replicates) have been tested in technical duplicates. Comparison between IgA1  and IgA2 co-culture in non-IBD  (H), and CD  (I). These IgA  samples were from the same patients  throughout each experiment. Two-way ANOVA with Holm-Sidak correction after D'Agostino-Pearson nomality test, p-values are as follows: (F) Grey curve: 4h - p=0,0004, 5h - p=0,0014; Black curve: 4h and 5h - p<0,0001. (G) De-glycosylated CD  vs. De-glycosylated non-IBD: 4h - p=0,0003, 5h - p<0,0001. (H) Native vs. de-glycosylated: 4h and 5h - p<0,0001; De-glycosylated IgA1  vs. De-glycosylated IgA2: 5h - p=0,0012. (H) Native vs. de-glycosylated: 4h - p=0,001 and 5h - p= 0,006; De-glycosylated IgA1  vs. De-glycosylated IgA2: 5h - p<0,0001.",
    "diseases": "CD, IBD"
  },
  {
    "caption": "(A) Combined FISH-IF staining  for each probe. (B) Total fluorescence detected per probe and per biopsy. Erec482   - *: p=0,00233; Ato291  - *: p=0,0268; Bac303  - *: p=0,0196. (C) Percent of co-occurred IgA2  and FISH-bound particles. Erec482  - *: p=0, 0073.Two-way ANOVA with Holm-Sidak correction after D'Agostino-Pearson nomality test. Non-IBD: n = 3; Active CD: n= 6; Inactive CD: n=4. All patient  samples (biological replicates) have been tested in technical duplicates.",
    "diseases": "CD, IBD"
  },
  {
    "caption": "IKKε expression was assessed semi-quantitatively using a 0-3 grade scale (\"0\": no staining; \"1\": weak; \"2\": moderate; \"3\": strong) on human breast cancer sections using immunohistochemistry. Representative images according to the IKKε staining grade are shown. Scale bar: 100 μm. Distribution table of IKKε expression in the cohort of 66 human breast carcinomas according to the staining grade.",
    "diseases": "breast cancer, breast carcinomas"
  },
  {
    "caption": "Correlation between IKBKE mRNA levels (log2 ratio) and immune signature (Yoshihara et al, 2013) in the METABRIC transcriptomic dataset from 1981 breast cancer patients (Curtis et al, 2012). Pearson's correlation rho coefficient and significance of difference from slope = 0 (p) are shown. IKBKE gene copy number and mRNA levels (log2 ratio) from the METABRIC transcriptomic dataset (see D) are plotted. Estimated +1 copy number values are shown by the dotted vertical line. No significant correlation by Pearson's correlation rho coefficient and significance of difference from slope = 0 (p) was detected.",
    "diseases": "breast cancer"
  },
  {
    "caption": "PSAT1 expression was assessed semi-quantitatively using a 0-3 grade scale ("0": no staining; "1": weak; "2": moderate; "3": strong) on human breast cancer sections using immunohistochemistry. Representative images according to the PSAT1 staining grade are shown. Scale bar: 50 ­μm.",
    "diseases": "breast cancer"
  },
  {
    "caption": "Correlation of mRNA levels of the SBP enzyme genes PSAT1 (E), PHGDH (F), PSPH (G) with the immune signature (Yoshihara et al, 2013) in the METABRIC transcriptomic dataset from 1981 breast cancer patient (Curtis et al, 2012).",
    "diseases": "breast cancer"
  },
  {
    "caption": "A-J)Ten per group female C57Bl/6 mice heterozygous for the PyMT-MMTV started high fat diet (HFD) when 6-7 weeks old (prior of mammary tumour development) together with control mice on normal diet (ND; n=10). Wild-type mice on HFD gain more weight compared to ND mice. *p < 0.05 by one-tailed students t-test.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "A-J)Ten per group female C57Bl/6 mice heterozygous for the PyMT-MMTV started high fat diet (HFD) when 6-7 weeks old (prior of mammary tumour development) together with control mice on normal diet (ND; n=10). Average adipocytes size (major diameter) in mammary fat pads is larger in HFD mice compared to ND mice based on the analysis of at least 100 adipocytes per mice on H&E stained sections. *p < 0.05 by two-tailed students t-test.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "A-J)Ten per group female C57Bl/6 mice heterozygous for the PyMT-MMTV started high fat diet (HFD) when 6-7 weeks old (prior of mammary tumour development) together with control mice on normal diet (ND; n=10). The number of F4/80+ macrophages in mammary fat pads is increased in HFD mice compared to ND mice. The average of F4/80+ macrophages in at least 10 fields of view per mouse is shown. *p < 0.05 by two-tailed students t-test.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "A-J)Ten per group female C57Bl/6 mice heterozygous for the PyMT-MMTV started high fat diet (HFD) when 6-7 weeks old (prior of mammary tumour development) together with control mice on normal diet (ND; n=10). Mice were administered amlexanox (17 mM) or vehicle control daily by oral gavage (Reilly et al, 2013). A control group (wild-type mice) was also included to confirm the efficacy of the diet and to control for possible unpredicted interactions of the MMTV-PyMT gene. PyMT-MMTV+/- mice on HFD gain more weight compared to ND mice. *p < 0.05 by one-tailed students t-test. Amlexanox does not affect weight gain either in mice on F) ND or G) HFD.",
    "diseases": "mammary tumour"
  },
  {
    "caption": "A-J)Ten per group female C57Bl/6 mice heterozygous for the PyMT-MMTV started high fat diet (HFD) when 6-7 weeks old (prior of mammary tumour development) together with control mice on normal diet (ND; n=10). Mice were administered amlexanox (17 mM) or vehicle control daily by oral gavage (Reilly et al, 2013). A control group (wild-type mice) was also included to confirm the efficacy of the diet and to control for possible unpredicted interactions of the MMTV-PyMT gene. Mammary tumours are developing earlier in PyMT-MMTV+/- mice on HFD compared to ND mice. Amlexanox does not affect tumour development in PyMT-MMTV+/- mice on ND, but delays tumour formation in J) HFD mice.",
    "diseases": "mammary tumour, Mammary tumours"
  },
  {
    "caption": "B Fresh primary   leukemic cells  from two pediatric patients, one with common B-ALL at relapse (left) and one with T-ALL at diagnosis (right), both with poor response to second line chemotherapy, were treated with LBW242  and VCR  at the indicated concentrations. Apoptosis  was measured after 24 h as described in A.",
    "diseases": "B-ALL, T-ALL"
  },
  {
    "caption": "A Expression  of XIAP  mRNA in samples obtained from BM  of healthy individuals (Ctrl, n=10) or patients  with AML  (n=517) or ALL  (n=306). Data are expressed as median, 25th and 75th percentile, whiskers indicate min/max; ** p<0.01; **** p<0.0001 by Games-Howell post-hoc test.",
    "diseases": "ALL, AML"
  },
  {
    "caption": "B Protein levels of XIAP  normalized to loading control in PDX ALL  samples from pediatric  and adult patients, analyzed by protein immunoassay (Simple Western) and depicted as mean (n=2, biological replicates); PBMC  = peripheral blood mononuclear cells",
    "diseases": "ALL"
  },
  {
    "caption": "Four-week-old AG6 mice  were infected with DENV (2,500 p.f.u.) by footpad  inoculation. Blood  samples were collected for DENV viremia  detection from Day 1 to Day 7. The  viral loads from AG6 mice  infected with DENV2-Asian I  (E), were measured by qRT-PCR and were normalized against mouse GAPDH. Data information: n = 6 biological replicates. data are presented as mean ± SEM. The data were analyzed statistically using the Mann-Whitney test The P value represents a comparison between the mutants and corresponding WT within genotypes. *p < 0.05, **p < 0.01, ***p < 0.001, n.s., not significant (p > 0.05).",
    "diseases": "viremia"
  },
  {
    "caption": "Four-week-old AG6 mice  were infected with DENV (2,500 p.f.u.) by footpad  inoculation. Blood  samples were collected for DENV viremia   detection from Day 1 to Day 7. The  viral loads from AG6 mice  infected with DENV2-Asian American (F), DENV3-I (G) were measured by  qRT-PCR  and were normalized against mouse GAPDH. Data information: , n = 6 biological replicates. In (F), n = 5 biological replicates. data are presented as mean ± SEM. The data were analyzed statistically using the Mann-Whitney test The P value represents a comparison between the mutants and corresponding WT within genotypes. *p < 0.05, **p < 0.01, ***p < 0.001, n.s., not significant (p > 0.05).",
    "diseases": "viremia"
  },
  {
    "caption": "Four-week-old AG6 mice  were infected with DENV (2,500 p.f.u.) by footpad  inoculation. Blood  samples were collected for DENV viremia   detection from Day 1 to Day 7. The viral loads from AG6 mice  infected with DENV4-I  (H) were measured by qRT-PCR  and were normalized against mouse GAPDH. Data information: n = 6 biological replicates. data are presented as mean ± SEM. The data were analyzed statistically using the Mann-Whitney test The P value represents a comparison between the mutants and corresponding WT within genotypes. *p < 0.05, **p < 0.01, ***p < 0.001, n.s., not significant (p > 0.05).",
    "diseases": "viremia"
  },
  {
    "caption": "Four-week-old AG6 mice  were infected with 2,500 p.f.u. of viruses by footpad  inoculation. The viremia   of infected AG6 mice  from Day 1 to Day 7 was measured using qRT-PCR. Data information: , n = 5 biological replicates. the data are presented as means ± SEM. The data were analyzed statistically using the Mann-Whitney test The P value represents a comparison between the mutants and the 16681 WT strain. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, n.s., not significant (p > 0.05).",
    "diseases": "viremia"
  },
  {
    "caption": "Mosquitoes  were thoracically  infected with 10 p.f.u. of viruses. Ten days postinfection, five infected mosquitoes  were allowed to bite one four-week-old AG6 mouse. From Day 1 to Day 8, infected mice  were subjected to daily biting by naive A. aegypti, and blood  samples were collected for DENV2 viremia   detection by  qRT-PCR (J). Data information: In (J), n = 4 biological replicates. In J), the data are presented as means ± SEM. The data were analyzed statistically using the Mann-Whitney test J). The P value represents a comparison between the mutants and the 16681 WT strain. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, n.s., not significant (p > 0.05).",
    "diseases": "viremia"
  },
  {
    "caption": "B Immunoblots for total and phosphorylated eEF2 of tumor engraftment from (A). (NS, Non-Specific signal.)C Bar graph shows relative phosphorylation intensities of eEF2 compared with total eEF2 determined by densitometry analysis. Mean ± s.e.m. are shown (n=4). P values were calculated using 2way ANOVA followed by Bonferroni posttest ; **P value ≤ 0.01.",
    "diseases": "tumor"
  },
  {
    "caption": "D. Representative images of the intestine  of Casp8WT and Casp8ECko mice, with mild and severe hemorrhages  at a late disease stage.",
    "diseases": "hemorrhages"
  },
  {
    "caption": "G-H. Quantification of intestinal pathology (enteropathy score, G; n= 8 WT, 7 ECko; two tailed unpaired Student's t-test) and hemorrhages  into the mucosa (H; n= 4 WT, 5  ECko; two tailed unpaired Student's t-test) at a late disease stage in Casp8WT and Casp8ECko mice. Data information: Data shown as mean ± SEM. **P <0.01, *** P <0.001, **** P <0.0001, ns: not significant.",
    "diseases": "hemorrhages"
  },
  {
    "caption": "J. Representative images of H&E staining  of the small intestine of  Casp8WT (j') and  Casp8ECko mice  with mild (j'') and more severely (j''') affected areas at a late disease stage (white arrows point to hemorrhages, asterisk points to   focal erosion of the epithelium). Scale bars: 100µm.",
    "diseases": "hemorrhages"
  },
  {
    "caption": "I. Representative pictures of CD45  and NIMPR14  staining  at late disease stages (n= 5 WT, 5 ECko), showing accumulation of CD45+ and  NIMPR14+ cells (black arrowheads) in Casp8ECko intestine  at sites of impaired epithelial  barrier integrity and tissue necrosis   (red asterisks). Scale bars: 100µm.",
    "diseases": "necrosis"
  },
  {
    "caption": "A. Representative pictures showing Peyer´s Patches in Casp8WT mice, and different severities of hemorrhage  formation in Casp8ECko mice  at an early disease stage. Scale bars: 1mm.",
    "diseases": "hemorrhage"
  },
  {
    "caption": "D-F. Representative images (D) and quantifications (E, F) of stainings   for CD31, Lyve1  and DAPI (nuclei) in  small intestinal wholemounts at an early disease stage (blue arrowheads point to defective lacteals, white arrowheads indicate edema) in Casp8ECko mice  (E; n= 7 WT, 6 ECko. F; n= 7 WT, 10 ECko; two tailed unpaired Student's t-test). Scale bars: 100µm. Data information: Data shown as mean ± SEM. * P <0.05, ** P <0.01, *** P <0.001, **** P <0.0001, ns: not significant.",
    "diseases": "edema"
  },
  {
    "caption": "A. Representative pictures of TUNEL staining together with CD31  and  Lyve-1  in  Peyer's Patches  of Casp8WT and Casp8ECko mice. TUNEL+ LECs, but not  BECs could already be seen in non-hemorrhagic Peyer's Patches  (a'), and further accumulated in hemorrhagic Peyer's Patches (a''). White dotted areas outline location of the lymphatic plexus. White arrowheads point to TUNEL+ LECs  (note that necroptotic LECs only weakly express Lyve-1). Scale bars: 50µm, insets: 10µm.",
    "diseases": "hemorrhagic"
  },
  {
    "caption": "mucosal hemorrhages   (G; n= 5 WT, 6  ECko, two tailed unpaired Student's t-test). Data information: Data shown as mean ± SEM. ns: not significant.",
    "diseases": "hemorrhages"
  },
  {
    "caption": "F-H. Representative images of H&E staining  (F), quantification of intestinal pathology  (G) and mucosal hemorrhages  (H) in  Casp8WT and Casp8ECko mice treated with antibiotics  compared to untreated Casp8ECko mice (G; n= 6 WT, 4 ECko+ antibiotics, 5  ECko; one-way ANOVA with tukey's multiple comparison, H; n= 6 WT, 4 ECko+ antibiotics, 4 ECko; one-way ANOVA with tukey's multiple comparison). Data information: Data shown as mean ± SEM. ** P <0.01, *** P <0.001, **** P <0.0001; ns: not significant. Scale bars: 100μm.",
    "diseases": "hemorrhages"
  },
  {
    "caption": "Western blot analysis of BRD7 and γH2AX protein levels in breast cancer cell lines: MCF7 parental or doxorubicin-resistant MCF7/ADR (ADR, 0.5μg/ml) and irradiation-resistant MCF7/IR (IR, 10Gy), MDA-MB-231 parental or doxorubicin-resistant MDA-MB-231/ADR (ADR, 0.5μg/ml) or cisplatin-resistant MDA-MB-231/DDP (1μg/ml), non-small lung cancer cell lines: A549 parental or cisplatin-resistant A549/DDP (1μg/ml).",
    "diseases": "breast cancer, non-small lung cancer"
  },
  {
    "caption": "(F) Single tube qPCR experiments showing the down-regulation of the synaptic genes NLGN3, SLC6A, TRIM9, SYT1, SYNGR1, and SNAP91 in ALSC9orf72 MN (Welch's t-test). n=3 independent cultures for each hiPSC line. Data information: *p<0.05; **p<0.01; ***p<0.001. Error bars represent SEM. Arrow indicates the structure displayed at higher magnification. Exact p-values are reported in Appendix Table S1.",
    "diseases": "ALS"
  },
  {
    "caption": "(G-H) Time course analysis of nuclear pCREBS133 levels and MN survival  in  ALSC9orf72 and Healthy cultures (two-way ANOVA). n=3 independent cultures for each hiPSC line (for each time point). Scale bar: 25 µm. Data information: *p<0.05; **p<0.01; ***p<0.001. Error bars represent SEM. Arrow indicates the structure displayed at higher magnification. Exact p-values are reported in Appendix Table S1.",
    "diseases": "ALS"
  },
  {
    "caption": "(A) Both K+  channel blockers exert a neuroprotective effect in ALSC9orf72 cultures by increasing the neurite length of mutant MN (one-way ANOVA followed by Dunnett's multiple comparison test). n=3 independent treatments with each hiPSC line. Scale bar: 50 µm Data information: *p<0.05; **p<0.01; ***p<0.001. Error bars represent SEM. Arrow indicates the structure displayed at higher magnification. Exact p-values are reported in Appendix Table S1.",
    "diseases": "ALS"
  },
  {
    "caption": "(C) Apamin  and XE991 decrease the size of aberrant aggresomes, confirming enhanced autophagy  degradation (one-way ANOVA followed by Dunnett's multiple comparison test). n=3 independent treatments with the ALSC9orf72 I line. Scale bar: 5 Data information: *p<0.05; **p<0.01; ***p<0.001. Error bars represent SEM. Arrow indicates the structure displayed at higher magnification. Exact p-values are reported in Appendix Table S1.",
    "diseases": "ALS"
  },
  {
    "caption": "(E) The load of aggregated SQSTM1/p62 is also reduced by the treatments in ALSC9orf72 cultures (one-way ANOVA followed by Dunnett's multiple comparison test). n=3 independent treatments for each cell line. Scale bar: 20 µm. Data information: *p<0.05; **p<0.01; ***p<0.001. Error bars represent SEM. Arrow indicates the structure displayed at higher magnification. Exact p-values are reported in Appendix Table S1.",
    "diseases": "ALS"
  },
  {
    "caption": "(F) Treatment with the   K+ channel blockers reduces the number of GGGGCC toxic RNA foci in ALSC9orf72 MN. n=3 independent treatments with each hiPSC line (one-way ANOVA followed by Dunnett's multiple comparison test). Scale bar: 5 µm. Dashed line represents the cell soma. Data information: *p<0.05; **p<0.01; ***p<0.001. Error bars represent SEM. Arrow indicates the structure displayed at higher magnification. Exact p-values are reported in Appendix Table S1. ",
    "diseases": "ALS"
  },
  {
    "caption": "(E)  Apamin and XE991 increase the  levels  of pCREBS133 in all the  ALSC9orf72 lines (one-way ANOVA followed by Dunnett's multiple comparison test). n=3 independent treatments with each hiPSC line. Scale bar: 10 µm. Data information: *p<0.05; **p<0.01. Error bars represent SEM. Exact p-values are reported in Appendix Table S1.",
    "diseases": "ALS"
  },
  {
    "caption": "(F) ALSC9orf72 MN showed an increased number  of  Homer1b/c+  synaptic contacts after treatment with the K+ channel blockers, which in contrast had no significant effect on Healthy MN. n=3 independent treatments with each hiPSC line (two-way ANOVA). Scale bar: 5 µm Data information: *p<0.05; **p<0.01. Error bars represent SEM. Exact p-values are reported in Appendix Table S1.",
    "diseases": "ALS"
  },
  {
    "caption": "PMO   was administered intravenously into 3-week old DKO mice  at 50 mg/kg/week for 3 weeks with dietary supplementation of glycine  for 3 consecutive days per week prior to PMO   introduction, followed by 50 mg/kg/month for 5 months with dietary supplementation of glycine  for 7 consecutive days per month prior to PMO   introduction, in combination with metformin  daily via drinking water. (C) Measurement of kyphosis  index of DKO mice  treated with PMO-GM (scale bar=5mm) and wild-type C57BL/6 mice  (scale bar=8mm)(n=3, *P<0.05; One way- ANOVA post hoc Student-Newman-Keuls test). Data information: Error bars indicate s.e.m. Data shown are representative of biological replicates as specified.",
    "diseases": "kyphosis"
  },
  {
    "caption": "PMO   was administered intravenously into 3-week old DKO mice  at 50 mg/kg/week for 3 weeks with dietary supplementation of glycine  for 3 consecutive days per week prior to PMO   introduction, followed by 50 mg/kg/month for 5 months with dietary supplementation of glycine  for 7 consecutive days per month prior to PMO   introduction, in combination with metformin  daily via drinking water. (G) Masson trichrome's staining for cardiac fibrosis   and quantitative analysis of fibrotic  areas in treated DKO mouse hearts  (scale bar=800 μm). Boxed areas are magnified (n=3, **P<0.001;One way-ANOVA post hoc Student-Newman-Keuls test). Data information: Error bars indicate s.e.m. Data shown are representative of biological replicates as specified.",
    "diseases": "fibrosis, fibrotic"
  },
  {
    "caption": " (B-D) Behaviors of MPTP-PD mice assessed by pole (B), beam (C) at 3-6 weeks post-MPTP injection, and locomotor activity (total distance & average speed, D) tests at 6 weeks post-MPTP injection. n= 20 GSK-650394-treated MPTP-PD mice, 14 vehicle-treated MPTP-PD mice, and 8 MPTP-untreated non-PD mice. Data are represented as mean ± SEM. Significantly different at p=0.0012#, 0.0001*, 3.09E-08##, 8.21E-08** in graph B and p=0.0009#, 0.0035*, 1.03E-06##, 0.00003** in graph C and p=0.0001*, 0.0284**, 0.0101# (total distance), 1.49E-08*, 0.0005**, 0.0001# (average speed) in graph D. ",
    "diseases": "PD"
  },
  {
    "caption": " Therapeutic effects of GSK-650394 in SNCA-PD model mice. Behaviors (L-N) of the SNCA-PD mice were assessed at 6-12 weeks post- SNCA injection Significantly different at p=0.008#, 0.021*, 0.00001##, 0.0009** in graph L and p=0.00002#, 0.0344*, 0.0005##, 0.0067** in graph M and p=0.0057#, 0.0345* (total distance), 0.0001#, 0.0375##, 0.0338* (average speed) in graph N. ",
    "diseases": "PD"
  },
  {
    "caption": " Therapeutic effects of GSK-650394 in SNCA-PD model mice. mDA neuron degeneration in the SN of the SNCA-PD mice were assessed at 12 weeks post- SNCA injection after sacrifice SNCA pathology assessed by p129-α-syn immunoreactivity in TH+ mDA neurons in the SN. n= 5 GSK-650394-treated SNCA-PD mice, 5 vehicle-treated SNCA-PD mice, and 8 SNCA-untreated non-PD mice. ",
    "diseases": "PD"
  },
  {
    "caption": " Therapeutic effects of GSK-650394 in SNCA-PD model mice. mDA neuron degeneration in the SN (O-U) of the SNCA-PD mice were assessed 12 weeks post- SNCA injection after sacrifice SNCA pathology assessed by p129-α-syn immunoreactivity in TH+ mDA neurons in the SN. n= 5 GSK-650394-treated SNCA-PD mice, 5 vehicle-treated SNCA-PD mice, and 8 SNCA-untreated non-PD mice. ",
    "diseases": "PD"
  },
  {
    "caption": " SGK1 knockdown effect in vivo by treatment with shSgk1-AAV9. Total SGK1 mRNA levels were estimated in the midbrain SN of the PD mice injected with shSgk1(shControl as control) AAV9 using real time-PCR (D).",
    "diseases": "PD"
  },
  {
    "caption": " Data are represented as mean ± SEM. n=4 mice in each group. Significantly different at p=0.0004# in graph D and p=0.049*, 0.007**, 0.002*** in graph E. (F-H) Behavior of the PD mice assessed by pole (F), beam (G) at 6-12 weeks, and locomotor activity (H) tests at 12 weeks post- SNCA injection. Significantly different at p=0.0003#, 0.0428*, 7.46E-06##, 0.0012** in graph F and p=8.04E-08#, 0.004*, 1.62E-09##, 3.3E-06** in graph G and p=0.0002#, 0.0194* (total distance), 9.54E-06#, 0.0047* (average speed) in graph H. ",
    "diseases": "PD"
  },
  {
    "caption": " Histologic assessment of p129-SNCA immunoreactivity ( I,J), TH+ mDA neuron counts (I,K), neurite lengths (L), and cell body sizes (M) in the SN Significantly different at p=0.0001* in graph J, p=2.35E-25#, 1.09E-16##, 4.36E-08* in graph K and p=1.5E-40#, 1.08E-24##, 2.32E-07* in graph L and p=9.07E-20#, 2.59E-16##, 0.05* in graph M and p=4.62E-22#, 5.11E-12##, 3.49E-06* (TH), n= 7 sh-SGK1-AAV9-treated PD mice, 7 sh-cont-AAV9-treated PD mice, and 8 SNCA-untreated mice. Data are represented as mean ± SEM. One-way ANOVA. Scale bar, 100µm. ",
    "diseases": "PD"
  },
  {
    "caption": " Histologic assessment of TH+ and DA transporter (DAT) fiber intensities in the striatum n= 7 sh-SGK1-AAV9-treated PD mice, 7 sh-cont-AAV9-treated PD mice, and 8 SNCA-untreated mice. Data are represented as mean ± SEM. One-way ANOVA. Scale bar, 100µm. ",
    "diseases": "PD"
  },
  {
    "caption": " A-C, Quantitative and morphometric analyses of microglia in the SN area of SNCA-PD mice. Shown in A are representative views of Iba1+ microglia neighboring TH+ mDA neurons in the SNs of PD mice treated with GSK-650394 and vehicle. Insets, enlarged views for the boxed areas. Data are represented as mean ± SEM. n=3 mice per group. Significantly different at p=1.49E-11* in graph B and p=0.000003* in graph C. ",
    "diseases": "PD"
  },
  {
    "caption": " F and G, mRNA expression of NLRP3-inflammasome components and pro-inflammatory cytokines in MPTP (F) and SNCA (G) PD mice injected with the SGK1 inhibitor or vehicle (control). Each bar represents the mean ± SEM of 3 PCR values from each animal, n=3 mice per group. Significantly different at p=0.0372*, 0.0173**, 0.0003*** in graph F and p=0.002#, 0.0113##, 0.0053###, 0.0001#### in graph G. ",
    "diseases": "PD"
  },
  {
    "caption": " H-J, ASC expression in the SNs and SN microglia of SNCA-PD mice. n=5 mice per group. Data are represented as mean ± SEM. Significantly different at p=1.91E-09* in graph I and p=0.0079* in graph J. ",
    "diseases": "PD"
  },
  {
    "caption": " K and L, β-gal-stained cell senescence in SNCA-PD mouse SN. Data are represented as mean ± SEM. n=5 mice per group. Significantly different at p=0.0001* ",
    "diseases": "PD"
  },
  {
    "caption": "Representative images of LINC00115 expression in clinical GBM tumors and adjacent tissue using RNAscope analysis. Images are representative of two independent experiments. Scale bars: 50 μm.",
    "diseases": "GBM"
  },
  {
    "caption": "Kaplan-Meier analysis of patients with high versus low LINC00115-expressing GBM tumors from B. Median survival (in months): low, 13.9; high, 8.1. Black bars, censored data. Data information: , *, p < 0.05, by log-rank test.",
    "diseases": "GBM"
  },
  {
    "caption": "Expression levels of LINC00115 are higher in LGG (low grade gliomas) versus normal brain tissues and GBM versus LGG. Expression data of LINC00115 were downloaded from the REMBRANDT dataset. Data are presented as mean ± SEM. **, p < 0.01, ***, p < 0.001, by two-tailed t test.",
    "diseases": "LGG, low grade gliomas, GBM"
  },
  {
    "caption": "E to G. Kaplan-Meier analysis of patients with high versus low LINC00115-expressing Grade III and GBM tumors from the REMBRANDT (E) or the TCGA (G) 26[], and GBM from GSE83300 50[] (F) datasets. Median survival (in months) in E: low, 20.2; high, 15.9; in F: low, 19.4; high, 13.0; in G: low, 33.2; high, 25.4. Black bars, censored data. Data information: , *, p < 0.05, by log-rank test.",
    "diseases": "Grade III, GBM"
  },
  {
    "caption": "A and B. Correlation of expression between LINC00115 and ZEB1 from TCGA GBM RNA-Seq dataset (A) and REMBRANDT GBM array dataset (B). ***, p < 0.001, by two-tailed t-test.",
    "diseases": "GBM"
  },
  {
    "caption": "J and K. Correlation of expression between LINC00115 and ZEB1 from TCGA GBM RNA-Seq dataset (J) and REMBRANDT GBM array dataset (K). **, p < 0.01, by two-tailed t-test.",
    "diseases": "GBM"
  },
  {
    "caption": "Representative images of RNAscope for LINC00115 and IHC for ZEB1 and ZNF596 expression in two GBM specimens, Sample #1 (positive) and Sample #2 (negative). Scale bar, 50 μm. Images are representative of two independent experiments.",
    "diseases": "GBM"
  },
  {
    "caption": "Correlation of detected expression between ZEB1 or ZNF596, and LINC00115 from a separate cohort of a total of 75 paraffin-embedded clinical GBM samples. Statistical analysis was performed by Chi-square test.",
    "diseases": "GBM"
  },
  {
    "caption": "Kaplan-Meier survival analysis of patients with GBM tumors expressing high or low levels of LINC00115 with high or low levels of ZEB1 or ZNF596 expression. Median survival (in months): LINC00115hi/ZEB1hi, 5.4; LINC00115lo/ZEB1lo, 27.9; LINC00115hi/ZNF596hi, 4.2; LINC00115lo/ZNF596lo, 23.8. Statistical analysis was performed by log-rank test.",
    "diseases": "GBM"
  },
  {
    "caption": "(H) Assessment of DLL4 & PDGF-BB-treated WT and genetically corrected DMD hiMP migration through a layer of endothelial cells. Representative images showing the lower side of the trans-well membrane on which treated and untreated hiMPs (stained with the transient dye CFDA, in green) are simultaneously seeded on HUVECs for 8 hours. Bar graphs quantifying the average number of CFDA-positive cells/ mm2, that have migrated through the endothelial layer in each considered condition. (experimental replicates = 3). A minimum of 10 (1.5 mm2) fields per condition was quantified (error bars: SEM). (I) Bar graph showing fold-change in trans-endothelial migration (error bars: SEM). Statistical significance based on one-way ANOVA with Bonferroni's multiple comparison.",
    "diseases": "DMD"
  },
  {
    "caption": "D, CSF-1 protein (pg/mg total protein) measured by ELISA in the sera of naïve mice, mice bearing mock-irradiated tumours, and mice bearing irradiated tumours analysed at time points as indicated (n=4/group). Data are presented as mean ± SEM and analysed by Kruskal-Wallis test with Dunn's multiple comparison.",
    "diseases": "tumours"
  },
  {
    "caption": "E-F, MC38 (E)and KPC (F) tumours were irradiated with 10Gy. Average tumour volume (red line) is shown with mean TAM infiltrate (blue line) for each time point. For TAM quantification, tumours were disaggregated and CD11b+/F480+ TAMs identified by flow cytometry. Data are presented as mean ± SEM for TAMs and SEM for tumour volume (n=6).",
    "diseases": "tumour, tumours"
  },
  {
    "caption": "G-H, Immunofluorescent staining of MC38 (G) and KPC (H) tumour sections; blue=DAPI, green = CD68 (TAMs).",
    "diseases": "tumour"
  },
  {
    "caption": "I-J, Flow cytometric analysis of immune cell populations within MC38 (I) and KPC (J) tumours 5 days following 10Gy IR compared to mock-irradiated tumours. Macrophages (CD11b+ F480+), neutrophils (CD11b+ Ly6G+), myeloid-derived suppressor cells (CD11b+ Gr1+), CD8 T cells (CD45+ CD3+ CD8+), CD4 T cells (CD45+CD3+CD4+, Natural Killer cells (CD45+ NK1.1+) were identified. Pie charts represent the proportion of CD45+ leukocytes out of the total cells.",
    "diseases": "tumours"
  },
  {
    "caption": "A, Quantification of iNOS expression on gated macrophages (CD11b+ F480+) from MC38 and KPC tumours, with representative histograms. Data are presented as mean ± SEM and analysed by Mann-Witney (n=6 mice/group).",
    "diseases": "tumours"
  },
  {
    "caption": "B, Quantification of CD206 expression on macrophages (CD11b+ F480+) from MC38 and KPC tumours, with representative histograms. Data are presented as mean ± SEM and analysed by Mann-Witney (n=6 mice/group).",
    "diseases": "tumours"
  },
  {
    "caption": "C, Quantification of the percentage of TAMs (CD11b+ F480+) in MC38 control tumours compared with irradiated tumours (n=6 mice/group).",
    "diseases": "tumours"
  },
  {
    "caption": "D-E Quantification of iNOShi (D) macrophages as a percentage of total cells in MC38 tumours (n=6).",
    "diseases": "tumours"
  },
  {
    "caption": "D-E, Quantification of CD206hi (E) macrophages as a percentage of total cells in MC38 tumours (n=6).",
    "diseases": "tumours"
  },
  {
    "caption": "F, The total number of iNOShi TAMs were divided by CD206hi TAMs to derive a M1/M2 ratio in MC38 and KPC tumours receiving mock or 10Gy irradiation. Data are presented as mean ± SEM and analysed by Mann-Witney (n=6 mice/group).",
    "diseases": "tumours"
  },
  {
    "caption": "G-H, TAMs (CD11b+F480+) were isolated by FACS. Expression of selected immune stimulatory and immunosuppressive genes in TAMs was determined by RT-qPCR (n=3). Data are presented as mean fold change ± SEM compared to TAMs from mock-irradiated tumours (n=3). Statistical significance was determined by Mann-Witney.",
    "diseases": "tumours"
  },
  {
    "caption": "I-J, Assessment of TAM suppression of T cells was assayed by evaluation of inhibition of T cell proliferation. TAMs were isolated by magnetic bead separation using F480 microbeads and co-cultured at a 1:1 ratio with CFSE labelled CD8+ T cells. CFSE dilution was analysed by flow cytometry to measure proliferation. Percentages of CFSElo T cells were analysed by Kruskal-Wallis with Dunn's multiple comparisons test. Representative histograms are shown (right panel). Experiments were repeated twice for each tumour cell line (n=3 mice/group) *P <0.05 **P <0.01 ***P <0.001.",
    "diseases": "tumour"
  },
  {
    "caption": "B-C Flow cytometric analysis of TAMs (CD11b+ F480+) in MC38 (B) and KPC (C) tumours receiving indicated treatments. Tumours were harvested 5 days following IR and disaggregated for analysis by flow cytometry. The left panels in B and C show the data derived from the flow cytometry with representative plots shown in the right panels. Data are presented as mean SEM and analysed by one-way ANOVA with Tukey post-hoc adjustment (n=6 mice/group, 3 independent experiments).",
    "diseases": "tumours, Tumours"
  },
  {
    "caption": "D-E, Tumour growth kinetics of MC38 (D) and KPC (E) tumours receiving the indicated treatments. Data are presented as mean tumour volume ± SEM and analysed by one-way ANOVA with Tukey post-hoc adjustment.",
    "diseases": "Tumour, tumours"
  },
  {
    "caption": "F-G, shows flow cytometric analysis of CD206hi (F) TAMs in MC38 and KPC tumours 5 days following IR. Data are presented as mean ± SEM and analysed by one-way ANOVA with Tukey post-hoc adjustment (n=6 mice/group).",
    "diseases": "tumours"
  },
  {
    "caption": "F-G, shows flow cytometric analysis of iNOShi (G) TAMs in MC38 and KPC tumours 5 days following IR. Data are presented as mean ± SEM and analysed by one-way ANOVA with Tukey post-hoc adjustment (n=6 mice/group).",
    "diseases": "tumours"
  },
  {
    "caption": "H-I, CD11b+ F480+ TAMs were isolated from MC38 (H) and KPC (I) tumours 5 days following irradiation (+/-aCSF) and expression of selected immune stimulatory and immunosuppressive genes was analysed by RT-qPCR (n=3). Data are presented as mean ± SEM (10Gy vs 10Gy + aCSF n=6 mice/group). Statistical significance was determined by Mann-Witney. *P <0.05 **P <0.01 ***P <0.001.",
    "diseases": "tumours"
  },
  {
    "caption": "A-B MC38 (A) and KPC (B) tumours were harvested 5 days following 10Gy IR ± aCSF as indicated. The left panels show the percentage of CD45+ CD3+ CD8+ T cells in these tumours after the indicated treatments. Representative flow cytometry plots from the irradiated groups are shown in the right panels. Tumours that did not receive irradiation were harvested when tumours reached 500mm3. Data are presented as mean SEM and analysed by one-way ANOVA with Tukey post-hoc adjustment (A) and Kruskal-Wallis test with Dunn's multiple comparison (B) (n=6 mice/group, 3 independent experiments).",
    "diseases": "tumours, Tumours"
  },
  {
    "caption": "C, Flow cytometric analysis of Ki67 expression in the CD8+ T cells in MC38 tumours from A. Data are presented as mean SEM and analysed by Kruskal-Wallis test with Dunn's multiple comparison (n=6/group).",
    "diseases": "tumours"
  },
  {
    "caption": "D, Flow cytometric analysis of PD-1 expression on CD8+ T cells from MC38 in tumours as in A. Data are presented as mean SEM and analysed by Kruskal-Wallis test with Dunn's multiple comparison (n=6/group).",
    "diseases": "tumours"
  },
  {
    "caption": "E-F Flow cytometric analysis of IFN-γ expression in CD8+ T cells isolated from MC38 tumours in A. Data presented as mean SEM and analysed by Kruskal-Wallis test with Dunn's multiple comparison (n=6 mice/group, 3 independent experiments).",
    "diseases": "tumours"
  },
  {
    "caption": "E-F, Flow cytometric analysis of Granzyme B expression in CD8+ T cells isolated from MC38 tumours in A. Data presented as mean SEM and analysed by Kruskal-Wallis test with Dunn's multiple comparison (n=6 mice/group, 3 independent experiments).",
    "diseases": "tumours"
  },
  {
    "caption": "G-H, Immunofluorescent staining of MC38 (G) and KPC (H) tumour sections, blue=DAPI, green = CD8.",
    "diseases": "tumour"
  },
  {
    "caption": "I-J, Tumour growth in CD8 depleted C57BL6 wild-type mice bearing MC38 (I) and KPC (J) tumours receiving treatment as indicated (n=6 mice/group).",
    "diseases": "tumours"
  },
  {
    "caption": "K, Flow cytometric quantification of intra-tumoural CD8 T cells following anti-CD8 treatment. Data presented as mean SEM and analysed by unpaired t-test (n=5 mice/group).",
    "diseases": "tumoural"
  },
  {
    "caption": "L-M, Tumour growth in athymic nude mice bearing MC38 (I) and KPC (J) tumours receiving treatments as indicated (n=6 mice/group). Data are presented as mean tumour volume ± SEM and analysed by one-way ANOVA with Tukey post-hoc adjustment. *P <0.05 **P <0.01 ***P <0.001.",
    "diseases": "tumour, tumours"
  },
  {
    "caption": "A-B, CD8+ T cells were isolated from the spleens of MC38 tumour bearing mice. The tumours were radiated with 10Gy and cells were harvested 5 days later. Quantification (A) and representative images (B) of MC38 tumour cell specific tumour-derived CD8 T cell responses detected by IFN-γ ELISpot. The tumour specific CD8+ T cell response was evaluated after T cell incubation with naïve or irradiated MC38 cells for 24 hours. Data presented as mean SEM and analysed by Kruskal-Wallis test with Dunn's multiple comparison (n=3 mice/group).",
    "diseases": "tumour, tumours"
  },
  {
    "caption": "C-D, Flow cytometric detection of major histocompatibility complex I (MHCI) expressed on MC38 (C) and KPC (D) tumour cells 48 hours following exposure to 10Gy IR. The left graph shows the overall data, with representative flow cytometry plots on the right. Data presented as mean ± SEM and analysed by Mann-Witney (n=3/group).",
    "diseases": "tumour"
  },
  {
    "caption": "E-F, Flow cytometric quantification of major histocompatibility complex I (MHCI) expression in vivo. Gated MC38 (E) and KPC (F) tumour cells were analysed 48 hours following exposure to 10Gy IR. Data presented as mean ± SEM and analysed by unpaired t-test (n=3/group).",
    "diseases": "tumour"
  },
  {
    "caption": "G-H, Flow cytometric quantification of dendritic cells (CD11b+ CD11c+ MHCII+) in MC38 (G) and KPC (H) tumours receiving treatment as indicated and as in E-F. Data presented as mean SEM and analysed by unpaired t-test (n=5 mice/group).",
    "diseases": "tumours"
  },
  {
    "caption": "J-K, Tumour growth in mice bearing two MC38 tumours receiving 10Gy IR to the primary lesion (J) ± systemic aCSF therapy (K). The differences in tumour volume 9 days following IR was analysed by unpaired t-test (n=5 mice/group). L-M, Tumour growth in mice bearing two KPC tumours receiving 10Gy IR to the primary lesion (J) ± systemic aCSF therapy (M). The difference in mean tumour volume 10 days following IR was analysed by unpaired t-test (n=8 mice/group).",
    "diseases": "Tumour, tumours"
  },
  {
    "caption": "N-O, Flow cytometric analysis of macrophages (N) and CD8 T cells (O) in primary and secondary MC38 tumours. Data presented as mean SEM and analysed by Kruskal-Wallis test with Dunn's multiple comparison (n=5 mice/group). *P <0.05 **P <0.01 ***P <0.001.",
    "diseases": "tumours"
  },
  {
    "caption": "PD-L1 expression on MC38 and KPC cells 48 hours following 10Gy irradiation in tissue culture (A,B) or 10 Gy irradiation of tumours (C,D) analysed by flow cytometry. Data presented as mean SEM and analysed by Mann-Witney (n=3, A,B). Data presented as mean SEM and analysed by unpaired t-test (n=5 mice/group, C,D).",
    "diseases": "tumours"
  },
  {
    "caption": "E-F, Flow cytometric analysis of PD-L1 (E) and PD-L2 (F) on TAMs in MC38 tumours receiving treatment as indicated above. Data presented as mean SEM and analysed by Mann-Witney (n=5 mice/group)",
    "diseases": "tumours"
  },
  {
    "caption": "G-H, Tumour growth in mice bearing MC38 (G) and KPC (H) tumours receiving the indicated treatments. Data presented for individual mice. Pie charts indicate the number of regressions observed.",
    "diseases": "tumours"
  },
  {
    "caption": "I-J, Tumour growth in mice bearing KPC tumours mice receiving 10Gy IR + systemic aPD-L1 to the primary lesion (I) ± systemic aPD-L1 + aCSF therapy (J). The difference in tumour volume 8 (I) or 10 (J) days following IR was analysed by unpaired t-test (n=8 mice/group). *P <0.05 **P <0.01 ***P <0.001.",
    "diseases": "tumour, tumours"
  },
  {
    "caption": "(C) H&E staining of representative colon tumor sections from AhR WT and KO mice, scale bar 200 μm.",
    "diseases": "colon tumor"
  },
  {
    "caption": "(E, F) (E) Adenoma and (F) adenocarcinoma multiplicity in AhR WT and KO mice.",
    "diseases": "adenocarcinoma, Adenoma"
  },
  {
    "caption": "(H) FoxM1 mRNA expression in normal (uninvolved) crypts adjacent to colonic tumors. Images were quantified and expressed as FoxM1 positive area per crypt (n=5 mice per group). Scale 200 µm. Dashed line indicates median and dotted lines indicate 25th/75th quartiles.",
    "diseases": "colonic tumors"
  },
  {
    "caption": "(I) FoxM1 mRNA expression in colon tumors. FoxM1 mRNA ISH area was averaged per tumor on each slide (n=5 mice per group). Scale 200 µm. Dashed line indicates median and dotted lines indicate 25th/75th quartiles.",
    "diseases": "colon tumors"
  },
  {
    "caption": "A The mRNA value of AKT2 was analyzed in the GEO Profiles from the  liver explant of  Hepatitis B virus (HBV)-associated acute liver failure (ALF) patients (GDS4387/225471_s_at), and from bronchial epithelial cells  with pandemic and seasonal H1N1 influenza virus infections in vitro (GDS4855/203808_at). normal, n=10; HBV, n=17; control, n=3; influenza A, n=9. Data information: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 and ns, not significant (P > 0.05); using unpaired t-test Error bars mean ± SD",
    "diseases": "acute liver failure, ALF"
  },
  {
    "caption": "J. qRT-PCR analysis of the relative mRNA  expression levels of AKT2 (left panel) and IFNA  (middle panel) or  IFNβ1 (right panel) in CD14  positive monocytes isolated from SLE patients  (n=9) or healthy donors (n=9). Data information: *P < 0.05, **P < 0.01 and ****P < 0.0001; using unpaired t-test or correlation analyses Data are pooled from different individuals Error bars mean ± SD).",
    "diseases": "SLE"
  },
  {
    "caption": "K Immunofluorescence of  IRF3 (Red), AKT2  (Green),  DAPI (Blue, nucleus) in CD14+ cells from SLE patients followed by analysis of the cells about mean amount of AKT2 in this cell as well as mean amount of IRF3 in the same nucleus  with Image J software. Cells (n=39) were collected 3 patients. Bar, 2 μm. Data information: *P < 0.05, **P < 0.01 and ****P < 0.0001; using correlation analyses Data are pooled from different individuals or representative of three independent experiments",
    "diseases": "SLE"
  },
  {
    "caption": "The percentage of myofibroblast-like cells in total endometrial cells between controls and patients with IUA (n=3 samples for each group). Data are presented as mean ± SEM. Two-tailed Student's t-test. *, P<0.05; **, P<0.01; ***, P<0.001.",
    "diseases": "IUA"
  },
  {
    "caption": "Masson trichrome staining   and immunostaining  of α-SMA  and Collagen 1 in endometrium  of controls and patients  with IUA  (n=5 samples for each group). Scale bars: 100μm. Data are presented as mean ± SEM. Two-tailed Student's t-test. *, P<0.05; **, P<0.01; ***, P<0.001.",
    "diseases": "IUA"
  },
  {
    "caption": "Flow cytometric  analysis of the proportion of CD14+ cells, CD301+ macrophages, CD80+ macrophages  and CD163+ macrophages  in the endometrium  of normal controls and patients  with IUA. Macro, macrophage  (n=20 samples for each group). Data are presented as mean ± SEM. Two-tailed Student's t-test. *, P<0.05; **, P<0.01; ***, P<0.001. NS, not significant.",
    "diseases": "IUA"
  },
  {
    "caption": "Representative immunostaining  images of CD301  and CD68  from samples of normal controls and patients  with IUA  (n=5 samples for each group). Representative immunostaining  images of CD301  and α-SMA  from samples of normal controls and patients  with IUA  (n=5 samples for each group). Scale bar: 100μm. Data are presented as mean ± SEM. Two-tailed Student's t-test. *, P<0.05; **, P<0.01; ***, P<0.001. NS, not significant.",
    "diseases": "IUA"
  },
  {
    "caption": "Localization  of GAS6  and CD301  in endometrium  of normal controls and patients  with IUA  examined by immunofluorescence  (n=5 samples for each group). Localization  of AXL  and α-SMA in endometrium  of normal controls and patients  with IUA  examined by immunofluorescence  (n=5 samples for each group). Scale bar: 100μm. Data are presented as mean ± SEM. Two-tailed Student's t-test. *, P<0.05; **, P<0.01; ***, P<0.001. NS, not significant.",
    "diseases": "IUA"
  },
  {
    "caption": "Representative immunostaining  images of p-p65  in endometrium  of normal controls and patients  with IUA  (n=5 samples for each group). Scale bar: 100μm. Data are presented as mean ± SEM. (D) Two-tailed Student's t-test. *, P<0.05; **, P<0.01; ***, P<0.001.",
    "diseases": "IUA"
  },
  {
    "caption": "Representative images of Masson trichrome staining  and immunostaining  for  Collagen 1 between endometrium  of Sham and IUA mice  (n=5 mice  for each group). Scale bar: 100μm. Data are presented as mean ± SEM. Two-tailed Student's t-test. *, P<0.05; **, P<0.01; ***, P<0.001.",
    "diseases": "IUA"
  },
  {
    "caption": "Flow cytometric analysis of the proportions of CD11b+F4/80+ cells (pan-macrophages) and CD301b+ macrophages   in the uterus  of Sham and IUA mice  (n=5 mice  for each group). Macro, macrophage. Data are presented as mean ± SEM. Two-tailed Student's t-test. *, P<0.05; **, P<0.01; ***, P<0.001.",
    "diseases": "IUA"
  },
  {
    "caption": "Representative images of immunostaining  for GAS6  (red) and CD301b  (green) in the endometrium  of Sham and IUA mice  (n=5 mice  for each group). Scale bar: 100μm. Data are presented as mean ± SEM. Two-tailed Student's t-test. *, P<0.05; **, P<0.01; ***, P<0.001.",
    "diseases": "IUA"
  },
  {
    "caption": "Representative images of immunostaining  for AXL  in the endometrium  of Sham and IUA mice  (n=5 mice  for each group). Scale bar: 100μm. Data are presented as mean ± SEM. (F) Mann-Whitney U test. *, P<0.05; **, P<0.01; ***, P<0.001.",
    "diseases": "IUA"
  },
  {
    "caption": "qRT-PCR analysis of Acta2  and Col1a1  expression in the uterus  of Sham, IUA  and IUA+DT mice  (n=5 mice  for each group). Data are presented as mean ± SEM. One-way ANOVA with Tukey's post hoc analysis. *, P<0.05; **, P<0.01; ***, P<0.001.",
    "diseases": "IUA"
  },
  {
    "caption": "Representative images of immunostaining  for AXL, Collagen 1  and p-p65  and Masson trichrome staining in the endometria  of Sham, IUA  and IUA+DT mice  (n=5 mice  for each group). Scale bar: 100μm. Data are presented as mean ± SEM. One-way ANOVA with Tukey's post hoc analysis. *, P<0.05; **, P<0.01; ***, P<0.001.",
    "diseases": "IUA"
  },
  {
    "caption": "qRT-PCR analysis of Acta2  and Col1a1  expression in the uterus  of IUA+PBS  and IUA+BEM mice  (n=5 mice  for each group). Data are presented as mean ± SEM. (B, Two-tailed Student's t-test.",
    "diseases": "IUA"
  },
  {
    "caption": "Representative images of immunostaining  for AXL, Collagen 1, p-p65   and Masson trichrome staining  in the endometrium  of IUA+PBS  group and IUA+BEM  group (n=5 mice  for each group). Scale bar, 100μm. Data are presented as mean ± SEM. C for AXL  and Collagen 1 Two-tailed Student's t-test. (C for p-p65) Mann-Whitney U test. *, P<0.05; **, P<0.01; ***, P<0.001.",
    "diseases": "IUA"
  },
  {
    "caption": "mice.a. Gross pathology and histopathology of lungs from WT-HB-01 mice (3 dpi), ACE2-Mock mice (3 dpi) and ACE2-HB-01 mice (3 dpi and 5 dpi). Postmortem examinations showed focal dark red lesions (red arrow) throughout the dorsal of the right middle lobe of the lung at 3dpi. The lesions progressed into multifocally scattered-dark reddish purple areas and palpable nodules (red arrow) throughout the right lobe of the lung at 5 dpi. Histopathological observation indicated that moderate interstitial pneumonia with thickened alveolar septa (black arrows) and infiltration of lymphocytes (red arrows). The swollen and degenerative alveolar macrophages (green arrows) are scattered within the alveolar cavities at 3dpi and 5 dpi.",
    "diseases": "interstitial pneumonia"
  },
  {
    "caption": "P Detection of FST expression, p-ERK1/2, and p-CREB in mononuclear cells from normal peripheral blood stem cell (PBSC) and FLT3/ITD AML patients (diagnostic samples with leukemia blasts > 80%) by Western blotting. ^: non-specific staining of p-ATF1 protein due to the conserved motif.",
    "diseases": "AML, leukemia"
  },
  {
    "caption": "A FST expression in different AML cell lines was detected by Western Blotting.",
    "diseases": "AML"
  },
  {
    "caption": "Overall survival analysis of patients from TCGA-AML based on the differential expression of IL2RA",
    "diseases": "AML"
  },
  {
    "caption": "Overall survival analysis of patients from TCGA-AML based on the differential expression of CCL5.",
    "diseases": "AML"
  },
  {
    "caption": "Serum FST level was significantly increased in primary AML-derived xenografted mouse at week 6 post injection. Human leukemic engraftments were confirmed by flow cytometry of human CD45 and mouse CD45.1 cells in recipient mouse BM aspiration (J).",
    "diseases": "AML, leukemic"
  },
  {
    "caption": "Serum FST level was significantly increased in primary AML-derived xenografted mouse at week 6 post injection. Serum FST from pre-injection and post-engraftment mouse were measured (K, one mouse for each primary AML sample). Data information: data were presented as scatter dot plot. n.s: not significant, *P<0.05, **P<0.01 (Student's t-test).",
    "diseases": "AML"
  },
  {
    "caption": "L Correlation between serum FST levels and leukemia blast percentage from FLT3/ITD-mutated AML at diagnosis. Correlation analysis (Pearson correlation coefficient) was performed by Graphpad Prism 6.",
    "diseases": "AML, leukemia"
  },
  {
    "caption": "Serum FST decreased in CR and increased after relapse in 4 AML patients receiving Quizartinib monotherapy. Data information: data were presented as mean ± SEM. *P<0.05, **P<0.01 (Student's t-test).",
    "diseases": "AML"
  },
  {
    "caption": "C, D. Oxidative stress  biochemical markers (lipid peroxidation, ROS production, GSH levels) (C) and p-ERK expression (D) in PD and control (CNTR) fibroblasts (n=6). E, F. Oxidative stress  biochemical markers (lipid  peroxidation, ROS production, GSH levels) (E) and p-ERK expression (F) in  PD  and control (CNTR) myoblasts (n=4). In all instances indicators of stress were increased in PD, compared to the respective control samples. Data information: In each experiment at least biological triplicates were analyzed for each cell line or tissue sample; each assay was performed at least in duplicate. Data are presented as mean ± SD. Student's t-test was applied. Statistically significant comparison p-values are indicated. Fi ",
    "diseases": "PD"
  },
  {
    "caption": "A, B. Western Blot  analysis of the autophagy marker LC3 (A) and quantitative analyses (B) in untreated control fibroblasts  (CNTR) and in 2 PD fibroblasts cell lines (PD1, PD2). PD cells were untreated (NT) or subjected to different treatments to modulate autophagy (starvation, STAR; rapamycin, RAPA; MK6-83; bafilomycin, BAFI). Data information: Starvation of cells was performed for 4 hours; treatments with 20 µM rapamycin or 30 µM MK6-83 or 100nM bafilomycin was performed for 24 hours. Data presented as mean ± SD. P values were calculated with ANOVA Šídák's multiple comparisons test. Statistically significant comparison p-values are indicated.",
    "diseases": "PD"
  },
  {
    "caption": "C. ROS production, lipid peroxidation, and GSH levels in PD fibroblasts (n=3). CNTR (white bars), CNTR after treatment (dark grey bars), PD samples (black bars) and PD after treatment (light grey bars). Physiological or pharmacological enhancement of autophagy resulted in correction of oxidative stress in PD  cells, while bafilomycin treatment further increased stress in CNTR and  PD  cells. Data information: Starvation of cells was performed for 4 hours; treatments with 20 µM rapamycin  or 30 µM MK6-83 or 100nM bafilomycin was performed for 24 hours. Data presented as mean ± SD. P values were calculated with ANOVA Šídák's multiple comparisons test. Statistically significant comparison p-values are indicated.",
    "diseases": "PD"
  },
  {
    "caption": "A, B, C. Correlations between the levels of single stress indicators and correction of GAA activity  by rhGAA in 6 different PD fibroblasts. ROS production and lipid peroxidation inversely correlate with the  GAA levels attained in cells after incubation with rhGAA for 4 hours. The analysis of correlation was calculated, and the coefficient of Pearson is indicated. D ",
    "diseases": "PD"
  },
  {
    "caption": "A.  Cell viability in control and  PD fibroblasts (3 different cell lines) measured by MTT assay in the presence of increased concentrations (0-100 µM) of either sodium arsenite  (ARS) or  tert-butyl-peroxide (TBP) at different time points. Data presented as a mean ± SD. B. ROS  production,  lipid  peroxidation, and GSH levels in fibroblasts (3 different cell lines) after 6 hours of treatment with 100 µM ARS and or 10 µM TBP. Both oxidative agents induced increases in oxidative stress in control (CNTR) and in  PD cells. Data presented as a mean ± SD. Significance was calculated by one-way ANOVA followed by Šídák's multiple comparisons test. C Data information: statistically significant p-values are indicated.",
    "diseases": "PD"
  },
  {
    "caption": "A. Effect of antioxidants on ROS production,  lipid  peroxidation, and GSH levels in PD fibroblasts (3 different cell lines for each treatment, each cell line assayed at least in ducplicate). Cells were incubated for 24 hours with: idebenone (IDE) 0.5 µM; edaravone (EDA) 50 µM; N-acetylcysteine (NAC) 0.5 mM;  resveratrol  (RESV) 30 µM. Mean of control (CNTR) values are taken as equal to 100. The results are shown as mean ± SD. Data information: To calculate statistical significance one-way ANOVA was applied for all experiments followed by Dunnett's test. Statistically significant p-values are indicated.",
    "diseases": "PD"
  },
  {
    "caption": "E. Confocal immunofluorescence analysis of GAA and LAMP2; representative fibroblast  cell lines (PD1). Confocal 63x images; Scale bar 50 µm; Brightness +20%. F. Percent of GAA/LAMP2 colocalization  in PD1. The results are expressed as means ± SD of 5 images for each condition. G. Percent of GAA/LAMP2 colocalization; mean of the analyses performed in 3 PD fibroblast cell lines. For each PD patient, 5 images for each condition were quantified. The results are expressed as means ± SD of 5 images for each condition. Data information: To calculate statistical significance one-way ANOVA was applied for all experiments followed by Dunnett's test. Statistically significant p-values are indicated. ",
    "diseases": "PD"
  },
  {
    "caption": "D. Mean of results obtained in control (two cell lines in duplicate) and PD fibroblast (3 different cell lines, each cell line tested in duplicate in three different experiments). For each cell line, the amount of  M6PR positive cells was normalized, taking that observed in not-treated fibroblasts as 1. Data presented as mean ± SD. Data information: For statistical analysis a one-way ANOVA followed by Šídák's post hoc test was applied. ",
    "diseases": "PD"
  },
  {
    "caption": "(A) Top panel: Scheme illustrating the tetracycline inducible Flp-In 293 system that controls the expression of HA-IKKε or HA-GFP. Bottom panel: Representative western blot showing induced expression of HA-IKKε in Flp-In 293 cells treated with doxycycline (Dox, 50 ng/ml) for 16 hours compared to endogenous IKKε in T47D, MDA-MB-231 and MDA-MB-468 breast cancer cell lines.",
    "diseases": "breast cancer"
  },
  {
    "caption": "Representative western blot showing level of IKKε in IKBKE (IKKε)-silenced (A) T47D breast cancer cell lines.",
    "diseases": "breast cancer"
  },
  {
    "caption": "Representative western blot showing level of IKKε in IKBKE (IKKε)-silenced (B) MDA-MB-468 breast cancer cell lines.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(C) Basal mitochondrial oxygen consumption rate (OCR) in a panel of IKBKE (IKKε)-silenced breast cancer cell lines, measured using Seahorse XF96e or XF24 analysis.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(A) qRT-PCR analysis of PHGDH, PSAT1 and PSPH mRNA levels in a panel of IKBKE (IKKε)-silenced breast cancer cell lines. Data are expressed as fold changes, relative to levels in a non-silenced control of each cell line and normalised to β-Actin (n≥3 biological replicates).",
    "diseases": "breast cancer"
  },
  {
    "caption": "(B) Representative western blot showing levels of IKKε and the SBP enzymes in IKBKE (IKKε)-silenced ZR-75-1, T47D, MDA-MB-468 and MCF7 breast cancer cell lines.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(C-E) Levels of the SBP enzymes in a panel of IKBKE (IKKε)-silenced breast cancer cell lines. (C) PHGDH, (D) PSAT1 and (E) PSPH levels in indicated cell lines normalised to Vinculin. Densitometry analysis quantified single sample density as a percentage of total blot density per cell line prior to vinculin normalisation (n≥3 biological replicates).",
    "diseases": "breast cancer"
  },
  {
    "caption": "(F) qRT-PCR analysis of PHGDH, PSAT1 and PSPH mRNA levels in ATF4-silenced ZR-75-1, T47D and MDA-MB-468 breast cancer cell lines. Data are expressed as fold changes, relative to levels in non-silenced control cells and normalised to β-Actin (n=3 biological replicates).",
    "diseases": "breast cancer"
  },
  {
    "caption": "(G) Representative western blot showing levels of PHGDH, PSAT1 and PSPH in ATF4-silenced ZR-75-1, MDA-MB-468, MDA-MB-231, T47D and HCC1143 breast cancer cell lines.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(A) Correlation of change in OCR (ΔOCR) in a panel of IKBKE (IKKε)-silenced breast cancer cell lines (from Fig. 3C) and the change in cell confluency (Δconfluency) upon treatment of the panel of cell lines with NCT502 (from Fig. EV5A).",
    "diseases": "breast cancer"
  },
  {
    "caption": "(B) Correlation of ΔOCR in a panel of IKBKE (IKKε)-silenced breast cancer cell lines (from Fig. 3C) and the Δconfluency upon treatment of the panel of cell lines with 6-Diazo-5-oxo-L-norleucine (DON) (from Fig. EV5C).",
    "diseases": "breast cancer"
  },
  {
    "caption": "A) Correlations of mean fold-changes of the proteins changing PD-dependently in the Columbia and LCC cohorts. Only proteins quantified in both cohorts are shown (n=330). Proteins overlapping between the two cohorts are labeled with their name.",
    "diseases": "PD"
  },
  {
    "caption": "B) Mean fold-changes for each of the 33 proteins that were LRRK2-dependently regulated in both cohorts using a pairwise t-test comparing the four subgroups (HC, NMC, iPD and LRRK2 PD).",
    "diseases": "iPD, PD"
  },
  {
    "caption": "A) Pearson correlation scores and associated p-values [-log10] of all protein intensities with the MoCA total score. Either all PD patients (left), iPD patients (middle) or LRRK2 PD patients (right) were included in the analysis. Significantly correlated proteins with an FDR of 5% after Benjamini-Hochberg correction are highlighted in red.",
    "diseases": "iPD, PD"
  },
  {
    "caption": "B) Pearson correlation scores and associated p-values [-log10] of all protein intensities with the UPDRS-III score. Either all PD patients (left), iPD patients (middle) or LRRK2 PD patients (right) were included. Significantly correlated proteins with an FDR of 5% after Benjamini-Hochberg correction are highlighted in red.",
    "diseases": "iPD, PD"
  },
  {
    "caption": "(H) Western blot analysis of  ATXN1  after a treatment with RSK3 inhibitor (BI-D1870) on SCA1 patient iPSC-derived neurons (n = 3). Data information: Mean ± SD, *P<0.05, **P<0.01, ***P<0.001 ****P<0.0001, one-way ANOVA.",
    "diseases": "SCA1"
  },
  {
    "caption": "(I) Western blot  analysis of total and phospho-S776 ATXN1 after a co-treatment with MSK1 (SB-747651A) and RSK3 inhibitor (BI-D1870) on SCA1 patient iPSC-derived neurons (n = 3). Data information: Mean ± SD, *P<0.05, **P<0.01, ***P<0.001 ****P<0.0001, one-way ANOVA.",
    "diseases": "SCA1"
  },
  {
    "caption": "(B) Improvement of motor performance by the knockdown of Sk6II  in  Drosophila SCA1 model expressing ATXN1(82Q) in the central nervous system. Mean ± SEM, *P < 0.05, Linear mixed-effect model ANOVA, n = 10/genotype, four times of measurements.",
    "diseases": "SCA1"
  },
  {
    "caption": "(C) A representative  image of a  mouse brain  4 weeks after AAV injection of shRsk3 into 12 weeks old SCA1 mice (Atxn1154Q/2Q) cerebellum. Scale bar: 2 mm.",
    "diseases": "SCA1"
  },
  {
    "caption": "(D)  Western blot analysis of wild-type (2Q) and mutant Atxn1 (154Q) in the cerebella of 16 weeks old SCA1 mice  dissected 4 weeks after the stereotaxic injection of AAV9 harboring shControl (n = 3), shRsk3 (n = 3), or shAtxn1 (n = 2). Mean ± SD, *P<0.05, ***P<0.001 ****P<0.0001, one-way ANOVA.",
    "diseases": "SCA1"
  },
  {
    "caption": "(D) Western blot  analysis of total and active form of Rsk3 and  Msk1 in the  cerebella and brainstem of 12 weeks old WT and SCA1 mice (n = 4). Relative Rsk3 and Msk1 levels were represented into log2 scale. The  protein levels of the two kinases are significantly different between the two brain regions. Mean ± SD, *P<0.05, **P<0.01, ****P <0.0001, two-way ANOVA. Data information: BS: brainstem, CBM: cerebellum",
    "diseases": "SCA1"
  },
  {
    "caption": "(E)  Western blot  analysis of  ATXN1, RSK3, pRSK3, MSK1, and pMSK1 in the postmortem cerebella, pons, and medulla oblongata of human controls and  SCA1 patients  (n = 3 per genotype). Total protein was used for normalization, and  protein levels  are represented relative to cerebellar protein levels in control group. C: Cerebellum, P: Pons, M: medulla oblongata. Values from P and M are combined and presented in BS. Mean ± SEM, *P<0.05, **P<0.01, two-way ANOVA, n = 3 (CBM) and 6 (BS). Data information: BS: brainstem, CBM: cerebellum",
    "diseases": "SCA1"
  },
  {
    "caption": "(A) Western blot analysis of total and pS776 wild-type and mutant Atxn1  in the brainstem of 8 weeks old SCA1 mice with heterozygous knockout of either one or both kinases. Mean ± SD, *P<0.05, **P<0.01, ****P<0.0001, one-way ANOVA, n = 7, 6, 4, 7 following the order of genotypes in the western blot, respectively.",
    "diseases": "SCA1"
  },
  {
    "caption": "(G) Kaplan-Meier survival  graphs of SCA1 mice with heterozygous knockout of either one or both kinases. The data of Msk1+/-, Rsk3+/-, and Msk1+/-; Rsk3+/- mice overlap those of wild-type mice. *P<0.05, Gehan-Breslow-Wilcoxon test, n = 15, 15, 12, 13, 22, 11, 20, 19 following the order of genotypes in the legend on top of the figure, respectively.",
    "diseases": "SCA1"
  },
  {
    "caption": "(A) Western blot  analysis of total and pS776 wild-type and mutant Atxn1 in the cerebella of 8 weeks old SCA1 mice with heterozygous knockout of either one or both kinases. Mean ± SD, **P<0.01, ***P<0.001, one-way ANOVA, n = 7, 6, 4, 7 following the order of genotypes in the western blot, respectively.",
    "diseases": "SCA1"
  },
  {
    "caption": "(B) Rotarod motor performance test  result of 11-12 weeks old  SCA1 mice with heterozygous knockout of either one or both kinases. Mean ± SEM, *P<0.05, two-way ANOVA, n = 18, 12, 13, 11, 19, 13, 15, 13 following the order of genotypes in the legend on top of the figure, respectively.",
    "diseases": "SCA1"
  },
  {
    "caption": "Cortical malformations observed in six novel BBSOAS patients Patient (P)1 shows abnormally elongated occipital convolutions (arrowheads in A), whereas abnormal gyrification of supramarginal and angular gyri is present in five out of six individuals (P2-P6 B', C' and C'' highlight the abnormally convoluted regions boxed in B and C.",
    "diseases": "BBSOAS"
  },
  {
    "caption": "Cortical malformations observed in six novel BBSOAS patients Patient (P)1 shows abnormal gyrification of supramarginal and angular gyri is present in five out of six individuals (P2-P6;",
    "diseases": "BBSOAS"
  },
  {
    "caption": "A, Teratoma volume (mm3) 20-25 days after subcutaneous injection of wild-type iPSCs or miiPSCs expressing GFP. Data are represented as mean ± s.e.m. (n=8 tumors per genotype; 292,8 ± 66,67 versus 1216 ±140,1; difference between means: 923,5 ± 155,2; 95% confidence interval: 1256 to -590,7); ***P<0.001 (Student´s t-test).",
    "diseases": "Teratoma"
  },
  {
    "caption": "B, Incidence and representative images of specific highly differentiated tissues in teratomas. The number of tumors included in the analysis is indicated in the panel. ***P<0.001 (Student´s t-test). Scale bars, 50 μm.",
    "diseases": "teratomas"
  },
  {
    "caption": "D) Proline biosynthesis protein levels in breast cancer subtypes (Log2 ratios of light vs. SILAC standard). The upper and lower limits of the box show values from the first to the third quartile, with the horizontal line indicating the median. The whiskers extend 1.5 times the interquartile range from the edges of the box. Outlier values were plotted outside the whiskers. Significance was determined using paired Student's t-test and p values were corrected using permutation based FDR . *p < 0.05 and *** p < 0.001.",
    "diseases": "breast cancer"
  },
  {
    "caption": "E) High abundance of PYCR1 in the cancer tissue was validated by immunohistochemistry on matched tissue specimens from patients in this study (n=3); Scale bar: 200 μm.",
    "diseases": "cancer"
  },
  {
    "caption": "G) Kaplan Meier survival curve for PYCR1 levels in residual cancer in the current proteomics data. Cox univariate p value, risk table and hazard ratio with 95% CI indicated.",
    "diseases": "cancer"
  },
  {
    "caption": "(A) Chromatin features mapped here displayed differences between CLL (patient CLL1) and an NBC donor (H7) as shown for the TCF4 locus, which encodes for a transcription factor from the E protein family. Based on the increased H3K4me1, H3K27ac and ATAC signal, two predicted enhancer loci were marked that became active in CLL. Note that the y-axis for RNA-seq is scaled differently for CLL (8000) and NBCs (100) to visualize that the TCF4 gene was not completely silenced but lowly expressed also in NBCs as evident also from the H3K36me3 mark. Light grey depicts active chromatin region and dark grey the confined enhancer locus coinciding with an open chromatin region.",
    "diseases": "CLL"
  },
  {
    "caption": "(D) Distribution of ~24,400 annotated differentially accessible regions (ATAC-seq) in NBC and CLL samples according to the chromatin state annotation. In total 7,605 annotated regions gained an ATAC-seq signal in CLL, while it was lost at 16,790 loci.",
    "diseases": "CLL"
  },
  {
    "caption": "(A) Left, example of a large PMD on chromosome 2 derived from a consensus of CLL samples (n=11). Right, genome-wide quantification of PMDs across CLL samples (n=11) and NBCs (n=6). Red, methylated DNA; blue, unmethylated DNA.",
    "diseases": "CLL"
  },
  {
    "caption": "(D) Upper panel: Average signal of histone modification marks normalized to H3 and standard deviation in 5-kb windows around the ±50 kb flanking regions of PMD boundaries. Normalized fold changes were calculated by dividing to the average signal flanking outside the PMD boundaries. Blue box, within PMDs; thin line, outside PMDs, nor. - normalized. Lower panel: Distribution of bound CTCF sites in CLL cells as determined by ChIP-seq (blue line) around the ±50 kb flanking regions of PMD boundaries in 5 kb windows. The height of the curves gives the sum of the next nearest CTCF peak at the given distance to the PMD boundary.",
    "diseases": "CLL"
  },
  {
    "caption": "(J) Heatmap displaying changes in H3K27ac read occupancy in CLL upon panobinostat treatment for 24 h. A general gain of H3K27ac in enhancers upon panobinostat treatment was observed.",
    "diseases": "CLL"
  },
  {
    "caption": "(E) Expression of the genes nearest to target enhancers with constitutively bound ("stable") CTCF vs. enhancers that lost CTCF in CLL. Loss of CTCF binding correlated with reduced gene expression.",
    "diseases": "CLL"
  },
  {
    "caption": "(A) Representative immunohistochemistry  (IHC) images of SMIM26  protein level in multiple types of tumoral tissues (T) and adjacent non-tumorous tissues (N), showing that SMIM26  has significantly decreased expression  in kidney cancer only. Mann-Whitney test, **P < 0.01; n = 5; Bar, SEM; Scale bar,100 μm.",
    "diseases": "kidney cancer"
  },
  {
    "caption": "(B) Representative IHC  images of SMIM26  protein levels in 368 ccRCC  tissues (T) and 281 non-tumorous renal  tissues (N). Mann-Whitney test, *** P < 0.001; Scale bar, 200 μm.",
    "diseases": "ccRCC"
  },
  {
    "caption": "(C) A  Kaplan-Meier survival  analysis of ccRCC patients  with high or low expression levels of SMIM26  (P < 0.05, log-rank test).",
    "diseases": "ccRCC"
  },
  {
    "caption": "(E, The protein level (E) of SMIM26  were detected in five ccRCC  cell lines by western blotting",
    "diseases": "ccRCC"
  },
  {
    "caption": "(G) The protein level of SMIM26  (up) and RNA level of LINC00493  (down) in ccRCC  tissues (T) and their adjacent non-tumoral tissues (N) were detected by IHC staining  and RNA in situ hybridization  (ISH) staining. The right scatter plot shows no significant correlation between SMIM26 protein expression  and LINC00493  RNA expression in ccRCC  tissues (green dots, P=0.94) and adjacent non-tumorous renal  tissues (purple dots, P=0.53). n = 72. Scale bar, 200 μm.",
    "diseases": "ccRCC"
  },
  {
    "caption": "(D) The expression of PABPC4  and SMIM26  in ccRCC  tissues compared with adjacent non-tumor tissues was detected by western blotting.",
    "diseases": "ccRCC"
  },
  {
    "caption": "(D) Transwell assays were used to test the migration and invasion abilities of both ccRCC cells transfected with indicated constructs. Unpaired two-tailed Student's t-test, *P < 0.05, **P < 0.01, ***P < 0.001. n.s, nonsignificant. Data are shown as mean ± SEM of three biological replicates. Scale bar, 600 μm.",
    "diseases": "ccRCC"
  },
  {
    "caption": "(J) NOD-SCID mice  were transplanted with ACHN-luci  cells with or without overexpression of SMIM26 via tail vein injection, respectively. Bioluminescent was visualized 5 weeks later by using an IVIS 200 Imaging System. Data are shown as mean ± SD of 5 mice  per group. Unpaired two-tailed Student's t-test, ****P < 0.0001. n.s, nonsignificant.",
    "diseases": "SCID"
  },
  {
    "caption": "(P) Transwell assays were used to test the migration and invasion abilities of both ccRCC cells with indicated treatment. Unpaired two-tailed Student's t-test, *P < 0.05, **P < 0.01. Data are shown as mean ± SEM of three biological replicates.",
    "diseases": "ccRCC"
  },
  {
    "caption": "Microarray analysis was performed following doxycycline-regulated specific AR-V7 depletion (using a tet-plKO backbone) in 22Rv1 PC cells compared to doxycycline-treated shGFP controls. The genes that were significantly regulated by shAR-V7 (in either direction, p value < 0.05) were distributed among the gene modules defined by WGCNA in panel A. Upregulated genes (red) are those in which expression decreased following AR-V7 depletion and conversely downregulated genes (blue) are those that increased following AR-V7 depletion.",
    "diseases": "PC"
  },
  {
    "caption": "Hornberg et al., 2011 gene expression profiling array data was analyzed to determine the expression levels of the seven genes in human CRPC bone metastases, grouped by their relative levels of AR-VS, mainly AR-V7. (High-levels of AR-V7 (top quartile) or lower levels of AR-V7 (quartiles 1-3). Data are plotted as the mean ± s.e.m.. Non-parametric Mann-Whitney test was performed (two-tailed). Note that BUB1B expression was not measured in these microarrays. ** Significant at a p value < 0.05. N (AR-V7 low) = 20; N (AR-V7 high) = 10.",
    "diseases": "bone metastases, CRPC"
  },
  {
    "caption": "The Kaplan-Meier curves for Disease-Free Survival (DFS) and overall survival were built using the Prostate Adenocarcinoma TCGA dataset (465 samples) (upper graphs). The black curves denote cases with normal expression of the gene set, and red represents cases where the mRNA levels of the seven genes were upregulated (z-score threshold ≤ 1.96). For DFS: p-value = 0.0009; for death: p-value = 0.026. An independent dataset was analyzed (Prostate Adenocarcinoma MSKCC, Cancer Cell 2010, 123 samples) (lower graphs). The black curves denote cases with normal expression of the gene set, and red represents cases where the mRNA levels of at least five genes of the gene set were upregulated (z-score threshold ≤ 1.96). For DFS: p-value = 0.0007; for death: p-value = 0.00546.",
    "diseases": "Prostate Adenocarcinoma"
  },
  {
    "caption": "Cell proliferation was examined in the CRPC cell line 22Rv1 following individual depletion of mRNAs for the seven genes or shGFP controls, using shRNA against the coding region for each gene (shRNA #2). Cell number was measured using a non-perturbing nuclear restricted dye and quantified after 72 hours using Incucyte Zoom System. Data shown are mean ± s.e.m. of 8 to 12 replicates normalized to their shGFP control. Kruskal-Wallis test (p value < 0.0001, two-tailed) and Dunn's multiple comparisons test were performed.",
    "diseases": "CRPC"
  },
  {
    "caption": "The CRPC cell line 22Rv1 was cultured in 2% CSS media and was treated for 72 hours with vehicle (DMSO), doxorubicin (DOX), N9-isopropylolomoucine (N-9), or the combination of DOX and N-9 at different concentrations. Cell confluence was monitored using Incucyte Zoom System and the experiments were done with eight replicates each. The data were analyzed using Compusyn software, and a normalized isobologram was built. The table shows the Combination Index (CI) for the different drug combinations. CI=1 represents additivity, CI<1 synergism, and CI>1 antagonistic effects.",
    "diseases": "CRPC"
  },
  {
    "caption": "The non-tumorigenic prostate epithelial cell line RWPE1, the AR-null PC cell line PC3, the androgen dependent cell line LNCaP, and the CRPC cell lines C4-2B and 22Rv1 were treated for 72 hours with vehicle (DMSO), DOX (100 ng/mL [184 nM]), N-9 (200 ng/mL [613 nM]), or the combination of DOX (100 ng/mL [184 nM]) and N-9 (200 ng/mL [613 nM]). C4-2B and 22Rv1 cells were kept in 10% CSS media, and the other cell lines in 10% FBS. Cell confluence was monitored using the Incucyte Zoom System. Data represent two independent experiments, with four to six replicates each, showing the mean ± s.e.m., and normalized to vehicle controls (Kruskal-Wallis test, P value <0.0001, two-tailed). *Significant at a p value < 0.05, ** p value < 0.01, *** p value < 0.001.",
    "diseases": "PC, CRPC"
  },
  {
    "caption": "The non-tumorigenic prostate cell line RWPE-1 and the CRPC cell line 22Rv1 were treated for 72 hours with vehicle (DMSO) or the combination of DOX and N-9 at 100 ng/mL and N-9 200 ng/mL, respectively. Cell confluence was monitored using the Incucyte Zoom System.",
    "diseases": "CRPC"
  },
  {
    "caption": "B | hFwe-Lose mRNA expression is more abundant in elderly people. hFwe-Lose mRNA expression was analyzed by RT-qPCR in 86 lung tissue biopsies taken from non-COVID patients with age between 20 and 82 years. Older patients show a significant upregulation of hFwe-Lose expression. A log-Linear regression model demonstrates a positive correlation between age and hFwe-Lose expression (R2= 0.13; slope confidence interval of 95% (CI) = [2.0-12.2]; p-value of the linear regression model < 6⋅10-4).",
    "diseases": "COVID"
  },
  {
    "caption": "C | hFwe-Lose expression is elevated in lung tissue biopsies from patients with comorbidities. Box plot illustrates an increased expression of hFwe-Lose in lungs of patients with hypertension (HT; n = 129), obesity (n = 45), chronic obstructive pulmonary disease (COPD n = 51), diabetes (n = 48), cardio-vascular disease (CVD; n = 63) versus disease-free control lungs (n = 42). Patient`s age is depicted in color. Two-sided Student's t-test was performed for each comorbidity (compared to disease-free patients), and p-values are presented on the plot. The central band shows the median, the box indicates the interquartile range, the whiskers extend to the most extreme points within the 1.5-fold distance of the interquartile range above and below the box.",
    "diseases": "cardio-vascular disease, CVD, chronic obstructive pulmonary disease, COPD, diabetes, HT, hypertension, obesity"
  },
  {
    "caption": "D | hFwe-Lose expression is upregulated in lung tissue of COVID-19 patients. Box plot illustrates an increased expression of hFwe-Lose in lung tissue of patients diagnosed with COVID-19 (n = 11), individuals affected with host comorbidities (n = 216) versus disease-free control lungs (n = 42). Patient's age is depicted in color. Two-sided Student's t-test was performed (compared to disease-free patients), and p-values are presented on the plot. The central band shows the median, the box indicates the interquartile range, the whiskers extend to the most extreme points within the 1.5-fold distance of the interquartile range above and below the box.",
    "diseases": "COVID-19"
  },
  {
    "caption": "F | Healthy lungs show very low cleaved caspase-3 positive cells. IHC staining for cleaved caspase-3 (20x). G | Expression of cleaved (active) caspase-3 yielding apoptotic and pre-apoptotic cells: IHC for cleaved (active) caspase-3 showing a brown nuclear staining signal in respective cells. 31.5% cells were found to be caspase positive, 11.7% with high caspase-3 positivity and another 19.8% with low. These cells are mainly located in the interstitium, but also in some alveolar epithelial and endothelial compartments. In the lower right, the edge of an alveolar space containing several (pre-)apoptotic pneumocytes is seen, while in the upper left a completely denuded/deepithelialized alveolus with two apoptotic remnants is observable (IHC for cleaved caspase-3, 20x). Abbreviations: a- Apoptotic large mononuclear cells; b-Apoptotic alveolocyte / pneumocyte; i- Amplification of apoptotic alveolocyte / pneumocyte. As shown in the round inlets of 1E2 and 1E4, homogeneous dark nuclear condensation up to a size of 2μm (karyopyknosis), homogeneous pinkish-greyish nuclear condensation, large nuclear inclusion with marginalization of the condensed chromatin, coarse nuclear angulation, nose-like/polar body-like nuclear protrusions, the latter two being karyorrhectic debris, were all morphologically considered evidence of apoptosis. This has been correlated with and was reflected by the results of the cleaved caspase-3 staining on step sections. All cells were counted on the 20X fields for n = 42 disease-free and n = 3 COVID-19 autopsy patients. The expression of hFwe-Lose in COVID-19 patients is significantly higher than in disease-free individuals, regardless of cleaved caspase-3 staining (Cas POS: p < 0.004; Cas NEG: p < 0.006). In COVID-19 patients we observed a significantly higher expression of hFwe-Lose in sections with positive cleaved caspase-3 staining (p < 0.004). Two-sided Student's t-test was performed (compared to disease-free samples and NEG samples, respectively), and p-values are presented on the plot. The central band shows the median, the box indicates the interquartile range, the whiskers extend to the most extreme points within the 1.5-fold distance of the interquartile range above and below the box.",
    "diseases": "COVID-19"
  },
  {
    "caption": "B | hFwe-Lose expression is elevated in nasopharyngeal swab probes from patients with comorbidities. Box plots illustrate an increased relative expression of hFwe-Lose in nasopharyngeal swabs of patients with diabetes (n = 129), COPD (n = 20), obesity (BMI > 30; n = 152), cardiomyopathy ("CM", n = 19), heart failure ("HF", n = 35), hypertension ("HT", n = 121), chronic kidney disease ("CKD", n = 60) versus disease-free patients (n = 96). Two-sided Student's t-tests were performed (compared to disease-free patients), and p-values are presented on the plot. The vertical axis represents relative hFwe-Lose expression normalized to the mean of non-hospitalized patients. The color refers to the COVID-19 disease outcome: gray for not hospitalised, blue for hospitalised and red for deceased patients. The shape of data points reflects the cohorts: circles for the training cohort (n = 203) and triangles for the validation cohort (n = 80). The central band shows the median, the box indicates the interquartile range, the whiskers extend to the most extreme points within the 1.5-fold distance of the interquartile range above and below the box.",
    "diseases": "cardiomyopathy, CM, chronic kidney disease, CKD, COPD, COVID-19, diabetes, heart failure, HF, HT, hypertension, obesity"
  },
  {
    "caption": "D | Elevated hFwe-Lose expression in the nasal swab samples associates with patients' condition severity and respective medical treatment. Box plots illustrate an increased expression of hFwe-Lose in nasal swabs of patients, who were hospitalized within 14 days of disease progression (n = 177), admitted to intensive care unit (ICU) (n = 34), underwent intubation (n = 58), had respiratory rate greater than 30 (GT30) (n = 76), had blood oxygenation level (SpO2) less than 94% (n = 147), and who died within 30 days of disease progression (n = 21) versus patients without respective conditions. Pairwise two-sided Student's t-tests were performed (compared to patients without respective conditions), and p-values are presented on the plot. The vertical axis represents hFwe-Lose expression normalized to the mean of non-hospitalized patients. The color refers to the COVID-19 disease outcome: gray for not hospitalised, blue for hospitalised and red for deceased patients. The shape of data points reflects the cohorts: circles for the training cohort (n = 203) and triangles for the validation cohort (n = 80). The central band shows the median, the box indicates the interquartile range, the whiskers extend to the most extreme points within the 1.5-fold distance of the interquartile range above and below the box.",
    "diseases": "COVID-19"
  },
  {
    "caption": "E |Elevated hFwe-Lose expression in nasal swab associates with patients' disease outcome. Box plot emphasizes an increased expression of hFwe-Lose in nasal swabs of patients, who were hospitalized within 14 days of disease progression (n = 177), and who died within 30 days of disease progression (n = 21) versus patients without respective conditions. Two-sided Student's t-tests were performed (compared to non-hospitalised patients), and p-values are presented on the plot. The vertical axis represents hFwe-Lose expression normalized to the mean of non-hospitalized patients. The color refers to the COVID-19 disease outcome: gray for not hospitalised, blue for hospitalised and red for deceased patients. The shape of data points reflects the cohorts: circles for the training cohort (n = 203) and triangles for the validation cohort (n = 80). The central band shows the median, the box indicates the interquartile range, the whiskers extend to the most extreme points within the 1.5-fold distance of the interquartile range above and below the box.",
    "diseases": "COVID-19"
  },
  {
    "caption": "(A) Western blot  showing the protein expression of ASCL1 and/or  NEUROD1  in  NCI-H69, NCI-H82, NCI-H146, NCI-H510A, NCI-H526, SHP-77 and  DMS-53 SCLC cells (lanes 4-10); A549  and NCI-H460 NSCLC  cells and a  IMR-90  HFL cell lines (lanes 1-3). Tubulin (α-Tub) is shown as loading control. Each blot  is representative from at least three independent experiments.",
    "diseases": "NSCLC, SCLC"
  },
  {
    "caption": "(a)  Western blot  showing RNAPII  across the panel of;  A549 and NCI-H460 NSCLC cells; IMR-90 HFL cells; NCI-H146, NCI-H82, DMS-53, NCI-H510A, NCI-H526  and SHP-77 SCLC cells before (-) and after (+) treatment with lurbinectedin. α-Tubulin  (α-Tub) is shown as loading control; lower panel, Histogram showing the average of RNAPII before (dark blue) and after (light Blue) lurbinectedin treatment in arbitrary units (a.u.) normalized against α-Tub. Data is presented as Mean ± SEM as determined by Two Way RM ANOVA and Šídák's multiple comparisons test (n=3 biological replicas). ****P ≤0.0001.",
    "diseases": "NSCLC, SCLC"
  },
  {
    "caption": "(A) LncRNA CRNDE expression level was measured by qRT-PCR  in cancerous  tissues  and adjacent normal tissues obtained from 35 cases of gastric cancer  (GC) patients. Data information: Data are expressed as mean ± SD. Student's t-test **P<0.01.",
    "diseases": "gastric cancer, GC"
  },
  {
    "caption": "(C) LncRNA CRNDE expression level was measured by qRT-PCR in adjacent normal tissue-derived  macrophages (NTMs) and tumor-associated macrophages (TAMs) obtained from 7 cases of GC patients. Data information: Data are expressed as mean ± SD. Student's t-test **P<0.01.",
    "diseases": "GC"
  },
  {
    "caption": "Adipocyte hypertrophy is visible in the absence of ATMs. Representative images of hematoxylin and eosin staining (H&E) (E) and corresponding adipocyte diameters (F) of lean and obese (HFD 16 weeks) eWAT from WT or CD169-DTR mice treated for 7 or 12 days with DT. Scale bar, 50 μm. Each group comprised 3-5 mice. Statistical significance was determined using one-way ANOVA test. **P < 0.01; ****P < 0.0001; ns: no significant difference. The box and whisker plots show the median value and 10-90 percentiles of adipocyte diameters.",
    "diseases": "Adipocyte hypertrophy"
  },
  {
    "caption": "C  Kaplan-Meier survival curve of leukemic mice  (n = 11-12 mice/group, median survival  is 16.5 for vehicle and not reached for AG636  and doxycycline, P < 0.0001 by Log-rank test). Data information: Dox  - doxycycline.",
    "diseases": "leukemic"
  },
  {
    "caption": "E-F qPCR showing down-regulation of genes encoding ribosomal  proteins in MN  cells (E) and human AML  cell lines (F) treated for 24 hours with AG636  (n = 3 biological replicates for each cell line). Data information: data in E, F are presented as mean ± s.e.m.; P values were calculated using a one-tailed Student's unpaired t-test; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001;",
    "diseases": "AML"
  },
  {
    "caption": "F Western blot of YY1 expression  in human AML  cell lines treated with AG636  for 24 hours.",
    "diseases": "AML"
  },
  {
    "caption": "H Barcode plots showing downregulation of the Reactome Translation gene set in YY1  knockout pro B cells and human melanoma  cells upon YY1  knockdown",
    "diseases": "melanoma"
  },
  {
    "caption": "A-B  Proliferative competition assays  in AML  cells transduced with indicated sgRNAs and cultured in AG636  or DMSO  (n = 2 biological replicates). Data information: data represented as mean ± s.e.m; P values were calculated using one-tailed Student's unpaired t-test in A and B ; *P < 0.05, **P < 0.01, ***P < 0.001, ***P < 0.0001.",
    "diseases": "AML"
  },
  {
    "caption": "F AML  cells were treated with AG636, Roscovitine  or the combination for 17 days. Cumulative live cell counts are shown (n = 2 biological replicates). Data information: data represented as mean ± s.e.m; P values were calculated using Brown-Forsythe and Welch ANOVA test in F; *P < 0.05, **P < 0.01, ***P < 0.001, ***P < 0.0001.",
    "diseases": "AML"
  },
  {
    "caption": "A-C Bar chart with individual points showing the levels of propionate acetate and butyrate in wt and mdx mice receiving DFZ or vehicle, measured by NMR or GC-MS. Data are expressed as μg/ml or bin intensity (arbitrary unit - a.u.) D-F Bar chart with individual points showing the levels of pyruvate, succinate and lactate in wt and mdx mice receiving vehicle or DFZ, measured by NMR. G",
    "diseases": "mdx"
  },
  {
    "caption": "A-B Muscle coordination and strength were measured in 19 weeks old control and mdx mice treated with vehicle (DMSO), NaB (100 mg kg−1/daily) or DFZ (1.2 mg kg−1/daily) for 3 weeks using the rotarod and weight test. Bar charts show the latency to fall or drop the weight of wt and dystrophic mice.",
    "diseases": "mdx, dystrophic"
  },
  {
    "caption": "A-I Bar chart with individual points showing the mRNA expression levels of the indicated genes measured in the gastrocnemius of control and mdx mice treated with or without NaB and DFZ.",
    "diseases": "mdx"
  },
  {
    "caption": "A-B Levels of AEA and 2-AG in plasma samples of wt and mdx mice expressed as pmol mg−1 of wet tissue weight.",
    "diseases": "mdx"
  },
  {
    "caption": "A-C Bar charts with individual points showing the mRNA expression levels of Ulk, Pink and Becn1 measured in control and mdx mice treated with rimonabant (0.5 mg kg-1).",
    "diseases": "mdx"
  },
  {
    "caption": "A-E Bar chart showing the mRNA expression levels of IL6, COX2, ULK 1, ATG13 and ATG4 mRNA in primary human myoblasts isolated from one healthy donor (HD) and five DMD donors (D1- D5).",
    "diseases": "DMD"
  },
  {
    "caption": "A. Interaction surface built using the estimated combination index (CI) for the Salinomycin and JQ1 drug combination, in four different breast cancer cell lines (top panels). The CI is represented in 2D color code interaction surface. The color code spans from strong synergism (dark blue, CI<1) to strong antagonism (red, CI>1). The concentrations of each particular drug in the combinations are denoted on each axis. On the bottom panels, neighborhood Z-core matrix estimating the significant synergistic interaction. The color code spans from a statistically significant synergism (dark blue, CI<1, p<0.01) to a statistically significant antagonism (dark red, CI>1, p<0.01).",
    "diseases": "breast cancer"
  },
  {
    "caption": "C. Kaplan-Meier relapse-free survival curve according to subnetwork metagenes expression levels in breast tumors. Curves were compared with a log-rank test (p-value).",
    "diseases": "breast tumors"
  },
  {
    "caption": "(B) Phenotypes of affected individuals. Camptodactyly, absent flexion crease, and limited forearm supination were observed.",
    "diseases": "Camptodactyly"
  },
  {
    "caption": "STXBP4 is downregulated in human kidney cancer. The mRNA level of STXBP4 is analyzed in the Firebrowse web database (A), where 14,729 tumor sample data generated by TCGA were included. The first quartile, median and third quartile values were indicated as the boxplots. Outliers were plotted as individual points. Error bars indicated the standard deviation above and below the mean of the data.",
    "diseases": "kidney cancer"
  },
  {
    "caption": "STXBP4 is downregulated in human kidney cancer. The expression of STXBP4 was also examined using kidney tissue microarray, where percentage of the indicated tissue samples with downregulated STXBP4 was shown (B). The p value was calculated by using the paired Student's t-test.",
    "diseases": "kidney cancer"
  },
  {
    "caption": "(C) Kaplan-Meier curves of overall survival of patients with ccRCC is stratified by STXBP4 expression level. Clinical data of STXBP4 were analyzed in TCGA-KIRC project containing total 611 patient samples. The p value was calculated by using the Log-rank (Mantel-Cox) test.",
    "diseases": "ccRCC, KIRC"
  },
  {
    "caption": "(D) Immunohistochemical staining of STXBP4 and YAP were performed in a kidney cancer tissue microarray, where the indicated regions in the box were shown three times enlarged. Brown staining indicates positive immunoreactivity. Scale bar, 100 μm.",
    "diseases": "kidney cancer"
  },
  {
    "caption": "(E) Correlation analyses between STXBP4 and YAP in human normal kidney and clear cell carcinoma samples are shown as tables. Statistical significance was determined by chi-square test. R, correlation coefficient. N, nuclear localization. C, cytoplasmic localization.",
    "diseases": "clear cell carcinoma"
  },
  {
    "caption": "(F) STXBP4 expression is examined in a panel of ccRCC cell lines by Western Blotting.",
    "diseases": "ccRCC"
  },
  {
    "caption": "H. Immunofluorescence images against CB1 and the Purkinje cell marker calbindin in the cerebellum of age-matched control and ASMD-affected children. Graph shows mean ± SEM intensity associated to CB1 in the Purkinje cells expressed as percentage of the values obtained in the control child (16 and 15 replicates in control and ASMD, respectively). Scale bar, 10 μm.",
    "diseases": "ASMD"
  },
  {
    "caption": "Immunofluorescence images against CB1 in Purkinje cells of the cerebelllum of age-matched control and NPC affected children. Graph shows mean ± SEM intensity associated to CB1 in the Purkinje cells expressed as percentage of the control values (16 and 57 cells in control and NPC, respectively). Scale bar, 10 μm.",
    "diseases": "NPC"
  },
  {
    "caption": "Graph shows mean ± SEM SM levels, expressed as percentage of vehicle values, in cultured fibroblasts from a NPC patient treated with vehicle or with PF at 50μM or 100μM (n= 2 different cultures)",
    "diseases": "NPC"
  },
  {
    "caption": "Graph shows mean ± SEM cholesterol levels, expressed as percentage of vehicle values, in cultured fibroblasts from a NPC patient treated with vehicle or with PF at 50μM or 100μM (n=2 different cultures)",
    "diseases": "NPC"
  },
  {
    "caption": "Immunofluorescence images of CB1 and Lamp1 in cultured fibroblasts from control subject and NPC patient treated with vehicle or with PF at 100μM. Graph shows mean ± SEM Mander´s coefficient for the colocalization of CB1 with Lamp1 (n= 2 different cultures). Scale bar, 5 μm.",
    "diseases": "NPC"
  },
  {
    "caption": "Immunofluorescence images against the microglia marker F4/80 in the cerebellum of WT and Npc1nmf164 after 48 hours of a single dose of 5mg/kg PF. Graphs show mean ± SEM number (upper) and area (lower) of F4/80 positive cells (upper graph ****P< 0.0001; lower graph ***PWT Veh vs NPC Veh = 0.0008; *PWT Veh vs. NPC PF = 0.0286; ****PWT PF vs. NPC Veh < 0.0001; **PWT PF vs. NPC PF = 0.0022, n = 3 mice per group, > 20 cells analyzed per mouse, one - way ANOVA, Bonferroni post hoc). Scale bar, 10 μm.",
    "diseases": "NPC"
  },
  {
    "caption": "B) Number of non-synonymous mutations per sample. Bars are colored by PAM50 subtypes Luminal A (dark blue), Luminal B (light blue), HER2-enriched (pink), basal-like (red), Normal-like (green) and Unclassified (gray).",
    "diseases": "basal-like, Normal-like, HER2-enriched, Luminal A, Luminal B"
  },
  {
    "caption": " Overall survival stratified by tumor mutational burden (TMB) across treatment groups in 3,217 patients. Samples were classified as TMB-high if the amount of non-synonymous mutations per expressed MB (rnaMB) was ≥ the median number of non-synonymous mutations per rnaMB across the whole SCAN-B cohort (0.082 mutations per rnaMB) and TMB-low otherwise. In each Kaplan-Meier plot, TMB-low cases are plotted in blue, TMB-high cases are plotted in red, the log-rank P value is given, and the hazard ratio (HR) for TMB-high is given with a 95% CI and after uni-variable and multi-variable (MV) Cox regression adjustment. Covariables included in the MV analysis were age at diagnosis, lymph node status, tumor size, and the variables denoted by the following symbols: ¶, ER, PgR, HER2, and NHG; ¤, ER, PgR, and NHG; $, HER2 and NHG; #, NHG. Abbreviations: TMB, tumor mutational burden; ER, estrogen receptor; PgR, progesterone receptor; HER2, human epidermal growth factor receptor 2; NHG, Nottingham histological grade; HoR, hormone receptor; TNBC, triple-negative breast cancer. ",
    "diseases": "TNBC, triple-negative breast cancer"
  },
  {
    "caption": "P Representative result of MARS expression was detected by IHC in tumor tissues (T) and adjacent noncancer tissues (N) of UCC samples. Scale bar: 50 μm.",
    "diseases": "UCC"
  },
  {
    "caption": "Q Ki67 and MARS expression was analysed by IHC in HCC samples. Scale bar: 20 μm.",
    "diseases": "HCC"
  },
  {
    "caption": "H Total protein N-Hcy levels in maternal mice liver homogenates were determined and quantified in correlation to the corresponding prevalence of NTDs in affected foetuses (i). Western blot was used to detect N-Hcy levels (ii). Data are presented as the mean ± SEM and were compared using an unpaired Student's t test. nsnot significant, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. One-way ANOVA with Dunnett's correction was used for multiple comparisons.",
    "diseases": "NTDs"
  },
  {
    "caption": "J Superoxide (a), apoptosis (b), and Wnt signalling (c, d) were over-activated in ATRA-treated mice neural tubes and restored by AHT or NAC treatment. (a) Whole mount DHE staining of E10.5 mice embryos. Scale bar: 500 μm. Neural tube defect (white arrows) and heart (green arrow) regions show especially higher fluorescence intensities. (b) TUNEL (green) staining detected apoptotic cell death in E8.5 neural tube (E) sections. MARS (red). Scale bar: 300 μm. (c, d) IHC staining for β-catenin (green) in E8.5 (c) and E10 (d) mice neural tube sections. Scale bar: 300 μm (c), 150 μm (d). DAPI (blue).",
    "diseases": "Neural tube defect"
  },
  {
    "caption": "N Hcy-treated eggs exhibited NTDs phenotypes at embryonic stage 8 (E8). A normal embryo (a) and neural tube defect phenotypes (b, c) are shown. Exencephaly (white arrows) and spina bifida (blue arrows) are indicated. Scale bar: 500 μm.",
    "diseases": "Exencephaly, NTDs, spina bifida"
  },
  {
    "caption": "Effect of nucleoside (NS) cocktail treatment from 1-3 dpf on the incidence of cardiac edema in WT and yap-/- mutant larvae. Each point represents the percentage of affected embryos in each independent clutch. n>7, **p<0.01, two-sided Student's t-test; values represent the mean s.e.m",
    "diseases": "edema"
  },
  {
    "caption": "Dot plots showing the correlation between GLUT1 and YAP1 mRNA expression in the cancer cell line encyclopedia (CCLE, 967 lines). Pearson coefficient is 0.46 Dot plots showing the correlation between GLUT1 and AMOTL2 mRNA expression in the cancer cell line encyclopedia (CCLE, 967 lines). Pearson coefficient is 0.45",
    "diseases": "cancer"
  },
  {
    "caption": "(E, F) The representative images of STAT1 and pY-STAT1 in the brain of AD patients probed by co-immunohistochemical staining and quantitative analysis (hematoxylin stains nuclei, purple; DAB stains the target proteins, brown; n=5-6 slices). Arrowheads indicated typical nuclear staining of STAT1/pY-STAT1. Data information: Data were presented as mean ± SD. *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP, wt or Ctrl.",
    "diseases": "AD"
  },
  {
    "caption": "(G) The increased AT8 (pS202/pT205), STAT1 and pY-STAT1 in cortex total extracts of AD patients measured by Western blotting (n=3, Student's t test). Data information: Data were presented as mean ± SD. *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP, wt or Ctrl.",
    "diseases": "AD"
  },
  {
    "caption": "B.  Kaplan-Meier  plots of overall  survival of 496 stage I and II breast cancer patients with different levels of promoter/CpG island  methylation of RASSF1A, previously reported to be associated with outcome in breast cancer patients. P values were obtained from a log-rank test.",
    "diseases": "breast cancer"
  },
  {
    "caption": "C. Left: heatmap depicting methylation  patterns across the RASSF1  gene. In light green, RASSF1-2γ  CpG island is depicted; in dark green, RASSF1-1α CpG island is depicted. Right: Kaplan‑Meyer survival curves  depicting interaction of RASSF1A    and RASSF1C methylation to predict the outcome of early stage breast cancer patients. P values were calculated from a log-rank test. Color legend: yellow, low RASSF1A   and low RASSF1C; green, low RASSF1A  and high RASSF1C; red, high RASSF1A  and low RASSF1C; grey, high RASSF1A and high RASSF1C.",
    "diseases": "breast cancer"
  },
  {
    "caption": "B. Follow-up of the clinical signs of mice under different treatments. Heatmaps were established based on a progressive 0-7 clinical score scale (0: no apparent changes | 1: ruffled fur | 2: slow movement, hind limb ataxia | 3: apathy | 4: monoplegia | 5: hind limb paralysis, tremors | 6: paralysis, conjunctivitis/ keratitis, urine staining of the haircoat of the perineum | 7: death). Each line represents one animal throughout time.",
    "diseases": "apathy, ataxia, conjunctivitis, keratitis, paralysis, monoplegia, tremors"
  },
  {
    "caption": "A-R. Histopathological analysis of the brain in Tha-RABV-infected non-treated mice (at 11 dpi), versus surviving mice (at 100 dpi) treated with intramuscular and intracerebroventricular administration of the RVC20 and RVC58 monoclonal antibodies cocktail. The detection of Tha-RABV, using immunohistochemistry (IHC) on brain sections, revealed a heterogeneous invasion between the non-treated mice, ranging from extensive (A) to multifocal (B). Higher magnification of extensive invasion in the cortex (F), hippocampus (G), brain stem (H) and cerebellum (I). (C,J,K,L,M) In contrast, even if a non-specific IHC signal was sometimes observed, no virus was detected on the brain sections of treated mice at 100 days post-infection. Only rare signs of neuro-inflammation were observed, as perivascular cuffing (D) (2/7 mice) and minimal meningitis (E) (3/7 mice). Data information: A-C and F-M: Tha-RABV IHC D-E: HE staining. F-I are high magnifications of A; J-M are high magnifications of C",
    "diseases": "neuro-inflammation, meningitis"
  },
  {
    "caption": "Colorectal tumor outcomes in WT (n=7), IL-33KO (n=4) and ST2KO (n=3) mice at the completion of the AOM/DSS carcinogenesis protocol. (A) Tumor volumes at the endpoint (each dot represents a tumor, mice with no tumor are marked as zero), Skin tumor outcomes in WT (n=7), IL-33KO (n=6) and ST2KO (n=7) mice at the completion of the DMBA/DNFB carcinogenesis protocol. (D) Tumor volumes at the endpoint (each dot represents a tumor, mice with no tumor are marked as zero),",
    "diseases": "Colorectal tumor, Skin tumor"
  },
  {
    "caption": "(J) Representative images of IL-33 and p-SMAD2/3 immunostaining on the adjacent sections of human squamous cell carcinoma (SCC) and normal skin (scale bar: 100 μm). Data information: Graphs show mean + SD, NS: not significant, unpaired t-test. ",
    "diseases": "SCC, squamous cell carcinoma"
  },
  {
    "caption": "(B) Il33 and Smad6 mRNA levels in caerulein-treated WT pancreas compared with PBS-treated controls at the completion of chronic pancreatitis protocol (n=8 in caerulein and n=9 in PBS group for Il33, n=9 in caerulein and n=10 in PBS group for Smad6, unpaired t-test).",
    "diseases": "chronic pancreatitis"
  },
  {
    "caption": "A The expression  of LINC00839   in CRC  tissues and normal mucosa  tissues in the UALCAN database. B, C, D The expression  of LINC00839  in unpaired CRC  and normal samples in the LnCAR database (GSE37364, GSE71187, and GSE33113). Data information: In A, B, C, D middle lines represent the median, and the upper and lower lines represent the upper and lower quartiles. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "diseases": "CRC"
  },
  {
    "caption": "E, F The expression  levels of LINC00839  in tumour tissues and NATs from the CRC  cohort (n = 45). nmCRC denotes CRC patients without metastases, and mCRC denotes CRC patients  with metastases. Data information: In E, F, the data are presented as the mean ± SD and were analysed by Student's t test, n = 3 technical replicates. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "diseases": "CRC, metastases"
  },
  {
    "caption": "G Representative ISH staining  of LINC00839  in paraffin-embedded samples of CRC  tumour tissues and NATs. (a) Expression  of LINC00839  in tumour tissues and NATs. Scale bars, 100 μm. (b) Magnification of normal mucosal  area and (c) magnification of the tumour area. Scale bars, 50 μm. (d) Weakly positive staining  of LINC00839  in normal mucosa. Scale bars, 50 μm. (e) Strong positive staining  of LINC00839  in tumours and (f) magnification of the local area. Scale bars, 100 μm.",
    "diseases": "CRC"
  },
  {
    "caption": "I Differential expression  of LINC00839  in nonmetastatic CRC patients  (nmCRC) and metastatic CRC patients  (mCRC). Data information: In I, the data are shown as the mean ± SD and were analysed by Student's t test. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "diseases": "CRC, metastatic"
  },
  {
    "caption": "J Expression  of LINC00839  in CRC patients  with early-stage (stage I  and II) and advanced-stage (stage III  and IV) disease. Data information: In J, middle lines represent the median, and the upper and lower lines represent the upper and lower quartiles. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "diseases": "CRC"
  },
  {
    "caption": "Kaplan-Meier  analysis of overall survival rate of the ISH CRC  cohort.",
    "diseases": "CRC"
  },
  {
    "caption": "L Kaplan-Meier  analysis of overall disease-free survival rate of the ISH CRC  cohort. M Kaplan-Meier  analysis of the disease-free survival rate of CRC patients  in the LnCAR database (GSE33113).",
    "diseases": "CRC"
  },
  {
    "caption": ". G The CRC  orthotopic mouse  model revealed the effect of LINC00839  on tumour development. Representative images of primary tumours (yellow arrowheads) and liver metastasis  (blue arrowheads) in the model (upper panel), analysis of tumour volume and the number of mice  with liver metastasis   (medium panel), and H&E staining  of tumours and metastases  (n = 6 for each cohort). Scale bars, 100 μm (n = 6 biological replicates . Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.000",
    "diseases": "CRC"
  },
  {
    "caption": "H Interaction  of endogenous Ruvb1  and Tip60  in CRC  cells was confirmed by Co-IP.",
    "diseases": "CRC"
  },
  {
    "caption": "G Analysis of NRF1 expression  in CRC  tissues (T) and normal tissues (N) the GEPIA database. Data information: In G, the middle lines represent the median, and the upper and lower lines represent the upper and lower quartiles; the data were analysed by ANOVA. Across experiments, the P values are as follows: ns = not significant, *P < 0.05",
    "diseases": "CRC"
  },
  {
    "caption": "F ISH staining  of LINC00839  and IHC staining  of NRF1, H4K5ac, and H4K8ac in paraffin-embedded samples of CRC  tumour tissues and NATs. Scale bars, 200 μm.",
    "diseases": "CRC"
  },
  {
    "caption": "G, H, Correlation analysis of the expression  of LINC00839     and NRF1  (G), H4K5ac (H) in CRC patients   (n = 120). Data information: In G, H show the Pearson correlation coefficient results. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "diseases": "CRC"
  },
  {
    "caption": "I Correlation analysis of the expression    of LINC00839   and H4K8ac (I) in CRC patients  (n = 120). Data information: In I show the Pearson correlation coefficient results. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "diseases": "CRC"
  },
  {
    "caption": "J Correlation of NRF1  expression with the overall survival rate in patients  with CRC  (n = 120). NRF1  expression was stratified as high and low according to the median expression level.",
    "diseases": "CRC"
  },
  {
    "caption": "VGLL4 protein expression levels in 6 murine tumor cell lines. Total cell lysates were analyzed by western blot",
    "diseases": "tumor"
  },
  {
    "caption": "Control or shVgll4 LLC cells were transplanted into C57BL/6 mice, and tumor-growth kinetics was measured at the indicated times. n=12 tumors for each group",
    "diseases": "tumors"
  },
  {
    "caption": "Control or shVgll4 LLC cells were transplanted into nude mice, and tumor-growth kinetics was measured at the indicated times. n=8 tumors for each group. (F) Quantification of tumor weights 15 days after transplantation of control or shVgll4 LLC cells into nude mice from (E). n=8 tumors for each group. n.s. p>0.05, two-tailed Student"s t-test. The solid line represents the average weight",
    "diseases": "tumors"
  },
  {
    "caption": "Control or shVgll4 MB49 cells were transplanted into C57BL/6 mice, and tumor-growth kinetics was measured at the indicated times. n=9 tumors for each group Quantification of tumor weights 30 days after transplantation of control or shVgll4 MB49 cells into C57BL/6 mice",
    "diseases": "tumors"
  },
  {
    "caption": "Control or shVgll4 MB49 cells were transplanted into nude mice, and tumor-growth kinetics was measured at the indicated times. n=8 tumors for each group Quantification of tumor weights 15 days after transplantation of control or shVgll4 MB49 cells into nude mice from (I). n=8 tumors for each group",
    "diseases": "tumors"
  },
  {
    "caption": "Immunofluorescent staining of CD3, CD8 and CD45 (red) counterstained with DAPI for DNA (blue) using control or shVgll4 LLC tumors from C57BL/6 mice. Statistical analysis of the percentage of CD3, CD8 and CD45 positive cells in the tumors is shown in the right panel respectively. n=3 tumors for each group",
    "diseases": "tumors"
  },
  {
    "caption": "Quantification of tumor weights 30 days after transplantation of shVgll4 MB49 cells into C57BL/6 mice receiving anti-CD4 alone, anti-CD8 alone, or both anti-CD4 and anti-CD8 blocking antibodies. n=20 tumors for each group",
    "diseases": "tumors"
  },
  {
    "caption": "Overexpression of mouse PD-L1 in Vgll4 knockdown LLC cells restored the tumor growth in C57BL/6 mice. Tumor weights of shVgll4 or shVgll4-lenti-mPD-L1 LLC cells were determined 21 days after tumor cell transplantation into C57BL/6 mice (left panel). Expression of mPD-L1 was shown in the right panel by immunoblot analysis with anti-mPD-L1 antibody. n=10 tumors for each group",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "Knockdown of VGLL4 in A549 cells enhances T cell-meditated tumor cell killing. Activated T cells and A549 cells were co-cultured in 24-well plates for 4 days and then surviving tumor cells were visualized by crystal violet staining. Relative fold ratios of surviving cell intensities are shown in right panel",
    "diseases": "tumor"
  },
  {
    "caption": "Expression of VGLL4-HF4A rescues tumor growth of VGLL4-knockdown LLC cells in C57BL/6 mice. Control, Vgll4 knockdown or Vgll4 knockdown together with VGLL4-HF4A overexpressing LLC cells were transplanted into nude mice or C57BL6 mice. Tumor volumes were measured 15 days for nude mice and 21 days for C57BL/6 mice after tumor cell inoculation",
    "diseases": "tumor"
  },
  {
    "caption": "Expression of VGLL4-HF4A attenuates the T cell-meditated tumor cell killing. Activated T cells and A549 cells were co-cultured in 24-well plates for 4 days and Relative fold ratios of surviving cells are shown by measuring the intensities of surviving cells stained with crystal violet",
    "diseases": "tumor"
  },
  {
    "caption": "Correlation between protein expression of VGLL4 and IRF2BP2 in 6 murine tumor cell line with the indicated antibodies",
    "diseases": "tumor"
  },
  {
    "caption": "Representative immunohistochemical staining for VGLL4 and IRF2BP2 in human non-small cell lung cancer tissues. IHC score is indicated. Scale bar: 50 μm",
    "diseases": "non-small cell lung cancer tissues"
  },
  {
    "caption": "Staining of VGLL4 and IRF2BP2 on human non-small cell lung cancer tissue arrays  containing 71 samples was quantified as described in the Materials and Methods section. Correlation of VGLL4 and IRF2BP2 expressions was significant (Pearson correlation test; R = 0.6341, P < 0.001) Correlation analysis of VGLL4 and PD-L1 expression on human non-small cell lung cancer tissue arrays containing 71 samples",
    "diseases": "non-small cell lung cancer, lung cancer"
  },
  {
    "caption": "Kaplan-Meier survival analysis of patients with high (n=74) or low (n=130) VGLL4 mRNA levels from GSE31210, a lung cancer data set. Survival curves are calculated according to the Kaplan-Meier method",
    "diseases": "lung cancer"
  },
  {
    "caption": "D The social avoidance behavior for the stressed mice after knocking down CD39 (n = 15, 15, 14 mice. Interaction F2, 41 = 17.96, P < 0.0001; Target F1, 41 = 3.75e-005, P = 0.9951; Drug F2, 41 = 6.099, P = 0.0048; For Target CSDS - LV-GFP vs Ctrl - LV-GFP, P < 0.0001; CSDS - LV-siCD39 vs CSDS - LV-GFP, P < 0.0001. Two-way ANOVA with Tukey's post-test).",
    "diseases": "CSDS"
  },
  {
    "caption": "B. Neutrophil  gene signature comparing human skin  day 3 wounds  to human DFUs  demonstrating decreased presence of neutrophils  in human DFUs.",
    "diseases": "DFUs, wounds"
  },
  {
    "caption": "C. qPCR  validations of neutrophil  genes. n=7 DFUs  and n=3 Skin  D3 wounds. **P < 0.01 (two-tailed unpaired Student's t-test). Data presented as mean ± SD.",
    "diseases": "DFUs, wounds"
  },
  {
    "caption": "A. Upstream regulators found to be activated in human skin wounds  that are suppressed or partially regulated in human DFUs  involved in neutrophil  response.",
    "diseases": "DFUs, wounds"
  },
  {
    "caption": "A. Representative images of wounded skin  after topical treatment with either vehicle (IgG isotype control) or ⍺-TREM1 activator at 0, 2, 4, 6, and 8 days after wounding. Percent of wound  area at each time  following vehicle or ⍺-TREM1  activator treatment relative to the original wound  area. Quantification of wound areas in n = 10 for vehicle diabetic  and 12 wounds  for ⍺-TREM1  treated wounds  were performed with Fiji software. Data presented as mean ± SD. **P < 0.01, and ****P < 0.0001 (two-way ANOVA followed by Tukey's post-hoc test).",
    "diseases": "diabetic, wound, wounds"
  },
  {
    "caption": "B. Representative pictures of vehicle (IgG isotype control) and ⍺-TREM1  treated diabetic wounds   at day 4 show basal keratin   marker K5, and neutrophil  marker Ly6G, FOXM1   and  citH3. Treatment of wounds  with ⍺-TREM1   resulted in increased FOXM1+ and decreased citH3+ neutrophils  compared to vehicle treated diabetic wounds. (Scale bar: 50µm). Quantification of mean fluorescence intensity was performed with Fiji software. n= 7 diabetic  vehicle wounds  and 6 diabetic  ⍺-TREM1 wounds. Data presented as mean ± SD. *P < 0.05, *P < 0.05, and **P < 0.01 (two-tailed unpaired Student's t-test).",
    "diseases": "diabetic wounds, diabetic, wounds"
  },
  {
    "caption": "A. qPCR  of TREM1  and genes involved in neutrophil  recruitment demonstrate increased expression  in healing DFUs  compared to nonhealing DFUs  (n = 5 healing   and n= 6 nonhealing). Data presented as mean ± SD. *P < 0.05. **P < 0.01 (two-tailed unpaired Student's t-test).",
    "diseases": "DFUs"
  },
  {
    "caption": "B. Representative images of healing   and nonhealing DFUs  show basal keratin   marker K5  and TREM1  and corresponding quantification from healing  (n=4) and nonhealing  (n=4) is shown in the graph. Data presented as mean ± SEM. *P < 0.05 (two-tailed unpaired Student's t-test). (Scale bar: 50µm).",
    "diseases": "DFUs"
  },
  {
    "caption": "C. Representative images of cit-H3 immunohistochemistry  show increase staining  in nonhealing DFUs  when compared to healing DFUs, which was confirmed by corresponding quantification from healing  (n=3) and nonhealing  (n=3), shown in the graph. Data presented as mean ± SD. *P < 0.05 (two-tailed unpaired Student's t-test). (Scale bar: 50µm).",
    "diseases": "DFUs"
  },
  {
    "caption": "(F) qRT-PCR analysis of hypertrophy-related genes in left ventricles. n=9:9:11:8.",
    "diseases": "hypertrophy"
  },
  {
    "caption": "(A) Representative images of hearts from LC or CMNKO mice subjected to sham operation or AAC for 2 weeks. Scale bar: 0.5cm.",
    "diseases": "AAC"
  },
  {
    "caption": "(B) VW/BW of LC or CMNKO mice 2 weeks after sham operation or AAC. n=9:9:16:15.",
    "diseases": "AAC"
  },
  {
    "caption": "(F) qRT-PCR analysis of hypertrophy-related genes in left ventricles. n=8:7:15:15.",
    "diseases": "hypertrophy"
  },
  {
    "caption": "(H) Quantification of fibrotic areas. n=11:10:10:9.",
    "diseases": "fibrotic"
  },
  {
    "caption": "(I) qRT-PCR analysis of fibrosis-related genes in left ventricles. n=8:7:15:15.",
    "diseases": "fibrosis"
  },
  {
    "caption": "(L) Lung weight to body weight ratio (LW/BW) of LC or CMNKO mice 2 weeks after sham operation or AAC. n=8:7:16:15.",
    "diseases": "AAC"
  },
  {
    "caption": "(M) Cumulative survival rate of LC or CMNKO mice subjected to AAC. n=12:10. Two-way ANOVA followed by Bonferoni post-tests was used for statistical analysis.",
    "diseases": "AAC"
  },
  {
    "caption": "(B) VW/BW of mice 2 weeks after sham operation or AAC. n=7:7:12:12.",
    "diseases": "AAC"
  },
  {
    "caption": "(F) qRT-PCR analysis of hypertrophy-related genes in left ventricles. n=8:8:11:11.",
    "diseases": "hypertrophy"
  },
  {
    "caption": "(H) Quantification of fibrotic areas. n=5:5:7:7.",
    "diseases": "fibrotic"
  },
  {
    "caption": "(I) qRT-PCR analysis of fibrosis-related genes in left ventricles. n=8:8:11:11.",
    "diseases": "fibrosis"
  },
  {
    "caption": "(J) Ejection fraction measured before, 2 weeks and 4 weeks after AAC. n=6:6. Two-way ANOVA followed by Bonferoni post-tests was used for statistical analysis.",
    "diseases": "AAC"
  },
  {
    "caption": "(K) Fractional shortening measured before, 2 weeks and 4 weeks after AAC. n=6:6. Two-way ANOVA followed by Bonferoni post-tests was used for statistical analysis.",
    "diseases": "AAC"
  },
  {
    "caption": "D Immunohistochemistry of 10-12 month old end-stage SCA8 BAC mice brain tissue shows accumulation of novel polySer RAN protein (detected by unique antibody to the polySer protein C-terminus, α-SerCT) in cerebellar white matter, brainstem, hippocampus and layer II of the frontal cortex. Representative polySer aggregates are indicated by black arrows. No aggregates are found in age matched non-transgenic (NT) littermates (n=6 for each cohort).",
    "diseases": "SCA8"
  },
  {
    "caption": "F Immunohistochemistry of human SCA8 autopsy tissue (n=4-7) shows accumulation of novel polySer RAN protein in cerebellar white matter, brainstem and frontal cortex.",
    "diseases": "SCA8"
  },
  {
    "caption": "A Immunohistochemistry (IHC) of end-stage SCA8 BAC mouse cerebellum shows that polySer but not polyGln is found in the molecular layer and cerebellar white matter and that polyGln but not polySer accumulates in Purkinje cells. Representative polySer aggregates are indicated by black arrows. Inset: higher magnification of molecular layer and white matter.",
    "diseases": "SCA8"
  },
  {
    "caption": "B IF double staining shows no co-localization of polyGln and polySer in frontal cortex, pons or hippocampus of end-stage SCA8 BAC mice.",
    "diseases": "SCA8"
  },
  {
    "caption": "C IF double staining of end-stage SCA8 BAC frontal cortex shows exclusive localization of polyGln (mouse α-Gln, red, bottom panel) in neurons (rabbit α-NeuN, green, bottom panel). In contrast, polySer (Rabbit α-SerCT, red, top panel) shows widespread accumulation in the frontal cortex including within neurons (mouse α-NeuN, green, top panel).",
    "diseases": "SCA8"
  },
  {
    "caption": "D IHC of SCA8 human cerebellum shows that PolySer accumulates in the white matter but not in the Purkinje cells (left panels) while polyGln accumulates in Purkinje cells but not cerebellar white matter (right panels).",
    "diseases": "SCA8"
  },
  {
    "caption": "A Representative images of the vestibular nucleus (upper panels), cuneate nucleus (middle panels) and motor cortex layers II/III (lower panels) of SCA8 BAC mice at 2 months (left panels), 6 months (middle panels) and end-stage (10 months, right panels) stained with α-SerCT. Representative aggregates are indicated by black arrows. Corresponding quantifications of polySer aggregates for each region on the right (n=3; mean ± SEM; One-way ANOVA with Tukey's post-hoc test; * p<0.025, ** p<0.005, *** p<0.0005, **** p<0.0001)",
    "diseases": "SCA8"
  },
  {
    "caption": "B Open field analysis of 2 month old animals show a significant decrease in ambulatory distance (cm) and ambulatory time (s) and a significant increase in resting time (s) (NT n=19, SCA8 BAC n=23, ** p<0.01, *** p<0.001; mean ± SEM; unpaired t test).",
    "diseases": "SCA8"
  },
  {
    "caption": "A Disease-specific sensitivity to vacuolization after prolonged storage in ethanol shown by H&E in cerebellar white matter and brainstem of 10-12 month old end-stage SCA8 BAC mice but not in age matched NT (n=3) (panels 1&2). Demyelination shown by luxol fast blue staining (LFB) (panel 3) and axonal degeneration shown by α-SMI-32 (panel 4; degenerated axons are indicated by black arrows) observed in sites of polySer accumulation shown by α-SerCT (panel 5; representative aggregates are indicated by black arrows) in deep cerebellar white matter and brainstem in SCA8 BAC mice (lower panels) but not in NT mice (upper panels) (n=3).",
    "diseases": "SCA8"
  },
  {
    "caption": "Demyelination shown by luxol fast blue staining (LFB) (panel 1) and axonal degeneration shown by α-SMI-32 (panel 2) observed sites of polySer accumulation shown by a-SerCT2 (panel 3) in deep cerebellar white matter was found in SCA8 autopsy tissue but not in control brains (n=3).",
    "diseases": "SCA8"
  },
  {
    "caption": "C Immunohistochemistry using CC1 (α- APC) antibody shows significantly lower numbers of mature oligodendrocytes in SCA8 BAC mice compared to NT mice (NT n=5, SCA8 BAC n=5; **** p<0.0001; mean ± SEM; unpaired t test).",
    "diseases": "SCA8"
  },
  {
    "caption": "D Immunofluorescence using α-GFAP antibody shows significant increase in astrogliosis in SCA8 BAC mice compared to NT mice (NT n=3, SCA8 BAC n=3, ** p<0.01; mean ± SEM; unpaired t test).",
    "diseases": "SCA8"
  },
  {
    "caption": "qRT-PCR showing Eif3f expression levels are increased 2-fold in SCA8 cerebellar white matter compared to SCA8 cerebellar grey matter (n=3, **p<0.01; mean ± SEM; unpaired t test).",
    "diseases": "SCA8"
  },
  {
    "caption": "(G) In vivo imaging using IVIS spectrum-chromatography CT system. Intraperitoneal administration of rRv2626c-CA/Cy5.5 was carried out at intervals of 0, 6, 12, and 18 h in a CLP-induced sepsis model. Pharmacokinetics and biodistribution were observed in spleen, liver, lung, and kidney tissues.",
    "diseases": "sepsis"
  },
  {
    "caption": "(H) The percentage of F4/80+ macrophages cells and rRv2626c-CA-His were found in the spleen, liver and lung using Fluorescence-activated cell sorting analysis in the background of CLP-induced sepsis.",
    "diseases": "sepsis"
  },
  {
    "caption": "(B) The percentage of F4/80+ macrophages cells and rRv2626c-CA-His or its mutants were found in the spleen or lung using Fluorescence-activated cell sorting analysis in the background of CLP-induced sepsis.",
    "diseases": "sepsis"
  },
  {
    "caption": "TMZ induction of phospho-eIF2α and ATF6-p90 expression. Human glioblastoma cells transduced with RGD4C/AAVP-Grp78 were analyzed by Western blot following treatment with TMZ (100 μM for LN229 and SNB19, 60 μM for U87). GAPDH was used as a control.",
    "diseases": "glioblastoma"
  },
  {
    "caption": "RT-PCR analysis of constitutive expression and splicing of XBP1 in glioblastoma cells transduced with RGD4C/AAVP-Grp78, in the presence of TMZ. Sizes of the PCR products were 289 bp for unspliced XBP1 and 263 bp for spliced XBP1, the lower size band is not specific. Time points were selected among those tested in the Western blot in (A), subsequently the image containing 0, 1 and 2 hours was juxtaposed to images of 6, 12 and 24 hours. A white line has been added between the gel pieces that have been juxtaposed.",
    "diseases": "glioblastoma"
  },
  {
    "caption": "Tumor cell killing in vitro by the HSVtk/GCV approach. Glioblastoma cells stably transduced with RGD4C/AAVP-Grp78-HSVtk or RGD4C/AAVP-CMV-HSVtk were treated with either GCV (10 μM) or TMZ (100 μM for LN229 and SNB19, 60 μM for U87) or combination of both GCV and TMZ. Cells were stained with MitoSOX and analyzed by FACS at day 4 post-treatment. Data shown are representative of three experiments, n=3. Two-way ANOVA with Tukey's multiple comparison test (GraphPad Prism 6) was used for data analysis.",
    "diseases": "Glioblastoma"
  },
  {
    "caption": "Immuofluorescent staining for αv integrin expression in brain sections including intracranial tumor (T) and the surrounding healthy brain (B). Scale bar, 100μm.",
    "diseases": "intracranial tumor"
  },
  {
    "caption": "Quantification of the relative homing ability of RGD4C/AAVP-Grp78-HSVtk to brain tumors, brain tissue and pancreas after intravenous administration. The data were normalized both to non-targeted vector and to tissue weight then expressed as relative TU. Data shown are representative of two experiments, n=5. One-way ANOVA with Tukey's multiple comparison test (GraphPad Prism 6) was used for data analysis.",
    "diseases": "brain tumors"
  },
  {
    "caption": "Average tumor Luc activity showing glioblastoma progression in each experimental group. Pre-treatment day 9 was set at 100%. Data shown are representative of two experiments, n=5.",
    "diseases": "glioblastoma"
  },
  {
    "caption": "Immunofluorescent staining for αv, β3 or β5 integrins in primary HSJD-GBM-001 and G26 GBM cells.",
    "diseases": "GBM"
  },
  {
    "caption": "Analysis RAB2A expression was performed on the Invasive Breast Cancer Consecutive Cohort (n = 622) operated in the European Institute of Oncology, Milano, Italy, in the year 2000. Expression was measured by IHC on TMA.(a) Images are representative of RAB2A expression scoring according to intensity staining in TMA. In tumor tissues the IHC signals were associated with the tumor cell component and not with the adjacent or infiltrating stroma.",
    "diseases": "tumor"
  },
  {
    "caption": "Analysis RAB2A expression was performed on the Invasive Breast Cancer Consecutive Cohort (n = 622) operated in the European Institute of Oncology, Milano, Italy, in the year 2000. Expression was measured by IHC on TMA.(b) Correlation of RAB2A expression with clinicopathological parameters. Only for 520 of 622 samples expression data for RAB2A was available. Note that the number of scored cases is lower than the total number of cases since: i) in some cases, individual cores detached from the slides during the manipulations; ii) clinical information was not available for all patients. In tumor tissues the IHC signal was associated with the tumor cell component and not with the adjacent or infiltrating stroma.",
    "diseases": "tumor"
  },
  {
    "caption": "Representative images showing tumorigenesis (red circle area) of hOSE-YAPS127A cells with or without pRB knockdown or LATS2 deletion. Tumors formed by hOSE-YAPS127A cells with RB1 knockdown or LATS2 deletion are shown in red circle area. Right panel showing representative tumors formed by hOSE-YAPS127A-LATS2KO and hOSE-YAPS127A-shRB1 cells. Please note that no tumor xenografts formed in hOSE-YAPS127A alone group.",
    "diseases": "tumor, tumorigenesis, Tumors, tumors"
  },
  {
    "caption": "Representative images showing expression of YAP, Ki67 and LATS2 in hOSE-LATS2KO-YAPS127A cell-derived tumors examined by immunohistochemistry.",
    "diseases": "tumors"
  },
  {
    "caption": "(A) Picrosirius red (PSR) staining of collagens (red) in PDAC tissue following surgical resection. Scale bar represents 200 µm. (B) Quantification of PSR in low-grade (1-2) and high-grade (3) tumors indicated in panel A as percentage of area. n=15 primary PDAC samples. Data information: data are represented as mean±SD, Student's t-test.",
    "diseases": "PDAC"
  },
  {
    "caption": "(C) Quantification of tumor cell percentage as scored by pathologists in low- and high-grade PDAC indicated in panel A. n=15 primary PDAC samples. Data information: data are represented as mean±SD, Student's t-test.",
    "diseases": "PDAC"
  },
  {
    "caption": "(D) PSR and α-SMA staining of indicated PDAC cell lines which were injected in NSG mice. Scale bar represents 200 µm for PSR and 100 µm for α-SMA images. (E) Quantification of stainings indicated in panel D. Three tumor ROIs of a tumor derived from epithelial cell lines (Capan-2 and AsPC-1) and mesenchymal cell lines (MIA PaCa-2 and PANC-1) are displayed and averages were pooled for analysis. Data information: data are represented as mean±SD, Student's t-test.",
    "diseases": "PDAC"
  },
  {
    "caption": "(F) IHC staining of α-SMA in 3D organotypic co-cultures of PS-1 cells and indicated PDAC cell lines. Scale bar represents 100 µm.",
    "diseases": "PDAC"
  },
  {
    "caption": "(A) Gene expression level of stromal activation markers COL1A1, ACTA2, SPARC, FN1 and FAP in PS-1 cells which were exposed for 72 hrs to CM from control (CM of PS-1 cells ), epithelial (blue) or mesenchymal (red) PDAC cell lines using qPCR. Values were normalized to control and n=6 per group, 3 biological replicates for each cell line. Data information: data are represented as mean±SD, Student's t-test.",
    "diseases": "PDAC"
  },
  {
    "caption": "(B) Heatmap representation of COL1A1 and ACTA2 relative gene expression levels measured with qPCR in PS-1 cells after treatment using a large cohort of PDAC cell lines and primary cell cultures 67 and 53m. Values were Log2 transformed and normalized to Suit-2 expression. Data information: data are represented as mean±SD, Student's t-test.",
    "diseases": "PDAC"
  },
  {
    "caption": "(E) Brightfield images of primary human CAFs exposed to 72 hrs of treatment with CM from control (CM of primary CAFs) or mesenchymal PDAC cell lines. Scale bar represents 100 µm.",
    "diseases": "PDAC"
  },
  {
    "caption": "(C) Graphical representation of 64 cyto- and chemokines present in CM of epithelial and mesenchymal PDAC cell lines using forward-phase protein array. Significantly differential expression of proteins (triangles) and genes (green triangles) are identified between epithelial and mesenchymal cell lines. Dotted line indicates P=0.05. Data information: data are represented as mean±SD, Student's t-test.",
    "diseases": "PDAC"
  },
  {
    "caption": "(D) Brightfield images of PS-1 cells after 72 hrs of treatment with CM of control (CM of PS-1s) or epithelial PDAC cells supplemented with recombinant human CSF-1. Scale bar represents 100 µm.",
    "diseases": "PDAC"
  },
  {
    "caption": "(A) Brightfield images of PS-1 cells after 72 hrs of treatment with CM of control (CM of PS-1s) or mesenchymal PDAC cell lines supplemented with anti-CSF-1. Scale bar represents 100 µm.",
    "diseases": "PDAC"
  },
  {
    "caption": "(A) IHC staining of CSF-1 in PDAC tissue following surgical resection representative image of CSF-1 expression in grade 1 and grade 3 PDAC is depicted. Scale bar represents 100 µm. (B) For each tumor of panel A, CSF-1 expression in ductal adenocarcinoma cells was quantified. Student's t-test. Shown is mean±SD. n=15 primary PDAC samples.",
    "diseases": "adenocarcinoma, PDAC"
  },
  {
    "caption": "(C) A validation cohort of PDAC patients (n=21) that underwent direct resection was stained for CSF-1 (scale bar represents 100 µm), PSR (scale bar represents 500 µm) and α-SMA (scale bar represents 200 µm). OK8 is low in CSF-1 expression and high in PSR and α-SMA expression, while the opposite accounts for OK7. (D) Correlation of % of PSR in the tumor and CSF-1 expressing tumor cells, as indicated in panel C. R2 and P-value were analyzed with linear regression. n=21 primary PDAC samples (E) Correlation of % of α-SMA in the tumor and CSF-1 expressing tumor cells, as indicated in panel C, R2 and P-value were analyzed with linear regression. n=21 primary PDAC samples ",
    "diseases": "PDAC"
  },
  {
    "caption": "mRNA expression of ANG in colonic tissues from normal controls (n = 25) and UC (n = 27) or CD (n = 46) patients.",
    "diseases": "CD, UC"
  },
  {
    "caption": "Representative western blotting of ANG in colonic tissues from normal controls and UC or CD patients.",
    "diseases": "CD, UC"
  },
  {
    "caption": "Representative images showing ANG immunohistochemical (IHC) staining in normal control and UC or CD sample.",
    "diseases": "CD, UC"
  },
  {
    "caption": "Corresponding statistical analysis of ANG expression score in normal controls (n = 10) and UC (n = 10) or CD (n = 15) patients.",
    "diseases": "CD, UC"
  },
  {
    "caption": "Representative images showing hematoxylin-eosin (HE) staining and ANG IHC staining in mild and severe IBD samples.",
    "diseases": "IBD"
  },
  {
    "caption": "Statistical analyses of ANG expression scores in mild (n = 18) and severe (n = 19) UC (F) or mild (n = 20) and severe (n = 20) CD (G) patients.",
    "diseases": "CD, UC"
  },
  {
    "caption": "Colon length of colonic section from these chimera colitis mice on day 8 with (n = 7) or without (n = 5) 2.5% DSS treatment.",
    "diseases": "colitis"
  },
  {
    "caption": "serum FITC-Dextran level, of colonic section from these chimera colitis mice on day 8 with (n = 7) or without (n = 5) 2.5% DSS treatment.",
    "diseases": "colitis"
  },
  {
    "caption": "representative HE staining image, and (F) histopathological score of colonic section from these chimera colitis mice on day 8 with (n = 7) or without (n = 5) 2.5% DSS treatment.",
    "diseases": "colitis"
  },
  {
    "caption": "Representative images showing cleaved-caspase 3 staining in colonic section from WT or Ang-/- colitis mice (n = 3) at indicated time point; arrows indicate cleaved-caspase 3 positive cells; two fields per colon section are quantified.",
    "diseases": "colitis"
  },
  {
    "caption": "the number of apoptotic cells in colonic section from WT or Ang-/- colitis mice (n = 3) at indicated time point",
    "diseases": "colitis"
  },
  {
    "caption": "Cell apoptotic status of IECs from WT or Ang-/- colitis mice (n = 5) on day 4.",
    "diseases": "colitis"
  },
  {
    "caption": "Cell apoptotic status of IECs from WT or Ang-/- colitis mice (n = 5) on day 4.",
    "diseases": "colitis"
  },
  {
    "caption": "Representative images showing Ki67 staining in colonic section from WT or Ang-/- colitis mice (n = 3) at indicated time point; five representative crypts per colon section are quantified.",
    "diseases": "colitis"
  },
  {
    "caption": "the number of proliferating cells per crypt in colonic section from WT or Ang-/- colitis mice (n = 3) at indicated time point; five representative crypts per colon section are quantified.",
    "diseases": "colitis"
  },
  {
    "caption": "Cell-cycle status of IECs from WT or Ang-/- colitis mice (n = 5) on day 4.",
    "diseases": "colitis"
  },
  {
    "caption": "Representative images showing cleaved-caspase 3 staining in colonic section from Angfl/fl and LyzMCre;Angfl/fl, or AAV-shControl- and AAV-shPlxnb2- treated colitis mice on day 4 (n = 3); arrows indicate cleaved-caspase 3 positive cells; two fields per colon section are quantified.",
    "diseases": "colitis"
  },
  {
    "caption": "the number of apoptotic cells in colonic section from Angfl/fl and LyzMCre;Angfl/fl, or AAV-shControl- and AAV-shPlxnb2- treated colitis mice on day 4 (n = 3)",
    "diseases": "colitis"
  },
  {
    "caption": "Ki67 staining and (L) the number of proliferating cells per crypt in representative colonic section from Angfl/fl and LyzMCre;Angfl/fl, or AAV-shControl- and AAV-shPlxnb2- treated colitis mice on day 4 (n = 3); five representative crypts per colon section are quantified.",
    "diseases": "colitis"
  },
  {
    "caption": "tiRNA and 5'-tiRNAAla production in IECs isolated from WT and Ang-/- colitis mice at indicated time point.",
    "diseases": "colitis"
  },
  {
    "caption": "47S pre-rRNA transcription level in IECs from WT and Ang-/- colitis mice at indicated time point.",
    "diseases": "colitis"
  },
  {
    "caption": "Body weight loss of the pre-treated WT colitis mice (n = 8).",
    "diseases": "colitis"
  },
  {
    "caption": "DAI of the pre-treated WT colitis mice (n = 8).",
    "diseases": "colitis"
  },
  {
    "caption": "Colon length of colon section from the pre-treated WT colitis mice on day 8 (n = 8).",
    "diseases": "colitis"
  },
  {
    "caption": "serum FITC-dextran level of colon section from the pre-treated WT colitis mice on day 8 (n = 8).",
    "diseases": "colitis"
  },
  {
    "caption": "representative HE staining image, and (H) histopathological score of colon section from the pre-treated WT colitis mice on day 8 (n = 8).",
    "diseases": "colitis"
  },
  {
    "caption": "Body weight loss of the treated WT colitis mice (n = 8).",
    "diseases": "colitis"
  },
  {
    "caption": "DAI of the treated WT colitis mice (n = 8).",
    "diseases": "colitis"
  },
  {
    "caption": "Colon length of colon sections from the treated WT colitis mice on day 8 (n = 8).",
    "diseases": "colitis"
  },
  {
    "caption": "serum FITC-dextran level of colon sections from the treated WT colitis mice on day 8 (n = 8).",
    "diseases": "colitis"
  },
  {
    "caption": "representative HE staining image, and (P) histopathological score of colon sections from the treated WT colitis mice on day 8 (n = 8).",
    "diseases": "colitis"
  },
  {
    "caption": "(B) Representative time-course of 2 mmol/L phosphate on calcification of LmnaG609G/+ VSMCs (up). Calcification was visualized with Alizarin red. Representative microscopic images (10x; scale bar: 100 µm) showing calcification of treated and untreated LmnaG609G/+ VSMCs (down).",
    "diseases": "calcification, Calcification"
  },
  {
    "caption": "(G) The calcification inhibitory capacity was calculated as the difference in calcium deposition between living and fixed cells (ΔCa2+).",
    "diseases": "calcification"
  },
  {
    "caption": "(E and F) Ki67 staining showing the proliferative potential of cluster C1 (CCNE2+) and cluster C2 (CCNB2+) cells in xenografts (E) and clinical CRC tissues (F). Scale bar, 60 μm. Quantification of the immunostaining for (F) shown on the right. Error bars represent SEM of five fields in each section. P-value was calculated based on two-tailed Student's t-test. ns (p>0.05), no significant.",
    "diseases": "CRC"
  },
  {
    "caption": "(K) Left: Representative H&E images of liver tissue sections and quantification (number of mice with liver metastasis) showing the metastatic potential of cluster C4 cells (PLAUR+). AP20187 was applied to ablate cluster C4. Yellow arrows indicate liver metastasis. Scale bars, left, 2 mm; right, 50 μm. Right: Quantification of liver metastasis in mice with intrasplenic injection. Error bars denote mean ± SEM of three mice per group. P-value was calculated based on Student's t-test. ***, p<0.001.",
    "diseases": "liver metastasis"
  },
  {
    "caption": "(G) Representative immunohistochemistry images for the expression of PLAUR (cluster C4 maker gene) in primary CRC tumors and liver metastasis from CRC patients. Scale bar, 200 μm.",
    "diseases": "CRC, liver metastasis"
  },
  {
    "caption": "(H and I) Representative immunohistochemistry images for ATF6 expression (H) and RNA-FISH for CFAP54 expression (I) in paired CRC tissues collected from CRC patients before chemotherapy or after chemotherapy. Scale bars, left, 200 μm; right, 40 μm. Data represent the mean ± SEM. Three to five technical replicates were analyzed. P-value was calculated based on two-tailed Student's t test. *, p<0.05; **, p<0.01; ***, p<0.001.",
    "diseases": "CRC"
  },
  {
    "caption": "(J and K) Kaplan-Meier survival curves for CRC patients (n=326) with different proportions of cluster C4 (J) and cluster C3 (K). P value was calculated based on log-rank test.",
    "diseases": "CRC"
  },
  {
    "caption": "(B and C) IC50  values for MPA-response curves using cell viability assay were shown. Human AML  cell lines (with MLL-fusions: MV4;11, MOLM13, NOMO1  and THP1, without MLL-fusions: HL60, Kasumi-1, OCI-AML3 and U937), human cord blood (CB) CD34+ cells, and those expressing  MLL-AF9  (CB-MLL-AF9#1, 2, 3) or MLL-ENL  (CB#MLL-ENL-1, 2), and patient  cells with or without MLL-fusions (AML#1, 2, 3 or AML#4, 5, 6) were treated with titrating doses of MPA  (1-100 μM) for 72 hours in three technical replicates. Data information: All data are shown as mean ± SEM.",
    "diseases": "AML"
  },
  {
    "caption": "(F) Mouse bone marrow c-Kit+ cells derived from Trp53-/- mice  were transduced with MLL-AF9-GFP  and were transplanted into mice  to generate p53-deficient (p53-/-) leukemia  cells. GFP+ MLL-AF9 leukemia  cells  were collected from  bone marrows  of vehicle- or  FF-10501-01-treated wild-type and p53-/- leukemic mice. Expression levels of p53  and Tubulin  were assessed by western blotting 24 hours after the treatment.",
    "diseases": "leukemic, leukemia"
  },
  {
    "caption": "(H) Kaplan-Meier survival curves of p53-/- MLL-AF9 leukemia mice  treated with vehicle or FF-10501-01or  DS-5272 (n = 6 per group). Statistical significance was evaluated by the log-rank test (left). Frequency of GFP+ leukemia  cells in peripheral blood at day 19 (right, n = 6 per group). A two-tailed unpaired t-test was used for the comparison. Data information: All data are shown as mean ± SEM.",
    "diseases": "leukemia"
  },
  {
    "caption": "A Normal lung cells (IMR90 and MRC5) and lung cancer cells (A549 and H1975) were treated with various concentrations of PM2.5 for 24 h, and cell viability was assessed by a trypan blue assay. The values are the mean ± SD of three independent experiments.",
    "diseases": "lung cancer"
  },
  {
    "caption": "A Expression of TMPRSS2 was examined by Western blots of four lung cancer cell lines (H460, A546, H1299, and H1975) and two normal fibroblasts (MRC5 and IMR90). The results shown in (A are from one of three similar experiments. β-actin was used as the loading control.",
    "diseases": "lung cancer"
  },
  {
    "caption": "B IHC staining of TMPRSS2, IL18, and nuclear AhR in lung cancer tissues that displayed high or low expression of TMPRSS2. Scale bars, 2.5 mm (low magnification) and 100 μm (high magnification).",
    "diseases": "lung cancer"
  },
  {
    "caption": "(D) FAM134B S151 phosphorylation in cells treated with CAMK2 activator (100nM EB1089 for 1h) or/and inhibitor (10μM KN93 for 2h). 293T or SKN-SH (a cell line derived from neuroblastoma) cells were treated with drugs as indicated, whole cell lysates were analyzed by phospho-FAM134B (S151) antibody.",
    "diseases": "neuroblastoma"
  },
  {
    "caption": "Immunolabeling of phosphorylated Tau (PHF1=pS396/404, AT8=pS199/pS202/pT205, AT180=pT231) in AD brain section. Both 3,3′-Diaminobenzidine (DAB) and fluorescence labeling show Tau accumulating in a layer at the nuclear envelope  (NE) in non-tangle neurons with or without cytosolic (CYT) Tau accumulations. Control brain does not show Tau labeling in neuronal cell bodies. Scale bars= 20 and 10 μm, as indicated.",
    "diseases": "AD"
  },
  {
    "caption": "A, Tumor growth [(A), (Vehicle, n = 5; DSF, n = 4, one tumor had disappeared)] (n = 10 mice  per group)] in DSF  (suspended in 0.5% NaCMC)- and Vehicle (equal volume of 0.5% NaCMC)-treated mice  after B16F10 melanoma  inoculation. Data information: , data are representative of 3 independent experiments, ns, not significant two-way ANOVA in (A)",
    "diseases": "melanoma"
  },
  {
    "caption": "survival curves  [(C), (n = 10 mice  per group)] in DSF  (suspended in 0.5% NaCMC)- and Vehicle (equal volume of 0.5% NaCMC)-treated mice  after B16F10 melanoma  inoculation. Data information: data are representative of 3 independent experiments, mean ± SD. * ns, not significant [ , log-rank (Mantel-Cox) test in (C)",
    "diseases": "melanoma"
  },
  {
    "caption": "D - Phenotypic analysis of tumor-infiltrating  T cells at day 21 after melanoma inoculation (Vehicle, n = 5; DSF, n = 4, one tumor had disappeared). Data information: , data are representative of 3 independent experiments, mean ± SD. *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001. ns, not significant [multiple t tests between the two groups in (D)",
    "diseases": "melanoma"
  },
  {
    "caption": "immunofluorescence  (E) analysis of tumor-infiltrating  T cells at day 21 after melanoma  inoculation (Vehicle, n = 5; DSF, n = 4, one tumor had disappeared). Scale bars, 20 µm. Statistics data are from 40× field of view.",
    "diseases": "melanoma"
  },
  {
    "caption": "F Phenotypic analysis of tumor-infiltrating  T cells  at day 21 after melanoma  inoculation (Vehicle, n = 5; DSF, n = 4, one tumor had disappeared). Data information: data are representative of 3 independent experiments, mean ± SD.",
    "diseases": "melanoma"
  },
  {
    "caption": "G Phenotypic analysis of IFNγ  and TNFα  production in  T cells isolated from draining lymph nodes at day 19 after melanoma  inoculation (n = 3). Data information: data are representative of 3 independent experiments, mean ± SD. *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001. ns, not significant [multiple t tests between the two groups in (G)",
    "diseases": "melanoma"
  },
  {
    "caption": "H, I Tumor growth [(H), (n = 5 mice  per group)] and  survival curves [(I), (n = 5 mice  per group)] in Vehicle- and DSF-treated mice  injected s.c. with B16F10-melanoma  cells followed by intraperitoneal (i.p.) injection with PD-1  antibody on days 0 and 4 and then every third day (n = 5). Data information: data are representative of 3 independent experiments, mean ± SD. ns, not significant two-way ANOVA in (H), log-rank (Mantel-Cox) test in (I)].",
    "diseases": "melanoma"
  },
  {
    "caption": "A Tumor growth in Vehicle- and DSF-treated mice  injected s.c. with B16F10 melanoma  cells followed by intraperitoneal (i.p.) injection with CD8(2A3) antibody on days −1, 0, and 2 and then every second day (n = 5). Data information: data are representative of 3 independent experiments, mean ± SD. ns, not significant [two-way ANOVA in (A)",
    "diseases": "melanoma"
  },
  {
    "caption": " (A-D) Serum NfL concentrations of preataxic (green) and ataxic (red) SCA3 subjects and controls (blue) were measured in two independent cohorts, each with a different Simoa approach: cohort #1, recruited by the ESMI consortium (A, C), and cohort #2, recruited by the EuroSCA/RiSCA consortium (B, D). Boxes show the ranges between lower and upper quartiles, the central bands show the medians, and the whiskers show data within 1.5∙IQR of the median, with dots representing outliers. Groups were compared with Mann Whitney U tests (*** p<.001, ** p<.01, ns p≥.05, two-tailed, Bonferroni-corrected; In the scatter plots, the individual NfL values were plotted as a function of subjects' age. The dashed grey lines visualise the optimal cut-offs for differentiating ataxic SCA3 subjects from controls in each cohort (cohort #1: 20.0 pg/ml, 98.7% sensitivity, 92.2% specificity; cohort #2: 50.9 pg/ml, 92.6% sensitivity, 100% specificity; cut-offs were derived by maximising Youden's index irrespective of age). Note the logarithmic scale of the y-axes. ",
    "diseases": "ataxic, preataxic, SCA3"
  },
  {
    "caption": " (E, F) Serum pNfH levels of preataxic and ataxic SCA3 subjects and controls were also measured in both cohorts, each with a different Simoa approach (two-tailed Mann Whitney U tests, Bonferroni-corrected; ",
    "diseases": "ataxic, preataxic, SCA3"
  },
  {
    "caption": " (A) Serum NfL levels of ataxic SCA3 subjects significantly correlated with disease severity, as quantified by the Scale for the Rating and Assessment of Ataxia (SARA) score (r=0.43, p<.001, Pearson's correlation, two-tailed test). ",
    "diseases": "Ataxia, ataxic, SCA3"
  },
  {
    "caption": "(C) We modelled serum NfL levels (log-transformed) in SCA3 carriers (n=123) with the predictors age and ATXN3 CAG repeat length, their squares and all possible interactions (for details, see Results and Methods). The highly significant predictors (age, its square, and repeat length, and the intercept, all p<.001, explained variance: R2=0.37) were used to generate the diagram. For a given age, each increase in CAG repeat count was associated with higher NfL concentrations. The steepness of the slopes declined with increasing age. In controls (black, n=125), the relation between NfL level (log-transformed) and age was linear.",
    "diseases": "SCA3"
  },
  {
    "caption": " (A) Serum NfL levels in preataxic SCA3 subjects (cross-sectional data) were plotted over the time from the individually estimated ataxia onset. NfL levels increased significantly with proximity to the estimated onset (F(1,21)=39.68, p<.001, R2=0.64). For benchmarking the levels of preataxic subjects, the blue dashed line visualises the optimal cut-off for differentiating ataxic SCA3 subjects from controls in the pooled cohort (20.3 pg/ml, 99.0% sensitivity, 95.2% specificity). ",
    "diseases": "ataxia, ataxic, preataxic, SCA3"
  },
  {
    "caption": " (B) To determine the time at which NfL levels become significantly increased in the preataxic stage of SCA3, NfL levels of preataxic carriers need to be related to NfL levels of controls at the same age, as NfL levels physiologically increase with age. For each preataxic subject, the difference between the measured NfL value (green dot) and the NfL value predicted for control subjects of the same age (solid blue line) was visualised by the length of the vertical green line. Standardisation of this difference relative to the NfL distribution in controls ",
    "diseases": "preataxic, SCA3"
  },
  {
    "caption": " (C) In preataxic SCA3 subjects, NfL z-scores increased significantly (F(1,21)=30.78, p<.001, R2=0.58) with subjects approaching the expected age of onset. NfL levels of preataxic subjects were significantly increased compared to controls (i.e. z-score >1.96) 7.5 years before the expected onset, indicated by the non-overlapping 95% confidence intervals of SCA3 subjects (black solid line) and controls (blue dashed line). ",
    "diseases": "preataxic, SCA3"
  },
  {
    "caption": " (A, B) Longitudinal intraindividual stability of NfL (A) and pNfH (B) serum levels over 6 weeks, assessed in both ataxic (red) and preataxic (green) SCA3 and control (blue) subjects (n=21). Data of the same individuals are linked by lines. ICC, intraclass correlation coefficient (estimate and 95% CI). ",
    "diseases": "ataxic, preataxic, SCA3"
  },
  {
    "caption": "(C) Sample size estimations were performed for future intervention trials using the reduction of Nf levels towards control levels as outcome measure. The estimated number of subjects per study arm is plotted over the assumed therapeutic effect for lowering the Nf level in SCA3 subjects to levels observed in healthy controls (NfL: dashed line, pNfH: dotted line).",
    "diseases": "SCA3"
  },
  {
    "caption": "(A-B) Plasma concentrations of NfL (A) and pNfH (B) were measured in the 304Q knock-in SCA3 mouse model. Heterozygous animals become symptomatic at ≈8 months of age.",
    "diseases": "SCA3"
  },
  {
    "caption": " The figure shows the degree to which each variable differs between heterozygous SCA3 mice and wildtype controls for a given age. For each variable, we quantified the deviation of hetero­zygous mice from controls of the same age by calculating the effect size r of the group comparison (independent t-tests). An effect size of 0 indicates that the value in heterozygous mice is not different from controls, while an effect size of 1 would indicate strong abnormality. Note that the drop in the effect size of Nf levels from 12 months to 18 months thus does not imply a putative reduction of Nf levels, but rather the loss of the effect in mutants relative to controls, as controls show strong age-related Nf increases at 18 months of age. Negative effect size values were set to 0. ",
    "diseases": "SCA3"
  },
  {
    "caption": " (A) We assessed samples of cerebellar cortex, deep cerebellar nuclei, frontal cortex, pons and pyramidal tract by immunohistochemistry with ataxin-3 staining, comparing heterozygous 304Q SCA3 mice at 2, 6, 12 and 18 months of age with wildtype animals at 18 months. ML: molecular layer, PC: Purkinje cells, GL: granular layer, scale bars: 20 µm. ",
    "diseases": "SCA3"
  },
  {
    "caption": " (B) We histologically assessed the number and integrity of Purkinje cells in the cerebellar cortex by NfL, pNfH, Nissl and calbindin staining, comparing heterozygous 304Q SCA3 mice at 2, 6, 12 and 18 months of age with wildtype animals. ML: molecular layer, PC: Purkinje cells, GL: granular layer, scale bars: 20 µm. ",
    "diseases": "SCA3"
  },
  {
    "caption": "(C) Expression profile of the indicated ion channel analyzed by RT-PCR in the WM266.4 and 451Lu metastatic melanoma cell lines (middle and bottom panels, respectively). Expected amplicons sizes (positive controls in top panel) are in base pairs (bp); TRPV1=120, TRPV2=199, TRPV3=226, TRPV4=190/370, TRPV6=208, TRPC1=201, TRPC6=121, TRPM2=303, TRPM7=226, TRPA1=140, Orai1=161, STIM1=109, STIM2=114).",
    "diseases": "melanoma"
  },
  {
    "caption": "(F) TRPV2 immunoblotting in 36 out of the 60 NCI-60 cell lines. Tubulin was used as a loading control. Note that after longer exposure times, TRPV2 expression was also detected in some breast and prostate cancer cell lines, as it has been previously described (Elbaz et al, 2018; Gambade et al, 2016; Monet et al, 2010).",
    "diseases": "breast, prostate cancer"
  },
  {
    "caption": "(G) TRPV2 protein expression in melanoma cell lines harboring either B-RAF (black) or N-Ras (blue) mutations. β-Actin was used as a loading control.",
    "diseases": "melanoma"
  },
  {
    "caption": "(A) Analysis for total and plasma membrane (PM) TRPV2 expression in melanoma cell lines. β-actin was used as loading and cell integrity control. PM fractions were isolated using the surface protein biotinylation technique. The higher molecular weight bands of TRPV2 correspond to the glycosylated and mature channel",
    "diseases": "melanoma"
  },
  {
    "caption": "(C) TRPV2 overexpression in the non-invasive 501mel cell line (GFP-TRPV2) or downregulation by lentiviral-delivery of TRPV2 specific shRNAs (shRNA V2-1 and V2-2) in the WM266.4 and 451Lu metastatic melanoma cell lines assessed by western-blot. β-actin was used as a loading control.",
    "diseases": "melanoma"
  },
  {
    "caption": "(B) Representative confocal images of the in situ detection of endogenous TRPV2 interactions with paxillin and vinculin by proximity-ligation assays (PLA). Low confluency WM266.4 and 451Lu metastatic melanoma cells plated on fibronectin-coated coverslips were stained for F-actin (green), cell nuclei (blue) and PLA reaction using antibodies specific of the indicated proteins (red) (scale bar = 20 µm ; identical for all pictures). Red fluorescent spots indicate the association of the two proteins of interest, close to 40 nm. Scatter plots represent the quantification of the number of PLA spots per cell (bars indicate the medians) between TRPV2 and a control antibody (IgG), paxillin (PAX) or vinculin (VCL). (n=29-51 cells from at least three independent experiments).",
    "diseases": "melanoma"
  },
  {
    "caption": "A-D Representative bioluminescence imaging (BLI) data of mice injected intravenously with the non-metastatic melanoma cell line 501mel-Luc transfected with either GFP-TRPV2 or GFP control (A-B), or with the invasive 451Lu-Luc melanoma cell line expressing either control shRNA or TRPV2 targeting shRNA (C-D). Tumor growth and metastasis formation were monitored for 64 days (501mel-Luc) or 35 days (451Lu-Luc) after injection. Graphs presented in A and C show in vivo normalized photon flux quantification at the end time point (ns P = 0.0903 (A) and **P = 0.0064 (C), the Mann-Withney test). Graphs presented in B and D show the number of metastatic foci per animal (B) or per lungs (D) counted at necropsy (*P = 0.0397 (B) and ns P = 0.0691 (D), unpaired t-tests). For (D) Representative ex vivo BLI images of lung metastasis are shown",
    "diseases": "lung metastasis, melanoma"
  },
  {
    "caption": "(A) TRPV2 RNA expression levels (microarray probe: 219282_s_at) measured in normal skin (n=7 biological replicates), nevi (n=9 biological replicates) , primary (n=31 biological replicates) and metastatic (n=73 biological replicates) melanomas (GEO: GSE46517)(Data ref: Kwong LN, 2013). TRPV2 levels are increased in malignant lesions compared to normal skin and nevi. Data is represented as a whisker-box plot with outliers plotted as individual points (Boxes extend from the 25th to 75th percentiles, whiskers from the 10th to 90th percentiles, the horizontal line in each box is plotted at the median; ns P = 0,1383, *P = 0,0488 and **P = 0,0016, the Kruskal-Wallis test). The horizontal dotted line corresponds to TRPV2 median expression in nevi.",
    "diseases": "melanomas, nevi"
  },
  {
    "caption": "(B) Representative melanoma tissue lesions from a tissue microarray (TMA) comparing TRPV2 staining between a benign nevus and a malignant melanoma (See also appendix Fig S10) (Scale bar = 200µm). Top right insets show the same images stained with an anti-melanoma triple cocktail (HMB45+A103+T311). Regions depicted with a black line represent the interface between the diffusely stained tumor (T) and the surrounding normal stroma (S). Right panel shows the scatter plot of the complete quantification of TRPV2 staining in 77 patients with malignant melanoma compared to 16 nevi tissues (dot, single patient sample) with lines for mean ± SEM (*P = 0.0473, the Mann-Whitney test).",
    "diseases": "melanoma, nevi, nevus"
  },
  {
    "caption": "(F) Analysis of TRPV2 expression by quantitative RT-PCR (left panel) and western-blot (right panel) in the WM115/WM266.4 pair of isogenic melanoma cell lines. The WM115 cell line was derived from an in situ tumor while the WM266.4 was established from a skin metastasis of the same patient. Relative transcript levels are presented as mean ± SEM from n=4-9 biological replicates (**P = 0.0028, the Mann-Whitney test).",
    "diseases": "melanoma, skin metastasis, tumor"
  },
  {
    "caption": "(G) Kaplan-Meier plot showing the association of TRPV2 expression (10% highest versus 10% lowest expressers in the skin cutaneous melanoma cohort TCGA data set) with melanoma patient survival ((*)P = 0,0144, the Log-rank (Mantel-Cox) test).",
    "diseases": "melanoma"
  },
  {
    "caption": "(A) RT-qPCR of early passage RMS tumoroid  models shows positivity for at least one gene used in standard-of-care pathology analysis (DES, MYOG, or MYOD1). Conventional RMS  cell lines (RD  and RH30) were used as positive controls, while two  Synovial Sarcoma (SS000DAZ  and SS077) tumoroid  models were used as negative controls. Gene expression was normalized to the expression of a house-keeping gene and human  reference RNA (HREF) via the ΔΔCq method. Each tumoroid  line was measured once with four technical replicates with the error bars representing the standard deviation of said technical replicates.",
    "diseases": "RMS, Synovial Sarcoma"
  },
  {
    "caption": "(C) Morphological  (via H&E) and immunohistochemical  (IHC) comparison of RMS tumors  and derived RMS tumoroid  models shows retained marker protein (Desmin, Myogenin  and MYOD1) expression  and cellular morphology. Scale bars equal 200 µm (RMS012, RMS102) or 100 µm (RMS000HQC).",
    "diseases": "RMS"
  },
  {
    "caption": "(A)  Copy number frequency plots  of RMS tumors  (upper row) and derived RMS tumoroid  models (lower row) divided by fusion-status (columns). Chromosomes  are annotated on the x-axis from left to right while the y-axis shows the percentage of samples in this group carrying a gain (red) or loss (blue) in this genomic region.",
    "diseases": "RMS"
  },
  {
    "caption": "(C) Table depicting pathogenic single-nucleotide variants (SNVs) in RMS tumors  (T) and tumoroid  models (O). Circle color indicates SNV type while circle size indicates variant allele fraction (VAF). Vertical dotted lines separate samples derived from individual patients. Highlighted are genes previously reported for this RMS  subtype.",
    "diseases": "RMS"
  },
  {
    "caption": "(D) Correlogram of bulk mRNA sequencing expression  profiles of pediatric kidney tumors  (controls) as well as RMS tumoroid  models and RMS tumors. CCRCC  = Clear Cell Renal Cell Carcinoma, CMN  = Congenital Mesoblastic Nephroma, WT  = Wilms Tumor, Cor = correlation.",
    "diseases": "CCRCC, Clear Cell Renal Cell Carcinoma, CMN, Congenital Mesoblastic Nephroma, RMS, Wilms Tumor, WT"
  },
  {
    "caption": "(A) Clustered heatmap of viability  measurements per RMS tumoroid  model (x axis) and drug (y axis), showing the Area Under the Curve (AUC) after treatment of the cells for 120 h with a dose-range of 0.1 nM to 10 µM. Low AUC (red) indicates high drug efficacy  while high AUC (blue) indicates low drug efficacy. Annotated clusters of (1) MEK/ERK  and  γ-secretase inhibitors showing specific efficacy in RMS tumoroid  models without (RMS007, RMS012, RMS444) or low (RMS000HQC) fusion transcript expression, and (2) drugs that show broad efficacy across RMS tumoroid  models.",
    "diseases": "RMS"
  },
  {
    "caption": "(B)  Western Blot analysis of TP53  wildtype (WT) and knockout (KO) RMS  tumoroid line   RMS012. Histone 3 (H3) served as loading control.",
    "diseases": "RMS"
  },
  {
    "caption": "YTHDF1 staining in matched samples of human CRC tissue and adjacent non-tumor tissue. Scale bar, 450 μm. The right panel shows the statistics of IHC scores. Chi-square test; n = 75 for each group.",
    "diseases": "CRC"
  },
  {
    "caption": "(C) Patients suffering from major depressive disorder (MDD) show a blunted ACTH response to CRH (black line, N=10), compared with control (gray line, N=10) - data from (von Bardeleben et al, 1988), shown are mean ± SEM.",
    "diseases": "major depressive disorder, MDD"
  },
  {
    "caption": "(D) Patients suffering from anorexia and admitted to treatment show a blunted ACTH response and hypercortisolemia, which resolves within 6-24 months after weight normalization- data from (Gold et al, 1986a). However, 3-4 weeks after weight normalization, cortisol dynamics are normal whereas ACTH dynamics are blunted. Pregnancy is associated with elevated cortisol levels due to CRH secretion by the placenta. 3 weeks after delivery, cortisol levels and dynamics return to normal, whereas ACTH dynamics are blunted- data from (Magiakou et al, 1996). After 12 weeks, ACTH dynamics normalize as well, while cortisol dynamics remain normal. Individuals recovering from alcohol abuse show hypercortisolemia and blunted ACTH response after admission - data from (von Bardeleben et al, 1989). After 2-6 weeks, these individuals show normal cortisol dynamics, but blunted ACTH responses persist. In all panels, control patient data are denoted by thin gray line (Anorexia: N=13. Pregnancy: N was unspecified. Alcohol abuse disorder: N=11), and case data by a thicker black line (Anorexia: left panel, N=9, center panel, N=5, right panel, N=6. Pregnancy: N=17. Alcohol abuse disorder: N=20). Shown are mean ± SEM for all panels.",
    "diseases": "hypercortisolemia, alcohol abuse, Alcohol abuse disorder, anorexia, Anorexia"
  },
  {
    "caption": "A. Human breast cancer  cell line MDA-MB-231 shows cellular accumulation of Fn14  upon γ-secretase inhibition. The cells were treated overnight with  γ-secretase inhibitor DAPT  (1 μM), broad spectrum metalloprotease  inhibitor TAPI-1 (50 μM), or the corresponding amount of vehicle DMSO  as indicated. Lysates were blotted  for Fn14  with an antibody that targets the C-terminal end of the protein, or against calnexin  as loading control. The asterisk labels an N-terminally truncated form of Fn14. B. Quantification of blots  from panel A. The control condition, where the cells were only treated with vehicle (DMSO), was used as baseline, and its average normalized to 1. Data Information: All quantification data is shown as mean ± SEM. All the panels have N=3 biological replicates. For panels B the tested conditions were compared against control (DMSO) condition by ordinary one-way ANOVA and Dunnett's multiple comparison test. The p-values that are above 0.05 have not been included into the panels.",
    "diseases": "breast cancer"
  },
  {
    "caption": "C. Human ovarian cancer  cell line  SKOV-3 shows cellular accumulation of Fn14  upon  γ-secretase  inhibition. The cells were treated overnight with γ-secretase inhibitor DAPT  (1 μM), broad spectrum metalloprotease inhibitor TAPI-1 (50 μM), or corresponding amount of vehicle DMSO  as indicated. Lysates were blotted  for Fn14  with an antibody that targets the C-terminal end of the protein, or against calnexin  as loading control. The asterisk labels an N-terminally truncated form of Fn14. D. Quantification of blot  from panel C. The control condition, where the cells were only treated with vehicle (DMSO), was used as baseline, and its average normalized to 1. Data Information: All quantification data is shown as mean ± SEM. All the panels have N=3 biological replicates. For panels D, the tested conditions were compared against control (DMSO) condition by ordinary one-way ANOVA and Dunnett's multiple comparison test. The p-values that are above 0.05 have not been included into the panels.",
    "diseases": "ovarian cancer"
  },
  {
    "caption": "A. Cellular Fn14  in ex vivo glioblastoma  samples increased upon  γ-secretase inhibition. Primary cells from four different glioblastomas  were treated with DAPT  (1 μM) or vehicle overnight. Lysates were blotted  against Fn14  and calnexin  as loading control. B. Quantification of the blot  in panel A. For each glioblastoma, the relative (rel.) mean intensity of the normalized Fn14  vehicle condition was used for normalization. Data information: All quantification data is shown as mean ± SEM. The tested conditions were compared against their corresponding control (DMSO) condition using two-tailed unpaired t-tests. The p-values that are above 0.05 have not been included into the panels. For all the panels, three biological replicates were performed.",
    "diseases": "glioblastoma, glioblastomas"
  },
  {
    "caption": "B. Plasma  samples from 10 controls and GBM patients  with an initial diagnosis of GBM  (iGBM, 40 patients) or a recurrent GBM  (rGBM, 20 patients) were collected and sFn14  levels were measured by ELISA. Data information: For panel B median of the measurements, along with interquartile range borders are displayed. In panel B, ordinary one-way ANOVA with Tukey's multiple comparison test was applied, but no value passed our p-value display threshold of 0.05.",
    "diseases": "GBM"
  },
  {
    "caption": "C. Plasma  samples from 10 ovarian cancer patients  with low/middle and 19 patients  with high tumor burden were collected and sFn14 levels were measured by ELISA. The tumor burden was clinically determined by computer tomographic scans. Data information: For panel C, median of the measurements, along with interquartile range borders are displayed. For panel C, a two-tailed unpaired t-test was applied, but no value passed our p-value display threshold of 0.05.",
    "diseases": "ovarian cancer"
  },
  {
    "caption": "D. Serum  samples from 10 patients  with refractory   multiple myeloma were collected pre- and post-treatment  with 25 mg LY3039478  administered in 3 daily doses over 5 days. sFn14 levels in these samples are displayed (N=10). Data information: For panel D, ratio-paired t-test was used to compare the sFn14 levels pre- and post-treatment.",
    "diseases": "refractory   multiple myeloma"
  },
  {
    "caption": "(F) Assessment of the mitotic index of tumor cells by phosphorylated-histone H3 (pHH3)-positive nuclei density in KP mice LUAD tumors at 21 weeks after infection with control sgTom, sgNf1.1, sgNf1.2, or sgNf1.3 (n = 50 tumors each). For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "diseases": "LUAD"
  },
  {
    "caption": "(G) Nf1 mRNA expression in LUAD tumor sections 21 weeks after infection with control sgTom, sgNf1.1, sgNf1.2, or sgNf1.3. For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "diseases": "LUAD"
  },
  {
    "caption": "(H) Representative hematoxylin and eosin (H&E) and p-Fak1 immunohistochemical (IHC) staining of LUAD tumor sections 21 weeks after infection with control sgTom (grade 1 depicted), sgNf1.1 (grade 3 depicted), sgNf1.2 (grade 3 depicted), or sgNf1.3 (grade 3 depicted) (n = 50 tumors each). H&E scale bars (low-magnification top row = 100 μm, high-magnification bottom row = 250 μm); p-Fak1 IHC scale bars (low-magnification top row = 250 μm, high-magnification bottom row = 500 μm).",
    "diseases": "LUAD"
  },
  {
    "caption": "(I) Quantification of p-Fak1 IHC signals in LUAD tumor sections 21 weeks after infection with control sgTom, sgNf1.1, sgNf1.2, or sgNf1.3. For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "diseases": "LUAD"
  },
  {
    "caption": "(J) Quantification of p-Fak1 IHC signals in sgNf1.3 LUAD tumor sections analyzed by tumor grade. For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "diseases": "LUAD"
  },
  {
    "caption": "(K) Quantification of Psat1 mRNA expression in LUAD tumor sections 21 weeks after infection with control sgTom, sgNf1.1, sgNf1.2, or sgNf1.3. For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "diseases": "LUAD"
  },
  {
    "caption": "(L) Quantification of Psat1 mRNA expression in sgNf1.3 LUAD tumor sections analyzed by tumor grade. For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "diseases": "LUAD"
  },
  {
    "caption": "(E) Two patient-derived KRAS;NF1-mutant LUAD cell lines (PDKN1, PDKN2), as well as the control patient-derived KRAS-mutant/NF1-WT LUAD cell line (PDK), were passaged for 14 population doublings prior to collection. The heatmap displays the most significantly upregulated genes in the PDKN1 and PDKN2 cell lines (relative to the PDK control), with the degree of upregulation depicted by color as indicated in the legend.",
    "diseases": "LUAD"
  },
  {
    "caption": "(J-L) Cumulative population doublings of patient-derived KRAS-mutant LUAD cell lines that are either (J, K) NF1-mutant (PDKN1 and PDKN2) or (L) NF1-WT (PDK) after selection with sgTom- or sgPsat1-containing vectors (n = 4 biological replicates).",
    "diseases": "LUAD"
  },
  {
    "caption": "Relative responses of subcutaneous patient-derived NF1-mutant (PDKN1 and PDKN2) and NF1-WT (PDK) LUAD tumors treated with vehicle, (I) CB-839 starting from day 12 and measured until day 30 (n = 6 tumors per cell line per treatment). Relative response = average tumor volume with treatment / average tumor volume with vehicle.",
    "diseases": "LUAD"
  },
  {
    "caption": "Relative responses of subcutaneous patient-derived NF1-mutant (PDKN1 and PDKN2) and NF1-WT (PDK) LUAD tumors treated with vehicle (J) AOA starting from day 12 and measured until day 30 (n = 6 tumors per cell line per treatment). Relative response = average tumor volume with treatment / average tumor volume with vehicle.",
    "diseases": "LUAD"
  },
  {
    "caption": "Relative responses of orthotopic patient-derived NF1-mutant (PDKN1 and PDKN2) and NF1-WT (PDK) LUAD tumors treated with vehicle, (K) CB-839 starting from day 12 and measured until day 27 (n = 12 mice per cell line per treatment). Relative response = average tumor volume with treatment / average tumor volume with vehicle. Quantification of tumor growth by photon flux luminescence after orthotopic transplantation with KP or KPΔNF1 cells transduced with a luciferase vector.",
    "diseases": "LUAD"
  },
  {
    "caption": "Relative responses of orthotopic patient-derived NF1-mutant (PDKN1 and PDKN2) and NF1-WT (PDK) LUAD tumors treated with vehicle, (L) AOA starting from day 12 and measured until day 27 (n = 12 mice per cell line per treatment). Relative response = average tumor volume with treatment / average tumor volume with vehicle. Quantification of tumor growth by photon flux luminescence after orthotopic transplantation with KP or KPΔNF1 cells transduced with a luciferase vector.",
    "diseases": "LUAD"
  },
  {
    "caption": "c-n, Mice were assessed at 3 (c-h) or 5 (i-n) days post-infection for serum ALT (c,i), viral titers in liver (d,j) and spleen (e,k), and liver necrosis and inflammation (f-h, l-n).",
    "diseases": "inflammation, necrosis"
  },
  {
    "caption": "C Clustering of mitophagosomes (white arrows) co-labeled by antibodies against LC3 and Cyto c or p62 and HSP60 within swollen/dystrophic presynaptic terminals indicated by synaptophysin (SYP) surrounding amyloid plaques in AD mouse brains.",
    "diseases": "AD"
  },
  {
    "caption": "F,G Mitophagic accumulation at Aβ-enriched synapses in AD mouse brains. Note that the levels of mitophagic/autophagic proteins (red box) along with Aβ (green box) are increased in synaptic fractions isolated from AD mouse brains. Equal amounts (10 μg) of synaptosomal preparations (Syn) and post-nuclear supernatants (PNS) from WT and mutant hAPP mouse brains were sequentially immunoblotted with antibodies against hAPP/Aβ, Rheb, LC3, p62, and Rab7, as well as mitochondrial proteins TOM20 and SOD2 on the same membrane after stripping between each antibody application. The purity of synaptosomal fractions was confirmed by relative enrichment of SYP and less abundance of p115 and GAPDH (F). Relative protein levels in the synaptosomal preparations from mutant hAPP mice were compared to those in WT littermate controls. Data were quantified from five repeats (G).",
    "diseases": "AD"
  },
  {
    "caption": "H,I Representative blots (H) and quantitative analysis (I) showing increased levels of Rheb along with LC3-II, p62, and Rab7 (red box) in Mito fractions purified from AD mouse brains. The purity of Mito fractions was confirmed by enrichment of mitochondrial proteins VDAC and TOM20 and by the absence of GAPDH and p115, relative to PNS fractions. Data were quantified from four repeats.",
    "diseases": "AD"
  },
  {
    "caption": "Representative images showing increased mitochondrial association with Rheb in AD axons, relative to that of WT littermate controls. Note that CCCP treatment enhances Rheb localization to mitochondria. The percentages of white arrow-marked mitochondria that were targeted by Rheb in WT and mutant hAPP axons in the absence and presence of CCCP",
    "diseases": "AD"
  },
  {
    "caption": "C- Representative dual-channel kymographs showing defective retrograde transport and mitophagic accumulation within AD axons. mitochondria within AVs in WT or mutant hAPP axons with and without CCCP were quantified",
    "diseases": "AD"
  },
  {
    "caption": "F,G Quantitative analysis (F) and representative blots (G) showing that ∆ψm depolarization augments mitophagy activation in cortical neurons cultured from AD mouse brains. Note increased localization of Rheb along with LC3-II and Rab7 to mitochondria in mutant hAPP Tg neurons after CCCP treatment (red box). Data were quantified from three independent repeats. P: post-nuclear supernatants; M: mitochondria-enriched membrane fractions; S: cytosolic supernatants.",
    "diseases": "AD"
  },
  {
    "caption": "representative images showing abnormal accumulation of oxidatively damaged mitochondria in AD axons, which is exacerbated after dissipating ∆ψm. Mean fluorescence intensity ratios evoked by the two excitation wavelengths (405 nm and 488 nm) at individual mitochondria in mutant hAPP axons with and without CCCP treatment were quantified and normalized to those of WT controls",
    "diseases": "AD"
  },
  {
    "caption": "Representative dual-channel kymographs (A) and quantitative analysis (B showing that overexpression of Snapin, but not Snapin-L99K, a Snapin mutant deficient in dynein motor binding, reduces mitophagic accumulation within AD axons incubated with CCCP.",
    "diseases": "AD"
  },
  {
    "caption": "Representative quantitative analysis showing that overexpression of Snapin, but not Snapin-L99K, a Snapin mutant deficient in dynein motor binding, enhances retrograde transport of mitophagosomes within AD axons incubated with CCCP.",
    "diseases": "AD"
  },
  {
    "caption": "D Mean fluorescence intensity ratios evoked by 405 nm and 488 nm excitation wavelengths at individual mitochondria in mutant hAPP axons expressing Snapin or Snapin-L99K were quantified and normalized to those of mutant hAPP controls. Note that oxidatively stressed mitochondria are reduced within AD axons expressing Snapin after CCCP treatment.",
    "diseases": "AD"
  },
  {
    "caption": "A Representative images showing gene delivery into the hippocampus of AD mice injected with AAV-mCherry or AAV-mCherry-Snapin. mCherry fluorescence indicated by white arrows is present in the soma and processes of transduced neurons in the hippocampal CA3 and dentate gyrus (DG) of mutant hAPP mouse brains. NeuN, a neuronal nuclear marker, indicates neurons.",
    "diseases": "AD"
  },
  {
    "caption": "Attenuation of mitophagic accumulation in the hippocampal mossy fibers of AD mice transduced with AAV-mCherry-Snapin. Note a marked reduction of mitophagosomes (white arrows) in mutant hAPP Tg mouse brains with elevated Snapin expression Cyto c*: color is converted from blue to red for better contrast",
    "diseases": "AD"
  },
  {
    "caption": "Attenuation of mitophagic accumulation in the hippocampal mossy fibers of AD mice transduced with AAV-mCherry-Snapin. Note a marked reduction of mitophagosomes (white arrows) in mutant hAPP Tg mouse brains with elevated Snapin expression",
    "diseases": "AD"
  },
  {
    "caption": "D,E Quantitative analysis (D) and representative images (E) showing increased density of presynaptic terminals in the hippocampal mossy fibers of AD mice infected with AAV-mCherry-Snapin. Blue indicates the signal of DAPI staining. The percentage area of SYP-labeled presynaptic terminals was quantified and normalized to that of control AD mice injected with AAV-mCherry (D). Data information: Data were quantified from a total number of 40-44 imaging slice sections of three pairs of mutant hAPP Tg mice with AAV injection.",
    "diseases": "AD"
  },
  {
    "caption": "Representative immunofluorescence images of gastric units after vehicle or 72h high-dose tamoxifen (HDT) treatment stained for GIF (red, granules), GSII (green, neck cells and SPEM marker), BRDU (white, proliferation) and DAPI (blue, nuclei). Top row is wild-type, bottom row is Atf3−/−. Yellow arrowheads point to areas of base dropout where ZCs have been lost. Scale bar, 50μm. Stomach units outlined by dashed white line.",
    "diseases": "SPEM"
  },
  {
    "caption": "Serial sections of human tissue. Representative immunohistochemistry of GSII (top; spasmolytic polypeptide-expressing metaplasia [SPEM] marker and neck cells) counterstained with hematoxylin (blue) and eosin (pink). Representative staining of ATF3 (bottom) counterstained with eosin (pink). Tissue was taken from regions adjacent to gastric adenocarcinoma. Scale bars left - 50μm right - 20μm. Arrowheads indicate strongly expressing ATF3 cells and the corresponding region in the same gland labeled with GSII in a serial tissue section. GSII at the base of gastric glands in the body of the stomach indicate transition to SPEM.",
    "diseases": "spasmolytic polypeptide-expressing metaplasia, gastric adenocarcinoma, SPEM"
  },
  {
    "caption": "(A) NSCLC  PDX models treated with or without chemotherapy  for the first 2 weeks were analyzed for tumor growth at the indicated time. Mean±SEM from 6 experiments. Data information: Paired t-test with Bonferroni method. **p < 0.01, ***p < 0.001, ****p < 0.0001.",
    "diseases": "NSCLC"
  },
  {
    "caption": "(B) Frequencies of CD133-expressing CSCs  from NSCLC xenografts  treated with or without chemotherapy   were determined after 4 weeks. Mean±SEM from 6 experiments. Data information: Paired t-test with Bonferroni method. **p < 0.01, ***p < 0.001, ****p < 0.0001.",
    "diseases": "NSCLC"
  },
  {
    "caption": "(C-E) Flow cytometric analyses of protein expressions  of TLR9, activated Notch1, and phosphor-AMPKα  in cancer cells from NSCLC xenografts  treated with or without chemotherapy   after 4 weeks. Mean±SEM from 6 experiments. Data information: Paired t-test with Bonferroni method. **p < 0.01, ***p < 0.001, ****p < 0.0001.",
    "diseases": "NSCLC"
  },
  {
    "caption": "(F) NSCLC  PDX models were treated with chemotherapy  alone or together with the indicated inhibitors, respectively, for the first 2 weeks.  Tumor volume was determined at the indicated time. Mean±SEM from 6 experiments. (G) Frequencies of CD133-expressing CSCs  from NSCLC xenografts  treated with chemotherapy  alone or with the indicated inhibitors after 4 weeks. Mean±SEM from 6 experiments. Data information: ANOVA test with Turkey's method. **p < 0.01, ***p < 0.001, ****p < 0.0001.",
    "diseases": "NSCLC"
  },
  {
    "caption": "(A) Representative images of ILEI immunohistochemistry  on healthy (upper panels) and psoriatic  (lower panels) skin  sections, scale bar 100 µm. Inlets show a magnification of the marked regions, scale bar 50 µm.",
    "diseases": "psoriatic"
  },
  {
    "caption": "(B) Distribution of ILEI  protein content per keratinocyte  (n=5000-15000 cells per skin  sample) in healthy and psoriatic skin. Box and whiskers plot: Central band shows median, box extends from the 25th to 75th percentiles and whiskers go from the smallest (min) to the largest (max) value.",
    "diseases": "psoriatic"
  },
  {
    "caption": "(C) Median ILEI  content of keratinocytes  per person  shown as mean ± SEM of healthy (n=6) and psoriasis  (n=5) conditions. Data information: (C, Statistical significance was determined by Student's t-test and marked with asterisks (**p<0.01).",
    "diseases": "psoriasis"
  },
  {
    "caption": "Western blotting showing GPRC5A upregulation by hypoxia in a panel of colorectal tumour cell lines.",
    "diseases": "colorectal tumour"
  },
  {
    "caption": "IHC analysis of serial sections from human colorectal tissue from patients with mesenteric ischaemia (strangulated colon). GPRC5A is co-expressed with CA9 in the colonic epithelial cells (scale bars: 50um).",
    "diseases": "colorectal, mesenteric ischaemia"
  },
  {
    "caption": "B Quantitative analysis of the body weight (g) of nondiabetic and diabetic mice transplanted with FI or PI+MVF from day -8 to day 28 (n = 7 each). Mean ± SD.",
    "diseases": "diabetic"
  },
  {
    "caption": "C AUC of the body weight of nondiabetic and diabetic mice transplanted with FI or PI+MVF from day 0 to day 28 (n = 7 each). Mean ± SD.",
    "diseases": "diabetic"
  },
  {
    "caption": "D Quantitative analysis of blood glucose level (mg/dL) of diabetic mice transplanted with FI or PI+MVF and nondiabetic controls from day -8 to day 28 (n = 7 each). Mean ± SD. One-way ANOVA and Tukey's multiple comparisons post hoc test were used for statistical analysis. *P < 0.05 vs. FI; #P < 0.05 vs. PI+MVF.",
    "diseases": "diabetic"
  },
  {
    "caption": "E AUC of the blood glucose levels of diabetic mice transplanted with FI or PI+MVF and nondiabetic controls from day 0 to day 28 (n = 7 each). Mean ± SD. One-way ANOVA and Tukey's multiple comparisons post hoc test were used for statistical analysis. *P < 0.05 vs. FI; #P < 0.05 vs. PI+MVF.",
    "diseases": "diabetic"
  },
  {
    "caption": "F Quantitative analysis of blood glucose level (mg/dL) according to the IPGTT of diabetic mice transplanted with FI or PI+MVF and nondiabetic controls to the indicated time points (n = 5 each). Mean ± SD. One-way ANOVA and Tukey's multiple comparisons post hoc test were used for statistical analysis. *P < 0.05 vs. FI.",
    "diseases": "diabetic"
  },
  {
    "caption": "G AUC of IPGTT of diabetic mice transplanted with FI or PI+MVF and nondiabetic controls (n = 5 each). Mean ± SD. One-way ANOVA and Tukey's multiple comparisons post hoc test were used for statistical analysis. *P < 0.05 vs. FI; #P < 0.05 vs. PI+MVF.",
    "diseases": "diabetic"
  },
  {
    "caption": "H Plasma insulin level (µU/mL) of diabetic mice transplanted with FI or PI+MVF and nondiabetic controls at 180 min after IPGTT (n = 4 each). Mean ± SD.",
    "diseases": "diabetic"
  },
  {
    "caption": "Activated GFAP+ astrocytes in white matter MS lesions with inflammatory infiltrates and demyelination show an upregulation of OTUB1 (arrows). Photomicrographs are obtained from case 9 (A) and case 5 (B) listed in Table EV1. Data are representative for all 10 MS patients analyzed. Double immunofluorescence with rabbit anti-OTUB1 (Cy3) and mouse anti-GFAP (FITC); original magnification ×400; scale bars correspond to 50 µm.",
    "diseases": "MS"
  },
  {
    "caption": "Activated GFAP+ astrocytes in the spinal cord upregulate OTUB1 in EAE at maximal disease activity (day 15 p.i.) in an OTUB1fl/fl mouse (arrowheads), but not in a GFAP-Cre OTUB1fl/fl mouse. Note the OTUB1-expressing neuron in an OTUB1fl/fl mouse which is surrounded by GFAP-expressing processes of an activated astrocyte (asterisk). At day 22 p.i., astrocytes have downregulated OTUB1 expression while neurons express OTUB1 in an OTUB1fl/fl mouse (asterisk). Astrocytes in a GFAP-Cre OTUB1fl/fl mouse are OTUB1-negative while neurons express OTUB1 (asterisk). At day 22 p.i., demyelination in a GFAP-Cre OTUB1fl/fl mouse is much more severe and extended as compared to an OTUB1fl/fl mouse. Inflammation persists in the GFAP-Cre OTUB1fl/fl mouse, whereas it has resolved in an OTUB1fl/fl mouse. All photographs are representative of three mice per group; original magnification ×400; scale bars correspond to 50 µm. (A, C) Double immunofluorescence with rabbit anti-OTUB1 (Cy3) and mouse anti-GFAP (FITC). (B, D) CV-LFB staining.",
    "diseases": "EAE"
  },
  {
    "caption": "EAE was induced in GFAP-Cre OTUB1fl/fl mice (n = 29) and OTUB1fl/fl control littermates (n = 29) by MOG35-55 peptide immunization with pertussis toxin. Graph represents data pooled from 4 experiments with 7-8 mice per group and shows the mean clinical scores + SEM. Statistical analysis performed using Mann-Whitney U test; * p < 0.05. EAE was induced in GFAP-Cre OTUB1fl/fl mice (n = 12) and OTUB1fl/fl control littermates (n = 12) by MOG35-55 peptide immunization without pertussis toxin. Graph represents the mean clinical scores + SEM. Statistical analysis performed using Mann-Whitney U test; * p < 0.05.",
    "diseases": "EAE"
  },
  {
    "caption": "(A) Immunofluorescence images of PDAC tissues from KPC mice treated with vehicle control of tamoxifen, scale bar 100 μm",
    "diseases": "PDAC"
  },
  {
    "caption": "(B Quantification of GLUT1 (hypoxia marker Control (n=5), 2mg (n=5), and 5mg (n=4). In all cases, bars represent mean ± s.e.m",
    "diseases": "hypoxia"
  },
  {
    "caption": "(C) Relative values of protein levels for Glut1 in PDAC tumors assessed by proteomic analysis (6 mice per condition and samples were analysed in duplicates)",
    "diseases": "PDAC"
  },
  {
    "caption": "(G) Immunofluorescence images of PDAC tissues from KPC mice treated with vehicle control and 5mg of tamoxifen, scale bar 100 μm",
    "diseases": "PDAC"
  },
  {
    "caption": "(H) Quantification of HIF-1A in PDAC tissues Control (n=5), and 5mg (n=4). In the box-and-whisker plot, the central box represents values from the lower to upper quartile. The middle line represents the mean. The vertical line extends from the minimum to the maximum value",
    "diseases": "PDAC"
  },
  {
    "caption": "(E) Relative values of protein levels for LOX members in PDAC tumors assessed by proteomic analysis (6 mice per condition and samples were analysed in duplicates",
    "diseases": "PDAC"
  },
  {
    "caption": "(F) Immunofluorescence images of PDAC tissues from KPC mice treated with vehicle (control), and 2mg and 5mg of tamoxifen, scale bar 50 μm. (G) Quantification of LOX-L2 for images in F. n ≥ 4 mice per condition, and n> 10 sections per animal",
    "diseases": "PDAC"
  },
  {
    "caption": "(E) Relative values of protein levels for collagen in PDAC tumors assessed by proteomic analysis (6 mice per condition and samples were analysed in duplicates)",
    "diseases": "PDAC"
  },
  {
    "caption": "quantification of MMP-2 levels in PDAC tissues from KPC mice treated with vehicle (control), and 2mg and 5mg of tamoxifen, scale bar 100 μm (n=4 animals per condition and n≥ 5 sections per animal)",
    "diseases": "PDAC"
  },
  {
    "caption": "Immunohistochemistry image of MMP-2 levels in PDAC tissues from KPC mice treated with vehicle (control), and 2mg and 5mg of tamoxife",
    "diseases": "PDAC"
  },
  {
    "caption": "(J) Relative values of protein levels for MMP-2 in PDAC tumors assessed by proteomic analysis (6 mice per condition and samples were analysed in duplicates)",
    "diseases": "PDAC"
  },
  {
    "caption": "(E) Immunohistochemistry images of PDAC tissues from KPC mice treated with vehicle control, and 2mg, and 5mg of tamoxifen. (n=4 animals per condition, and n ≥ 5 sections per animal). (F) FN fiber thickness colour-code map in E represented through the BoneJ plugin",
    "diseases": "PDAC"
  },
  {
    "caption": "(G) Relative values of protein levels for FN in PDAC tumors assessed by proteomic analysis",
    "diseases": "PDAC, tumors"
  },
  {
    "caption": "(A) Immunofluorescence images of PDAC tissues from KPC mice treated with vehicle control, and 2mg of tamoxifen, scale bar is 100 μm. Upper panels: Ki67 staining is used as a surrogate of proliferation. White arrows indicate Ki67 positive nuclei in epithelial cells. Lower panels: Cc3 staining shows the cells undergoing caspase-mediated apoptosis. Tamoxifen panels show higher levels of yellow staining, which indicates higher percentage of apoptotic epithelial cells. (B) Quantification of staining in panel A (n=4 animals per condition, and n≥ 5 sections per animal, two experimental repetitions). Histogram bars represent mean ± s.e.m.; ***P<0.001, t-test",
    "diseases": "PDAC"
  },
  {
    "caption": "B-D [U-13C]Glucose (n=3 mice) (B), [U-13C]Glutamine (n=5 mice) (C) and [U-13C]Acetate (n=6  mice) (D) tracing into  βOHB in poorly differentiated PDA   explants from KIC  mice. Data are expressed as mean ± SEM.",
    "diseases": "PDA"
  },
  {
    "caption": "(B) Box-and-whisker plots of    ketone bodies   (KB) metagene score defined as first component of   PCA  of genes in primary tumors (n=728), in all metastases  (n=76), and in   liver metastases specifically (n=35). Box-and-whisker plot were defined with default parameters by median value (central band at the 50th percentile), interquartile ranges (IQR, box limited by 25th and 75th percentile) and whisker boundaries defined at 1.5x IQR. Significance was defined by Student's t-test.",
    "diseases": "liver metastases, metastases"
  },
  {
    "caption": "D-F Effect of  βOHB treatment on  liver metastatic incidence, size and status. Representative  HPS staining  of liver lobes from  metastatic mice treated with βOHB (100mg/kg/day, i.p.) or 0.9%  NaCl (i.p.) (n=8  mice/group). Metastatic areas are separated from  liver by yellow dotted lines. Scale bar: 1mm and 500 µm for insets (D). Number and size of metastasis   per lobe and classified in small, medium and large size (E). Pathological status of metastasis  from mice treated with βOHB or NaCl (n=13 or 5 lobes/group, respectively). Data are expressed as percentage of total metastasis   in all liver lobes presenting metastasis  (F).",
    "diseases": "metastasis"
  },
  {
    "caption": "(D, E) Kaplan-Meier curve analysis was conducted to evaluate the relapse-free survival or overall survival probabilities of colon cancer (n=1342) or lung cancer (n=2166) patients based on low or high levels of FBL expression. Data were sourced from an online tool website (https://kmplot.com/analysis/). The lower quartile-based partitioning method was used to select upper and lower thresholds to subset tumor samples into low and high groups. A cut-off value of the 25th percentile was defined as the low level of FBL in colon or lung cancer patients.",
    "diseases": "colon cancer, lung cancer"
  },
  {
    "caption": "A H&E staining  of sections of intestinal tissues obtained from endoscopic biopsy of COVID-19 patients who presented with gastrointestinal  (GI)  symptoms. The inflammatory infiltrates were indicated by a yellow arrow. The edema  area was indicated by a red star. Scale bars, 100 µm. B The bar chart shows the degrees of intestinal inflammation   in patients  with COVID-19. Number of samples for each group as indicated. Data information: All data are shown as mean ± SD.",
    "diseases": "gastrointestinal  (GI)  symptoms, COVID-19, edema, inflammation"
  },
  {
    "caption": "C Cytokine  levels in the plasma  of COVID-19 patients  with (n=12) or without (n=6) GI  symptoms by  cytokine assay. Data information: All data are shown as mean ± SD. P values are determined by Student's t-test.",
    "diseases": "GI  symptoms, COVID-19"
  },
  {
    "caption": "D Levels of plasma VEGF in COVID-19 patients with (n=8) or without (n=10) disease progression by  cytokine assay. Data information: All data are shown as mean ± SD. P values are determined by Student's t-test.",
    "diseases": "COVID-19"
  },
  {
    "caption": "E Temporal course of plasma VEGF at the early and late stage of COVID-19 infection by cytokine assay. Data shown are the levels of plasma VEGF in patients with (n=8) and without (n=10)  disease progression at the early stage (one to three days after laboratory-confirmed for COVID-19) and late stage (more than three days after laboratory-confirmed for COVID-19).",
    "diseases": "COVID-19"
  },
  {
    "caption": "F Levels of plasma VEGF in COVID-19 patients with (n=7) or without (n=6)  interstitial vasodilation by cytokine assay. G Levels of plasma VEGF in COVID-19 patients with (n=8) or without (n=5) interstitial edema by  cytokine assay. Data information: All data are shown as mean ± SD. P values are determined by Student's t-test.",
    "diseases": "interstitial edema, interstitial vasodilation, COVID-19"
  },
  {
    "caption": "A Levels of VEGF-A mRNA in the intestinal tissues from  COVID-19 patients (n=5) or healthy controls (n=5) by RNA-seq. Data information: All data are shown as mean ± SD. For (A), P values are determined by Student's t-test",
    "diseases": "COVID-19"
  },
  {
    "caption": "C, D Representative  H&E  images (C) and the quantitative analysis of inflammation (D) of the intestinal tissues from animals treated by the protocol shown in (B). The inflammatory infiltrates were indicated by a yellow arrow. Scale bar, 100 µm. Control-Fc, n = 5; Spike RBD-Fc, n = 6. n, biologically independent samples (mice).",
    "diseases": "inflammation"
  },
  {
    "caption": "C Immunofluorescence analysis of VEGF, cytokeratin (CK) and CD34 protein in the intestinal tissues of COVID-19 patients. CK and CD34 staining in green, VEGF staining in red and nuclear staining in blue. Scale bars, 50 µm.",
    "diseases": "COVID-19"
  },
  {
    "caption": "F, G Immunohistochemical staining shows ERK (E) and pERK (F) expression in the duodenum of COVID-19 patients and healthy controls. Scale bars, 100 μm. For each group, n=7. n, biologically independent samples (human specimen). Data information: All data are shown as mean ± SD. For (F) and (G), P values are determined by Student's t-test",
    "diseases": "COVID-19"
  },
  {
    "caption": "C, D Immunohistochemical staining shows levels of VE-cad (C) and pVE-Cad (731) (D) in the duodenum  tissue from  COVID-19 patients and healthy controls. Scale bars, 100 μm. For each group, n=7. n, biologically independent samples (human specimen). Data information: All data are shown as mean ± SD. for (C) and (D), P values are determined by Student's t-test",
    "diseases": "COVID-19"
  },
  {
    "caption": "C, D Representative  H&E images (C) and the degrees of inflammation (D) of intestinal tissues from animals treated with SCH772984 or Bevacizumab. The inflammatory infiltrates were indicated by a yellow arrow. The edema area was indicated by a red star. Scale bar, 100 µm. For each group, n = 4. n, biologically independent samples (mice). Data information: All data are shown as mean ± SD. P values are determined by one-way ANOVA.",
    "diseases": "edema, inflammation"
  },
  {
    "caption": "miR-499-5p qPCR analysis of total RNA isolated from PBMCs of control (female= 26, male= 31), BD (female= 26, male= 37), or MDD (female= 18, male=24) subjects. Wilcoxon rank sum test after correction for age and antidepressant treatment (linear model of the form Fold Change ~ Group*Sex + Age + Antidepressant treatment). 2-way ANOVA with correction for sex, age and antidepressant treatment (linear model of the form Fold Change ~ Group*Sex + Age + Antidepressant treatment). Control vs. BD: ****p=8.89e-07; control vs. MDD: n.s. p=0.12674. Data are presented as violin plots with median, quartiles and data points.",
    "diseases": "BD, MDD"
  },
  {
    "caption": "miR-499-5p qPCR analysis of total RNA isolated from PBMCs of control (female= 8, male= 10) and SZ (female= 8, male= 15) subjects. 2-way ANOVA, Main effect Sex: p=0.9785; main effect Group: p= 0.0924; main effect Interaction: p= 0.9802. Tukey's HSD: p=0.0924, ns. Data are presented as violin plots with median, quartiles and data points.",
    "diseases": "SZ"
  },
  {
    "caption": "miR-499-5p qPCR analysis of total RNA isolated from PBMCs of control (female= 26, male= 31), BD I (female= 9, male= 9), or BDI II (female= 12, male=16) subjects. 2-way ANOVA, Main effect Sex: p=0.174; main effect Group: ****p=4.07e-09; Interaction Group x Sex: p=0.311. Tukey's HSD: control vs. BDI: ****p=0.0000037. control vs. BDII:p=0.0000002. Data are presented as violin plots with median, quartiles and data points.",
    "diseases": "BD"
  },
  {
    "caption": "miR-499-5p qPCR analysis of total RNA isolated from PBMCs of control subjects (female= 26, male= 31), and BD subjects in different mood states (depressive (female= 7, male=11), euthymic (female= 7, male=4), hypomanic (female=2, male=6), manic (female=2, male=1), mixed (female=1, male=1). 2-way ANOVA, main effect Sex: p=0.260; main effect Group: p=1.26e-07; Interaction Group x Sex: p=0.059; Tukey's HSD: control vs. depressive ***p=0.0002621, control vs. euthymic ***p=0.0008533, control vs. hypomanic ****p=0.0000470. Data are presented as violin plots with median, quartiles and data points.",
    "diseases": "BD"
  },
  {
    "caption": "(A) Secreted FKN in cell cultures of a collection of 10 LUAD and LUSC cancer cell lines quantified by ELISA. Results are presented as means ± SD. Samples were assayed in duplicates from a pool of three independent replicates. Statistical differences among groups were analyzed by ANOVA followed by Tukey's tests.",
    "diseases": "LUAD, LUSC"
  },
  {
    "caption": "Kaplan-Meier survival curves showing the first progression survival of lung cancer patients in a publicly available lung cancer dataset according to ST3GAL5 expression (n=982).",
    "diseases": "lung cancer"
  },
  {
    "caption": "Box plots of ST3GAL5 gene expression levels in lung cancer tissues and normal tissues in the Bhattacharjee Lung database. The central bands indicate the medium expression values of ST3GAL5, boxes indicate the expression level ranges of ST3GAL5. Data are presented as the means ± SDs from the indicated number of tissues.",
    "diseases": "lung cancer"
  },
  {
    "caption": "Representative images of ST3GAL5 immunohistochemistry in a human lung tissue microarray including normal and cancer tissues. Wide field and magnified images (outlined with dotted squares) are shown.",
    "diseases": "cancer"
  },
  {
    "caption": "Scatter plot showing the expression of ST3GAL5 in normal and cancerous lung tissues. Each point represents the H-score of a single tissue sample with ST3GAL5 staining ranging from completely absent (H-score 0) to very strong (H-score 300). H-scores are presented as the means ± SDs; normal tissues, n=48; cancer tissues, n=97; ****, P < 0.0001 based on unpaired Student's t test.",
    "diseases": "cancer, cancerous"
  },
  {
    "caption": "(A) UHMK1 levels in tumor tissues (T) and corresponding nontumor tissues (N) from five GC patients were analyzed using Western blotting and qRT-PCR. The relative mRNA expression of UHMK1 was presented as mean ± standard deviation from three replicates. Pairwise, two-tailed statistical significance was assessed by Student's t‐test. Data information: *P< 0.05, **P< 0.01, ***P< 0.001.",
    "diseases": "GC"
  },
  {
    "caption": "(B) Immunoblotting and qRT-PCR were used to measure the levels of UHMK1 in GES-1 and GC cell lines. The relative mRNA expression of UHMK1 was presented as mean ± standard deviation from three replicates. Pairwise, two-tailed statistical significance was assessed by Student's t‐test. Data information: *P< 0.05, **P< 0.01, ***P< 0.001.",
    "diseases": "GC"
  },
  {
    "caption": "(C) IHC analysis of UHMK1 expression in a GC patient tissue array (n=102). Representative images are shown. Scale bars=100μm.",
    "diseases": "GC"
  },
  {
    "caption": "(E) UHMK1 expression in 100 GC patients was analyzed based on the following parameters: tumor stage, tumor status, and lymph node invasion status. Fisher's test was applied to calculate the exact P value. Data information: *P< 0.05, **P< 0.01, ***P< 0.001.",
    "diseases": "GC"
  },
  {
    "caption": "(F) Patients with GC were stratified by the UHMK1 level (n=100); OS and DFS were assessed by Kaplan-Meier analysis. Data information: *P< 0.05, **P< 0.01, ***P< 0.001.",
    "diseases": "GC"
  },
  {
    "caption": "A) GC cells (SGC7901 and MGC803) were transfected with (A) shUHMK1-#1,-#2, -#3, or control shRNA lentiviral vector, or (B) with a shRNA-resistant expression construct, UHMK1Δ. Western blotting was used to measure the levels of UHMK1. NIH ImageJ software was used to quantify the band intensity. Western blotting assay were conducted for three replicates. SGC7901 cells were transfected with or without shUHMK1-#1 or the shRNA-resistant expression construct UHMK1Δ. CCK-8 assays were conducted. Scale bars=5mm. Data information: **P< 0.01, ***P< 0.001, # marked no significance.",
    "diseases": "GC"
  },
  {
    "caption": "(D and E) The volumes of subcutaneous gastric tumors derived from SGC7901 cells in NOD/SCID mice were determined at different time points. Tumors and representative bioluminescence images are also shown. UHMK1 silencing in the mouse model was confirmed by western blotting (three biological replicates). Data were presented as mean ± standard deviation from shcontrol and shUHMK1#1 mice (n = 10 mice/group). Unpaired, two-tailed statistical significance was assessed by Student's t‐test. Scale bars=1cm.. Data information: **P< 0.01, ***P< 0.001, # marked no significance.",
    "diseases": "SCID, subcutaneous gastric tumors"
  },
  {
    "caption": "(F, G) UHMK1 silencing (F) and overexpression (G) affected GC cell abdominal metastasis. The quantitative number of metastatic nodules (left panel) in nude mice (n = 10 mice/group). Representative images of abdominal metastases are also shown (right panel). Scale bars=1cm. Data information: **P< 0.01, ***P< 0.001, # marked no significance.",
    "diseases": "GC"
  },
  {
    "caption": "(H) Heatmap of the top 500 genes upregulated in GC patients with high UHMK1 expression.",
    "diseases": "GC"
  },
  {
    "caption": "(G, H) The effects of WT-NCOA3, and the NCOA3-S1062A/T1067A, and NCOA3-S1062E/T1067E mutants on GC growth and metastasis in the mouse model (n = 10 mice/group). Scale bars=1cm. Data information: Unpaired, two-tailed statistical significance was assessed by Student's t‐test.Data represent mean ± SD. *P< 0.05, **P< 0.01, ***P< 0.001.",
    "diseases": "GC"
  },
  {
    "caption": "(F) ATF4 deficiency and overexpression regulated the activity of the UHMK1 promoter in GC cells. Data information: Data represent mean ± SD. **P< 0.01, ***P< 0.001.",
    "diseases": "GC"
  },
  {
    "caption": "(D) Immunoblotting of UHMK1, NCOA3 phosphorylated at S1062/T1067, NCOA3, and ATF4 in the samples (E) An ATF4 luciferase reporter assay was carried out in BGC823 cells with or without H. pylori infection. Data were presented as mean ± standard deviation from three replicates. (F) (Fi) The domain architecture of UHMK1 and the positions of human GC-associated mutations. (Fii and Fiii) IP kinase assay. Briefly, UHMK1 from HEK293 cells expressing WT-UHMK1 or its mutants was immunoprecipitated with anti-HA antibodies. The immunoprecipitated proteins were mixed with a synthetic peptide of the CATS protein (a known substrate of UHMK1) and [32P] ATP. A phosphocellulose paper assay was used to measure kinase activity. The results were normalized to a value of 1.0 for WT-UHMK1(three biological replicates). (G) The effects of human GC-associated UHMK1 mutations on the proliferation and colony formation of GC cells (three biological replicates). (H) The effects of human GC-associated UHMK1 mutations on GC cell invasion and migration (three biological replicates). Data information: Unpaired, two-tailed statistical significance was assessed by Student's t‐test. Data represent mean ± SD. *P< 0.05, **P< 0.01,. ",
    "diseases": "GC"
  },
  {
    "caption": "(A) Images showing UHMK1, p-NCOA3 (S1062/T1067), and ATIC protein expression in two human GC specimens. Scale bars=100μm. (B) Pearson correlation analysis about of the levels of UHMK1, p-NCOA3 (S1062/T1067) and ATIC proteins in patients with GC (n=120) by IHC. ",
    "diseases": "GC"
  },
  {
    "caption": "(C) (Ci)OS data from GC patients stratified by the level of UHMK1. (Cii)Combination of UHMK1 and p-NCOA3 (S1062/T1067) expression predicts more exact OS of GC patients. Survival curves were plotted according to Kaplan-Meier method, with the log-rank test applied for comparison.",
    "diseases": "GC"
  },
  {
    "caption": "A) ELISA quantification of PD-L1,  pTau 181 and  Aβx-42 in the CSF  of control and AD patients (n=10 +/-SEM, Student's t-test, * p<0.05, *** p<0.001, PD-L1: t=2.47 df = 18,  Aβx-42: t=4.83 df=18, pTau 181: t=5,768 df=18).",
    "diseases": "AD"
  },
  {
    "caption": "B, C) (B) Colocalization of PD-L1 and  GFAP in AD and (C) in control patients (MX-O4 = amyloid deposits, upper picture: bar = 100 µm, lower picture: bar=30 µm). D) Immunohistochemical  detection of PD-L1 in 9-month-old female APP/PS1 mice (bar = 50 µM). E) Immunohistochemical  detection of PD-L1 in 4-month-old female  APP/PS1 mice  (bar = 20 µm). ",
    "diseases": "AD"
  },
  {
    "caption": "A) Colocalization of PD-1 and CD11b (MX-04=methoxy-XO4, stains amyloid  deposits) in AD by  immunohistochemistry (bar=50 µm). B) Colocalization of PD-1 and Iba1 or PD-1 and  Aβ in a female APP/PS1 mouse at 9 months of age by  immunohistochemistry (bar=20 µm). ",
    "diseases": "AD"
  },
  {
    "caption": "D, E)  Mice were analyzed for (D) percentage of the covered areas (5 sections per  mouse analyzed with the mean representing an individual data point; biological replicates with n=6 for APP/PS1 and n=9 for  APP/PS1 PD-1-/-, mean +/-SEM, one-way ANOVA (DF=1, F=0.905, p=0.90), Tukey's HSD, ** p<0.01, *** p<0.001) and (E) the number of  plaques per mm2 (5 sections per mouse  analyzed with the mean representing an individual data point; biological replicates with n=6 for  APP/PS1 and n=9 for  APP/PS1 PD-1-/-, mean +/-SEM, one-way ANOVA (DF=1, F=4.08, p=0.054), Tukey's HSD, ** p<0.01, *** p<0.001).",
    "diseases": "plaques"
  },
  {
    "caption": "(E) Heatmap depicting mRNA levels of SMAD3-signature in BRAF(V600E) non-treated melanoma patients (dataset from TCGA; SKCM, BRAF(V600E) mutated: n=118). Three pigmentation genes (MITF, MLANA and TYR) have been added to highlight the differentiation states of tumors. ~20% of tumors are considered as dedifferentiated tumors (red box) with a high SMAD3-signature.",
    "diseases": "melanoma"
  },
  {
    "caption": "E Representative mIHC of immune components in CC tumors and adjacent normal tissues. T cells: CD3 (red), B cells: CD20 (green), macrophages: CD68 (pink), NK cells: CD56 (yellow), epithelial cells: Pan-CK (orange). Scale bar =100 μm.",
    "diseases": "CC"
  },
  {
    "caption": "H Heatmap showing the expression of marker genes in each subtype of epithelial cells. SCC, squamous cell carcinoma; SCJ, squamocolumnar junction; Imm, immune-related genes; Prolif, hyperproliferation; Colu, columnar epithelium; EMT, epithelial-mesenchymal transition;",
    "diseases": "SCC, squamous cell carcinoma"
  },
  {
    "caption": "I Representative mIHC of plasma cells in CC tumor area. plasma cells: CD38+Pan-CK-, scale bar = 100 μm;",
    "diseases": "CC"
  },
  {
    "caption": "A, B B cell subsets localization in CC tissues are exhibited by mIHC via differential markers as follow: total B cell: CD20+, GCB: CD20+BCL6-, PC: CD20-CD38+; with scale =500 μm for A, scale = 200 μm for B;",
    "diseases": "CC"
  },
  {
    "caption": "E Representative mIHC of CC tumor with CD4+PD-1+CXCL13+ Tfh cells located in TLS (yellow arrows). scale bars =100 μm for left panel, scale bars = 20 μm for right panel;",
    "diseases": "CC"
  },
  {
    "caption": "Blistered samples at P1. (B) Hematoxylin and eosin (H&E, top) and alkaline phosphatase (AP, bottom) staining. Hair follicles (HFs) remaining in the dermis (indicated by arrows). Scale bar: 500 μm. (C) α6 Integrin (ITGA6, indicated by arrowheads) and type IV collagen (COL4, arrows) labeling (left). Laminin 332 (L332, arrows) staining (right). Scale bar: 100 μm. (D) Ultrastructural findings of blistered skin (left image: blister roof, right image: blister bottom) . Hemidesmosomes (white arrowheads) and lamina densa (arrows) are indicated. Scale bar: 1 μm.",
    "diseases": "blister, Blistered, blistered"
  },
  {
    "caption": "Keratin 14 (K14) and keratin 10 (K10) staining of the nonlesional (intact) and lesional (blistered) skin at P2 (upper images and inlets: sections, lower images: whole-mount imaging). HFs are indicated by arrows in the whole-mount images. Scale bar: 30 μm.",
    "diseases": "blistered"
  },
  {
    "caption": "BrdU labeling of blistered samples at P2. Scale bar: 100 μm. BrdU-positive cells are indicated by arrows. Blisters are indicated by stars. (Bottom) Quantification of BrdU-positive cells in the epidermis (left) and HFs (right) (n=4 biological replicates). The data are shown as the mean ± SE. *0.01 test, followed by Tukey's test. NS, no significance. ",
    "diseases": "blistered, Blisters"
  },
  {
    "caption": "α5 integrin (ITGA5) labeling at P2 (left image: section, right image: whole-mount). Scale bar: 100 μm. Blister edges (epidermal tongue) and HFs are indicated by arrowheads and arrows, respectively. Blisters are indicated by stars.",
    "diseases": "Blister, Blisters"
  },
  {
    "caption": "BrdU labeling of Col17a1-/- skin at P2. Scale bar: 100 μm. (Bottom) Quantification of BrdU-positive cells in the epidermis surrounding blisters (n= 3 (control) and 4 (Col17a1-/-) biological replicates). The data are shown as the mean ± SE. Student's t-test. NS, no significance.",
    "diseases": "blisters"
  },
  {
    "caption": "K10/K14 (low magnification, left) and K14 (high magnification, middle and right) labeling of Col7a1-/- mouse (bottom) and littermate control (top) blistered skin at P2. Scale bar: 30 μm. Quantification of BrdU-positive cells per μm HF length (n=55 HFs from three control and 143 HFs from four Col7a1-/- mice). The data are shown as violin plots. Student's t-test. NS, no significance. Length of the major axis of keratinocytes in the regenerated epidermis (n=244 (control, L), and 132 (Col7a1-/-, L) cells from four mice, respectively) and in the surrounding intact epidermis (basal cells; n=200 (control, NL), 299 (Col7a1-/-, NL), from four mice, respectively). NL: nonlesional area. L: lesional area. The data are shown as violin plots. ****p<0.0001, one-way ANOVA test, followed by Tukey's test. NS, no significance.",
    "diseases": "blistered"
  },
  {
    "caption": "K10/K14 (left) and K14 (high magnification, right) labeling of WT blistered skin treated with CaCl2 (middle and bottom) or PBS (top) at P2. Scale bar: 30 μm. Quantification of BrdU-positive cells per μm HF length (n=83 (PBS), 95 (1.8 mM CaCl2), and 97 (9.0 mM CaCl2) HFs from four mice). One-way ANOVA test, followed by Tukey's test. NS, no significance. Length of the major axis of keratinocytes in the regenerated epidermis (n=433 (PBS, L), 451 (1.8 mM CaCl2, L), and 425 (9.0 mM CaCl2, L) cells from four mice) and in the surrounding intact epidermis (basal cells; n=311 (PBS, NL), 279 (1.8 mM CaCl2, NL), 302 (9.0 mM CaCl2, NL) cells from four mice). NL: nonlesional area. L: lesional area. The data are shown as violin plots. ****p<0.0001, one-way ANOVA test, followed by Tukey's test. NS, no significance.",
    "diseases": "blistered"
  },
  {
    "caption": "(a) Eyes from Pald1+/LacZ mice collected at P17 from untreated animals or animals with oxygen-induced retinopathy (OIR). Pald1-promoter driven LacZ expression and X-gal staining generated signals in capillaries, veins and arteries in the OIR retina at P17 compared to the normoxia control with predominantly arterial LacZ expression. Scale bar: 1 mm.",
    "diseases": "retinopathy"
  },
  {
    "caption": "A Two independently derived CRISPR/Cas9 PC3-LN4 EDC3 S161A mutants (EDC3 SA#1, #2) and wild type cells were injected subcutaneously in the flank (5X106) of SCID mice (n=8/group), and tumor growth was monitored until the control group reached 1000 mm3. The subcutaneous tumor volume measurement (mm3) was done as outlined in Materials and Methods. Data are presented as mean ± SEM, (n = 8/group).",
    "diseases": "SCID"
  },
  {
    "caption": "B Phosphorylated EDC3 levels were examined in normal immortalized breast cell lines, MCF10A and MCF12A, human breast cancer cell lines HCC38, HCC1954, MDA-MB-231, MDA-MD-468, BT-549, MRKNU1, and mouse 4T1 by Western blotting with the indicated Abs.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(K) IF staining showing Siglec-8 and Iba1, and MHC-II in cortical white matter tissue from a patient with late-onset AD (20x wide-field; Case ID: 01-43). Scale bars = 50 μm. Images are 60x super-resolution max z-stack projections.",
    "diseases": "late-onset AD"
  },
  {
    "caption": "(L-M) Percent area coverage of Siglec-8 localized to Iba1 or MHC in individuals with non-AD or AD. In (K) each point represents one WM or GM region average from each individual. In (L) values and statistics are shown for each image analyzed. Boolean mask operators indicate: ° = mask dilation, ⋂ = intersection, ⋃ = union, NOT = inverse mask. Box indicates quartiles and whiskers indicate the last datum within 1.5 inter-quartile range; n = 8-43 images (n = 1 ND, 3 early-onset AD, 4 late-onset AD); *: p < 5e-2, **: p < 1e-2, ***: p < 1e-3, ****: p < 1e-4; ns: not significant, using unpaired Student's t-test, two-sided.",
    "diseases": "AD, late-onset AD, early-onset AD"
  },
  {
    "caption": "A. The expression of EP subtypes in bone marrow myeloid cells and colon tumor myeloid cells. The short black lines indicate individual expressions, the blue and yellow lines indicate the average expression level in each condition. The grey dotted lines represent the overall average between Ptger1 and Ptger3 or Ptger2 and Ptger4.",
    "diseases": "colon tumor"
  },
  {
    "caption": "E. Growth curves (left panel) and relative change after 18 days treatment (right panel) in colon cancer (MC38) xenograft tumors in C57BL/6 mice (n = 7). Tumor volumes reached 100-200 mm3 on day 7.",
    "diseases": "colon cancer"
  },
  {
    "caption": "G. The representative bioluminescence images (left panel) and quantitative growth curves (right panel) of an orthotopic colorectal cancer mouse model, CT26-Luc model (n = 4).",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "total number of colon tumors per mouse (C, left) and tumor size distribution (C, right), and colon length (D) after 5 weeks of indicated treatment (n=7).",
    "diseases": "colon tumors"
  },
  {
    "caption": "(A) Netrin-1 gene expression profiling by array of substantiae nigrae from PD and non-PD (Control) patients using the GEO dataset GSE7621 that has a total of 25 samples (n=9 control and n=16 PD cases). Unpaired t-test, ***P < 0.0005, Mean ± SD are shown.",
    "diseases": "PD"
  },
  {
    "caption": "(B) Immunoblot of netrin-1, DCC, UNC5B, active caspase-3, alpha synuclein FL, alpha synuclein pS129, and Tyrosine Hydroxylase (TH) levels in age-matched controls (n=3) vs Parkinson's disease patients brain samples (n=3) (left panel). Band quantification bar graph (right panel). Bars and error bars represent the mean ± SEM. Statistical significance was determined using a one-way ANOVA followed by post hoc Tukey test for multiple group comparison. P**< 0.01. N=3 replicates",
    "diseases": "Parkinson's disease"
  },
  {
    "caption": " Therapeutic leads generated using PDN were directly tested for survival benefit using a murine model of endotoxemia. Select compounds were injected 24 hours before and on the day of LPS administration, using routes and doses specified in the methods. C57bl/6 female mice were injected with a high-lethality dose of E. coli LPS (38-40 μg/g) followed by a subcutaneous injection of sterile saline. Significant differences in concentration between drug and vehicle-treated pre- and post-pubertal mice are labeled with **** (p<0.0001), *** (p<0.001, ** (p<0.01), or * (p<0.05). Percent survival was compared using a log rank Mantel Cox test ",
    "diseases": "endotoxemia"
  },
  {
    "caption": "Immunohistochemical assay was performed to determinate RBM10 and BRCA1 levels in ovarian cancer microarray samples. Representative images are shown in (B).",
    "diseases": "ovarian cancer"
  },
  {
    "caption": "(C) Survival curves after the injection of EL4 lymphoma cells (n = 6/group).",
    "diseases": "lymphoma"
  },
  {
    "caption": "B Volcano Plot of top 10 miRNAs upregulated and 2 miRNAs downregulated in HGPS cells compared to control.",
    "diseases": "HGPS"
  },
  {
    "caption": "C The level of top 10 upregulated miRNAs in HGPS cells was assessed by qPCR.",
    "diseases": "HGPS"
  },
  {
    "caption": "D The level of novel-miR-27, miR-3656 and miR-59 in HGPS patient cells (HGAFDFN003 p21 and HGAFDFN167 p19) versus control (CRL-1474 cells p28) was assessed by qPCR.",
    "diseases": "HGPS"
  },
  {
    "caption": "Compared HGPS patient cells (HGAFDFN003 p22 and HGAFDFN167 p20) with control (CRL-1474 p26), the protein expression (H) of HMGAs were assessed.",
    "diseases": "HGPS"
  },
  {
    "caption": "Compared HGPS patient cells (HGAFDFN003 p22 and HGAFDFN167 p20) with control (CRL-1474 p26), mRNA level (I) of HMGAs were assessed.",
    "diseases": "HGPS"
  },
  {
    "caption": "In Flag-HMGA1 or Flag-HMGA2 infected CRL-1474 and HGPS cells (HGAFDFN003), the level of cyclin A2, lamin B1 was detected by western blot (A).",
    "diseases": "HGPS"
  },
  {
    "caption": "In Flag-HMGA1 or Flag-HMGA2 infected CRL-1474 and HGPS cells (HGAFDFN003), SA-β-gal staining were performed, the percentage of SA-β-gal positive cells was calculated.",
    "diseases": "HGPS"
  },
  {
    "caption": "In Flag-HMGA1 or Flag-HMGA2 infected CRL-1474 and HGPS cells (HGAFDFN003), Expression of Ki67 was analyzed by immunofluorescence. Scale bars: 50 μm (C).",
    "diseases": "HGPS"
  },
  {
    "caption": "Infection with control shRNA (shCtrl) or HMGA1/HMGA2 shRNA (shHMGA1 and shHMGA2) in anti-miR-59-transfected HGPS cells (HGAFDFN003), cells were subjected to SA-β-gal staining. Scale bars: 100 μm (F). Cells were subjected to immunofluorescence using anti-Ki67(red) antibody (left). The percentage of the Ki67 positive cells was calculated. Scale bars: 50 μm (G).",
    "diseases": "HGPS"
  },
  {
    "caption": "Infection with control shRNA (shCtrl) or HMGA1/HMGA2 shRNA (shHMGA1 and shHMGA2) in anti-miR-59-transfected HGPS cells (HGAFDFN003) The level of cyclin A2, lamin B1, HMGA1 and HMGA2 was detected by western blot (H).",
    "diseases": "HGPS"
  },
  {
    "caption": "P Infection with siCtrl or siCDK7 in Flag-HMGA1-transfected HGPS cells (HGAFDFN003), cyclin A1, RNAPII, the RNAPII Ser2P and RNAPII Ser5P was detected.",
    "diseases": "HGPS"
  },
  {
    "caption": "The mRNA level of cell cycle genes in HGPS patient cells (HGAFDFN003 and HGAFDFN167) (D) was assessed by qPCR.",
    "diseases": "HGPS"
  },
  {
    "caption": "The mRNA level of cell cycle genes in HGPS and 88- and 92-year-old cells (E) was assessed by qPCR.",
    "diseases": "HGPS"
  },
  {
    "caption": "Masson staining showed the perivascular interstitial fibrosis in the heart and quadriceps muscle (B) The boxes and arrows denoted the aortic adventitia.",
    "diseases": "perivascular interstitial fibrosis"
  },
  {
    "caption": "Masson staining showed the adventitial fibrosis (blue areas) and the adventitial width of aorta (C). The boxes and arrows denoted the aortic adventitia.",
    "diseases": "fibrosis"
  },
  {
    "caption": "Pulmonary surface nodules   and hematoxylin  and eosin  (H&E) staining  in Trim27+/- PyMT mice  and Trim27-/- PyMT mice  J). Scale bar, 1mm. (K). Bar chart showing quantification for the number of metastatic nodules  per lung lope (Trim27+/-, n=6 mice; Trim27-/- n=6 mice), when compared at the same final timepoint. Each symbol represents a mouse; Data are presented as mean ± s.d. from three independent experiments; ***P<0.001 (unpaired student's t-test).",
    "diseases": "metastatic"
  },
  {
    "caption": "CAC was induced in control (n = 7) and ColVIcre-Kif3aflx/flx (n = 7) female mice according to the timeline shown in Figure 2A. (E) Representative images of hematoxylin and eosin staining of paraffin-embedded colon sections. Areas with high-grade dysplasia are delimited by black lines.",
    "diseases": "CAC, dysplasia"
  },
  {
    "caption": "CAC was induced in control (n = 7) and ColVIcre-Kif3aflx/flx (n = 7) female mice according to the timeline shown in Figure 2A. (F,G,H,I) Box-and-whisker plots depicting area (F,G) and number (H,I) of low- and high-grade dysplasia per mouse.",
    "diseases": "CAC, dysplasia"
  },
  {
    "caption": "(D,E,F) At the end of the protocol described in (A) mice were sacrificed and colons were analyzed by histology for colitis severity including areas of irregular crypts (i.e., non-parallel crypts, variable crypt diameters, bifurcation and branched crypts; D,E) and crypt loss (i.e. mucosa devoid of crypts; D,F).",
    "diseases": "colitis"
  },
  {
    "caption": "(N) Decreased number of PC in inflamed tissue of patients with ulcerative colitis. Shown are the results of matched-pair analysis for PC expression per vimentin+ cells as arbitrary unit (AU, see material and methods). The lines link values obtained for regions of ulceration in the ileum with those of normal regions from the same patient, demonstrating the difference in each pair.",
    "diseases": "ulceration, ulcerative colitis"
  },
  {
    "caption": "(A) Representative image of vimentin+ fibroblasts (in green) expressing PC (identified using Arl13b, in red) in a normal colon. Nuclei were stained with DAPI (in blue). Most PC are detected on vimentin+ cells (arrow), and few on vimentin-negative epithelial cells (arrow head). (B,C) Quantitative analysis of PC presence on tumoral and peri-tumoral regions of colons from CRC patients (n=28) at tumor (T) stages 1 to 4. The panels represent quantification of PC expression (B) of vimentinpositive cells per mm2 and (C) per vimentinpositive cells as arbitrary unit (AU, see material and methods). Images were acquired on an Andor Dragonfly Spinning Disk Confocal microscope and analyzed with the Imaris software. Quantification of PC and Vimentin+ fibroblasts was done on at least 5 random fields (about 1mm2 each) per sample using ImageJ software.",
    "diseases": "CRC"
  },
  {
    "caption": "(B) Schematic representation of plasmid constructs used for in utero lentiviral infection. Whole-mounts or sections of adult infected epidermis with empty vector (EV) or Gata6-ires-GFP (G6OE) lentivirus were stained for GFP and Fasn. In vivo overexpression of Gata6 leads to ectopic Fasn expression in the HF/SG unit. White dotted lines define SG, and yellow dotted lines define a cyst. Note that the cyst is mostly negative for Fasn in agreement with its SD-like phenotype. White arrows indicate GFP-positive infected cells. These cells are stained with Fasn only in G6OE condition. H&E-stained skin from G6OE mice shows a cyst with SG elements in the HF unit (black arrows). Staining for Gata6 (both endogenous and exogenous) shows that Gata6 expression occurs in a limited number of cells (representative image in upper right panel). Bottom left graph shows quantification of the percentage of clones labelled for both Fasn and GFP in the SG, HF and IFE compartments. Data are means ± SD and originate from 4 EV mice and 8 G6OE mice (average of 11 clones per mouse). (C) Whole-mounts adult infected epidermis with EV or G6OE lentivirus stained with LipidTOX. Ectopic Gata6 cells are not stained with LipidTOX indicating an incomplete sebaceous maturation. Data information: Scale bars: 50 μm.",
    "diseases": "infected, infection"
  },
  {
    "caption": "(A) Sections of mouse skin tumors were stained with antibodies to Gata6 and Krt14. A papilloma tumor found in WT mice treated with DMBA and TPA (left panel), is compared with sebaceous tumors found in K14ΔNLef1 mice (right panels). Data information: Scale bars: 100 μm.",
    "diseases": "tumors, papilloma tumor, sebaceous tumors"
  },
  {
    "caption": "(B) Tumor burden and tumor incidence in DMBA-treated K14ΔNLef1 (n=11) and K14ΔNLef1:cKO (n=8) mice. (***) p-value < 0.001; Wilcoxon matched-pairs signed rank test. Data information: Data are means ± SEM.",
    "diseases": "Tumor, tumor"
  },
  {
    "caption": "(C) Representative H&E-stained tumors of K14ΔNLef1 and K14ΔNLef1:cKO mice with quantification of each tumor type relative to the total number of tumors in each group (middle panel) and as the average absolute number of tumors per mice (right panel). A total of 268 tumors were analyzed. 143 tumors were found in 7 K14ΔNLef1 mice (103 sebaceous tumors and 40 papillomas), while 125 were found in 5 K14ΔNLef1:cKO mice (55 sebaceous tumors and 70 papillomas). (**) p-value < 0.005, Student's t-test. Data information: (C) Scale bar: 1 mm.",
    "diseases": "tumor, tumors, papillomas, sebaceous tumors"
  },
  {
    "caption": "(D) Representative images of mouse skin tumor sections labelled with antibodies to Plet1 and Atp6v1c2. Data information: D) Scale bars: 100 μm.",
    "diseases": "skin tumor"
  },
  {
    "caption": "(C) MSI analysis performed on skin tumors from DMBA-treated K14ΔNLef1 and K14ΔNLef1:cKO mice (5 mice in each group). Representative microsatellite profiles of K14ΔNLef1 and K14ΔNLef1:cKO tumors. Peak heights were normalized to the highest peak in each microsatellite profile to obtain the relative frequency of each allele for 5 different markers. \"0\" indicates the position of the highest peak in bp. (*) p-value < 0.05; (**) p-value < 0.001; paired t-test.",
    "diseases": "tumors, skin tumors"
  },
  {
    "caption": "(D) Representative immunohistochemistry stainings against Mlh1 performed on skin tumors from DMBA-treated K14ΔNLef1 and K14ΔNLef1:cKO mice. 4 mice were included in each group. A technical control is displayed (without primary antibody incubation). Semi-quantitative analysis of Mlh1 staining and statistical analysis (χ2 test) were performed. Data information: Scale bar: 250 μm.",
    "diseases": "skin tumors"
  },
  {
    "caption": "(A) Normal human scalp skin sections stained with Gata6 and PanKeratin antibodies. Endogenous Gata6 expression is found in the JZ, upper SG and SD. As in mouse skin, Gata6 is not expressed in sweat glands (SwG). (B) Representative sections of human skin tumors stained with Gata6 and PanKeratin antibodies. Quantification of the percentage of Gata6-positive tumors within each histopathological group (middle left panel) and quantification of the percentage of Gata6-positive cells within each positive sample (middle right panel). Note that the least positive sample showed about 3% of Gata6-positive cells. The analysis was performed on 73 different tumor samples. SSC : squamous cell carcinoma, SCAP: syringocystadenoma papilliferum, EMPD: extramammary Paget's disease, nod./superf./scler. BCC: nodular/ superficial/ sclerodermiform basal cell carcinoma, Steatocystoma M.: steatocystoma multiplex, FSCH: folliculosebaceous cystic hamartoma. Heat-map displaying the -log(p-value) of χ2 test computed between the different tumor types (bottom left panel). (C) Gata6 expression (measured in Transcripts Per Million, TPM) in human SCC (n=6), BCC (n=6) and sebaceous carcinoma (n=14) samples from (North et al, 2018). Data are means ± SD. (**) p-value ≤ 0.005, Student's t-test. Data information: (A and B) Scale bars: 100 μm. ",
    "diseases": "folliculosebaceous cystic hamartoma, FSCH, BCC, nod./superf./scler. BCC, nodular/ superficial/ sclerodermiform basal cell carcinoma, tumor, tumors, EMPD, extramammary Paget's disease, sebaceous carcinoma, skin tumors, SCC, squamous cell carcinoma, SSC, Steatocystoma M, steatocystoma multiplex, SCAP, syringocystadenoma papilliferum"
  },
  {
    "caption": "(A) Differentiation status (poor, moderate or well-differentiated), circumscription (not infiltrative, focally infiltrative or infiltrative), log10 total number of mutations and Gata6 mutations in 32 human sebaceous carcinomas (SebC) separated in 3 subgroups: pauci-mutational, MSI-related and UV-related For Gata6 mutations, the most deleterious mutation is displayed. n.a.: not assessed.",
    "diseases": "sebaceous carcinomas, SebC"
  },
  {
    "caption": "(C) Gata6 expression (measured in Transcripts Per Million, TPM) in human pauci-mutational (pauci-mut) SebC (n=4), MSI-related SebC (n=4), UV-related SebC (n=5) samples. Data are means ± SD. (*) p-value ≤ 0.05, Student's t-test.",
    "diseases": "SebC"
  },
  {
    "caption": "(D-F) Graphs showing the number of mutations per megabase (Mutations/Mb) (D), the number of Somatic Single-Nucleotide Variants (SSNV) (E) and indel (F) of Gata6mut (n=3) or Gata6wt (n=6) MSI-related SebC (left panels) and of Gata6mut (n=3) or Gata6wt (n=7) UV-related SebC (right panels). Data are means ± SD.",
    "diseases": "SebC"
  },
  {
    "caption": "(G) Heat-map displaying the mean expression level of MMR genes (measured in TPM) in Gata6wt (n=10) and Gata6mut (n=3) SebC.",
    "diseases": "SebC"
  },
  {
    "caption": "High and constitutive expression of CXCR4 in the membrane of SW1417 CRC cells as measured by flow cytometry.",
    "diseases": "CRC"
  },
  {
    "caption": "Lack of human SDF-1α release from cultured SW1417 CRC cells, as measured by ELISA, whereas human control 1BR3.G fibroblasts express high SDF-1α levels, after 48h or 72h of growth in culture. (N=2 experiment in duplicate)",
    "diseases": "CRC"
  },
  {
    "caption": "Nanoconjugate internalization in CXCR4 overexpressing (CXCR4+) SW1417 CRC cells after 1 hour exposure at 1µM, as measured by fluorescence emission using flow cytometry. (N=3 experiments in duplicate) Significant difference at p= 0.002 between T22-GFP-H6-FdU and AMD3100+T22-GFP-H6-FdU groups",
    "diseases": "CRC"
  },
  {
    "caption": "Selective T22-GFP-H6-FdU nanoconjugate biodistribution in subcutaneous CXCR4+ SW1417 CRC tumor tissue 5h after a 100µg single intravenous dose, as measured by fluorescence emission using IVIS Spectrum 200 (N=5/group). Biodistribution is similar to that achieved by the T22-GFP-H6 targeting vector and undetectable after Buffer or free oligo-FdU treatment. (N=5 mice/group)",
    "diseases": "CRC"
  },
  {
    "caption": "T22-GFP-H6-FdU depletes CXCR4+ cancer cells from SW1417 CRC tumor tissue after a 100 µg single dose administration. Note the reduction in CXCR4+ cell fraction in the tumor 24h after injection, their almost complete elimination at 48h and the re-emergence of CXCR4+ cells 72h post-administration, using anti-CXCR4 IHC. In contrast, the CXCR4+ cancer cell fraction (CXCR4+ CCF) in tumor tissue remains constant along time after free oligo-FdU treatment. The three day time-lapse for CXCR4+ tumor cell re-appearance defines the dosage interval used in a repeated dose schedule of nanoconjugate administration in the experiments to evaluate its antimetastatic effect. (N=5: 5 mice/group; 1 samples/mouse). Scale bar, 50 µm. Data expressed as mean±s.e.m",
    "diseases": "CRC"
  },
  {
    "caption": "Representative CXCR4 IHC images of the reduction in CXCR4+ CCF induced by T22-GFP-H6-FdU (or its absence in free oligo-FdU mice) at the end of treatment, in the M5 patient-derived CRC model, which quantitation is reported in panel B. In the M5 model, the highest reduction in foci number and size occurs in liver metastases, which show the highest reduction in CXCR4+ CCF.",
    "diseases": "CRC"
  },
  {
    "caption": "A. Schematic diagram of the OIR model (top) and representative images of P17 OIR retinas are shown (bottom). Neonatal mice were exposed to 75% oxygen from P7 to P12 to induce vessel loss. Then mice received intravitreal injections of PBS vehicle, mouse-specific anti-VEGF (as a positive control) delivered at 0.1 μg/μl, or F4L5.13v2 (a second-generation F4L5.13 modality, in which the N-terminal FZD4-specific diabody was replaced with a FZD4-specific Fab) at 50nM or 500nM target vitreous concentrations. Mice were returned to room air from P12 to P17 to induce maximum pathologic neovascularization at P17. At P17, retinas from injected mice were collected, dissected as flat‐mounts and stained with Isolectin B4. Scale bar = 500 µm. B. Quantification of the ratio of neovascular and avascular area on total area of vascularization. Data are presented as mean ± SEM, n=11-13 retinas per group. Significance was calculated by one-way ANOVA with Bonferroni's multiple comparisons test (indicated p-values are in comparison to Vehicle). E ",
    "diseases": "neovascular, neovascularization"
  },
  {
    "caption": "A) Kaplan-Meier plots showing overall survival  of ADARlow and ADARhigh patients stratified by DHX58 levels in bladder cancer (BLCA; n=407), breast cancer (BRCA; n=1099) and sarcoma (SARC; n=263) TCGA datasets. Median cut-offs were used for patient  stratification and logrank test P values are shown.",
    "diseases": "BRCA, breast cancer, SARC, sarcoma, bladder cancer, BLCA"
  },
  {
    "caption": "H. Violin plots depicting the transcript levels of inflammation-related genes in luminal-C cells of sham and CTX Pten(i)pe-/- mice. P-values were determined by Wilcoxon rank sum test.",
    "diseases": "inflammation"
  },
  {
    "caption": "D. Representative western blot analysis of CPARP and CC3 in human C4-2B PCa cells treated for 24 h with PX-478, increasing concentrations of enzalutamide (Enz), or a combination of both. Beta-actin was used as loading control.",
    "diseases": "PCa"
  },
  {
    "caption": "A, Unsupervised cluster analysis of patients with cutaneous malignant melanoma based on global gene expression (RNA-seq) in metastases (n=367). Partitioning around medoids clustering algorithm was used (k=2).",
    "diseases": "cutaneous malignant melanoma"
  },
  {
    "caption": "B, Heat-map displaying the expression of bromodomain genes in metastases from patients with cutaneous malignant melanoma (n=367). BRD4, SMARCA4, TRIM28 and BRPF1 are highlighted by a black bar. Gene expression is represented by z-score.",
    "diseases": "cutaneous malignant melanoma"
  },
  {
    "caption": "C, Kaplan-Meier analysis of overall survival of patients with stage III melanoma in cluster C1 (median survival 79.5 months) and C2 (median survival 25.9 months), and of patients with stage III melanoma with high (median survival 61.5 months) or low (median survival 107 months) TRIM28 expression. The log-rank test was used for statistical testing of survival data.",
    "diseases": "stage III melanoma"
  },
  {
    "caption": "B: PCA plot of gene expression from POI mice at different disease stages and naïve mice; n=3 for each group.",
    "diseases": "POI"
  },
  {
    "caption": "K-M: qPCR analysis of indicated gliosis markers in td+ glia cells from naïve mice and mice that underwent IM (n=5-7, POI mice).",
    "diseases": "POI"
  },
  {
    "caption": "A. Glioma tumour micro arrays (grade II-IV gliomas) were stained to visualise MDGI (red). Samples from the epileptic brain served as a negative control. Scale bar 100 µm.",
    "diseases": "Glioma, gliomas, epileptic"
  },
  {
    "caption": "B. Overall survival of grade II and III glioma patients (n = 76) was significantly better when none/low MDGI (blue line) was detected compared to patients with moderate/high MDGI (red line) expression (P = 0.007). The cumulative survival rates were estimated by using the Kaplan-Meier method.",
    "diseases": "glioma"
  },
  {
    "caption": "C. Analysis of the association of MDGI mRNA expression with glioma patient survival using the GlioVis data portal. In the TCGA GBMLGG dataset (n = 667), patients with low MDGI expression (green line; n = 333, events = 101, median = 67,5) show significantly better survival than patients with high MDGI (red line; n = 334, events = 138, median = 41.5) expression (P = 2e-04). HR = 0.62 (0.48 - 0.8). The cumulative survival rates were estimated by using the Kaplan-Meier method.",
    "diseases": "glioma"
  },
  {
    "caption": "D. In glioblastoma samples, highest MDGI expression was observed in the mesenchymal subtype (M) compared to the classical (Cl) or pro-neural (PN) ones. However, it did not reach the statistical significance. GlioVis data portal, TCGA GBM dataset, n = 156. Pairwise t-test with corrections for multiple testing, p-values with Bonferroni correction.",
    "diseases": "glioblastoma"
  },
  {
    "caption": "E. MDGI expression was high in the leading edge of the tumour (LE) and in infiltrating tumour cells (IT) in the IVY_Gap dataset (n = 122) where the gene expression profile in different anatomical structures of glioblastomas was analysed. LE, leading edge; IT, infiltrating tumour cells; CT, cellular tumour (cells within the tumour mass); PC, pseudopalisading cells; MP, microvascular proliferation. Numbers in the graph depict the P values: Pairwise t-test with corrections for multiple testing, p-values with Bonferroni correction.",
    "diseases": "glioblastomas"
  },
  {
    "caption": "F. Western blot analysis shows MDGI expression in human glioma cells including patient-derived spheroids (S24, ZH161, ZH305, BT3, BT11, BT12, BT13), patient-derived adherent cells (BT5 and BT5R), and long-term cell lines (U87MG, LN229, LN308). Numbers above the lanes show the relative expression of MDGI compared to the levels of β-tubulin that served as loading control in each cell line. Representative Western blot image of 3 separate experiments is shown.",
    "diseases": "glioma"
  },
  {
    "caption": "G. High MDGI and HIF-1α expression in the patient-derived glioblastoma spheroids decreased significantly when cells were cultured in medium containing 10 % of serum (FBS) for seven days. Numbers show the relative expression of MDGI and HIF-1α compared to the levels of β-tubulin. Expression in the serum-free medium was set as 1. Representative Western blot image of 2 separate experiments is shown.",
    "diseases": "glioblastoma"
  },
  {
    "caption": "H. MDGI expression in adherent glioma cell lines and in glioma cell spheroids after 24h culture under hypoxia (1 % O2) or normoxia (21 % O2). Numbers show the relative MDGI expression compared to the levels of β-tubulin. Expression under normoxia was set as 1. Representative Western blot image of 3 separate experiments is shown.",
    "diseases": "glioma"
  },
  {
    "caption": "A, B Representative whole coronal section micrographs of murine brain injected with GFP (A) or MDGI-GFP (B) expressing U87MG glioma cells. Xenografted human cells were visualised by using anti-human vimentin (hVim) antibodies (red). Nuclei were visualised by using DAPI (white). Scale bar: 1 mm.",
    "diseases": "glioma"
  },
  {
    "caption": "Micrographs of consecutive (separating distance: 9 µm) brain sections stained for human glioma cells using antibodies specific for human vimentin (hVim red in C and D), Dashed lines separate the primary tumour mass and the normal brain. Nuclei were visualised by using DAPI (blue). Arrows in D point to the angiotropic tumours. Scale bar: 50 µm.",
    "diseases": "glioma"
  },
  {
    "caption": "Micrographs of consecutive (separating distance: 9 µm) brain sections stained for human glioma cells using antibodies specific for MDGI (green in E and F), and CD31 (red in E and F). Dashed lines separate the primary tumour mass and the normal brain. Nuclei were visualised by using DAPI (blue). Arrows in F point to the MDGI-expressing angiotropic tumour cells. Scale bar: 50 µm.",
    "diseases": "glioma"
  },
  {
    "caption": "I, J Representative micrographs of whole murine brain coronal sections injected with GFP (I) or GFP-MDGI (J) expressing LN229 glioma cells. Xenografted human cells were visualised by using anti-human vimentin (hVim) antibodies (red). Nuclei were visualised by using DAPI (white). Scale bar: 1 mm.",
    "diseases": "glioma"
  },
  {
    "caption": "Micrographs of consecutive (separating distance: 9 µm) brain sections stained for human glioma cells using antibodies specific for human vimentin (hVim red in K and L) Dashed lines separate the primary tumour mass and the normal brain. Nuclei were visualised by using DAPI (blue). ). Arrows in L point to the angiotropic tumours. Scale bar: 50 µm.",
    "diseases": "glioma"
  },
  {
    "caption": "Micrographs of consecutive (separating distance: 9 µm) brain sections stained for human glioma cells using antibodies specific for MDGI (green in M and N), and CD31 (red in M and N). Dashed lines separate the primary tumour mass and the normal brain. Nuclei were visualised by using DAPI (blue). ). Arrows in N point to the MDGI-expressing angiotropic tumour cells. Scale bar: 50 µm.",
    "diseases": "glioma"
  },
  {
    "caption": "E, F Representative whole coronal section micrographs of murine brain injected intracranially with control (BT12 Scr, n = 5) and MDGI-silenced (BT12 sh1, n = 5) BT12 cells. After four weeks animals were sacrificed, the brains were excised and prepared for immunohistochemistry. Control (Scr) cells grew very similarly to the parental BT12 cells forming a tumour mass with invasive tumour cells (single cell invasion) that eventually co-opted existing blood vessels (angiotropism) and formed secondary tumours (upper panels). No tumour growth was observed when MDGI-silenced cells were implanted (lower panels). Glioma cells were visualised by using anti-human vimentin (hVim red) and blood vessels using anti-podocalyxin antibodies (green). Nuclei were visualised by using DAPI (white). Scale bar: 1 mm (E) and 50 µm (F).",
    "diseases": "Glioma"
  },
  {
    "caption": "A. Measurement of the BT12, BT13, and ZH305 glioblastoma cell viability using the MTT-assay at the indicated clemastine concentrations and time points (n = 12). A dashed line marks the 50 % cell viability.",
    "diseases": "glioblastoma"
  },
  {
    "caption": "C. Representative micrographs of BT12, BT13, and ZH305 glioblastoma cells treated with 1 µg/ml of clemastine for 24 h and stained with anti-galectin-1 (LGALS1) antibody (green). Non-treated cells served as control. Nuclei were visualised by using DAPI (blue). Scale bar: 20 µm.",
    "diseases": "glioblastoma"
  },
  {
    "caption": "A. Representative whole coronal section micrographs of murine brain intracranially implanted with various glioblastoma cells), and daily treated with saline vehicle (Ve) or 50 mg/kg clemastine (Cle, 100 mg/kg single dose administered at day 1) for 12 days starting at day 15 after tumour implantation. BT12 (parental (wt, Ve n = 9, Cle n = 12) and control shRNA infected (Ve n = 5, Cle n = 5), ZH305 (Ve n = 10, Cle n = 10), and BT13 (Ve n = 10, Cle n = 9). Human glioma cells were visualised with an anti-human vimentin (hVim, red). Nuclei were visualised by using DAPI (white). Scale bar: 1 mm.",
    "diseases": "glioma, glioblastoma"
  },
  {
    "caption": "B, C Quantification of the number of the invading single BT12 wt glioblastoma cells (B) and distance of the invaded cells from the primary tumour (C) of vehicle (black bars, Ve) and clemastine-treated (white bars, Cle) animals (Ve n = 9, Cle n = 12). Data are represented as mean ± SEM. ****P < 0.0001, two-tailed, nonparametric Mann-Whitney's U-test.",
    "diseases": "glioblastoma"
  },
  {
    "caption": "(A) Bar chart showing the relative abundance (signal intensity) of the phosphorylated tau species identified using an exploratory IP-MS approach using HT7 antibody on TBS-soluble control and Alzheimer's disease (AD) pools. Blue dashed line indicates the two phosphorylated tau peptides that underwent targeted IP-MS: mono-phosphorylated p-tau231 and double phosphorylated p-tau(231+235).",
    "diseases": "AD, Alzheimer's disease"
  },
  {
    "caption": "(A) Box-and-whiskers plot showing the levels of CSF p-tau235 in neurological controls (n=21) and biologically defined Alzheimer's disease (AD) cases (n=19).",
    "diseases": "AD, Alzheimer's disease"
  },
  {
    "caption": "(A) Box-and-whiskers plot showing CSF p-tau235 concentrations in the different groups: amyloid-negative cognitively unimpaired (CU-) participants (n=50), participants across the Alzheimer's disease (AD) continuum (amyloid-positive cognitively unimpaired (CU+, n=32); amyloid-positive mild cognitive impairment (MCI+, n=20); AD (n=20) and non-AD cases (n=19). CSF p-tau235 is highly specific for AD pathology. Cut-off value for CSF p-tau235 positivity is displayed with black dashed line (19.92 pg/mL).",
    "diseases": "AD, Alzheimer's disease"
  },
  {
    "caption": "(A) Box-and-whiskers plot showing CSF p-tau235 concentrations in A-T- participants and across preclinical Alzheimer's disease (AD, dichotomised as A+T- and A+T+). CSF p-tau235 was increased already in A+T-, which represents the early cases within preclinical AD. A prominent increase was observed from A+T- to A+T+ cases, the latter representing late preclinical AD cases. Cut-off value for CSF p-tau235 positivity is displayed with black dashed line (19.92 pg/mL).",
    "diseases": "AD, Alzheimer's disease"
  },
  {
    "caption": "Trajectories of the different tau biomarkers in preclinical AD using a local weighted regression method (Loess curve). Changes on biomarkers levels in CSF are represented as z-scores using Aβ PET in centiloid scale (CL) as a proxy of disease progression. Abnormal biomarker levels were determined as two standard deviations (SD) above the mean. Incipient Aβ pathology positivity was determined as Aβ PET higher than CL 12 (Mila-Aloma et al., 2020). All samples were run in singlicates.",
    "diseases": "AD"
  },
  {
    "caption": "(C) To track ILC210 in vivo, CD45.2+ ILC210 were co-transplanted with islets in diabetic CD45.1+ C57BL/6 mice. Representative FACS analysis showing the proportion of locally transplanted ILC210 (CD45.2+ST2+) in the total CD45+ cell compartment from islet graft at day 5 and 80 post-islet transplantation or at the day when grafts were considered rejected.",
    "diseases": "diabetic"
  },
  {
    "caption": "Quantification of heart weight (HW)/tibia length (TL) ratio (B) N=4 to 18 mice/group, all 6 weeks after TAC or sham surgery.",
    "diseases": "TAC"
  },
  {
    "caption": "Quantification of lung weight (LuW/TL) ratio (C) N=4 to 18 mice/group, all 6 weeks after TAC or sham surgery.",
    "diseases": "TAC"
  },
  {
    "caption": "Quantification of , echocardiographic fractional area change (D) N=4 to 18 mice/group, all 6 weeks after TAC or sham surgery.",
    "diseases": "TAC"
  },
  {
    "caption": "Quantification of left ventricular enddiastolic area (LVEDA; E) N=4 to 18 mice/group, all 6 weeks after TAC or sham surgery.",
    "diseases": "TAC"
  },
  {
    "caption": "Quantification of dP/dt max and dP/dt min (Millar catheter; F, G) N=4 to 18 mice/group, all 6 weeks after TAC or sham surgery.",
    "diseases": "TAC"
  },
  {
    "caption": "Quantification of α-MHC transcript abundance N=4 to 18 mice/group, all 6 weeks after TAC or sham surgery.",
    "diseases": "TAC"
  },
  {
    "caption": "Quantification of β-MHC transcript abundance N=4 to 18 mice/group, all 6 weeks after TAC or sham surgery.",
    "diseases": "TAC"
  },
  {
    "caption": "fibrosis quantification (K) of indicated mice 6 weeks after TAC or sham surgery.",
    "diseases": "TAC, fibrosis"
  },
  {
    "caption": "Quantification of cardiomyocyte area of isolated adult cardiac myocytes (N=4 to 11 mice/group) of indicated mice 6 weeks after TAC or sham surgery. *P<0.05. One-way ANOVA with Sidak´s multiple comparisons test.",
    "diseases": "TAC"
  },
  {
    "caption": "Microscopy images of heart sections of indicated mice 6 weeks after TAC surgery stained for Isolectin B4 (green) and WGA (red, M)",
    "diseases": "TAC"
  },
  {
    "caption": "(P) Western blot analysis for TIP30 and GAPDH in hearts from TIP30 wild-type (WT) and heterozygous (Het) after AAV-TropT-TIP30 or AAV-Control (AAV-Con) injection followed by 6 weeks of TAC surgery.",
    "diseases": "TAC"
  },
  {
    "caption": "Quantification of HW/TL ratio (Q) ratio in AAV-Con or AAV-TropT-TIP30 treated Tip30 heterozygous (Het) or WT mice 6 weeks after TAC or sham surgery (N=5 to 11 mice/group).",
    "diseases": "TAC"
  },
  {
    "caption": "Quantification of LuW/TL (R) ratio in AAV-Con or AAV-TropT-TIP30 treated Tip30 heterozygous (Het) or WT mice 6 weeks after TAC or sham surgery (N=5 to 11 mice/group).",
    "diseases": "TAC"
  },
  {
    "caption": "(G) Western blot for TIP30 and Actin in mouse hearts with AAV9 mediated overexpression of TIP30 (AAV-TIP30) or from mice treated with a control AAV9 construct (AAV-Con) followed by 2 weeks of TAC surgery.",
    "diseases": "TAC"
  },
  {
    "caption": "Quantification of HW/TL ratio (H), N=8 to 13 mice/group 2 weeks after sham or TAC surgery in AAV-Con or AAV-TIP30 treated C57BL/6 WT mice. *",
    "diseases": "TAC"
  },
  {
    "caption": "Quantification of cardiomyocyte area (I), N=4 to 5 mice/group 2 weeks after sham or TAC surgery in AAV-Con or AAV-TIP30 treated C57BL/6 WT mice.",
    "diseases": "TAC"
  },
  {
    "caption": "(J) Serial echocardiography with quantification of echocardiographic fractional area change 2, 4 and 6 weeks after sham or TAC surgery in AAV-Con or AAV-TIP30 treated C57BL/6 WT mice (N=10 to 14 mice/group and time point).",
    "diseases": "TAC"
  },
  {
    "caption": "(J) Quantitative Real-Time PCR analysis of eEF1A1 and eEF1A2 mRNA abundance in hearts from neonatal mice, adult wild-type mice (Adult) and adult wild-type mice 2 weeks after TAC surgery (Adult TAC, N=3 to 4 mice/group). *P<0.05, ***P<0.001. One-way ANOVA with Sidak´s multiple comparisons test.",
    "diseases": "TAC"
  },
  {
    "caption": "(K) Western blot analysis for eEF1A1, eEF1A2 and GAPDH in hearts from wild-type mice at the age of 7 days (7d) and 8 weeks (8w) as well as 2 weeks (TAC 2w) after TAC surgery.",
    "diseases": "TAC"
  },
  {
    "caption": "(F) Microscopy images of adult mouse cardiomyocytes isolated from hearts 3 days (d) after TAC or sham surgery and subsequent PLA. Red: eEF1A1-eEF1B2 interaction; Blue: DAPI (scale bar: 100µm). (G) Quantification of eEF1A1-eEF1B2 interaction in adult mouse cardiomyocytes isolated from hearts 3 days after TAC or sham surgery and subsequent PLA (N=4 to 6 mice/group). *",
    "diseases": "TAC"
  },
  {
    "caption": "Western blot analysis for TIP30, eEF1A1 and GAPDH in C57BL/6 WT mice 3 days (A, B), N=4 mice/group, 2 weeks (C, D), N=4 to 8 mice/group and 6 weeks (E, F), N=4 to 8 mice/group after TAC or sham surgery and their quantification. KO denotes TIP30 homozygous knock-out.",
    "diseases": "TAC"
  },
  {
    "caption": "(G, H) Western blot for TIP30, eEF1A1 and Actin in TIP30 Het mice 6 after TAC surgery and their quantification (N=4 mice/group).",
    "diseases": "TAC"
  },
  {
    "caption": "(I, J) Western blot for TIP30, eEF1A1 and Actin 2 weeks after sham or TAC surgery in AAV-Con or AAV-TIP30 treated C57BL/6 WT mice and their quantification (N=4 mice/group). A ratio of TIP30 and eEF1A1 expression was calculated for each condition.",
    "diseases": "TAC"
  },
  {
    "caption": "Quantification of Tip30 and eEF1A1 mRNA transcript abundance in patients with Hypertrophic Cardiomyopathy (HCM; B, N=4 to 8 hearts/group) A ratio of Tip30 and eEF1A1 expression was calculated",
    "diseases": "HCM, Hypertrophic Cardiomyopathy"
  },
  {
    "caption": "Quantification of HW/TL ratio (E), N=6 to 10 mice/group, in Tip30 Het or WT mice 2 weeks after TAC. Animals were treated with Narciclasine daily for 14 days after TAC as indicated.",
    "diseases": "TAC"
  },
  {
    "caption": "Quantification of , echocardiographic wall thickness (F), N=6 to 10 mice/group, in Tip30 Het or WT mice 2 weeks after TAC. Animals were treated with Narciclasine daily for 14 days after TAC as indicated.",
    "diseases": "TAC"
  },
  {
    "caption": "Quantification of cardiomyocyte area (G), N=5 mice/group in Tip30 Het or WT mice 2 weeks after TAC. Animals were treated with Narciclasine daily for 14 days after TAC as indicated.",
    "diseases": "TAC"
  },
  {
    "caption": "Quantification of fractional area change (FAC, H, N=6 to 10 mice/group) in Tip30 Het or WT mice 2 weeks after TAC. Animals were treated with Narciclasine daily for 14 days after TAC as indicated.",
    "diseases": "TAC"
  },
  {
    "caption": "(I) Western blot analysis of puromycin incorporation in hearts of Tip30 Het and WT mice 3 days after TAC or sham surgery and daily Narciclasine (Narci) injection and their quantification (N=2 to 4 mice/group). Puromycin was injected 3 hours prior to sacrifice.",
    "diseases": "TAC"
  },
  {
    "caption": "B. ERα methylation SDMA, PRMT5 and MEP50 expression were studied as in A on a Tam-resistant formalin-fixed PDX model HBCx-34 Tam R treated or not with Tam. ERα methylation SDMA was analyzed as described above and the H-score for nuclear PRMT5 and MEP50 was evaluated as in A. The scale bar is 50 µM. The mean ± SEM of 3 tumors is shown. P-values were determined using a Student t-test.",
    "diseases": "HBC"
  },
  {
    "caption": "C. ERα methylation SDMA, PRMT5 and MEP50 expression were studied as in A on a Tam-resistant formalin-fixed the PDX model HBCx-22 Tam R treated or not with Tam. ERα methylation SDMA was analyzed as described above and the H-score for nuclear PRMT5 and MEP50 was evaluated as in A. The scale bar is 50 µM. The mean ± SEM of 7 tumors is shown.",
    "diseases": "HBC"
  },
  {
    "caption": "C, D Cell survival of DHA treated primary human glioblastoma cells from cancer patients and in combination with (C) the Ppox inhibitor acifluorfen (BTL90 cells) or upon (D) 5-ALA administration (VBT12 cells). Viability was assessed using CellTiter-Glo after 72h. Experiments were performed in triplicate.",
    "diseases": "glioblastoma"
  },
  {
    "caption": "E, F (E) ROS levels (DHE staining, PE 582/15 nm - MFI) and (F) cell survival of DHA (0.5μM), 5-ALA (0.25mM) or Ppox inhibitor (10μM) treated human neuroblastoma cells (SHSY5Y). Fluorescence of DHE (ROS levels) and cell numbers (survival) were assessed by flow cytometry and automated cell counting. The experiments were performed two times, in triplicate each.",
    "diseases": "neuroblastoma"
  },
  {
    "caption": "A Fluorescence (left panel) and brightfield (right panel) images of 5-ALA and DHA treated human cerebral tumor organoids (glioblastoma-like). Organoids were monitored on day 1, day 5, day 8 and day 11. One experiment is shown, representative of two independent experiments. Scale bar 500μm. B, C Image analysis and quantification of GFP-positive tumor areas of the treated organoids. Four organoids per group were analyzed on day (B) d5 and (C) d11, normalized to day 1. Data is shown as box plots (25th-75th percentiles, median) n=4. D",
    "diseases": "glioblastoma"
  },
  {
    "caption": "A Representative brightfield images of 5-ALA and DHA treated patient-derived glioblastoma spheroids (VBT92). Images were taken on day 3 of culture left untreated or exposed to the indicated treatments. Scale bar 500μm.",
    "diseases": "glioblastoma"
  },
  {
    "caption": "B Re-plating of spheroids after 3 days of 5-ALA and DHA treatment (duplicates). Representative brightfield images are shown for glioblastoma VBT92.",
    "diseases": "glioblastoma"
  },
  {
    "caption": "B In vivo efficacy comparison of solvents (control), 5-ALA, artesunate (ARS) and combined treatment in an orthotopic glioblastoma model. 11-14 days after stereotactic intracerebral injection of 2 x 105 VBT529 cells, mice received the following treatments: Control (solvents), 5-ALA (80 mg/kg), ARS (40 mg/kg), or 5-ALA plus ARS 5 times per week via intraperitoneal injection (n ≥ 5).",
    "diseases": "glioblastoma"
  },
  {
    "caption": "G Kaplan-Meier survival curves of mice injected with VBT529 glioblastoma cells into the flank and brain (same mice as in C-F; n = 6). Mice were treated with solvents (control) or 5-ALA plus ARS (same mice as in C-F).",
    "diseases": "glioblastoma"
  },
  {
    "caption": "(A) Masson's trichrome representative images of pulmonary fibrosis and quantification.",
    "diseases": "pulmonary fibrosis"
  },
  {
    "caption": "(F) Masson's trichrome representative images and correlation between lung fibrosis and vascular wall thickness in PF and PF-PH patients. Out of the 14 PF and PF-PH patients, 3 of them had no non-fibrotic area and therefore were excluded for comparison between non-fibrotic and fibrotic areas (n=11/group; Ashcroft score non-fibrosis: 0-2; mild-fibrosis: 3-5; severe-fibrosis >5) (* compared to non-fibrotic areas of the same group of patients).",
    "diseases": "fibrosis, fibrotic, lung fibrosis, PF, PH"
  },
  {
    "caption": "(G) Masson's trichrome representative images of vascular wall thickening in non-fibrotic area (Ashcroft score 0-2) and fibrotic area (Ashcroft score >2) and quantification in PF and PF-PH. The number of samples per group for each experiment are written within each bar graph.",
    "diseases": "fibrotic, PF, PH"
  },
  {
    "caption": "(A) Representative images of Ki67-positive pulmonary vascular endothelial cells (EC, vWF in green) and smooth muscle cells (SMC, aSMA in white) and quantification (* vs PF, *p<0.05, ***p<0.001).",
    "diseases": "PF"
  },
  {
    "caption": "Relative expression of Slug mRNA (B) normalized to GAPDH in PF and PF-PH patients.",
    "diseases": "PF, PH"
  },
  {
    "caption": "Relative expression of Slug protein (C) normalized to GAPDH in PF and PF-PH patients.",
    "diseases": "PF, PH"
  },
  {
    "caption": "(F) Representative images of Slug (red) expression in macrophages (Mф , CD68 in green) in non-fibrotic and fibrotic areas of the lung in PF and PF-PH patients and quantification. The number of samples per group for each experiment are included within each bar graph.",
    "diseases": "fibrotic, PF, PH"
  },
  {
    "caption": "Relative expression of Prolactin-induced protein (PIP) mRNA (D) normalized to GAPDH in PF and PF-PH patients.",
    "diseases": "PF, PH"
  },
  {
    "caption": "Relative expression of Prolactin-induced protein (PIP) expression normalized to GAPDH in PF and PF-PH patients.",
    "diseases": "PF, PH"
  },
  {
    "caption": "(A) Masson's trichrome representative images of lung fibrosis and quantification two weeks after PBS or bleomycin instillation.",
    "diseases": "lung fibrosis"
  },
  {
    "caption": "(M) Masson's trichrome representative images and quantification of the vascular remodeling between fibrotic and non-fibrotic areas in the experimental model. The number of samples per group for each experiment are included within each bar graph.",
    "diseases": "fibrotic"
  },
  {
    "caption": "(F) Representative images of Slug (red) expression in macrophages (Mф , CD68 in green) in non-fibrotic and fibrotic areas of the lung in in Bleo and Bleo-MCT rats and quantification. The number of samples per group for each experiment are included within each bar graph.",
    "diseases": "fibrotic"
  },
  {
    "caption": "(D) right ventricular systolic pressure (RVSP) and (E) right ventricular hypertrophy index in PF-PH rats treated with Si-Slug compared to Si-Scrm.",
    "diseases": "PF, PH"
  },
  {
    "caption": "(K) Masson's trichrome representative images and quantification of the vascular remodeling between non-fibrotic and fibrotic areas of the lung.",
    "diseases": "fibrotic"
  },
  {
    "caption": "(C) Representative images and quantification of Slug-positive macrophages between non-fibrotic and fibrotic areas of the lung.",
    "diseases": "fibrotic"
  },
  {
    "caption": "(A, B) Upregulation of GFAP in the retina of USH1C pigs at an age of 3 weeks (3w). (A) Representative immunofluorescence staining of GFAP in Müller glia cells which extend throughout almost the entire retina from the OLM (arrow) to the ganglion cell layer (GCL) of the retina. The consistent increase of GFAP expression in the Müller glia of USH1C pigs indicates Müller cell activation and gliosis. IS, inner segment; ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; scale bar: 20 µm. (B) Left panel: Western blot analysis of GFAP protein expression in 3w old USH1C piglets and age matched controls. Anti-actin Western blot was used as loading control. Right panel: Quantification of Western blot bands in 4 gels by the LI-COR Odyssey system revealed a strong increase GFAP expression in 3w USH1C piglets when compared to age-matched WT controls (2 piglets, 3w, 2 retinas each, 2 TRs, error bars represent standard deviation (SD) of the mean, two-tailed Student's t tests, *p<0.05).",
    "diseases": "gliosis"
  },
  {
    "caption": "(A) Heatmap of genes in the livers  of HFD-feeding induced NAFL mice  and WD/CCl4-treatment induced NASH mice. n=5. The color gradient represents log2(Fold change).",
    "diseases": "NAFL, NASH"
  },
  {
    "caption": "(B) Relative mRNA levels of KLF10  in the livers  from NAFL  and NASH mice. n=5. Results represent three independent experiments. Data information: * P <0.05, ** P <0.01-. Results are shown as mean ± SD. Student's t test",
    "diseases": "NAFL, NASH"
  },
  {
    "caption": "(D) Representative immunohistochemistry  of KLF10 protein expression in the liver  sections from NAFL  and NASH mice. The bar chart showed the fold change of KLF10  positive cells per field (NASH  vs. NAFL). n=5. Data information: * P <0.05, ** P <0.01-. Results are shown as mean ± SD. Student's t test",
    "diseases": "NAFL, NASH"
  },
  {
    "caption": "(E) Correlations between KLF10  and NAS, inflammation  score, fibrosis  scores, and hepatic triglyceride  contents (TG) from NAFL mice  (n=7) and NASH mice  (n=8). Data information: * P <0.05, ** P <0.01-. Results are shown as mean ± SD. Spearman's correlation (E",
    "diseases": "fibrosis, inflammation, NAFL, NASH"
  },
  {
    "caption": "(F) H&E staining, Sirius red staining, and KLF10 immunofluorescence staining  of liver  sections from NAFL  and NASH patients. n=3.",
    "diseases": "NAFL, NASH"
  },
  {
    "caption": "(G)  Gene expression analysis in liver  tissues from NAFL  and NASH patients  using GEO datasets (GSE48452 and GSE61260) from NCBI database. In the dataset GSE48452, n=17 for NAFL patients  and n=15 for NASH patients. In the dataset GSE61260, n=21 for NAFL patients  and n=24 for NASH patients. Data information: * P <0.05, ** P <0.01-. Results are shown as mean ± SD. Student's t test G).",
    "diseases": "NAFL, NASH"
  },
  {
    "caption": "(H) Spearman correlations between KLF10 expression   and NAS in liver  tissues from NAFL  and NASH patients  using GEO datasets (GSE48452). Left panel, n=32 (including 17 NAFL patients  and 15 NASH patients). Right panel, n=21 (including 6 NAFL  and 15 NASH patients). Data information: * P <0.05, ** P <0.01-. Results are shown as mean ± SD. Spearman's correlation H).",
    "diseases": "NAFL, NASH"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (G) Relative mRNA levels of genes involved in the hepatic inflammation  and fibrosis. Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "diseases": "fibrosis, inflammation"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through  tail vein  injection, and then kept on HFD-feeding for 12 weeks. n=5 per group. (O) Relative mRNA levels of genes involved in the hepatic inflammation  and fibrosis. Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "diseases": "fibrosis, inflammation"
  },
  {
    "caption": "(C-D) Spearman correlations between KLF10  and zDHHC7  in liver  tissues from NASH  and NAFL patients  using GEO datasets (GSE48452 and GSE61260). In the dataset GSE61260 (C), n=83 (including 38 healthy controls, 21 NAFL patients  and 24 NASH patients). In the dataset GSE48452 (D), n=73 (including 41 healthy controls, 17 NAFL patients  and 15 NASH patients). Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Spearman's correlation (C, D).",
    "diseases": "NAFL, NASH"
  },
  {
    "caption": "(I)  Chromatin immunoprecipitation  analysis of KLF10 binding  activity at the zDHHC7  promoter. Soluble chromatin  was prepared from the livers  of WD/CCl4  treatment-induced NASH mice  and immunoprecipitated  with antibodies against KLF10  or against IgG. The final DNA extractions were amplified using pairs of primers that cover the regions of zDHHC7  and GAPDH  gene promoters. (J) Quantitative real-time RCR results of ChIP  assays. IgG, immunoglobulin G. n=3. Results represent three independent experiments. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test J).",
    "diseases": "NASH"
  },
  {
    "caption": "Albumin-cre mice  were crossed with KLF10flox/flox to generate hepatocyte-specific KLF10  knockout mice  (KLF10hep-/-). Then, 8-week-old male KLF10hep-/- mice   and KLF10flox/flox were treated with WD/CCl4  for 12 weeks. KLF10flox/flox mice  were used as the control (Ctrl). n=5 per group. (M) Relative mRNA level of genes involved in the liver inflammation  and fibrosis. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test",
    "diseases": "fibrosis, inflammation"
  },
  {
    "caption": "(G) Immunostaining of pS6 (Ser240/244) in skin lesions from control and LL37-induced mice. Bottom right panels, magnified images of boxed areas. DAPI staining (blue) indicates nuclear localization. Scale bar: 50 μm. Right panel, the quantification of relative fluorescence intensity for pS6 (Ser240/244) in control and LL37 group (n=5 for each group). Data represent the mean ± SEM. **P < 0.01. two-tailed unpaired Student's t-test was used.",
    "diseases": "skin lesions"
  },
  {
    "caption": "(F) The mRNA expression levels of Tnf-α, Il6, Mmp9 and Vegf in skin lesions (n = 6 for each group).",
    "diseases": "skin lesions"
  },
  {
    "caption": "(A) The mRNA expression level of human cathelicidin (CAMP) in skin lesions from healthy individuals (n = 10) and patients with rosacea (n = 15). Data",
    "diseases": "rosacea, skin lesions"
  },
  {
    "caption": "(G) The mRNA expression levels of NF-κB family of transcription factors (Nfκb1, Nfκb1, Rela and Relb) in mice skin lesions (n=6 for each group).",
    "diseases": "skin lesions"
  },
  {
    "caption": "(I) IHC of p65 on skin sections from HS and rosacea. Scale bar, 50 μm. (J) Percentage of nuclear p65 positive cells in the epidermis from HS (n = 8) and rosacea (n = 13). All results are representative of at least 3 independent experiments. Data represent the mean ± SEM. **P < 0.01. 1-way ANOVA with Bonferroni's post hoc test (F and G) or two-tailed unpaired Student's t-test (J) was used. ",
    "diseases": "rosacea"
  },
  {
    "caption": "(B) The mRNA expression levels of mouse chemokines (Cxcl11, Cxcl12, Ccl2 and Ccl3) in skin lesions (n=6 for each group).",
    "diseases": "skin lesions"
  },
  {
    "caption": "(E) Heatmap of upregulated chemokines and cytokines in rosacea skin lesions determined by RNA-sequencing. All results are representative of at least 3 independent experiments. Data represent the mean ± SEM. *P < 0.05, **P < 0.01. 1-way ANOVA with Bonferroni's post hoc test was used.",
    "diseases": "rosacea, skin lesions"
  },
  {
    "caption": "Topical rapamycin treatment twice daily for 4 weeks showed an obvious therapeutic effect in rosacea patients. (C) The change of patients' CEA score showed in scatter histogram at 0 week and 4th week. (D) The change of patients' IGA score showed in scatter histogram at 0 week and 4th week. \"The Change value < 0\" indicates that skin lesions show positive improvement after treatment; \"The Change value > 0\" indicates skin lesions show exacerbation after treatment; \"The Change value = 0\" indicates that skin lesions show no change after treatment; Data represent the mean ± SEM, and two-tailed unpaired Student's t-test was used (C, D).",
    "diseases": "rosacea, skin lesions"
  },
  {
    "caption": "Peripheral blood mononuclear cells (PBMCs) were isolated from a WOREE patient and from his healthy parents and were reprogrammed into  iPSCs, and subsequently were differentiated into COs.   Week 10 WSM COs stained for the  progenitor marker SOX2, neuronal  marker  β3-Tubulin and WWOX (WSM F1: n=2 from 1 batch, WSM M2: n=2 from 1 batch, WSM S2: n=2 from 1 batch, WSM S5: n=2 from 1 batch, WSM S5 W-AAV3: n=2 from 1 batch, WSM S5 W-AAV6: n=2 from 1 batch). Scale = 50µm.   ",
    "diseases": "WOREE"
  },
  {
    "caption": "Peripheral blood mononuclear cells  (PBMCs) were isolated from a WOREE patient and from his healthy parents and were reprogrammed into iPSCs, and subsequently were differentiated into  COs. Average firing rate over 24 neurons from WSM P COs (4 organoids), 41 neurons from WSM S COs (3 organoids) and 40 neurons  from WSM S W-AAV organoids (3 organoids). Statistical significance was determined using one-way ANOVA with Tukey's multiple comparisons test. Bars represents the mean ± SEM. Data information: ns (non-significant), *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "diseases": "WOREE"
  },
  {
    "caption": "Peripheral blood mononuclear cells (PBMCs) were isolated from a WOREE patient and from his healthy parents and were reprogrammed into iPSCs, and subsequently were differentiated into  COs. GAD67 and  VGLUT1 immunostaining in week 10 WSM COs  (WSM F1: n=2 from 1 batch, WSM M2: n=2 from 1 batch, WSM S2: n=2 from 1 batch, WSM S5: n=2 from 1 batch, WSM S5 W-AAV3: n=2 from 1 batch, WSM S5 W-AAV6: n=2 from 1 batch). Scale = 50µm.   Quantification of the data shown in fig 5D. Statistical significance was determined using one-way ANOVA with Tukey's multiple comparisons test (WSM F1: n=2 from 1 batch, WSM M2: n=2 from 1 batch, WSM S2: n=2 from 1 batch, WSM S5: n=2 from 1 batch, WSM S5 W-AAV3: n=2 from 1 batch, WSM S5 W-AAV6: n=2 from 1 batch).  Data information: ns (non-significant), *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.  ",
    "diseases": "WOREE"
  },
  {
    "caption": "RT-qPCR analysis was used to determine the relative SLC1A3 mRNA expression (to GAPDH) in different prostate and breast cancer cell lines, as indicated. Data information: Results were calculated based on three replicates (except for SUM159 and BT549 in B, n=2) and presented as mean ± SD. The p-value was calculated by two-tailed unpaired t test in Prism7. **p<0.01, ***p<0.001. a.u. indicates arbitrary unit.",
    "diseases": "breast cancer, prostate"
  },
  {
    "caption": "SUM159PT human breast cancer cells were orthotopically injected into the mammary glands of NSG mice. Once SUM159PT tumors reached 250mm3 volume, mice were treated with mock or ASNase (60U per day) for 5 consecutive days (n=3). Following treatment, mice were sacrificed, and blood, mammary glands and tumors were collected and subjected to mass spectrometry to determine the asparagine level. Essential amino acids were used for the raw data normalization. Data are presented as mean ± SD. Data information: The pretreatment started 2 days before the injection of cancer cells. And mice were either injected with 60 U ASNase or saline per day. The p-value was calculated by two-tailed unpaired t test in Prism7, unless otherwise stated. *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "breast cancer"
  },
  {
    "caption": "The mouse breast cancer cell lines 4T1 and 4T1-V5-SLC1A3 were orthotopically implanted into the mammary glands of pretreated NSG mice. Presented is the volume measurements of arising tumors at day 9. (n=13 mice for each group, except for 4T1+ASNase, n=12). Data are presented as mean ± SEM. Data information: The pretreatment started 2 days before the injection of cancer cells. And mice were either injected with 60 U ASNase or saline per day. The p-value was calculated by two-tailed unpaired t test in Prism7, unless otherwise stated. *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "breast cancer"
  },
  {
    "caption": "tumors were surgically removed once reached a volume of ~500mm3 and collected and subjected to LC-MS to determine the levels of asparagine, aspartate, glutamine and glutamate. Leucine level was used as a control. Results are based on five tumor samples and presented as mean ± SEM. Data information: The pretreatment started 2 days before the injection of cancer cells. And mice were either injected with 60 U ASNase or saline per day. The p-value was calculated by two-tailed unpaired t test in Prism7, unless otherwise stated. *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "The human breast cancer cell lines MDA-MB-231 and MDA-MB-231-V5-SLC1A3 cells were intravenously injected into pretreated NSG mice. Once mice showed breathing problems, they were sacrificed, and lung and liver were collected and blindly scored for metastasis lesions. The p-value was calculated by one-tailed unpaired t test in Prism7. Data are presented as mean ± SEM (n=8). Data information: The pretreatment started 2 days before the injection of cancer cells. And mice were either injected with 60 U ASNase or saline per day. The p-value was calculated by two-tailed unpaired t test in Prism7, unless otherwise stated. *p<0.05, **p<0.01, ***p<0.001.",
    "diseases": "breast cancer"
  },
  {
    "caption": "CTLs exhibit extensive differences in lytic activity in vivo. Mice with established B cell lymphoma expressing OVA and the caspase 3 reporter were adoptively transferred with LifeAct-GFP-expressing  OT-I CTLs. Intravital imaging of the  bone marrow was performed two days after T cell transfer. (E) Representative  two-photon time-lapse images showing a representative CTL with high lytic capacity (killing 4 targets) and a  CTL with no lytic activity  for up to 4 hours. Blue arrows mark  apoptotic  tumor cells. Live and apoptotic tumors appear in grey and blue, respectively. CTLs  appear in green. Scale bar, 10 µm. Representative of 3 independent experiments.",
    "diseases": "B cell lymphoma"
  },
  {
    "caption": " D, Apoptotic assay of KRAS-mutant cancer cells (H358, H441, A549, and SW620) and KRAS-WT lung cancer cells (EBC-1) treated with vehicle (DMSO), AZD4547 (5 µM) and BI2536 (5 nM), alone or in combination for 48h. Data are presented as mean ± SD (n=3). ***P<0.001 and ****P<0.0001 by two-way ANOVA with Tukey's multiple comparisons test. ",
    "diseases": "lung cancer"
  },
  {
    "caption": " A, Growth curve of a KRAS-mutant lung cancer PDX (BE564T) treated with vehicle, HCQ (30 mg/kg/day), AZD4547 (10 mg/kg/day) and BI6727 (5 mg/kg/day), alone or in combination. *P<0.05, ***P<0.001 and P＞0.05 (ns) by one-way ANOVA with Tukey's multiple comparisons test. Data are the mean of tumor volume of each group (5 mice/group); error bar: SD ",
    "diseases": "lung cancer"
  },
  {
    "caption": " F-K, Growth curves (F, I) of KRAS-mutant lung cancer PDXs (PF139, PF563) treated with vehicle, HCQ (30 mg/kg/day), AZD4547 (10 mg/kg/day) and BI6727 (5 mg/kg/day), alone or in combination. *P<0.05, **P<0.01, ***P<0.001 by one-way ANOVA with Tukey's multiple comparisons test. Data are the mean of tumor volume of each group (4 mice/group); error bar: SD Relative tumor volume (G, J) and weights (H, K) of the PDX tumors after the treatment. *P<0.05, **P<0.01, ***P<0.001 and P＞0.05 (ns) by unpaired two-tailed t-test. Data are the mean ± SD (error bar) of tumor weights of each group (4 mice/group). ",
    "diseases": "lung cancer"
  },
  {
    "caption": "(B) Immunoblot analysis of Wap-Myc mammary tumor lysates for the indicated TGFβ signaling markers and hepsin (T# denotes individual tumors). GAPDH was used as the loading control. Lysates were derived from Wap-Myc mammary tumors from 6 mice with and 6 mice without DOX-induced hepsin overexpression",
    "diseases": "mammary tumor"
  },
  {
    "caption": "(A) ATX serum protein levels were measured in blood serum samples from IBD patients and healthy controls using ELISA: active UC (n=26), active CD (n=34), control (Con) (n=26).",
    "diseases": "CD, IBD, UC"
  },
  {
    "caption": "(B) Age- and sex-matched Atx∆ΜΕ/∆ΜΕ;Il10-/- mice (n=9) and Atx+/+;Il10-/- littermates (n=9) were examined for the development of spontaneous colitis. Body weight changes were monitored every other day, starting at the age of 37 days and ending at the age of 6 months. Results are means ± SD. Data were compared by Two-way ANOVA (with treatment and times), followed by the multiple-comparison Bonferroni t test to assess differences between groups.",
    "diseases": "colitis"
  },
  {
    "caption": "A, PTPN3 wildtype, phosphatase-dead D811A and ICC-derived mutant L232R exhibit similar patterns of subcellular localization and co-localization with TβRI. HaCaT cells were transfected with HA-TβRI and Flag-PTPN3 (wildtype or its mutants). 24 h later, cells were harvested for immunofluorescence with the indicated antibodies. Scale bar = 10 μm.",
    "diseases": "ICC"
  },
  {
    "caption": "H, Clinical significance of PTPN3 expression in LIHC based on TCGA database. In the boxplots, Y-axis represents the expression level of PTPN3 in normal and tumor samples. The boxes show the median (horizontal line in the box) ± 1 quartile; the upper and lower box limits represent the upper and lower quartiles, respectively. The whiskers (vertical lines) extend from the hinge to the smallest or larget value within 1.5 interquartile range from the box boundaries.",
    "diseases": "LIHC"
  },
  {
    "caption": "(E) Efficacy of thioparib in the PDX model BR-05-0028 (BRCA1-deficient). Mice bearing BR-05-0028 tumors derived from a patient with breast cancer (n = 6) were treated with 10 or 30 mg/kg thioparib or 100 mg/kg olaparib for 6 weeks. Data are depicted as mean ± SEM. ***P < 0.0001.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(B) Concentration-dependent effects of thioparib on the viability of malignant hematologic cells. Cells were treated with thioparib or other PARP inhibitors for 72 h and then subjected to CCK8 assay. Data from three independent experiments were presented as mean ± SEM.",
    "diseases": "malignant hematologic"
  },
  {
    "caption": "A The mRNA expression of FAM189A2/ENTREP in the primary human mammary epithelium HMEC and human breast cancer  cell lines. In  qRT-PCR analyses, the  expression was normalized to the immortalized normal human mammary epithelium HMEC4tertshp16. Relative expression ratios shown as mean + SD from three biological replicates.",
    "diseases": "breast cancer"
  },
  {
    "caption": "B Relative expression of FAM189A2/ENTREP in the normal (white) and cancer (green) tissues of breast (Curtis  Breast), lung (Okayama Lung), colorectal (TCGA Colorectal) and  head  and neck (Estilo Head-Neck). Data were downloaded from the Oncomine database P-values obtained by Student's t-tests and the number of cases are listed on the top and bottom of figures, respectively. P < 0.05 was considered as statistically significant. Box-whisker plot represents the interquartile range (25th and 75th percentiles) as a box and the median as a line. The maximn and minimun values within 1.5 x interquartile range are shown as whiskers. Outlier data are plotted as dots. C Relative  expression of FAM189A2/ENTREP in the primary (green) and the metastatic sites (blue) including lymph node, bone, liver,  lung, soft tissues of prostatic cancer (Grasso  Prostate) (left) and in the normal (white), primary (green) and metastatic sites (three cases of sentinel lymph node) (blue) of breast cancer (TCGA Breast) (right). Note that only three cases of the  metastatic breast cancer were available in the dataset. Data were downloaded from the Oncomine database P-values obtained by Student's t-tests and the number of cases are listed on the top and bottom of figures, respectively. P < 0.05 was considered as statistically significant. Box-whisker plot represents the interquartile range (25th and 75th percentiles) as a box and the median as a line. The maximn and minimun values within 1.5 x interquartile range are shown as whiskers. Outlier data are plotted as dots.",
    "diseases": "breast cancer, prostatic cancer"
  },
  {
    "caption": "D-F  Relapse-free survival  (RFS) of  breast cancer patients. Data were downloaded from the  Kaplan-Meier plotter",
    "diseases": "breast cancer"
  },
  {
    "caption": " A. Immunohistochemical staining of tissue arrays containing 142 breast carcinoma samples (grade I: n=29, grade II: n=69, grade III: n=44) and 20 normal mammary tissues for TRIM46 and HDAC1 expression. Representative images are shown on the left panel. The positively stained cells were analyzed, and the mean intensity was scored by Image-Pro Plus software on the right panel. In the boxplot, the central lines, the box limits, and the whiskers represented medians, 25th/75th percentile, and min/max, respectively. (*P<0.05, **P<0.01, ****P < 0.0001, one-way ANOVA). ",
    "diseases": "breast carcinoma"
  },
  {
    "caption": "B. Total proteins from 20 paired samples of breast cancer "T" versus adjacent normal breast tissues "A" were extracted for western blotting analysis with antibodies against TRIM46 or HDAC1.",
    "diseases": "breast cancer"
  },
  {
    "caption": " E. Kaplan-Meier survival analysis of TCGA BRCA dataset for the correlation between overall survival of breast cancer patients and TRIM46, BRCA1, or BLM expression. ",
    "diseases": "breast cancer"
  },
  {
    "caption": "Kaplan-Meier analysis of the correlation between expression level of LOC113230 and overall survival of colon adenocarcinoma (COAD) patients from TCGA database. P<0.001. P-value for Kaplan-Meier curves was determined using log-rank test.",
    "diseases": "COAD, colon adenocarcinoma"
  },
  {
    "caption": "qRT-PCR analysis of LOC113230 expression level in 65 paired CRC samples.",
    "diseases": "CRC"
  },
  {
    "caption": "Representative RNA-Scope immunostaining images of LOC113230 levels in CRC tissue and corresponding normal tissue from TMA chips. Scale bar represents 100 μM.",
    "diseases": "CRC"
  },
  {
    "caption": "Kaplan-Meier analysis for overall survival of CRC patients with high and low expression of LOC113230 from TMA chips. *P < 0.001. P-value for Kaplan-Meier curves was determined using log-rank test.",
    "diseases": "CRC"
  },
  {
    "caption": "Overexpression of LOC113230 in SW-1116 cells inhibited lung metastasis. Left: Exponentially growing SW-1116 - LOC113230-Luc and SW-1116-Vector-Luc cells were injected into the tail vein of 8-week-old nude mice and intensities of lung metastatic tumor cells at the 8th week were analyzed by in vivo photon flux imaging equipment. The red circles in images are to help to see the tumors. Right: Box plot (central band: median; box limits: first and third quartile; whiskers: minimum and maximum) of lung photon flux at the 8th weeks.",
    "diseases": "metastasis, metastatic"
  },
  {
    "caption": "E, F Tumours excised from mice as in (A-C) were paraffin-embedded for immunohistofluorescence analyses using an anti-cleaved caspase-3 antibody (scale bar = 100 μm) (E). Cleaved caspase-3 quantification was performed by counting the mean number of positive cells per field in five independent tumours (mean ± SD) (F) (*P = 0.036, **P = 0.009).",
    "diseases": "Tumours, tumours"
  },
  {
    "caption": "G, H Tumours excised from mice as in (D) were paraffin-embedded for immunohistofluorescence analyses using an anti-cleaved caspase-3 antibody (scale bar = 100 μm) (G). Cleaved caspase-3 quantification was performed by counting the mean number of positive cells per field in five independent tumours (mean ± SD) (H) (*P = 0.027).",
    "diseases": "Tumours"
  },
  {
    "caption": "e. Retrospective immunohistochemistry DAB staining of IgG4 and IgG on archival temporal lobe resection tissue. As suggested by the consensus statement on the pathology of IgG4-RD (Deshpande et al, 2012), three 40x fields with the highest number of IgG4+ and IgG+ cells were selected, counted and averaged within these fields. Cell counts as indicated.",
    "diseases": "RD"
  },
  {
    "caption": "f. C-X-C motif chemokine 13 (CXCL13) concentrations measured by ELISA from inflammatory pseudotumor (IPT) CSF, control CSF, and MS patient-derived CSF. Individual values, mean ± SEM; n=4 experiment repeats with technical replicates.",
    "diseases": "inflammatory pseudotumor, IPT, MS"
  },
  {
    "caption": "g. Stacked bar chart depicting mean relative expression levels of T helper cell-associated indicated cytokines in T cell subsets as identified by Seurat v4 reference mapping in inflammatory pseudotumor CSF as in (a). TEM, T effector memory; TCM, T central memory; Treg, regulatory T cell.",
    "diseases": "inflammatory pseudotumor"
  },
  {
    "caption": "h. Violin plot depicting relative expression levels of IL4R (left) and IL10RA (right) in B cell subsets as identified by Seurat v4 reference mapping in inflammatory pseudotumor CSF.",
    "diseases": "inflammatory pseudotumor"
  },
  {
    "caption": "a. Relative abundances of cell types identified by Seurat v4 reference mapping as in Figure 1a in IPT CSF compared to control or MS patient-derived CSF. Boxplot depicting 25th-75th percentiles with median shown as central band and whiskers extending from minimum to maximum values.",
    "diseases": "IPT, MS"
  },
  {
    "caption": "Mitochondria carrying the 3243A>G mutation in the tRNA Leu(UUR) gene from the same MELAS myoblasts were transferred into ρ0 206 cell line to generate ρ0206_A (100% wild-type mtDNA) and ρ0206_B (~90% m.3243A>G mtDNA) cell lines. ρ0206_A and ρ0206_B cell lysates were analyzed by Western blotting with anti-ATAD3 or anti-Tubulin antibodies. Relative protein levels of proteins were further evaluated by densitometry analysis using ImageJ software. Quantification of the relative protein level of ATAD3B to Tubulin was shown at right panels. Data are presented as mean ± SD (n =3 independent experiments), statistical significance was assessed by student's t-test, ***p < 0.001.",
    "diseases": "MELAS"
  },
  {
    "caption": "Normal or MELAS patient fibroblasts cell lysates were analyzed by Western blotting with anti-ATAD3 or anti-Tubulin antibodies. Relative protein levels of proteins were further evaluated by densitometry analysis using ImageJ software. Quantification of the relative protein level of ATAD3B to Tubulin was shown at right panels. Data are presented as mean ± SD (n =3 independent experiments), statistical significance was assessed by student's t-test, ***p < 0.001.",
    "diseases": "MELAS"
  },
  {
    "caption": "MELAS patient fibroblasts were infected with control, ATAD3A-Flag, ATAD3B-Flag or ATAD3B(mLIR)-Flag. After two weeks, total DNA was isolated from fibroblasts and used to calculate the mutation rate of 3243A>G by quantitative real-time PCR using the TaqMan Probe. Data are presented as mean ± SD (n =3 independent experiments), statistical significance was assessed by a one-way ANOVA, N.S., not significant, **p < 0.01.",
    "diseases": "MELAS"
  },
  {
    "caption": "B Immunohistochemical analysis of DDR1 and DDR2 levels on human melanoma tissue microarrays. Representative IHC images and quantification (right bar histograms) of DDR1 and DDR2 expression in normal skin, naevus, primary melanoma (PM) and lymph node melanoma metastases (MM). Scale bar, 100 µm. Histological scoring of the samples was performed in blinded fashion. Samples were scored as low, medium or high for DDR1 or DDR2 expression (naevus, n = 12; PM, n = 30; MM, n = 20).",
    "diseases": "melanoma, melanoma metastases, MM, PM, primary melanoma, naevus"
  },
  {
    "caption": "Immunoblotting of equal amounts of protein extracts from melanoma cell lines (C) using antibodies against DDR1, DDR2 or markers of the melanoma cell differentiation AXL, MITF or SOX10. ERK2, loading control.",
    "diseases": "melanoma"
  },
  {
    "caption": "Immunoblotting of equal amounts of protein extracts patient-derived short-term cell cultures (D) using antibodies against DDR1, DDR2 or markers of the melanoma cell differentiation AXL, MITF or SOX10. ERK2, loading control.",
    "diseases": "melanoma"
  },
  {
    "caption": "The Cancer Genome Atlas (TCGA RNAseq dataset) was used on the GlioVis platform (Bowman et al, 2007) to analyze the probability of survival (log-rank p-value) of 155 GBM patients, for each gene encoding for the mediators of the NF-κB pathway.",
    "diseases": "GBM"
  },
  {
    "caption": "Kaplan-Meier curve of the probability of survival for 155 GBM patients with low or high MALT1 RNA level, using median cut-off, based on the TCGA RNAseq dataset.",
    "diseases": "GBM"
  },
  {
    "caption": "Box and whisker plot of MALT1 mRNA expression in low-grade glioma (LGG, grades II and III) or in GBM (grade IV) (TCGA GBMLGG, RNAseq dataset) (D).",
    "diseases": "GBM"
  },
  {
    "caption": "Alternatively, MALT1 mRNA expression was plotted in non-tumor samples versus GBM samples (TCGA RNAseq dataset) (E). Each dot represents one clinical sample.",
    "diseases": "GBM"
  },
  {
    "caption": "(Left) Kaplan-Meier curve of the probability of survival for 155 GBM patients with low or high QKI RNA level, using median cut-off, based on the TCGA RNAseq dataset. (Right) Differential expression analysis related to either MALT1 or QKI expression highlighted a lysosomal lumen GO function. Venn diagram of overlapping lysosomal enriched protein encoding genes from this comparison showed 7 shared genes, together with 9 and 10 specific genes for MALT1 and QKI expression, respectively. (Bottom) Correlation between MALT1 and QKI expression was analyzed using The Cancer Genome Atlas (TCGA, HG-U133A dataset) on the GlioVis platform (Bowman et al, 2007). Pearson correlation factor=-0.21, p-value=0.03.",
    "diseases": "GBM"
  },
  {
    "caption": "(D) Efficacy of ND-011992-Q203 combination treatment in a mouse model of acute tuberculosis. Bacterial load (CFU) were enumerated in the lungs of mice before treatment, and after 5 days of treatment with either the vehicle control (brown squares), Q203 at 5 mg/kg (red squares), ND-011992 at 25 mg/kg (green triangles), or ND-011992 at 25mg/kg with Q203 at 5 mg/kg (orange diamonds). **P = 0.0006 unpaired Student's t-test, two-tailed; n = 4; comparing Q203 alone vs Q203 + ND-011992.",
    "diseases": "tuberculosis"
  },
  {
    "caption": "Immunofluorescence staining of apoE44 (n=3) and apoE23 (n=2) genotyped iNPH patient right frontal cortex biopsy samples Two representative microscopy images from six separate images show: (A) Colocalization of (red) apoE44 and (green) FH in the presence of (white) Aβ plaques. Scale bar = 50 μm. (B) Colocalization of (red) apoE23 and (green) FH around brain capillaries. The blue nuclei were detected using DAPI staining. (C) Colocalization of (red) apoE44 and (green) FH in the presence of (white) Aβ plaques from a biopsy sample obtained from an iNPH patient diagnosed with Alzheimer's clinical syndrome (ACS). Colocalization of apoE on Aβ is shown with an arrow. The negative staining control is shown. (D) ApoE-FH colocalization analysis of all detected colocalized foci in six microscope images from the apoE44 (n=3) and apoE23 (n=2) genotyped iNPH patient biopsy samples. Six microscope images from Alzheimer's clinical syndrome (ACS) biopsy sample are included in the apoE44 dataset (red dots).",
    "diseases": "iNPH, ACS, Alzheimer's clinical syndrome"
  },
  {
    "caption": "Immunofluorescence staining of apoE44 (n=3) and apoE23 (n=2) genotyped iNPH patient right frontal cortex biopsy samples (I) MST showing binding of NT647-labeled full-length FH to different apoE isoforms, (J) NT647-labeled apoE2(1-165) fragment to increasing concentrations of FH402Y and FH402H variants and FH domains 1-4 and 19-20 and (K) NT647-labeled recombinant N-terminal apoE2(1-165) to increasing concentrations of FH5-7 402Y and FH5-7 402H fragments.",
    "diseases": "iNPH"
  },
  {
    "caption": "(A and B) Immunofluorescence staining of apoE44 (n=2) and apoE23 (n=2) genotyped iNPH patient right frontal cortex biopsy samples showing localization of FH (green) with Iba-1 stained cells (red) and clustering around cells and brain capillaries. Presence of (white) Aβ plaques in apoE44 samples and (arrow) FH in both samples are shown.. C-E (C) Iba-1, (D) Aβ and (E) FH intensity analysis was calculated from all detected foci in six microscope images from the apoE44 (n=2) and apoE23 (n=2) genotyped iNPH patient biopsy samples.",
    "diseases": "iNPH"
  },
  {
    "caption": "(A) Immunofluorescence staining of iNPH patient biopsy samples (apoE33) showing (arrow) colocalization of complement activator, (red) C1q, and complement regulator (green) FH. (B) (arrow) Colocalization of (green) apoE and (red) C1q on (white) Aβ plaques. Colocalization analysis is calculated from colocalized foci in two separate microscope images.",
    "diseases": "iNPH"
  },
  {
    "caption": "(D) (left) Combined analysis of complement activation markers C3, C4, CFH and Clusterin obtained from the detected MS1 spectra between samples from apoE44 (n=3), apoE43 (n=5), apoE33 (n=7) and apoE23 (n=2) carriers (four markers/patient). (center) Combined analysis of complement activation markers C3, C4, CFH and Clusterin obtained from the detected MS1 spectra between samples that were positive (n=10) or negative (n=7) for Aβ pathology (four markers/patient). (right) Expression levels of Phosphodiesterase A control, showing similar expression levels in frontal cortex, between samples from apoE44 (n=3), apoE43 (n=5), apoE33 (n=7) and apoE23 (n=2) carriers The data were normalized against neutral apoE33 samples with no apoE association.",
    "diseases": "Aβ pathology"
  },
  {
    "caption": "I, The log-rank (Mantel-Cox) test of overall survival of 239 Chinese lung cancer patients based on rs1663689 genotype.",
    "diseases": "lung cancer"
  },
  {
    "caption": "(a) Representative micro-CT pictures of hind legs of 20-30 week-old control (A20WT) and A20myel-KO littermates. Note the severe osteoporosis in A20myel-KO mice. (b) Trabecular parameters, calculated on micro-CT scans of hind legs of 20-30 week-old control (A20WT) and A20myel-KO littermates. Each dot represents an individual mouse (A20WT, n=10; A20myel-KO, n=8).",
    "diseases": "osteoporosis"
  },
  {
    "caption": "Bar graphs showing audiogenic seizure scores following auditory stimuli (5, 10, 15, 20, 40 kHz or white noise (WN) at 70, 80, 90, or 100 dB) in control (E) and Cdc50a cKO (F) mice (n = 8 for each group).",
    "diseases": "audiogenic seizure"
  },
  {
    "caption": "A Correlation of Rcan1 expression in liver and gonadal adipose tissue with HOMA-IR, using male mice from over 100 strains from the hybrid mouse diversity panel. Regression line (red), r = biweight midcorrelation, p = p-value.",
    "diseases": "IR"
  },
  {
    "caption": "B, C Correlation of Rcan1 expression in gonadal adipose and liver with body weight, plasma insulin and plasma triglycerides, in a data set comparing backgrounds susceptible (BTBR background) or resistant (C57BL/6 background) to diabetes when carrying the leptinob/ob (ob) mutation. Measures are reported as the ratio of the mean log10 intensity (ml ratio). Regression line (black), r = linear regression, p = p-value.",
    "diseases": "diabetes"
  },
  {
    "caption": "(E-F) Expression of CSAG1 (E) and CSAG2 (F) in normal adjacent (blue) or tumor tissue (red) from TCGA RNA-Seq data. N.D. represents normal adjacent is not available. Data visualized by firebrowse. Number of biological replicates are as follows: ACC 41, BLCA 307, BRCA 524, CESC 175, CHOL 11, COAD 153, COADREAD 232, DLBC 36, ESCA 121, HNSC 416, KICH 46, KIPAN 515, KIRC 411, KIRP 58, LAML 7, LGG 528, LUAD 301, LUSC 400, MESO 31, OV 183, PCPG 70, PRAD 204, READ 79, SARC 156, SKCM 422, STAD 288, STES 409, TGCT 126, THCA 408, THYM 75, UCEC 306, and UCS 37. Central band indicates median, boxes define 25 and 75 percentiles, and whiskers define 5 and 95 percentiles.",
    "diseases": "PCPG, STES, THCA, LAML, ACC, BLCA, BRCA, CESC, CHOL, COAD, COADREAD, DLBC, ESCA, LGG, KIRP, KICH, KIPAN, KIRC, LUAD, LUSC, MESO, OV, PRAD, READ, SARC, SKCM, HNSC, STAD, TGCT, THYM, UCS, UCEC"
  },
  {
    "caption": "(G) Xq28 MAGE and CSAG genes are frequently co-expressed in lung squamous carcinoma tumors (n=184). RNA-Seq gene expression data analyzed from TCGA. Statistics shown were calculated by linear regression analysis.",
    "diseases": "lung squamous carcinoma"
  },
  {
    "caption": "(E-F) Knockdown of CSAG2 in A375 (F) or HCT116 (E) cells decreases xenograft tumor growth in mice. Cells with doxycycline-inducible shRNAs were implanted into NOD SCID gamma mice. Doxycycline (2 mg/mL) was administered via drinking water. Tumor growth was monitored over time. Data are represented as the mean ± SD, n=6 mice for each group.",
    "diseases": "SCID"
  },
  {
    "caption": "In vivo efficacy of HF and DWN12088 was determined in a bleomycin-induced lung fibrosis model. The indicated concentrations of HF or DWN12088 were orally administered to mice once a day for two weeks from a week after intratracheal injection of bleomycin (D). The saturation of percutaneous oxygen (SpO2) (E) was determined as a measurement of lung function. BLM, bleomycin; ; HF (0.05), HF 0.05 mg/kg; HF (0.1), HF 0.1 mg/kg; DWN12088 (10), DWN12088 10 mg/kg",
    "diseases": "lung fibrosis"
  },
  {
    "caption": "In vivo efficacy of HF and DWN12088 was determined in a bleomycin-induced lung fibrosis model. The indicated concentrations of HF or DWN12088 were orally administered to mice once a day for two weeks from a week after intratracheal injection of bleomycin The collagen level was determined by hydroxyproline assay (G) BLM, bleomycin HF (0.05), HF 0.05 mg/kg; HF (0.1), HF 0.1 mg/kg; DWN12088 (10), DWN12088 10 mg/kg;",
    "diseases": "lung fibrosis"
  },
  {
    "caption": "In vivo efficacy of HF and DWN12088 was determined in a bleomycin-induced lung fibrosis model. The indicated concentrations of HF or DWN12088 were orally administered to mice once a day for two weeks from a week after intratracheal injection of bleomycin (D). Masson's trichrome staining of lung tissues. ; HF (0.05), HF 0.05 mg/kg; HF (0.1), HF 0.1 mg/kg; DWN12088 (10), DWN12088 10 mg/kg; b, bronchiole; v, blood vessel.",
    "diseases": "lung fibrosis"
  },
  {
    "caption": "(A) Gene set enrichment analysis (GSEA) of differentially expressed genes in colorectal cancer from the GEO database (GDS4382). ES, enrichment score; NES, normalized enrichment score. n = 3 biological samples.",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "(B) Kaplan-Meier survival curves for colon cancer patients with or without dysfunction of iron homeostasis in the GSE dataset (n = 590 samples, P = 0.016, Log-rank (Mantel-Cox) test). \"Normal\" represents the patients with unaltered expression of iron homoeostasis-related genes, including LTF, CP, FTH1, SLC30A1 and TFRC; \"Dysfunctional iron homoeostasis\" represents the patients with altered expression of iron homoeostasis-related genes.",
    "diseases": "colon cancer"
  },
  {
    "caption": " (C) Immunoblot analysis of protein levels of IREB2 in colorectal adenocarcinoma and its matched adjacent normal tissues (Left), the relative protein level of IREB2 was assessed by ImageJ software (Right) (n = 8 human samples, *P = 0.0114, two-tailed paired Student's t-test). ",
    "diseases": "colorectal adenocarcinoma"
  },
  {
    "caption": " (D) Endogenous IREB2 was immunoprecipitated from the lysates of primary colorectal adenocarcinoma and its matched adjacent normal tissue, and was subsequently analyzed by anti-ubiquitin antibody for the assessment of ubiquitination. ",
    "diseases": "colorectal adenocarcinoma"
  },
  {
    "caption": " (A) RT-qPCR analysis of OTUD1 mRNA levels in colon tumors and matched adjacent normal tissues (n = 101 human samples, ***P < 0.001, two-tailed paired Student's t-test) ",
    "diseases": "colon tumors"
  },
  {
    "caption": " (B) Correlation of mRNA expression of TFRC and OTUD1 in colorectal cancer (n = 101 human samples, two-tailed Pearson correlation analysis, ****P < 0.0001). ",
    "diseases": "colorectal cancer"
  },
  {
    "caption": " (C) Immunoblot analysis of protein levels of OTUD1 and TFRC in colorectal adenocarcinoma and its matched adjacent normal tissues (n = 4 human samples), the protein levels relative to GAPDH are marked. ",
    "diseases": "colorectal adenocarcinoma"
  },
  {
    "caption": " (D) Immunohistochemical staining of OTUD1 in colorectal adenocarcinoma and its matched adjacent normal tissue (The scale bars represent 1000 μm). ",
    "diseases": "colorectal adenocarcinoma"
  },
  {
    "caption": " (E) Analysis of OTUD1 protein levels in colorectal adenocarcinoma patients with different clinical stages from tissue microarray CoI05-118e. ",
    "diseases": "colorectal adenocarcinoma"
  },
  {
    "caption": " (A) Representative pictures of colon tumors in AOM/DSS-induced Colitis-Associated Cancer (CAC) model (n = 6 biological replicates). ",
    "diseases": "Colitis, colon tumors"
  },
  {
    "caption": " (D) Representative H&E (Hematoxylin-eosin) staining pictures of colon tumors (The scale bars represent 1000 μm). ",
    "diseases": "colon tumors"
  },
  {
    "caption": " (G) Representative immunohistochemistry staining pictures of CD3+ T cells in colon tumors (The scale bars represent 400 μm ). ",
    "diseases": "colon tumors"
  },
  {
    "caption": "(A) Heat map shows the top 20 genes encoding cell surface markers found to be highly expressed in  iHCC samples compared to the corresponding PHHs. Within these 20 genes, seven genes highlighted in red were selected because their expression  was correlated with poor prognosis of HCC patients   based on TCGA-HCC  (TCGA-LIHC) analysis",
    "diseases": "HCC"
  },
  {
    "caption": "(D-G) GSEA analysis of 327 repressed (D) or 330 activated (F) Pax5  target genes identified in  pro-B cells as compared with the ranked log2-fold gene expression changes in  Pax5Jak2/+ (PJ)  B-ALLs versus control (Ctrl)  Pax5+/- Cdkn2ab+/- B-ALLs (left). NES, normalized enrichment score. The expression of five genes that are upregulated in  Pax5Jak2/+ B-ALL cells (upper row) and Pax5-/- (KO) pro-B cells (lower row) is shown in (E). Likewise, the  expression of five genes that are upregulated in control B-ALL cells (upper row) and Pax5+/+ (WT) pro-B cells  (lower row) is shown in (G). TPM, transcripts per million. Mean TPM values with SEM are shown for the following RNA-seq experiments: 3 (WT  pro-B), 2 (KO pro-B), 2 (Ctrl B-ALL), and 4 (PJ B-ALL).",
    "diseases": "B-ALL, B-ALLs"
  },
  {
    "caption": "(H) Expression of the Ptprc  (CD45) gene from exon 3 to exon 8, as determined by  RNA-seq  of Pax5Jak2/+ and  Pax5+/- Cdkn2ab+/- B-ALL cells. The alternatively spliced exons 4 (A), 5 (B) and 6 (C) are indicated in orange in the respective exon-intron structure of the Ptprc  gene. Ptprc  transcripts of B220+ Pax5+/- Cdkn2ab+/- B-ALL cells contain all three exons, thus giving rise to expression of the CD45 isoform   RABC  (known as   B220). In contrast, reads at exon 4 are barely detectable and reads at exon 6 are strongly reduced in the mRNA of Pax5Jak2/+ B-ALL  cells, which likely gives rise to the  CD45 isoforms RBC and RB",
    "diseases": "B-ALL"
  },
  {
    "caption": "(H)  Flow-cytometric analysis of  B220 and CD19 expression  in  B-ALL  tumor cells from the  lymph node  of a Cd79a-Cre Ikzf1neo/+ Pax5LSL-Jak2/+ mouse (black; left). Pax5 expression  in these B-ALL  tumor cells (black line) and control  Pax5+/+ lymph node B cells (grey filled) was determined by intracellular  Pax5 staining (right).",
    "diseases": "B-ALL"
  },
  {
    "caption": "(B) Genome-wide  binding of Pax5-Jak2 in in vitro cultured pro-B cells from Pax5Jak2/+ Rosa26BirA/+ mice  at the age of 3 weeks (expressing  Pax5) and ex vivo Pax5Jak2/+ Rosa26BirA/+ B-ALL tumors (lacking Pax5), as determined by Bio-ChIP-seq analysis The DNA-binding  pattern of full-length  Pax5  was determined by  Bio-ChIP-seq  analysis of ex vivo sorted Pax5Bio/Bio pro-B cells, which carried a C‐terminal biotin acceptor sequence together with an  IRES‐BirA gene insertion in the 3' untranslated region of  Pax5  Two independent Bio-ChIP-seq experiments were performed for each cell type. Representative  binding patterns of Pax5 and Pax5-Jak2 in the three B cell  types are shown for a selected genomic region, with horizontal bars indicating Pax5  or Pax5-Jak2  peaks that were identified by MACS peak calling (left). The number of Pax5 (white) and  Pax5-Jak2  (grey or black) peaks, which were defined by stringent MACS peak calling with a P value of < 10-10 in the three B cell types, are shown to the right.",
    "diseases": "B-ALL"
  },
  {
    "caption": "(D) Immunoblot analysis of whole-cell extracts prepared from Pax5Jak2/+ and control  Pax5Etv6/+ Cdkn2ab+/- B-ALL   cells as well as from the human HEL, TMD8 and  K1106 cell lines. Phosphorylated (p) STAT5 was detected with an anti-STAT5 (pY694) antibody and the pY41-peptide with the purified anti H3Y41ph antibody One to five pY41-peptides were coupled to  ubiquitin, which was added in the range of 50 ng per well. The Gapdh and histone H3 proteins were analyzed as loading control. An unspecific protein is denoted by an asterisk. One representative of 5 immunoblot experiments is shown.",
    "diseases": "B-ALL"
  },
  {
    "caption": "(F) Flow cytometric analysis of p-STAT5  levels in pro-B cells (B220+CD19+Kit+IgM-) and leukemic B220low B cells  of Pax5Jak2/+ mice (black) as well as in control pro-B cells of Pax5+/+ (WT) mice (grey) at the age of 4-5 weeks. A representative  flow cytometric analysis of the bone marrow  of a Pax5Jak2/+ mouse (left) and representative intracellular p-STAT5 stainings  (middle) are shown. The p-STAT5 levels in  pro-B and  leukemic B220low B cells (right) are quantified as MFI values relative to that of  Pax5+/+ pro-B cells. Statistical data are presented as mean values with SEM and were analyzed by the two-tailed unpaired Student's t-test: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Each dot corresponds to one mouse.",
    "diseases": "leukemic"
  },
  {
    "caption": "(I) Upregulation of the genes Cxcr5, Syndig1l  and Sema4a in Pax5Jak2/+ (PJ) B-ALL cells. Mean TPM values with SEM are shown for the following RNA-seq  experiments: 2 (Ctrl B-ALL), 4 (PJ B-ALL)",
    "diseases": "B-ALL"
  },
  {
    "caption": "(C) Lung cancer A549 cells, human normal bronchial epithelial cells (HBEpc), and HBEpc-differentiated cells (airway organoids) were harvested for immunoblotting with the indicated antibodies.",
    "diseases": "Lung cancer"
  },
  {
    "caption": "(C-F) Sections of human normal third-trimester placentas post-partum (n=4 normal placentas) and IUGR-complicated placentas of the same gestational age (n=4 IUGR placentas) were stained for senescence-related markers of p15 (C), p16 (D), p21 (E), and p53 (F) in the syncytiotrophoblast (n=3 sections, derived from each normal and IUGR placenta). Percentages of positively stained syncytia were quantified (n= at least 12 fields of view from all sections). Scale bar, 100 µm. Arrowheads indicate syncytiotrophoblast cells. Data information: Values are means + SEM of at least three experimental repeats. Statistical significance was determined by unpaired two-tailed Student's t-test (*) p < 0.05; (**) p < 0.01; (***) p < 0.001.",
    "diseases": "IUGR"
  },
  {
    "caption": "(G) Immunoblot analysis of the protein content of p16, p21, p53 and DCR in normal (n=4 placentas) and in IUGR-complicated placentas (n=4 placentas). Each lane represents one independent placenta.",
    "diseases": "IUGR"
  },
  {
    "caption": "(H) Quantitative RT-PCR analysis of p16, p21 and DCR2 expression in IUGR-complicated and in normal placentas. Results were obtained from four human normal and four IUGR placentas. Data information: Values are means + SEM of at least three experimental repeats. Statistical significance was determined by unpaired two-tailed Student's t-test (*) p < 0.05; (**) p < 0.01; (***) p < 0.001.",
    "diseases": "IUGR"
  },
  {
    "caption": "(F, G) Representative images (F) and quantification (G) of in-situ zymography of human normal third trimester post-partum placentas and placentas from IUGR-complicated pregnancies of the same gestational age (n>=9 fields of view of normal and IUGR placentas). Scale bar, 100 µm. Data information: Values are means + SEM of at least three experimental repeats. Statistical significance was determined by unpaired two-tailed Student's t-test (*) p < 0.05; (**) p < 0.01; (***) P<0.001.",
    "diseases": "IUGR"
  },
  {
    "caption": "(H) Immunoblot analysis of the protein content of p-p65, p65, p-STAT3 and STAT3 in normal placentas (n=4) and placentas from IUGR-complicated pregnancies (n=4). Each lane represents one independent placenta.",
    "diseases": "IUGR"
  },
  {
    "caption": "(I) Quantitative RT-PCR analysis of expression of MMP2, MMP9, IL6, and the JAK-STAT targets IFNAR1 and IFNAR2, in normal placentas and placentas from IUGR-complicated pregnancies. Results are from four human normal placentas and four placentas from IUGR-complicated pregnancies. Data information: Values are means + SEM of at least three experimental repeats. Statistical significance was determined by unpaired two-tailed Student's t-test (*) p < 0.05; (**) p < 0.01; (***) P<0.001.",
    "diseases": "IUGR"
  },
  {
    "caption": "Monocyte-derived macrophages from healthy controls and PD patients carrying the G2019S (Donor 2-3) or R1441C (Donor 1) LRRK2 mutation were pre-treated with 0.1 μM MLi-2 and treated with 1 mM LLOMe for 30 min. (A) Rab8A and Rab8A pT72 levels were analysed by Western blot. ",
    "diseases": "PD"
  },
  {
    "caption": "(H)-(J) mRNA expression of (H) U2AF1, (I)  SMN2-FL, or (J) SMN2∆7 in SMA patient-derived fibroblasts  (red bars) 72 hours post-transfection with SMN2  SSO, scrambled siRNA, or U2AF1  siRNA at the indicated dose. Unaffected, SMA carrier fibroblasts  (blue bars) treated with scrambled siRNA. Data information: *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001; empirical p-values are determined by a simulation and sampling method The error bars show the Standard Error of Mean (SEM). Data represent 3 biological replicates. Three technical replicates were performed during qPCR  for each biological replicate and averaged. Scrambled siRNA condition for each experiment was set to 1.",
    "diseases": "SMA"
  },
  {
    "caption": "(d-e) Scatter plots of BTMs enriched (p>0.05) in blood-culture positive samples in Nepal (y-axis) versus Oxford (x-axis) for typhoid fever (d) and paratyphoid fever (e). For further details on BTMs refer to reference (Chaussabel et al., 2014).",
    "diseases": "paratyphoid fever, typhoid fever"
  },
  {
    "caption": "(a) Single-sample GSEA Normalised Enrichment Scores (NES) of IFN and DC BTMs of individuals with blood-culture confirmed enteric fever in Nepal and Oxford.",
    "diseases": "enteric fever"
  },
  {
    "caption": "(d) Combined expression score for samples based on the 5-gene signature for samples in the discovery cohort (top) and validation cohort (bottom). Ox.CTRL: Oxford controls (D0); CTRL: Nepali control samples. PTB: pulmonary TB; DENV: Dengue samples; bsPf: blood-stage P. falciparum; SPT: S. Paratyphi A; ST: S. Typhi. ST and SPT samples are derived from the challenge models as well as from Nepal.",
    "diseases": "Dengue, DENV, blood-stage P. falciparum, bsPf, PTB, pulmonary TB"
  },
  {
    "caption": "(b) Dot plot of prediction probability of being class EF versus the expression score calculated on the bases of the 5-gene signature (based on gene array data).",
    "diseases": "EF"
  },
  {
    "caption": "(c) qPCR gene expression scores of the 5-gene signature (∆∆CT over PPIA) for CTRLs, 03NP-sEF, 03NP-SPT and 03NP-ST samples from Nepal. Yellow diamonds in the 03NP-sEF category represent the 9 patients classified as EF based on the random forest algorithm.",
    "diseases": "EF"
  },
  {
    "caption": "(d) qPCR expression values (∆∆Ct over PPIA) of the 5-gene signature in control samples (Oxford and Nepal), S. Paratyphi A (03NP-SPT) or S. Typhi (03NP-ST) in Nepal, samples at day 7 after challenge of participants who stayed well following challenge with S. Typhi (nD7), or typhoid diagnosis after challenge (TD) in the Vi-TCV study",
    "diseases": "typhoid"
  },
  {
    "caption": "(f) Temperature and CRP for samples of which data was available (CRP was only measured in the Oxford CHIM). D0 = pre-challenge baseline Vi-TCV study; nD7 = day 7 samples of participants who stayed well following challenge (Vi-TCV study); SPT = S. Paratyphi A (03NP); ST = S. Typhi (03NP); TD = Typhoid diagnosis (Vi-TCV study). (g) Spearman's rank correlation of the 5-gene combined expression score and (left) temperature (only nD7 and TD samples from the Oxford CHIM - Vi-TCV and SPT and ST cases from Nepal at presentation to hospital were included) and (right) CRP (CRP was only available for Oxford CHIM - Vi-TCV samples and we excluded D0 baseline measures).",
    "diseases": "TD, Typhoid"
  },
  {
    "caption": "A Representative IHCs in human reactive lymphoid tissue, where HK2 expression is mainly restricted to proliferating blasts within germinal centers (center), and in patient B-CLL cells. Scale bar 100 µm.",
    "diseases": "B-CLL"
  },
  {
    "caption": "Effect of cl-HK2pep on human B-CLL cells freshly isolated from patients. HK2-expressing B-CLL cells (B; GAPDH and respiratory complex III subunit UQCRC2 are cytosol and mitochondrial loading controls, respectively) Cells are treated with 5 µM cl-HK2pep; PD150606 (50 μM) is pre-incubated for 1 h. Experiments are carried out on samples from at least 10 patients and on CD19+, primary B lymphocytes from 5 healthy controls.",
    "diseases": "B-CLL"
  },
  {
    "caption": "Effect of cl-HK2pep on human B-CLL cells freshly isolated from patients. HK2-expressing B-CLL cells undergo mitochondrial depolarization assessed by TMRM staining (C) Experiments are carried out on samples from at least 10 patients and on CD19+, primary B lymphocytes from 5 healthy controls. data are presented as mean±SEM; all data were obtained from 3 technical replicates in all analyzed patient samples. two-way ANOVA: p<0.0001 (cl-HK2pep treatment vs cl-HK2pep+PD150606 or cl-SCRpep treatments) Student's t test; ***p<0.01, *p<0.05.",
    "diseases": "B-CLL"
  },
  {
    "caption": "ffect of cl-HK2pep on human B-CLL cells freshly isolated from patients. cell death, measured by cytofluorimetric analysis of Annexin V-FITC and 7-AAD staining Cells are treated with 5 µM cl-HK2pep; PD150606 (50 μM) is pre-incubated for 1 h. Experiments are carried out on samples from at least 10 patients and on CD19+, primary B lymphocytes from 5 healthy controls. In C, D, F and G data are presented as mean±SEM; all data were obtained from 3 technical replicates in all analyzed patient samples. wo-way ANOVA: p<0.0001 (cl-HK2pep treatment vs cl-HK2pep+PD150606 or cl-SCRpep treatments); tudent's t test; ***p<0.01, *p<0.05.",
    "diseases": "B-CLL"
  },
  {
    "caption": "Effect of cl-HK2pep on human B-CLL cells freshly isolated from patients. cell death, measured by cytofluorimetric analysis of Annexin V-FITC and 7-AAD staining Cells are treated with 5 µM cl-HK2pep; PD150606 (50 μM) is pre-incubated for 1 h. Experiments are carried out on samples from at least 10 patients and on CD19+, primary B lymphocytes from 5 healthy controls.",
    "diseases": "B-CLL"
  },
  {
    "caption": "Effect of cl-HK2pep on human B-CLL cells freshly isolated from patients. cell death, measured by cytofluorimetric analysis of Annexin V-FITC and 7-AAD staining Cells are treated with 5 µM cl-HK2pep; PD150606 (50 μM) is pre-incubated for 1 h. Experiments are carried out on samples from at least 10 patients and on CD19+, primary B lymphocytes from 5 healthy controls. data are presented as mean±SEM; all data were obtained from 3 technical replicates in all analyzed patient samples. Bonferroni post-test in graph ***p<0.001(cl-HK2pep vs cl-SCRpep and cl-HK2pep vs PD150606+cl-HK2pep) Student's t test; ***p<0.01, *p<0.05.",
    "diseases": "B-CLL"
  },
  {
    "caption": "Effect of cl-HK2pep on human B-CLL cells freshly isolated from patients. cell death, measured by cytofluorimetric analysis of Annexin V-FITC and 7-AAD staining Cells are treated with 5 µM cl-HK2pep; PD150606 (50 μM) is pre-incubated for 1 h. Experiments are carried out on samples from at least 10 patients and on CD19+, primary B lymphocytes from 5 healthy controls. data are presented as mean±SEM; all data were obtained from 3 technical replicates in all analyzed patient samples. Bonferroni post-test in graph ***p<0.001(cl-HK2pep vs cl-SCRpep and cl-HK2pep vs PD150606+cl-HK2pep) Student's t test; ***p<0.01, *p<0.05.",
    "diseases": "B-CLL"
  },
  {
    "caption": "Effect of HK2 targeting on in vitro tumorigenicity. HK2-silencing with two different shRNAs (shHK2-1 and shHK2-2) in CT26 colon cancer cells (A) Data information: Throughout the Figure, cl-SCRpep or SCRpep are used as peptide negative control.",
    "diseases": "colon cancer"
  },
  {
    "caption": "Effect of HK2 targeting on in vitro tumorigenicity. HK2-silencing with two different shRNAs (shHK2-1 and shHK2-2) in CT26 colon cancer cells inhibits growth in soft agar (B; colony area±SEM; n=6 replicates obtained from 3 independent experiments; Student's t test ***p<0.001; A.U., arbitrary units). Data information: Throughout the Figure, cl-SCRpep or SCRpep are used as peptide negative control.",
    "diseases": "colon cancer"
  },
  {
    "caption": "Effect of HK2-targeting on in vivo neoplastic growth. the same effect is observed on allografts of breast carcinoma 4T1 cells (H; 5 injections of 60 nmol peptide every 12 h; SCRpep n=5; HK2pep n=7 mice) in Balb/c female mice. Data information: Throughout the Figure, cl-SCRpep or SCRpep are used as peptide negative control. normalized volume±SEM; a two-way ANOVA is performed (p<0.001 - HK2pep vs SCRpep); Bonferroni post-test in the graphs *p<0.05; ***p<0.001.",
    "diseases": "breast carcinoma"
  },
  {
    "caption": " D MOAP-1 spontaneously localizes to the p62 bodies at resting state in the liver cancer cell lines, HepG2, Huh-1, JHH5 and JHH7. The liver cancer cell lines were transfected with the plasmid encoding Myc-MOAP-1. 14 hours later, transfected cells were subjected to IF analysis with anti-Myc (in green) and anti-p62 (in red) antibodies. Data information: nuclei were counterstained with DAPI (blue) ",
    "diseases": "liver cancer"
  },
  {
    "caption": " H MOAP-1 deficient mice bear higher tumor burden in the DEN-mediated liver cancer model. Representative images of liver tumors dissected from the 8.5-month-old male WT and MOAP-1 KO mice injected with a single dose of DEN (25 µg/g body weight) at 15-day-old. Scale bar: 5 mm. I Measurements of the number, maximum diameter of the tumor nodules and total liver weight from WT and MOAP-1 KO mice (n=13 and 14 respectively) injected with DEN as described in (H). Error bar represents S.E.M. **P<0.01, ***P<0.001, student's t-test. ",
    "diseases": "liver cancer"
  },
  {
    "caption": "(A) Cell count-based comparison of cellular proliferation   of T-ALL  cells after treatment with dexamethasone  (Dexa). Individual and mean values of three biological replicates ± SD analyzed by two-way ANOVA are shown. Data information: For all displayed experiments dimethyl sulfoxide  (DMSO; was used as a solvent control. ns = not significant, * p < 0.05, ** p < 0.01, *** p < 0.001.",
    "diseases": "T-ALL"
  },
  {
    "caption": "(B) Flow cytometric  analysis of  cell death by AnnexinV staining  in T-ALL cell lines upon treatment with indicated Dexa  concentrations. Cell death is represented by the number of AnnexinV  positive (AnnexinV+), apoptotic cells as a percentage (%) of total cells. Mean values of n≥4 biological replicates ± SD are shown. Data information: ns = not significant, * p < 0.05, ** p < 0.01, *** p < 0.001.",
    "diseases": "T-ALL"
  },
  {
    "caption": "(C) Expression  levels of human GRα   and LRH-1 mRNA in human T-ALL  cell lines were determined by probe-based real-time quantitative PCR, calculated as relative expression  compared to  beta-actin and used to determine the GR:LRH-1 ratio (right). Individual and mean values of four biological replicates ± SD are shown and statistically significant differences between CEM-C7  and GC-resistant cell lines were determined by one-way ANOVA.",
    "diseases": "T-ALL"
  },
  {
    "caption": "(D) Immunoblots  of GR, BimEL, BimL  and BimS  and Tubulin  from  T-ALL  cells treated for 24 h with 20 µM 3d2  or 30 µM Dexa. Representative results from n=2 biological replicates are shown. Data information: For all displayed experiments dimethyl sulfoxide (DMSO; represented by Ø was used as a solvent control. ns = not significant, * p < 0.05, ** p < 0.01, *** p < 0.001.",
    "diseases": "T-ALL"
  },
  {
    "caption": "(E) Immunoblots  of GR, PARP  (nuclear  loading control) and Tubulin  (cytoplasmatic  loading control) from cytoplasmic  (CP) and nucleoplasmic  (NP) lysates of  T-ALL  cells treated with Dexa. Note: Nuclear  extracts were more highly concentrated (approx. 6-fold) than cytosolic fractions. Representative results from two biological replicates are shown.",
    "diseases": "T-ALL"
  },
  {
    "caption": "(F) GR  activity in human T-ALL  cells transfected with a control luciferase  reporter plasmid (pGL3) (F) GR  responsive (GRE) luciferase  reporter and treated with 3d2  and/or Dexa.  β-galactosidase  (bGal) was co-transfected as an internal transfection control. Luciferase reporter activity was normalized to bGal  activity and calculated as relative to the DMSO-treated pGL3 control. Individual and mean values analyzed by two-way ANOVA of three biological replicates ± SD are shown for Jurkat  and CEM-C7  whereas technical triplicates ± SD of a representative experiment (n=3 biological replicates) are shown for MOLT-4. Data information: For all displayed experiments dimethyl sulfoxide  (DMSO; was used as a solvent control. ns = not significant, * p < 0.05, ** p < 0.01, *** p < 0.001.",
    "diseases": "T-ALL"
  },
  {
    "caption": "(G) LRH-1  activity in human T-ALL cells transfected with a control luciferase  reporter plasmid (pGL3) and (G) LRH-1 responsive (5xRE) luciferase  reporter and treated with 3d2 β-galactosidase (bGal) was co-transfected as an internal transfection control.  Luciferase reporter activity was normalized to bGal  activity and calculated as relative to the DMSO-treated pGL3 control. Individual and mean values analyzed by two-way ANOVA of three biological replicates ± SD are shown for Jurkat  and CEM-C7 whereas technical triplicates ± SD of a representative experiment (n=3 biological replicates) are shown for  MOLT-4. Data information: For all displayed experiments dimethyl sulfoxide (DMSO; was used as a solvent control. ns = not significant, * p < 0.05, ** p < 0.01, *** p < 0.001.",
    "diseases": "T-ALL"
  },
  {
    "caption": "(A) Daily cell counting-based comparison of  cellular proliferation   of T-ALL cells after (A) treatment with 3d2  Individual and mean values of technical triplicates of one representative experiment (n=3 biological replicates) ± SD anlyzed by two-way ANOVA are shown. Data information: For all displayed experiments dimethyl sulfoxide (DMSO; was used as a solvent control. ns = not significant, * p < 0.05, *** p < 0.001.",
    "diseases": "T-ALL"
  },
  {
    "caption": "(B) Daily cell counting-based comparison of cellular proliferation   of  T-ALL  cells after (B) small hairpin RNA-mediated LRH-1  knockdown (shLRH-1). Individual and mean values of technical triplicates of one representative experiment (n=3 biological replicates) ± SD anlyzed by two-way ANOVA are shown. Data information: ns = not significant, * p < 0.05, *** p < 0.001.",
    "diseases": "T-ALL"
  },
  {
    "caption": "(C) Cell cycle distribution of  T-ALL cells treated for 24 h with indicated concentrations of 3d2  as measured by propidium iodide flow cytometry. Representative results from n=3 biological replicates are shown. Stacked bars represent the mean of technical triplicates ± SD. Data information: ns = not significant, * p < 0.05, *** p < 0.001.",
    "diseases": "T-ALL"
  },
  {
    "caption": "(E) Flow cytometric  analysis of cell death by AnnexinV staining  in T-ALL cell lines upon treatment with indicated 3d2  concentrations. Mean values of n=4 biological replicates ± SD are shown. Data information: ns = not significant, * p < 0.05, *** p < 0.001.",
    "diseases": "T-ALL"
  },
  {
    "caption": "(A) Ex vivo response of human T cell acute lymphoblastic leukemia (T-ALL) patient-derived xenografts   (PDX), co-cultured on hTERT-immortalized primary  bone marrow MSCs, to treatment with indicated concentrations of 3d2  and/or dexamethasone  (Sample 1, 3 and 4: 1 nM; Sample 2: 0.1 nM). Cell viability  was quantified by fluorescent live cell staining using CyQuant combined with automated image analysis and calculated as percentage (%) of the  dimethyl sulfoxide treated control. Data information: All displayed experiments display one biological replicate.",
    "diseases": "T cell acute lymphoblastic leukemia, T-ALL"
  },
  {
    "caption": "(B) Synergy scores (Z-scores) between 3d2  and dexamethasone  of human T-ALL patient-derived xenografts  (PDX) were calculated from the viability  curves of PDX samples treated with increasing concentrations of 3d2  and/or dexamethasone  using SynergyFinder tool. Z-scores ≥ 0 indicate additivity or synergism and < 0 antagonism. Data information: All displayed experiments display one biological replicate.",
    "diseases": "T-ALL"
  },
  {
    "caption": "(E) In vivo leukemia  progression of  human T-ALL PDX transplanted into NSG mice  treated for 3 weeks with vehicle (PBS  control), 40 mg/kg 3d2  and or 10 mg/kg Dexamethasone  starting 3 days post transplantation. Engraftment  was calculated as % of human  vs total (human+mouse) CD45  positive (CD45+) cells as assessed by  flow cytometric analysis of peripheral blood. Data information: All displayed experiments display one biological replicate.",
    "diseases": "leukemia, T-ALL"
  },
  {
    "caption": "Quantification of human EGFL7 by qRT-PCR in primary GBM biopsies and corresponding PDX xenografts upon implantation of GBM-derived organotypic spheroids (n = 3; Mann-Whitney U-test; mean ± SEM); B - GBM biopsy; G - generation.",
    "diseases": "GBM"
  },
  {
    "caption": "Alignment of EGFL7 expression along with stromal (VWF, VEGFR1, VEGFR2, ACTA2, CD248, ITGAX, AIF1, CD68, CD4, and PTPRC) or tumor markers (EGFR, PDGFRA, VEGFA, VIM, and NES) in primary GBM biopsies or GBM-derived organotypic spheroids (PDX xenografts).",
    "diseases": "GBM"
  },
  {
    "caption": "Immunohisto­chemical (IHC) analyses revealed EGFL7 expression in blood vessels (arrow) and neurons (arrowheads) of healthy gray matter. Expression in malignant brain tumor specimens was restricted to blood vessels, in particular with a large diameter (arrows). Scale bar represents 50 µm. Quantitative scoring of EGFL7 staining in glioma specimens yielded about 25-40% EGFL7-positive blood vessels (n = 13 astrocytoma WHO° grade II, n = 25 astrocytoma WHO° grade III, n = 24 GBMs WHO° grade IV).",
    "diseases": "astrocytoma, glioma, brain tumor, GBMs"
  },
  {
    "caption": "Residual EGFL7 expression in BTPC11 glioma cells was reduced by a lentivirus-based approach. Knock-down of EGFL7 (shE7_1 or shE7_2) prolonged the median survival time of glioma-bearing mice (68 d or 69 d) as compared to scrambled control (shScr; 56 d; n = 6; log-rank test).",
    "diseases": "glioma"
  },
  {
    "caption": "EGFL7 promoted density and maturation state of glioma vessels Enhanced maturation of glioma vessels in the presence of hE7 or mE7 was verified by increased co-localization of PDGFRβ (pericytes) with CD31 (n = 3; one-way ANOVA; quantifications normalized to CD31). Data presented as mean ± SEM, AU-arbitrary units. Scale bars represent 60 µm.",
    "diseases": "glioma"
  },
  {
    "caption": "Enhanced maturation of glioma vessels in the presence of hE7 or mE7 was verified by increased co-localization of SMA (smooth muscle cells), with CD31 (n = 3; one-way ANOVA; quantifications normalized to CD31). Data presented as mean ± SEM, AU-arbitrary units. Scale bars represent 60 µm.",
    "diseases": "glioma"
  },
  {
    "caption": "Enhanced maturation of glioma vessels in the presence of hE7 or mE7 was verified by increased co-localization of (I+J) Col IV (basement membrane) with CD31 (n = 3; one-way ANOVA; quantifications normalized to CD31). Data presented as mean ± SEM, AU-arbitrary units. Scale bars represent 60 µm.",
    "diseases": "glioma"
  },
  {
    "caption": "Ectopic expression of murine EGFL7 (mE7) in GL261 mouse glioma cells followed by intracranial implantation into the striatum of immune-competent mice reduced overall survival but was rescued upon treatment with an integrin α5β1-inhibiting antibody (n = 6; log-rank test). Data presented as mean ± SEM. TCL-total cell lysate, AU-arbitrary units.",
    "diseases": "glioma"
  },
  {
    "caption": "Glioma-bearing mice were injected with anti-EGFL7 or anti-VEGF antibodies, a combination of both (Combo), or isotype negative controls. Mice were sacrificed upon showing first symptoms of disease and brains were analyzed by magnetic resonance imaging (MRI). Resulting brain tumor sections were analyzed for blood vessel density and maturation state by immunohistochemistry. (A+B) CD31 staining revealed that blocking of EGFL7, VEGF, or a combination of both lead to decreased tumor vessel density (n = 3; one-way ANOVA).",
    "diseases": "Glioma, brain tumor"
  },
  {
    "caption": "Glioma-bearing mice were injected with anti-EGFL7 or anti-VEGF antibodies, a combination of both (Combo), or isotype negative controls. Mice were sacrificed upon showing first symptoms of disease and brains were analyzed by magnetic resonance imaging (MRI). Resulting brain tumor sections were analyzed for blood vessel density and maturation state by immunohistochemistry. Staining for (C+D) PDGFRβ (n = 3; one-way ANOVA),",
    "diseases": "Glioma, brain tumor"
  },
  {
    "caption": "Glioma-bearing mice were injected with anti-EGFL7 or anti-VEGF antibodies, a combination of both (Combo), or isotype negative controls. Mice were sacrificed upon showing first symptoms of disease and brains were analyzed by magnetic resonance imaging (MRI). Resulting brain tumor sections were analyzed for blood vessel density and maturation state by immunohistochemistry. Staining for SMA (n = 3; one-way ANOVA)",
    "diseases": "Glioma, brain tumor"
  },
  {
    "caption": "Glioma-bearing mice were injected with anti-EGFL7 or anti-VEGF antibodies, a combination of both (Combo), or isotype negative controls. Mice were sacrificed upon showing first symptoms of disease and brains were analyzed by magnetic resonance imaging (MRI). Resulting brain tumor sections were analyzed for blood vessel density and maturation state by immunohistochemistry. Staining for Col IV (n = 3; one-way ANOVA) revealed decreased amounts of blood vessel-associated pericytes, smooth muscle cells and Col IV in the basement membrane of blood vessels upon treatment with anti-EGFL7, anti-VEGF and most significantly, a combination of both antibodies.",
    "diseases": "Glioma, brain tumor"
  },
  {
    "caption": "Glioma-bearing mice were injected with anti-EGFL7 or anti-VEGF antibodies, a combination of both (Combo), or isotype negative controls. Mice were sacrificed upon showing first symptoms of disease and brains were analyzed by magnetic resonance imaging (MRI). Resulting brain tumor sections were analyzed for blood vessel density and maturation state by immunohistochemistry. This resulted in an increased intratumoral vessel permeability as measured by T1-weightened MRI analyses of extravasating Gadovist (n = 6; one-way ANOVA).",
    "diseases": "Glioma, brain tumor"
  },
  {
    "caption": "Treatment with anti-EGFL7 (47 d), anti-VEGF (51 d), or a combination of both antibodies increased the median survival time of glioma-bearing Rag1-/- mice (58 d) as compared to isotype-treated controls (37 d; n = 6; log-rank test).",
    "diseases": "glioma"
  },
  {
    "caption": "Treatment of glioma-bearing NOD SCID mice with temozolomide (TMD) as a chemotherapeutic agent and a combination of anti-EGFL7 and anti-VEGF antibody increased the median survival time (Combo; 87 d; n = 5; log-rank test) as compared to anti-VEGF alone (80 d; n = 5; log-rank test) or isotype-treated controls (69 d; n = 5; log-rank test). Data presented as mean ± SEM, AU-arbitrary units. Scale bars represent 60 µm.",
    "diseases": "glioma"
  },
  {
    "caption": "(J, K) Representative IHC images (J), and analysis (K) of MYC, ALKBH5, SPI1 and PHF12 expressions in normal lymphocyte tissue (normal) and lymphoma specimens. Scale bar: 50 um. Data are presented as mean (±SEM), clinical samples n = 30 for normal group, n = 28 for low MYC expression group, n = 27 for high MYC expression group, P value was presented between indicated groups (Student's t‐test).",
    "diseases": "lymphoma"
  },
  {
    "caption": "G. Representative  western blots  comparing levels of cleaved  caspase-3 (17/19 kDa) and procaspase-3  (35 kDa) with respect to GAPDH  (38 kDa) loading control in synaptosomes  isolated from human  NDC, AD, NDC TREM2  and AD TREM2 brains. 1 lane represents 1 patient.",
    "diseases": "AD"
  },
  {
    "caption": "H. Western blot densitometry  analysis showing cleaved caspase-3 levels (left graph) and the ratio of cleaved caspase-3/procaspase-3 (right graph) in synaptosomes  (SN) isolated from human  NDC, AD, TREM2  NDC and TREM2  variants. N= 9 NDC, 11 AD, 5 TREM2  NDC, 10 TREM2 AD  cases. Data information: Data shown as mean ± SEM. The top and the bottom of the box plot (H) represent the 75th and 25th percentiles, respectively, and the line represents the median. The whiskers represent the highest and lowest values that are not outliers. One-way (H) ANOVA followed by Bonferroni's post-hoc test. P-values shown as ns P>0.05; *P<0.05; **P<0.01, ****P<0.0001.",
    "diseases": "AD"
  },
  {
    "caption": "(D) Frequency of apnea of 9 WT, 10 KO, 14 KO/HTTSD, and 9 KO/HTTSA mice at P35 and P55. (Kruskal-Wallis test with Dunn's comparison). Data information: Data are presented as the means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns = not significant.",
    "diseases": "apnea"
  },
  {
    "caption": "We treated 30-day-old Mecp2 KO mice (n=10) and Mecp2 KO/HTTSA mice (n=10) with 5mg/kg FK506 three times a week by intraperitoneal injection and assessed them in various behavioral tests. (D) Frequency of apnea of FK506-treated KO, FK506-treated KO HTTSA and vehicle-treated KO mice at P35 and P55 (Mann-Whitney test). Data information: *p < 0.05, **p < 0.01, ***p < 0.001, ns = not significant. Data are means ± SEM.",
    "diseases": "apnea"
  },
  {
    "caption": "(B-D) Kaplan-Meier survival  plots comparing the survival  probability of all melanoma patients  (B), BRAF-mutated patients  (C) and BRAF  wild-type (WT) patients  (D) with high- (magenta) and low (black) MCUA mRNA expression.",
    "diseases": "melanoma"
  },
  {
    "caption": "(E-G) Kaplan-Meier survival  plots comparing the survival  probability of patients  of indicated cancer types that are divided into either high- (magenta) or low (black) MCUA mRNA expression. P-values were calculated by using a log-rank test. Abbreviations: KICH  = kidney chromophobe; KIRC  =  kidney renal clear cell carcinoma; KIRP  = kidney renal papillary cell carcinoma; LUAD  = lung adenocarcinoma; LUSC  =  lung squamous cell carcinoma; PAAD  = pancreatic adenocarcinoma.",
    "diseases": "KICH, kidney chromophobe, kidney renal clear cell carcinoma, KIRC, LUAD, lung adenocarcinoma, lung squamous cell carcinoma, LUSC, PAAD, pancreatic adenocarcinoma, kidney renal papillary cell carcinoma, KIRP"
  },
  {
    "caption": "(E) Representative images of 1205Lu  shCTRL (black frame), shMCU_1 (darker blue frame) and shMCU_2 (lighter blue frame) melanoma spheroids  after 72 h invasion  in collagen. Live cells   are shown in green. Scale bar: 100 µm. (F) Quantification of 1205Lu  stable  MCUA_KD spheroid core size (n=6 biological replicates/condition, shown also by individual data points). Data information: Data are presented as mean ± SEM. Statistical significance was determined using unpaired, two‐tailed Student's t‐test (shMCU  cells were compared to their respective control, shCTRL), (*) p < 0.05; (**) p < 0.01; (***) p < 0.005; no asterisk means no statistical significance (p > 0.05).",
    "diseases": "melanoma"
  },
  {
    "caption": "(G) Representative images of WM3734  shCTRL (black frame), shMCU_1 (darker orange frame) and shMCU_2 (lighter orange frame) melanoma spheroids. Live cells are shown in green. Scale bar: 100 µm. (H) Quantification of WM3734  stable MCUA_KD spheroid core size  (n=5 biological replicates/condition, shown also by individual data points). Data information: Data are presented as mean ± SEM. Statistical significance was determined using unpaired, two‐tailed Student's t‐test (shMCU cells were compared to their respective control, shCTRL), (*) p < 0.05; (**) p < 0.01; (***) p < 0.005; no asterisk means no statistical significance (p > 0.05).",
    "diseases": "melanoma"
  },
  {
    "caption": "(L) Representative images of 451Lu  wild-type (grey frame), 451Lu-BR3 (lighter green frame), WM983B  wild-type (grey frame) and WM983B-BR (darker green frame) melanoma spheroids   after 72 h invasion  in collagen. Live cells  are shown in green. Scale bar: 100 µm. (M-N) Quantification of 451Lu  versus 451Lu-BR3 (M) and WM983B  versus  WM983B-BR (N)  spheroid core size   (n≥9 biological replicates/condition, shown also by individual data points). Data information: Data are presented as mean ± SEM. Statistical significance was determined using unpaired, two‐tailed Student's t‐test (shMCU  cells were compared to their respective control, shCTRL), (*) p < 0.05; (**) p < 0.01; (***) p < 0.005; no asterisk means no statistical significance (p > 0.05).",
    "diseases": "melanoma"
  },
  {
    "caption": " a Mortality curve showing that none of the Grin2a+/+ controls were affected, while audiogenic seizures (AGSs) followed by respiratory arrest (RA) were induced in all Grin2aS/S mice and in a subset of heterozygous Grin2a+/S mutants during the 11 kHz tone exposure [4 repetitions × 20 s tone, 2 s brake; pink squares; p < 0.0001 by Log-rank (Mantel-Cox) test]. ",
    "diseases": "respiratory arrest, AGS, audiogenic seizures"
  },
  {
    "caption": "b The c-Fos immunoreactivity was specifically increased in the hypothalamus (VMH), the inferior colliculus (IC), and periaqueductal gray (PAG) but not in the hippocampus (HPC) of a resuscitated Grin2aS/S mouse 90 min after AGS when compared to tone-exposed Grin2a+/+ littermates.",
    "diseases": "AGS"
  },
  {
    "caption": " c Memantine i.p. injection in Grin2aS/S mice, 3 h before tone exposure, rescued AGS susceptibility in Grin2aS/S mice. The rescue effect could still be observed in four out of eight, and in two out of eight, mice 27 and 51 h after memantine treatment, respectively. ",
    "diseases": "AGS"
  },
  {
    "caption": " d Increased c-Fos immunofluorescence (in grayscale) in the medial amygdala (MeA) and the VMH of a Grin2aS/S animal with AGS (saline injection) compared to a memantine rescued Grin2aS/S littermate. In the paraventricular nucleus of the thalamus (PVT), the hippocampus (HPC) and cortex (Cx) there was no difference in c-Fos expression between memantine-injected and saline-injected animals (for fluorescence images, see Supplementary Fig. 5). ",
    "diseases": "AGS"
  },
  {
    "caption": " f Decreased c-Fos DAB immunosignal in an MK-801 AGS-rescued Grin2aS/S animal (bottom) in the medial amygdala (MeA), the VMH and the PVT when compared to saline-injected Grin2aS/S littermate (top). Scale bars are in mm (for statistics: Supplementary Statistics to Fig. 4). ",
    "diseases": "AGS"
  },
  {
    "caption": "A. Hierarchical clustering of proteins significantly differentially abundant between NASH (n=20), cirrhosis (n=10) and control groups (n=15). Significance was calculated by ANCOVA, followed by Benjamini-Hochberg correction for multiple hypothesis testing (FDR < 0.05). Two major clusters of proteins were identified with Cluster 1 mainly upregulated in cirrhosis  compared to NASH  and controls and Cluster 2 downregulated. No additional replications of the experiment was done in laboratory.",
    "diseases": "cirrhosis, NASH"
  },
  {
    "caption": "D. Box‐and‐whisker plot showing the distribution of log2‐intensity values of statistical significantly regulated proteins across three groups. Number of independent biological replicates is n=15, 20 and 10 for the control, NASH  and cirrhosis  group, respectively. The black line in the middle of the box is the median, the top and the bottom of the box represent the upper and lower quartile values of the data and the whiskers represent the upper and lower limits for considering outliers (Q3+1.5*IQR, Q1‐1.5*IQR) where IQR is the interquartile range (Q3-Q1). Significance was defined by ANCOVA followed by Benjamini-Hochberg correction for multiple hypothesis testing (FDR < 0.05) with a significance level of ***P < 0.001. E. Heatmap of CYP 450 family members that are statistically significantly abundant between three groups. Data was presented as mean protein abundance followed by Z-score normalization across. Number of replicates is same as Panel (C). F. Extracellular matrix (ECM) remodeling in liver cirrhosis. Upper and lower panel shows the abundance rank of proteins involved in ECM  organization in the control (upper) and cirrhosis  (lower) groups, highlighting top shifted ECM  components in the cirrhosis  group as compared with the control group.",
    "diseases": "cirrhosis, liver cirrhosis, NASH"
  },
  {
    "caption": "(D-E) Representative immunofluorescence detection of LMP2 (red), CD8+ (green) and PD-1(red) in control and IPF lungs, arrows indicate double positive CD8+ PD-1+ cells, magnifications 10X, 20X and 40X correspond to a scale bar of 100 µm. Arrows indicate epithelial cells (E) or macrophages (M) and cells stained positive for CD8.",
    "diseases": "IPF"
  },
  {
    "caption": "(F) Flow cytometric analysis of CD3, CD8, and CCR7 expression on peripheral blood mononuclear cells (PBMCs) of control (n=21) and IPF (n=66) patients. Data are presented as gated % of parent. Data were analyzed with two-tailed unpaired Student's t-test. Asterisks indicate significance as *P<0.05.",
    "diseases": "IPF"
  },
  {
    "caption": "Comparison of the phenotype of ENCCs treated with the intestinal extract from hypoganglionosis rats at weeks 2, 4 and 6 after BAC treatment. The intestinal extracts from the sham-treated guts were used as controls. (A) Morphology of the ENCC-derived neurospheres on days 2 and 4. (B-C) The proliferation of ENCC-derived neurospheres is represented by neurosphere diameter (B) and change in diameter on day 4 compared with day 2 (C).",
    "diseases": "hypoganglionosis"
  },
  {
    "caption": "Comparison of the phenotype of ENCCs treated with the intestinal extract from hypoganglionosis rats at weeks 2, 4 and 6 after BAC treatment. The intestinal extracts from the sham-treated guts were used as controls. (D) ENCC viability assessed by CCK-8 assay.",
    "diseases": "hypoganglionosis"
  },
  {
    "caption": "Comparison of the phenotype of ENCCs treated with the intestinal extract from hypoganglionosis rats at weeks 2, 4 and 6 after BAC treatment. The intestinal extracts from the sham-treated guts were used as controls. (E) ENCCs number analyzed by nuclear staining with DAPI.",
    "diseases": "hypoganglionosis"
  },
  {
    "caption": "Comparison of the phenotype of ENCCs treated with the intestinal extract from hypoganglionosis rats at weeks 2, 4 and 6 after BAC treatment. The intestinal extracts from the sham-treated guts were used as controls. (F) Migration of ENCCs evaluated by transwell plate assay and stain with crystal violet,",
    "diseases": "hypoganglionosis"
  },
  {
    "caption": "Comparison of the phenotype of ENCCs treated with the intestinal extract from hypoganglionosis rats at weeks 2, 4 and 6 after BAC treatment. The intestinal extracts from the sham-treated guts were used as controls. (G) ENCC apoptosis determined by AnnexinV-FITC/PI stain and flow cytometry.",
    "diseases": "hypoganglionosis"
  },
  {
    "caption": "Comparison of fecal microbial species and inflammation in the hypoganglionosis and sham rats. For hypoganglionosis, fecal samples from the narrow segments (NS, BAC-treated, hypoganglionic) and expanded segments (ES, proximal to narrow segments, with abnormal ganglion) colon are analyzed, respectively. (A-D) Cluster analysis at the (A) phylum and (C) genus levels. A column accumulation diagram of the top 10 most abundant (B) phyla and (D) genera.",
    "diseases": "hypoganglionic, hypoganglionosis, inflammation"
  },
  {
    "caption": "Comparison of fecal microbial species and inflammation in the hypoganglionosis and sham rats. For hypoganglionosis, fecal samples from the narrow segments (NS, BAC-treated, hypoganglionic) and expanded segments (ES, proximal to narrow segments, with abnormal ganglion) colon are analyzed, respectively. Inter-group diversity analysis to compare the differences in (H) intestinal microbiota The species indicated in red are linked to SCFAs production.",
    "diseases": "hypoganglionic, hypoganglionosis"
  },
  {
    "caption": "Comparison of fecal microbial species and inflammation in the hypoganglionosis and sham rats. For hypoganglionosis, fecal samples from the narrow segments (NS, BAC-treated, hypoganglionic) and expanded segments (ES, proximal to narrow segments, with abnormal ganglion) colon are analyzed, respectively. metabolic mass spectrometry to compare the differences (I) SCFAs metabolites between the hypoganglionosis and sham rats.",
    "diseases": "hypoganglionic, hypoganglionosis, inflammation"
  },
  {
    "caption": "Comparison of fecal microbial species and inflammation in the hypoganglionosis and sham rats. For hypoganglionosis, fecal samples from the narrow segments (NS, BAC-treated, hypoganglionic) and expanded segments (ES, proximal to narrow segments, with abnormal ganglion) colon are analyzed, respectively. (J) Representative HE staining and quantification to assess the intestinal mucosal injury.",
    "diseases": "hypoganglionic, injury, hypoganglionosis, inflammation"
  },
  {
    "caption": "Comparison of fecal microbial species and inflammation in the hypoganglionosis and sham rats. For hypoganglionosis, fecal samples from the narrow segments (NS, BAC-treated, hypoganglionic) and expanded segments (ES, proximal to narrow segments, with abnormal ganglion) colon are analyzed, respectively. (K) Representative IHC stain and quantification of CRP and TNF-α levels.",
    "diseases": "hypoganglionic, hypoganglionosis, inflammation"
  },
  {
    "caption": "Comparison of fecal microbial species and inflammation in the hypoganglionosis and sham rats. For hypoganglionosis, fecal samples from the narrow segments (NS, BAC-treated, hypoganglionic) and expanded segments (ES, proximal to narrow segments, with abnormal ganglion) colon are analyzed, respectively. (L) Representative immunofluorescence stain and quantification of β-catenin levels. Nuclei were stained blue with DAPI.",
    "diseases": "hypoganglionic, hypoganglionosis, inflammation"
  },
  {
    "caption": "Comparison of ENCC-derived neurospheres treated with the intestinal extract from hypoganglionosis rats, hypoganglionosis treated with Fecal microbiota transplantation (FMT) and sham rat. The diameter of ENCC-derived neurospheres on day 2 (A).",
    "diseases": "hypoganglionosis"
  },
  {
    "caption": "Comparison of ENCC-derived neurospheres treated with the intestinal extract from hypoganglionosis rats, hypoganglionosis treated with Fecal microbiota transplantation (FMT) and sham rat. ENCC viability assessed by CCK-8 assay (B).",
    "diseases": "hypoganglionosis"
  },
  {
    "caption": "Comparison of ENCC-derived neurospheres treated with the intestinal extract from hypoganglionosis rats, hypoganglionosis treated with Fecal microbiota transplantation (FMT) and sham rat. (C-D) Migration of ENCCs using transwell plate assay and stain with crystal violet (C), scale bar, 200 µm. (D) Quantification of C. (E-F) ENCC apoptosis determined by AnnexinV-FITC/PI stain and flow cytometry (E). (F) Quantification of E.",
    "diseases": "hypoganglionosis"
  },
  {
    "caption": "Comparison of ENCC-derived neurospheres treated with the intestinal extract from hypoganglionosis rats, hypoganglionosis treated with Fecal microbiota transplantation (FMT) and sham rat. (G) Graphical protocol and weight change in the hypoganglionosis: untreated and treated with ENCCs only, or ENCCs+FMT.",
    "diseases": "hypoganglionosis"
  },
  {
    "caption": "Comparison of ENCC-derived neurospheres treated with the intestinal extract from hypoganglionosis rats, hypoganglionosis treated with Fecal microbiota transplantation (FMT) and sham rat. (H) Laparoscopic analysis indicating that the same segments were treated with BAC in all the groups.",
    "diseases": "hypoganglionosis"
  },
  {
    "caption": "Comparison of ENCC-derived neurospheres treated with the intestinal extract from hypoganglionosis rats, hypoganglionosis treated with Fecal microbiota transplantation (FMT) and sham rat. (I) Delay in distal colonic transit time.",
    "diseases": "hypoganglionosis"
  },
  {
    "caption": "Comparison of ENCC-derived neurospheres treated with the intestinal extract from hypoganglionosis rats, hypoganglionosis treated with Fecal microbiota transplantation (FMT) and sham rat. Comparison of neuronal markers. (J) Immunofluorescence stain and number of PGP9.5+ cells. Nuclei were stained blue with DAPI; Triangles indicate the PGP9.5+ cell.",
    "diseases": "hypoganglionosis"
  },
  {
    "caption": "Comparison of ENCC-derived neurospheres treated with the intestinal extract from hypoganglionosis rats, hypoganglionosis treated with Fecal microbiota transplantation (FMT) and sham rat. Comparison of neuronal markers. (K) Representative immunofluorescence images of Tuj1 and GFP localization at the injection and adjacent sides. Asterisks and triangles indicate the Tuj1+/GFP+ cells and Tuj1+/GFP- cells, respectively. Nuclei were stained blue with DAPI. (L-M) Number of Tuj1+, Tuj1+/GFP+ cells (L) and Tuj1+/GFP- cells(M).",
    "diseases": "hypoganglionosis"
  },
  {
    "caption": "Comparison of fecal microbial species, short-chain fatty acids and inflammation between hypoganglionosis: untreated (Hypoganglionosis) or treated with broad-range antibiotics (, Antibiotic), broad-range antibiotics followed by FMT (FMT) and sham groups. (A-D) Cluster analysis at the (A) phylum and (C) genus. Column accumulation diagrams of the top abundant microbiota at the (B) phylum and (D) genus levels.",
    "diseases": "hypoganglionosis, Hypoganglionosis, inflammation"
  },
  {
    "caption": "Comparison of fecal microbial species, short-chain fatty acids and inflammation between hypoganglionosis: untreated (Hypoganglionosis) or treated with broad-range antibiotics (, Antibiotic), broad-range antibiotics followed by FMT (FMT) and sham groups. (G) SCFAs subsets in the feces and intestinal extracts, analyzed by targeted mass spectrometry.",
    "diseases": "hypoganglionosis, Hypoganglionosis, inflammation"
  },
  {
    "caption": "Comparison of fecal microbial species, short-chain fatty acids and inflammation between hypoganglionosis: untreated (Hypoganglionosis) or treated with broad-range antibiotics (, Antibiotic), broad-range antibiotics followed by FMT (FMT) and sham groups. (H) IL-10, IL-17, and TNF-α levels in serum and intestinal extracts, assessed by ELISA.",
    "diseases": "hypoganglionosis, Hypoganglionosis, inflammation"
  },
  {
    "caption": "Comparison of fecal microbial species, short-chain fatty acids and inflammation between hypoganglionosis: untreated (Hypoganglionosis) or treated with broad-range antibiotics (, Antibiotic), broad-range antibiotics followed by FMT (FMT) and sham groups. Correlation analysis of acetate, propionate or butyrate with IL-17 in the intestinal extracts.",
    "diseases": "hypoganglionosis, Hypoganglionosis, inflammation"
  },
  {
    "caption": "B) Volcano plot for the F test on differential expression between healthy individuals and DMD patients.",
    "diseases": "DMD"
  },
  {
    "caption": "E) Volcano plot for the F test on differential expression between treated and untreated DMD patients.",
    "diseases": "DMD"
  },
  {
    "caption": "A. Protein lysates from the melanocytic-like melanoma  cells 501mel, MM011, MM074 and MM117 or the mesenchymal-like  melanoma  cells MM029, MM047  and MM099 were immuno-blotted for proteins as indicated. Molecular mass of the proteins is indicated (kDa).",
    "diseases": "melanoma"
  },
  {
    "caption": "B. Melanoma  cells were treated with increasing concentrations of THZ1 as indicated for 72h. Mean growth is shown relative to vehicle (DMSO)-treated cells. IC50 for each cell line is indicated. Melanocytic-type (MITF-High, proliferative) melanoma cells are shown in red, while mesenchymal-like (MITF-low, invasive) melanoma cells are shown in blue. Data information: data are presented as mean values + Standard Deviation (SD) for three replicates (n=3).",
    "diseases": "Melanoma, melanoma"
  },
  {
    "caption": "A. Rab25 expression correlates with glycogen levels in patienttumours. Total RNA and total cellular extracts, isolated from 31 ovarian cancer patient specimens, were subjected to Rab25 gene expression and glycogen content analysis using qPCR and glycogen assay, respectively.",
    "diseases": "tumours"
  },
  {
    "caption": "C) Kaplan Meier survival curve for neuroblastoma patients with low (red) or high (blue) expression of H2AFZ (H2A.Z.1) obtained from R2 genomics.",
    "diseases": "neuroblastoma"
  },
  {
    "caption": "F. Western blot analysis of PKD phosphorylation in proximal jejunum of morbidly obese female patients. Samples are loaded according to fasting triglyceride levels (lower to higher). n=7.",
    "diseases": "obese"
  },
  {
    "caption": "B and C, A human PCa  progression  tissue microarray was used for immunohistochemistry staining. Representative staining  images are shown in B. TRIM33 staining  by Gleason Scores is summarized in the histogram. Scale bar: 100 μm.",
    "diseases": "PCa"
  },
  {
    "caption": "A, The AR-TRIM33   coactivated gene signature was compared with two PCa patient-derived AR   gene signatures in multiple publicly available patient  datasets.",
    "diseases": "PCa"
  },
  {
    "caption": "C, Hierarchical clustering of PCa patients  from the TCGA Prostate  dataset (n = 480) resulted in two distinct clusters indicated in orange (high) and blue (low) based on the average expression  of our 36-gene signature.",
    "diseases": "PCa"
  },
  {
    "caption": "(E) Rapamycin-treated keratinocytes  (YF29  passage IV) can fully regenerate an epidermis  when transplanted onto SCID mice; grafts were harvested after 71 days and immunostained  with an HLA-1 antibody to identify the human  cells (white dotted line indicates the boundary between mouse  and human epidermis). Scale bar, 100 μm.",
    "diseases": "SCID"
  },
  {
    "caption": "(E) Percent of NK cells within the tumor in mice treated or not with LPS and depleted or not of DCs n (number of animals per group) ≥ 4. NT, control; DT, diphtheria toxin treated animals to deplete DCs; LPS, mice treated with LPS. Error bars depict SEM. Statistical significance was determined with a two-tail t test. NT, untreated.",
    "diseases": "tumor"
  },
  {
    "caption": "(B) Detection of blood vessels by immunohistochemistry using anti-CD31 antibody (brown staining) in frozen sections of tumors from mice treated or not with with LPS as in the scheme in (A). Nuclei are stained with hematoxylin. Two representative sections are shown, magnification 20X. Left panel scale bars, 500m; right panel scale bars 100 m. Quantification of vessel mean dimensions and area coverage by vessels is also shown. Three sections from three tumors have been analyzed. Error bars depict SEM. Statistical significance was determined with a two-tail t test. NT, untreated.",
    "diseases": "tumors"
  },
  {
    "caption": "(D) Percent of IFN-γ+ NK cells within the tumor in mice treated or not with LPS and with FTY720. n (number of animals per group)=4. Error bars depict SEM. FTY: FTY720. Statistical significance was determined with a two-tail t test. NT, untreated.",
    "diseases": "tumor"
  },
  {
    "caption": "(F) Percent of IFN-γ+ NK cells within the tumor in mice treated or not with LPS and with the anti-CD62L antibody.",
    "diseases": "tumor"
  },
  {
    "caption": "(A)  C-circle assay  for tumor samples. The presence of C-circles was tested in 22 osteosarcomas  by Rolling Circle Amplification  (RCA) assay using Φ29 DNA polymerase. Φ29 DNA polymerase  negative controls and Φ29 DNA polymerase-based reactions starting respectively with 75, 37.5, and 18.75 ng of DNA   were applied to dot blots  and C-circles were detected by hybridization  with a 32P-(CCCTAA)4 telomeric  probe. U2OS  and HeLa  cells correspond to positive and negative control samples, respectively.",
    "diseases": "osteosarcomas"
  },
  {
    "caption": "(B) Representative images of telomere FISH  (red) and PML IF  (green) colocalizations  (APBs) in osteosarcoma  tumor samples. DNA is counterstained  blue with DAPI. APBs  are indicated by white arrows. Scale bars are 5 μm.",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "(C) Representative image of TeSLA Southern Blot of two representative samples of ALT-positive (left) and telomerase-positive (right) osteosarcomas. Nine TeSLA PCRs  (30 pg each reaction) were done for each DNA  sample. DIG-labelled MW ladder has been added a posteriori. (D) Plot of cumulative TeSLA  fragment sizes (in kb) in ALT-positive (n=16) and ALT-negative (n=6) osteosarcomas. Points and error bars (± SEM) represent cumulative percentage of TeSLA  fragments from all the TeSLA PCRs  (n=9 per tumor sample) from all the patients  in both groups (n=16 in ALT-positive group, and n=6 in ALT-negative group). The Kolmogorov-Smirnov test was applied to identify statistical differences in TeSLA  fragments distributions (p=0.0016). (E) Individual TeSLa  fragment lengths in ALT-positive (n=16) and ALT-negative (n=6) osteosarcomas. Each dot represents a TeSLA  fragment, bars represent the median value for individual patient's  samples.",
    "diseases": "osteosarcomas"
  },
  {
    "caption": "(B) Tissue sections of two representative high-grade osteosarcomas  with HES (hematoxylin eosin saffron) staining  (left panel), anti-ATRX  (HPA064684) immunochemistry  (middle panel), and anti-DAXX  (HPA008736) immunochemistry  (right panel), showing ATRX protein expression in two ALT-positive samples. In the top panel, intratumoral ATRX  expression is negative (positive control osteoclasts  are shown). In the bottom panel, intratumoral ATRX  expression is high. Scale bars are 250 μm.",
    "diseases": "osteosarcomas"
  },
  {
    "caption": "(A) Copy-number-alteration (CNA) profiles of osteosarcomas. Representation of the GISTIC analysis with false discovery rate (FDR (q-value)) for all cases (n=22; left panel), ALT-positive/ATRX-wt cases (n=11; middle panel), and ALT-positive/ATRX-mutated cases (n=5; right panel).",
    "diseases": "osteosarcomas"
  },
  {
    "caption": "(B) Gain/amplification of TOP3A  gene region (17p11) is a genomic signature of ATRX-wt osteosarcomas. For each ATRX-mutated (top part) and ATRX-wt (bottom part) case, from the left to the right, the chromosome 17 and regional genomic profiles were established, with CGH  Analytics software. A focus was made within the genomic interval (17.25-19.11 Mb) of the short arm of  chromosome 17 (hg38 human genome mapping; Build 38 from NCBI, December 2013 version) including TOP3. Color profiles corresponding to the different tumors are defined at the top of each group. Most ATRX-wt cases show gain or amplification of this region (bottom part), whereas no ATRX-mutated cases display this alteration (top part).",
    "diseases": "osteosarcomas"
  },
  {
    "caption": "(A) Volcano plot of the supervised analysis of mRNA expression  profiles of osteosarcomas   according to ALT-positive vs. ALT-negative samples, showing upregulated (in red) and downregulated (in green) genes. Twelve tumors had sufficient RNA quality to be analyzed: seven ALT-positive ATRX-wt, two ALT-positive/ATRX-mutated and three ALT-negative.",
    "diseases": "osteosarcomas"
  },
  {
    "caption": "(A) Western blot showing ATRX protein expression in nine osteosarcoma  cell lines and HTC116  as positive control.",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "(B)  Western blot  showing TOP3A protein expression in nine osteosarcoma  cell lines and NY  siTOP3A as control.",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "(E) C-circle assay showing rescue of ATRX  ectopic expression by TOP3A  overexpression in U2OS osteosarcoma  cells Error bars represent the mean ± SEM from n = 2 experiments, n.s. = non-significant, *p < 0.05, Mann-Whitney test. Western blot and quantification of TOP3A  expression is shown for U2OS  cells overexpressing TOP3A.",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "(B) Representative images of telomeric  DNA (green) and PML  protein (red) colocalizations  (APBs) in osteosarcoma  and in vitro-immortalized ATRX-mutated or ATRX-wt cell lines according to TOP3A  KD. Scale bars are 5 μm. (C) Quantification of APB  frequency in osteosarcoma  and in vitro-immortalized ATRX-mutated or ATRX-wt cell lines according to TOP3A  KD; Error bars represent the mean ± SEM from n = 3 experiments, n = 150 cells scored per treatment, n.s., non-significant; Mann-Whitney test. (D) Effect of TOP3A  KD on Telomere  Dysfunction-Induced Foci (TIFs) in osteosarcoma  and in vitro-immortalized cell lines; Error bars represent the mean ± SEM from n = 3 experiments, n = 150 cells scored per treatment, *p < 0.05, **p < 0.005; Mann-Whitney test.",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "(E) Distributions of TeSLA  fragments in osteosarcoma  and in vitro-immortalized ATRX-mutated or ATRX-wt cell lines according to TOP3A  KD (left panel; each dot represents a TeSLA  fragment), and representative TeSLA Southern Blot image for NY  (right panel).",
    "diseases": "osteosarcoma"
  },
  {
    "caption": "Expression of USP28 (left) and TP63 (right) in human lung squamous cell carcinomas (SCC, n=498), adenocarcinomas (ADC, n=513) and normal non-transformed tissue (normal SCC=338, normal ADC=348). Xena UCSC software. In box plots, the centre line reflects the median, the cross represents the mean and the upper and lower box limits indicates the first and third quartile. Whiskers extend 1.5x the IQR and outliers are marked as dots.",
    "diseases": "ADC, adenocarcinomas, lung squamous cell carcinomas, SCC"
  },
  {
    "caption": "Correlation of mRNA expression of USP28 and TP63 in lung SCC (left, n=498), ADC (right, n=513) and normal, non-transformed tissue (normal SCC=338, normal ADC=348). R: Spearmans correlation coefficient; m=Slope. Xena UCSC software.",
    "diseases": "ADC, lung SCC, SCC"
  },
  {
    "caption": "IHC analysis of USP28 and ∆Np63 protein abundance in lung cancer and non-transformed human samples (n=300). The staining intensity was quantified in arbitrary units from 0 up to 3 by three independent pathologists. In box plots, the centre line reflects the median, the cross represents the mean and the upper and lower box limits indicates the first and third quartile. Whiskers extend 1.5x the IQR and outliers are marked as dots. p-values were calculated using two-tailed t-test.",
    "diseases": "lung cancer"
  },
  {
    "caption": "Kaplan-Meier estimator of NSCLC patients stratified by USP28 (left, n=1145) and TP63 (right, n=1926) expression. p-values were calculated using log-rank test. HR: hazard ratio. Kmplot software.",
    "diseases": "NSCLC"
  },
  {
    "caption": "Kaplan-Meier estimator of lung SCC patients stratified by USP28 expression (n=271). The p-value was calculated using a logrank test. HR: hazard ratio. Kmplot software.",
    "diseases": "lung SCC"
  },
  {
    "caption": "Relative expression of SCC marker genes KRT5, 14 and 19 in A-431 cells stably transduced with constitutive shRNA-non-targeting control (NTC), two independent shRNA-ΔNp63, two independent shRNA-USP28 or ΔNp63 in shRNA-USP28#1, normalised to ACTIN. Quantitative graph is represented as mean ± SD of three experiments (n=3).",
    "diseases": "SCC"
  },
  {
    "caption": "Genomic signature of primary human lung SCC samples comprising USP28, ∆Np63, KRT5, KRT14, KRT19, DSG3, MKI67, PCNA and GPRC5A. Samples were sorted dependent on relative USP28 expression (high to low). n=553. Xena UCSC software.",
    "diseases": "lung SCC"
  },
  {
    "caption": "GSEA of consensus squamous cancer marker genes (se Appendix Table S2) in A-431 cells stably transduced with sh-∆Np63#2 or sh-NTC. (N)ES: (normalised) enrichment score GSEA of consensus squamous cancer marker genes in A-431 cells stably transduced with sh-USP28#1 or sh-NTC. (N)ES: (normalised) enrichment score",
    "diseases": "squamous cancer"
  },
  {
    "caption": "Correlation of mRNA expression of consensus squamous cancer marker genes and TP63 in lung SCC and non-transformed lung tissue (Normal). R: Spearmans correlation coefficient. n=836. Gepia software. Correlation of mRNA expression of consensus squamous cancer marker genes and USP28 in lung SCC and non-transformed lung tissue (Normal). R: Spearmans correlation coefficient. N=836. Gepia software.",
    "diseases": "lung SCC, squamous cancer"
  },
  {
    "caption": "Representative IHC staining for ADC (TTF-1) and SCC (KRT5 and ∆Np63) marker expression as well as Usp28 abundance in KPL (n=6) and KPLU (n=5) lung tumours. Scale bar: 20µm.",
    "diseases": "ADC, SCC"
  },
  {
    "caption": "Representative qPCR of SCC and ADC marker expression in two independent KP lung tumour clones, resulting in KPADC and KPSCC; (ACTIN served as loading control). Quantitative graph is represented as mean ± SD of three experiments (n=3).",
    "diseases": "ADC, SCC"
  },
  {
    "caption": "Immunoblot against endogenous USP28 in the murine KPSCC cell line upon targeting with two independent shRNA sequences. ACTIN served as loading control.",
    "diseases": "SCC"
  },
  {
    "caption": "Representative haematoxylin and eosin (H&E) images of tumour bearing animals 8 weeks post intratracheal transplantation of 2 × 105 cells/animal. KPSCC sh-NTC (n=3); KPSCC sh-USP28 (n=3), Scale bar = 5000µm",
    "diseases": "SCC"
  },
  {
    "caption": "Quantification of % tumour area (top, normalised to total lung area) and lung tumour numbers (bottom) on KPSCC sh-NTC (n=6) and KPSCC sh-USP28 (n=6) animals.",
    "diseases": "SCC"
  },
  {
    "caption": "Representative IHC staining for ADC (TTF-1) and SCC (KRT5 and ∆Np63) marker expression as well as Usp28 and GFP abundance in KPSCC sh-NTC (n=3) and KPSCC sh-USP28 (n=3) lung tumours. Scale bar =50 µm",
    "diseases": "ADC, SCC"
  },
  {
    "caption": "Analysis of occurring TP63 genetic alterations in lung squamous (LUSC), cervical (CESC), oesophagus (ESCA), head and neck (HNSC) and pancreatic (PAAD) tumours. Cbioportal.",
    "diseases": "lung squamous (LUSC), cervical (CESC), oesophagus (ESCA), head and neck (HNSC), pancreatic (PAAD)"
  },
  {
    "caption": "Expression of TP63 (left) and USP28 (right) in human Lung (n=498), Cervix (n=254), Oesophagus (n=96) and HNSC (n=522) SCC tumours and normal non-transformed tissue (nLung=338 nCervix=3, nOesophagus=11 and nHNSC=44). In box plots, the centre line reflects the median, the cross represents the mean and the upper and lower box limits indicates the first and third quartile. Whiskers extend 1.5x the IQR. p-values were calculated using two-tailed t-test statistical analysis. Xena UCSC software.",
    "diseases": "HNSC, SCC"
  },
  {
    "caption": "Correlation of mRNA expression of KRT14 / KRT7 and TP63 in ADC and SCC tumours for Lung (nADC=513 and nSCC=498), Cervix (nADC=47 and nSCC=254) and Oesophagus (nADC=89 and nSCC=96). Blue dots: ADC; Red dots: SCC; R= Spearmans correlation coefficient; m: Slope. Xena UCSC.",
    "diseases": "ADC, SCC"
  },
  {
    "caption": "Cells were seeded at equal cell density and counted after five days, Brigth field images of control or sh-USP28#2 infected H1299, LUDLU-1adh, Hela, CaSKI, PANC-1 and BXPC-3 cells before quantification. Scale bar = 30µm Relative number of H1299, LUDLU-1adh, Hela, CaSKI, SiHa, PANC-1 and BXPC-3 sh-USP28#2 cells compared with sh-NTC control cells. p-values were calculated using two-tailed t-test statistical analysis. SiHa* = Notably, the human SCC cell line SiHa was negative for ΔNp63.",
    "diseases": "SCC"
  },
  {
    "caption": "LUDLU-1ADH, H1299, Ca Ski, Hela and SiHa cells were seeded at equal cell density and cultured in the presence of either DMSO, 1µM, 10µM or 30µM AZ1 for 48h. Scale bar for LUDLU-1adh and H1299 = 500µm. Scale bar for Ca Ski, Hela and SiHa = 250µm. SiHa* = Notably, the human SCC cell line SiHa was negative for ΔNp63. Number of cells were quantified with the Operetta imaging system using Hoechst staining. 50% growth inhibition (GI50) was calculated. n=30 fields analysed",
    "diseases": "SCC"
  },
  {
    "caption": "Representative staining of H&E and IHC for USP28 and ∆Np63 of SCC tumours from mice treated with PBS/DMSO/0,1% Tween80 or indicated concentrations of AZ1. Boxes indicate highlighted tumour areas. First line Scale bars = 500µm; Lower scale bars = 20µm. n=3   ∆Np63 staining intensity of lung tumours treated with PBS/DMSO/0,1%Tween80 or indicated concentrations of AZ1. nControl = 33712 cells ; nAZ1 125mg/kg = 7382 cells; nAZ1 375mg/kg = 4967 cells. Cells were analysed from three independent animals.   ",
    "diseases": "SCC"
  },
  {
    "caption": "A Proliferation of melanoma cell lines treated with LDHA inhibitor GSK-2837808A (10 μM) for the indicated duration under hypoxic (1% O2) and normoxic conditions. Data information: Statistical analysis was performed by two-way Anova for time-dependent proliferation changes and by one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. In (A) statistical comparison for the treatments that showed a significant change.",
    "diseases": "melanoma"
  },
  {
    "caption": "B (left) Immunoblotting of LDHA in melanoma cell lines transfected with non-targeting siRNA (NT-siRNA) or LDHA-specific siRNA for 72 hr. (right) Proliferation of melanoma cell lines transfected with NT-siRNA or LDHA-specific siRNA for the indicated timepoints. Data information: Statistical analysis was performed by two-way Anova for time-dependent proliferation changes and by one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. In (B), statistical comparison for the treatments that showed a significant change.",
    "diseases": "melanoma"
  },
  {
    "caption": "B, C Glucose (B) and glutamine (Gln, C) levels in the medium after treatment of melanoma cell lines with LDHAi for 72 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Unpaired t-test was used for the comparison of two groups, N.D., not determined. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "diseases": "melanoma"
  },
  {
    "caption": "D Medium Gln levels after transfection of melanoma cells with non-targeting (NT) or LDHA-specific siRNA for 96 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Unpaired t-test was used for the comparison of two groups N.D., not determined. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "diseases": "melanoma"
  },
  {
    "caption": "F qRT-PCR analysis of expression of the indicated SLC family transporters in MeWo (left) and A375 (right) melanoma cells after treatment with LDHAi for 48 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Unpaired t-test was used for the comparison of two groups N.D., not determined. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "diseases": "melanoma"
  },
  {
    "caption": "G Immunoblotting of SLC1A5 in melanoma cells treated with LDHAi for 96 hr.",
    "diseases": "melanoma"
  },
  {
    "caption": "H Immunoblotting of LDHA and SLC1A5 in melanoma cell lines transfected with NT-siRNA or indicated si-LDHA for 96 hr.",
    "diseases": "melanoma"
  },
  {
    "caption": "L Proliferation of melanoma cell lines for the indicated timepoints following treatment with LDHA-i, si-SLC1A5 or both. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. two-way Anova was used for the proliferation. N.D., not determined. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "diseases": "melanoma"
  },
  {
    "caption": "M (left) Long-term viability of melanoma cells treated as indicated for 8 days. (right) corresponding quantification showing change in viability. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Unpaired t-test was used for the comparison of two groups, N.D., not determined. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "diseases": "melanoma"
  },
  {
    "caption": "N Immunoblotting of SLC1A5 and cleaved caspase-3 in melanoma cells subjected to mock (NT-siRNA + DMSO) or si-SLC1A5 treatment for 24 hr followed by exposure to LDHAi for 72 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Unpaired t-test was used for the comparison of two groups, N.D., not determined. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "diseases": "melanoma"
  },
  {
    "caption": "Immunoblotting of total and phosphorylated S6, ULK1, and eIF4EBP1 in melanoma cells (D) treated with LDHAi for 96 hr Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "diseases": "melanoma"
  },
  {
    "caption": "Immunoblotting of total and phosphorylated S6, ULK1, and eIF4EBP1 in melanoma cells (E) transfected with non-targeting (NT) or LDHA-specific siRNAs for 96 hr Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "diseases": "melanoma"
  },
  {
    "caption": "Immunoblotting of total and phosphorylated S6, ULK1, and eIF4EBP1 in melanoma cells (F) si-SLC1A5-transfected for 24 hr followed by treatment with LDHAi for 72 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "diseases": "melanoma"
  },
  {
    "caption": "H Proliferation of melanoma cells treated with LDHAi, m-TORC1 inhibitor (Rapamycin, 100 nM), or a combination of the two. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Unpaired t-test was used for the comparison of two groups, and two-way Anova was used for the proliferation. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "diseases": "melanoma"
  },
  {
    "caption": "I (top) Long-term viability of melanoma cells treated as indicated for 10 days. (bottom) corresponding quantification showing change in viability. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "diseases": "melanoma"
  },
  {
    "caption": "J Immunoblotting of cleaved caspase-3 and p-(S780)-Rb in melanoma cells treated as indicated for 72 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "diseases": "melanoma"
  },
  {
    "caption": "Immunoblotting of ATF4 in melanoma cell lines (A) treated with the LDHA inhibitor LDHAi for 96 hr Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups.",
    "diseases": "melanoma"
  },
  {
    "caption": "Immunoblotting of ATF4 in melanoma cell lines (B) transfected with non-targeting (NT) or LDHA-specific siRNAs for 96 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups.",
    "diseases": "melanoma"
  },
  {
    "caption": "D Immunoblotting of ATF4, c-MYC and SLC1A5 in melanoma cell lines treated with LDHAi for 2, 24, or 48 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups.",
    "diseases": "melanoma"
  },
  {
    "caption": "E Immunoblotting of ATF4 and SLC1A5 in melanoma cell lines mock- or si-ATF4-treated for 24 hr and then incubated with LDHAi for 48 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups.",
    "diseases": "melanoma"
  },
  {
    "caption": "F qRT-PCR analysis of SLC1A5 transcript levels in melanoma cell lines transfected with si-ATF4 for 24 hr and then incubated with LDHAi for 24 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "diseases": "melanoma"
  },
  {
    "caption": "H Proliferation of melanoma cell lines mock- or si-ATF4-transfected and incubated with LDHAi as indicated for up to 96 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Unpaired t-test was used for the comparison of two groups, and two-way Anova was used for the proliferation. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "diseases": "melanoma"
  },
  {
    "caption": "A GC-MS-based quantification of intracellular Asp (upper) and Ser (lower) levels in melanoma cell lines treated with LDHAi for 72 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups and unpaired t-test for the comparison of two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "diseases": "melanoma"
  },
  {
    "caption": "B (upper) GC-MS-based 13C6-glucose fractional isotope labeling of Ser and Asp in melanoma cells treated for 72 hr with LDHAi. (lower) GC-MS-based 13C5-glutamine fractional isotope labeling of Asp in melanoma cell lines treated for 72 hr with LDHAi. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups and unpaired t-test for the comparison of two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "diseases": "melanoma"
  },
  {
    "caption": "C Athymic nude mice were injected subcutaneously with A375 melanoma cells expressing inducible (Tet-On) sh-LDHA expression vector. Starting day 5, animals were treated on alternate days with 1 g/L doxycycline, 4 mg/kg rapamycin, or with a combination of the two (n=8 in each group). The tumor growth was determined by measuring the tumor volume. Statistical analysis was performed using Welch's t-test (two-tailed). Data are shown as the mean ± SEM ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "diseases": "melanoma"
  },
  {
    "caption": "D Immunoblot analysis of retinal lysates from 6-7 week old WT and NYKO mice. GFAP was used as a marker for reactive astrogliosis and SDHA as a loading control. Data were analyzed using unpaired t-test, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001, ns = not significant. Data are means ± SEM.",
    "diseases": "astrogliosis"
  },
  {
    "caption": "c, ISX association proteins (PCAF, BRD4, CBP, CREB, and RNA Pol II) determined by Western blot in anti-ISX immunoprecipitates of tumor tissues from patients with lung cancer. Data information: Each experiment was repeated at least three times.",
    "diseases": "lung cancer"
  },
  {
    "caption": "Cell migration (wound healing, h) ssay of A549 lung cancer cells treated with Garcinol. V, vehicle. Data are presented as mean ± SD in graph (***, p < 0.001 , Student's t‐test) of 3 independent experiments, each performed in triplicate. Scale bar, 100μm. Data information: Each experiment was repeated at least three times. ",
    "diseases": "lung cancer"
  },
  {
    "caption": "i, Cell invasion (transwell, i) assay of A549 lung cancer cells treated with Garcinol. V, vehicle. Data are presented as mean ± SD in graph (***, p < 0.001 , Student's t‐test) of 3 independent experiments, each performed in triplicate. Scale bar, 100μm. Data information: Each experiment was repeated at least three times.",
    "diseases": "lung cancer"
  },
  {
    "caption": "a, IHC staining with ISX (brown) or PCAF (brown) antibody in lung tumors from patients with lung cancer. N, normal tissue; T, tumor mass; Nuclei, hematoxylin (blue); Blue and red arrow, cytosol and nuclear ISX (PCAF). Scale bar, 500μm (400X); Scale bar, 2mm (100X).",
    "diseases": "lung cancer"
  },
  {
    "caption": "b, Confocal immunofluorescence detection of ISX (green) and BRD4 (red) in lung tumors from patients with NSCLC. Cell nuclei were visualized by DAPI (blue); Yellow arrows indicate co-localization; IgG, negative control. N, normal tissue; T, tumor mass.",
    "diseases": "NSCLC"
  },
  {
    "caption": "c, Confocal immunofluorescence detection of ISX (green) and PCAF (red) in lung tumors from patients with NSCLC. Cell nuclei were visualized by DAPI (blue); Yellow arrows indicate co-localization; IgG, negative control. N, normal tissue; T, tumor mass.",
    "diseases": "NSCLC"
  },
  {
    "caption": "Correlation analysis of mRNA expression for, (d) ISX and BRD4, in 157 lung cancer samples.",
    "diseases": "lung cancer"
  },
  {
    "caption": "e, Correlation analysis of mRNA expression for, (e) ISX and PCAF in 157 lung cancer samples.",
    "diseases": "lung cancer"
  },
  {
    "caption": "f, Protein expression of ISX, ISX(69Kac) and Vimentin in tumor and normal parts from patients with NSCLC by western blotting. N, normal tissue; T, tumor mass; Arrow, target protein; *, unspecific band.",
    "diseases": "NSCLC"
  },
  {
    "caption": "The Kaplan-Meier survival curve was used to analyze survival correlation between patients (n=157) with NSCLC and ISX (g) levels. On the basis of the cut-off values of fold differences, the study population was dichotomized into the \"high\" and \"low\" expression group. p‐values were calculated by log‐rank (Mantel-Cox) test comparing the two Kaplan-Meier curves.",
    "diseases": "NSCLC"
  },
  {
    "caption": "g and h, The Kaplan-Meier survival curve was used to analyze survival correlation between patients (n=157) with NSCLC and PCAF (h) levels. On the basis of the cut-off values of fold differences, the study population was dichotomized into the "high" and "low" expression group. p‐values were calculated by log‐rank (Mantel-Cox) test comparing the two Kaplan-Meier curves.",
    "diseases": "NSCLC"
  },
  {
    "caption": "A) MALDI imaging was performed on tumor-containing brain sections at a lateral resolution of 100µm and (M-H) ions were analysed in negative mode with a FTICR Mass Spectrometer (analytical range 100-1000Da). Hematoxylin-eosin (HE) staining of the same sections was performed after MALDI analysis. Patient-derived glioma xenografts (PDXs) with IDH wildtype (IDHwt), IDH mutant (IDHm), and control brain tissue (CB) were analyzed in a non-targeted and targeted approach using regions of interest (ROI) of different sizes to compare tumor (T, yellow line) and contralateral control brain (CB, blue line). The non-targeted approach was used for statistical pair-wise comparisons between samples, while the targeted approach on a selected set of metabolites allowed distribution and quantification analyses.",
    "diseases": "tumor"
  },
  {
    "caption": "B) Histological sections of 3 IDHwt PDXs (P3, T434, P8) and 3 IDHm PDXs ((T394, E478, T186) showing a large ROI (boxed rectangle, >500 pixels) within the tumor area applied for targeted quantification of selected metabolites. Left rectangle in P3 PDX was used as control contralateral brain (CB) for quantifications. Middle panel shows tissue distribution of D-2-hydroxyglutarate (D2HG) by MSI, which is exclusively detected in IDHm PDXs (D2HG in IDHwt tumours is below detection limit). Right panel shows tissue distribution of a key metabolite (m/z 778.51) presenting strong accumulation in IDHm lower grade gliomas (LGG) versus glioblastomas (GBM) independent of IDH status. An intensity-dependent color code indicates the relative amount of a specific compound (defined by m/z value) throughout the tissue section.",
    "diseases": "tumor"
  },
  {
    "caption": "C) Energetic charge defined as the ratio of (ATP+1/2ADP)/(ATP+ADP+AMP) was calculated at each pixel to present its distribution throughout the tumor.",
    "diseases": "tumor"
  },
  {
    "caption": "(D) The energetic charge ratio was confirmed by the LC-MS data performed on separate tumor extracts (n=3/ sample/ group). Indicated statistical significant group differences are based on T test, pv: p-values.",
    "diseases": "tumor"
  },
  {
    "caption": "B) Quantification of metabolite distribution by MSI in 6 PDX with IDH1wt and IDH1m status (n=3 / group) and in contralateral control brain (CB). No significant differences between IDH groups were detected, although significant differences are found between tumors and control brain (glutamate, apsartate). Color code as in Fig. 1, NAA: N-acetylaspartic acid; NAAG: N-acetylaspartylglutamic acid.",
    "diseases": "tumors"
  },
  {
    "caption": "A) Gene expression of multiple cachexia-associated markers in gastrocnemius muscles of individual animals from Study 1 (n=5 for tumor-bearing groups; n=6 for tumor-free groups). Expression was determined by qRT-PCR and presented as described in the Materials and Methods (Geometric Mean ± Geometric STD). B) Androgen receptor (AR) mRNA expression in gastrocnemius muscles from Study 1. Statistics: p values provided in Appendix Table S5A-B. Dunnett's multiple comparison test. CEBPδ, n=4, insufficient sample to analyze all tumor-bearing GTx-024-treated animals.",
    "diseases": "cachexia"
  },
  {
    "caption": "A) Effect of GTx-024 and AR-42 monotherapies on cachexia-related differentially regulated genes (DEGs) from RNA-seq analyses of Study 1 gastrocnemius muscles. All three panels consist of individual genes plotted with respect to their log2 fold change and -log10 Benjamini-Hochburg adjusted p-values from the comparison of cachexia vs tumor-free controls. Colors of the points reflect the DEG status of each gene for the given comparison.",
    "diseases": "cachexia"
  },
  {
    "caption": "C) Significance values from GSEA using combined STAT3 gene sets identified in B. Each treatment group is compared to tumor-bearing control (cachexia) transcriptomes.",
    "diseases": "cachexia"
  },
  {
    "caption": "E) Results of GSEA using combined ATF-1 gene sets identified in B across treatment groups versus tumor-bearing control (cachexia) transcriptomes.",
    "diseases": "cachexia"
  },
  {
    "caption": "A Domain structure of UBQLN2 in upper region. HEK 293 cells were transfected with FLAG-tagged UBQLN2-WT or ALS-linked mutants (∆UBA, ∆UBL, P497H or P509S), along with mCherry-Parkin. After 24 h, the cells were treated with 5 µg/mL A/O for 5 h. The cells were stained with anti-FLAG (green) and anti-TOM20 (gray) antibodies, and then were visualized using confocal microscopy. Scale bars, 10 µm. Insets were higher magnifications of the dashed box area. Scale bars, 2.5 µm.",
    "diseases": "ALS"
  },
  {
    "caption": "C The cells were transfected with mCherry-Parkin and HA-tagged UBQLN2-WT or ALS-mutants as A and subjected to immunofluorescent assay as in A, but were treated with 1 µg/mL A/O for 24 h. Scale bar, 10 µm. Yellow arrow indicates uncleared mitochondria.",
    "diseases": "ALS"
  },
  {
    "caption": "The DLBCL  cell lines DoHH2, SU-DHL-6, Karpas 422 and HBL-1 were treated with the indicated concentrations of IACS-010759 and ascorbate, and cell viability  determined after 24 hours. (A) Live cell counts. n=3 biological replicates; error bars: SD.",
    "diseases": "DLBCL"
  },
  {
    "caption": "The indicated lymphoma  cell lines and PDX samples were xenografted  in recipient animals and tumors allowed to develop to detectable sizes prior to randomization and treatment with  IACS-010759 (IACS) by oral gavage  and/or ascorbate  (Asc) by intraperitoneal injection, as indicated (see Materials and methods). Daily doses and the number of animals per group (n) are indicated in parenthesis. (A, B) Tumor progression  (mm3) in CD1 nude mice  bearing subcutaneous Ramos  (A) or DoHH2  tumors (B). Data information: In each panel, the plot on the right shows the data for individual groups on the indicated day. Error bars: SD; n = animals per group. Right: one-way between-group ANOVA. * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001.",
    "diseases": "lymphoma"
  },
  {
    "caption": "The indicated lymphoma  cell lines and PDX samples were xenografted  in recipient animals and tumors allowed to develop to detectable sizes prior to randomization and treatment with IACS-010759 (IACS) by oral gavage and/or ascorbate  (Asc) by intraperitoneal injection, as indicated (see Materials and methods). Daily doses and the number of animals per group (n) are indicated in parenthesis. (C, D) Tumor progression  in NSG mice  injected with the luciferase-positive DHL-derived PDX lines DFBL-20954 (C) or  DFBL-69487 (D), as determined by in vivo imaging and quantification of bilateral femur radiance efficiency. Examples from the control and double-treated groups are shown at the bottom. Data information: In each panel, the plot on the right shows the data for individual groups on the indicated day. Error bars: SD; n = animals per group. Right: one-way between-group ANOVA. * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001.",
    "diseases": "lymphoma, DHL"
  },
  {
    "caption": "A Expression  of PTPN11 (gene encoding SHP2) in skin lesions in psoriatic patients  compared with skin  from healthy donors based on microarray data (No. GSE14905). B Expression of ptpn11  in human PBMCs  of psoriatic patients (n=14) and normal controls (n=16). Data information: Data are represented mean ± SEM. P values are determined by two-tailed Mann-Whitney U test *P<0.05, **P<0.01.",
    "diseases": "psoriatic"
  },
  {
    "caption": "C Representative SHP2 staining in skin sections of psoriatic patients  (n=13) and normal controls (n=5). Scale bars: 200 μm.",
    "diseases": "psoriatic"
  },
  {
    "caption": "D Western blot analysis of PBMCs lysates derived from psoriatic patients and normal controls.",
    "diseases": "psoriatic"
  },
  {
    "caption": "E The catalytic activity of SHP2 was measured in human PBMCs lysates derived from psoriatic patients (n=25) and normal controls (n=25). Data information: Data are represented mean ± SEM. P values are determined by two-tailed unpaired Student's t-test *P<0.05, **P<0.01.",
    "diseases": "psoriatic"
  },
  {
    "caption": "F Representative p-ERK staining of skin sections of psoriatic patients and normal controls. Scale bars: 200 μm.",
    "diseases": "psoriatic"
  },
  {
    "caption": "I  Quantitative PCR analysis of mRNA levels in human PBMCs derived from psoriatic patients (n=20) and normal healthy controls (n=20). Data information: Data are represented mean ± SEM. P values are determined by two-tailed unpaired Student's t-test *P<0.05, **P<0.01.",
    "diseases": "psoriatic"
  },
  {
    "caption": "ELISA  quantification of protein levels of cytokines in mouse serum. Quantitative PCR analysis of mRNA encoding  psoriasis-related cytokines in the dorsal skin of C57BL/6 mice treated with indicated dose of SHP099  or vehicle for 4 days. Results were normalized to Gapdh  expression. Data information: Data are represented mean ± SEM. P values are determined by two-tailed unpaired Student's t-test *P<0.05, **P<0.01.",
    "diseases": "psoriasis"
  },
  {
    "caption": "I Skin sections from  psoriatic patients  and healthy controls were  immune-stained  for TLR7  together with a marker of the early  endosome  (EEA1) or late endosome/lysosome (LAMP1) prior to analysis by  confocal microscopy, showing TLR7 localization in different organelles (arrows). Scale bar: 50 μm.",
    "diseases": "psoriatic"
  },
  {
    "caption": "Tlr7wt/wt female mice  (n=6) and Tlr7-Y1025D mutant Tlr7ki/wt female mice (n=6) and Tlr7ki/ki female mice (n=5) were treated with indicated dose of IMQ  for 4 days. D Quantitative PCR analysis of mRNA encoding IL-23/IL-17A axis cytokines and other psoriasis-related cytokines in the dorsal skin. Results were normalized to  Gapdh expression. Data information: Data are represented mean ± SEM. P values are determined by two-tailed Mann-Whitney U test *P<0.05, **P<0.01.",
    "diseases": "psoriasis"
  },
  {
    "caption": "G, The number of metastatic colonies in lungs in the pulmonary metastasis model using the indicated cells stably transfected with ZBTB2 expression vector (ZBTB2) or its empty vector (EV) (left) and the representative images of lungs (right).",
    "diseases": "pulmonary metastasis"
  },
  {
    "caption": "A, Tissue microarrays of human lung adenocarcinoma (243 samples) stained with anti-ZBTB2 antibodies. High magnification images are shown in the left lower side of each image. Scale bar, 500 and 100 μm in the low and high magnification images, respectively.",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "C, Kaplan-Meier analysis of the disease-free survival of the lung cancer patients stratified by the expression levels of ZBTB2 and p53 status.",
    "diseases": "lung cancer"
  },
  {
    "caption": "D-F, TCGA-based Kaplan-Meier analysis of overall survival of lung adenocarcinoma patients stratified by the expression levels of ZBTB2 and those of BAX (D), ZMAT3 (E), and CEACAM1 (F).",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "(B) The upper panel showing qRT-PCR analysis of four identified LUAD-associated RBPs (ADARB1, CELF2, QKI and ZFP36) mRNA levels in 61 LUAD tissues and matched paracarcinoma tissues. The lower panel showing relative mRNA expression (T/N) of the four RBPs in metastatic (n = 28) and non-metastatic (n = 33) LUAD tissues. LUAD tissues were classified into metastatic and non-metastatic tissues as described in Materials and Methods. T, LUAD tissues; N, paracarcinoma tissues. Y axis represents the log10 transformed fold change of mRNA expression (T/N) of four RBPs.",
    "diseases": "LUAD"
  },
  {
    "caption": "(E-G) Kaplan-Meier survival curves of LC, LUAD and LUSC patients (n=1540, n=865 and n=675, respectively) with high or low expression levels of QKI. The log-rank test was used to analyze the difference between two groups.",
    "diseases": "LUAD, LC, LUSC"
  },
  {
    "caption": "(H) qRT-PCR analysis of endogenous mRNA levels of QKI-5, QKI-6, and QKI-7 in human bronchial epithelial cell line BEAS-2B, LUAD cell lines A549 and H1299.",
    "diseases": "LUAD"
  },
  {
    "caption": "(J) Kaplan-Meier survival curves of LUAD patients (n=865) with high or low expression levels of TGFβR1. The log-rank test was used to compare the difference between two groups.",
    "diseases": "LUAD"
  },
  {
    "caption": "(A) Mettl14 cKO leads to perinatal lethality. Newborn cKO pups are smaller with tight and shiny skin.",
    "diseases": "perinatal lethality"
  },
  {
    "caption": "(G) Wound healing as monitored by  wound  size 8 days post injury. n=3; P<0.01 (Student's t-test). Error bar represents S.D. (standard deviation).",
    "diseases": "wound"
  },
  {
    "caption": "H) Histological staining of skin sections at the wound edges. Halves of wound sections are shown. Note significant reduction of  HPE (hyperproliferative epidermis) in cKO skin. Es: eschar. Dotted lines denote epidermal boundaries. (I) Quantification of Ki67-positive cells present in wound HPE. The plot indicates the mean (open circles within the box), 25th percentile (bottom line of the box), median (middle line of the box), 75th percentile (top line of the box), 5th and 95th percentile (whiskers), 1st and 99th percentile (solid triangles) and minimum and maximum measurements (solid squares). n=19, P<0.01 (Student's t-test). ",
    "diseases": "wound"
  },
  {
    "caption": "(G) Representative photographs of  fly eyes expressing GMR-GAL4 driven (GGGGCC)28-EGFP  at 29˚C along with the quantifications of necrosis and eye width. n=28-30/genotype. Error bars represent mean +/- SD.",
    "diseases": "necrosis"
  },
  {
    "caption": "(B) Correlation between replicate mock infections. Path-seq reads were recovered from samples of macrophage RNA spiked with 0.1% MTB RNA. Scatter plot of log2 RPKM values is shown with Pearson correlation, P-value < 0.0001. Inset summarizes the mock infection replicates and their fraction of MTB reads (of all aligned reads) from Path-seq and standard RNA-seq methods.",
    "diseases": "infection, infections"
  },
  {
    "caption": "(A) Path-seq profiles of desA1, desA2 in MTB infected BMDMs. Error bars show the standard deviation from three biological samples. Representative results from two experiments are presented.",
    "diseases": "infected"
  },
  {
    "caption": "(B) Upper panel: dissolved oxygen curve over 120 h time course showing controlled depletion (1), sustained hypoxia (2) and controlled reaeration (3). Points represent the average of three biological replicates and were measured via fiber optic technology that non-invasively probes oxygen levels in the culture (PreSens Precision Sensing GmbH). Lower panel: expression profiles (RNA-seq) of desA1 and desA2 over the time course and oxygen levels. Error bars show the standard deviation from three biological samples.",
    "diseases": "hypoxia"
  },
  {
    "caption": "(B) Heatmap of TFs with decreased (purple) or increased (green) activity at specific time points during in vitro or in vivo infection.",
    "diseases": "infection"
  },
  {
    "caption": "(C) Rv0681 regulon genes differentially expressed in vitro and the evidence for predicted high Rv0681 activity (induced expression of target genes). (D) Zur regulon genes differentially expressed in vitro and the evidence for decreased Zur activity (de-represses target genes). (E) Rv0691c regulon genes differentially expressed in vitro and in vivo; evidence for increased Rv0691c activity (increased up- and down-regulation of target genes) at 24 h from both in vitro and in vivo infection.",
    "diseases": "infection"
  },
  {
    "caption": " (A) Expression of PARP1 and KLF4 in mammary gland epithelial cell and various types of breast cancer cell lines. ",
    "diseases": "breast cancer"
  },
  {
    "caption": " (B). Accumulation of PARP1 and KLF4 protein were detected in human breast cancer tissues with 183 breast invasive ductal carcinoma and 10 pairs of primary cancer and adjacent normal tissue specimens by IHC in comparison with adjacent normal breast tissues. Scale bars, 100 μm. ",
    "diseases": "breast cancer, breast invasive ductal carcinoma"
  },
  {
    "caption": "(E) Statistical analysis of PARP1 staining among normal (n=10), ER/PR positive (ER/PR) (n=68), HER2 positive (n=62), and triple negative breast cancer (TNBC) (n=48). The p values were labeled in figure, one-way ANOVA was used for the statistical analysis.",
    "diseases": "TNBC, triple negative breast cancer"
  },
  {
    "caption": " (F) Statistical analysis of KLF4 protein staining among normal (n=10), ER/PR positive (n=68), HER2 positive (n=62) and TNBC (n=47). The p values were labeled in figure, one-way ANOVA was used for the statistical analysis. ",
    "diseases": "TNBC"
  },
  {
    "caption": " Elevated expression of PARP1 and KLF4 are significantly correlated in 183 breast invasive ductal carcinoma human breast cancer tissue specimens (same batch of staining as (B)). Represents of paired IHC staining of PARP1 and KLF4 (case 1-3) are shown (G). Scale bars, 100 μm. ",
    "diseases": "breast cancer, breast invasive ductal carcinoma"
  },
  {
    "caption": " (H) Statistic analysis of IHC staining indicates that PARP1 expression is positively correlated with KLF4 expression in breast cancer. n=183, r=0.434, p=8.68x10-10, Pearson correlation coefficients. ",
    "diseases": "breast cancer"
  },
  {
    "caption": " (I) Survival analysis of KLF4 protein expression in 117 breast cancer patients. Compared to patients with low KLF4 protein expression, patients with high KLF4 levels had an inferior cumulative survival rate (Kaplan-Meier assay, LogRank P=0.012); Low, staining weak and moderate; High, staining strong. ",
    "diseases": "breast cancer"
  },
  {
    "caption": " (J) Survival analysis of both KLF4 and PARP1 protein expression in 66 breast cancer patients. Compared to patients with both low KLF4 and PARP1 protein expression levels, patients with both high KLF4 and PARP1 levels had lower cumulative survival rate (Kaplan-Meier assay, LogRank P=0.022). ",
    "diseases": "breast cancer"
  },
  {
    "caption": " (A) Depletion of KLF4 significantly enhances the efficacy of Olaparib in killing TNBC cells (4T1). 4T1 cells with stable expression of shKLF4 were implanted into mammary fat pad of BALB/c Nude mice. Drug treatment was started at 10th day. Placebo or Olaparib at the dose of 100 mg/kg was administrated daily for twelve days. Tumor volumes were measured every other day. Tumor volumes were measured every other day. n=9 per group, p values were labeled in figure, one-way ANOVA assay. ",
    "diseases": "TNBC"
  },
  {
    "caption": "Flow cytometric analysis showing the frequency of LK and KSL cells in lineage-negative cells (left panel) and LT-HSC in KSL (right panel) in: IF injection of EV from Molm-14 cells (red, n=8), AML plasma EV (Orange, n=6) and human CD34 EV (Blue, n=4) relative to the vehicle-injected contralateral femurs. Data were obtained from at least two independent experiments.",
    "diseases": "AML"
  },
  {
    "caption": "A heatmap showing the highly-deregulated ribosomal proteins in AML-EV exposed cells.",
    "diseases": "AML"
  },
  {
    "caption": "Flow cytometric analysis showing the histograms and MFI of O-propagyl-puromysin (OPP) incorporation in LT-HSC in: IF injection of EV from Molm-14, U-937, HL-60 (red, n=5,43), AML patients plasma (Orange, n=6), or human CD34+ cells (blue, n=3) normalized to vehicle-injected contralateral femurs after subtracting the background fluorescence.",
    "diseases": "AML"
  },
  {
    "caption": "A. Representative images of IHC staining  of PCIF1  in three CRC  tissues and adjacent noncancerous tissues. Scale bar, 50 μm (left). Analysis of the PCIF1 protein expression in normal and CRC  tissues. Each dot represents one sample (right). Data are the mean ± SEM. **P < 0.01, by Student's t-test.",
    "diseases": "CRC"
  },
  {
    "caption": "B. Kaplan-Meier plots of  overall survival  of 27 CRC patients  with low tumor PCIF1  expression (0-4.5 staining  score, n = 18) or high tumor PCIF1  expression (4.6-9.0 staining  score, n = 9). Data are the mean ± SEM. ***P < 0.001 by Student's t-test.",
    "diseases": "CRC"
  },
  {
    "caption": "C. Western blot  analysis of PCIF1  in normal colon  cells (CCD841CON) and various CRC  cell lines. GAPDH  served as a loading control.",
    "diseases": "CRC"
  },
  {
    "caption": "Matrigel invasion  assay  (B), of the indicated control and PCIF1-depleted CRC  cell lines. Representative images and quantification of cells are shown at the left and right, respectively, of each panel. Data are the mean ± SD of n=3 replicates/condition. *P < 0.05, **P < 0.01, ***P < 0.001 by Student's t-test.",
    "diseases": "CRC"
  },
  {
    "caption": "fibronectin adhesion  assay (C), of the indicated control and PCIF1-depleted CRC  cell lines. Representative images and quantification of cells are shown at the left and right, respectively, of each panel. Data are the mean ± SD of n=3 replicates/condition. *P < 0.05, **P < 0.01, ***P < 0.001 by Student's t-test.",
    "diseases": "CRC"
  },
  {
    "caption": "colony formation assay (D) of the indicated control and PCIF1-depleted CRC cell lines. Representative images and quantification of cells are shown at the left and right, respectively, of each panel. Data are the mean ± SD of n=3 replicates/condition. *P < 0.05, **P < 0.01, ***P < 0.001 by Student's t-test.",
    "diseases": "CRC"
  },
  {
    "caption": "wound healing migration assay  (E) of the indicated control and PCIF1-depleted CRC  cell lines. Representative images and quantification of cells are shown at the left and right, respectively, of each panel. Data are the mean ± SD of n=3 replicates/condition. *P < 0.05, **P < 0.01, ***P < 0.001 by Student's t-test.",
    "diseases": "CRC"
  },
  {
    "caption": "G. Positive correlation between FOS  and PCIF1 protein levels in tumors from 29 patients  with CRC  (R2 =0.6902, P < 0.001).",
    "diseases": "CRC"
  },
  {
    "caption": "(A) Photos of the midbrain  of a control subject (left) and PD patient  harboring the CHCHD2T61I mutation (right). The dashed lines indicate the SNpc. A portion of the midbrain  of the control subject was lost when slicing.",
    "diseases": "PD"
  },
  {
    "caption": "(B-G) Colocalization  of extra-mitochondrial CHCHD2T61I with  CSNK1E/D, p-NEFL472, and p-α-SYN129 in the brain  of a PD patient  harboring the CHCHD2T61I mutation. Each brain  section was deparaffinized and immunostained  with anti-CHCHD2   and anti-ANT1/2 (B), anti-CSNK1E/D (C), anti-p-NEFL472 (D, E), or anti-p-α-SYN129 antibodies (F, G). Arrowheads indicate extra-mitochondrial CHCHD2T61I puncta (B), and puncta showing colocalization  of CHCHD2T61I with CSNK1E/D (C), p-NEFL472 (D), and p-α-SYN129 (F). Arrows indicate weaker colocalization  between  CHCHD2T61I and the indicated proteins in the control brain  (C, D, F). Dashed lines indicate cell shapes. In (E, G), the amount of p-NEFL472 (E) and p-α-SYN129 (G) was measured by the average fluorescence intensity per cell (n  = 30 cells in each experiment). Red bars indicate mean values. Comparisons were performed using the unpaired two-tailed Student t-tests. **p < 0.01",
    "diseases": "PD"
  },
  {
    "caption": "iPSCs  were prepared from a healthy control and a PD patient  harboring the CHCHD2T61I mutation. An isogenic control iPSC  line was generated by the correction of the gene mutation Then, these iPSC  cells were differentiated into dopaminergic (DA) neurons, and analyzed by immunofluorescence  using anti-CHCHD2 (A-E), anti-ANT1/2 (A), anti-CSNK1E/D (B), anti-p-NEFL472 (C), and anti-p-α-SYN129 antibodies (D) Arrowheads indicate extra-mitochondrial CHCHD2T61I (A), puncta showing colocalization  of CHCHD2T61I with CSNK1E/D (B), p-NEFL472 (C, , and p-α-SYN129 (D, Dashed lines indicate cell shapes.",
    "diseases": "PD"
  },
  {
    "caption": "A Representative picture of in situ hybridization (ISH) staining of miR-31 in skin biopsies of healthy individuals and psoriasis patients (n=5 individuals in each group). Quantification of results showing the average level of miR-31 in skin epidermis (right panel). B, basal layer; S+G, spinous and granular layers. Scale bars: 100 μm.",
    "diseases": "psoriasis"
  },
  {
    "caption": "B Representative pictures of Immunohistochemical staining of GLUT1, GLS, and GS in skin biopsies of HC and Ps (n=5 individuals in each group). Scale bars: 200 μm.",
    "diseases": "Ps"
  },
  {
    "caption": "IHC staining and the expression scored in a tissue array of 75 pairs of human lung cancer patient tissues. Scale bar represents 1000 μm.",
    "diseases": "lung cancer"
  },
  {
    "caption": "Representative figures of p-T172-BCL9 IHC staining in interphase cells of breast cancer (D) or lung cancer (E) patient tissue. Scale bars represent 100 μm.",
    "diseases": "breast cancer, lung cancer"
  },
  {
    "caption": "Log-rank (Mantel-Cox) survival analysis based on high and low p-T172-BCL9 expression scored by immunohistochemical staining in two tissue arrays with (G) 75 lung cancer samples or (H) 145 breast cancer samples.",
    "diseases": "breast cancer, lung cancer"
  },
  {
    "caption": "(A) EAE severity in 6-to-8-week-old female (left panel) and male (right panel) wild-type (WT) and ERα-/- mice (n=7-9 mice per group). (B) EAE sensitivity to IFNβ in 6-to-8-week-old female (top panel) and male (bottom panel) WT and ERα-/- mice. Vehicle (Veh) or IFNβ (47 μg/kg) were i.p. injected. every other day from 0 to 10 dpi (n= 8-12 mice per group).",
    "diseases": "EAE"
  },
  {
    "caption": "(D) Sensitivity of EAE to IFNβ in Cyp19-/- ovary-transferred female WT mice and WT ovary-transferred Cyp19-/- mice (n=5-6 mice).",
    "diseases": "EAE"
  },
  {
    "caption": "(A) Brightfield micrograph of ventral horns of Golgi-Cox stained lumber (L)5 spinal cord section of male WT and ERα-/- EAE mice at 33 dpi with quantitation of area stained in gray matter. The white dotted line indicates the division between white and gray matter, V.H. represents the ventral horn (n=5 mice per group).",
    "diseases": "EAE"
  },
  {
    "caption": "(A) Upregulated and downregulated genes in RNAseq analysis were evaluated by qPCR. Splenic CD4+ T cells from male WT EAE and ERα-/- EAE mice at 9 dpi were used (n=5-8 mice).",
    "diseases": "EAE"
  },
  {
    "caption": "(D) Neurite outgrowth of the neurons in Golgi-stained spinal sections of Tcra-/- recipient mice that received passive intrathecal injections of CD4+ splenic cells from male WT EAE and ERα-/- EAE mice at 14 dpi quantified using the Sholl technique. Sholl rings are separated by 10 μm (n=4 mice per group, 20 neurons analyzed per animal) with an end radius of 100 μm.",
    "diseases": "EAE"
  },
  {
    "caption": "(C) Neurite outgrowth of the neurons in Golgi-stained spinal sections of Tcra-/- recipient mice that received passive intrathecal injections of CD4+ splenic cells from male WT EAE and cERα-/- EAE mice at 14 dpi quantified using the Sholl analysis method. Sholl rings are separated by 10 μm (n=4 mice per group, 20 neurons analyzed per animal) with an end radius of 100 μm.",
    "diseases": "EAE"
  },
  {
    "caption": "(A) Number of membrane-bound lymphotoxin (mLT)+ DCs (derived from spleen and LNs) in male cERα-/- EAE mice at 9 dpi (n=5 mice per group). DC population were gated as Ly6G- and CD11c+ (EV Fig.1 A).",
    "diseases": "EAE"
  },
  {
    "caption": "D Average frequency distribution of nucleosome positions relative to each other. Data was aligned to each mapped nucleosome in the genome and plotted for a 600 bp window for pl-iPSC, NPC and the chronic myelogenous leukaemia (Cml) derived cell line, K562. In all cases, a prominent single nucleosome is presented with only minor flanking peaks, indicating that the majority of nucleosomes do not occur as evenly spaced arrays in human cells.",
    "diseases": "chronic myelogenous leukaemia, Cml"
  },
  {
    "caption": "B ChIP gel images showing the relative enrichment by H3K4me3 in controls (n=9) and PD patients (n= 18). PCR amplified a 188-bp region of SNCA from intron 1 where H3K4me3 peak was at its optimum. Mouse IgG (mIgG) was used as control and the bands were normalized by unbiased amplification from respective inputs. Data information: Data represent mean ± standard error of the mean.",
    "diseases": "PD"
  },
  {
    "caption": "D The graph represents the statistically significant difference of relative H3K4me3 enrichment between PD (n=7) and controls (n=6). Neuronal nuclei from PD brain samples show significantly higher enrichment of H3K4me3 at SNCA intron 1 (p=0.01) compared to controls. *P < 0.05. Data were analyzed using non-parametric t-test followed by Mann-Whitney post-hoc corrections. Two-tailed p-values were calculated for all. Data information: Data represent mean ± standard error of the mean.",
    "diseases": "PD"
  },
  {
    "caption": "E ChIP on H3K4me3 at the SNCA promoter between sPD1-1 lines after locus-specific epigenomic modulation. Differentiated cells were transiently transfected with either sgA-dCas9 5xGCN4-scFV-JARID1A or sg A-dCas9 5xGCN4-scFV-empty backbone vectors. A significant reduction in H3K4me3 at the SNCA promoter was observed in cells transfected with JARID1A. Data information: Three independent repeats were performed for both ChIP experiments. *P < 0.05; ****P<0.0001. Data were analyzed using non-parametric t-test followed by Mann-Whitney post-hoc corrections. One-tailed p-values were calculated for ChIP analysis",
    "diseases": "sPD"
  },
  {
    "caption": "A Immunohistochemical  positive staining  for NALCN  in human prostate adenocarcinoma  tissues, but not in normal or hyperplastic prostate   tissues (tissue microarray: PR484, US Biomax, Inc). T2N0M0  - tumor invaded submucosa  without any regional or distant metastases  (stage II); T3aN0M0  - tumor had broken through the capsule  of the prostate gland and invaded through  muscularis propria  (stage III); T3N1M0  - tumor invaded through muscularis propria  with 1 to 3 regional lymph node metastases  (stage IV). Data information: The images: scale bar is 100 µm.",
    "diseases": "metastases, prostate adenocarcinoma, hyperplastic"
  },
  {
    "caption": "C Immunohistochemistry: significant correlation (P<0.0001) between positive staining  of NALCN  and Src  in clinically localized prostate cancer, but not in non-cancerous prostate. Data information: The images: scale bar is 100 µm.",
    "diseases": "prostate cancer"
  },
  {
    "caption": "D Immunohistochemistry: positive staining  of NALCN  in bone metastases produced by breast  and colon cancers, but not in corresponding normal tissues. Data information: The images: scale bar is 100 µm.",
    "diseases": "bone metastases, colon cancers"
  },
  {
    "caption": "E Left: x-ray  3D images obtained from mice  8 weeks after intracardiac injections with control (PC-3 Luc) and cells stably overexpressing NALCN  (+hNALCN). Right: box plots compare the incidence and total volume of bone lesions between the two groups of 11 mice: central band shows the mean, the boxes show lower and upper quartiles and whiskers show maximum data values. Data information: Red numbers and/or arrows in the images depict tumour take incidence/bone lesions. *P<0.05, **P<0.01, and n.s., not significant, two-tailed Mann-Whitney U test.",
    "diseases": "bone lesions"
  },
  {
    "caption": "(c) Representative images from colon cancer tissues by immunohistochemistry staining. Negative correlation between Beclin1 and Dvl was observed in late stages of tumours, whereas positive correlation between p62 and Dvl in late stages of tumours. Scale bar, 25 μm.",
    "diseases": "tumours"
  },
  {
    "caption": "(d) Immunoblotting of human colon tumour samples versus normal tissues using indicated antibodies. N, normal tissue; T, tumour.",
    "diseases": "tumour"
  },
  {
    "caption": " B An Integrative Genomics Viewer (IGV) screenshot of the Notch de novo TE insertion site from sample P47 (clonal neoplasia) and its head control, sample P48. Bars represent sequencing reads. Reads supporting the TE insertion are colored according to homology to a specific TE insertion sequence. Multiple colors at a putative insert site frequently indicate homology to different reference copies of the same TE family. Two types of supporting reads can be seen: soft-clipped reads - spanning the insertion site and mapping partially to the reference genome and partially to the TE, and mate pair support reads - flanking the insertion site and mapping to the reference genome but with mates (not seen) mapping to the TE. ",
    "diseases": "neoplasia"
  },
  {
    "caption": " D PCR validation of 4 somatic, neoplasia-specific TE insertions. Primers were designed to target regions flanking the insertion sites. Yellow arrowheads indicate PCR products containing an insertion amplified in the clonal DNA but not in the neighboring gut tissue (non-clonal), head or thorax for the same fly. Short wild-type amplicon was detectable in all samples. Thorax DNA sample was not available for sample P15. ",
    "diseases": "neoplasia"
  },
  {
    "caption": "DBA/2J mice were injected s.c. with 1× 105 P388 murine leukemia cells, followed by injection of the anti-hTAPBPL mAb (25, 50, or 100µg) or isotype Ab (25, 50, or 100 µg) 3 times per week. Tumors size was measured over time. The mean tumor diameter (mm3) + S.D. at the indicated time points are shown.",
    "diseases": "leukemia"
  },
  {
    "caption": "In contrast, Ndrg4fl/fl and Ndrg4fl/fl-VillinCre mice have a similar bodyweight (I) and develop an equal number of adenomas (J) with an equivalent diameter (K,L). N=13 vs. 12 in I, n=13 vs. 11 in J and n=10 vs. 8 in K.",
    "diseases": "adenomas"
  },
  {
    "caption": "Box plot reflecting the quantitative nanoLC-MS/MS analysis results shows the up-regulation of NID1 and FBLN2 in the colorectal cancer tissue secretome (n=17) compared to the normal colon tissue secretome (n=17). Data are analyzed with R version 3.5.2 and the ibb R package. Within the box plots, each dot represents the log10 transformed raw count of an individual sample; the inside band is the median value; the bottom and top of the box the first and third quartile, respectively; and the whiskers reflect the minimum and maximal values within 1.5× the interquartile range.",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "Representative images of human colonic cancer epithelium (n=3) shows a high scattered expression of NID1 and FBLN2 within the cancerous epithelium. Scale bar, 50 μm.",
    "diseases": "cancerous, colonic cancer"
  },
  {
    "caption": "(D - I) Examples of drug-stimulus interactions, for each category. Plots show the natural logarithm of the relative viability  of 192 CLL  samples after treatment with the respective drug and stimulus. Each line represents one patient  sample linked across treatments. Black horizontal lines in each single treatment indicate the expected viability  based on linear modelling. Black and blue horizontal lines in the combinatorial treatment indicate the expected viability  based on the additive effect of the drug and stimulus (blue), and the expected viability  accounting for the additive effect and the interaction (black). (D+E) Ibrutinib, a clinically used BTK  inhibitor, is blocked by IL4  and IFNγ. (F) The JAK  inhibitor pyridone-6 inhibits the pro-survival effect of sCD40L  + IL4  stimulation. (G) The p38  inhibitor ralimetinib  and IFNγ  show a synergistic pro-survival effect not observed in either single treatment. (H) TLR  agonists, including CpG ODN (shown) increase sensitivity to BTK  inhibition by ibrutinib, despite increasing viability  as single treatments. (I) Soluble anti-IgM  sensitises CLL  samples to HSP90  inhibition by luminespib.",
    "diseases": "CLL"
  },
  {
    "caption": "Beeswarm-boxplots of the natural logarithm of the relative viability  of 169 CLL  samples, for (C) fludarabine  + CpG ODN and combinatorial treatments, faceted by IGHV  status and trisomy 12 status. P-values from paired Student's t-test . The central bar, boxes and whiskers of the plot represent the median, first and third quartiles, and 1.5-times IQR, respectively.",
    "diseases": "trisomy 12, CLL"
  },
  {
    "caption": "Beeswarm-boxplots of the natural logarithm of the relative viability  of 169 CLL  samples, for (D) ibrutinib  + IL4  single and combinatorial treatments, faceted by IGHV  status and trisomy 12 status. P-values from paired Student's t-test . The central bar, boxes and whiskers of the plot represent the median, first and third quartiles, and 1.5-times IQR, respectively.",
    "diseases": "CLL"
  },
  {
    "caption": "(A Mean (A) pSTAT6 staining  intensity in CLL-infiltrated (n=100 for pSTAT and tumour-free lymph node  biopsies (n=98 for pSTAT6 after background subtraction (y axis), p-values from Student's t-test. Each dot represents the mean of all cells in the  tissue microarray cores per patient  sample. The central bar, boxes and whiskers of the plot represent the median, first and third quartiles, and 1.5-times IQR, respectively.",
    "diseases": "CLL"
  },
  {
    "caption": "B) Mean (B) pIRAK4 staining  intensity in CLL-infiltrated (n=100 for pIRAK4) and tumour-free lymph node biopsies n=100 for pIRAK4) after background subtraction (y axis), p-values from Student's t-test. Each dot represents the mean of all cells in the  tissue microarray cores per patient  sample. The central bar, boxes and whiskers of the plot represent the median, first and third quartiles, and 1.5-times IQR, respectively.",
    "diseases": "CLL"
  },
  {
    "caption": "Example images of immunohistochemistry  sections: (C + D) pSTAT6  levels in (C) CLL-infiltrated and (D) tumour-free samples. Scale bar defines 20µm in all images.",
    "diseases": "CLL"
  },
  {
    "caption": "Example images of immunohistochemistry  sections: (E + F) pIRAK4  levels in (E) CLL-infiltrated and (F) tumour-free samples. Scale bar defines 20µm in all images.",
    "diseases": "CLL"
  },
  {
    "caption": "(G) qPCR analysis of stomach-restricted gene set between KL ADC and KLN mucinous tumor sections (n=3 or 4 per group). Results were shown in a box and whisker plot with the minimum value, first quartile, median, third quartile and maximum value. The box represented the 50% of the central data, with a line inside represented the median. The significance was calculated by two-tailed unpaired Student's t-test with Welch's correction. *p=0.0260 (Hnf4α), *p=0.0275 (Vsig1), *p=0.0122 (Gkn3), *p=0.0324 (Ctse), **p=0.0084 (Onecut2).",
    "diseases": "ADC, mucinous tumor"
  },
  {
    "caption": "(D) Western blot for NANOG and TUBULIN in 7 paired human normal lungs (N) and ADC samples (T) and human ESCs. Mr, relative molecular mass. kDa, killoDalton.",
    "diseases": "ADC"
  },
  {
    "caption": "(H) Statistic analysis of LKB1 expression in ADC and IMA. The tumor tissues were analyzed by IHC staining and graded as low, medium, high expression. Significance was calculated by χ2 test for trend.",
    "diseases": "ADC, IMA"
  },
  {
    "caption": "(I) The expression grade of IHC staining of NANOG, NKX2-1, LKB1 in 76 human IMA (1 sample/row).",
    "diseases": "IMA"
  },
  {
    "caption": "(B-D) H&E staining of tumors, IHC staining (B) and quantification of NICD (C) and HES1 (D) in KL ADC and KLN IMA. Representative images were shown. Scale bar, 50 μm. Results were shown as mean ± SD. The numbers of tumors analyzed over KL ADC and KLN IMA were 15, 18 for NICD, 16, 15 for HES1. Significance was calculated by two-tailed unpaired Student's t-test with Welch's correction. *p=0.0188 (C), **p=0.0040 (D).",
    "diseases": "ADC, IMA"
  },
  {
    "caption": "(I, J) Statistical analysis of Ki67 (I) and CC3 (J) activity in ADC and IMA lung sections of vehicle and phenformin (Phen) groups. The numbers of tumors analyzed over vehicle group and phenformin groups for ADC and IMA were 17, 8, 9 for Ki67, 10, 10, 7 for CC3. Results were shown as mean ± SEM. Significance was calculated by one-way ANOVA with Dunnett's multiple comparisons test. **p=0.0010 (I), ***p=0.0009 (I), *p=0.0427(J).",
    "diseases": "ADC, IMA"
  },
  {
    "caption": "Four to six-week-old C57BL/6  mice were injected i.p. with 104-107 PFU of  WNV-poly(A), 104 PFU of WT  WNV  or PBS (negative control) in a volume of 200 μL. Histological analysis  of mouse brain. Scale bars represent 100 μm and 50 μm for left and right panels, respectively. Severe vacuolization (black arrows) and  inflammation (yellow arrow) in brain small vessels as well as degenerative changes in neurons with  cytoplasmic rarefaction (blue arrow) and  necrosis  with nuclear compaction (red arrow) were indicated. Scale bars represent 100 μm and 50 μm for left and right panels, respectively",
    "diseases": "inflammation, necrosis"
  },
  {
    "caption": "B-C. Wound healing assays were performed using IBIDI® chambers to evaluate the role of the AhR  on cell migration. Images of the wound  were captured using an Axio Vert.A1 inverted microscope (Carl Zeiss®) at 5x magnification. The histogram represents the mean ± s.d. Wound  closure was determined by measuring the distance between the edges of the wound  at time  0 and 15 h (n = 3 independent technical experiments for each cell lines or conditions) and compared using unpaired t-tests with the Sidak-Bonferroni method. B. Results obtained with BRAFi-sensitive or resistant SK28  cells KO for the AhR  in the absence of treatment. (n = 3 independent technical experiments for each cell lines). C. Results obtained for the migration assay  (0 to 15 h) for SK28  R cells KO or not for the AhR  after treatment or not with 10 μM CH-223191. (n = 3 independent technical experiments for each cell lines or conditions, mean ± s.d.). Statistical analysis using unpaired t-tests with the Sidak-Bonferroni method has been performed between the mean of the 3 independent experiments.",
    "diseases": "wound, Wound"
  },
  {
    "caption": "B. Protein levels of the AhR, p-SRC  (Y416), SRC, p-FAK  (Y576/577), and FAK  in the four different melanoma  cell lines (n=3). The level of BRAFi resistance corresponds to our measure of IC50  (Vemurafenib) for the different cell lines 501Mel  (0,23uM), SKMel28  (0,29uM), M229  (0,89uM) and M238  (2,16uM). These cell lines correspond to the sensitive parental cells.",
    "diseases": "melanoma"
  },
  {
    "caption": "(c) MYC IHC in tumours from Vil Apc and Vil Apc Huwe1hom mice. Scale bars = 50 µm.",
    "diseases": "tumours"
  },
  {
    "caption": "(d) MYC Western blot in protein extracts from Vil Apc and Vil Apc Huwe1hom tumours. Levels of MYC protein are significantly increased in tumours lacking HUWE1 (Mann Whitney, p = 0.04, n = 3).",
    "diseases": "tumours"
  },
  {
    "caption": "(e) QRT-PCR analysis of Myc expression in tumours from Vil Apc and Vil Apc Huwe1hom mice.",
    "diseases": "tumours"
  },
  {
    "caption": "(b) Quantification of total tumour numbers per gut in sacrificed Vil Apc Pten, Vil Apc Pten Huwe1, Vil Apc Pten Myc and Vil Apc Pten Huwe1 Myc mice. Heterozygous deletion of Myc did not reduce the number of tumours in Huwe1 deleted mice (Vil Apc Pten Huwe1 vs Vil Apc Pten Huwe1 Myc. Mann Whitney, n ≥ 10).",
    "diseases": "tumours"
  },
  {
    "caption": "(d) γ-H2AX IHC of Vil Apc and Vil Apc Huwe1hom tumours, note increased positivity in Huwe1 deficient tumours. Scale bars = 50 µm.",
    "diseases": "tumours"
  },
  {
    "caption": "(a) Caspase 3 IHC of tumours from Lgr5 Apc and Lgr5 Apc Huwe1 mice either untreated or 6h post treatment with 7.5mg/kg cisplatin. Arrows identify caspase 3 positive cells. Scale bars = 50 µm. (b) Quantification of cisplatin treatment showing a significant increase in apoptosis in Huwe1 deficient tumour cells (Mann-Whitney, n = 3 vs 5).",
    "diseases": "tumour, tumours"
  },
  {
    "caption": "(c) Comparison of somatic mutation rate (mutations / Mb) between human tumours carrying HUWE1 mutations or not. Note the significant increase in mutational burden in HUWE1 mutated tumours (Mann-Whitney, p = 0.0002, n ≥ 15).",
    "diseases": "tumours"
  },
  {
    "caption": "(d) Comparison of somatic mutation rate (mutations / Mb) between human tumours carrying HUWE1 mutations or not grouped according to MLH1 status. Note that the increased mutation rate is found primarily in tumours where MLH1 is not silenced indicating increased mutation rate (and HUWE1 mutation itself) is not due to silencing of MLH1 (Mann-Whitney, p = 0.0007, n ≥ 11).",
    "diseases": "tumours"
  },
  {
    "caption": "(c) Lysozyme IHC demonstrating increased lysozyme positive cell numbers in tumours from Lgr5 Apc Huwe1 mice. Scale bars = 200 µm (low magnification), 100 µm (high magnification inset). (d) OLFM4 IHC demonstrating expanded stem cell population in Lgr5 Apc Huwe1 tumours. Scale bars = 200 µm (low magnification), 100 µm (high magnification inset).",
    "diseases": "tumours"
  },
  {
    "caption": "(a) MCL1 Western blot in protein extracts from Vil Apc and Vil Apc Huwe1hom tumours. Levels of MCL1 protein are significantly increased in tumours lacking HUWE1 (Mann Whitney, p = 0.04, n = 3).",
    "diseases": "tumours"
  },
  {
    "caption": "(A, B) Quantification of effect of CPT on ROS level as detected by staining with the H2O2 dye CMH2DCFDA (A), and on NAD+/NADH ratio (B) in control, FAD, and DS iPSC-derived neurons.",
    "diseases": "FAD, DS"
  },
  {
    "caption": "500 or 1000 T cells isolated from lymph nodes of Bbs4FL/FL OT-I Rag2KO/KO (OT-I) and CD4-Cre Bbs4FL/FL OT-I Rag2KO/KO (Bbs4 cKO, OT-I) littermates were adoptively transferred into RIP.OVA mice followed by infection with Listeria monocytogenes expressing ovalbumin (LM-OVA) on the next day. (E) Glucose level in the urine of mice was monitored on a daily basis. The mouse was considered diabetic when it had urine glucose level ≥ 1000 mg/dL for two consecutive days. Statistical significance was calculated by Log-rank (Mantel-Cox) test.",
    "diseases": "diabetic"
  },
  {
    "caption": "(A Results of the blood tests of BBS patients from the Guy's Hospital and Great Ormond Street Hospital were extracted from the medical records and compared to two sets of healthy controls obtained from the UK Biobank. The BMI-random controls were age- and gender-matched to the set of BBS patients, with random BMIs. The BMI-matched controls were matched for age, gender, and BMI. BBS patients n=43 for parameters White blood cell count n=41 for parameters Neutrophils, Lymphocytes, Monocytes, Eosinophils Both data sets of healthy controls were selected as 10-fold larger than the set of BBS patients. Median is shown. Kruskal-Wallis test was used for the statistical analysis in (A",
    "diseases": "BBS"
  },
  {
    "caption": "Results of the blood tests of BBS patients from the Guy's Hospital and Great Ormond Street Hospital were extracted from the medical records and compared to two sets of healthy controls obtained from the UK Biobank. The BMI-random controls were age- and gender-matched to the set of BBS patients, with random BMIs. The BMI-matched controls were matched for age, gender, and BMI. In (C), the percentage of patients or controls having CRP≥5 were compared using Fisher's exact test with post-hoc Sidak correction for multiple comparisons, BBS patients n=42.",
    "diseases": "BBS"
  },
  {
    "caption": "Results of the blood tests of BBS patients from the Guy's Hospital and Great Ormond Street Hospital were extracted from the medical records and compared to two sets of healthy controls obtained from the UK Biobank. The BMI-random controls were age- and gender-matched to the set of BBS patients, with random BMIs. The BMI-matched controls were matched for age, gender, and BMI. BBS patients n=43 for parameters Mean cell volume, Hemoglobin n=39 for parameters Red Blood cells, Mean cell Hemoglobin and red cell distribution width (RDW). Both data sets of healthy controls were selected as 10-fold larger than the set of BBS patients. Median is shown. Kruskal-Wallis test was used for the statistical analysis in",
    "diseases": "BBS"
  },
  {
    "caption": "Results of the blood tests of BBS patients from the Guy's Hospital and Great Ormond Street Hospital were extracted from the medical records and compared to two sets of healthy controls obtained from the UK Biobank. The BMI-random controls were age- and gender-matched to the set of BBS patients, with random BMIs. The BMI-matched controls were matched for age, gender, and BMI. BBS patients n=43 for parameters Platelets; Both data sets of healthy controls were selected as 10-fold larger than the set of BBS patients. Median is shown. Kruskal-Wallis test was used for the statistical analysis in F).",
    "diseases": "BBS"
  },
  {
    "caption": "Immunoblo of mGPD in GA muscles from obese patient",
    "diseases": "obese"
  },
  {
    "caption": "IH of mGPD in GA muscles from obese patient",
    "diseases": "obese"
  },
  {
    "caption": "B) Representative CD3 immunohistochemistry staining of a muscle biopsy from a patient with inclusion body myositis (6-IBM).",
    "diseases": "IBM, inclusion body myositis"
  },
  {
    "caption": "C) Violin plots displaying the normalized expression level of selected genes per cluster in muscle T cells (n=6 IIM, n=1 undefined myopathy). Data information: CM: central memory; EM: effector memory; TRM: tissue resident memory; Tregs: regulatory T cells. IIM: Idiopathic Inflammatory Myopathies.",
    "diseases": "IIM, undefined myopathy, Idiopathic Inflammatory Myopathies"
  },
  {
    "caption": "D) Violin plots displaying the normalized expression level of selected genes per patient in the four TRM clusters (n=6 IIM, n=1 undefined myopathy). IMNM: Immune-Mediated Necrotizing Myopathy; DM: DermatoMyositis; ASyS: AntiSYnthetase Syndrome; IBM: Inclusion Body Myositis",
    "diseases": "AntiSYnthetase Syndrome, ASyS, IIM, Immune-Mediated Necrotizing Myopathy, IMNM, undefined myopathy, DermatoMyositis, DM, IBM, Inclusion Body Myositis"
  },
  {
    "caption": "E) Representative immunofluorescence stainings of HOBIT (red), CD3 (green), dystrophin (purple) and Hoechst 33342 (blue) performed on muscle tissue for patient 6 (IBM), patient 3 (DM) and 4 (ASyS). Images were acquired using a LSM 880 confocal without Airyscan microscope (63x oil objective). Scale bar=20μm. The white arrows show HOBIT+ T cells. DM: DermatoMyositis; ASyS: AntiSYnthetase Syndrome; IBM: Inclusion Body Myositis",
    "diseases": "AntiSYnthetase Syndrome, ASyS, DermatoMyositis, DM, IBM, Inclusion Body Myositis"
  },
  {
    "caption": "F) Isotype mouse and rabbit IgG1 immunofluorescence stainings. IBM: Inclusion Body Myositis",
    "diseases": "IBM, Inclusion Body Myositis"
  },
  {
    "caption": "G) Quantification of HOBIT+ T cells in muscle biopsies of patient 6 (IBM), patient 16 (IBM), patient 3 (DM) and 4 (ASyS). The number of counted CD3-positive T cells is indicated under each bar as n. ASyS: AntiSYnthetase Syndrome; IBM: Inclusion Body Myositis",
    "diseases": "AntiSYnthetase Syndrome, ASyS, DM, IBM, Inclusion Body Myositis"
  },
  {
    "caption": "A) Stacked bar plots showing the frequency of T-cell clones per patient in the muscle (left) and peripheral blood (PB) (right), including non-expanded (unique, lightest shade) and expanded clones (colored from light to dark shades, from less expanded to more expanded clones)). IMNM: Immune-Mediated Necrotizing Myopathy; DM: DermatoMyositis; ASyS: AntiSYnthetase Syndrome IBM: Inclusion Body Myositis; IIM: Idiopathic Inflammatory Myopathies.",
    "diseases": "AntiSYnthetase Syndrome, ASyS, IIM, IMNM, DermatoMyositis, DM, IBM, Inclusion Body Myositis, Idiopathic Inflammatory Myopathies"
  },
  {
    "caption": "B) Feature plots of IFI44L expression levels in each patient at early diagnosis in muscle T cells (upper panel) and peripheral blood memory T cells (lower panel). Data information: IMNM: Immune-Mediated Necrotizing Myopathy; DM: DermatoMyositis ASyS: AntiSYnthetase Syndrome; IBM: Inclusion Body Myositis;",
    "diseases": "AntiSYnthetase Syndrome, ASyS, Immune-Mediated Necrotizing Myopathy, IMNM, DermatoMyositis, DM, IBM, Inclusion Body Myositis"
  },
  {
    "caption": "a) Kaplan-Meier to first fever (≥38°C) episode within 24 hours of receiving vaccines administered at 4 months of age; control n=88 and 4CMenB n=89.",
    "diseases": "fever"
  },
  {
    "caption": "c) Exemplar genes differentially expressed at 4 hours and 24 hours, respectively, between infants who experienced a fever within 24 hours of vaccination and afebrile infants. The plotted lines are the LOESS (locally estimated scatterplot smoothing) regression curves with the 95% confidence intervals in grey. The false-discovery rate (FDR) was derived by comparing fold-changes in gene expression between infants who experienced post-vaccination fever and those who remained afebrile. P-values were obtained from the moderated t-statistic, after adjustment for multiple testing (Benjamini and Hochberg's method). Pre-vaccination samples n= 125, 4 hour samples n= 28, 24 hour samples n = 31, 3 day sample n= 30, 7 day samples n= 36.",
    "diseases": "fever"
  },
  {
    "caption": "(B) Expression of CH25H in heathy donors and COVID-19 patients. The box plot shows the expression of CH25H in macrophages of bronchoalveolar lavage fluids from three healthy donors, three moderate COVID-19 patients and six severe COVID-19 patients by scRNA-seq analysis (Liao et al., 2020).",
    "diseases": "COVID-19"
  },
  {
    "caption": " (E) Acoustic auditory brainstem responses (average of 1000 stimuli at a stimulation rate of 10 Hz) upon click stimulation from 20-100 dB SPL before (left) and after deafening (right; star: threshold). (F) Optically evoked auditory brainstem responses before (left) and after deafening (right), elicited by ~35 mW pulses of 1 ms duration, delivered by a laser-coupled fiber (1000 stimuli presented at 10 Hz), recorded from the same animal. Optogenetic activation of the auditory system was still possible after deafening. Differences in amplitude and waveform before and after deafening are likely due to different positioning of recording electrodes and the optical fiber. ",
    "diseases": "deafening"
  },
  {
    "caption": " (G-H) Exemplar STCs in response to SGN illumination with all µLEDs in a CatCh-transduced, kanamycin-deafened gerbil before (G) and after (H) sacrifice. ",
    "diseases": "deafened"
  },
  {
    "caption": " (I) Maximum strength of ICC responses (mean ± standard deviation) evoked by oCI stimulation with 1 (indiv.; n = 129/77 µLEDs in N = 9/3 hearing/deaf gerbils), 4 (block; n = 62/27 blocks in N = 9/3 hearing/deaf gerbils), and 16 (all; n = 24/9 oCIs in N = 9/3 hearing/deaf gerbils) active µLEDs, and with a laser-coupled optical fiber (~35 mW; n = 9/3 fiber stimulations in N = 9/3 hearing/deaf gerbils) in CatCh-transduced gerbils (One-way ANOVA (F-value: 73.25, 4 degrees of freedom, p = 5.19*10-45) and post-hoc multiple comparison test; indiv. vs. block: p = 9.9*10-9; block vs. all: p = 0.0096; all vs. fiber: p = 0.0016; all CatCh vs. all WT: p = 9.9*10-9;**: p < 0.01, ***: p < 0.001, n.s. = non-significant). oCI stimulation with all µLEDs has also been performed in WT animals (n = 7/7 oCIs, N = 2/2 hearing/deaf gerbils) and in sacrificed CatCh-transduced animals (post-mortem; n = 5/1 oCIs in N = 5/1 hearing/deaf gerbils). Brown dots indicate data recorded from deafened animals. (J) Number of active electrodes (d´ > 1; mean ± standard deviation) upon oCI stimulation with 1 (n = 129/77 µLEDs in N = 9/3 hearing/deaf gerbils), 4 (n = 62/27 blocks in N = 9/3 hearing/deaf gerbils), and 16 µLEDs (n = 24/9 oCIs in N = 9/3 hearing/deaf gerbils), and with optical fiber stimulation (n = 9/3 fiber stimulations in N = 9/3 hearing/deaf gerbils) in CatCh-transduced gerbils (One-way ANOVA (F-value: 30.18, 4 degrees of freedom, p = 1.42*10-21) and post-hoc multiple comparison test; indiv. vs. block: p = 6.8*10-5; block vs. all: p = 0.006; all vs. fiber: p = 0.25; all CatCh vs. all WT: p = 9.9*10-9;**: p < 0.01, ***: p < 0.001, n.s. = non-significant). Responses to oCI stimulation with all µLEDs were also observed in hearing WT animals (n = 3 oCIs in 2 gerbils). No active electrodes were found in response to 4/7 oCI stimulations in 2/2 hearing/deaf wildtype gerbils). (K) Thresholds (d´ = 1, measured at the best electrode (BE)) for ICC activation evoked with 16 active µLEDs on an oCI (n = 24/9 in N = 9/3 hearing/deaf gerbils) and with a laser-coupled optical fiber (n = 9/3 in N = 9/3 hearing/deaf gerbils; p = 0.012, Wilcoxon rank sum test). Central horizontal line indicates the median, lower, upper horizontal lines indicate the minimum and maximum values, and box edges indicate the 25th and 75th percentile, respectively. ",
    "diseases": "deaf, deafened"
  },
  {
    "caption": "(D) Representative H&E staining of primary (arrow) and disseminated tumors (asterisk) arising from orthotopic xenograft of parental and SOX9-expressing medulloblastoma initiating cells (MIC and MIC-Sox9, respectively). Quantification of primary and metastatic tumors arising from both of MIC (n=16) and MIC-SOX9 (n=8) is shown in the histogram (p=0.0000136).",
    "diseases": "tumors"
  },
  {
    "caption": "(A-B) Representative Hematoxylin and Eosin (H&E) staining, and immunohistochemistry of phosphorylated FAK on tyrosine (Y) 397 (pY397 FAK), alpha-Smooth Muscle Actin (α-SMA), and Fibroblast Activated Protein alpha (FAP-α) in serial sections of human normal pancreas (Ct1), of human normal adjacent PDAC tissue (Ct2) and of human PDAC tissues (PDAC1-3); scale bar, 100 μm (A), and 300 µm (B).",
    "diseases": "PDAC"
  },
  {
    "caption": "(C) Quantification of pY397 FAK level in cancer-associated fibroblasts from human PDAC microarray: 40 different PDAC patient samples and 10 normal human pancreas have been stained for pY397 FAK and double blinded quantified (based on intensity and positive cell number) on a scale between 0 (no staining) and 6 (Y397 FAK highly positive) in whole cell (left), cytoplasm (middle) and nucleus (right).",
    "diseases": "PDAC"
  },
  {
    "caption": "(A) Representative images of Definiens® Tissue studio multi-resolution segmentation algorithm on two PDAC TMA examples (X, Y). From left to right: IHC for pY397 FAK; ROI detection of tumour cells (dark blue), stroma (orange) and other (light blue/grey); Nuclear/ cytoplasm detection in blue and green respectively; IHC staining classification for pY397 FAK intensity signal (dark red for high signal, orange for medium signal, yellow for low signal and white for negative signal).",
    "diseases": "PDAC"
  },
  {
    "caption": "(H) Left: Representative immunohistochemistry pictures of phosphorylated FAK on tyrosine (Y) 397 and of CD206 in serial sections of human PDAC tissues. Scale bar: 200µm Middle: Correlation plot between fibroblastic pY397 FAK score and CD45 or CD206+ cell number within human PDAC samples. Fibroblastic pY397 FAK score and percentage of CD206 positive cell quantifications were performed on a 47 patient cohort based on IHC staining. Spearman r = 0.4145, p=0.0019. Right: Percentage of CD206 positive cells in PDAC patient expressing either low or high fibroblastic FAK activity score.",
    "diseases": "PDAC"
  },
  {
    "caption": "(D) Quantification of the percentage change of Y397 FAK, total FAK, collagen I (coll I), collagen III (coll III), collagen IV (coll IV), LOXL2, periostin (POSTN), osteopontin (OPN) expression by human CAFs treated or not (NT) with FAK inhibitor (1µM), based on immunofluorescence analyses. Values are means ± SEM obtained from at least 5 primary hCAFs, isolated from 5 to 12 different fresh human PDAC samples.",
    "diseases": "PDAC"
  },
  {
    "caption": "Growth suppression determined by the ATP-based CTG assay in colorectal cancer patient-derived organoids (colo-PDO) after treatment with APR-246 +/- MK-571 (n = 3).",
    "diseases": "colorectal cancer"
  },
  {
    "caption": " ABCC1 mRNA Expression, RSEM (Batch normalized from Illumina HiSeq_RNASeqV2) in lung cancer (luad & lusc studies, *p<0.0001) and colon adenocarcinoma (coad study, *p=0.005) grouped into having no alterations or putative driver missense mutations in TP53. Statistical analysis by Mann Whitney test, n is indicated in the figure. Data information: TP53 status is indicated for each cell line. Data are represented as mean ± SEM. See also Figure EV5 and Appendix Figure S5. ",
    "diseases": "colon adenocarcinoma, lung cancer"
  },
  {
    "caption": "A. Representative immunostainings for dystrophin in cross-sections of muscles of mdx mice after transplantation of hskMPs or eMPs. Scale bars in the two left-hand side images = 300 μm. Scale bars in inserts 1 and 2 = 50 μm. B. Number of dystrophin positive fibers in mdx muscles injected with vehicle (Ctrl), eMPs and hskMPs. C. Maximal distance of clusters of dystrophin positive fibers in cross-sections of mdx muscles transplanted with eMPs and hskMPs. A-C. 10 days post-transplantation. hiPSC donor 1.",
    "diseases": "mdx"
  },
  {
    "caption": " (F) Overlay plot of Jurkat-S cells that were incubated with anti-EGFR mAb conjugated to Bv421 and serum from either donor #15 or from a pre-COVID-19 donor and followed by a secondary anti-human IgG1 antibody conjugated to PE. ",
    "diseases": "COVID-19"
  },
  {
    "caption": " (A) Overlay histograms of Jurkat-S staining with different human sera diluted 1:50. A pre-COVID19 serum sample is taken as negative control (grey histogram). ",
    "diseases": "COVID19"
  },
  {
    "caption": " (A) Box and whiskers plot of MFI and absorbance data in human sera according to their clinical classification of COVID-19 symptoms. Clinical classification was done according to the following parameters: Asymptomatic, no symptoms; Mild, 3 or more of the following symptoms: non-productive cough, hyperthermia, headache, odynophagia, dyspnea, asthenia , myalgia, ageusia, anosmia, cutaneous involvement; Moderate, 3 or more of the above symptoms plus gastrointestinal symptoms, or more than 3 of the above for 7 or more days; Moderate-Severe, 3 or more of the above symptoms plus pneumonia. Box and whiskers are shown to represent the minimum and maximum values as well as the median. All datapoints are shown. ",
    "diseases": "anosmia, hyperthermia, odynophagia, ageusia, asthenia, non-productive cough, COVID-19, dyspnea, headache, myalgia, pneumonia"
  },
  {
    "caption": " (C) Titration of selected human sera by ELISA using the S1 protein and by flow cytometry with Jurkat-S cells. Samples with antibodies detected by flow cytometry and not by ELISA are indicated (#8, #46, #48, #49). Data represent the mean±SD of duplicates. An unpaired two-tailed t-test was carried out to compare the results of 1:50, 1:150 and 1:450 dilutions of sera #8, #46, #48 and #49 by FC to the pre-COVID-1 sample as a negative control. *, p<0.05; **, p<0.005; ***, p<0.0005. ",
    "diseases": "COVID"
  },
  {
    "caption": " (B) Validation of the neutralization method was carried out with cell HEK-293T cell culture supernatants containing lentiviral particles pseudotyped with either the S protein or with the VSV G protein. The supernatants were mixed with sera from donor #66 at the indicated dilutions or from a pre-COVID sample as a control before addition onto HEK-293T-ACE2+ cell cultures. No serum, refers to a control containing no human sera. Data represent the mean±SD of triplicates. ",
    "diseases": "COVID"
  },
  {
    "caption": " (C) The presence of neutralizing antibodies in sera from donors #46 and #48, found negative by ELISA and positive by flow cytometry (Fig. 3C) was demonstrated as in panel B. Data represent the mean±SD of triplicates. *, p<0.05; **, p<0.005; ****, p<0.00005 (Paired two-tailed t-test comparing all serum dilutions to the pre-COVID sample). ",
    "diseases": "COVID"
  },
  {
    "caption": " (A) A total of 52 serum samples from Hospital Universitario La Princesa (HUP) and 52 samples of pre-COVID donors stored at the CBMSO were tested by the flow cytometry method and classified according to the S/EGFR-based Score. Of the 52 HUP samples, a total of 40 were from donors testing positive by PCR and by an ELISA test, 6 were from donors testing negative by PCR but positive by ELISA, 1 from an individual testing negative by ELISA and positive by PCR, and 5 were not tested by PCR. Box and whiskers are shown to represent the minimum and maximum values as well as the median. All datapoints are shown. The broken line indicates the threshold for a Score value of 0.024. ",
    "diseases": "COVID"
  },
  {
    "caption": " C) Four HUP serum samples giving discrepant results by flow cytometry method were tested in the neutralization assay of pseudotyped lentivirus (Fig. 4A). Data represent the mean±SD of duplicates. *, p<0.05; **, p<0.005; ****, p<0.00005; (Paired two-tailed t-test comparing all serum dilutions to the pre-COVID sample) ",
    "diseases": "COVID"
  },
  {
    "caption": " (B) A neutralization assay with S protein-pseudotyped lentivirus was carried out to resolve the discrepancies. Data represent the mean±SD of duplicates. *, p<0.05; **, p<0.005; ***, p<0.0005; *****, p<0.000005 (Paired two-tailed t-test comparing all serum dilutions to the pre-COVID sample). ",
    "diseases": "COVID"
  },
  {
    "caption": "A. Colitis was induced by intravenous coinjection of CD4+CD25-CD62Lhigh T cells and congenically distinct (CD45.2) CD4+CD25high Treg cells into Rag2-/- mice (n=8/group; 1x106 and 2x105 cells per Rag2-/- recipient, respectively). Changes in body weight over time were monitored and are expressed as a percentage of the original weight.",
    "diseases": "Colitis"
  },
  {
    "caption": "MC38 colon carcinoma, B16F10 melanoma cell lines were s.c. injected into the shaved flanks of Usp44fl/flFoxp3Cre+ mice and their wild type (Usp44fl/flFoxp3Cre-) littermates (1x105 cells/mouse; n=5-9 mice/group). Tumor dimensions were measured every 2 days, and changes in the mean tumor volume over time were observed (lower panels). Upper panels depict representative photographs of excised tumors.",
    "diseases": "colon carcinoma, melanoma"
  },
  {
    "caption": "EL4 thymoma cell lines were s.c. injected into the shaved flanks of Usp44fl/flFoxp3Cre+ mice and their wild type (Usp44fl/flFoxp3Cre-) littermates (1x105 cells/mouse; n=5-9 mice/group). Tumor dimensions were measured every 2 days, and changes in the mean tumor volume over time were observed (lower panels). Upper panels depict representative photographs of excised tumors.",
    "diseases": "thymoma"
  },
  {
    "caption": "F. Histopathological analysis, 3 days post-inoculation, of the lung of K18-hACE2 mice infected with 104 PFU of BANAL-236 (a-d) or SARS-CoV-2 Wuhan-372 (e,f) viruses. Interstitial pneumonia characterized by interstitial inflammation, often centered on blood vessels (perivasculitis, black arrows) or bronchi/bronchioles (black arrowheads), and endothelial cell injury and inflammation (endothelitis). Lesions were globally more severe after Wuhan-372 infection (n=4; all of moderate severity) than after BANAL-236 infection (n=4; 3/4 of minimal severity (a-c) and 1/4 of moderate severity (d)). Scale bar: 100 µ. Low magnification images are provided in Figure S3.",
    "diseases": "endothelitis, interstitial inflammation, Interstitial pneumonia, perivasculitis, inflammation"
  },
  {
    "caption": "(A-C) Results of Pseudoneutralisation (PNT), Luciferase immunoprecipitation (LIPS) and LuLISA tests are shown. Pre-pandemic French sera (black) were used as negative controls and Laotian sera samples from confirmed SARS-CoV-2 infection (green) were used as cross-reacting positive controls. Laotian sera samples collected in the general population before 2019 (blue, n=100) or late 2020 (gray, n=100) or in people exposed to bats (purple, n=74) were tested for BANAL-236 (A), BANAL-52 (B) and BANAL-103 (C) antibody responses. The ANOVA non-parametric Kruskal-Wallis test was conducted to compare each sub-population to the reference French population (* P<0.05; **P<0.005; ***P<0.0005; ****P<0.0001). The red bars represent the median.",
    "diseases": "SARS-CoV-2 infection"
  },
  {
    "caption": "B. Quantification of PNRC1 expression levels in primary normal (blue circles) and cancer (red circles) samples by Real Time PCR.",
    "diseases": "cancer"
  },
  {
    "caption": "Immunofluorescence stainings of PNRC1 (red) and Ki-67 (green) performed on a malignant lymphoma (D). DAPI was used to stain cell nuclei. Scale bars:50µm.",
    "diseases": "malignant lymphoma"
  },
  {
    "caption": "A,  Oil-red-O staining  of control (healthy) and steatotic liver. Scale bar: 100 µm.",
    "diseases": "steatotic"
  },
  {
    "caption": "B, Reconstructed MSOT image (800 nm) with linear unmixing and difference value of  lipid in  lower abdominal section. Unmixing result: blue for  Hb, red for  HbO2, yellow for lipid, jet for 700 nm - 930 nm difference. The colour bar shows the colour coding of MSOT a.u. from 0 to maximum (bottom to top) (Maximum value control/steatosis: Hb: 1.1/0.5;  HbO2: 1.9/0.8; Lipid: 21000/24000; 700-900nm: 3000/3000) Scale bar: 4 mm.",
    "diseases": "steatosis"
  },
  {
    "caption": "A, HE  staining of  livers with grade 0 - 3  steatosis. Scale bar: 100 µm.",
    "diseases": "steatosis"
  },
  {
    "caption": "F, Longitudinal track of  lipid in mouse livers. Each line represents data from one animal. Each data point is from a single measurement of each animal at each  time point. All animals have grade 3  steatosis at the endpoint confirmed by histology.",
    "diseases": "steatosis"
  },
  {
    "caption": "A, Reconstructed MSOT image (800 nm) with linear unmixing data of ICG from  mice with and without  steatosis. The colour bar shows the colour coding of MSOT  a.u. from 0 to maximum (bottom to top) (Maximum value control/steatosis: 0.07/0.02) Scale bar: 4 mm.",
    "diseases": "steatosis"
  },
  {
    "caption": "E, Representative fluorescence microscopy and HE  staining  images of control and steatotic liver. Scale bar: 100 µm.",
    "diseases": "steatotic"
  },
  {
    "caption": "C. TSPO-PET in human FTLD patients: Visual interpretation of axial TSPO-PET SUVR images in upper cranial layers reveals increased microglial activity in frontal and parietal cortices (white arrows) of a FTLD patient with a GRN loss of function mutation in comparison to a FTLD patient without a GRN mutation. PET results are illustrated upon an MRI template; 60-80 min p.i. emission recording; global mean scaling. Both patients were low-affinity binder.",
    "diseases": "FTLD"
  },
  {
    "caption": "C, The concentration of plasma INSL5 in healthy controls (normal EBV (-)), non-tumor individuals with VCA-IgA positive (normal EBV (+)) and NPC patients, in training cohort.",
    "diseases": "NPC"
  },
  {
    "caption": "E, The concentration of plasma INSL5 in healthy controls (normal EBV (-)), non-tumor individuals with VCA-IgA positive (normal EBV (+)) and NPC patients, in validation cohort 1(GZ). F, The concentration of plasma INSL5 in healthy controls (normal EBV (-)), non-tumor individuals with VCA-IgA positive (normal EBV (+)) and NPC patients, in validation cohort 2(ZS). ",
    "diseases": "NPC"
  },
  {
    "caption": "A-C, Kaplan-Meier curves showing the overall survival (OS) curves of NPC patients with low or high INSL5 concentration (A), low (≤4000 copy/ml) or high (>4000 copy/ml) EBV DNA copy number (B), and the combination of INSL5 concentration with EBV DNA copy number (C).",
    "diseases": "NPC"
  },
  {
    "caption": "D-F, Kaplan-Meier curves showing the disease-free survival (DFS) curves of NPC patients with low or high INSL5 concentration (D), low or high EBV DNA copy number (E), and the combination of INSL5 concentration with EBV DNA copy number (F).",
    "diseases": "NPC"
  },
  {
    "caption": "(C) After transplantation in immunodeficient mice of CUP cells described above, the volume of ADX43- and (D) ADX901-shPlxnB2 tumors was assessed, in comparison with the respective controls. Plotted values indicate the mean ± SD (n = 8 each group). The statistical significance was assessed by two-way ANOVA with Sidak's correction for multiple comparisons: **p = 0.0060; ****p < 0.0001.",
    "diseases": "CUP"
  },
  {
    "caption": "(C) Wound healing scratch assays on monolayers of MCF7 cells engineered as described above. The graph shows the mean ± SD of values obtained in N=3 independent experiments (with at least three technical replicates for each). The statistical significance was verified by one-way ANOVA with Tukey's correction for multiple comparisons: *p = 0.0350; **p = 0.0029; ***p = 0.0002. Representative phase contrast images of the wounded monolayers are further shown in larger size in Appendix Figure S4B.",
    "diseases": "wounded"
  },
  {
    "caption": "(D) Western blotting analysis of endogenous and overexpressed PlxnB2 (either WT or G842C-mutated isoforms) in CUP cells AS906 (both full length molecules at 250 kDa and processed 80 kDa fragments). Vinculin staining provided protein loading controls.",
    "diseases": "CUP"
  },
  {
    "caption": "(E) The invasive capacity of CUP cells AS906 (shown in previous panel), overexpressing WT or G842-mutated PlxnB2 (or mock control), was assessed across Matrigel-coated transwell inserts. The graph shows the mean ± SD of values obtained in N=3 independent experiments (including technical duplicates, in two cases). Below the graph, are shown representative fields of the semipermeable membranes (additional larger size images can be found in appendix Figure S4C); scale bar: 100μm. The statistical significance was verified by one-way ANOVA with Bonferroni correction for multiple comparisons: *p=0.0406; **p=0.0045; ***p=0.0003.",
    "diseases": "CUP"
  },
  {
    "caption": "(A) Volcano plot of phosphorylation changes in iKras PDAC cells in response to KrasG12D induction. Phospho- to total proteomic changes were quantified from three independent biological replicates of Dox treated vs. untreated cells, via TMT (Dataset EV8). 872 phosphorylations were found to be significantly increased, while 82 phosphorylations were significantly decreased (FDR < 0.05). Significantly changing phosphorylations on RBPs whose RNA-binding activity was significantly increased (red) or decreased (blue) as per Fig 1C are highlighted on the plot.",
    "diseases": "PDAC"
  },
  {
    "caption": "(E) KrasG12D induction enhances phosphorylation of CK2α (T360/S362), in an Erk1/2-dependent manner. IKras PDAC cells were grown in the absence of Dox for 48 hrs, before its addition to the indicated cells, with or without Trametinib (10 nM), for a further 24 hrs. Cells were then lysed and analyzed by immunoblotting (IB) with the indicated antibodies. The red triangle marks the main phospho band which overlaps with the total CK2α.",
    "diseases": "PDAC"
  },
  {
    "caption": "(G) Analysis of the RNA-binding activity of WT, Phospho-defective (S4A), and phospho-mimicking (S4D) mutants of Ncl by OOPS. IKras PDAC cells were transiently transfected with myc-tagged WT, S4A, and S4D Ncl constructs. Cells were subsequently grown in the absence of Dox for 48 hrs, followed by Dox addition for 24 hrs to induce KrasG12D expression. Cells were then subjected to OOPS to isolate the interface (RNA-bound proteins), or whole cell lysis (total lysate), followed by immunoblotting with anti-Ncl antibody. For comparison, Gapdh, which also binds RNA but does not show a change in its RNA-binding activity (Dataset EV1), was also blotted for. A fraction of each interface or total lysate sample was also subjected to RNA extraction, which was resolved and quantified by capillary electrophoresis (CE) as loading control.",
    "diseases": "PDAC"
  },
  {
    "caption": "(B) Immunofluorescence analysis of WT, S4A, and S4D Myc-Ncl subcellular localization. IKras PDAC cells ectopically expressing either WT, S4A, or S4D Myc-Ncl were fixed and immunostained with anti-Myc-tag antibody, along with anti-Fibrillarin (Fbl) antibody as a Nucleolar marker, and Hoechst, followed by confocal microscopy analysis.",
    "diseases": "PDAC"
  },
  {
    "caption": "(A) Nascent RNA imaging in control and Ncl depleted iKras PDAC cells, in presence or absence of KrasG12D. Cells were transfected with a non-targeting control siRNA, or two independent siRNAs against Ncl, grown for 48hrs in presence or absence of Dox, prior to pulse labeling with FUrd. Cells were then fixed and immunostained with anti-FUrd antibody (green) to visualize nascent RNA, along with anti-Fibrillarin (Fbl) antibody as a Nucleolar marker (red), and Hoechst (blue) as the Nuclear stain, followed by confocal microscopy analysis. (B) Quantification of Nucleolar FUrd levels in images from (A). FUrd fluorescence densities in single nucleoli were quantified from 182-220 individual cells per condition, combined from 2 independent biological replicate experiments (****: P < 0.0001; n.s.: not significant - calculated from one-way ANOVA with Šídák's multiple comparisons test).",
    "diseases": "PDAC"
  },
  {
    "caption": "(C) RT-qPCR analysis of 5'ETS-containing pre-rRNA transcript levels in control and Ncl depleted iKras PDAC cells, in presence or absence of KrasG12D. Cells were transfected with a non-targeting control siRNA, or two independent siRNAs against Ncl, and grown for 48hrs in presence or absence of Dox, before RT-qPCR analysis with a specific probe against the mouse 5'ETS region. A probe against mouse Actb mRNA was used as loading control for normalization. A total of 4 biological replicate experiments were quantified (***: P < 0.001; n.s.: not significant - calculated from one-way ANOVA with Šídák's multiple comparisons test).",
    "diseases": "PDAC"
  },
  {
    "caption": "(E) Assessment of the overall protein synthesis rates in control and Ncl depleted iKras PDAC cells, in presence or absence of KrasG12D, by puromycinylation. Cells were transfected with a non-targeting control siRNA, or two independent siRNAs against Ncl, and grown for 48hrs in presence or absence of Dox, before pulse labelling with Puromycin (10 μg/ml) for 15 min to label nascent proteins. Cells were subsequently lysed and analyzed by immunoblotting with the indicated antibodies. (F) Quantification of puromycin incorporation from (E), as an indicator of the overall protein synthesis rate. Total Erk1/2 levels were used as loading control. A total of 4 independent biological replicate experiments were quantified. Error bars depict SD. (**: P < 0.01; n.s.: not significant - calculated from one-way ANOVA with Šídák's multiple comparisons test). (",
    "diseases": "PDAC"
  },
  {
    "caption": "(G) Nascent RNA imaging of WT, S4A, and S4D Myc-Ncl expressing iKras PDAC cells, in presence or absence of KrasG12D. Vectors encoding Myc-tagged WT, S4A, and S4D Ncl were transiently transfected into iKras PDAC cells, before reseeding and growing the cells for 48hrs in presence or absence of Dox. Cells were then subjected to pulse labeling with FUrd, fixation, and immunostaining with anti-FUrd antibody (green), anti-Myc-tag antibody (red), and Hoechst (blue), followed by confocal microscopy analysis. Scale bar = 10 µm. (H) Quantification of FUrd levels in Myc-positive nucleoli from (E). FUrd fluorescence densities in single nucleoli were quantified from 160-281 individual cells per condition, combined from three independent biological replicate experiments (****: P < 0.0001; n.s.: not significant - calculated from one-way ANOVA with Šídák's multiple comparisons test). (",
    "diseases": "PDAC"
  },
  {
    "caption": "(I) RT-qPCR analysis of 5'ETS-containing pre-rRNA transcript levels in WT, S4A, and S4D Myc-Ncl expressing iKras PDAC cells, in presence or absence of KrasG12D. Vectors encoding Myc-tagged WT, S4A, and S4D Ncl were transiently transfected into iKras PDAC cells, before reseeding and growing the cells for 48hrs in presence or absence of Dox, followed by RT-qPCR analysis with a specific probe against the mouse 5'ETS region. A probe against mouse Actb mRNA was used as loading control for normalization. A total of 5 to 8 biological replicate experiments per condition were quantified (****: P < 0.0001; n.s.: not significant - calculated from one-way ANOVA with Šídák's multiple comparisons test).",
    "diseases": "PDAC"
  },
  {
    "caption": "(A) Colony formation of control and Ncl depleted iKras PDAC cells, in presence or absence of KrasG12D. Cells were transfected with a non-targeting control siRNA, or two independent siRNAs against Ncl, followed by clonogenic assay for 7 days in presence or absence of Dox. Colonies were visualized by Crystal Violet staining. (B) Quantification of Crystal Violet staining levels from (A). A total of 6 biological replicate experiments were quantified. Error bars depict SD. (****: P < 0.0001; n.s.: not significant - calculated from two way ANOVA with Šídák's multiple comparisons test). (",
    "diseases": "PDAC"
  },
  {
    "caption": "(C) 3D proliferation of control and Ncl depleted iKras PDAC cells, in presence or absence of KrasG12D. Cells were transfected with a non-targeting control siRNA, or two independent siRNAs against Ncl, before being reseeded onto 3D Collagen-I gels, with or without Dox, and allowed to grow for 48 hrs. Cells were subsequently imaged live by phase contrast microscopy. Scale bar = 200 µm. (D) Analysis of the relative percentage of viable cells in 3D collagen-I cultures from (C). Cells were subjected to luminescence-based viability assay by CellTiter-Glo to quantify the percentage of viable cells. A total of 3 biological replicate experiments were quantified. Error bars depict SD. (****: P < 0.0001; n.s.: not significant - calculated from two way ANOVA with Šídák's multiple comparisons test). (",
    "diseases": "PDAC"
  },
  {
    "caption": "(A) Dose response analysis of CX-5461 impact on nascent rRNA expression. IKras PDAC cells were grown in the absence of Dox for 48hrs. Cells were subsequently treated with or without Dox for 24 hrs to induce KrasG12D expression, followed by pre-treatment with the indicated concentrations of CX-5461 for 30 mins prior to pulse labeling with FUrd. Cells were then fixed and immunostained with anti-FUrd antibody to visualize nascent RNA (green), anti-Ncl antibody to reveal the Nucleolus (red), and Hoechst (blue) as the Nuclear stain, followed by confocal microscopy analysis. (B) Quantification of Nucleolar FUrd levels in images from (A). FUrd fluorescence densities in single nucleoli were quantified from 251-479 individual cells per condition, combined from 2 independent biological replicate experiments (****: P < 0.0001; n.s.: not significant - calculated from one-way ANOVA with Šídák's multiple comparisons test).",
    "diseases": "PDAC"
  },
  {
    "caption": "(G) MRI imaging of orthotopic iKras tumors in untreated or CX-5461 treated mice. IKras PDAC cells were engrafted into the pancreas of Dox-fed nude mice and allowed to form tumors for 4 days. Animals were then divided into two groups, with the first group treated by daily oral administration of CX-5461 (50mg/kg) for a further 10 days, whilst the second group was left untreated for the same period. T2 scans were taken on the indicated days, post-engraftment. Green areas mark the tumors.",
    "diseases": "PDAC"
  },
  {
    "caption": "(K) H&E analysis of the extracted pancreas tissues from (I). Representative pancreatic tissue images from the untreated and CX-5461 treated mice, showing typical PDAC histology with malignant ductal structures surrounded by stroma in the untreated, but a largely normal pancreas histology with a small malignant (M) component (marked by the dashed line) in the treated mice.",
    "diseases": "PDAC"
  },
  {
    "caption": "(G, H) The human tumour tissues (T) from Oesophagus (G) and Colon (H) and their adjacent normal tissues (N) were homogenized for protein extraction. Protein extracts were analysed by western blotting with the indicated antibodies. The data are representative of three biological replicates. The blots in (G, H) were qualified and the ratio of LC3II/LC3I to actin was then calculated and shown in Supplementary Figure 9A and B.",
    "diseases": "tumour"
  },
  {
    "caption": "in postmortem brain sections from AD patients, we detected nuclear pStat3 (arrows) in the majority of peri-plaque reactive astrocytes (identified by GFAP) in the cortex and hippocampus (plaques were stained with methoxy-XO4, arrowheads). Scale bar, 50 µm.",
    "diseases": "AD"
  },
  {
    "caption": "Weight curve of female Rag-/- mice after T-cell transfer colitis induced via transfer of naïve WT CD45.1 conventional CD4+ T cells alone (n=5 recipients) or in combination with Tregs isolated from Tet1/3fl/fl and Rorc(t)CreTg Tet1/3fl/fl littermates (n=5 recipients/group). Data is means +/- SEM, Two-Way ANOVA with Geisser-Greenhouse correction. Experiment was replicated 2 times.",
    "diseases": "colitis"
  },
  {
    "caption": "Representative flow plots and quantification of percent Tbet+, Rorγt+ and FoxP3+ of CD45.1 CD4+ effector cells isolated from the MLN of female Rag-/- mice 7 weeks post T cell transfer induced colitis. Respective cohorts were Naïve CD45.1 T cells only (n=5 mice), WT CD45.1+ Tet1/3fl/fl Tregs (n=5 mice) and WT CD45.1+Rorc(t)CreTg Tet1/3fl/fl Tregs (n=4 mice). Cells were pre-gated on Live CD45.1+TCRβ+ cells. Data is means+/- SEM, Two-Way ANOVA with Tukey's Multiple comparison test. Experiment was replicated 2 times.",
    "diseases": "colitis"
  },
  {
    "caption": "(A) Representative images of vasculature stained by an antibody anti-CD31 in A375 xenografts treated as indicated. Bar graphs indicate quantitative micro vessel density (MVD) and micro vessel area (MVA) analysis (n=5 tumors), ***P < 0.001 versus vehicle (MVD: bevacizumab P = 5.94E-25; COMBO P = 1.84E-04) (MVA: PLX4720 P = 4.98E-09; bevacizumab P = 1.16E-19; COMBO P = 3.00E-08).",
    "diseases": "tumors"
  },
  {
    "caption": "(B) Representative images of vessel lumen in A375 xenografts treated as indicated. Bar graphs indicate the quantitative analysis of lumen diameters in A375 and COLO205 xenografts (n=3 tumors), *P < 0.05, **P < 0.01, ***P < 0.001 versus vehicle (A375: PLX4720 P = 0.0078; COMBO P = 0.0012) (COLO205: PLX4720 P = 2.01E-06; COMBO P = 1.33E-07).",
    "diseases": "tumors"
  },
  {
    "caption": "(C) Representative images of perfusing fluorescent beads and their relationship with microvessels in A375 xenografts treated as indicated. Bar graphs indicate the % of CD31+ vessels co-stained with fluorescent beads (n=4 tumors), **P < 0.01 versus vehicle (PLX4720 P = 0.0031; COMBO P = 0.0033).",
    "diseases": "tumors"
  },
  {
    "caption": "(D) GSEA enrichment plots for \"Reactome Cytokine Signaling in Immune System\" and \"Reactome Innate Immune System\" (upper panels) and \"Reactome Extracellular Matrix Organization\" and \"Reactome Collagen Formation\" (lower panels) highlight significant enrichment of the pathways relative to the immune response and a decreased expression of the pathways relative to extracellular matrix remodeling in COMBO treated tumors as compared to the other treatments (vehicle, PLX4720, bevacizumab).",
    "diseases": "tumors"
  },
  {
    "caption": "(A) Representative images of leukocytes infiltration determined by immunofluorescence CD45 staining in of A375 xenografts treated as indicated. Bar graphs indicate the CD45+ area/tumor area in A375 and COLO205 xenografts (n=5 tumors), ***P < 0.001 versus vehicle (A375: P = 2.19E-20) (COLO205: P = 1.81E-06).(B) Representative images of macrophage infiltration determined by F4/80 immunofluorescence staining in A375 xenografts treated as indicated. Bar graphs indicate the F4/80+ area/tumor area in A375 and COLO205 xenografts (n=5 tumors) ***P < 0.001 versus vehicle (A375: COMBO P = 3.42E-13) (COLO205: COMBO P = 1.94E-06).",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "(C) A375 xenograft tumors after 14 days of treatment were subjected to FACS and tumor infiltrate was analyzed. Gating strategy for CD45+ cells and graph showing the quantification of FACS analysis of infiltrating CD45+ leukocytes in vehicle (n=4 tumors) compared to COMBO (n=6 tumors) treated tumors, **P < 0.01 versus vehicle (P = 0.0064).",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "(D) Graph showing the quantification of FACS analysis of infiltrating F4/80+ macrophages and CD11c+MHCII+ dendritic cells in vehicle (n=4 tumors) compared to COMBO (n=6 tumors) treated tumors, **P < 0.01 versus vehicle (TAM P = 0.0061; DC P = 0.0091).",
    "diseases": "tumors"
  },
  {
    "caption": "(A) Real-time quantitative PCR of the indicated genes (M1-like and M2-like macrophages markers) of A375 xenograft treated with PLX4720, bevacizumab or COMBO. Data are presented as expression fold change (log2) compared with vehicle after normalization for housekeeping gene TBP (n=3 tumors), (*P < 0.05, **P < 0.01, ***P < 0.001 versus vehicle (PLX4720: m-Arg1 P = 5.65E-06) (bevacizumab: m-Ccl5 P = 0.025) (COMBO: m-Ccl5 P = 0.0070; m-Cd40 P = 0.00099; m-Cxcl10 P = 0.043; m-Cxcl9 P = 0.046; m-Il1b P = 0.0367; m-Stat1 P = 0.049; m-Tlr2 = 0.00182; m-Arg-1 P = 0.0013).",
    "diseases": "tumors"
  },
  {
    "caption": "(B) Representative images of COMBO-treated tumor sections co-stained with an antibody against CD68 and an antibody anti-CCR7 (M1-like polarization) or anti-CD206 (M2-like polarization).",
    "diseases": "tumor"
  },
  {
    "caption": "(C) Graphs showing the quantification of FACS analysis of infiltrating F4/80+ tumor macrophages and average percentage of median fluorescence intensity (MFI) of TNFα+ or INOS+ on F4/80+ cells after ex vivo stimulation with PMA and ionomycin in vehicle (n=4 tumors) and COMBO (n=6 tumors), *P < 0.05 versus vehicle (TNFα P = 0.037; INOS = 0.038).",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "(D) Graphs showing the quantification of FACS analysis of infiltrating CD11b+Ly6C+ tumor monocytes and average percentage of MFI of TNFα+ or INOS+ on CD11b+Ly6C+ cells after ex vivo stimulation with PMA and ionomycin in vehicle (n=4 tumors) and COMBO (n=6 tumors), *P < 0.05 versus vehicle (TNFα P = 0.048; INOS = 0.038).",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "(E) Graph showing the quantification of circulating CD11b+Ly6C+ monocytes in peripheral blood analyzed by FACS in vehicle- (n=4 tumors) and COMBO- (n=6 tumors) treated tumors.",
    "diseases": "tumors"
  },
  {
    "caption": "(A) Representative images of collagen deposition determined by collagen I immunofluorescent staining in A375 xenografts treated as indicated. Bar graphs indicate the collagen I+ area/tumor area (n=5 tumors), ***P < 0.001 versus vehicle (P = 2.93E-06).(B) Representative images of CAF density determined by α-SMA immunofluorescence staining in A375 xenografts treated as indicated. Bar graphs indicate α-SMA+ area/tumor area (n=5 tumors), ***P < 0.001 versus vehicle (P = 0.0006).(C) Representative images of Lysyl Oxidase enzyme determined by LOX immunofluorescence staining in A375 xenografts treated as indicated. Bar graphs indicate the LOX+ area/tumor area (n=3 tumors), *P < 0.05 versus vehicle (bevacizumab P = 0.033; COMBO P = 0.040).",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "(E) Quantitative Real-time PCR of h-TGFB1 and m-Tgfb1 of A375 xenograft treated with PLX4720, bevacizumab or COMBO. Data are presented as expression fold change (log2) compared with vehicle after normalization for the housekeeping gene TBP (n=3 tumors), *P < 0.05 versus vehicle (P = 0.043).",
    "diseases": "tumors"
  },
  {
    "caption": "(F) Western blot for human TGFβ in total protein extract from A375 tumors treated as indicate. Vinculin was used as an internal control.",
    "diseases": "tumors"
  },
  {
    "caption": "(B) Representative images of macrophage infiltration determined by F4/80 immunofluorescence staining in A375 xenografts treated as indicated. Bar graphs indicate the F4/80+ area/tumor (n=3 tumors), ***P < 0.001 versus vehicle (P = 1.53E-25).(C) Representative images of collagen deposition determined by collagen I immunofluorescence staining in A375 xenografts treated as indicated. Bar graphs indicate the collagen I+ area/tumor (n=3 tumors).",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "(E) Representative images of macrophage infiltration determined by F4/80 immunofluorescence staining in a responder and a relapsing A375 xenografts. Bar graphs indicate the F4/80+ area/tumor (n=3 mice), ***P < 0.001 versus vehicle (P = 1.25E-06).(F) Representative images of collagen deposition determined by collagen I immunofluorescence staining in a responder and a relapsing A375 xenografts. Bar graphs indicate the collagen I+ area/tumor (n=3 mice), ***P < 0.001 versus vehicle (P = 4.03E-05).",
    "diseases": "tumor"
  },
  {
    "caption": "(G) Real-time quantitative PCR of h-TGFB1 of A375 xenograft treated with PLX4720, bevacizumab or COMBO. Data are presented as expression fold change (log2) of relapsing tumors compared to responder tumors after normalization for housekeeping gene TBP (n=3 tumors) ***P < 0.001 versus vehicle (P = 0.0006).",
    "diseases": "tumors"
  },
  {
    "caption": "(A-B) Overall survival of ER-negative metastatic breast cancer (n=226) (A) and lung adenocarcinoma (n=719) (B) patients according to MARK4 mRNA levels found in their tumors was represented using the Kaplan Meier-plotter [25].",
    "diseases": "tumors"
  },
  {
    "caption": "(C) A cDNA array for 24 matched lung cancers and surrounding normal tissue was analysed for MARK4 expression. Expression levels from tumors were normalised to their respective normal control and the percentage of cases for the indicated fold expression in the tumor represented as a pie-chart.",
    "diseases": "tumor"
  },
  {
    "caption": "(D-F) MARK4 protein expression was determined by histoimmunochemistry in (D-E) a tissue microarray comprising 90 lung tumor and 10 normal lung samples or (F) a home-made tissue microarray comprising 100 matched cases of primary and metastatic tumors. (D-E) The percentage of positivity for MARK4 staining in lung tumors versus normal lung samples (D) or in lung tumors according to their histological subtypes (E) is represented. (F) The percentage of cases with increased, decreased or unchanged levels of MARK4 in metastatic lesions as compared to the corresponding primary tumors is represented.",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "Expression of TGFβR1 and TGFβR2 in cell lysates harvested from KIC (mPLRB8, mPLRB9), KPC (KPC-M01, KPC-M09) and KPfC (BMFA3, CT1BA5) mouse cancer cells, mouse macrophages (RAW 264.7), and mouse fibroblasts (NIH 3T3 and pancreatic stellate cells). RAW 264.7 cells were induced into M1 (30 ng/ml LPS for 18 hours) or M2 (20 ng/ml IL-4 for 18 hours) macrophages. Tubulin was used as a loading control.",
    "diseases": "cancer"
  },
  {
    "caption": "Pearson and Spearman correlation of the expression of IL6 and TGFBR2 in PDA patients from TCGA (n = 223) using R.",
    "diseases": "PDA"
  },
  {
    "caption": "3D culture: cells were seeded on poly-HEMA-coated 96-well plates and cultured for 4 days (5000 cancer cells for monoculture, 3000 cancer cells + 2000 NIH 3T3 for co-culture). IL-6 neutralizing antibody (100 ng/ml).",
    "diseases": "cancer"
  },
  {
    "caption": "3D culture: cells were seeded on poly-HEMA-coated 96-well plates and cultured for 4 days (5000 cancer cells for monoculture, 3000 cancer cells + 2000 NIH 3T3 for co-culture). IL-6 neutralizing antibody (100 ng/ml).",
    "diseases": "cancer"
  },
  {
    "caption": "An in vitro NK cell cytotoxicity assay was performed. Human NKL cells were used as effector cells, and mouse pancreatic cancer BMFA3 cells were used as target cells in normal DMEM (control), conditioned medium collected from TGFβ (30 ng/ml)-treated human pancreatic CAFs (CAF-PC2; CAF TGFβ-CM), CAF TGFβ-CM + IL-6 antibody (100 ng/ml) or normal DMEM + TGFβ (TGFβ). Living cells were labeled with CFSE, and dead cells were labeled with 7-AAD. Samples were analyzed by flow cytometry. Cytotoxicity percentage was calculated using the formula (7-AAD positive cells %) / (7-AAD positive cells % + CFSE positive cells %) x 100%. n = 4/group, P values by t test are shown.",
    "diseases": "pancreatic cancer"
  },
  {
    "caption": "Human pancreatic cancer cell line Colo357 was orthotopically implanted into NOD SCID mice. After tumor establishment, mice were randomized to receive rat IgG Mac84 (control), 2G8 or anti-mouse IL-6 antibody MP5-20F3 (each 30 mg/kg 2x/week, n = 6/group) for 3 weeks. For NK cell depletion, prior to therapies, mice received 50 μg of control rabbit IgG or anti-Asialo-GM1 three days in a row. For maintenance, 25 μg of control rabbit IgG or anti-Asialo-GM1 were given 2X/week throughout the whole study. Tumors were harvested for analysis and metastatic burden was determined by histologic evaluation of H&E-stained liver tissue. Ten sections of the anterior lobe of the liver (n = 6 per group) were scored for lesions.",
    "diseases": "pancreatic cancer"
  },
  {
    "caption": "Overall survival of PDA patients from TCGA with and without TGFBR2 mutation.",
    "diseases": "PDA"
  },
  {
    "caption": "Loss-of-function mutation of Tgfbr2 was generated by CRISPR with two different gRNAs (mut1 and mut2) in the mouse PDA cell line BMFA3 derived from KPfC model. Control cell line (Tgfbr2wt) and two Tgfbr2-mutant cell lines (Tgfbr2mut1 and Tgfbr2mut2) were treated with TGFβ (30 ng/ml) for 5 hours. Cell lysates were harvested and western blotting for P-SMAD2, SMAD2, SMAD4, P-ERK1/2, ERK1/2, P-P38, P38, and actin was performed.",
    "diseases": "PDA"
  },
  {
    "caption": "(A) NSCLC expressing single site mutants of EGFR, PC9 (3X106) or H3255 (8X106), were seeded in 10-cm dishes. On the next day, complete media were replaced with media containing serum (1%) and the cells were treated for 24 hours with different EGFR-specific TKIs (erlotinib, 50 nM; osimertinib, 50 nM, or afatinib, 10 nM), either alone or in combination with 2XmAbs (cetuximab and trastuzumab, 5 μg/ml each). Thereafter, cells were washed with cold saline and extracted. Proteins were separated using gel electrophoresis and transferred onto nitrocellulose membranes. After blocking, membranes were incubated overnight with the indicated primary antibodies, followed by incubation with horseradish peroxidase-conjugated secondary antibodies (60 minutes), and treatment with Clarity™ Western ECL Blotting Substrates (Bio-Rad). ECL signals were detected using the ChemiDoc™ Imaging System (Bio-Rad) and images were acquired using the ImageLab software. Signals (relative to Control) were quantified and normalized to the signals of GAPDH (numbers shown below each lane).",
    "diseases": "NSCLC"
  },
  {
    "caption": "I-M Quantification of IHC staining  from skin-biopsy sections of L-CTCL patients  (n = 6) and healthy individuals (n = 5) As the number of STAT5A/B positive cells was negligible (less than 0.03/per mm2) in healthy skin  biopsy sections, healthy control samples were considered negative for pY-STAT5, and levels were set to 0. Statistical significance was calculated using an unpaired Welch's t-test. P-value: <0.05 (*).The bold dashed line in the middle of the violin plot denotes the median value, while the thin dotted lines denote the interquartile range.",
    "diseases": "L-CTCL"
  },
  {
    "caption": "A-C Graphic depicts the aberration patterns on (A) chromosome 17 (STAT3/5), (B) chromosome 2 (STAT1) and (C) chromosome 16 (SOCS1) in the CTCL  cell lines used in the study. Aberration patterns are represented as the log2 ratio of the fluorescence intensity of the tumor DNA vs. reference DNA and were generated by aCGH. Immunoblotting  for total protein STAT1/3/5 and activation levels: phospo-Tyr (701)-STAT1/phospho-Tyr (705)-STAT3/phospho-Tyr (694/699)-STAT5, and SOCS1 protein levels. The cytokine-dependent cell line, SeAx, was collected 30 min after 5 ng/ml  IL-2 and IL-4 cytokine addition. HSC70  was used as loading control. One representative out of three independent experiments is shown.",
    "diseases": "CTCL"
  },
  {
    "caption": "Real-Time apoptosis/necrosis  assay in the (D, SeAx  and (F, Myla  cell lines treated with 2.5µM JPX-0750 RLU, Apoptosis  [RLU] = relative luminescence; Necrosis  [RFU] = relative fluorescence units. Error bars represent mean +/-SD. One experiment in technical triplicates was performed.",
    "diseases": "Necrosis"
  },
  {
    "caption": "Real-Time apoptosis/necrosis  assay in the E) SeAx  and G) Myla  cell lines treated with 2.5µM IQDMA. RLU, Apoptosis  [RLU] = relative luminescence; Necrosis  [RFU] = relative fluorescence units. Error bars represent mean +/-SD. One experiment in technical triplicates was performed.",
    "diseases": "Necrosis"
  },
  {
    "caption": "H-I The effect of (H) JPX-0750 and (I) IQDMA  on the viability  of CTCL  cells in comparison to viability  of primary  juvenile fibroblasts (JF) and keratinocytes  (HaCat) at a low dose range (0.7-3µM). One experiment, in triplicates, was performed with JF  and HaCat  cells, and three experiments, in triplicates with the CTCL  cells. Error bars represent mean +/-SD. Statistical significance was calculated by two-way ANOVA with Tukey's multiple comparisons test. P-value: <0.05 (*), <0.01 (**), <0.001 (***), <0.0001 (****).",
    "diseases": "CTCL"
  },
  {
    "caption": "E Heatmap showing the IC50  values upon treatment of primary PBMCs  isolated from L-CTCL patients  with JPX-0750, IQDMA  and FRAx597. One experiment performed in triplicates using CellTiter-Glo viability assays  upon 48h drug treatment is shown. The relative STAT3/5 log2 ratio value is depicted in grey.",
    "diseases": "L-CTCL"
  },
  {
    "caption": "(C) RT-qPCR analysis of ROCKI expression in dendritic cell samples from uninfected and M. tuberculosis-infected donors.",
    "diseases": "M. tuberculosis-infected"
  },
  {
    "caption": "H GB glioblastima neurospheres [5 × 104 cells (indicated by the dashed line)] were infected with the indicated lentiviruses. After 96 h, the number of viable cells was counted. Bars indicate mean ± s.d. (n = 4).",
    "diseases": "glioblastima"
  },
  {
    "caption": "B: HIFα- inducible colon cancer signature (HIFi-CCS). Left and middle/left: List of HIFα targets and overall survival in TCGA (left) or aggregated microarray data (middle/left) from colon adenocarcinomas. Cases are classified as low (blue) or high (red) HIFi-CCS according to their relationship to the median. Kaplan-Meier analysis followed by log-rank test. Middle/right: HIFi-CCS and lymph node (LN) invasion status. Data are standardized as z-scores. t(194) = 4.399 and P< 0.0001 by Student t-test with Welch's correction. Right: HIFi-CCS is associated with accelerated distant metastasis. Cases are classified as low (blue) or high (red) HIFi-CCS according to their relationship to the median. Kaplan-Meier analysis followed by log-rank test. ",
    "diseases": "colon adenocarcinomas, colon cancer"
  },
  {
    "caption": "C: HIFα- inducible breast cancer signature (HIFi-BCS). Left and middle/left: List of HIFα targets and overall survival in METABRIC (left) or recurrence- free survival in microarray (middle/left) from breast adenocarcinomas. Cases are classified as low (blue) or high (red) HIFi-BCS according to their relationship to the median. Kaplan-Meier analysis followed by log-rank test. Middle/right: HIFi-BCS and estrogen receptor (ER) status. Data are standardized as z-scores. t(112) = 3.789 and P= 0.0002 by Student t-test with Welch's correction. Right: HIFi-BCS is associated with worsened distant metastasis-free survival. Cases are classified as low (blue) or high (red) HIFi-BCS whenever they are below or above the distribution median. Kaplan-Meier analysis followed by log-rank test. ",
    "diseases": "breast adenocarcinomas, breast cancer"
  },
  {
    "caption": "J. Hyperglycemia  in Rb∆K7 but not Rb∆K4 mice. Blood glucose in 10-12-month old fasting Rb∆K7 (left, n=11) or 18-month old fasting Rb∆K4 (right, n=15) mice versus control littermates (n=6 and n=8, respectively). Mean ±SD; P values by two-tailed unpaired student's t-test.",
    "diseases": "Hyperglycemia"
  },
  {
    "caption": "F Western blot  analysis of liver  lysates (100 µg) from either CodopN6 intein-treated mice  (n=6) or untreated haemophilic mice  (n=2). A lysate from HEK293  cells transfected with the N6 full-length plasmid was used as positive control (50 µg). Arrows point at N6 full-length protein (N6), the 5' half of N6 (5'N6) and 3' half of N6 (3'N6).",
    "diseases": "haemophilic"
  },
  {
    "caption": "Human WAS patient CD4+T cells- APC conjugates display synapse symmetry defects similar to those observed in mouse WASP-/- CD4+ T cells. CD4+T cells purified from healthy controls or WAS patients were incubated with superantigen loaded HUVEC cells for 5' (APC; see 'Methods') and imaged using confocal microscopy. Each image represents a maximum intensity projection of the synaptic area. Graph in the middle shows values normalized to the mean value of the 'Healthy' case. In the case of 'actin' and 'actin foci', n= 87 for healthy and n= 63 for WAS; in the case of pCasL, n=56 for healthy and n= 21 for WAS; for 'AR' graph, n= 88 for healthy and n= 63 for WAS case. P values; ***P <0.001; n.s. P=0.09, as determined by using Mann-Whitney two-tailed test between populations of cells within the same experiment.",
    "diseases": "WAS"
  },
  {
    "caption": "(G) Histology by H&E staining of teratoma tissues derived by D-CiPS cells. n = 3 biological replicates. Scale bar, 200 μm.",
    "diseases": "teratoma"
  },
  {
    "caption": "(C) STAM mice were fed a high-fat diet and orally administered 0.0375 mg/g body weight of DFP, 0.075 mg/g body weight of DFP or distilled water from 4 weeks of age to 16 weeks of age (n=6). Arrows indicate liver tumors. Scale bar: 1.0 cm. The number and maximum size of liver tumors were compared among the three groups. The central horizontal bar and the error bards indicate mean ± SD. The Tukey's honestly significant test was used for statistical analysis. *: P<0.05, **: P<0.01.",
    "diseases": "liver tumors"
  },
  {
    "caption": "(E) Histology of the hepatocellular carcinoma using H&E staining in STAM mice fed a high-fat diet. The boxed area is enlarged on the right (x40 in left panel and x400 in right panel). The tumor has increased cell density, an increased ratio of nucleus to cytoplasm, and thickened trabeculae Scale bar: 100 μm.",
    "diseases": "hepatocellular carcinoma"
  },
  {
    "caption": "(D, E) STAM mice (D) were fed a high-fat diet without DFP treatment or orally administered with 0.075 mg/g body weight of DFP from the age of 4 weeks, injected with FTMT siRNA (10 μl/g body weight) or negative control siRNA through the tail vein every 2 weeks for 8 weeks prior to sacrifice, and followed until 16 weeks of age (n=6). DMBA + HFD mice (E) were fed a high-fat diet, treated with DFP and siRNA in the same manner with STAM mice, and followed until 30 weeks of age (n=6). The number and maximum size of liver tumors were compared among the three groups (control without DFP, negative control siRNA, and FTMT siRNA with DFP). The central horizontal bar and the error bards indicate mean ± SD. The Tukey's honestly significant test was used for statistical analysis. *: P<0.05, **: P<0.01. Representative liver images are shown in the upper panel. Scale bar: 1 cm.",
    "diseases": "liver tumors"
  },
  {
    "caption": "(A) IGV screen shots of  PolII S5P ChIL  signals are shown for representative genes in breast cancer tissues. For each lane, individual samples were selected from each progressive stage of breast cancer.",
    "diseases": "breast cancer"
  },
  {
    "caption": "B-E) Expression of Hep-ID (n=13 genes), Hep-IDCONNECT (n=26 genes) and remaining TF-encoding genes from cluster G (Others; n=82 genes) was monitored in indicated transcriptomic data Box plots show log2 fold changes between adult versus newborn mouse livers (B), MPH of Hnf4ahep-/- (Hnf4a KO) versus wild-type mice (C), a meta-analysis of severe mouse liver injuries versus control livers and microdissected hepatocytes from alcohol-related human liver cirrhosis (alcoholic steatohepatitis) versus control livers (E). Box plots are composed of a box from the 25th to the 75th percentile with the median as a line. Whiskers extent to the most extreme data point which is no more than 1.5 times the interquartile range from the box. Statistical significance was assessed using one-sided Wilcoxon rank sum test with Benjamini-Hochberg correction for multiple testing to determine if the mean log2 FC was statistically lower (B, D, E) or higher (C) than 0. *q<0.05.",
    "diseases": "alcoholic steatohepatitis, liver cirrhosis, liver injuries"
  },
  {
    "caption": "B) Overall survival of patients with HCC expressing low (n=289) or high (n=73) levels of the Hep-IDCONNECT TF encoding genes. Differential overall survival analysis was assessed by Kaplan-Meier (KM) log rank adjusted for 100 permutations",
    "diseases": "HCC"
  },
  {
    "caption": "B Representative TIRF-M of DCP1-GFP (DCP1pro:DCP1-GFP transgene) in the lateral PM of epidermal cells showing the transient attachment of DCP1-positive puncta to the PM. Yellow arrowheads denote a PB that shows motility at the PM focal plane; blue arrowheads show a PB that transiently localizes to the PM. Scale bars: 2 μm. The corresponding kymographs are shown to the right. Right: distribution of immobile and mobile DCP1 molecules relative to the motility log(D) value of -0.75 (threshold; see Material and methods for details), in NS or HS conditions (D, diffusion coefficient). Inset: individual trajectories of mobile DCP1-GFP in NS and HS conditions (500 frames, n = 120), showing a combination of directional and Brownian motion for both NS/HS. The green arrowheads denote the beginning of the NS and HS tracks for DCP1-GFP.",
    "diseases": "TIRF-M"
  },
  {
    "caption": "I Representative images of 6E10 staining  in brain  of sodium propionate or  sodium butyrate-treated AppNL-G-F mice. Scale bar: 1 mm. J Quantification of Aβ  plaque area and number in whole sagittal section of the brain  (n=3 mice; one section per mouse). Data information: Bars represent mean ± SEM. Statistics were performed with one-way ANOVA Bonferroni's post hoc test for multiple comparisons. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "diseases": "Aβ  plaque"
  },
  {
    "caption": "F Plaques  were divided into small (< 250 μm2), medium (250-600 μm2), and large (> 600 μm2), and the number of microglia  per plaque  was quantified (n=5-6 mice; 3-5 plaques per mouse). Data information: Bars represent mean ± SEM. Statistics were performed with one-way ANOVA Bonferroni's post hoc test for multiple comparisons.*p < 0.05, **p < 0.01.",
    "diseases": "plaque, Plaques"
  },
  {
    "caption": "A. CCNA and CCNB2 expression transcripts were analyzed by RT-qPCR in cDNA derived from tumours of control (saline) or zoledronic acid (ZA)-treated mice (ref. 31). N=3 mice per group. P-values were calculated with two-tailed t-test.",
    "diseases": "tumours"
  },
  {
    "caption": "A) Representative P2YR12 immunostaining  (green) of microglia  of wild type male mice showing morphological  differences between control microglia  (a) and ischemic microglia  (b-d). Ischemic microglial cells show typical phagocytic pouches (arrows). Nuclei  are labeled with TO-PRO-3 (blue). Image (d) is a magnification of the area marked with a square in (c). Scale bar a, b: 20 μm; c: 10 μm; d: 4 μm.",
    "diseases": "ischemic, Ischemic"
  },
  {
    "caption": "C) PLIN2 protein expression  in mouse brain  tissue, as assessed by Western blotting. Values were obtained from the ipsilateral hemisphere  1h (n=3), 4h (n=3), 15h (n=4), 24h (n=5) and 96h (n=5) post-ischemia, and 15h (n=4), 24h (n=2), and 96h (n=2) after sham-operation. Values of sham mice  were pooled together since they did not differ between time points. Samples of the contralateral hemisphere (Contra) of ischemic mice  (1h, n=2; 24h, n=3; and 96h, n=3) were also evaluated. Ischemia  increased PLIN2  expression at day 4 vs. the sham group (**p=0.0032, Kruskal-Wallis test and Dunn's multiple comparisons test).  β-tubulin is the protein loading control. The 'Std' lane indicates the molecular weight standard. Quantification of band intensity where values are expressed as fold versus control (non-ischemic). Points correspond to independent male mice  and group values are expressed as violin plot. Values were obtained 1h (n=3), 4h (n=3), 15h (n=4), 24h (n=5) and 96h (n=5) post-ischemia, and 15h (n=4), 24h (n=2), and 96h (n=2) after sham operation. Values of sham mice  were pooled together since they did not differ between time points. Samples of the  contralateral hemisphere  (Contra) of ischemic mice  (1h, n=2; 24h, n=3; and 96h, n=3) were also evaluated. Ischemia  increased PLIN2  expression at day 4 (**p=0.0032, Kruskal-Wallis test and Dunn's multiple comparisons test vs. the sham group). Data are presented as violin plots with lines at the median and quartiles (dashed lines).",
    "diseases": "ischemia, Ischemia, ischemic"
  },
  {
    "caption": "D) Immunofluorescence  with antibodies against PLIN2  (green) and Iba-1 (red) in brain  tissue 1 day after induction of ischemia  in female mice. Nuclei  are stained  with DAPI  (blue). Control is the contralateral hemisphere. Scale bar: 10 μm.",
    "diseases": "ischemia"
  },
  {
    "caption": "E) Transmission electron microscopy showing  microglial cells  in control or ischemic  tissue one-day post-ischemia. Ischemia  induces the formation of  lipid droplets (LD) in microglia. LD  are often seen near lysosomes  (Lys). Insets in the lower panels are magnifications of the regions marked with a square. Scale bar 2 μm.",
    "diseases": "ischemia, Ischemia, ischemic"
  },
  {
    "caption": "F) Flow cytometry  gates to identify Bodipy+ microglia  for control and ischemic brain  tissue. Gates were set based on fluorescence minus one (FMO) intensity values.",
    "diseases": "ischemic"
  },
  {
    "caption": "G) Quantification of the percentage of CD11b+CD45low microglia  containing  lipid droplets as Bodipy+ microglia  using flow cytometry in male mice  deficient in Stat1  (Stat1-/-) (n=4) and corresponding Stat1+/+ mice  (n=7) shows ischemia-induced increases in Stat1+/+ mice  (** p=0.0086) but not in Stat1-/- mice  (p=0.927) (Two-way ANOVA and Šídák's multiple comparisons test). Graph shows values of the non-ischemic  (-) and ischemic  (+) brain  hemispheres of individual mice  and the mean±SD.",
    "diseases": "ischemia, ischemic"
  },
  {
    "caption": "D) Quantification of  flow cytometry  shows that microglia renewal  reduced the percentage of Bodipy+ microglia  in old mice  in sham (***p=0.0001) and ischemic  (*p=0.0057) conditions (one-way Anova and Holm-Šídák's multiple comparisons test). For illustrative purposes the values of young mice  are also shown (original  old  vs. young: ***p<0.001 in the sham group and **p=0.0026 in the ischemic  group). Values show individual mice  and bars show the mean±SD.",
    "diseases": "ischemic"
  },
  {
    "caption": "C). The MRI lesion   volume, as illustrated in the corresponding false color images below, showed no differences in infarct volume in mice  with (n=16) or without (n=15) microglia  renewal. Results correspond to day four post-ischemia. Representative MRI  images obtained on day four post-ischemia  using T2w MRI  and day 14 using a Modified Driven Equilibrium Fourier Transform (MDEFT) MRI  sequence (7.0 T BioSpec 70/30, Bruker BioSpin). Values show data for individual mice  and/or the mean±SD.",
    "diseases": "ischemia"
  },
  {
    "caption": "C -Relationship between TGM2 and GLUT-1 (top) and GLUT-3 (bottom) expression across 265 HGSOCs. Expression comparisons were performed using Spearman's rank correlation test.",
    "diseases": "HGSOCs"
  },
  {
    "caption": "(C) A3A interacts with CCT in  leukemia  cells. HA immunoprecipitation in  hematopoietic cell lines with inducible  A3A-HA  was analyzed by immunoblot. HA, CCT1, and CCT5  antibodies were used to evaluate co-precipitation of CCT subunits with  A3A.",
    "diseases": "leukemia"
  },
  {
    "caption": "(C) Quantification of APOBEC3  mutational signatures among three tumor types that have previously been associated with high APOBEC3 activity. Breast, bladder, and cervical cancer samples from the TCGA database were divided into CCT-mutated and non-mutated genomes, as above. The number of mutations contributing to SBS 2 and SBS 13 in each tumor type was quantified and displayed as an average. Comparison by Wilcoxon rank sum test yielded p-values denoted.",
    "diseases": "cervical cancer"
  },
  {
    "caption": "Cell death measured by flow cytometry using propidium iodide exclusion in human lung adenocarcinoma H1299 cells with tet-inducible expression of human p53EE. Cells with overexpression of human p53EE mutant display a trend of increased cell death after treatment with 0.5 µg/ml Doxo.",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "Cell death measured by flow cytometry using propidium iodide exclusion in human lung adenocarcinoma H1299 cells with tet-inducible expression of human p53EE. Cells with overexpression of human p53EE mutant display a trend of increased cell death after treatment with 0.5 µg/ml Doxo. This effect is enhanced by addition of Nutlin and blocked by the pan-caspase inhibitor QVDOph, but not the ferroptosis inhibitor Ferrostatin-1 (Ferr) as control. (A) n=3; (B) n=2.",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "p53 IHC for representative samples from (D) and (E) illustrates constitutive stabilization of p53EE in cancer cells; scale bars 25 µm.",
    "diseases": "cancer"
  },
  {
    "caption": "Apoptosis in Eµ-Myc lymphoma cells of indicated genotype was measured by flow cytometry (FITC-VAD-FMK staining) at indicated time points after treatment with 3 µg/ml MAF. Significance was calculated versus untreated. n≥5.",
    "diseases": "lymphoma"
  },
  {
    "caption": "Enrichment of p53 shRNA-expressing Eµ-Myc;p53EE lymphoma cells under MAF treatment. Non-silencing control shRNA served as control. n=3.",
    "diseases": "lymphoma"
  },
  {
    "caption": "mRNA expression of p53 target genes was measured relative to β-actin by RTqPCR following treatment of Eµ-Myc lymphoma cells of indicated genotype with 3 µg/ml MAF. n≥3.",
    "diseases": "lymphoma"
  },
  {
    "caption": "Kaplan-Meier survival plots for cyclophosphamide-treated versus untreated control mice transplanted with Eµ-Myc lymphoma cells of indicated genotype at day 0. Treatment started ~10 days later when peripheral lymph nodes became palpable. The time course of the experiment is illustrated in a scheme.",
    "diseases": "lymphoma"
  },
  {
    "caption": "Residual disease in the spleen of mice from (D) was quantified 24 hours and 7 days after therapy using a quantitative PCR assays with primers specific to the Eµ-Myc transgene (present only in lymphoma cells). Shown is the copy number of the Eµ-Myc transgene relative to a control locus present in all cells. Untreated Eµ-Myc mice (Myc tg) were used as positive control. Non-transgenic mice (no Myc tg) served as negative controls to define the detection limit. Significance was tested by t-test (two-sided, unpaired).",
    "diseases": "lymphoma"
  },
  {
    "caption": "Representative bioluminescence imaging (BLI) pictures of mice transplanted with AE9+Nras AML cells. Day 0 indicates the start of combination therapy with cytarabine (AraC) + doxorubicin (Doxo).",
    "diseases": "AML"
  },
  {
    "caption": "Kaplan-Meier survival plots for animals from (G). Statistical significance of differences calculated by Log-rank (Mantel-Cox) test between treated Eµ-Myc;p53EE/EE AML and all other groups is indicated in the table. C, untreated control; T, therapy (AraC+Doxo).",
    "diseases": "AML"
  },
  {
    "caption": "(A) CRMP2 deficiency leads to callosal hypoplasia. Shortening of corpus callosum (arrowheads) is apparent in both sagittal (first row) and coronal sections (second row) of adult brains. Scale bars: 1 mm.",
    "diseases": "hypoplasia"
  },
  {
    "caption": "Elevated plus maze test (n=10 mice/genotype). (E) Total distance walked is similar in WT and crmp2-/- (WT 7.9±0.45 m, crmp2-/- 8.6±0.5 m, p=0.3). (F) Frequency of open arm (OA) visits is increased in crmp2-/- mice suggesting decreased anxiety. CA denotes closed arms, MID denotes the transition zone between arms, Total arm visits represents a sum of visits in all four arms. (CA frequency: WT 13.7±0.9/5 min, crmp2-/- 10.5±1.1/5 min, p=0.04; OA frequency: WT 7.7±0.8/5 min, crmp2-/- 14.6±1.7/5 min, p=0.002; MID frequency: WT 20.6±1/5 min, crmp2-/- 24.6±1.6/5 min, p=0.06 mean ± SEM, *p<0.05, ***p<0.001, t-test.",
    "diseases": "anxiety"
  },
  {
    "caption": "Elevated plus maze test (n=10 mice/genotype). (G) duration of open arm (OA) visits is increased in crmp2-/- mice suggesting decreased anxiety. CA denotes closed arms, MID denotes the transition zone between arms, Total arm visits represents a sum of visits in all four arms. Total arm visits: WT 21.4±1/5 min, crmp2-/- 25.1±1.5/5 min, p=0.07; CA duration: WT 177±17 s., crmp2-/- 75.3±12.6 s, p<0.001; OA duration: WT 42±12.6 s, crmp2-/- 144.4±21 s, p<0.001; MID duration: WT 80.26±11.5 s., crmp2-/- 80.17±12.6 s., p=0.99), mean ± SEM, *p<0.05, ***p<0.001, t-test.",
    "diseases": "anxiety"
  },
  {
    "caption": "(C) Benign breast epithelial MCF10A and breast carcinoma BT-474 cells were embedded in 3D collagen as single cells or as spheroids, respectively, and the growth was followed for 5 days. Light micrographs show filamentous actin (phalloidin) and nuclei (Hoechst) in representative cell colonies. Quantitative assessment of the nuclei counts per colony show the induced proliferation in MCF10A cells after ECHCD1 sgRNA knockout. At 72 hours, MCF10A mock versus ECHDC1_sgRNA_1 and ECHDC1_sgRNA_2 P < 0.05; at 96 hours mock versus ECHDC1_sgRNA_1, ECHDC1_sgRNA_2 and ECHDC1_sgRNA_3 P < 0.001; at 120 hours mock versus ECHDC1_sgRNA_1, ECHDC1_sgRNA_2 and ECHDC1_sgRNA_3 P < 0.0001. Nuclei count relative to mock 0 hours. Error bars indicate mean ± SEM; n ≥ 10 colonies. Statistical significance was assessed with one-way ANOVA with Tukey's multiple comparison test. Scale bar 50 µm.",
    "diseases": "breast carcinoma"
  },
  {
    "caption": "(E) Measured metabolite levels of intermediates in propanoate metabolism in select breast cancer cell lines with or without the ECHDC1 rCCS status (n=7 in both groups). Boxes represent the interquartile range, whiskers represent the range of the values and solid line within the box correspond to the median value. Outlier points indicates values not included between the whiskers. Statistical significance was assessed with Wilcoxon test.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(H) Survival analysis based on mRNA expression levels of DDX27 in patients with endometrial cancer in the TCGA dataset. Expression levels were divided into 2 classes, high (n=203) and low (n=322), based on mean expression level of DDX27 (logFPKM=18.27). Patients in the high class showed lower survival probability than those in the low class (P=.4.2×10-4; log-rank test).",
    "diseases": "endometrial cancer"
  },
  {
    "caption": "Quantification of IL-1β concentration (pg/ml) in the supernatant of primary macrophage cultures from COVID-19 patients (n = 44; red bars) or SC-naïve individuals (n = 24; blue bars) stimulated with LPS or S-protein (0.1 µg/ml). To activate IL-1β secretion nigericin was added for 2h. For statistical analysis, two-way ANOVA with tukey post hoc test was used. TNF-α (pg/ml) secreted from macrophages derived from SC-naïve and COVID-19 patients as described above. Cells were stimulated with LPS (SC-naïve/COVID-19 n = 4), LPS with nigericin (SC-naïve n = 4; COVID-19 n = 6), S-protein (SC-naïve n = 5; COVID-19 n = 4), S-protein with nigericin (SC-naïve n = 3; COVID-19 n = 4) or left unstimulated (SC-naïve n = 3; COVID-19 n = 4). Significances shown in the figure are always in comparison to the unstimulated control.",
    "diseases": "COVID-19"
  },
  {
    "caption": "Representative confocal microscope pictures of macrophages from SC-naïve (top) and COVID-19 patients (bottom). Nuclei are stained with DAPI (blue) and ASC speck are labeled by immunofluorescence staining (green). Macrophages were stimulated with LPS (left) and S-Protein (right) for 4h followed by stimulation with nigericin in both cases. Pictures were taken with a 60x objective using the same microscope settings.",
    "diseases": "COVID-19"
  },
  {
    "caption": "Subgroup analysis of IL-1β secretion of macrophages after stimulation with S-protein and nigericin from COVID-19 patients with severe (red/black; n=23) or mild (white/red; n=21) disease. Student's t-test with Welsh corrections was used to calculate statistical differences. Graph shows mean ± SEM.",
    "diseases": "COVID-19"
  },
  {
    "caption": "Volcano plot showing DEGs in S-protein stimulated macrophages from convalescent COVID-19 patients (SC-conv) compared to unstimulated cells. Negative log10 adjusted p-values are plotted against the log2 fold-change. Select genes are labeled. P-values are calculated using Wald test and p-adjusted values using the FDR/Benjamini-Hochberg approach.",
    "diseases": "COVID-19"
  },
  {
    "caption": "IL-1β concentration (pg/ml) in supernatants of COVID-19 patient derived macrophages pretreated with DMSO (n = 44), KINK-1 (n = 11) and MMG-11 (n = 19) and subsequent stimulation with LPS and nigericin. For statistical analysis, one-way ANOVA was used.",
    "diseases": "COVID-19"
  },
  {
    "caption": "IL-1β concentration (pg/ml) in supernatants from macrophages of SC naïve (blue; n = 7) and COVID-19 patients (red; n = 11). Macrophages were pre-treated with DMSO (SC-naïve n = 7; COVID-19 n = 11), KINK-1 (SC-naïve n = 6; COVID-19 n = 7) and MMG-11 (SC-naïve n = 4; COVID-19 n = 4) for 2h and then stimulated with zymosan (4h) and nigericin (2h) as indicated. For statistical analysis, two-way ANOVA with tukey post hoc test was used.",
    "diseases": "COVID-19"
  },
  {
    "caption": "IL-1β concentration (pg/ml) in supernatants from COVID-19 patients which were stimulated for 2h with a blocking anti-TLR2 monoclonal antibody in different concentrations as indicated. Subsequently, macrophages were stimulated with LPS (1 ng/ml: n = 6; 10 and 100 ng/ml: n = 7) and S-Protein (1 ng/ml: n = 12; 10 and 100 ng/ml: n = 13) for 4h and both groups for 2h with nigericin. For statistical analysis, one-way ANOVA was used",
    "diseases": "COVID-19"
  },
  {
    "caption": "Volcano plot showing DEGs in unstimulated COVID-19 patient-derived macrophages (SC-conv) compared to macrophages from SARS-CoV-2 naïve individuals (SC-naïve). Negative log10 padj values are plotted against the log2 fold-change. Selected genes of interest are labeled.",
    "diseases": "COVID-19"
  },
  {
    "caption": "Quantification of IL-1β concentrations (pg/ml) in the supernatant of primary macrophage cultures from patients with active/untreated tuberculosis (n = 6; red/black bars) or healthy/SARS-CoV-2 naïve individuals (n = 3; blue bars) or the same patients after 6 months of anti-tuberculous treatment; n = 6; white/red bars) stimulated with LPS or S-protein (0.1 µg/ml) for 4h and subsequent incubation with nigericin for 2h. For statistical analysis, two-way ANOVA with tukey post hoc test was used.",
    "diseases": "tuberculosis, tuberculous"
  },
  {
    "caption": "E.  Immunohistochemical staining  of tissue arrays containing 24 breast carcinoma samples paired with adjacent normal mammary tissues for hTrmt13 expression. Representative images are shown (left), and the mean  staining  intensity was calculate using Image-Pro Plus software (right). Statistical analysis was performed using t-tests.",
    "diseases": "breast carcinoma"
  },
  {
    "caption": "F. Kaplan-Meier survival analysis of Kaplan-Meier plotter (http://kmplot.com/analysis/) for the relationship between the  relapse-free survival (RFS) or overall survival time (OS) of  breast cancer patients (BRCA, n=349 (low)/205 (high)),  liver cancer patients (LIHC, n=270 (low)/100 (high)), patients with kidney renal clear cell carcinoma (KRIC, n=156 (low)/374 (high)), and  patients with kidney renal papillary cell carcinoma (KIRP, n=208 (low)/79 (high)) and their expression of hTrmt13.",
    "diseases": "BRCA, breast cancer, kidney renal clear cell carcinoma, KRIC, LIHC, liver cancer, kidney renal papillary cell carcinoma, KIRP"
  },
  {
    "caption": "Analysis of the indicated gene expression datasets for mRNA levels of P5CS: (i) lung tissue from mice with pulmonary fibrosis induced by bleomycin (Bleo) treatment compared to saline treatment (GSE112827);",
    "diseases": "pulmonary fibrosis"
  },
  {
    "caption": "two datasets (GSE110147, GSE32537) from lungs of patients with idiopathic pulmonary fibrosis (IPF) compared to normal controls (Ctrl). AU, arbitrary units. The number of patients per group is indicated.",
    "diseases": "idiopathic pulmonary fibrosis, IPF"
  },
  {
    "caption": "Analysis of the indicated gene expression datasets for mRNA levels of Slc25a1, as described in Figure 3: (j) lung tissue from mice with pulmonary fibrosis induced by bleomycin (Bleo) treatment compared to saline treatment (GSE112827);",
    "diseases": "pulmonary fibrosis"
  },
  {
    "caption": "Analysis of the indicated gene expression datasets for mRNA levels of Slc25a1, as described in Figure 3: two datasets (GSE110147, GSE32537) from lungs of patients with idiopathic pulmonary fibrosis (IPF) compared to normal controls (Ctrl). AU, arbitrary units. The number of patients per group is indicated.",
    "diseases": "idiopathic pulmonary fibrosis, IPF"
  },
  {
    "caption": "Pearson correlation of Slc25a1 and P5CS mRNA levels in IPF patients from GSE32537. IPF patients from GSE32537 were assigned into P5CSlow/SLC25A1high and P5CShigh/SLC25A1low groups based on the expression level of P5CS and SLC25A1. "High" represents patients with P5CS or SLC25A1 expression values being above the 75% percentile of the respective gene expression; "low" represents patients with expression values being below the 25% percentile of gene expression. The forced vital capacity (FVC) before bronchodilator (pre-BD) as percentage of what was predicted for each patient was compared between the groups.",
    "diseases": "IPF"
  },
  {
    "caption": "C-E, boxplots showing the serum  level of phenylacetylglutamine, mandelic acid  and homovanillic acid  in different CHF  subgroups in the REM-HF  cohort. NGT: n = 23; NGT+CHF: n = 48; Prediabetes+CHF: n = 83; T2D+CHF: n = 56; Prediabetes+CHF+CKD: n = 34; T2D+CHF+CKD: n = 16 (biological replicates). Data information: the central band in each box represents the median, the top and bottom of the box the 25th and 75th percentiles, and the whiskers 1.5 times the interquartile range. Wilcoxon rank-sum test was used for all group comparisons.",
    "diseases": "CKD, CHF, HF, Prediabetes, T2D"
  },
  {
    "caption": "F, the boxplot showing the serum  level of ImP  in the Swedish prediabetes  versus the Chinese REM-HF  cohorts. For Swedish prediabetes  cohort, NGT: n = 125; prediabetes: n = 262; T2D: n = 17 (biological replicates). For Chinese REM-HF  cohort: NGT: n = 23; NGT+CHF: n = 48; Prediabetes+CHF: n = 83; T2D+CHF: n = 56; Prediabetes+CHF+CKD: n = 34; T2D+CHF+CKD: n = 16. Data information: the central band in each box represents the median, the top and bottom of the box the 25th and 75th percentiles, and the whiskers 1.5 times the interquartile range. Wilcoxon rank-sum test was used for all group comparisons.",
    "diseases": "CKD, CHF, HF, prediabetes, Prediabetes, T2D"
  },
  {
    "caption": "G, differences in ImP  when stratified by left ventricular ejection fraction (LVEF; two-tailed Wilcoxon rank-sum tests). NGT: n = 23; HFpEF: LVEF  ≥50, n = 66; HFmEF: 40<LVEF<50, n = 68; HFrEF: LVEF ≤40, n = 103 participants. Data information: the central band in each box represents the median, the top and bottom of the box the 25th and 75th percentiles, and the whiskers 1.5 times the interquartile range. Wilcoxon rank-sum test was used for all group comparisons.",
    "diseases": "HF"
  },
  {
    "caption": "A, the Kaplan-Meier survival curve based on the Framingham and GWTG-HF  risk scores. 240 participants with clinical variables for Framingham and GWTG-HF  risk scores calculation were included in survival  analysis (biological replicates). P values were calculated based on the log-rank test.",
    "diseases": "HF"
  },
  {
    "caption": "C, the time-dependent   receiver operating characteristic (ROC) curves  for the performance of GWTG-HF  scores, metabolite-based risk score and the combination of both scores in CHF  prognosis. The AUC values were determined by bootstrap resampling with 1,000 iterations.",
    "diseases": "CHF, HF"
  },
  {
    "caption": "b, Experimental procedure in vivo: flow chart and pictures of an in vivo screen to identify DUBs that promote breast cancer metastasis in mice (left panel). Low metastatic MDA-MB-231-Luciferase/GFP breast cancer cells were infected with viral vectors expressing DUB cDNAs and subsequently intracardially injected into nude mice. The mice were monitored for 4 weeks by in vivo BLI: of the 30 mice injected with cells expressing DUB cDNA pool; 3 had metastases in the brain and bone (3/30), 4 had metastases on the back and in the bone (4/30), and 9 had micro-metastasis (9/30); the 30 mice injected with control cells showed no detectable metastasis (30/30). Right panel: hints of the identified DUBs were shown.",
    "diseases": "breast cancer"
  },
  {
    "caption": "c, The expression distribution of USP8 gene in breast cancer tumor tissues (n = 1097) and normal tissues (n = 572), where the horizontal axis represents different groups of samples, the vertical axis represents the gene expression distribution (left panel). The box-and-whisker plots represent the medians (middle line), first quartiles (lower bound line), third quartiles (upper bound line), and the ±1.5× interquartile ranges (whisker lines). Kaplan-Meier curves showing the metastasis-free survival of individuals was negatively correlated with USP8 expression by log-rank test (right panel).",
    "diseases": "breast cancer"
  },
  {
    "caption": "a, Heatmap of USP8-correlated genes in a comparison of breast cancer patients with USP8-high (n = 38) versus with USP8-low (n = 39).",
    "diseases": "breast cancer"
  },
  {
    "caption": "b, Pre-ranked gene set enrichment analysis (GSEA) in USP8-high (n = 38) versus USP8-low (n = 39) breast cancer patients.",
    "diseases": "breast cancer"
  },
  {
    "caption": "l, Expression of USP8 of normal tissues (n = 11) and breast cancer patients (n = 110).",
    "diseases": "breast cancer"
  },
  {
    "caption": "n, Percentage of specimens displaying low or high USP8 expression compared to the expression levels of TβRII and P-SMAD2 in human breast cancer tissue (n = 110). p values from Student's t tests were indicated.",
    "diseases": "breast cancer"
  },
  {
    "caption": "o, GEPIA analysis curves showing the metastasis-free survival of breast cancer patients was significantly correlated with USP8 expression by log-rank test in the TCGA and GTEx datasets (http://gepia.cancer-pku.cn/). Cutoff-high = 67%, cutoff-low = 25%.",
    "diseases": "breast cancer"
  },
  {
    "caption": "a, Comparison of the pre-treatment levels of USP8 mRNA in patient-derived tissue samples by qRT-PCR (left panel), enzyme activity of USP8 in patient-derived tissue samples by Ub-VME (middle panel) and TβRII+ crEVs level in the plasma from breast cancer patients by ELISA (right panel) between breast cancer patients with or without clinical response to PTX. R, responders; n = 16; NR, non-responders; n = 14.",
    "diseases": "breast cancer"
  },
  {
    "caption": "b, Pearson correlation of the USP8 mRNA or USP8 enzyme activity in patient-derived tissue samples with the EV-TβRII levels in the plasma from breast cancer patients without clinical response to PTX as in a (NR, n = 14).",
    "diseases": "breast cancer"
  },
  {
    "caption": "d, Pearson correlation of the percentage of IFN-γ+ of CD8+ cells to the TβRII+ crEV level in the plasma from breast cancer patients without clinical response to PTX as in a (NR, n = 14).",
    "diseases": "breast cancer"
  },
  {
    "caption": "e, TβRII+ crEVs (left panel), the USP8 enzyme activity (midde panel) and USP8 mRNA (right panel) from breast cancer patients with or without clinical response to combined therapy using anti-PD-L1 (Atezolizumab) and paclitaxel. R, responders; n = 10 (left panel), n = 5 (middle and right panels, only 5 patient-derived tissue samples obtained). NR, non-responders; n = 10 (left panel), n = 6 (middle and right panels, only 5 patient-derived tissue samples obtained).",
    "diseases": "breast cancer"
  },
  {
    "caption": "c, Immunoblot analysis of total cell lysates derived from MDA-MB-231 breast cancer cell treated with USP8 inhibitor and TGF-β (2.5 ng/ml) as indicated.",
    "diseases": "breast cancer"
  },
  {
    "caption": "g, Gene signatures indicating the up-regulated epithelial-mesenchymal-transition (EMT) (upper panel) and breast cancer progenitors-related gene set (bottom panel) are significantly enriched in control cells; shown by pre-ranked gene-set enrichment analysis (GSEA).",
    "diseases": "breast cancer"
  },
  {
    "caption": "A) Serum TSH and T4 levels in 3-month-old Tubb1-/- and wild-type mice. Numbers of animals tested were 10 wild-type males and 14 Tubb1-/- males for TSH and for 14 wild-type and 22 Tubb1-/-males for T4. Tubb1-/- mice had hypothyroidism with elevated TSH and decreased T4 versus wild-type mice. Student\"s test, ** p<",
    "diseases": "hypothyroidism"
  },
  {
    "caption": "A. Detection of  FadA in  subgingival plaque samples by IHC. Three  patients with periodontitis are shown here who provided plaque samples from their healthy sites (probing depth ≤ 3 mm, left panels) as well as periodontal diseased sites (probing depth ≥ 7 mm, middle panels). IHC was performed as described using mAb 7H7 at 1:800 dilution. Anti-mouse IgG isotype control of the diseased site is shown (right panels). The  images were taken using 100X objective. Scale bar equals 50 μm.",
    "diseases": "periodontal, periodontitis"
  },
  {
    "caption": "B. Double  immunofluorescence staining of paired normal and  carcinoma tissues from two  CRC patients. The frozen tissue sections were incubated with mAb 7H7 at 1:50 dilution and anti-amyloid  antibody A11  at 1:25 dilution, or mouse and rabbit IgG control, followed by incubation with Alexa Fluor 555-conjugated  goat anti-mouse and Alexa Fluor 680-conjugated donkey anti-rabbit, both at 1:1000 dilution. Co-staining of FadA (red) and  amyloid oligomers  (green) was observed in the carcinoma but not normal tissues. The  images were taken under 60X objective. Scale bar equals 10 μm.",
    "diseases": "CRC"
  },
  {
    "caption": "A Immunohistochemical analysis of LONP1 expression in CKD children with mild (n=11), moderate (n=10), or severe fibrosis (n=9). N=4 in Normal group.",
    "diseases": "CKD, fibrosis"
  },
  {
    "caption": "D Western blot analysis for the expression of LONP1 in UUO models at different time points.",
    "diseases": "UUO"
  },
  {
    "caption": "F Deposition of total fibrosis in kidney tissues was determined by Masson's trichrome staining. Scale bar: 50μm. G Sirius red staining in WT and cKI mice after UUO. Scale bar: 50μm.",
    "diseases": "fibrosis, UUO"
  },
  {
    "caption": "J, K Western blot and densitometric analysis for the expression of FN1, Collagen I, Collagen III and TGF-β1 (monomer) in WT and cKI mice after UUO (n=3 or 4, biological replicates).",
    "diseases": "UUO"
  },
  {
    "caption": "M Succinate dehydrogenase (SDH) staining in WT and cKI mice after UUO. Scale bar: 50μm.",
    "diseases": "UUO"
  },
  {
    "caption": "N Transmission electron microscopy images of the mitochondria in tubular cells in WT and cKI mice after UUO. Scale bar: 500nm.",
    "diseases": "UUO"
  },
  {
    "caption": "A Deposition of total fibrosis in kidney tissues was determined by Masson's trichrome staining. Scale bar: 50μm. B Sirius red staining in WT and cKO mice after UUO. Scale bar: 50μ",
    "diseases": "fibrosis, UUO"
  },
  {
    "caption": "D, E Western blot and densitometric analysis for the expression of FN1, Collagen I, Collagen III and α-SMA in WT and cKO mice after UUO (n=3, biological replicates).",
    "diseases": "UUO"
  },
  {
    "caption": "I Transmission electron microscopy images of the mitochondria in tubular cells in WT and cKO mice after UUO. Scale bar: 500nm.",
    "diseases": "UUO"
  },
  {
    "caption": "A Immunohistochemical analysis of HMGCS2 expression in CKD children. Scale bar: 50μm. B Immunohistochemical semi-quantitative IOD analysis of HMGCS2 (n=8 in Control group, n=15 in CKD group).",
    "diseases": "CKD"
  },
  {
    "caption": "Western blot analysis of HMGCS2 in WT and cKI mice of UUO model (n=3 or 4, biological replicates).",
    "diseases": "UUO"
  },
  {
    "caption": "A Fibrosis deposition of kidney tissues was determined by Sirius red staining in UUO model. Scale bar: 50μm. B Quantification of fibrotic area in UUO model (n=10 in each group, biological replicates).",
    "diseases": "Fibrosis, fibrotic, UUO"
  },
  {
    "caption": "G, H Fibrosis deposition of kidney tissues was determined by Sirius red staining and quantified in UIRI model (n=10 in each group, biological replicates). Scale bar: 50μm.",
    "diseases": "Fibrosis, UIRI"
  },
  {
    "caption": "F, G Frequencies of human lymphoma cells, as judged by hCD45 expression, among all (human and mouse, h+m) CD45+ leukocytes in the spleen (S), femoral bone marrow (BM) and jaw bone marrow (JB) at the study endpoint of the mice shown in D (four weeks post injection for U-2932, five weeks p.i. for RIVA and six weeks p.i. for RC-K8).",
    "diseases": "lymphoma"
  },
  {
    "caption": "MISTRG mice were reconstituted or not at birth with human CD34+ cord blood HSPCs, and intravenously injected with 10x106 U-2932 or RC-K8 cells at six weeks of age. The lymphoma burden at the study endpoint was quantified in the spleen (F) and bone marrow (G) by staining for hCD45 (as well as hCD19 and hCD20 for U-2932 and RC-K8, respectively)",
    "diseases": "lymphoma"
  },
  {
    "caption": "MISTRG mice were reconstituted or not at birth with human CD34+ cord blood HSPCs, and intravenously injected with RC-K8 cells at six weeks of age. The lymphoma burden at the study endpoint was quantified by ZsGreen expression and in the case of RC-K8 cells, also over time by IVIS (H).",
    "diseases": "lymphoma"
  },
  {
    "caption": "MISTRG and MISTRG6 mice were intravenously injected with 10x106 U-2932 or RC-K8 cells at six weeks of age and monitored weekly by IVIS until the study endpoint (A). The lymphoma burden at the study endpoint (six weeks p.i. for RC-K8 and four weeks p.i. for U-2932) was quantified in the spleen (B) and bone marrow (C) by flow cytometric staining for hCD45 and by ZsGreen expression.",
    "diseases": "lymphoma"
  },
  {
    "caption": "1x106 primary DLBCL cells obtained by passaging through a MISTRG6 mouse were intravenously injected into MISTRG or MISTRG6 recipients. The spleen weights (B, representative pictures in A) are shown",
    "diseases": "DLBCL"
  },
  {
    "caption": "1x106 primary DLBCL cells obtained by passaging through a MISTRG6 mouse were intravenously injected into MISTRG or MISTRG6 recipients. with representative H&E-stained spleen (MISTRG6) and lymph node (patient) sections in C",
    "diseases": "DLBCL"
  },
  {
    "caption": "1x106 primary DLBCL cells obtained by passaging through a MISTRG6 mouse were intravenously injected into MISTRG or MISTRG6 recipients. the lymphoma burden at the study endpoint eight weeks p.i., as quantified in the spleen and bone marrow in D Representative flow cytometry plots are shown in D for bone marrow and spleen (MISTRG, MISTRG6).",
    "diseases": "DLBCL, lymphoma"
  },
  {
    "caption": "x106 primary DLBCL cells obtained by passaging through a MISTRG6 mouse were intravenously injected into MISTRG or MISTRG6 recipients. the lymphoma burden at the study endpoint eight weeks p.i., as quantified in the spleen and bone marrow",
    "diseases": "DLBCL, lymphoma"
  },
  {
    "caption": "MISTRG mice were reconstituted or not at birth with human CD34+ cord blood HSPC, and intravenously injected with 1x106 primary DLBCL cells at six weeks of age. The lymphoma burden at the study endpoint was quantified in the bone marrow of reconstituted and un-reconstituted animals by flow cytometric staining for the indicated surface markers.",
    "diseases": "DLBCL, lymphoma"
  },
  {
    "caption": "Primary lymphoma cells harvested at the study endpoint express the IL-6R α chain (CD126, as assessed by flow cytometry, G) and are positive for phosphorylated STAT3 (G).",
    "diseases": "lymphoma"
  },
  {
    "caption": "Primary lymphoma cells harvested and the signaling chain gp130 (as assessed by immunohistochemistry, H)",
    "diseases": "lymphoma"
  },
  {
    "caption": "The expression of the IL-6Rα (CD126) and signaling chains (gp130) was assessed by flow cytometry (A) on a panel of DLBCL cell lines. ABC- and GCB-DLBCL cell lines are color-coded in red and green; RC-K8 are depicted in grey, as their subtype is a matter of debate",
    "diseases": "DLBCL"
  },
  {
    "caption": "The expression of the IL-6Rα (CD126) and signaling chains (gp130) was assessed by SYBR or Taqman qRT-PCR (B, C) respectively, on a panel of DLBCL cell lines. ABC- and GCB-DLBCL cell lines are color-coded in red and green; RC-K8 are depicted in grey, as their subtype is a matter of debate",
    "diseases": "DLBCL"
  },
  {
    "caption": "D and E. The expression of gp130 in 114 tumor biopsies of DLBCL patients was assessed by immunohistochemistry, and correlated with the ABC/non-GCB vs. GCB subtype, as assessed via Hans classification. Representative micrographs are shown in D, alongside the quantification of gp130+ cases among all samples, and among the two subtypes, in E. Scale bar, 100 μm.",
    "diseases": "DLBCL"
  },
  {
    "caption": "A IL-6 secretion of the indicated cell lines (ABC-DLBCL in red, GCB-DLBCL in green) and primary patient material, as quantified by ELISA and normalized to cell number (shown per 1000 cells). n.d., not detectable.",
    "diseases": "DLBCL"
  },
  {
    "caption": "STAT3 phosphorylation as assessed by Western blotting (B, D) of the indicated ABC-DLBCL and GCB-DLBCL cell lines, with and without 1h of exposure to 50ng/ml hIL-6 (B,D). STAT3 expression levels are shown as Western blot control.",
    "diseases": "DLBCL"
  },
  {
    "caption": "STAT3 phosphorylation as assessed by flow cytometry (C) of the indicated ABC-DLBCL and GCB-DLBCL cell lines, Histograms in C represent STAT3 phosphorylation in the absence of exogenously added IL-6.",
    "diseases": "DLBCL"
  },
  {
    "caption": "lymphoma burden as determined by lymph node weight (B), of cohorts of 9-12 mice each (n indicated in figure) of the indicated genotypes.",
    "diseases": "lymphoma"
  },
  {
    "caption": "Frequency of STAT3 phosphorylation (A), of DLBCL patients stratified according to subtype and disease stage Phospho-STAT3 positivity was defined as expression in ≥17% of tumor cells and more common found in ABC-DLBCL tumors, and in more advanced (stage 3 and 4, relative to stage 1 and 2) disease (A).",
    "diseases": "DLBCL"
  },
  {
    "caption": "overall as well as disease-specific survival probability (B) of DLBCL patients pSTAT3 positivity was a strong negative prognostic factor in the entire cohort (B)",
    "diseases": "DLBCL"
  },
  {
    "caption": "overall mortality of DLBCL patients stratified according to subtype and disease stage pSTAT3 positivity was associated with higher overall- as well as disease-specific mortality in both ABC- and GCB-DLBCL subtypes",
    "diseases": "DLBCL"
  },
  {
    "caption": "disease-specific mortality of DLBCL patients stratified according to subtype and disease stage pSTAT3 positivity was associated with higher overall- as well as disease-specific mortality in both ABC- and GCB-DLBCL subtypes",
    "diseases": "DLBCL"
  },
  {
    "caption": "Effect of IL-6R neutralization by twice-weekly injection of 250 μg/dose of tocilizumab or an isotype control antibody, starting two weeks post tumor cell injection, on (E and F) the spleen weights of MISTRG6 mice transplanted with 1x106 primary DLBCL cells (expanded by one serial passage through MISTRG6 mice),",
    "diseases": "DLBCL"
  },
  {
    "caption": "Effect of IL-6R neutralization by twice-weekly injection of 250 μg/dose of tocilizumab or an isotype control antibody, starting two weeks post tumor cell injection on the bone marrow lymphoma burden of OCI-Ly3-transplanted MISTRG mice (G) assessed at around four weeks post tumor cell injection.",
    "diseases": "lymphoma"
  },
  {
    "caption": "Effect of IL-6R neutralization by twice-weekly injection of 250 μg/dose of tocilizumab or an isotype control antibody, starting two weeks post tumor cell injection on the splenic lymphoma burden of RC-K8-transplanted MISTRG6 mice (H), all assessed at around four weeks post tumor cell injection.",
    "diseases": "lymphoma"
  },
  {
    "caption": "(F) Quantification of UBTD1 mRNA levels in prostate tumor (n=70) and adjacent normal tissues (n=47).",
    "diseases": "prostate tumor"
  },
  {
    "caption": "(G) Representative UBTD1 immunohistochemistry staining on sections of human prostate tumor and normal tissues (n=8).",
    "diseases": "prostate tumor"
  },
  {
    "caption": "(H) Representative UBTD1 immunohistochemistry staining on sections of human lung tumor and normal tissues (n=6).",
    "diseases": "lung tumor"
  },
  {
    "caption": "(I) The levels of UBTD1 mRNA in grade 3 prostate adenocarcinoma patients (56 patients) are correlated with overall survival (OS). OS was calculated from patient subgroups with mRNA levels that were less or greater than the first quartile value.",
    "diseases": "prostate adenocarcinoma"
  },
  {
    "caption": "(J) The levels of UBTD1 mRNA in lung adenocarcinoma patients (522 patients) are correlated with OS.",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "G Graph presents the survival rate of glioblastoma patients from A that present PRKDClow/MB21D1low, PRKDChigh/MB21D1low and PRKDChigh/MB21D1high expression.",
    "diseases": "glioblastoma"
  },
  {
    "caption": "A. Survival of patients with colorectal cancer from Kaplan-Meier database was analyzed Left panel of A were representative of 150 technical replicates, and right panel of A were representative of 499 technical replicates.",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "representative histology  images in human colorectal cancer specimens (1#-5#) and human colon  polyp specimens (6#-7#) were shown. Number of cells expressed BTNL2  or IL-22 was analysed in high power field (HPF), arrows indicate cells expressed BTNL2  or IL-22 (B).",
    "diseases": "colon  polyp, colorectal cancer"
  },
  {
    "caption": "B Serum levels of placensin and glucagon at different weeks of pregnancy measured using specific ELISA in normal and GDM patients. Numbers in parentheses represent number of patients.",
    "diseases": "GDM"
  },
  {
    "caption": "Confirmation of high expression of Twist1 and DDX3 in the lung tumors of the transgenic Twist1/KrasG12D mouse. Scale bar is 100 μm.",
    "diseases": "tumors"
  },
  {
    "caption": "(B) Quantitative analysis of cardiac fibrosis. Quantification was made as percentage of fibrosis area (in blue) in the left ventricle. Number of mice, (Control, S311A), 3m (7, 6), 1y (5, 6). *, P<0.05 versus Control.",
    "diseases": "fibrosis"
  },
  {
    "caption": "Scatter plot and correlation coefficient (r) of ASK1 mRNA expression and BMI Data were collected in lean subjects (n=14), obese subjects (n=23) and obese subjects with type 2 diabetes (n=19). Values are expressed as mean ± SEM (D).",
    "diseases": "type 2 diabetes"
  },
  {
    "caption": "Scatter plot and correlation coefficient (r) of ASK1 mRNA expression , plasma alanine aminotransferase (ALAT) (B) Data were collected in lean subjects (n=14), obese subjects (n=23) and obese subjects with type 2 diabetes (n=19). Values are expressed as mean ± SEM (D).",
    "diseases": "type 2 diabetes"
  },
  {
    "caption": "Scatter plot and correlation coefficient (r) of ASK1 mRNA expression and liver fat content (C). Data were collected in lean subjects (n=14), obese subjects (n=23) and obese subjects with type 2 diabetes (n=19). Values are expressed as mean ± SEM (D).",
    "diseases": "type 2 diabetes"
  },
  {
    "caption": "ASK1 mRNA expression in patients with different NASH scores Data were collected in lean subjects (n=14), obese subjects (n=23) and obese subjects with type 2 diabetes (n=19). Values are expressed as mean ± SEM (D). ***",
    "diseases": "NASH, type 2 diabetes"
  },
  {
    "caption": "Scatter plot and correlation coefficient (r) of ASK1 mRNA expression and ATG5 (E) mRNA expression. Data were collected in lean subjects (n=14), obese subjects (n=23) and obese subjects with type 2 diabetes (n=19). Values are expressed as mean ± SEM (D). ***",
    "diseases": "type 2 diabetes"
  },
  {
    "caption": "Scatter plot and correlation coefficient (r) of ASK1 mRNA expression and ATG7 Data were collected in lean subjects (n=14), obese subjects (n=23) and obese subjects with type 2 diabetes (n=19). Values are expressed as mean ± SEM (D).",
    "diseases": "type 2 diabetes"
  },
  {
    "caption": "Scatter plot and correlation coefficient (r) of ASK1 mRNA expression and ATG12 mRNA expression. Data were collected in lean subjects (n=14), obese subjects (n=23) and obese subjects with type 2 diabetes (n=19). Values are expressed as mean ± SEM (D). ***",
    "diseases": "type 2 diabetes"
  },
  {
    "caption": "(G) Top: expression of CTH in prostate tumors by immunocytochemistry analysis of commercial tissue arrays. Samples were sub-grouped by TNM stages. The representative images from different stages are shown. S: Stroma; Scale bars: 250μm. Bottom: The statistical significance was determined using the χ2 test",
    "diseases": "prostate tumors"
  },
  {
    "caption": "The RNA-seq data of CTH was downloaded from the TCGA database (H) The mRNA expression of CTH in PC specimens and normal tissues. Data are presented as means ± SD (n=50 cases for adjancent non-tumor parts and 469 cases for PC tumors). Student's t-test was used for the statistical analysis (**P<0.01).",
    "diseases": "PC"
  },
  {
    "caption": "(I) Kaplan-Meier survival analysis of PC patients with high or low CTH expression. The statistical significance was determined using the χ2 test.",
    "diseases": "PC"
  },
  {
    "caption": "(F) Real-Time RT-PCR analysis for CTH mRNA levels in PC3 orthotopic tumors from shCon or shCTH group. Data shown represent normalized means ± SEM (n=10 mice per group). Data information: Student's t-test was used for the statistical analysis (*P<0.05).",
    "diseases": "tumors"
  },
  {
    "caption": "Immunohistochemical analysis of paraffin-embedded xenograft prostate tumor using CD31 (G) antibody. The total vessels number per mm2 was quantified. Scale bars: 0.1 mm. Data are presented as means ± SEM (n=4-5 mice per group). Data information: Student's t-test was used for the statistical analysis (*P<0.05).",
    "diseases": "prostate tumor"
  },
  {
    "caption": "Immunohistochemical analysis of paraffin-embedded xenograft prostate tumor using LYVE-1 (H) antibody. The total vessels number per mm2 was quantified. Scale bars: 0.1 mm. Data are presented as means ± SEM (n=4-5 mice per group). Data information: Student's t-test was used for the statistical analysis (*P<0.05).",
    "diseases": "prostate tumor"
  },
  {
    "caption": "(A-B) Hemoglobin  (A) and hematocrit  (B) levels of healthy subjects and cachectic cancer patients  presenting a body weight loss superior to 10% of initial body weight (19 healthy subjects, 17  cachectic patients). Data information: For all data, n represents the number of biological replicates. Statistical significance was calculated by unpaired, two-tailed Student's T-test. Data are mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.",
    "diseases": "cachectic, cachectic cancer"
  },
  {
    "caption": "(C) TFR1 mRNA levels in  muscle biopsies from cancer-patients of late stage  cachexia (19 healthy subjects, 17  cachectic patients with at least 10% total body weight loss) Data information: For all data, n represents the number of biological replicates. Statistical significance was calculated by unpaired, two-tailed Student's T-test. Data are mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.",
    "diseases": "cachectic, cachexia"
  },
  {
    "caption": "(A) Brigthfield images of human patient derived organoids (PDOs) from gastric cancer with and without RTK/MAPK alterations (scale bar 100µm, zoom in 40µm).",
    "diseases": "gastric cancer"
  },
  {
    "caption": "(A)  Confocal  observation of  mitochondrial potential after TMRM staining of LMP1-negative or -positive   NPC   cells. Red fluorescence, which indicates normal mitochondrial potential, was converted into green fluorescence after a reduction in mitochondrial  potential. Images were analyzed using Image J software (scale bar, 10 μm). Data are presented as means ± S.E.M. (paired t-test, n = 6, biological replicates per group, * p < 0.05, ** p < 0.01).",
    "diseases": "NPC"
  },
  {
    "caption": "(C) Extent of  Ca2+-mediated  mitochondrial swelling in NPC cells. Data are presented as means ± S.E.M. (paired t-test, n = 6, biological replicates per group, ** p < 0.01).",
    "diseases": "NPC"
  },
  {
    "caption": "(A-B) The ADP/ATP exchange rate in EBV-LMP1-positive nasopharyngeal carcinoma cells is decreased. The fluorescence value of Magnesium Green ™ (1 μM) was measured at 505 nm (Ex)/535 nm (Em) by enzymography (A), and the  ADP/ATP  exchange rate was calculated after conversion to ATP (B). Data are presented as means ± S.E.M. (paired t-test, n = 5, biological replicates per group, ** p < 0.01).",
    "diseases": "nasopharyngeal carcinoma"
  },
  {
    "caption": "(C) LMP1-negative or -positive  NPC cells were treated with BKA (1 μM) or CATR (5 μM) for 24 h, Mitochondrial OCR assessed with the XF24 extracellular flux analyzer (Seahorse) under sequential treatment with oligomycin, FCCP, and antimycin A. Data are presented as means ± S.E.M. (n = 6, biological replicates per group). (D) Oxidative phosphorylation-related metrics based on OCR datas. Data are presented as means ± S.E.M. (paired t-test, n = 6, biological replicates per group, * p < 0.05,** p < 0.01). ",
    "diseases": "NPC"
  },
  {
    "caption": "(G) Flow cytometry  analysis of death of  NPC cells treated for 24 h with  CATR (1 μM) alone, cisplatin  (20 μM) alone, or cisplatin  (20 μM) combined with CATR  (1 μM). Data are presented as means ± S.E.M. (paired t-test, n = 5, biological replicates per group, * p < 0.05, ** p < 0.01).",
    "diseases": "NPC"
  },
  {
    "caption": "(H)  Trypan blue staining  was used to detect death of  NPC cells treated for 24 h with vehicle, cisplatin, CATR, or a combination of cisplatin and CATR (1 μM). Data are presented as means ± S.E.M. (paired t-test, n = 6, biological replicates per group, ** p < 0.01).",
    "diseases": "NPC"
  },
  {
    "caption": "(A) Western blot analysis of PARP1 in chromatin. Two Ewing Sarcoma cells (CHP100 and A4573) were treated with MMS (0.02%, 1 hour) with or without release (1 hour) from MMS (N.T: non treat, T: treat, R: release sample).",
    "diseases": "Ewing Sarcoma"
  },
  {
    "caption": "(B) U2OS and two Ewing Sarcoma cells were treated MMS (0.02%, 30 minutes) and subjected to immunofluorescence by PARP1 antibody after chromatin bound fraction. Scale bar indicates 20 μm (left). Red line indicates mean and more than 300 cells were analyzed. Significance determined by Two-way ANOVA, ***P < 0.001.",
    "diseases": "Ewing Sarcoma"
  },
  {
    "caption": "(C) Human Ewing Sarcoma histology samples were analyzed by immuno-histochemistry using PAR antibody. Scale bar represents 100 mm.",
    "diseases": "Ewing Sarcoma"
  },
  {
    "caption": "In vitro niche dependency of HGSOC tumor cells. Phase-contrast pictures illustrate that isolated ovarian cancer cells rely on EGF supplementation for growth, while they do not grow at all in Wnt3a supplemented medium. Also, inhibition of BMP signaling through Noggin has strong negative effect on the initial growth. Scale bar: 500 µm. E - EGF, F - FGF10, N -Noggin, R - R-spondin1, B - Basic medium, P - Passage",
    "diseases": "HGSOC, ovarian cancer"
  },
  {
    "caption": "Cancer organoids express HGSOC markers Pax8 and EpCAM and have lost the cystic phenotype suggesting complete breakdown of epithelial polarity as seen on confocal images from two representative organoid lines. Scale bar: 20 µm.",
    "diseases": "HGSOC, Cancer"
  },
  {
    "caption": "HGSOC organoids show differential response to carboplatin treatment, confirming patient-specific sensitivity of the cultures. Cell viability assay was performed after 5 days of treatment with different concentrations of carboplatin on mature organoids from three different donors. Data represent mean ±SD of technical triplicates.",
    "diseases": "HGSOC"
  },
  {
    "caption": "Overview of mutations found in organoid cultures and matching tumor tissue obtained by targeted sequencing of 121 HGSOC related genes confirms almost identical profile between parental tissue and in vitro long-term organoid culture. Color code indicates type of mutations which were detected.",
    "diseases": "HGSOC"
  },
  {
    "caption": "Strong nuclear p53 signal in immunostainings of HGSOC organoids is indicative of a gain-of-function TP53 mutation. Scale bars: 100 µm (Tissue) and 50 µm (Organoid).",
    "diseases": "HGSOC"
  },
  {
    "caption": "Box plots depicting overall constant level in normalized expression of major HGSOC marker genes between organoids and parental tissue. Data represent the median, quartiles, maximum, and minimum of the normalized expression from 8 different donors.",
    "diseases": "HGSOC"
  },
  {
    "caption": "Heat map of differentially expressed genes between cancer and healthy tissue/organoids reveals upregulation of several HGSOC biomarkers and reduction of FT differentiation markers in the cancer samples. Differential expression determined by single-color microarray for 8 different patient samples was significant for all genes with p < 0.05 except for OVGP1 and TOP2A in organoids.",
    "diseases": "HGSOC, cancer"
  },
  {
    "caption": "Triple KD (p53/PTEN/RB) organoids are characterized by a HGSOC gene expression signature as revealed by microarray analysis comparing WT and KD organoids grown in either OCM or FTM. Differential expression determined by dual-color microarray for 2 biological replicates was significant for all genes with p < 0.00005.",
    "diseases": "HGSOC"
  },
  {
    "caption": "Phase-contrast images of cancer organoids which entered growth arrest upon treatment with Wnt agonists (Wnt3a/RSPO1) over 2 passages (Scale bar: 500µm). Differences in cell number were confirmed by the respective cell viability assays (performed in technical triplicates). Data represent the mean ±SEM for 5 different OC organoid lines (n=5). *** p < 0.001, two-sided Student`s t-test.",
    "diseases": "cancer, OC"
  },
  {
    "caption": "Addition of conditioned medium collected from the parental Wnt3a cell line did not suppress growth of cancer organoids, proving that the growth inhibitory effect is due to the presence of Wnt agonists. The bar plot represents the mean ±SEM of triplicates performed with a luminescent cell viability assay. * p < 0.05, *** p < 0.001, two-sided Student`s t-test.",
    "diseases": "cancer"
  },
  {
    "caption": "Comparative analysis of microarray data revealed consistent up-regulation of MYCN, the canonical Wnt inhibitors KREMEN2 and DKK3 as well as differentiation marker FOXJ1, AR and PGR in HGSOC cancer organoids as well as triple KD FT organoids. Differential expression was determined either by single-color microarray for the cancer samples (8 replicates) or dual-color microarray for the knockdowns (2 replicates) and is significant for all genes with p < 0.05.",
    "diseases": "HGSOC, cancer"
  },
  {
    "caption": "Transcriptional induction of MYCN is confirmed by qPCR for three patients between cancer organoids and normal FT organoids as well as triple KD organoids grown in OCM vs. FTM conditions. Depicted is the mean ±SEM of the normalized MYCN mRNA expression level of three biological replicates (n=3). ** p < 0.01, *** p < 0.001, two-sided Student`s t-test.",
    "diseases": "cancer"
  },
  {
    "caption": "FOXJ1 expression was upregulated in HGSOC organoids in FTM compared to OCM as shown by qPCR analysis of 3 different patient samples. Data represent the mean ±SEM of technical triplicates.",
    "diseases": "HGSOC"
  },
  {
    "caption": "G. Escape latency during water maze training indicated severe learning impairment in Setd1b cKO mice (Control: n = 15, cKO: n = 15. Repeated measures ANOVA, genotype effect: F (1,28) = 82.34, **** p-value < 0.0001).",
    "diseases": "learning impairment"
  },
  {
    "caption": "H. Plots showing the specific search strategies during water maze training. Note the failure of Setd1b cKO mice to adopt hippocampus-dependent search strategies. I. The cognitive score calculated on the basis of the hippocampal search strategies reflects severe memory impairment in Setd1b cKO mice (Student t-test: *** p-value < 0.001).",
    "diseases": "memory impairment"
  },
  {
    "caption": "Boxplots showing differences of the APTT time (left) and ME1-enriched protein expressions (right) between mild (n=13) and severe (n=18) COVID-19 patients. Differences between groups were estimated using Mann-Whitney-Wilcoxon test. * p <0.05, ** p <0.01, *** p <0.001. The horizontal box lines in the boxplots represent the first quartile, the median, and the third quartile. Whiskers denote the range of points within the first quartile − 1.5× the interquartile range and the third quartile + 1.5× the interquartile range.",
    "diseases": "COVID-19"
  },
  {
    "caption": "Boxplots showing differences of IL-6 level, IL-10 level (left) and ME15-enriched protein expressions (right) between mild (n=13) and severe (n=18) COVID-19 patients. Differences between groups were estimated using Mann-Whitney-Wilcoxon test. * p <0.05, ** p <0.01, *** p <0.001. The horizontal box lines in the boxplots represent the first quartile, the median, and the third quartile. Whiskers denote the range of points within the first quartile − 1.5× the interquartile range and the third quartile + 1.5× the interquartile range.",
    "diseases": "COVID-19"
  },
  {
    "caption": "Boxplot showing the selected cell type specific proteins among control (n=12), mild (n=13) and severe (n=18) COVID-19 patients. Differences between groups were estimated using Kruskal-Wallis test. The horizontal box lines in the boxplots represent the first quartile, the median, and the third quartile. Whiskers denote the range of points within the first quartile − 1.5× the interquartile range and the third quartile + 1.5× the interquartile range.",
    "diseases": "COVID-19"
  },
  {
    "caption": "Heatmap of IFNG, GZMB and PRF1 gene expression in COVID-19 patients. Average expression values were centered and scaled. Red indicates a higher expression and blue indicates a lower expression.",
    "diseases": "COVID-19"
  },
  {
    "caption": "Heatmap of the expression of genes enriched in IL-17 signaling pathway between healthy control and COVID-19 patients. Average expression values were centered and scaled. Red indicates a higher expression and blue indicates a lower expression.",
    "diseases": "COVID-19"
  },
  {
    "caption": "COVID-19 severity is associated with significant changes in lipoprotein subclasses including high-density lipoprotein subclass-1 (HDL1), HDL4, low-density lipoprotein subclasses (LDL1, LDL4, LDL5), very low-density lipoprotein subclass-5 (VLDL5) and their compositional components (ApoA1, triglycerides, cholesterol). TG: triglycerides; FC: free cholesterol; CE: cholesteryl esters; CH: total cholesterol (i.e., FC + CE); PL: total phospholipids; A1: ApoA1; A2: ApoA2; L1TG: TG in LDL1; L1TG%: percentages of L1TG in total lipids of LDL1; L1%: percentage of LDL1 in all LDL; L-TG%: percentages of L-TG(TG in LDL) in total lipids of LDL; V5FC%, V5CE%: percentages of V5FC(FC in VLDL5) and V5CE(CE in VLDL5) in total lipids of VLDL5; L5CE%, L5CH%: percentages of L5CE(CE in LDL5) and L5CH(CH in LDL5) in total lipids of LDL5; H1FC%: percentages of H1FC (FC in HDL1) in total lipids of HDL1; H-A2: ApoA2 in both HDL and nascent HDL; H4A1, H4A2, H4CE, H4CH, H4FC, H4PL: ApoA1, ApoA2, CE, CH, FC and PL in HDL4;",
    "diseases": "COVID-19"
  },
  {
    "caption": "Plasma levels of key enzymes and proteins directly involving lipoprotein metabolism are indicators for COVID-19 severity. Data were represented as means ± SD and differences between groups were estimated using a Student's t test. * p < 0.05; ** p < 0.01; *** p < 0.001. Control, n=12; mild, n=29; severe, n=17; discharge, n=16; sLDLR: soluble low-density lipoprotein receptor; LCAT: lecithin-cholesterol acyltransferase; CEPT: cholesteryl-ester transfer protein.",
    "diseases": "COVID-19"
  },
  {
    "caption": "U87 GBM cells were treated with 20 µM LXR623 or 50 µM Simvastatin (Sim) for 48h. Thereafter, lysates were collected and analyzed for total cholesterol levels. Shown are means and SD (n = 3).",
    "diseases": "GBM"
  },
  {
    "caption": "GBM12 GBM cells (short term patient-derived xenograft), U87 GBM cells, HCT116 colonic carcinoma cells and A375 melanoma cells were treated with the indicated concentrations of ABT263, LXR623 or the combination for 72h. Thereafter, cellular viability was analyzed and statistical analysis was performed.",
    "diseases": "colonic carcinoma, GBM, melanoma"
  },
  {
    "caption": "U87, T98G and LN229 cells were treated with 1 µM ABT263, 20 µM LXR623 or the combination of both for 72h. Mewo melanoma and HCT116 colon carcinoma cells were treated with 1 µM ABT263, 10 µM LXR623 or the combination of both for 72h (MeWo) or for 48h (HCT116). Thereafter, cells were stained with annexin V/propidium iodide and analyzed by multi-parametric flow cytometry.",
    "diseases": "colon carcinoma, melanoma"
  },
  {
    "caption": ", Stem-like GBM cells, NCH644, NCH421k and NCH690 were treated with 1 µM ABT263, 20 µM LXR623 or the combination of both for 48h. Thereafter, cells were stained with annexin V/propidium iodide and analyzed by multi-parametric flow cytometry.",
    "diseases": "GBM"
  },
  {
    "caption": "HCT116 colonic carcinoma cells were treated with ABT263, LXR623 or the combination of both. Whole protein lysates were collected and subjected to capillary electrophoresis for the expression/cleavage of PARP, total caspase-9 (CP9) and Vinculin. CF: cleaved fragment, FL: full length.",
    "diseases": "colonic carcinoma"
  },
  {
    "caption": "HCT116 colonic carcinoma or NCH644 glioblastoma stem cells were treated with selective BH3-mimetics, WEHI-539 (Bcl-xL inhibitor), ABT199 (Bcl-2 inhibitor) or A1210477 (Mcl-1 inhibitor) in the presence or absence of LXR623 for 48h. Thereafter, cells were labeled with annexin V/propidium iodide and analyzed by multi-parametric flow cytometry.",
    "diseases": "colonic carcinoma, glioblastoma"
  },
  {
    "caption": "LN229 GBM cells were treated with 10 µM LXR623 (LXR), 1 µM ABT263 or the combination for 48h. Thereafter, protein lysates were prepared and immunoprecipitated with an antibody against BAK. Standard western blotting was performed (immunoprecipitation and the corresponding inputs) with antibody against BAK and Mcl-1. The arrows highlight the specific protein bands, while stars indicate the immunoglobulin light-chains.",
    "diseases": "GBM"
  },
  {
    "caption": "1x106 HCT116 colon carcinoma cells were implanted subcutaneously. Animals were treated intraperitoneally with vehicle, LXR623 (100-200 mg/kg), ABT263 (100 mg/kg) or both agents (3 days per week for 1.5 weeks. Tumor growth curves show the development of tumor size for each treatment group. Scatter plots display the quantitative representation of the tumor size among the different treatments toward the end of the experiment. Shown are means and SD (n ≥ 5). *p=0.022, **p=0.0063, ****p<0.0001. Statistical significance was determined by one-way ANOVA. B, E, GBM43 PDXs were implanted subcutaneously. Animals were treated intraperitoneally with vehicle, LXR623 (100 mg/kg), ABT263 (75 mg/kg) or both agents (3 days per week for 1.5 weeks). Tumor growth curves show the development of tumor size for each treatment group. Scatter plots display the quantitative representation of the tumor size among the different treatments toward the end of the experiment. Shown are means and SD (n ≥ 5). *p=0.022, **p=0.0031. Statistical significance was determined by one-way ANOVA. C, F, A375 BRAF V600E mutated melanomas were implanted subcutaneously. Animals were treated intraperitoneally with vehicle, LXR623 (100 mg/kg), ABT263 (75 mg/kg) or both agents (3 days per week for 1.5 weeks). Tumor growth curves show the development of tumor size for each treatment group. Scatter plots display the quantitative representation of the tumor size among the different treatments toward the end of the experiment. Shown are means and SD (n ≥ 5). *p=0.0109 (GW3965 vs Combination), *p=0.0166 (ABT263 vs Combination), **p=0.0047. Statistical significance was determined by one-way ANOVA. ",
    "diseases": "colon carcinoma"
  },
  {
    "caption": "(A) Left, western blotting  of PDI  protein in replicative senescent hMSCs  at early-passage (EP) and late-passage (LP). GAPDH  was used as the loading control. Right, statistical analysis of relative PDI protein expression levels. n = 3 independent experiments. (B) Left, western blotting of PDI  protein in wild-type (WT) and Werner syndrome (WS) hMSCs. GAPDH  was used as the loading control. Right, statistical analysis of relative PDI protein expression  levels. n = 3 independent experiments. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "diseases": "Werner syndrome, WS"
  },
  {
    "caption": "(A) Western blotting of PDI expression  in replicative senescent (RS) hMSCs, Hutchinson-Gilford Progeria Syndrome (HGPS) hMSCs, WS hMSCs  and human  primary hMSCs  from an old individual transduced with sgNTC or PDI-targeting sgRNA. GAPDH  was used as the loading control.",
    "diseases": "HGPS, Hutchinson-Gilford Progeria Syndrome, WS"
  },
  {
    "caption": "(B) Single clonal formation assay  in RS hMSCs, HGPS hMSCs, WS hMSCs  and human  primary hMSCs  from an old individual transduced with sgNTC or PDI-targeting sgRNA. n = 3 biological repeats. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "diseases": "HGPS, WS"
  },
  {
    "caption": "(C) SA-β-gal staining  in RS hMSCs, HGPS hMSCs, WS hMSCs  and human  primary hMSCs  from an old individual transduced with sgNTC or PDI-targeting sgRNA. n = 3 biological repeats. Scale bar, 200 µm. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "diseases": "HGPS, WS"
  },
  {
    "caption": "J Representative IHC images, and statistical analysis of immunoreactive score (IRS) of METTL14 expression in p53-WT (n = 63) and p53-MT (n = 41) CRC samples. The horizontal lines represent the median; the bottom and top of the boxes represent the 25% and 75% percentiles, respectively; and the vertical bars represent the range of the data. The insets show enlarged images of indicated p53-WT and p53-MT CRC tissues, respectively. Scale bars = 20 μm and 2 μm (inset).",
    "diseases": "CRC"
  },
  {
    "caption": "G Comparison of colorectum length between METTL14WT (n = 14, n = 24) and METTL14ΔIEC (n = 13, n = 21) mice from AOM/DSS-induced and AOM-induced CRC models, respectively. Data are expressed as mean ± SD.",
    "diseases": "CRC"
  },
  {
    "caption": "I Representative HE staining images of colorectum in METTL14WT (n = 14, n = 24) and METTL14ΔIEC (n = 13, n = 21) mice from AOM/DSS-induced and AOM-induced CRC models. Lower panels show enlarged images of indicated normal or CRC tissues. Scale bars = 2 mm (upper) and 40 μm (lower). Black dashed line refers to the border of tumor (T) and normal (N) tissues. Tumors are classified as adenomas with low to focal high-grade dysplasia. The percentages of mice with dysplasia are shown (right).",
    "diseases": "CRC, adenomas, dysplasia"
  },
  {
    "caption": "I Representative IHC staining images and quantitative analysis of SLC2A3 and PGAM1 in tumor tissues and non-tumor tissues from AOM/DSS-induced Mettl14ΔIEC and Mettl14WT mice CRC models. The insets show enlarged images of tumor tissues and non-tumor tissues, respectively. Scale bars = 40 μm and 4 μm (inset). Data are presented as mean ± SD (biological replicates, n = 6; **P < 0.01, ***P < 0.001).",
    "diseases": "CRC"
  },
  {
    "caption": "A Representative IHC and ISH staining images and corresponding quantitative analysis of miR-6769b-3p/SLC2A3 IRS and miR-499a-3p/PGAM1 IRS in p53-WT (n = 63) and p53-MT (n = 41) samples from Cohort 3. The insets show enlarged images of indicated p53-WT and p53-MT CRC tissues, respectively. Scale bars = 200 μm and 20 μm (inset). The horizontal lines represent the median; the bottom and top of the boxes represent the 25% and 75% percentiles, respectively; and the vertical bars represent the range of the data.",
    "diseases": "CRC"
  },
  {
    "caption": "B Representative IHC and ISH images of METTL14, SLC2A3, PGAM1, miR-6769b-3p and miR-499a-3p in CRC tissues with higher or lower METTL14 expression in p53-WT (n = 63) samples from Cohort 3. Right panels show enlarged images of indicated p53-WT CRC tissues. Scale bars = 200 μm (left) and 20 μm (right).",
    "diseases": "CRC"
  },
  {
    "caption": "F Kaplan-Meier survival curves of OS in CRC patients with wild type p53 (n = 63) and mutant p53 (n = 41) from Cohort 3 database based on expression levels of METTL14.",
    "diseases": "CRC"
  },
  {
    "caption": "C  Immunofluorescent  analyses of USP33 (red), the  hypoxia marker  CA9  (green), and the  stem cell  marker SOX2  (gray) in  human  primary GBMs. Arrows indicate the  USP33+/CA9+/SOX2+ cells. Scale bar, 80 µm.",
    "diseases": "GBMs"
  },
  {
    "caption": "A, Representative images of immunofluorescent analyses of USP33 (red) and HIF2α (green) in  human primary GBMs. Frozen sections of human GBMs were immunostained with antibodies against USP33 and HIF2α, and counterstained with DAPI to show nuclei (blue). Scale bar, 40 μm. (n = 5 sections; mean ± s.e.m.).",
    "diseases": "GBMs"
  },
  {
    "caption": "B Kaplan-Meier survival curves of mice bearing GBMs  derived from T387 GSCs  expressing shUSP33 or shNT from (A). Disruption of USP33  extended the survival  of mice bearing GSC-derived GBM tumors. (n= 5  mice for each group; shUSP33#42 vs shNT, p = 0.0185; shUSP33#45 vs shNT, p = 0.0027; two-tailed log-rank test).",
    "diseases": "GBM, GBMs"
  },
  {
    "caption": "E, F  Immunofluorescent  analysis (E) and statistical quantifications (F) of the cell proliferation marker Ki67  in xenografts  derived from T387 GSCs expressing shUSP33 or shNT. Disruption of USP33 in  GSCs reduced cell proliferation  in GBM xenografts. Scale bar, 80 μm. (n = 5 tumors for each group; ***, p < 0.001; mean ± s.e.m.; two tailed unpaired t-test).",
    "diseases": "GBM"
  },
  {
    "caption": "Kaplan-Meier curves for the overall survival of breast cancer patients based on BRCC3 (A), XIST (B), and BRCC3/XIST(C) expression levels. HR: hazard ratio.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(K) Ashcroft score quantitation of fibrosis (n=5).",
    "diseases": "fibrosis"
  },
  {
    "caption": "(E) Immunohistochemical analysis of SIRT2 protein in representative colorectal tissue specimens is shown (magnification ×100). Weak cytoplasmic staining for SIRT2 was observed in CRC tissues and metastatic tissues, whereas strong cytoplasmic staining was observed in noncancerous tissues.",
    "diseases": "CRC, metastatic"
  },
  {
    "caption": "(A) Expression levels of IDH1 K224Ac in human CRC (n=90) and CRN (n=90) tissue specimens, assessed by immunohistochemistry. CRC, colorectal carcinoma samples; CRN, matched adjacent non-cancerous colorectal tissue specimens.",
    "diseases": "CRC, colorectal carcinoma"
  },
  {
    "caption": "(B) Kaplan-Meier survival curves of CRC cases with elevated (n=49) and reduced (n=41) IDH1 K224Ac. CRC, colorectal carcinoma samples. The overall survival was analyzed by the log-rank test using the Kaplan-Meier method.",
    "diseases": "CRC, colorectal carcinoma"
  },
  {
    "caption": "(I) Survival  of control and Ntras-silenced mice under basal conditions (black, n = 21-23 mice  per group) and in hind limb ischemia (HLI; red, n = 8 mice  per group). Number of survivors is indicated; experimental outline on the left. Data information: (I) Mantel-Cox-test.",
    "diseases": "hind limb ischemia, HLI"
  },
  {
    "caption": "(G) Sera  from wild-type (WT) BKS and Leprdb/db mice, aged 4, 8, and 18 weeks, B6 mice, fed with a normal diet (ND) and a high fat diet  (HFD) for 4 weeks, and humans, healthy volunteers and diabetic patients (T2D), were quantified for Pdia4  level using an anti-Pdia4 ELISA kit. Data information: Data from 3 experiments more are presented as the mean ± SD. One-way ANOVA test was used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant.",
    "diseases": "diabetic, T2D"
  },
  {
    "caption": "D. Western blot analysis of total membrane, aqueous and lipid (GPI-anchor-containing) Triton X-114 extracts derived from wild type HeLa cells and two independent CRISPR CWH43 knockout (KO) HeLa cell lines in which a mutated CWH43 gene encodes a protein that is truncated near Leu533 and CWH43 mRNA and protein are markedly reduced. Cells were transfected to overexpress a control GFP plasmid, a plasmid encoding human wild type Cwh43 with GFP fused to the N-terminus, or a plasmid encoding human CWH43 harboring the iNPH-associated mutation (Lys696AsnfsTer23) with GFP fused to the N-terminus. The Western blot was stained using an antibody directed against CD59, a GPI-anchored protein.",
    "diseases": "iNPH"
  },
  {
    "caption": "(G) Viability of six PTEN-null VS five PTEN-WT TNBC cell lines - not carrying other known mutations in PIK3CA, PIK3CB or PIK3R1 genes - treated with PI3Kβi (AZD8186 90 nM), EGFRi (gefitinib 3 μM) alone or in combination for 6 days. Mean of 3 independent experiments ± SD. Statistical significance of two-tailed unpaired student t-test in PTEN-null PI3Kbi versus PI3Kbi+EGFRi **P=0.0059, PTEN-null EGFRi versus PI3Kbi+EGFRi **P=0.0047, PTEN-null PI3Kbi+EGFRi versus PTEN-WT PI3Kbi+EGFRi *P=0.0459, PTEN-WT PI3Kbi versus PI3Kbi+EGFRi *P=0.0108, PTEN-WT EGFRi versus PI3Kbi+EGFRi n.s. P=0.1926. PTEN-null cell lines used in the experiments were: MDA-MB-468, HCC70, HCC1937, HCC38, HCC1395 and BT-549; PTEN-WT cell lines were: MDA-MB-157, MDA-MB-231, HCC1187, HCC1428 and HCC1806.",
    "diseases": "TNBC"
  },
  {
    "caption": "(H) Synergy score for combinations of serial dilutions of PI3Kβi (AZD8186) plus EGFRi (gefitinib) tested on six PTEN-null and five PTEN-WT TNBC cell lines for 6 days in three independent experiments. The score was obtained analysing the viability data through the software Chalice Analyser. Mean of the synergy scores ± SD. Statistical significance of Mann Whitney two-tailed test *P=0.0303.",
    "diseases": "TNBC"
  },
  {
    "caption": "(I) Patient samples from METABRIC dataset classified as TNBCs were assigned to the groups \"PTEN-low\" when falling in the lower quartile for PTEN expression, \"PTEN-mut\" when harbouring a non-synonymous mutation on PTEN gene, \"PTEN-WT\" in all other cases. Comparison of the expression of EGFR between the PTEN low or mut and the PTEN-WT groups. Data presented in a box and whisker plot with the central band indicating the median, the upper and lower extremes of the box or hinge being the third and first quartiles respectively and the whiskers extending to the most extreme data values Mean ± SD. P value calculated by unpaired t-test.",
    "diseases": "TNBCs"
  },
  {
    "caption": "(E) Patient samples from METABRIC dataset classified as TNBCs (N=299) were assigned to the groups \"PTEN-low\" when falling in the lower quartile for PTEN expression, \"PTEN-mut\" when harbouring a non-synonymous mutation on PTEN gene, \"PTEN-WT\" in all other cases. Comparison of the expression of GNB2 between the PTEN low or mut and the PTEN-WT groups. Box & Whisker plot (Median/IQR/1.5*IQR Whiskers). P value calculated by unpaired t-test.",
    "diseases": "TNBCs"
  },
  {
    "caption": "(D) p-S6/loading control signal from western blots experiments in which a panel of six TNBC PTEN-null cell lines and HCC70 cells that acquired resistance to AZD8186 or MK2206 were treated with vehicle, vorapaxar (10 μM), GDC0941 (1 μM) or lapatinib (1 μM) alone or in the indicated combinations. The values were normalised to vehicle treatment for all cell lines. Mean of 2 independent experiments ± SD. P values calculated by two-tailed paired student t-test *P=0.0235 and **P=0.002. Cell lines used in the experiments were: MDA-MB-468, HCC70, HCC1937, HCC38, HCC1395, BT-549, HCC70 AZD8186-resistant and HCC70 MK2206-resistant.",
    "diseases": "TNBC"
  },
  {
    "caption": "(B) Relative expression of the top 20 up-regulated circRNAs from the GEO dataset GSE92675 (BCa tumor tissues compared to para-tumor tissues) in response to AR modulation in J82 and UMUC3 cells. The # indicates an RNA with a relatively low expression (qRT-PCR cycle number > 35), thus the circRNA was excluded for further analysis.",
    "diseases": "BCa"
  },
  {
    "caption": "B) The relative expression of circFNTA was elevated in multiple BCa cell lines (T24, J82, UMUC3, and 5637) compared to normal bladder epithelial cell line SVHUC as shown by qRT-PCR.",
    "diseases": "BCa"
  },
  {
    "caption": "K) FISH analyses revealed that circFNTA was significantly upregulated in BCa tissues as compared with the adjacent para-tumor tissues (N=41 patients) and representative images are shown. Scale bar, 250 μm.",
    "diseases": "BCa"
  },
  {
    "caption": "L) The qRT-PCR assays also demonstrated that circFNTA is significantly elevated in fresh BCa tissues compared to para-tumor tissues (N=23 patients).",
    "diseases": "BCa"
  },
  {
    "caption": "c, Log normalised expression of markers for epithelial (EPCAM), mature luminal epithelial (ESR1), myoepithelial (KRT5, KRT14 and ACTA2) and proliferating cancer cells (MKI67).",
    "diseases": "cancer"
  },
  {
    "caption": "Representative images of st30 medaka embryos injected with hccs-MO (B) alone or co-injected with miR-181a/b-MOs Co-injection of miR-181a/b-MOs rescues microphthalmia and microcephaly in both hccs-MO embryos. hccs-MO/miR-181a/b-MO- b-MO-injected embryos were treated with Baf-A1, PD98059 or HA14-1. Baf-A1 treatment counteracts the protective effect of miR-181a/b downregulation in hccs-MO/miR-181a/b-MO embryos PD98059 treatment does not interfere with the modulation of the MLS phenotype mediated by miR-181a/b downregulation HA14-1 treatment counteracts the effect of miR-181a/b downregulation in the hccs-MO/miR-181a/b-MO model Scale bars are 100μm.",
    "diseases": "microcephaly, microphthalmia, MLS"
  },
  {
    "caption": "Representative images of st30 medaka embryos injected with cox7b-MO (H) alone or co-injected with miR-181a/b-MOs Co-injection of miR-181a/b-MOs rescues microphthalmia and microcephaly in cox7b-MO embryos. cox7b-MO/miR-181a/b-MO-injected embryos were treated with Baf-A1, PD98059 or HA14-1. Baf-A1 treatment counteracts the protective effect of miR-181a/b downregulation in cox7b-MO/miR-181a/b-MO embryos PD98059 treatment does not interfere with the modulation of the MLS phenotype mediated by miR-181a/b downregulation Scale bars are 100μm.",
    "diseases": "microcephaly, microphthalmia, MLS"
  },
  {
    "caption": "Percentage of embryos with or without MLS phenotype in the different conditions in hccs-MO embryos. N≥300 embryos/conditions.",
    "diseases": "MLS"
  },
  {
    "caption": "Percentage of embryos with or without MLS phenotype in the different conditions in cox7b-MO (N) embryos. N≥300 embryos/conditions.",
    "diseases": "MLS"
  },
  {
    "caption": "(A) Graph derived from two published data available in the PubMed GEO database (GSE6919 and GSE35988). The box charts depict the relative expression of ESM1 in benign, primary, and metastatic prostate cancer patients. The centre line donates the median value while the box contains the 25th to 75th percentiles of dataset. The whiskers mark the 5th and 95th percentiles, and values beyond these upper and lower bounds are considered outliers.",
    "diseases": "prostate cancer"
  },
  {
    "caption": "(B) Relative ESM1 mRNA expression and ESM1 protein expression in two sets of human metastatic PCa cell lines. P: parental cells, M: metastatic cells.",
    "diseases": "PCa"
  },
  {
    "caption": "(E) Formalin-fixed, paraffin-embedded tissue microarray sections of 59 normal prostate tissues and 65 prostate adenocarcinoma tissues with and without metastasis (n=16 and n=49, respectively) were stained with an anti-ESM1 antibody. Tissue-bound ESM1 is shown in brown. Scale bar: 50 μm. Arrowheads indicate positively stained nucleus of cancer cells. Plot representation of scores according to immunohistochemical expression of ESM1 in normal prostate tissue related to the prostate adenocarcinoma tissue with and without metastasis. The scores are calculated by intensity (score 1-3) x percentage (score 1-4) of stained cells. The line in the middle of the box is plotted at the median. The box extends from the 25th to 75th percentiles. Whiskers above and below the box indicate the 5th and 95th percentiles.",
    "diseases": "prostate adenocarcinoma"
  },
  {
    "caption": "(B) Induction of colitis in Rag1-/- mice by adoptive transfer of naive CD4+ T cells from wildtype, Stim2fl/fl Cd4Cre, Orai1fl/fl Cd4Cre and Stim1fl/fl Cd4Cre mice. Weight curves of recipient Rag1-/- mice following injection of naive CD4+ T cells. Data are from two independent experiments with 8 recipient mice per group.",
    "diseases": "colitis"
  },
  {
    "caption": "(A,B) Ca2+ influx in human lamina propria CD4+ and CD8+ T cells from 3 IBD patient samples analyzed by flow cytometry. (A) Experimental design. (B) Ca2+ influx rates in T cells pre-incubated for 4 h in the presence of 15-1000 nM BTP2, which was present until data acquisition. SOCE was induced by stimulation with the sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) inhibitor thapsigargin (TG) in Ca2+ free buffer followed by the addition of 2 mM Ca2+. Bar graphs show the mean ± SEM of Ca2+ influx rates after Ca2+ readdition from 1 experiment (n=3 IBD patients).",
    "diseases": "IBD"
  },
  {
    "caption": "(D) viSNE plots of CD45+CD3+ LPMCs stimulated with 20 ng/ml PMA and 1 µg/ml ionomycin for 4 hours in the presence of 15-1000 nM BTP2. viSNE plots are colored according to the expression level of IL-2 (blue: low, red: high) and are representative of one CD patient.",
    "diseases": "CD"
  },
  {
    "caption": "(E) Dose-response curves of the frequencies of cytokine producing CD4+ and CD8+ T cells after PMA/ionomycin stimulation for 4h in the presence of increasing doses of BTP2. The frequencies of cytokine producing cells were normalized to control samples treated with PMA/ionomycin alone. Bar graphs show the mean ± SEM of 5 CD patient samples.",
    "diseases": "CD"
  },
  {
    "caption": "(G) Cytokine production by CD19+HLA-DR+ B cells and CD11c+ dendritic cells in the presence of increasing doses (15-1,000 nM) of BTP2. Left: Dose-response curves showing frequencies of cytokine-producing cells after 4h stimulation with PMA/ionomycin ex vivo. Data are normalized to control samples stimulated with PMA/ionomycin in the absence of BTP2. Error bars represent SEM obtained from 1 experiment (n=5 CD patients). Right: heatmaps showing the median fold change of cytokines and surface markers in CD19+HLA-DR+ B cells and CD11c+ dendritic cells treated as described for the left panel.",
    "diseases": "CD"
  },
  {
    "caption": "(A) Experimental setup for mass cytometric assays. Non-inflamed: n = 4, CD: n =6, UC: n =6. (B) FlowSOM plot of merged FCS files from LPMCs of non-inflamed controls, UC or CD patients after stimulation with PMA/ionomycin ± 1 μM BTP2 for 4h ex vivo. Colors of the t-SNE plot represent 20 clusters of distinct CD45+ LPMC lineages. The heatmap shows the expression levels of 21 markers used for defining cell clusters.",
    "diseases": "CD, UC"
  },
  {
    "caption": "(C) FlowSOM map of merged FCS files from CD45+ cells of non-inflamed controls, UC and CD patients that were left unstimulated or treated with PMA/ionomycin ± 1 μM BTP2. Colors indicate altered cell clusters in CD patients vs. controls, UC patients vs. controls and CD vs. UC patients. (D) viSNE plots of one exemplary non-inflamed control, UC and CD patient colored by marker expression levels (blue: low, red: high).",
    "diseases": "CD, UC"
  },
  {
    "caption": "(E) Quantified frequencies (%) of each cell subset defined by the cluster analysis. Statistical significance was calculated using the edgeR statistical framework with negative binomial GLM and a false discovery rate adjusted to 10% using the Benjiamini-Hochberg procedure (*padj< 0.05, **padj < 0.01, ***padj< 0.001). Boxes extend from the 25th to 75th percentiles. Whisker plots show the min (smallest) and max (largest) values. The line in the box denotes the median from 1 experiment (non-inflamed n = 4, CD: n =6, UC: n =6 patients).",
    "diseases": "CD, UC"
  },
  {
    "caption": "(F) Heatmaps representing the median fold change of cytokine and surface marker expression in CD45+ LPMCs that were isolated from non-inflamed, UC and CD samples and activated for 4h with PMA/ionomycin ex vivo. Statistical significance was calculated using an unpaired t test with FDR adjustment to 1% using the Benjamini, Krieger and Yekutieli procedure; *",
    "diseases": "CD, UC"
  },
  {
    "caption": "(A) FlowSOM plot of merged FCS files from samples treated with PMA/ionomycin ± 1 µM BTP2 (non-inflamed: n = 4, CD: n =6, UC: n =6). Colors of FlowSOM plot indicate 20 distinct clusters of CD45+CD3+ LPMCs. Heatmaps show the expression levels of 24 markers used for cluster determination. The table shows the mean ± SEM of frequencies (%) for each cell subset defined in non-inflamed controls, UC and CD patients after 4h stimulation with PMA/ionomycin in vitro. Statistical significance was calculated using the edgeR statistical framework with negative binomial GLM and a false discovery rate adjusted to 10% using the Benjiamini-Hochberg procedure.",
    "diseases": "CD, UC"
  },
  {
    "caption": "(B) Box plots showing frequencies (%) of each cell subset defined by the cluster analysis in non-inflamed, UC and CD samples following stimulation with PMA/ionomycin ± BTP2 for 4h in vitro. Statistical significances were calculated using a one-tailed paired Wilcoxon matched-pairs signed-rank test, *p < 0.05. Boxes range from the 25th to 75th percentiles. Whisker plots show the min (smallest) and max (largest) values. The line in the box denotes the median obtained from 1 experiment (non-inflamed: n = 4, CD: n =6, UC: n =6 patients).",
    "diseases": "CD, UC"
  },
  {
    "caption": "(C) viSNE plots of one exemplary CD patient. Identification of cell subsets (left) and expression levels of cytokines after PMA/ionomycin stimulation in the presence or absence of BTP2 (blue; low, red: high).",
    "diseases": "CD"
  },
  {
    "caption": "(A) FlowSOM plot of merged FCS files from unstimulated samples or samples treated with PMA/ionomycin ± 1 µM BTP2 (non-inflamed: n = 4, CD: n =6, UC: n =6). Colors of FlowSOM plot indicate 20 distinct clusters of CD45+CD3- LPMCs. Heatmap clusters showing the expression levels of 34 markers used for cluster determination. The table shows the mean ± SEM of frequencies (%) for each cell subset defined in non-Inflamed, UC and CD samples after stimulation with PMA/ionomycin for 4h. Statistical significance was calculated using the edgeR statistical framework with negative binomial GLM and a false discovery rate adjusted to 10% using the Benjiamini-Hochberg procedure",
    "diseases": "CD, UC"
  },
  {
    "caption": "(B) Box plots show frequencies (%) of each cell subset defined by the cluster analysis in samples of non-inflamed controls, UC or CD patients after stimulation with PMA/ionomycin ± BTP2 for 4h ex vivo. Statistical significances were calculated by one-tailed paired Wilcoxon matched-pairs signed-rank test, *p < 0.05. Boxes range from the 25th to 75th percentiles. Whisker plots show the min (smallest) and max (largest) values. The line in the box denotes the median obtained from 1 experiment (non-inflamed: n = 4, CD: n =6, UC: n =6 patients).",
    "diseases": "CD, UC"
  },
  {
    "caption": "(C) viSNE plots of one exemplary CD patient. Identification of cell subsets (left) and expression levels of cell markers after PMA/ionomycin stimulation in the presence or absence of BTP2 (blue; low, red: high).",
    "diseases": "CD"
  },
  {
    "caption": "(D) Human colonic spheroids were generated from primary human epithelial crypts obtained from colon resectates of 2 CD patients and cultured for 6 days in Wnt-free medium to induce differentiation into colonic organoids. Initial viability was determined on day 0. DMSO control or 1 μM BTP2 were added to the culture medium and viability was measured on days 2, 4 and 6.",
    "diseases": "CD"
  },
  {
    "caption": "(G) Representative H&E staining of the distal colon of Rag1-/- mice treated with vehicle or CM4620. Colitis scores of 9 mice per cohort. Each symbol represents one mouse.",
    "diseases": "Colitis"
  },
  {
    "caption": "Representative immunostaining of primary cilia and MeCP2 in cultured human fibroblasts from healthy controls (CTRL, n=3) and RTT patients. Fibroblasts were starved for 24 h and then stained for acetylated α-tubulin (green), MeCP2 (red) and DAPI (blue). Scale bar 50 µm.",
    "diseases": "RTT"
  },
  {
    "caption": "Histograms indicate (mean ± S.E.) the percentage of ciliated cells in control and RTT fibroblasts",
    "diseases": "RTT"
  },
  {
    "caption": "The effect of tubacin (TUB) treatment (250 nM, 24 h) on primary cilium length of controls (CTRL) and RTT fibroblasts is reported. The graph indicates the mean ± S.E of the cilium length analyzed in untreated (n=130 CTRL; n=73 705delG; n=57 Q244X; n=68 R255X) and treated cells (n=25 CTRL; n=26 705delG; n=26 Q244X; n=49 R255X) (***p<0.001 vs untreated CTRL, §p<0.05 vs corresponding mutated untreated fibroblasts by two-way ANOVA, followed by Bonferroni post hoc test). Statistical analysis reported a significant treatment effect (F (1,429) = 26.56; p<0.0001) and a significant genotype (F(3,429) = 42.85; p<0.001).",
    "diseases": "RTT"
  },
  {
    "caption": "Subcutaneous LLC tumor growth over the time (D) (pool of 2 independent experiments; 10 mice per condition in total).",
    "diseases": "LLC"
  },
  {
    "caption": "Quantification (F) of total metastatic area in LLC-tumor bearing mice preconditioned with IgG or anti-CSF1R antibody and treated with vehicle or glufosinate (20mg/Kg).",
    "diseases": "LLC"
  },
  {
    "caption": "representative images (G) of total metastatic area in LLC-tumor bearing mice preconditioned with IgG or anti-CSF1R antibody and treated with vehicle or glufosinate (20mg/Kg).",
    "diseases": "LLC"
  },
  {
    "caption": "Evaluation of neuronal toxicity following glufosinate treatment. grip strength for front paws (triangular bar) (F), as an indicator of the development of tactile allodynia in vehicle and glufosinate-treated mice (n=4), before the treatment (baseline), after 1 day (acute Toxicity) and after 15 days (chronic toxicity) (pool of 2 independent experiments; 10 mice per condition in total).",
    "diseases": "tactile allodynia"
  },
  {
    "caption": "Evaluation of neuronal toxicity following glufosinate treatment. grip strength for all paws (rectangle grid) (G), of the latency to fall off an accelerating rotarod (H), and of the mean paw withdrawal force that caused animals' response in the von Frey test (left hindpaw, I; right hindpaw, J) as an indicator of the development of tactile allodynia in vehicle and glufosinate-treated mice (n=4), before the treatment (baseline), after 1 day (acute Toxicity) and after 15 days (chronic toxicity) (pool of 2 independent experiments; 10 mice per condition in total).",
    "diseases": "tactile allodynia"
  },
  {
    "caption": "e Insoluble proteins from two ALS brain tissues were chemically denatured in guanidine hydrochloride and treated with either buffer (Vehicle), total RNA from Jurkat cells or the complementary strands of the M1x4 DNA oligonucleotides (M1 F/R) (Pellet 1, top panel). After removal of GuHCl, the soluble fraction from these samples was treated with RNase and any aggregated proteins (Pellet 2), analysed by western blot (middle panel). Remaining supernatants were then treated with Benzonase to degrade any remaining nucleic acids and aggregated proteins collected by centrifugation and analysed by western blot (bottom panel). Proteins aggregated by enzymatic RNA degradation in Jurkat cell lysates, which do not contain NF-H, were used as a control.",
    "diseases": "ALS"
  },
  {
    "caption": "Tissue microarrays (TMAs) from primary PCa (n=132) and CRPC (n=148) were stained via immunohistochemistry for poly(ADP-ribose) (PAR), and scored by a clinical pathologist (T. Parsons) for intensity (0-3) and percentage (0-3) PAR score was generated via the equation: (intensity x 1) + (percentage x 2). PAR scores were compared between primary and CRPC. ****=p value<0.0001 by Chi-square test",
    "diseases": "CRPC, PCa"
  },
  {
    "caption": "Manual PAR scores were divided in to quartiles and then were compared to progression-free survival in the CRPC TMAs. *=p<0.05, ns=not statistically significant by Log-rank (Mantel-Cox)",
    "diseases": "CRPC"
  },
  {
    "caption": "Top, left: Schematic representing the conditions utilized for transcriptomic analyses (n=2) of CRPC C4-2 cells. Cells were deprived of hormones for 72 hours, followed by either treatment with 2.5uM veliparib (PARPi) or vehicle control (DMSO) for for 16 hours. Top, right: Immunoblot with the indicated antisera. Bottom: Volcano plots of transcripts found to be differentially regulated PARPi v. vehicle control. Red dots indicate transcripts that were both statistically significantly altered (p<0.05) and more than 1.5-fold changed",
    "diseases": "CRPC"
  },
  {
    "caption": "Genes found to be down-regulated by PARPi as described above (p value < 0.05, 1.5-fold change) in either HT-sensitive cells (left) or CRPC cells (right) were queried against the expression of these genes in the Grasso et al data set in Oncomine. Benign = grey, primary PCa = blue, metastases = orange. Boxplot was generated using the mean expression of the PARPi down-regulated genes in the indicated data sets. Statistical significance determined by two-tailed Student"s t",
    "diseases": "CRPC"
  },
  {
    "caption": "Athymic nude mice were injected with C4-2 cell mixed with matrigel. Once tumors became 100mm3, mice were treated with either vehicle control or veliparib. 72 hours later, tumors were harvested, RNA was isolated and used for qPCR quantification of the indicated transcripts. Data are depicted as log2 absolute gene regulation of veliparib samples compared to control samples, +/- standard deviation of three independent xenograft tumors",
    "diseases": "tumors"
  },
  {
    "caption": "Athymic nude mice were injected with C4-2 cell mixed with matrigel. Once tumors became 100mm3, mice were treated with either vehicle control or veliparib. 72 hours later, tumors were harvested, RNA was isolated and used for qPCR quantification of the indicated transcripts. Data are depicted as log2 absolute gene regulation of veliparib samples compared to control samples, +/- standard deviation of three independent xenograft tumors",
    "diseases": "tumors"
  },
  {
    "caption": "Expression levels of indicated HR pathway genes in primary PCa vs normal patient samples. Violin plots represent FPKM normalized counts obtained from matched tumor and normal RNA-Seq data from TCGA (n=52) with p-values generated using paired t-tests",
    "diseases": "tumor"
  },
  {
    "caption": "A. Characteristics of IGR39 /IGR37 and WM115/WM266.4 melanoma cell lines (Upper Panel). Pigmentation of melanoma cells pellets (lower panel).",
    "diseases": "melanoma"
  },
  {
    "caption": "A. Absolute quantitation of 24, 25 and 27-hydroxycholesterol in primitive and metastatic melanoma cells as indicated. (T-test analysis, ***p-value<0.001, N=3 biological replicates, data are mean ±SD).",
    "diseases": "melanoma"
  },
  {
    "caption": "B. Histogram representing R square of correlation analysis between absolute quantitation of 24, 25 and 27-hydroxycholesterol and label free quantitation of APOE in a cohort of primitive (A375, IPC298) and metastatic (SKMEL5, SKMEL28) melanoma cell lines.",
    "diseases": "melanoma"
  },
  {
    "caption": "A-D. Immunofluorescence images with Proteostat (red) and DAPI (blue) staining on (A) human normal skin, (B) samples of primitive melanomas, (C) melanoma metastases in brain and (D) melanoma  metastases in lung.",
    "diseases": "melanoma, melanomas"
  },
  {
    "caption": "E. Details of brain metastases. Scale Bar is 30µm. F. Quantitation of Proteostat positive dots in primitive vs metastatic melanoma tissues: 6 tissues from metastatic lesions and 6 from primitive melanoma lesions were analysed. For each tissue two sections were quantified. T-test analysis was applied. T-test analysis, ** = p-value<0.01 (N=6, data are mean ±SEM).",
    "diseases": "melanoma"
  },
  {
    "caption": "B. Representative flow cytometry dot plots of CD11b+ and CD11b+/Cripto+ cells at day 2, 3 and 5 after injury. PE (Phycoerythrin/free channel). Data are mean±SEM (n=5 biological replicates; P≤0.00008, Student's t-test).",
    "diseases": "injury"
  },
  {
    "caption": "C. Representative flow cytometry dot plots of CD11b+/F4/80+/Ly6CHigh/Low and CD11b+/Cripto+/F4/80+/Ly6CHigh/Low cells at day 2, 3 and 5 after injury. D. Quantification of F4/80+/Ly6CHigh/Low cells in the CD11b+ and CD11b+/Cripto+ cell population from injured muscles at the indicated time points. Data represent mean±SEM (n=5 biological replicates; ***P<0.001, Student's t-test). ",
    "diseases": "injury"
  },
  {
    "caption": "A. Representative pictures of immunostaining for F4/80 (green) in Control and CriptoMy-LOF TA sections at day 2 (top panel) and 5 (bottom panel) after injury. B. Quantification of F4/80 staining/damaged area (μm2) at day 2 (top graph) and 5 (bottom graph) after injury. Data information: Nuclei were counterstained with DAPI (blue). Scale bar: 50 μm. Magnification of the boxes is 3.5 x. Data are expressed as box plots displaying minimum, first quartile, median, third quartile and maximum (n≥5 biological replicates; **P<0.01, Student's t-test).",
    "diseases": "injury"
  },
  {
    "caption": "C. Representative pictures of immunostaining for CD206 in Control and CriptoMy-LOF TA sections at day 2 (top panel) and 5 (bottom panel) after injury, respectively. D-E. Quantification of CD206+ MPs per area (mm2) at day 2 (D) and 5 (E) after injury. Data information: Nuclei were counterstained with DAPI (blue). Scale bar: 50 μm. Magnification of the boxes is 3.5 x. Data are expressed as box plots displaying minimum, first quartile, median, third quartile and maximum (n≥5 biological replicates; **P<0.01, Student's t-test).",
    "diseases": "injury"
  },
  {
    "caption": "A. Representative flow cytometry dot plots showing the percentage of GFP+ cell population in GFP-Control and GFP-CriptoMy-LOF muscles at day 2 (top panel) and 5 (bottom panel) after injury. Percentage of GFP+ cells expressing F4/80 in GFP-Control and GFP-CriptoMy-LOF muscles is shown at day 2 after injury (middle panel). Data are mean±SEM (n=4 biological replicates; P=ns; Student's t-test).",
    "diseases": "injury"
  },
  {
    "caption": "C. Representative pictures of immunostaining for GFP (green), CD206 (red), pSMAD3 (white) in GFP-Control and GFP-CriptoMy-LOF TA sections at day 5 after injury. Nuclei were counterstained with DAPI (blue). Scale bar: 100 μm. Magnification of the boxes is 3.5 x. D. Quantification of GFP+/CD206±/pSMAD3± cell distribution in TA sections from GFP-Control and GFP-CriptoMy-LOF at day 5 after injury. Nuclei were counterstained with DAPI (blue). Scale bar: 100 μm. Data are mean±SEM (n=5 biological replicates; **P<0.01, Student's t-test). ",
    "diseases": "injury"
  },
  {
    "caption": "E. Representative flow cytometry dot plots of F4/80+/Ly6CLow cell population gated on GFP+ cells from GFP-Control and GFP-CriptoMy-LOF muscles at day 5 after injury. Data are mean±SEM (n=3 biological replicates; P=ns; Student's t-test).",
    "diseases": "injury"
  },
  {
    "caption": "(F) Smear plot of RNA-seq data from GFP+/F4/80+/Ly6CLow cells FACS sorted from GFP-Control and GFP-CriptoMy-LOF muscles at day 5 after injury. Data show the expression level as Log2 fold-change (FC) [Log2(GFP-Control/GFP-CriptoMy-LOF)], against Log2(expression) [Log2(average of gene expression across all samples], for each individual gene. The blue lines correspond to LogFC of 1 and -1. (n=3 biological replicates).",
    "diseases": "injury"
  },
  {
    "caption": "E. Representative pictures of double immunostaining with Laminin (green) and eMHC (red) at day 5 (left panel) and 30 (right panel) after re-injury (CTX-II). Data information: Nuclei were counterstained with DAPI (blue).",
    "diseases": "injury"
  },
  {
    "caption": "A. Representative pictures of CD31 (red) immunostaining of Control and CriptoMy-LOF TA sections at day 5 (left panel) and 30 (right panel) after single injury (CTX-I). B-D. Quantification of CD31+ capillary number per area (mm2; B), average of capillary cross-sectional area (µm2; C) and percentage of small (<20 µm2) and large (>100 µm2) capillaries (D) in Control and CriptoMy-LOF injured muscles at indicated time points after single injury (CTX-I). Data are mean±SEM (n=5 biological replicates; *P<0.05; **P<0.01; ***P<0.001, Student's t-test). Data information: Nuclei were counterstained with DAPI (blue). Scale bar: 100 μm. Magnification of the boxes is 3.5 x.",
    "diseases": "injury"
  },
  {
    "caption": "E. Representative pictures of CD31 (red) immunostaining of Control and CriptoMy-LOF TA sections at day 5 (left panel) and 30 (right panel) after re-injury (CTX-II). Data information: Nuclei were counterstained with DAPI (blue). Scale bar: 100 μm. Magnification of the boxes is 3.5 x.",
    "diseases": "re-injury"
  },
  {
    "caption": "G-H. Quantification of CD31+ capillary number per area (mm2; G) and average of capillary cross-sectional area (µm2; H) in Control and CriptoMy-LOF injured muscles at the indicated time points after re-injury (CTX-II) Data are mean±SEM (n=6 biological replicates; *P<0.05; ***P<0.001, Student's t-test).",
    "diseases": "re-injury"
  },
  {
    "caption": "A. Representative pictures of double immunostaining with VEcad (red; left and middle panel) and KLF4 (green, left panel) or TCF4 (green, middle panel), and with CD31 (red; right panels, confocal pictures) and TCF4 (white, right panel) on Control and CriptoMy-LOF TA sections at day 5 after injury. B-D. Quantification of VEcad/KLF4 (B), VEcad/TCF4 (C) and CD31/TCF4 (D) double positive cells per area (mm2) in Control and CriptoMy-LOF TA sections at day 5 after injury. Data information: Nuclei were counterstained with DAPI (blue).",
    "diseases": "injury"
  },
  {
    "caption": "E. Representative Confocal pictures of CD31+ (red) and PDGFRα+ (green) immunostaining on Control and CriptoMy-LOF TA sections at day 5 after injury. F-G. Quantification of CD31+/PDGFRα+ (F) and CD31-/PDGFRα+ (G) cells per area (mm2). Data information: Nuclei were counterstained with DAPI (blue).",
    "diseases": "injury"
  },
  {
    "caption": "H-I. Representative pictures of triple immunostaining with VEcad (red), KLF4 (green) and pSMAD3 (white) on Control and CriptoMy-LOF TA sections at day 5 after injury (H) and quantification of VEcad/KLF4/pSMAD3 triple positive cells per area (mm2; I). Data information: Nuclei were counterstained with DAPI (blue).",
    "diseases": "injury"
  },
  {
    "caption": "Representative pictures of double immunostaining with VEcad (red) and KLF4 (green) on Control and CriptoMy-LOF TA sections at day 5 after re-injury (CTX-II Data information: Nuclei were counterstained with DAPI (blue).",
    "diseases": "re-injury"
  },
  {
    "caption": "Quantification of VEcad/KLF4 double positive cells per area (mm2) in Control and CriptoMy-LOF TA sections at day 5 after re-injury (CTX-II",
    "diseases": "re-injury"
  },
  {
    "caption": "(C) miR-574-5p and miR-574-3p were highly expressed in the explanted failing hearts from chronic HF patients (n=17) versus donor non-failing hearts (n=6).",
    "diseases": "chronic HF"
  },
  {
    "caption": "(C) Picrosirius red staining of murine hearts in the therapeutic models. Scale bar: 1 mm. The fibrotic area was quantified in the right panel (n=4-10 per group).",
    "diseases": "fibrotic"
  },
  {
    "caption": "(A,B) MPO staining  of liver  issue used as a marker for  myeloid cells including monocytes  in both  Nlrp3D301N-MRP8 and Nlrp3A350V-MRP8 mutant (n≥3 mice  per genotype, representative images shown, bar indicates 250 μM). H&E staining  of liver  tissue with histologic  scoring of  liver  inflammation (bar indicates 100 μM, representative images are shown). TUNEL staining  of liver  tissue (Representative images shown, bar indicates 250 μM). Data information: n≥6 mice  per genotype, significance determined by unpaired t test (* p < 0.05; ** p < 0.01; *** p < 0.001), data are expressed as mean +/− SD, dots represent individual biological replicats",
    "diseases": "liver  inflammation"
  },
  {
    "caption": "To monitor the progression of the CLL-like population, blood was collected from the animals every four weeks up to an age of 60 weeks and analyzed by flow cytometry. Representative FACSplots show examples of stainingsof B220lowCD5+B cells (CLL-like cells) and the selected gate for B).",
    "diseases": "CLL"
  },
  {
    "caption": "To monitor the progression of the CLL-like population, blood was collected from the animals every four weeks up to an age of 60 weeks and analyzed by flow cytometry. The diagram displays the percentage of CLL-like cells in relation to all lymphocytesover a period of 60 weeks. Shown are mean values with ±SD. Significant differences between groups were determined by one-way ANOVA with Kruskal-Wallis test (no normal distribution) and corrected for multiple comparison with Dunn's test, **p<0.01, ***p<0.001. Summarized data from more than 40 independent experiments for individual time points, comprising n=4-75 animals per time pointand genotype. X = no surviving TCL1 x Siglecg-/-animals at the ageof 60 weeks. + indicates that in these groups only 4 animals were used for the analysis and therefore no calculation of significance was possible.",
    "diseases": "CLL"
  },
  {
    "caption": "To monitor the progression of the CLL-like population, blood was collected from the animals every four weeks up to an age of 48 weeks and analysed by flow cytometry. Genotypes of the mice are: controls (Siglecg-R26ki/ki), Siglec-G overexpressing mice (Siglecg-R26ki/ki mb1cre), transgenic TCL1 controls (TCL1 x Siglecg-R26ki/ki) and transgenic TCL1 Siglec-G overexpressing mice (TCL1 x Siglecg-R26ki/ki mb1cre). Representative FACSplots show examples of stainingsof B220lowCD5+B cells (CLL-like cells) and the selected gate for B)",
    "diseases": "CLL"
  },
  {
    "caption": "To monitor the progression of the CLL-like population, blood was collected from the animals every four weeks up to an age of 48 weeks and analysed by flow cytometry. Genotypes of the mice are: controls (Siglecg-R26ki/ki), Siglec-G overexpressing mice (Siglecg-R26ki/ki mb1cre), transgenic TCL1 controls (TCL1 x Siglecg-R26ki/ki) and transgenic TCL1 Siglec-G overexpressing mice (TCL1 x Siglecg-R26ki/ki mb1cre). The diagram displays the percentage of B220lowCD5+cells in respect to lymphocytesover a time periodof 48 weeks. Shown are mean values with ±SD. Significant differences between groups were determined by one-way ANOVA with Kruskal-Wallis test (no normal distribution) and corrected for multiple comparison with Dunn's test. All time pointswere tested separately. *p<0.05, **p<0.01, ***p<0.001. Summarized data from more than 20 independent experiments with n=5-20 animals per time pointand genotype are shown.",
    "diseases": "CLL"
  },
  {
    "caption": "Peripheral blood B cells of CLL patients are pre-gated on single, living B lymphocytes (CD19+). The mean fluorescence intensity (MFI) of surface Siglec-10 is given from 35 IgV-mutated (left) and 18 IgV-unmutated CLL cases (right), always including tumor cells (CD20lowCD5high) and normal residual B cells (CD20highCD5-) as paired samples.",
    "diseases": "CLL"
  },
  {
    "caption": "The transcript expression (normalized counts from bulk mRNA sequencing) of SIGLEC10 is given from five healthy donors, discriminating naïve CD5- (five donors), mature CD5+ 86 donors) and CD27+ memory B cell (eight donors) subsets, from CLL tumor cells (n=9) and from five paired normal residual B (NRB) cells (n=5).",
    "diseases": "CLL"
  },
  {
    "caption": " (A) PI3Kγ is expressed by human hepatocytes and infiltrating immune cells in biopsies from patients with minimal to mild inflammatory activity. Triangles point to immune cells (clusters), including some neutrophils known to express PI3Kγ highly. In the negative control, the primary antibody was replaced by an equal volume buffer. The number of included patients, gender, and diagnosis are summarized ",
    "diseases": "inflammatory"
  },
  {
    "caption": "  (D) Survival of WT, PI3Kγ null (left) and liver-specific PI3Kγ knockout mice (PI3Kγ floxtg/tg x AlbCre(tg)/tg, middle) or systemic application of the PI3Kγ inhibitor, AS605240 (right) in a model of polymicrobial sepsis induced by peritoneal contamination with a human stool suspension. Animal numbers: B6: 86 (%male: 52, %female: 48), B6-Pi3kcgko/ko: 59 (%male: 51, %female 49), B6-Pi3kcgflox/flox x AlbCre(tg)/tg: 25 (%male: 68, %female 32), FVB/N Vehicle: 25 (%male: 44, %female 56), FVB/N AS: 43 (%male: 44, %female 56)  ",
    "diseases": "polymicrobial sepsis"
  },
  {
    "caption": " (A) Intravital microscopy of elimination of CDFDA, a fluorescent substrate subject to excretory elimination by hepatocytes via Mrp-2, allows direct visualization of excretory function in sham or septic (PCI) animals treated with vehicle or a hepatocyte-directed inhibitor of PI3Kγ (T-LipoAS). ",
    "diseases": "septic"
  },
  {
    "caption": "(b) Correlation analyses of RNA expression levels of uPA (PLAU gene), PAI-1 (SERPINE1 gene), and the neutrophil marker gene FPR1, and overall survival of breast cancer patients (stages 0 and 1) with high and low PLAU or SERPINE1 gene expression levels (cut-off z≥ 2.0) in the METABRIC breast cancer cohort.",
    "diseases": "breast cancer"
  },
  {
    "caption": "(d) Relative development rates and tumor weight in animals treated with WX-340 a priori or therapeutically after 1 week after tumor cell injection on a daily basis as assessed in an orthotopic model of 4T1 breast cancer in WT mice (mean±SEM for n=4-6 mice per group; *p<0.05 vs. drug vehicle; One-way ANOVA).",
    "diseases": "breast cancer"
  },
  {
    "caption": "(E-G) recovery time from tremor (E,F) and survival (G) of single flies overexpressing BomS6 ubiquitously (E,G) or in neurons (F-G) (biological replicates) compared to wild-type after injection of verruculogen; in (G) the inset represents the survival of vehicle control groups.",
    "diseases": "tremor"
  },
  {
    "caption": "(H-I) recovery time from tremor (H) and survival (I) of single flies overexpressing BomS6 in glia (pooled data from n=3 experiments, biological replicates) compared to wild-type after injection of verruculogen; in (I) the inset represents the survival of vehicle control groups. Recovery time (H) repo>mCherry vs. repo>BomS6, p=0.058, survival (I) repo>mCherry V vs. repo>BomS6 V, *p=0.016.",
    "diseases": "tremor"
  },
  {
    "caption": "(F) Immunoblot analysis of WT cells and two NME6 KO clones (#1, #2) generated in three different liver cancer cell lines: HLE, Huh6 and HepG2.",
    "diseases": "liver cancer"
  },
  {
    "caption": "(H) The relative growth of WT and NME6 KO liver cancer cell lines monitored on each day (d) using an ATP luminescence assay. P-values for HLE cells: two-way ANOVA P-value (time) = <0.0001, P-value (genotype) = <0.0001, P-value (interaction) = <0.0001; P-values for Huh6 cells: two-way ANOVA P-value (time) = <0.0001, P-value (genotype) = 0.0005, P-value (interaction) = <0.0001;p-values for genotype are shown (n=4 independent cultures).",
    "diseases": "liver cancer"
  },
  {
    "caption": "B) Kaplan-Meier analysis of overall (left) and progression-free (right) survival in patients with lung adenocarcinoma with high PTGES (top 10%) and low PTGES (bottom 90%) expression.",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "C) NK cell gene signature in normal and tumor tissues based on a TCGA lung adenocarcinoma cohort and quantification of NK cell gene signature in patients with different stages of lung adenocarcinoma.",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "E) Overall survival in patients with stage I (n=269) lung adenocarcinoma with high (top 50%) and low (bottom 50%) NK cell gene expression signature expression.",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "D. Representative H&E  images showing Ponatinib alleviates  LPS-induced inflammatory cell infiltration, septal thickening, alveolar edema in  mouse lungs. Scale bars 100 µm (upper) and 50 µm (lower).",
    "diseases": "septal thickening, alveolar edema"
  },
  {
    "caption": "Figure 3.Expression analysis of splicing factor mRNAs in various GBM datasets.A. The genes encoding splicing factors down-regulated by miR-10b are expressed at lower levels in various GBM datasets relative to their expression in normal brain tissues.B. In contrast, many splicing factors up-regulated by miR-10b are overexpressed in the GBM datasets.Six high-content GBMmicroarray datasets from the Oncomine resource (https://www.oncomine.org/resource/main.html), including TCGA_BrainGBM (2), Bredel Brain2 (31), Lee Brain (32), Liang Brain (33), Murat Brain (34) and Sun Brain (35), that collectively contain information for 858 GBM and 52 control samples, have been utilized for the analysis. The data is presented as log2 fold change between GBM and normal brain tissues.",
    "diseases": "GBM"
  },
  {
    "caption": "B. qRT-PCR analysis validates that mRNA of MBNL1-3, SART3, RSRC1 and other splicing factors are de-repressed by miR-10b ASO in different GSC and GBM cell lines. mRNA expression levels were normalized to GAPDH expression.",
    "diseases": "GBM"
  },
  {
    "caption": " C Bar graph showing the percentage of unique insertions in the top 7 genes normalized to the total number of insertions in a given sample. Genes are annotated with a gene symbol when available otherwise with UCSC ID transcript names. Data are from all the sequenced samples (tumour samples: 16 primary tumours; metastatic samples: 3 lung micro-metastases, 6 lung macro-metastases and 9 LM cell lines). Means ± s.d., two-tailed Mann-Whitney U-test, n.s. = not significant. ",
    "diseases": "LM, lung macro-metastases, lung micro-metastases"
  },
  {
    "caption": "D Bar graphs showing the percentage of unique insertions in Nfib and Foxp1 in tumours, LM1, LM8, LM9, and other LM cell lines normalized to the total number of insertions in a given sample. Dots represent individual samples (Tumours n = 16, LM1/8/9 n = 9, Other LM n = 9), means ± s.d., two-tailed Mann-Whitney U-test, n.s. = not significant.",
    "diseases": "LM"
  },
  {
    "caption": "G Immunoblot analysis of LM and HR1 cell lines showing NFIB and FOXP1 protein levels. ERK2 served as a loading control.",
    "diseases": "LM"
  },
  {
    "caption": "A The kinetics of LM1 (n = 10), LM9 (n = 4), LM1 Nfib KO (n = 4), and LM9 Nfib KO (n = 4) tumour growth upon orthotopic injection of 250 x 103 cells into NOD/SCID mice. Curves show means of tumour volume ± s.d., two-way ANOVA group analysis of the times to reach 250 mm3 (dashed line).",
    "diseases": "LM"
  },
  {
    "caption": " B Kaplan-Meier plot depicting metastatic onset after tumour removal in mice injected orthotopically with LM1 (n = 5), LM9 (n = 4), LM1 Nfib KO (n = 3), or LM9 Nfib KO (n = 4) cells, two-tailed log-rank test. ",
    "diseases": "LM"
  },
  {
    "caption": " C Nfib knockout abrogates metastasis in the orthotopic LM1 model. Representative bioluminescence images (left panel) and bar plot quantification (right panel) of lung metastases at 25 (LM1) and 40 (KO) days after primary tumour removal; n = 3 mice, means ± s.d., two-tailed Student's t-test. ",
    "diseases": "LM, lung metastases"
  },
  {
    "caption": " D Nfib knockout impairs experimental metastases formation in the LM models. Kaplan-Meier plot showing metastatic incidence of animals inoculated i.v. with LM1 (n = 4), LM9 (n = 4), LM1 Nfib KO (n = 3), or LM9 Nfib KO (n = 5) cells, two-tailed log-rank test. ",
    "diseases": "LM"
  },
  {
    "caption": " E Representative bioluminescence images (left panel) and bar plot quantification (right panel) of lung metastases 16 days after i.v. injection of LM1 or LM1 Nfib KO cells, n = 3 mice, means ± s.d., two-tailed Student's t-test. ",
    "diseases": "LM, lung metastases"
  },
  {
    "caption": " B Nfib overexpression in HR1 parental cells enhances metastasis in the orthotopic model. Representative bioluminescence images (left panel) and bar plot quantification (right panel) of lung metastases at day 20 (HR1 gCtrl) and day 2 (HR1 g4Nfib) after primary tumour removal. n = 4 mice, means ± s.d., two-tailed Student's t-test. ",
    "diseases": "lung metastases"
  },
  {
    "caption": " D Representative bioluminescence images (left panel) and bar plot quantification (right panel) of lung metastases 16 days after i.v. injection of HR1 gCtrl or HR1 g4Nfib cells. n = 4, means ± s.d., two tailed Student's t-test. ",
    "diseases": "lung metastases"
  },
  {
    "caption": " F Representative bioluminescence images (left panel) and bar plot quantification (right panel) of lung metastases 20 days after i.v. injection of SUM159PT gCTRL or SUM159PT gNFIB (n = 5), means ± s.d., two-tailed Student's t-test. ",
    "diseases": "lung metastases"
  },
  {
    "caption": " E Representative bioluminescence images (left panel) and bar plot quantification (right panel) of lung metastases 8 (SUM159PT gNFIB shCTRL) and 20 (SUM159PT gNFIB sh1 ERO1A or SUM159PT gNFIB sh2 ERO1A) days after i.v. injection of the respective cells. n = 4, means ± s.d., two-tailed Student's t-test. ",
    "diseases": "lung metastases"
  },
  {
    "caption": " C Left panel: Bar graph representing mean VEGFA mRNA expression in SUM159PT gCTRL and SUM159PT gNFIB breast cancer cell lines upon downregulation of ERO1A with two independent shRNAs (sh1 and sh2). Right panel: Bar graph representing mean VEGFA mRNA expression in lung extracts from animals inoculated i.v. with SUM159PT gNFIB shCTRL, SUM159PT sh1 ERO1A, or SUM159PT sh2 ERO1A cells. In both graphs n = 3 biological replicates and n = 2 technical replicates, means ± s.d., two-tailed Student's t-test, FC= fold change. ",
    "diseases": "breast cancer"
  },
  {
    "caption": " D Left panel: Representative images of CD31-positive endothelial structures in lungs. Scale bar, 1 mm. Right panel: Bar graphs showing lung metastases quantified as percentage of metastatic area per lung area and quantification of CD31 staining in the metastatic area. Means ± s.d., n = 8 shCTRL, n = 5 per sh1 ERO1A, and n = 6 sh2 ERO1A, two-tailed Student's t-test.",
    "diseases": "lung metastases"
  },
  {
    "caption": " E Left panel: Bar graph showing average of master segments counted after incubation of HUVEC cells with conditioned medium from LM1, HR1, 4T1 (Nfib high-expression and the respective Nfib low-expression or KO controls) and SUM159PT gNFIB shCTRL, SUM159PT gNFIB sh1 ERO1A, SUM159PT gNFIB sh2 ERO1A cells. Human VEGF121(0.4 ng/μl) was added to SUM159PT gNFIB sh1 and sh2 ERO1A cells, n = 2 technical replicates, means ± s.d., two-tailed Student's t-test. Right panel: Representative images showing tube formation four hours after addition of conditioned medium from HR1 gCtrl or g4Nfib.Scale bar 100 μm. ",
    "diseases": "LM"
  },
  {
    "caption": " A Representative images of NFIB, ERO1L, VEGFA-positive TNBC PDX primary tumours. Scale bar, 1 mm. ",
    "diseases": "TNBC"
  },
  {
    "caption": " B Representative images of NFIB, ERO1L, VEGFA-positive lung metastases from TNBC PDX. Scale bar, 1 mm. ",
    "diseases": "lung metastases, TNBC"
  },
  {
    "caption": "
 C Higher NFIB expression in iC10 and basal breast cancer subtype compared with the other subtypes using intClust (Dawson et al, 2013) and PAM50 classifications in the METABRIC cohort (n = 1980 across the 10 Intclust, iC). Boxplot represents NFIB expression values comprised between the 1st and the 3rd quartiles with the central band representing median expression value, and whiskers indicating the farthest data points that are still within the distance of 1.5 times the interquartile range (IQR). 
",
    "diseases": "breast cancer"
  },
  {
    "caption": " D, E Distant metastasis-free survival (D, n = 232) and overall survival (E, n = 241) plots generated using the Kaplan-Meier Plotter based on the mean expression using the signal intensity of the NFIB (213029_at) combined with the ERO1A (218498_s_at) probes. The cut-off was automatically set to split patients into two groups (median), high and low. The plots were generated using the signal intensity of the different probes in Affymetrix microarray gene expression data from TNBC patients of The Cancer Genome Atlas. Number of patients (n) and P values (two tailed log-rank test) are presented in the panels. ",
    "diseases": "TNBC"
  },
  {
    "caption": "(G,G') Representative spot views generated using Imaris from  in situ hybridization with miRCURY  LNA probe for dmiR-1  and used for quantification of dmiR-1  levels. Spot views of dmiR-1 in hearts  of one-week-old control (UAS-mblRNAi) (G) and DM1 flies  (Hand>mblRNAi) (G') are shown. Each spot represents a pool of dmiR-1 transcripts detected in the same area. The zoom region in G corresponds to area in which FISH  signal was quantified. Data information: Scale bar = 40 µm.",
    "diseases": "DM1"
  },
  {
    "caption": "(H, I) Scatter plot graph showing the signal intensity quantified in cardioblasts  of one- and five-week-old flies  for controls (UAS-Bru3, UAS-mblRNAi) and DM1  contexts (Hand>Bru3, Hand>mblRNAi). n = 9 hearts. Bars corresponds to mean ± SD. Data information: p-value<0.05 considered statistically significant. (*) p-value = 0.033, (**) p-value =0.021, (***) p-value =0.0002. (****) p-value<0.0001. Non-parametric Mann Whitney test was performed to compare control samples and samples of interest.",
    "diseases": "DM1"
  },
  {
    "caption": "(K,L) Graphs of Mp  signal quantification in cardioblasts  from adult flies aged  one and five weeks for controls (UAS-mblRNAi, UAS-Bru3) and DM1  contexts (Hand>mblRNAi, Hand>Bru3) using CTCF  method. For each genotype 9 hearts  were analyzed and fluorescence intensity was measured in two regions from segment A3 and two regions from segment A4. Bars correspond to mean ± SD. Data information: p-value<0.05 considered statistically significant; (*) p-value = 0.033; (**) p-value = 0.021; (***) p-value = 0.0002; (****) p-value<0.0001. Non-parametric test Mann Whitney test was performed to compare control samples and samples of interest.",
    "diseases": "DM1"
  },
  {
    "caption": "(A, B) (A) Col15A1   transcript levels tested by  RT-qPCR and (B) Col15A1  protein levels tested by Western blot in cardiac  samples from healthy donors and from DM1 patients  with (DCM+) and without DCM   (DCM-). Data information: p-value<0.05 considered statistically significant. (*) p-value = 0.033, (***) p-value =0.0002. (****) p-value<0.0001. Parametric t-test was performed to compare control samples and samples of interest in A, B",
    "diseases": "DCM, DM1"
  },
  {
    "caption": "(C) miR-1 levels tested by RT-qPCR in cardiac  samples from healthy donors and from DM1 patients. Data information: p-value<0.05 considered statistically significant. (*) p-value = 0.033, (***) p-value =0.0002. (****) p-value<0.0001. Parametric t-test was performed to compare control samples and samples of interest in C.",
    "diseases": "DM1"
  },
  {
    "caption": "(D, F) Box plots showing cardiac  variables (diastolic (D) and systolic (E) diameters and percent fractional shortening (F)) assessed by SOHA  approach for controls (UAS-Bru3; Mp  RNAi and UAS-UPRT; Bru3), Mp  rescue (Hand>Bru3; Mp  RANi) and DM1  context (Hand>UPRT; Bru3) at five weeks of age  showing rescue of diastolic   and systolic  diameters in Hand>Bru3; Mp  RNAi in comparison to controls (D,E) and rescue of cardiac  contractility (F) n = 20 hearts. Central band corresponds to median. Whiskers correspond to Min to Max. Box corresponds to interquartile range from 25th to 75th percentile. Data information: p-value<0.05 considered statistically significant. (*) p-value = 0.033, (***) p-value =0.0002. (****) p-value<0.0001. Non-parametric Mann Whitney test was performed to compare control samples and samples of interest in D,E,F.",
    "diseases": "DM1"
  },
  {
    "caption": "Kaplan-Meier curves showing the survival of patients stratified on the basis of MCOLN1 expression in BLCA and HNSC patients whose tumors were wild-type for HRAS (right) or carried oncogenic HRAS mutations (left). Statistical test employed was the Mantel-Cox log-rank test.",
    "diseases": "BLCA, HNSC"
  },
  {
    "caption": "Fraction of peaks shared between PDX and corresponding primary leukemia for ATAC peaks with a certain height (x-axis; average number of reads that map into an accessible region called by Macs2)",
    "diseases": "primary leukemia"
  },
  {
    "caption": "C-F GlaB inhibits MB‐SCs' self‐renewal and proliferation. (C) Suspension of single MB‐SCs isolated from Ptch1+/−mice. MBs were cultured in stem cell medium to allow the formation of primary neurospheres. Primary neurospheres were dissociated and treated with increasing concentrations of GlaB or DMSO only. After 7 days of treatment, the number of secondary neurospheres derived from a known number of single cells was counted. The self‐renewal MB‐SCs' capability is expressed as percentage of neurosphere‐forming cells (left). Representative bright field images of tumor neurospheres after GlaB treatment are also shown (right).",
    "diseases": "tumor"
  },
  {
    "caption": "E qRT-PCR analysis show Hh and proliferation target mRNA expression levels. For qRT-PCR, results were normalized to endogenous control (β2‐microglobulin and HPRT). Data show the mean ± SD of tumor (n = 6) for each treatment. *P 0.05 versus Ctr.",
    "diseases": "tumor"
  },
  {
    "caption": "F Western blot analysis show Hh and proliferation target protein expression levels. Data show the mean ± SD of tumor (n = 6) for each treatment. *P 0.05 versus Ctr.",
    "diseases": "tumor"
  },
  {
    "caption": "D-H GlaB inhibits Gli1‐dependent BCC tumor growth in ASZ001 BCC allografts in vivo. (H) qRT-PCR of Hh and proliferation target mRNA expression levels. Results were normalized to endogenous control (β2‐microglobulin and HPRT). Shown is the mean ± SD of tumor (n = 6) for each treatment. *P 0.05 versus Ctr.",
    "diseases": "tumor"
  },
  {
    "caption": "Incidence of spontaneous colitis observed in wild-type (WT) and CD4+ cell-specific Adar1 knockout (Cd4cre A1fl/fl) mice (n = 11 for each group;",
    "diseases": "colitis"
  },
  {
    "caption": "No incidence of spontaneous colitis observed in Ifih1-/- (n = 5) and Cd4cre A1fl/fl Ifih1-/- (n = 11) mice. For side-by-side comparison with Cd4cre A1fl/fl mice",
    "diseases": "colitis"
  },
  {
    "caption": "(A-C) Individuals in the neuropathology cohort were divided in groups of no significant primary pathology (N=31), AD (N=36), PD (N=13), and others (N=8), and analyzed together with N=9 additional subjects with primary non-AD tauopathies (PSP/CBD). Data is shown for plasma P-tau217 (panel A), plaque density (panel B), and tangle density (panel C). Plasma P-tau217 was not elevated in PSP/CBD compared to subjects without significant primary pathology. AD, Alzheimer's disease; CBD, corticobasal degeneration; PSP, progressive supranuclear palsy; PD, Parkinson's disease. The central band of the boxes are medians and the boxes show inter-quartile ranges. The whiskers are defined as the smallest (largest) observation greater (less) than or equal to the first (third) quartile minus (plus) 1.5 times the inter-quartile range.",
    "diseases": "CBD, CBDbutton type=\"button\" class=\"btn btn-success btn-xs\" ng-click=\"confirmPretag(true,'protein')\" , corticobasal degeneration, neuropathology, AD, Alzheimer's disease, Parkinson's disease, PD, progressive supranuclear palsy, PSP"
  },
  {
    "caption": "Determination of the levels of mtDNA (ND1/ACTB) by qPCR of mutant cybrids transfected with MERRF mitoTev-TALE",
    "diseases": "MERRF"
  },
  {
    "caption": "mtDNA levels in wild-type sorted cells transfected with the MERRF mitoTev-TALE. Data is expressed as percentage of the Untransfected cells (%UNT)",
    "diseases": "MERRF"
  },
  {
    "caption": "RFLP analyses of high mutant cybrids transfected with the MERRF mitoTev-TALE. The sorted cells were analyzed at different times of growth by PCR/RFLP as previously described",
    "diseases": "MERRF"
  },
  {
    "caption": "Patients with colon cancer were divided into four groups based on tumor stage. mRNA expressions of Dectin-3 in tumor tissues were detected by qPCR. The box represents the 25th to 75th percentile, and the whisker plots represent the minimum and maximum percentiles. Patients with colon cancer were divided into two groups based on fungal burden in the feces. mRNA expressions of Dectin-3 was compared between these two groups.",
    "diseases": "colon cancer"
  },
  {
    "caption": "HOIP co-localizes with Htt inclusion bodies in human HD frontal cortex. Perinuclear Htt aggregates visualized by immunofluorescence (B) in human HD frontal cortex. Scale bar, 10 µm (B)",
    "diseases": "HD"
  },
  {
    "caption": "HOIP co-localizes with Htt inclusion bodies in human HD frontal cortex. Perinuclear Htt aggregates visualized by DAB immunohistochemistry (C) in human HD frontal cortex. Scale bar, 15 µm (C).",
    "diseases": "HD"
  },
  {
    "caption": "M1-linked ubiquitin co-localizes with Htt-polyQ aggregates in cultured human HD frontal cortex (C). Autofluorescent lipofuscin appears in the green channel in human brain. Scale bar, 10 µm",
    "diseases": "HD"
  },
  {
    "caption": "(G) HOIP protein levels are decreased in human HD brain. Total protein lysates from human brain (anterior cingulate cortex) analyzed by immunoblotting using antibodies against HOIP and βIII-tubulin. HOIP-positive signals were normalized to βIII-tubulin. To verify the specificity of the HOIP antibody, WT and HOIP KO HAP1 cells were analyzed in parallel on a different gel. Data are displayed as mean ± SEM with n=5 for control and n=7 for HD patients from unpaired two-tailed Student's t-tests. *p ≤ 0.05, ***p ≤ 0.001.",
    "diseases": "HD"
  },
  {
    "caption": "(A) HOIP is recruited to disease-associated protein aggregates formed by Ataxin-3-Q84, SOD1 G85R, TDP-43 Q331K or Optineurin R96L. SH-SY5Y cells co-expressing disease-associated proteins (green) and HOIP (red) were analyzed by immunocytochemistry; DAPI (blue). Scale bar, 20 µ",
    "diseases": "disease"
  },
  {
    "caption": "Linear ubiquitin accumulates at disease-associated protein aggregates under endogenous LUBAC expression. M1-linked ubiquitin (red) and disease-associated proteins (green) were analyzed by immunocytochemistry in SH-SY5Y cells using the 1E3 antibody (Millipore) (B) DAPI (blue). Scale bar, 20 µm.",
    "diseases": "disease"
  },
  {
    "caption": "Linear ubiquitin accumulates at disease-associated protein aggregates under endogenous LUBAC expression. M1-linked ubiquitin (red) and disease-associated proteins (green) were analyzed by immunocytochemistry in primary striatal neurons using the 1F11/3F5/Y102L antibody (Genentech) (C). DAPI (blue). Scale bar, 20 µm.",
    "diseases": "disease"
  },
  {
    "caption": "(D) SDS-soluble SOD G85R and TDP-43 Q331K species are modified by linear ubiquitin chains. HEK293T cells were co-transfected with disease-associated proteins and either the plasmids indicated or with control siRNA or OTULIN siRNA. 48 h after transfection cells were lysed under denaturing conditions (1% SDS), followed by immunoprecipitation of SOD G85R and TDP-43 Q331K via the HA tag (1% Triton X-100, 0.1% SDS). Immunopurified proteins were detected by Western blotting using the M1 ubiquitin-specific antibody 1E3.",
    "diseases": "disease"
  },
  {
    "caption": "Kaplan-Meier curves for overall survival (OS) in lung adenocarcinoma TCGA_LUAD (RASSF1 mRNA high/low cutoff FKPM 5.85) and squamous cell carcinoma patients TCGA_LUSC (RASSF1 mRNA high/low cutoff FKPM 6.52). Significance derived from log-rank test.",
    "diseases": "LUAD, lung adenocarcinoma, LUSC, squamous cell carcinoma"
  },
  {
    "caption": "Size of lung primary tumours measured at day 30 after lung orthotopic injection either with H1299control (n=14 mice per group; experimental groups of 6 and 8 different shading within the groups represents two independent experiments) or with H1299RASSF1A cells stably re-expressing RASSF1A, (n=12 mice per group; experimental groups of 6 and 6). The size of primary tumours was measured by MRI software ITK-SNAP. Statistical significance via 2-tailed Student's t-test. Error bars represent mean ± S.E.M.",
    "diseases": "primary tumours"
  },
  {
    "caption": "Mass-spectrometry analysis of proteins purified from extracellular matrix isolated from H1299control and H1299RASSF1A lung adenocarcinoma cell lines with summary of results. Only proteins identified with two or more peptides were taken into consideration. The resulting list of proteins was restricted to ECM proteins (n=3).",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "Kaplan Meier plots depicting prognosis in TCGA_LUAD (lung adenocarcinoma) with high and low mRNA expression of ECM proteins revealed by proteomics. Significance derived from log-rank test. Data information: Unless otherwise indicated all statistical analyses were performed using Student's t-test (2-tailed) of n=3 experiments and error bars represent the mean ± S.E.M.",
    "diseases": "LUAD, lung adenocarcinoma"
  },
  {
    "caption": "Representative images of H&E and IHC staining for P4HA2, and quantification (bars) of two independent regions of n=5 H1299control and n=3 H1299RASSF1A primary lung tumours. Scale bars 100µm. Data information: Unless otherwise indicated all statistical analyses were performed using Student's t-test (2-tailed) of n=3 experiments and error bars represent the mean ± S.E.M.",
    "diseases": "primary lung tumours"
  },
  {
    "caption": "Bar graph representing quantification of stiffness by atomic force microscopy (Young modulus) in of n=5 H1299control and n=3 H1299RASSF1A primary lung tumours on day 30. Data information: All statistical analyses were performed using Student's t-test (2-tailed) of n=3 for in vitro experiments and error bars represent the mean ± S.E.M.",
    "diseases": "primary lung tumours"
  },
  {
    "caption": "Representative topographic images of stiffness map of H1299control and H1299RASSF1A lung primary tumours provided by AFM.",
    "diseases": "lung primary tumours"
  },
  {
    "caption": "AFM images of ECM fibre organization within primary lung tumours generated by H1299control and H1299RASSF1A cells on day 30.",
    "diseases": "primary lung tumours"
  },
  {
    "caption": "SHG images of organization and quantification (bars) of collagen fractions in primary lung tumours and metastases at day 30. Scale bars 10µm. Data information: All statistical analyses were performed using Student's t-test (2-tailed) of n=3 for in vitro experiments and error bars represent the mean ± S.E.M.",
    "diseases": "metastases, primary lung tumours"
  },
  {
    "caption": "Representative H&E and quantification (bars) of picrosirius red staining of two independent regions of n=5 H1299control and n=3 H1299RASSF1A primary lung tumours. Scale bars 100µm, zoom 20µm. Data information: All statistical analyses were performed using Student's t-test (2-tailed) of n=3 for in vitro experiments and error bars represent the mean ± S.E.M.",
    "diseases": "primary lung tumours"
  },
  {
    "caption": "Representative images of H&E and immunohistochemical staining for NANOG and YAP1 in primary lung tumours, (day 17). Scale bars 100µm. Right: Graph bars represent quantification of NANOG and YAP1 staining based on strong (3+, 2+) nuclear intensity (%) for at least 2 independent regions of n=4 H1299control and n=2 H1299RASSF1A primary tumours at day 17. Data information: Statistical significance was determined by Student's t-test (2-tailed) of n=3 experiments unless otherwise stated. Error bars represent the mean ± S.E.M.",
    "diseases": "primary lung tumours, primary tumours"
  },
  {
    "caption": "Relative mRNA expression levels of NANOG, OCT4 and SOX2 in H1299control and H1299RASSF1A lung adenocarcinoma cells. Data information: Statistical significance was determined by Student's t-test (2-tailed) of n=3 experiments unless otherwise stated. Error bars represent the mean ± S.E.M.",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "Representative images of H&E and immunohistochemical staining for lung differentiation markers TTF-1 and Mucin 5B for at least 2 independent regions of n=4 H1299control and n=2 H1299RASSF1A primary tumours at day 17 with quantification (right) of TTF-1 based on nuclear intensity. Scale bars 100µm. Statistical significance was determined by Student's t-test (2-tailed). Error bars represent the mean ± S.E.M",
    "diseases": "primary tumours"
  },
  {
    "caption": "isolates.BALB/c mice and Wistar rats were immunized with various doses of PiCoVacc or control (adjuvant only as the sham group) (n=10). Serums from recovered COVID19 patients (RECOV) and non-infected people (NI) act as positive and negative controls, respectively. The antibody responses were analyzed in mice (A), humans (B) and rats (C). Top: SARS-CoV-2-specific IgG response measured by ELISA",
    "diseases": "COVID19"
  },
  {
    "caption": "B Heatmap of selected immune mediator levels in plasma samples of healthy controls, vaccinated close contacts, COVID-19 vaccine breakthrough cases, and unvaccinated COVID-19 patients with primary infection. Each color represents the relative concentration of a particular analyte. Blue and red indicate low and high concentration, respectively.",
    "diseases": "COVID-19"
  },
  {
    "caption": "(C) IVIS images showing representative tumors generated by injecting luciferase-expressing MDA-MB-468 cells (NTC, shA DVL3 or shB DVL3) in the mammary fat pad of SCID mice. Color scale (luminescent signal intensity): blue, least intense signal; red, most intense signal. (D) Quantification of luminescence changes in tumors generated by injecting luciferase-expressing MDA-MB-468 cells (NTC, shA DVL3 or shB DVL3) in the mammary fat pad of SCID mice, Average luminescence was used to measure volume of tumor; n ≥ 9. ( ",
    "diseases": "SCID"
  },
  {
    "caption": "(G) IVIS images showing representative tumors generated by injecting luciferase-expressing MCF7 cells (NTC, shA DVL3) in the mammary fat pad of SCID mice. Color scale (luminescent signal intensity): blue, least intense signal; red, most intense signal. (H) Quantification of luminescence changes in tumors generated by injecting luciferase-expressing MCF7 cells (NTC, shA DVL3) in the mammary fat pad of SCID mice. Average luminescence was used to measure volume of tumor. n=7.",
    "diseases": "SCID"
  },
  {
    "caption": "(A) Kaplan-Meier disease-specific  survival curves based on ROR1  expression levels in PDAC patients  from the TCGA database (n = 154) . Data information: Graphs are presented as mean ± s.e.m., *, p < 0.05; log-rank test (A)",
    "diseases": "PDAC"
  },
  {
    "caption": "Growth curve showing parasite growth rate (parasitemia at Day X/parasitemia at Day 1) over five days for WT and two clones of SMC3-3HA-glmS parasites in the absence or presence of glucosamine (GlcN). Glucosamine treatment was started 96 h (two IDC cycles) before Day 1 to ensure SMC3 knockdown during the days sampled Uninfected red blood cells (Blood) served as reference of background. Error bars indicate standard deviation of three technical replicates (n = 3). A two-way ANOVA with Tukey post hoc test was used for statistical analysis. No significant differences were found.",
    "diseases": "parasitemia"
  },
  {
    "caption": "Neuroblastoma PDX and SK-N-BE(2)c cells treated with IBL inhibitors at indicated concentrations for 48 hours. pAkt (at Ser473 (A) and Thr308 (B) sites) levels in LU-NB-3 and SK-N-BE(2)c cells determined by western blotting. Total Akt levels were used as loading control.",
    "diseases": "Neuroblastoma"
  },
  {
    "caption": "Neuroblastoma PDX cells treated with IBL inhibitors at indicated concentrations for 48 hours. C. p-p70S6K and p-p85S6K levels in LU-NB-3 cells determined by western blotting. Actin, p70S6K, and p85S6K levels were used as loading controls.",
    "diseases": "Neuroblastoma"
  },
  {
    "caption": "Neuroblastoma PDX and SK-N-BE(2)c cells treated with IBL inhibitors at indicated concentrations for 48 hours. F. Gap43 protein levels in LU-NB-3 and SK-N-BE(2)c cells determined by western blotting. SDHA levels were used as loading control.",
    "diseases": "Neuroblastoma"
  },
  {
    "caption": "Neuroblastoma PDX cells treated with IBL inhibitors at indicated concentrations for 48 hours. G. N-Myc levels in LU-NB-2 and LU-NB-3 cells determined by western blotting. SDHA levels were used as loading control.",
    "diseases": "Neuroblastoma"
  },
  {
    "caption": "Neuroblastoma cells were treated with indicated concentrations of IBL-302 for 48 hours A. Expression of pAkt(Ser473) in LU-NB-3 and SK-N-BE(2)c cells. Total Akt and actin were used as loading controls. B. Expression of pAkt(Thr308) in LU-NB-3 and SK-N-BE(2)c cells. Total Akt and actin were used as loading controls.",
    "diseases": "Neuroblastoma"
  },
  {
    "caption": "Neuroblastoma cells were treated with indicated concentrations of IBL-302 for 48 hours C. Brightfield photomicrographs of LU-NB-3 and SK-N-BE(2)c cells treated with 50 nM IBL-302. Scale bars represent 100 μm (LU-NB-3) or 200 μm (SK-N-BE(2)c). D. Quantification of neurite outgrowth presented as number of neurites/cell in LU-NB-3 PDX and SK-N-BE(2)c cells treated with IBL-302. For LU-NB-3 PDX cells, representative areas (n=4) were used and n=460 and n=216 cells/condition for CTRL and IBL-302, respectively, were counted. For SK-N-BE(2)c cells, representative areas (n=5 and n=7 for CTRL and IBL-302 respectively) were used and n=124 and n=260 cells/condition for CTRL and IBL-301, respectively, were counted. Statistical significance was determined by two-sided student's t-test. p=0.009 for LU-NB-3 and p=0.0003 for SK-N-BE(2)c.",
    "diseases": "Neuroblastoma"
  },
  {
    "caption": "Neuroblastoma cells were treated with indicated concentrations of IBL-302 for 48 hours E. N-Myc protein expression determined by western blotting. SDHA was used as loading control.",
    "diseases": "Neuroblastoma"
  },
  {
    "caption": "Neuroblastoma cells were treated with indicated concentrations of IBL-302 for 72 hours F. Cell viability determined by CellTiterGlo.",
    "diseases": "Neuroblastoma"
  },
  {
    "caption": "Neuroblastoma cells were treated with indicated concentrations of IBL-302 for 48 hours G. Flow cytometry analyses of Annexin V and PI stainings following treatment with 50nM IBL-302 H. Quantification of live and dead cells. Dead cells=PI positive, Live cells=PI negative. Dot plots from two independent experiments and error bars represent SEM.",
    "diseases": "Neuroblastoma"
  },
  {
    "caption": "I. Neuroblastoma SK-N-BE(2)c carrying mice (n=5 in each group) were treated with vehicle (CTRL) or 40 mg/kg IBL-302 for up to 35 days and tumor growth was followed over time. Asterisks indicate each occasion a mouse within that particular group was sacrificed.",
    "diseases": "Neuroblastoma"
  },
  {
    "caption": "E. Tumor size in individual mice from Neuroblastoma PDX carrying mice (n=5 in each group) were treated with vehicle (CTRL), low-dose (20mg/kg) IBL-302, low-dose (1mg/kg) cisplatin, or the combination of low-dose IBL-302 and low-dose cisplatin for up to 70 days. Tumor size was measured over time. Asterisks indicate each occasion a mouse within that particular group was sacrificed.",
    "diseases": "Neuroblastoma"
  },
  {
    "caption": "F. Neuroblastoma PDX carrying mice (n=5 in each group) were treated with vehicle (CTRL), low-dose (20mg/kg) IBL-302, low-dose (1mg/kg) cisplatin, or the combination of low-dose IBL-302 and low-dose cisplatin for up to 70 days. Tumor size was measured over time. Asterisks indicate each occasion a mouse within that particular group was sacrificed.",
    "diseases": "Neuroblastoma"
  },
  {
    "caption": "Levels of differential free amino acids in MERRF patients' muscle (B) by LC-MS analysis, expressed relative to CTL. In panels the dashed line indicates the Mean CTL value set at 1. In panels B data are presented as Mean ± SEM. Muscle: MERRF (n=10), CTL (n=15)",
    "diseases": "MERRF"
  },
  {
    "caption": "(H) Western blots of muscle lysates separated by denaturing SDS-PAGE and probed for OGDH, ALT2, α-actin, and GOT2 (top panel), ALT1 and GAPDH (middle panel), GOT1 and GAPDH (bottom panel), C (CTL), M (MERRF).",
    "diseases": "MERRF"
  },
  {
    "caption": "(P) Ph-4EBP1/4E-BP1 ratio and SESTRIN 2 protein levels normalized by α-actin, estimated by band densitometry, in MERRF muscle expressed relative to CTL muscle set at 1. (Q) Representative western blot of MERRF and CTL muscle lysates separated by denaturing SDS-PAGE and probed for Ph-4EBP1, 4EBP1, SESTRIN 2, and α-actin. In panel P, data are presented as Mean ± SD. MERRF (n=4), CTL (n=4). *, p<0.05 MERRF vs. CTL. Statistically significant differences between the two groups for all panels were estimated by unpaired two-tailed Student's test.",
    "diseases": "MERRF"
  },
  {
    "caption": "(N) Levels of metabolites of trans-sulfuration pathway by LC-MS analysis in MERRF muscle and plasma expressed relative to CTL muscle and plasma. α-HB, α-hydroxybutyrate; GSH, glutathione. In panel N, data are presented as Mean ± SEM. Muscle: MERRF (n=10), CTL (n=15). Plasma: MERRF (n=9), CTL (n=25). * p<0.05 MERRF vs. CTL. Statistically significant differences between the two groups for all panels were estimated by unpaired two-tailed Student's test.",
    "diseases": "MERRF"
  },
  {
    "caption": "(K, L) Levels of acylcarnitine, 3-OH acylcarnitine, fatty acid and 3-OH fatty acid in MERRF muscle (K) and plasma (L) by LC-MS analysis, expressed relative to CTL. In panels data by LC-MS analysis are presented as Mean ± SEM. In panels A and C, 50, 100, 200d: COX10 KO (n=6), CTL (n=6). *, p<0.05 COX10 KO vs. same age CTL. In panels K and L, muscle: MERRF (n=10), CTL (n=15); plasma: MERRF (n=9), CTL (n=25). *, p<0.05 MERRF vs. CTL.",
    "diseases": "MERRF"
  },
  {
    "caption": "(M) MERRF plasma levels of 4-hydroxyl-L-proline by LC-MS analysis, expressed relative to CTL value set at 1.",
    "diseases": "MERRF"
  },
  {
    "caption": "(N) PYCR1 protein levels, estimated by band densitometry normalized by GAPDH, in MERRF muscle expressed relative to CTL muscle. In panel N, data are presented as Mean ± SD. MERRF (n=4), CTL (n=4). *, p<0.05 MERRF vs. CTL. Statistically significant differences between the two groups for all panels were estimated by unpaired two-tailed Student's test.",
    "diseases": "MERRF"
  },
  {
    "caption": "(G) Levels of glucocorticoids in MERRF plasma by LC-MS analysis, expressed relative to CTL value set at 1. In panels G data are presented as Mean ± SEM. MERRF (n=9), CTL (n=25).",
    "diseases": "MERRF"
  },
  {
    "caption": "(B) RNA samples extracted from normal breast epithelial cell, MCF10A, and different subtypes of breast cancer cell lines as indicated were subjected to RT-qPCR analysis to examine the expression of circPVT1 (n = 3 biological replicates, ±s.e.m., ns: non-significant, *P < 0.05, **P < 0.01, ***P < 0.001 by two-tailed Student's t-test).",
    "diseases": "breast cancer"
  },
  {
    "caption": "K Illustration of a cohort of patients (n=15) with available primary 2D PDAC cell lines. This cohort includes the ID188 (pre-FFX (FOLFIRINOX), red) and ID211 (post-FFX, blue) lines. These lines were screened for sensitivity towards three MEKi. L 15 primary human PDAC 2D cell lines were screened for MEKi (as indicated) sensitivity. The determined AUC was variance scaled and the z-scores are depicted. The ID188 and ID211 identity is color coded.",
    "diseases": "PDAC"
  },
  {
    "caption": "The location of causal candidate LN1   is indicated as is the position of the linked TAS rs2303565  associated with ALS. The structures of transcripts indicate the exons (blue) and introns (gray with >). The color key indicates the chromatin  states as defined by ChromHMM analysis of epigenomic  data from the NIH Roadmap Epigenomics Consortium. Chromatin  states are shown for brain  tissues, neural progenitor cells (NPCs), and a variety of other tissues. Next to the color key, NCBI dbVar ID for TE, SNP  ID for TAS, genic location of TAS, TE name, and r2 value are shown. * r2 value verified by genotyping PCR. ChIP-seq peaks of transcription factors from ENCODE are shown below ChromHMM  chromatin  states.",
    "diseases": "ALS"
  },
  {
    "caption": "The location of causal candidate LN2  is indicated as is the position of the linked TAS rs11759769  associated with migraine  disorder. The structures of transcripts indicate the exons (blue) and introns (gray with >). L1MA5 indicates the position of an L1  element fixed in the genome. The color key indicates the chromatin states as defined by ChromHMM analysis of epigenomic data from the NIH Roadmap Epigenomics Consortium. Chromatin  states are shown for brain  tissues, NPCs, and a variety of other tissues. Next to the color key, NCBI dbVar ID for TE, SNP ID for TAS, genic location of TAS, TE name, and r2 value are shown. * r2 value verified by genotyping PCR.  ChIP-seq peaks of transcription factors from ENCODE are shown below ChromHMM chromatin  states and peaks for two transcription factors known for heterochromatin  formation located around the site of LN2  insertion are labeled.",
    "diseases": "migraine"
  },
  {
    "caption": "The location of causal candidate LN16  is indicated as is the position of the linked TAS rs12185268  associated with PD. The structures of transcripts indicate the exons (blue) and introns (gray with >). The color key indicates the chromatin  states as defined by ChromHMM analysis of epigenomic data from the NIH Roadmap Epigenomics Consortium. Chromatin  states are shown for brain  tissues, NPCs, and a variety of other tissues. Next to the color key, NCBI dbVar ID for TE, SNP ID for TAS, genic location of TAS, TE name, and r2 value are shown. * r2 value verified by  genotyping PCR. ChIP-seq peaks of transcription factors from ENCODE are shown below ChromHMM chromatin  states. The position of the LN16  TE is enlarged in an inset.",
    "diseases": "PD"
  },
  {
    "caption": "(F) Subcutaneous xenograft tumor volume measurements of MDA-MB-231 cells expressing CPAP-WT (red) as control or CPAPΔT (blue) in nude mice. (i) Bar graph at right shows total tumor volume reduction at day 22. (ii) Each condition used 4 mice each containing 4 xenograft tumors. Error bars, mean ± SEM with n = 16 for CPAP-WT and n = 16 for CPAPΔT. Unpaired t-test ***P < 0.0001.",
    "diseases": "tumors, tumor"
  },
  {
    "caption": "(A) Real time live imaging of NSCLC (H1975T790M) 3D spheroids with vehicle, 5µM erlotinib or 5µM CCB02. At the end of live imaging, spheroids were fixed and stained for F-actin (green). Arrow indicates invasive (vehicle-treated) and non-invasive (CCB02-treated) structures in spheroids. Scale bar, 100µm",
    "diseases": "NSCLC"
  },
  {
    "caption": "(D) Antitumor activity of CCB02 in vivo. Left: Subcutaneous xenograft tumor volume measurements of H1975T790M (30mg/kg of weight, daily) in nude mice treated with vehicle or CCB02. Right: Bar graph shows total tumor volume at day 1 and day 24 of vehicle or CCB02 treated xenograft. Error bars, mean ± SD with n = 8 for control vehicle and n = 8 for CCB02 treatment. Unpaired t-test *P < 0.01.",
    "diseases": "tumor"
  },
  {
    "caption": "(A) Representative single immunofluorescent staining for dsDNA at 6 h, 24 h, and 3 d of reperfusion after MCAO in the penumbra as well as in the sham brain. Scale bars, 5 μm.",
    "diseases": "MCAO, reperfusion"
  },
  {
    "caption": "(C) Western blot analysis of cGAS and STING using lysates prepared from the indicated tissues of mice brain following MCAO. (D) Quantitative analysis for Western blot analysis.",
    "diseases": "MCAO"
  },
  {
    "caption": "(E) Immunohistochemical staining for cGAS at 3 d of reperfusion after tMCAO in peri-ischemic area as well as in the corresponding regions of sham control brains. Scale bars, 50 μm, 20 μm in insets. (F) Quantitative analysis of cGAS immunohistochemical staining. n = 6 mice per group. **P<0.01, two-tailed unpaired Student's t test.",
    "diseases": "tMCAO, ischemic, reperfusion"
  },
  {
    "caption": "Mice received daily intraperitoneal (IP) injections of A151 (300 μg) or an equal volume of vehicle for 3 consecutive days after MCAO induction. (A) The mRNA expression levels of the cGAS and STING after MCAO were determined using qRT-PCR. n = 6 mice per group. **",
    "diseases": "MCAO"
  },
  {
    "caption": "(D) The mRNA expression levels of the AIM2 inflammasome components (AIM2, ASC, and caspase-1), effector of pyroptosis GSDMD, IL-1β, and IL-18 after MCAO were determined using qRT-PCR. n = 6 mice per group.",
    "diseases": "MCAO"
  },
  {
    "caption": "(C) Representative images of double-immunofluorescent stained for GFAP and GSDMD, for Iba-1 and GSDMD, and for NeuN and GSDMD in post-ischemic brains after tMCAO.",
    "diseases": "tMCAO, ischemic"
  },
  {
    "caption": "(D) Representative images of double-immunofluorescent stained for Iba-1 and GSDMD, for Iba-1 and caspase-1, and for Iba-1 and IL-1β of sham+vehicle, MCAO+vehicle, and MCAO+A151 groups. Scale bars, 50 μm. (E) Bar graph shows the relative immunofluorescence intensity of GSDMD, caspase-1, and IL-1β in the brains of indicated groups. n = 6 mice per group. DAPI staining: nuclei.",
    "diseases": "MCAO"
  },
  {
    "caption": "(A) Gating strategy of brain-infiltrating immune cells including CD4+ T cells (CD3+ CD4+), CD8+ T cells (CD3+CD8+), B cells (CD3-CD19+), NK cells (CD3-NK1.1+), monocyte/macrophages (CD11b+CD45highF4/80+), neutrophils (CD11b+CD45highLy6G+), and microglia (CD11b+CD45int) and their expression of IL (interleukin)-6, TNF-α (tumor necrosis factor-α), TGF-β (transforming growth factor-β), and IL-4. FMO, fluorescence minus one. (B) Quantitative analysis of the counts of brain-infiltrating leukocytes in the brains of MCAO mice receiving indicated treatment. (C) Bar graph shows counts of leukocytes subtype in the spleens of MCAO mice receiving indicated treatment. n = 6 mice per group. (D) Quantitative analysis of the microglia in the brains of MCAO mice receiving indicated treatment. n = 6 mice per group. *",
    "diseases": "MCAO"
  },
  {
    "caption": "(E) Bar graph shows percentages of microglia expressing IL-6, TNF-α, TGF-β, and IL-10 in the brains of MCAO mice receiving indicated treatment. n = 6 mice per group.",
    "diseases": "MCAO"
  },
  {
    "caption": "(F) Representative images of immunofluorescent staining for ly6G in peri-infarct areas of MCAO mice receiving indicated treatment. (G) Bar graph shows the number of ly6G+ neutrophils. n = 6 mice per group.",
    "diseases": "infarct, MCAO"
  },
  {
    "caption": "(H) Representative images of immunofluorescent staining for Iba-1 in peri-infarct areas of MCAO mice receiving indicated treatment. (I) Bar graph shows the number of Iba-1+ microglia. n = 6 mice per group.",
    "diseases": "infarct, MCAO"
  },
  {
    "caption": "(B) Neurological tests were performed to evaluate the motor, sensory, and balance functions in mice receiving A151, or vehicle at days 1, 3, 7, and 14 after MCAO. n = 10 mice per group.",
    "diseases": "MCAO"
  },
  {
    "caption": "(C) Representative TTC staining of brain sections from MCAO mice on day 3 after MCAO, the infarct area is shown in white.",
    "diseases": "infarct, MCAO"
  },
  {
    "caption": "(D) Bar graph shows percentages of infarct volume of indicated groups. n = 10 mice per group. *",
    "diseases": "infarct"
  },
  {
    "caption": "(E) Flow cytometry plots and (F) summarized results show percentages of Annexin V+ PI+ cells in the brains of MCAO mice receiving A151 or vehicle. n = 6 mice per group.",
    "diseases": "MCAO"
  },
  {
    "caption": "(F) Representative images of TTC staining of brain sections from vehicle-treated WT MCAO mice, vehicle-treated cGAS-KO mice, and A151-treated cGAS-KO mice on day 3 after tMCAO. Three representative rostrocaudal levels of TTC staining are shown. (G) Bar graph shows percentages of infarct volume of indicated group. n = 6 mice per group. (H) Bar graph shows modified Neurological Severity Score (mNSS) in vehicle-treated WT MCAO mice, vehicle-treated cGAS-KO mice, and A151-treated cGAS-KO mice n = 10 mice per group.",
    "diseases": "tMCAO, infarct, MCAO"
  },
  {
    "caption": "Kainic acid mouse model of TLE: Daily EEG recordings obtained from the epileptogenic focus starting from one month after KA injection and spanning the period from 2 days before to 7 days after AAV-pDyn delivery (2x109 gp).",
    "diseases": "TLE"
  },
  {
    "caption": "A generalized seizure is depicted in Fig. EV1 D and E: The characteristic EEG features of this model, secondary generalized seizures (bars) and HPDs (lines) were reduced in number and in duration by AAV-pDyn (red; n = 3 (from day 60); 7 (till day 30) per time-interval), but not by AAV-ΔGFP or after sham treatment (blue; n = 4 (day 90); 5 (day 30 and 60); 6 (before day 30), per time-interval). The relatively high variability of seizure frequencies and duration is typical for this model and reflects the findings in human mTLE.",
    "diseases": "seizure, seizures, mTLE"
  },
  {
    "caption": "Injection of norBNI (20 mg/kg; i.p.) results in a transient reappearance of HPDs immediately and 24 hrs after application. One week after norBNI application (washout) suppression of HPDs was re-established. Data obtained from 4 epileptic animals before (black) and after (red) AAV-pDyn delivery (2x109 gp) are depicted. *",
    "diseases": "epileptic"
  },
  {
    "caption": "EEG recordings obtained from the ipsilateral dorsal hippocampus of rats after electrical self-sustained status epilepticus (SSSE) before (black) and after (red) AAV-pDyn delivery (4x109 gp) are depicted. Spike trains with a frequency of at least 2.5 Hz induced by SSSE were markedly reduced by AAV-pDyn (n=4).",
    "diseases": "status epilepticus"
  },
  {
    "caption": "epileptic mice, which were not able to learn the Barnes maze task one month after KA (J, M), AAV-pDyn application restored spatial memory one (K) and 2 months (L) after treatment.",
    "diseases": "epileptic"
  },
  {
    "caption": "epileptic mice, which were not able to learn the Barnes maze task one month after Treatment with AAV-ΔGFP did not result in improved memory (N,O).",
    "diseases": "epileptic"
  },
  {
    "caption": "d, Volcano plot of DEGs between normal mouse intestinal tissue and adenomas (GSE65461).",
    "diseases": "adenomas"
  },
  {
    "caption": "g, Gene expression of Hspb1 in normal (N) versus adenoma (A) tissue (***P=0.0002, n=4).",
    "diseases": "adenoma"
  },
  {
    "caption": "H, RNA-ISH for Hspb1 in murine intestinal adenoma. Scalebar, 100 μm. Zoom panel, 25 μm",
    "diseases": "adenoma"
  },
  {
    "caption": "i, Relative gene expression of human HSPB1 in paired sets of normal versus adenoma tissue, (****P<0.0001, paired t-test, n=59 pairs).",
    "diseases": "adenoma"
  },
  {
    "caption": "macroscopic images of adenoma development in the distal small intestine (k)",
    "diseases": "adenoma"
  },
  {
    "caption": "boxplots for the number of adenomas per intestinal region(**P=0.0013) (l), n=8 control, n=11 treated.",
    "diseases": "adenomas"
  },
  {
    "caption": "Immunofluorescence of c-Jun (green), CD1a or CD1c or CD14 (red) and DAPI in psoriatic lesions. Shown is a representative image (Magnification 25x, Scale Bar: 100µm) with an Inset (Magnification 63x, Scale Bar: 20 µm, Deconvoluted). Arrows indicate c-Jun+ DCs. Asterisk highlights a DC with prominent c-Jun expression as shown enlarged in 2 white-framed windows (DC Marker (red) + c-Jun (green, left) or DAPI (blue, right)).",
    "diseases": "psoriatic lesions"
  },
  {
    "caption": "D-E. Representative immunofluorescence of c-Jun (green), CD1a (red), CCL2 (D) or Il23p19 (E) (white) and DAPI in psoriatic lesions. Arrows indicate triple-positive cells and an asterisk highlights a representative one that is shown enlarged in a white-framed inlet. Magnification: 40x. Scale bar: 50 µm. (n = 2 patient samples).",
    "diseases": "psoriatic lesions"
  },
  {
    "caption": "A. Immunofluorescent staining for Rab11-FIP1 in TE1 and TE2 ESCC cell lines expressing a non-targeting control shRNA or shRNA against Rab11-FIP1. Scale bar= 50 μm B. Immunofluorescent staining for f-actin in TE1 and TE2 ESCC cell lines expressing a non-targeting control shRNA or shRNA against Rab11-FIP1. Scale bar= 50 μm C. Immunofluorescent staining for E-cadherin, in TE1 and TE2 ESCC cell lines expressing a non-targeting control shRNA or shRNA against Rab11-FIP1. Scale bar= 50 μm ",
    "diseases": "ESCC"
  },
  {
    "caption": "(A) Representative tissue immunostaining of  human melanoma, colon carcinoma and colon adenoma; confocal images from serial sections (scale bars: 50μm tissues). Arrowheads point to CD31+/p-EphrinB+; CD31+/p-SHP2+; CD31+/p-Tie2+ and CD31+/Ang2+ endothelial cells.",
    "diseases": "colon adenoma, colon carcinoma, melanoma"
  },
  {
    "caption": "(B) Gene expression in tumor (black bar) and control (white bar); top panel:  melanoma  (GSE7553, primary and metastatic; tumor n=54; control  skin n=5); bottom panel: colon cancer (TCGA, primary and metastatic; tumor n=269; control n=41. **P<0.01, ****P<0.0001; P values from Mann Whitney U-test.",
    "diseases": "colon cancer, melanoma"
  },
  {
    "caption": "(C) Impact of high and low (75% quartile)  mRNA levels  on the  survival probability of patients with primary melanoma; Kaplan-Meier  analysis using TCGA primary melanoma datasets (n=103); P values from Mann Whitney U-test. (D) Impact of high and low (median)  mRNA levels on the survival probability of patients with colon cancer; Kaplan-Meier analysis using TCGA colon cancer dataset (n=262). ",
    "diseases": "colon cancer, melanoma"
  },
  {
    "caption": "(L) Hypoxic tumor identified Hypoxyprobe (green) representative of 3 SHP099-treated tumors; confocal images (scale bar: 100μm), left; quantification of hypoxic areas in control (n=3) and  SHP099-treated (n=3) tumors by ImageJ. Data information: Error bars: ± S.D.; P values from two-tailed Student's t-test; *P<0.05, **P<0.01 and ***P<0.001.",
    "diseases": "hypoxic, Hypoxic"
  },
  {
    "caption": "F-H Number of Ki67-positive (F), number of γH2AX-positive (G), and number of active caspase-3-positive (H) cells per field in the subcutaneous tumors.",
    "diseases": "tumors"
  },
  {
    "caption": "I Representative images of aberrant giant nuclei and anaphase bridges in the Trf1-downregulated subcutaneous tumors compared to the normal nuclei of control tumors.",
    "diseases": "tumors"
  },
  {
    "caption": "M-O Number of Ki67-positive (M), number of γH2AX-positive (N), and number of active caspase-3-positive (O) cells per field in the lung tumors.",
    "diseases": "tumors"
  },
  {
    "caption": "Quantification of TRF1 levels by immunofluorescence in lung tumor-derived cell line treated with DMSO, with 10 μM ETP-47228 (24 h), and with 10 μM ETP-47037 (48 h). Representative images are shown to the right.",
    "diseases": "tumor"
  },
  {
    "caption": "Quantification of γH2AX levels by immunofluorescence in lung tumor-derived cell line treated with DMSO, with ETP-47228 (24 h), and with ETP-47037 (48 h). Representative images are shown to the right.",
    "diseases": "tumor"
  },
  {
    "caption": "Number of cells showing γH2AX foci in intestine and lung tumors samples of mice treated with vehicle or with ETP-47037 for 10 days. Representative images are shown to the right (n = 4).",
    "diseases": "tumors"
  },
  {
    "caption": "G Telomere length in untreated and ETP-47037-treated lung tumor samples. Representative images are shown to the right.",
    "diseases": "tumor"
  },
  {
    "caption": "(A) Immunohistochemistry analysis of MSR1 in patient ovarian, uterus and sarcoma cancers showing tumour-associated macrophages.",
    "diseases": "sarcoma"
  },
  {
    "caption": "(B) Pull-downs of K63 polyubiquitin chains and IB analysis of five human primary cancers shows a correlation between the amount of polyubiquitylated MSR1 and JNK activation in an ovarian tumour.",
    "diseases": "ovarian tumour"
  },
  {
    "caption": "O. Blood glucose following the administration of HFD (wt + HFD, n= 10; LowOXPHOS + HFD, n= 10). T2D onset occurred on day 80 in wt and day 60 in LowOXPHOS mice.",
    "diseases": "T2D"
  },
  {
    "caption": "P. Insulin (ITT) and glucose (GTT) tolerance tests on day 60 of HFD (wt + HFD, n= 10; LowOXPHOS + HFD, n= 10). LowOXPHOS but not wt mice appeared diabetic.",
    "diseases": "diabetic"
  },
  {
    "caption": "L. Blood glucose following the administration of HFD. T2D onset occurred on day 90 in wt and LowOXPHOS mice treated with edaravone. Data information: H-L: wt + HFD, n= 5; LowOXPHOS + HFD n= 4; wt + HFD + edaravone, n= 10; LowOXPHOS + HFD + edaravone n= 9. Bars are the mean ± s.e.m. of the indicated (n) mice/genotype. *p <0.05 when compared to wt by ANOVA and Student's t-test.",
    "diseases": "T2D"
  },
  {
    "caption": "G. Survival curves for  bone marrow transplanted sepsis  models induced by  E. coli peritoneal  infection within 7 days (n=4 for each group). Data information: Data are presented as percentage G) N represents biological replicates. P values were determined by log-rank test G) *P < 0.05; **P < 0.01; ***P < 0.001; n.s., not significant.",
    "diseases": "sepsis"
  },
  {
    "caption": "C. Activation of Spns2/S1P  signaling and suppression of the lactate-ROS  axis promoted the survival of Spns2-/- sepsis  models induced by heat-killed E. coli through the alleviation of hyerinflammation  (n=5 for Spns2-/- control group; n=4 for each treatment group). Data information: Data are presented as mean ± s.e.m. N represents biological replicates. P values were determined by unpaired t-test. **P < 0.01; ***P < 0.001.",
    "diseases": "sepsis"
  },
  {
    "caption": "Cells were plated, treated or not with K18-ATTO 594 fibrils at 1 μM (time 0) and placed into the IncuCyte incubator for six hours and next kept in culture for an additional 60 hours after medium change. (F) Monitoring the conversion of RD-YFP-expressing SH-SY5Y cells into inclusion-containing cells over a 70-hour period upon treatment with a cortex crude extracts from a AD-deceased patient. , the scatter plot shows means of 2 independent experiments ±SD for the green curve. IncuCyte (20x objective) was set to acquire images every 30 minutes, phase-contrast and green channel (Excitation 440-480 nm, 400 ms) were acquired (9 images/well). Analysis was performed with IncuCyte software to give the relative proportion of cells being converted to inclusion-containing cells (the end point of treated cells was arbitrarily set at 100%, black curve: non-treated cells, green curve: treated cells).",
    "diseases": "AD"
  },
  {
    "caption": "(D) RD-YFP SH cells were challenged with AD-derived brain extracts, trypsinized and replated 3 days later for an additional 24h before fixation, saponin-permeabilization and staining with antibody recognizing p62 or LAMP1 (in red). Images are confocal pictures (63x, zoom 1.6, px size = 60 nm, slice of 0.43 μm) representative of two independent experiments. Insets are threefold enlargements of the boxed regions; white arrows point to co-labelling; scale bars are 10 μm, 2 μm in the insets.",
    "diseases": "AD"
  },
  {
    "caption": "(E) Quantification of colocalization of RD-YFP material with p62-positive structures (left graph) or LAMP1-positive vesicles (right) upon AD extract-induced aggregation. Confocal pictures were analyzed in 3D with Imaris software from pictures obtained as in D, the graphs represent the mean percentage (+ SEM) of green material overlapping with p62 or LAMP1: aggregates if cells have been converted (agg) or soluble material otherwise. Below each graph, the corresponding Pearson correlation coefficient (PCC) is indicated. The number of cells analyzed over 2 independent experiments is 21 (sol), 27 (agg) for p62, 12 (sol), 17 (agg) for LAMP1.",
    "diseases": "AD"
  },
  {
    "caption": "(A, B) AP-2α levels normalized to GAPDH are significantly decreased in lysates of iPSC-derived neurons from late-onset AD patients carrying the TREM2 p.R47H (AD-TREM2-2 and AD-TREM2-4) variant compared to healthy controls (CON8 and CON9) set to 100% (ADAP-2α: 52.42±8.04%, p=0.020, N=3 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by one-sample Student's t‐test n.s.-non-significant.* indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "diseases": "AD"
  },
  {
    "caption": "C-E. Sections from a tumor collected from a 64 week-old HPV8/wt mouse (C,D) or from non-tumorigenic skin of 5 week-old HPV8/wt mice (E) stained with an anti-activin A antibody and counterstained with hematoxylin. E: Epidermis, D: Dermis, HF: Hair follicle. (D) Shows a higher magnification of the boxed area in (C). Scale bars: 200μm (C) and 100μm (D,E).",
    "diseases": "tumor"
  },
  {
    "caption": "(A) Representative micrographs  of human skin  sections stained with hematoxylin-eosin (H&E) (left) and anti-IL-38 antibody (right) from normal patients  (n = 11) and tumors of cSCC patients  (n = 13). Scale bars represent 100 μm. The graph shows the quantification of mean  IL-38 expression   per high-powered field in tissues. (B) Relative expression   of  IL-38 in human  normal tissues (n = 9) and cSCC  (n = 18) were analyzed using Geo Datasets (GSE98767). Error bars represent the mean ± SD. All data are biological replicates. *p < 0.05; **p < 0.01; ***p < 0.001; p values were calculated using Student's t test.",
    "diseases": "cSCC"
  },
  {
    "caption": "(C and D) The  dorsal hair of normal C57/BL6 mice  were shaved and treated with DMBA/TPA  twice a week for 32 weeks to induce skin  tumors. (C) Representative micrographs   of mouse normal skin  (n = 6) and tumor (n = 6) sections stained  with anti-IL-38  antibody. The graph shows the quantification of mean  IL-38 expression   per high-powered field in tissues. Scale bars represent 100 μm. (D) Relative expression   levels of Il-38 in normal skin  (n = 5) and tumors (n = 5) of mice  were quantified using qPCR. Error bars represent the mean ± SD. All data are biological replicates. *p < 0.05; **p < 0.01; ***p < 0.001; p values were calculated using Student's t test.",
    "diseases": "skin  tumors"
  },
  {
    "caption": "(A The  dorsal hair  of normal C57/BL6 mice  were shaved and treated with DMBA/TPA  twice a week for 3 weeks to induce the skin inflammation. (A) Representative micrograph  sections stained  with hematoxylin-eosin  (H&E) from the skin of Il-38f/f (n = 5) and  K14Cre/+-Il-38f/f mice (n = 5) Scale bars represent 100 μm. The graph shows average epidermal  thickness.",
    "diseases": "inflammation"
  },
  {
    "caption": "B) The dorsal hair  of normal C57/BL6 mice  were shaved and treated with DMBA/TPA  twice a week for 3 weeks to induce the skin inflammation. (B) Representative micrograph  sections stained  with anti-Ki67  antibody from the skin  of Il-38f/f (n = 6) and K14Cre/+-Il-38f/f mice  (n = 6). Scale bars represent 100 μm. The graph shows average numbers of Ki67+ cells per high-powered field.",
    "diseases": "inflammation"
  },
  {
    "caption": "Geometric mean-centered, hierarchical cluster heat map from microarray data. 1077 annotated lncRNAs (p<0.05) were represented in liver CSC (CD13+CD133+) compared with non-CSC (CD13-CD133-) cells sorted from three HCC primary cells of three patients. Top ten upregulated lncRNAs in CSCs are shown.",
    "diseases": "HCC"
  },
  {
    "caption": "In situ hybridization of HAND2-AS1 in HCC tumor tissues. HAND2-AS1 staining is shown in tumor tissues (left panel). Quantitation of HAND2-AS1+ cells in liver tissues was examined in 10 high-power fields (HPF) of sections from ten different HCC patients (right panel). Results are shown as means ± SEM. Scale bar, 100 μm.",
    "diseases": "HCC"
  },
  {
    "caption": "HAND2-AS1 knockout causes a declined oncosphere-forming capacity in HCC cells. The right panel represents statistical results as means ± SD (n=3 per group). Overexpression of HAND2-AS1 (oelnc) rescued the sphere formation reduced by HAND2-AS1 deletion. Scale bar, 100 μm.",
    "diseases": "HCC"
  },
  {
    "caption": "Limiting diluted HAND2-AS1 depletion or Ctrl HCC cells were subcutaneously implanted into BALB/c nude mice. n=12 for each group.",
    "diseases": "HCC"
  },
  {
    "caption": "Estimated frequency of TICs in HAND2-AS1 deficiency and control HCC cells during serial transplantations. Grey area indicates the 95% CI.",
    "diseases": "HCC"
  },
  {
    "caption": "Estimated frequency of TICs in HAND2-AS1 deficiency and control HCC cells during serial transplantations. Grey area indicates the 95% CI.",
    "diseases": "HCC"
  },
  {
    "caption": "HAND2-AS1 expression levels (normalized to 18S rRNA) in livers from BALB/c nude mice subcutaneously transplanted xenograft primary HCC cells then intraperitoneally administered 25 mg kg−1 ASOs on days 15, 20, 25, 30 and 35 (n = 5 per group). Three ASOs (1, 2, 3) against HAND2-AS1 were used to treat mice and showed similar depletion effects. Results are shown as means ± SD. n=6 mice per group.",
    "diseases": "HCC"
  },
  {
    "caption": "Mice were killed at the 40th day after HCC cell injection, and the tumors were excised and weighed. Representative tumors are shown. Scale bar, 1 cm. Statistical data are shown as means ± SD (n = 6 mice per group) (right panel).",
    "diseases": "HCC"
  },
  {
    "caption": "Estimated frequency of TICs in HAND2-AS1 overexpression and control HCC cells during serial transplantations.",
    "diseases": "HCC"
  },
  {
    "caption": "HAND2-AS1 was visualized by RNA FISH, followed by immunofluorescence staining of INO80 in HCC primary oncosphere cells. Scale bar, 100 μm.",
    "diseases": "HCC"
  },
  {
    "caption": "Heatmap results for HAND2-AS1 or INO80 deficiency in HCC cells.",
    "diseases": "HCC"
  },
  {
    "caption": "Based on GSEA results, significantly changed genes due to depletion of HAND2-AS1 and INO80 were attributed to the BMP signaling in HCC primary cells. NES, normalized enrichment score; FWER, familywise error rate.",
    "diseases": "HCC"
  },
  {
    "caption": "HAND2-AS1 deletion in HCC cells decreases BMPR1A expression and inactivates BMP signaling.",
    "diseases": "HCC"
  },
  {
    "caption": "BMPR1A is highly expressed in HCC tumor tissues provided by Wang's cohort (GSE14520).",
    "diseases": "HCC"
  },
  {
    "caption": "Kaplan-Meier analyses of liver cancer outcomes in the cancer genome atlas (TCGA). P value for Kaplan-Meier curves was determined using a Mantel-Cox log-rank test.",
    "diseases": "liver cancer"
  },
  {
    "caption": "Representative immunohistochemistry staining of BMPR1A was detected in HCC samples. Scale bar, 100 μm.",
    "diseases": "HCC"
  },
  {
    "caption": "BMPR1A overexpression rescues sphere formation ability reduced by HAND2-AS1 depletion in HCC samples. Representative sphere formation is shown on the left panel. Scale bar, 100 μm. Percentages of sphere-forming cells were calculated as means ± SD (right panel). n=4.",
    "diseases": "HCC"
  },
  {
    "caption": "Tumors were excised from livers of PDX liver cancer models. Scale bar, 0.5 cm.",
    "diseases": "liver cancer"
  },
  {
    "caption": "Representative H&E staining in liver sections from tumor-bearing mice treated with ASO1 and siBMPR1A in orthotopic transplants of tumors from HCC#50 and HCC#51. Scale bar, 100 μm.",
    "diseases": "HCC"
  },
  {
    "caption": "Northern blotting of HAND2-AS1 and immunobloting of BMPR1A in tumors from PDX HCC#50 after treatment.",
    "diseases": "HCC"
  },
  {
    "caption": "Kaplan-Meier survival analysis of B-NSG mice orthotopically transplanted with PDXs HCC#50 (I) and HCC#51 (J). Treatment with ASO1 combined siBMPR1A causes synergistic therapeutic effect than each treatment alone (n = 10 per group). P value for Kaplan-Meier curves was determined using a Mantel-Cox log-rank test.",
    "diseases": "HCC"
  },
  {
    "caption": "(L-N) B16N parental, O1C44, and O1DN cells were subcutaneously injected in the right flank of syngeneic C57Bl6 mice revealing the presence of O1C44 (but not B16N-WT) cells in abdominal organs and within the peritoneal wall (L). (M) H&E stains of the peritoneal wall revealing the presence of melanoma cells in the peritoneal wall. (N) Quantitative measurement of degree of invasion within and through the peritoneal wall. Data was analyzed using the Kruskal-Wallis Rank Sum test (P < 0.001). Within all panels, differences established through multiple comparisons are labeled as *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.",
    "diseases": "melanoma"
  },
  {
    "caption": "WM983 and UACC257 human melanoma cells were transfected with Perfringolysin O (PFO)-mCherry D4H cholesterol sensor and plated on glass coverslips. Cells were exposed to UV (0 or 175 J/m2) and incubated for 0, 2 or 5 weeks as indicated. (H) Representative cell images. (I) Fluorescence intensity from cells analyzed in (H) was measured and quantified using LASX analysis software (N≥8 biological replicates); data displayed are mean±SEM. Data was analyzed using 1-way ANOVA with multiple comparisons (WM983, p < 0.001; UACC257 p > 0.05). **p<0.01, ***p<0.001, ****p<0.0001.",
    "diseases": "melanoma"
  },
  {
    "caption": "Patient surgical explants were received from the biosample repository of FCCC. Cells were isolated from tumors using 50 μM Medicons and the Medimachine system and grown for 3 days before experimentation to eliminate non-melanoma cells. (A-B) Plated control or UV irradiated (175J/m2) cells were then incubated overnight on glass coverslips prior to Fura2 loading and administration of Tg in Ca2+-free media for 15 minutes. (A) Representative examples of SOCE responses in patient samples following the addition of Ca2+ (1 mM). Each trace represents 5 to 10 individual cells; solid line represents the mean and the dotted line represents SEM. (B) Each dot represents SOCE in cells obtained from a different patient sample (n=20; data displayed as mean±SEM). The effect of UV on SOCE was determined by one way ANOVA (p > 0.05). (C) Comparison of SOCE in cells collected from both primary tumors and metastatic lymph nodes from the same patient (from patients analyzed in panels A, B).",
    "diseases": "melanoma, metastatic"
  },
  {
    "caption": "(A) Lung cancer cells PC-9, prostate cancer cells 22RV1, bladder cancer cells UMUC3, breast cancer cells MCF-7, colonic adenoma-derived non-cancerous cells AA/C1 (aka C1) and AA/C1/SB (aka SB), or cancerous cells AA/C1/SB/10C (aka 10C) were incubated with wild-type F. nucleatum 12230 (Fn), the fadA-deletion mutant US1 (US1), or E. coli DH5α (E. coli) at multiplicity of infection (MOI) of 1,000:1. Cells numbers are mean values ± SEM. The experiment was performed in triplicates and repeated three times. **p<0.01, ***p<0.001, compared to untreated controls; #p<0.05, ### p<0.001, compared to US1-treated cells (two-way ANOVA).",
    "diseases": "colonic adenoma, breast cancer, cancerous, Lung cancer, bladder cancer"
  },
  {
    "caption": "(B) Attachment (left panel) and invasion (right panel) of wild-type F. nucleatum 12230 (Fn) to the non-cancerous SB cells, either untreated or transfected with antisense or sense ANXA1, and to the cancerous 10C cells, either untreated or transfected with control or ANXA1- or CDH1-specific siRNA or both (MOI 50:1). F. nucleatum attachment and invasion to the untreated SB cells were designated as 100%, respectively; all other values were expressed as relative to those obtained with untreated SB. Data are mean values ± SEM. The experiment was performed in triplicates and repeated four times. *p<0.05, **p<0.01 and ***p<0.001 (one-way ANOVA).",
    "diseases": "cancerous"
  },
  {
    "caption": "Relationship between ANXA1 mRNA expression levels and disease-free survival (DFS) in colon cancer patients. The relationship between ANXA1 mRNA expression levels and DFS was investigated in a database of 466 primary colon carcinomas, assembled by pooling four independent gene-expression array datasets from the NCBI-GEO online repository (GSE14333, GSE17538, GSE31595, GSE37892) The association between ANXA1 expression levels and DFS was tested using Kaplan-Meier survival curves, after patient stratification in groups with high, medium and low ANXA1 expression, using three different methods: (A) based on the median of ANXA1 mRNA expression levels (high 50% vs. low 50%); (B) based on the quartile distribution of ANXA1 mRNA expression levels (high 25% vs. middle 50% vs. low 25%); and (C) based on ANXA1 mRNA expression thresholds calculated using the StepMiner algorithm (low vs. high) Overall, high ANXA1 mRNA expression levels were associated with a statistically significant reduction in DFS (p<0.001, log-rank test), irrespective of the method used for the stratification. Differences in ANXA1 mRNA expression levels did not appear to correlate with differences in each tumor's relative content of epithelial cells in the analyzed biospecimens (i.e. tumor cell density) as revealed by the lack of visual correlations with the epithelial cell marker Desmoplakin (DSP).",
    "diseases": "colon cancer, primary colon carcinomas, tumor, tumor's"
  },
  {
    "caption": "(A) Real-time qPCR analysis of ANXA1 expression using mRNA extracted from the non-cancerous SB, cancerous 10C, and human CRC cell lines HCT116, DLD1 and RKO, each grown to 50% or 100% confluency. All results were normalized to the ANXA1 mRNA levels in SB cells of 100% confluency, which was designated as 1. Data are mean values ± SEM. The experiment was performed in triplicates and repeated twice. **p<0.01 and ***p<0.001 (student's t-test).",
    "diseases": "cancerous, CRC"
  },
  {
    "caption": "(C) Cell proliferation assay of adenoma-derived non-cancerous SB and cancerous 10C and human CRC cell lines HCT116, DLD1, SW480, HT29 and RKO either untreated (black lines) or following treatment with control siRNA (gray lines) or ANXA1-specific siRNA (green lines). Data are mean values ± SEM. The experiment was performed in triplicates and repeated three times. *p<0.05, ** p<0.01 and *** p<0.001, compared to the untreated cells (two-way ANOVA).",
    "diseases": "adenoma, cancerous, CRC"
  },
  {
    "caption": "(E) Xenografted tumor growth in nude mice following subcutaneous and bilateral inoculation of HCT116 cells transfected with control siRNA or ANXA1-specific siRNA. The tumor volumes were measured after 7 days post injection (left panel, n=4). For each mouse, the tumor resulting from ANXA1-specific siRNA treated cells was normalized to that from control siRNA-treated cells, which was designated 100%. The line represents the average. *p<0.05 (paired t-test). The individual tumor pairs are shown on the right panel: top, tumors arising from control siRNA treated cells; bottom, tumors arising from ANXA1-specific siRNA treated cells.",
    "diseases": "tumor, tumors"
  },
  {
    "caption": "(A) Colorectal tumors generated in Apcmin/+ mice following treatment with PBS, E. coli DH5α (E. coli), fadA-deletion mutant US1 (US1) or F. nucleatum 12230 (Fn). Each symbol represents one mouse. Horizontal lines represent mean values. Representative tumors formed in the mouse colon are shown on the right, pointed by blue arrows on the right. *p<0.05, **p<0.01 (one-way ANOVA).",
    "diseases": "Colorectal tumors, tumors"
  },
  {
    "caption": "(B) ANXA1 mRNA levels in Apcmin/+ mouse colonic tumors and normal colonic tissues as measured by real-time qPCR. Each symbol represents one mouse. Horizontal lines represent mean values. *p<0.05, **p<0.01 (two-way ANOVA).",
    "diseases": "colonic tumors"
  },
  {
    "caption": "(C) Positive correlation between fadA gene copy numbers (x-axis) and ANXA1 mRNA levels (y- axis) in F. nucleatum-induced Apcmin/+ mouse colonic tumors (n=34; Pearson's correlation). Each dot represents the average of qPCR results performed in duplicates",
    "diseases": "colonic tumors"
  },
  {
    "caption": "(D) Abundance of fadA in the paired normal and adenocarcinoma tissues from human CRC patients (n=18) expressed as ratio of fadA over total 16S rRNA genes determined by qPCR. Each symbol shows the average of duplicate qPCR results from one patient. Horizontal lines represent mean values. **p<0.01 (paired t-test).",
    "diseases": "adenocarcinoma, CRC"
  },
  {
    "caption": "(E) ANXA1 mRNA levels in paired normal and adenocarcinoma tissues from CRC patients (n=18). Each symbol shows the average of duplicate qPCR results from one patient. Horizontal lines represent mean values. **p<0.01 (paired t-test).",
    "diseases": "adenocarcinoma, CRC"
  },
  {
    "caption": "(F) Positive correlation between fadA gene copy numbers (x-axis) and ANXA1 mRNA levels (y-axis) in human colorectal adenocarcinoma tissues (n=18; Pearson's correlation). Each dot represents the average of qPCR results performed in duplicates.",
    "diseases": "adenocarcinoma, colorectal"
  },
  {
    "caption": "(G) Confocal microscopy analysis of paired normal and carcinoma tissues from two colon cancer patients. The frozen sections were incubated with rabbit anti-AnnexinA1 polyclonal antibodies and 5G11 mouse anti-FadA monoclonal antibodies. The slides were then stained with Alexa Fluor®680-conjugated donkey anti-rabbit and Alexa Fluor®555-conjugated goat anti-mouse, washed, and covered in mounting medium containing DAPI. The scanning confocal microscopy mages were taken with a Nikon Ti Eclipse inverted microscope at 200x magnification for the normal tissues and 400x for the carcinomas. Scale bar, 50 μm. Co-localization of FadA (red) and Annexin A1 (green) was observed in carcinomas but not in the paired normal tissues.",
    "diseases": "carcinoma, carcinomas, colon cancer"
  },
  {
    "caption": "(C) Real-time qPCR analysis of CCND1 expression using mRNA extracted from the cancerous 10C, and human CRC cells HCT116 and RKO, each grown to 50% or 100% confluency. Data are mean values ± SEM. The experiment was performed in triplicates and repeated twice. *p<0.05, ***p<0.001 (student's t-test).",
    "diseases": "cancerous, CRC"
  },
  {
    "caption": "B. Similar experiment using TPO-independent TF-1 TpoR CALRdel61 cells. C. Similar experiment using TPO-independent  TF-1 TpoR CALRdel52 cells at 8 hours. D. Similar experiment using PBMNCs from CALRdel52 PMF  primary cells at 8 hours. Additionally, cells were treated with 280 nM of ruxolitinib as a positive control.",
    "diseases": "PMF"
  },
  {
    "caption": "B. Graph showing the decreased fold change of CD41+CD61+  megakaryocytes cultured in  4D7  compared to IgG. FACS-sorted CD34+ from myelofibrosis patients with  CALR  or JAK2  mutation were cultured over 12 days without TPO in the presence of  SCF, IL-6  and IL-9. Black columns show JAK2V617F mutation positive samples (n= 4 technical replicates of samples from different patients). Data information: Unpaired students t-test used to determine statistical significance Bars represent standard deviations *, P = 0.05 - 0.01, **, P = 0.01 - 0.001, ***, P = 0.001 - 0.0001, ****, P <0.0001, n.s, not significant.",
    "diseases": "myelofibrosis"
  },
  {
    "caption": "C. Number of CD41+ megakaryocytes  derived from isolated  CD34+ progenitors from myelofibrosis patients. Number of  CD41/CD61+ cells counted on day 12 using  trypan blue  exclusion (n=1 technical replicate). D. Summary of fold change reduction of  CD41/CD61+ megakaryocytes by 4D7 in all tested CALR  mutated patient  samples compared to CALR wild type, normalised to IgG (n=11 samples from different patients, with 4 technical replicates per sample). Data information: Bars represent standard error of means Unpaired students t-test used to determine statistical significance *, P = 0.05 - 0.01, **, P = 0.01 - 0.001, ***, P = 0.001 - 0.0001, ****, P <0.0001, n.s, not significant.",
    "diseases": "myelofibrosis"
  },
  {
    "caption": "E Number of  CD41+ megakaryocyte  colonies from patient  samples after  4D7  treatment. CD34+ from  patients with myelofibrosis  with  CALRdel52 or CALRins5 were plated on  collagen-based matrix in presence of 20 µg/mL  4D7  or IgG control (n=3 biological replicates). Data information: Unpaired students t-test used to determine statistical significance Bars represent standard deviations *, P = 0.05 - 0.01, **, P = 0.01 - 0.001, ***, P = 0.001 - 0.0001, ****, P <0.0001, n.s, not significant.",
    "diseases": "myelofibrosis"
  },
  {
    "caption": "F. Kaplan-Meier survival curve of TF-1 TpoR CALRdel61 chloroma mice  treated with  4D7 or IgG until humane killing due to tumour diameter > 30 mm or ulceration. (n=3  mice  per treatment) G. Kaplan-Meier survival curve of NSG mice engrafted  with  ruxolitinib-resistant TF-1 TpoR CALRdel61 treated with 12.5 mg/kg  4D7  or IgG twice weekly (n=5 and 6 mice  for IgG and   4D7 respectively). Data information For all  survival curves  the log-rank Mantel-Cox test P value is shown.",
    "diseases": "chloroma"
  },
  {
    "caption": "A. Representative images of immunofluorescence of α-smooth muscle actin (α-SMA), pan Cytokeratin, Pan-hMENA, hMENA11a and E-cadherin expression in CAFs and autologous cancer cells (Ep-PDAC) obtained from enzymatically digested primary PDAC tissue of patient #36. Nuclei were stained with 4′,6-diamidino-2-phenylindole (DAPI). Scale bar: 20 μm.",
    "diseases": "PDAC"
  },
  {
    "caption": "B. Representative immunoblot (top) of hMENA/hMENA∆v6 expression levels (detected by Pan-hMENA mAb and by the specific anti-hMENAΔv6 antibody) in normal fibroblasts derived from transplant donor (P-NF), pancreatic serous cystadenoma #71 and cancer associated fibroblasts (n=10) obtained from primary PDAC tissues. Densitometry quantified data (bottom) of hMENA∆v6 expression. Quantification of P#110 is relative to the sample shown in the WB on the left. ",
    "diseases": "PDAC, pancreatic serous cystadenoma"
  },
  {
    "caption": "C. Representative immunoblot (top) of hMENA/hMENA∆v6 expression levels (detected by Pan-hMENA mAb and by the specific anti-hMENAΔv6 antibody) in normal lung fibroblasts (L-NF), cancer associated fibroblasts obtained from NSCLC tissues (n=4) and normal dermal fibroblasts (HNF). Densitometry quantified data (bottom) of hMENA∆v6 expression.",
    "diseases": "NSCLC"
  },
  {
    "caption": "A. Representative images of immunofluorescence of Pan-hMENA (yellow) and α-SMA (red) in the primary PDAC tissue of patient #138 from whom high hMENA∆v6 CAFs were obtained. Nuclei were stained with 4′,6-diamidino-2-phenylindole (DAPI). Scale bar: 50 μm. The inset of the dashed area is provided on the right as a zoomed-in and cropped fluorescence image. Scale bar: 20 μm. αSMA‑positive CAFs are also positive for Pan-hMENA (arrow).",
    "diseases": "PDAC"
  },
  {
    "caption": "B. Representative images of immunofluorescence of Pan-hMENA (yellow) and α-SMA (red) in NSCLC case #484 from whom high hMENA∆v6 CAFs were obtained. Nuclei were stained with 4′,6-diamidino-2-phenylindole (DAPI). Scale bar: 50 μm. The inset of the dashed area is provided on the right as a zoomed-in and cropped fluorescence image. Scale bar: 20 μm. As in A, α-SMA signal is evident in stromal cells which are also positive for Pan-hMENA (arrow).",
    "diseases": "NSCLC"
  },
  {
    "caption": "E. Boxplots showing the mRNA expression of GAS6 in normal lung fibroblasts (white) (n=15) versus primary NSCLC fibroblasts (light blue) (n=15) (GSE22862 data set). In each boxplot the median value (horizontal line), 25th-75th percentiles (box outline), and highest and lowest values within 1.5x of the inter-quartile range (vertical line) are shown. Statistical significance was calculated by Mann-Whitney U-test (two-sided) (P=0.0208).",
    "diseases": "NSCLC"
  },
  {
    "caption": "A. Overall survival (OS) curves in Pancreatic Adenocarcinoma patients (PDAC) (n=172) from The Cancer Genome Atlas (TCGA), showed that combined expression of AXL, GAS6 and ENAH (hMENA), is a prognostic signature in PDAC.",
    "diseases": "Pancreatic Adenocarcinoma, PDAC"
  },
  {
    "caption": "B. Overall survival (OS) curves in Lung Squamous cancer patients (LUSC) (n=501) from The Cancer Genome Atlas (TCGA), showed that combined expression of AXL, GAS6 and ENAH (hMENA), is a prognostic signature in LUSC.",
    "diseases": "Lung Squamous cancer, LUSC"
  },
  {
    "caption": "Quantitative expression of Lif mRNA in the colon of SPF mice treated with or without antibiotics (Abx) at the indicated time points during colitis induction (n=3 per group).",
    "diseases": "colitis"
  },
  {
    "caption": "Quantitative expression of Lif mRNA in LPLs and IECs from mice treated with or without Abx at the indicated time points during colitis induction (n=3 per group).",
    "diseases": "colitis"
  },
  {
    "caption": "wild-type (WT) (n=6) or Stat4 knockout(Stat4-KO) (n=6) mice receiving intraperitoneal injection of PBS or LIF during challenge with 3% DSS. Macroscopic changes in the colon of the mice on day 10 of colitis induction Comparison of the colon length in the mice on day 10 of colitis induction",
    "diseases": "colitis"
  },
  {
    "caption": "wild-type (WT) (n=6) or Stat4 knockout(Stat4-KO) (n=6) mice receiving intraperitoneal injection of PBS or LIF during challenge with 3% DSS. DAI (stool consistency and bleeding score) of colitis mice treated",
    "diseases": "colitis"
  },
  {
    "caption": "wild-type (WT) (n=6) or Stat4 knockout(Stat4-KO) (n=6) mice receiving intraperitoneal injection of PBS or LIF during challenge with 3% DSS. H&E histology of representative colons from colitis mice. Scale bar, 20μm.",
    "diseases": "colitis"
  },
  {
    "caption": "Rag1-/- (n=6) mice transferred with CD45RBhi CD4+ T cells and intraperitoneally injected with PBS or LIF for 8 weeks. H&E histology of representative mouse colons on day 54 of colitis induction",
    "diseases": "colitis"
  },
  {
    "caption": "Colons obtained from WT or Stat4-KO mice on day10 of the colitis model induced as in Figure 2A were immunostained with an antibody against phosphorylated STAT4. Scale bar, 50μm.",
    "diseases": "colitis"
  },
  {
    "caption": "Immunoblot analysis of STAT4 phosphorylation in spleen tissue from colitis mice.",
    "diseases": "colitis"
  },
  {
    "caption": "FACS staining of LPLs isolated on day10 from the colon of WT or Stat4-KO colitis mice receiving PBS or LIF (n=4 per group). The percentage of IL-17A+ and/or IFNγ+ CD4+ T cells in vivo was analyzed.",
    "diseases": "colitis"
  },
  {
    "caption": "Quantitative expression of Il17a mRNA in MLNs and LNs from colitis mice treated",
    "diseases": "colitis"
  },
  {
    "caption": "Quantitative mRNA expression analysis of the indicated genes in LPLs from colitis mice (n=3 per group).",
    "diseases": "colitis"
  },
  {
    "caption": "Quantitative mRNA expression analysis of the indicated genes in LPLs from colitis mice (n=3 per group).",
    "diseases": "colitis"
  },
  {
    "caption": "Ki67 and cleaved caspase3 staining of representative colons obtained from mice on day10 of colitis induction as described in Figure 2A. The number of proliferating cells per crypt in (A) (upper panel) or apoptotic cells per field in (B) was determined (n=5 per group, 5 crypts were counted per mouse). Scale bar, 50μm.",
    "diseases": "colitis"
  },
  {
    "caption": "Quantitative mRNA expression analysis of the indicated genes in colon tissues obtained from WT or Stat4-KO colitis mice treated",
    "diseases": "colitis"
  },
  {
    "caption": "16S rRNA sequencing analyses of the Proteobacteria distribution in feces from WT or Stat4-KO colitis mice. (n=5 per group).",
    "diseases": "colitis"
  },
  {
    "caption": "qPCR of the 16S rRNA genes of microbes in the phylum Proteobacteria, family Enterobacteriaceae, and genera Escherichia-Shigella in the feces of the indicated mice on day0 and day10 (n=6 per group) of colitis induction.",
    "diseases": "colitis"
  },
  {
    "caption": "E, F Osteoarthritis severity assessed using (E) OARSI scoring system 10 weeks after MLI; GFP (n= 7), GCP-2 (n=8) and GCP-2-T (n=7); p values were determined by fitting a generalized linear model followed by comparison of the estimated marginal means. F representative image (Safranin O staining) for each treatment; arrows indicate the tidemark;",
    "diseases": "MLI, Osteoarthritis"
  },
  {
    "caption": "G Quantification of osteophytes area; GFP (n= 7), GCP-2 (n=7) and GCP-2-T (n=8); H Representative images with osteophyte highlighted I Osteophyte maturity score (n=7); p values were determined by fitting a generalized linear model followed by pairwise comparison of the estimated marginal means.",
    "diseases": "osteophyte, Osteophyte, osteophytes"
  },
  {
    "caption": "(A) Kaplan-Meier  estimate of overall survival of patients diagnosed with primary melanoma stratified by  CCN4  transcript abundance, with patients at risk tabulated below graph, Original data obtained from SKCM arm of TCGA and stratified based on CCN4 mRNA expression (CCN4 high/positive > 1 FPKM: blue, CCN4 low/negative < 1 FPKM: red). P-value calculated using the Peto & Peto modified Gehan-Wilcoxon test.",
    "diseases": "primary melanoma, SKCM"
  },
  {
    "caption": "(B) The proportion of CCN4  positive  melanoma cells  obtained from patients with melanoma obtained prior to treatment (o, n = 15) and from patients that did not respond to immune checkpoint blockade (x, n = 10). Values shown as the proportion of CCN4  positive  melanoma cells  of the sample ± SE of the sample proportion, given a binomial distribution. A binomial test assessed significance between the proportion of CCN4 positive cells in the sample relative to a null proportion of 1% or less CCN4  positive melanoma cells. Samples with significantly enriched CCN4 positive cells are indicated in red.",
    "diseases": "melanoma"
  },
  {
    "caption": "(g, h). Reduction of Drp1S616 phosphorylation in dermal fibroblasts derived from PD patients with PINK1 mutations. Lysates of cells derived from three unrelated normal control individuals (Control, C) and four familial PD patients with PINK1 mutations (PINK1mutant) were immunoblotted with antibodies recognizing either phosphor-Drp1S616 (pS616) or Drp1 protein. β-actin was detected as a loading control (g). A quantitative analysis of phospho-Drp1S616 (pS616/Drp1) is shown (h). Student's test. **p<0.01, ns: no significance. Data was presented as mean ± SEM of three independent experiments.",
    "diseases": "familial PD, PD"
  },
  {
    "caption": "Drp1S616 phosphorylation in dermal fibroblasts derived from sporadic PD patients. Lysates of cells derived from five unrelated normal control individuals (Control, C) and seven unrelated sporadic PD patients (Sporadic PD, SP) were immunoblotted with antibodies recognizing either phospho-Drp1S616 (pS616) or Drp1 protein. β-actin was detected as a loading control (i).",
    "diseases": "SP, sporadic PD, Sporadic PD"
  },
  {
    "caption": "Drp1S616 phosphorylation in dermal fibroblasts derived from sporadic PD patients. A quantitative analysis of phospho-Drp1S616 (pS616/Drp1) in sporadic cases is shown (j). Student's test. *p<0.05. Data was presented as mean ± SEM of three independent experiments.",
    "diseases": "sporadic PD"
  },
  {
    "caption": "(b) shows succinate  quantification by NMR  from tracheal  aspirates collected in mechanically-ventilated patients with (pink bar, n=9) or without (orange bar, n=7) diagnostic of IAV pneumonia. *P < 0.05. (c)  IL-6 and IL-8 measurements by ELISA  from these same tracheal  aspirates. Data information: Data are mean ± SEM and statistical analysis was performed using the Mann-Whitney U-test.",
    "diseases": "pneumonia"
  },
  {
    "caption": "8-week-old female C57Bl/6 mice  were infected intranasally with 150 pfu of influenza A/Scotland/20/74 (H3N2) virus (IAV) and treated or not simultaneously with 4 mg of succinate (Suc; by the intranasal route). Some mice  were euthanized at 4 days post-infection and lungs  were collected to determine: (h) tissue lesions  in lung  sections stained  with hematoxylin-eosin  and further assessed by microscopy. Scale bar: x6/20 µm. All data are represented as the mean or the mean ± SEM and are cumulative of 2 independent experiments with 5 animals each. Data information: Statistical analysis was performed using the Mann-Whitney test , h, , (*P < 0.05).",
    "diseases": "lesions"
  },
  {
    "caption": "(D) C/EBP β and AEP immunofluorescent staining of colons from age-matched healthy control and AD patients. White arrows indicate that C/EBP β and AEP were co-localized in AD patient's colon. (E) AEP and cleaved APP C586 fragments immunofluorescent staining of colons from age-matched healthy control and AD patient. White arrows indicate that AEP and cleaved APP C586 were co-localized in AD patient's colon. (F) AEP and cleaved Tau N368 fragments immunofluorescent staining of colons from age-matched healthy control and AD patient. Scale bar: 20 μm. White arrows indicate that APP C586 and AEP were co-localized in AD patient's colon.",
    "diseases": "AD"
  },
  {
    "caption": "(C) Immunohistochemistry staining of human Aβ propagating along the vagus nerve from WT mice colonic-injected with PBS, AD brain extracts or 5xFAD brain extracts, using human specific Aβ antibody (BAN50). Black arrows indicate the human Aβ in mouse vagus nerve. (D) Immunohistochemistry staining of human Tau propagating along the vagus nerve from WT mice colonic-injected with PBS or AD brain extracts, using human Tau specific antibody (HT7). Black arrows indicate the human Tau in mouse vagus nerve.",
    "diseases": "FAD, AD"
  },
  {
    "caption": "(A) Immunofluorescent staining of AEP (red) and C/EBP β (green) in CA1 region from hippocampus of brains from colonic-injected PBS, colonic-injected AD brain extracts, and pre-Vagotomy colonic injected AD brain extracts 3xTg mice. Scale bar: 20μm. (B) Quantitative analysis of AEP positive cells and C/EBP β positive cells, respectively. The density of both AEP and C/EBP β positive cells were significantly increased by colonic-injection of AD brain extracts and decreased through vagotomy before colonic-injection. Representative data of three samples, data are shown as mean ± SEM. **P =0.016 (**P < 0.01), ****P<0.0001, one-way ANOVA. ",
    "diseases": "AD"
  },
  {
    "caption": "(C) Immunofluorescent staining of cleaved APPC586 (red) and Aβ (green) in cerebral cortex of brains from colonic-injected PBS, colonic-injected AD brain extracts, and pre-Vagotomy colonic injected AD brain extracts 3xTg mice. (D) Quantitative analysis of cleaved APP C586 positive cells and Aβ positive cells, respectively. The density of both cleaved APP C586 positive cells and Aβ positive cells were significantly increased by colonic-injection of AD brain extracts and decreased through vagotomy before colonic-injection. Representative data of three samples, data are shown as mean ± SEM. ****P<0.0001, one-way ANOVA. ",
    "diseases": "AD"
  },
  {
    "caption": "(E) Immunofluorescent staining of T22 (red) and HT7 (green) in cerebral cortex of brains from colonic-injected PBS, colonic-injected AD brain extracts, and pre-Vagotomy colonic injected AD brain extracts 3xTg mice. (F) Quantitative analysis of T22 positive cells. The density of T22 positive cells was significantly increased by colonic-injection of AD brain extracts and decreased through vagotomy before colonic-injection. Representative data of three samples, data are shown as mean ± SEM. ***P=0.0007 (***P < 0.001), ****P<0.0001, one-way ANOVA. ",
    "diseases": "AD"
  },
  {
    "caption": "A: Graph of the ratio of the median IC50 of the entire panel to that of each cell line generated from a screen of 23 pediatric cancer cell lines. Rhabdoid tumor cell lines (red) cluster towards the left of the graph indicating these cell lines are more sensitive to mithramycin. These results confirm a previously published screen (Osgood et al., 2016).",
    "diseases": "Rhabdoid tumor"
  },
  {
    "caption": "B: Graph of the ratio of the median IC50 of the entire panel to that of each cell line generated from a published screen of 445 agents in 62 sarcoma cell lines (Teicher et al., 2015). The rhabdoid tumor cell line, G401 (red), appears on the left side of the graph indicating this cell line is more sensitive to mithramycin.",
    "diseases": "rhabdoid tumor, sarcoma"
  },
  {
    "caption": "C: Dose response curves of rhabdoid tumor and Ewing sarcoma cell lines. RT cell lines (black) are sensitive to mithramycin treatment with a similar IC50 value as TC32 ES cells (grey). RT cell lines are not sensitive to three broadly-active chemotherapeutic agents: etoposide, doxorubicin or SN38. Data represents mean with standard deviation derived from three independent experiments.",
    "diseases": "rhabdoid tumor, RT, ES, Ewing sarcoma"
  },
  {
    "caption": "A, B: Western blot showing concentration dependent increase in γH2AX following 8-hour exposure to etoposide in BT12 and G401 RT cells (A). Red bar indicates the measured IC50 (Figure 1C). Despite induction of DNA damage, 15 μM etoposide does not lead to apoptosis as indicated by live cell imaging in the presence of cleaved caspase 3,7 (CC3,7) reagent that fluoresces with caspase activation (B). Scale bar (lower left): 150μm.",
    "diseases": "RT"
  },
  {
    "caption": "  C, D: Western blot showing concentration dependent increase in γH2AX following 8-hour exposure to mithramycin (MMA) in BT12 and G401 RT cells (C). Red bar indicates the measured IC50 (Figure 1C). 100 nM Mithramycin induces apoptosis at 8-hours as measured by CC3,7 fluorescence without the presence of DNA damage (D). Scale bar (lower left): 150μm. ",
    "diseases": "RT"
  },
  {
    "caption": " F, G: Western blot showing concentration dependent increase in γH2AX following 8-hour exposure to EC8042 in BT12 and G401 RT cells. Red bar indicates the measured IC50 (Figure 1C). In contrast to apoptotic induction, 75nM EC8042 exhibits evidence of mesenchymal differentiation, similar to 20nM MMA (E,G). Please note, solvent control for (E) and (G) is the same although different fields are shown. Scale bar (lower left): 150μm. ",
    "diseases": "RT"
  },
  {
    "caption": " A, B: Mithramycin displaces SMARCC1 and SMARCE1 SWI/SNF subunits from chromatin in a time-dependent manner in BT12 rhabdoid tumor (A) but not U20S osteosarcoma (B) cells. Western blot analysis showing whole cell lysate (Total), cytoplasmic soluble (CS), nuclear soluble (NS), and chromatin bound (Chr) fractions collected after exposure to solvent (S) or 100nM mithramycin for 8 or 18h and probed for the SWI/SNF subunits (BRD9, SMARCC1 or SMARCE1) or H3 (chromatin fraction control) and GAPDH (soluble fraction control). ",
    "diseases": "rhabdoid tumor, osteosarcoma"
  },
  {
    "caption": " E: Suppression of EZH2 expression and activity antagonizes mithramycin activity in BT12 rhabdoid tumor cells. Data represents dose response curves of mithramycin in BT12 cells following a 48h exposure in the presence of siRNA silencing of the PRC2 subunit EZH2 or treatment with the EZH2 inhibitor EPZ-6438 relative to mithramycin alone (media) or a non-targeting siRNA (siNeg). Data represents mean with standard deviation derived from three independent experiments. ",
    "diseases": "rhabdoid tumor"
  },
  {
    "caption": " F: Suppression of SMARCB1 sensitizes U2OS osteosarcoma cells (wild type SWI/SNF) to mithramycin. Data represents dose response curves of mithramycin in BT12 cells following a 48h exposure in the presence of siRNA silencing of the SWI/SNF subunit SMARCB1 relative to a non-targeting siRNA (siNeg). Data represents mean with standard deviation derived from three independent experiments. ",
    "diseases": "osteosarcoma"
  },
  {
    "caption": " E: IGV tracks of rhabdoid tumor genes previously identified to be occupied by non-canonical SWI/SNF (Michel et al., 2018). ID3 and JUND3 decrease in H3K27ac occupancy and chromatin accessibility following exposure to mithramycin for 8-hours or 18-hours. ",
    "diseases": "rhabdoid tumor"
  },
  {
    "caption": " F: IGV tracks of rhabdoid tumor genes previously identified to gain H3K27me3 upon SWI/SNF loss (Erkek et al., 2019). CDK6 and CDK2 decrease in H3K27ac occupancy and chromatin accessibility following exposure to 8-hours and 18-hours mithramycin treatment. ",
    "diseases": "rhabdoid tumor"
  },
  {
    "caption": "HUVECs transfected with control or CEP41 siRNAs were scratched (0 h) to induce wounding and then incubated for 12 h to allow wound closure. The wound margins were observed every 4 h in the CEP41#1 and #2 siRNA-transfected cells and compared to those of control cells. Representative images of cells subjected to the wound closure assay in (A). Scale bars, 600 μm. Quantification of the extent of wound closure in (B) presented graphically by measuring the distance between the dotted lines at each time point.",
    "diseases": "wound, wounding"
  },
  {
    "caption": "Depletion of Wip1 augments TGF-β-induced migration and invasion of MDA-MB231 breast cancer cells. MDA-MB231 cells transfected with Co siRNA or Wip1 siRNA were scratched with a 20-μL pipette tip and then incubated in the absence or presence of TGF-β1 for the indicated times (C, D)",
    "diseases": "breast cancer"
  },
  {
    "caption": "Depletion of Wip1 augments TGF-β-induced migration and invasion of MDA-MB231 breast cancer cells. MDA-MB231 cells transfected with Co siRNA or Wip1 siRNA were subjected to transwell assay with or without TGF-β1 for 20 h (E, F).",
    "diseases": "breast cancer"
  },
  {
    "caption": "(E-I) Morphological phenotypes of Wip1 morphants. Embryos were injected radially in the marginal zone with Co MO (80 ng), Wip1 MO (80 ng), wt Wip1 (1 ng) and Wip1(D277A) mRNA as indicated and cultured to tadpole stages. Embryos are shown in lateral views with anterior to the left. Un Co, uninjected control. Scale bar, 1 mm. (J) Quantification of the phenotypes shown in (E-I). Severe defects include microcephaly, shortened and kinked body axis, and no eye. Mild defects indicate normal body axis with malformed eyes. ",
    "diseases": "microcephaly"
  },
  {
    "caption": "(b) Upper panel: Representative images of BOEC colonies from PBMC cultivation 10 days post-seeding. Dotted line in each image outlines a BOEC colony. Lower panel: Stabilized BOEC cultures after passaging of colonies (scale bar, 250 µm). (c) Proliferation doubling time for NAFLD and healthy BOECs based on passages 2 and 3. Sample sizes are n = 9 healthy, n = 7 NAFLD; with 3 biological replicates per donor. Box-whisker plots indicate median (middle line), 25th, 75th percentile (box) and the lowest/ highest data points (whiskers). ns, not significant (t-test).",
    "diseases": "NAFLD"
  },
  {
    "caption": "(d) Left panel: Flow cytometry characterization of BOECs for endothelial, leukocyte and progenitor cell markers (grey - isotype control; red/blue/green/purple - cell lineage marker staining). HUVEC and monocytic THP-1 cells were used as positive controls for endothelial and leukocytic markers respectively. Right panel: Percentages of positively expressing cells. Sample sizes are n = 4-6 healthy, n = 2-7 NAFLD.",
    "diseases": "NAFLD"
  },
  {
    "caption": "(f) Left panel: Longitudinal monitoring of BOEC angiogenesis in fibrin gel bead-based sprouting assays over 24h (representative images; scale bar, 100 µm). Right panel: Box-whisker plots of quantifications of sprout lengths and numbers of sprout per bead at 24h. n = 3 healthy, n = 3 NAFLD, with 4-5 beads analyzed per donor and 5-11 sprouts per bead.",
    "diseases": "NAFLD"
  },
  {
    "caption": "(b) Volcano plot depicting differentially expressed genes comparing NAFLD BOECs with healthy BOECs. Red and blue dots represent upregulated and downregulated genes in NAFLD BOECs, respectively.",
    "diseases": "NAFLD"
  },
  {
    "caption": "(a) Fold change in gene expressions of CXCL10, CXCL11, CXCL12, CCL20 and CX3CL1 in NAFLD (n = 10) BOECs, normalized to healthy (n = 12) BOECs, with 2 technical replicates per donor. (c) Fold change in gene expressions of CXCL10, CXCL11, CXCL12, CCL20 and CX3CL1 in LPS+FFA-treated or non-treated NAFLD (n = 5) and healthy (n = 5) BOECs, normalized to non-treated healthy BOECs, with 3 technical replicates per donor.",
    "diseases": "NAFLD"
  },
  {
    "caption": "(b) Left: Representative images showing non-treated and LPS+FFA-treated NAFLD and healthy BOECs, stained with Nile Red (scale bars, 100 µm). Right: Fluorescence intensity of intracellular Nile Red stain was quantified at 515/585nm, and readings were normalized with blanks (n = 3 donors/ group).",
    "diseases": "NAFLD"
  },
  {
    "caption": "(d) Protein concentrations of chemokines in the conditioned culture media of healthy and NAFLD BOECs. *",
    "diseases": "NAFLD"
  },
  {
    "caption": "(a) Upper panel: Single-cell UMAP of sequenced PBMCs from 2 NAFLD patients and 4 healthy subjects; n = 10,786 cells. We identified 15 distinct cell types by DICE annotation. Lower panel: Expression patterns of CXCR3, CXCR4, ACKR3, CX3CR1, CCR6 across different cell types in NAFLD and healthy PBMC samples.",
    "diseases": "NAFLD"
  },
  {
    "caption": "(c) Graphic shows the percentage composition of identified cell types in NAFLD and healthy PBMCs single-cell analysis.",
    "diseases": "NAFLD"
  },
  {
    "caption": "(d) Upper panel: Representative flow cytometry dot plots, characterizing the isolated CD8+ T cells and CD8- immune cell fraction (mainly CD4+ T cells, NK cells and monocytes) from PBMCs of healthy and NAFLD subjects. Lower panel: Flow cytometry quantification of % of positively expressing CXCR4+ and CX3CR1+ cells within each immune subset. Sample sizes are n = 14 NAFLD; n = 6 healthy.",
    "diseases": "NAFLD"
  },
  {
    "caption": "(e) Heatmap of gene expressions of endothelial antigens relevant to interaction with T lymphocytes in NAFLD (n = 3) and healthy (n = 3) BOECs, with 3 biological replicates per donor.",
    "diseases": "NAFLD"
  },
  {
    "caption": "(f) Upper panel: Representative flow cytometry histograms of HLA-A/B/C, HLA-DM and IFN-γR1 expressions in NAFLD (red) and healthy (blue) BOECs. Grey, isotype control. Lower panel: Box-whisker plots reflect mean fluorescence intensity (a.u., arbituary unit), normalized to isotype control, as a readout for epitope density. Box-whisker plots indicate median (middle line), 25th, 75th percentile (box) and the lowest/ highest data points (whiskers). ns, non-significant (t-test). n = 4 donors; *p<0.05; ns, not significant (Mann-Whitney test for HLA-A/B/C and IFN-γR1; t-test for HLA-DM).",
    "diseases": "NAFLD"
  },
  {
    "caption": "(a) Left: Workflow schematic of adhesion assay. Middle: Representative images of labeled THP-1 and Jurkat cells attached to BOEC monolayers (Scale bars, 100 µm). Right: Box-whisker plots of the numbers of adhered leukocytes were determined fluorometrically. Sample sizes are n = 9 NAFLD and n = 7 healthy, with 3 biological replicates per donor.",
    "diseases": "NAFLD"
  },
  {
    "caption": "(c) CD8+ T cells and CD8- cell fractions were isolated from NAFLD and healthy subjects. Box-whisker plots show the number of recruited immune cells to their respective BOECs matched by health condition in coculture chemotaxis assays. Box-whisker plots indicate median (middle line), 25th, 75th percentile (box) and the lowest/ highest data points (whiskers). ns, non-significant (t-test). Sample sizes are n = 11 NAFLD and n = 6 healthy, with 3-4 technical replicates per donor.",
    "diseases": "NAFLD"
  },
  {
    "caption": "(d) Box-whisker plots show percentages of inhibition on immune cells chemotaxis by treatment with AMD3100 (CXCR4 small molecule inhibitor). Box-whisker plots indicate median (middle line), 25th, 75th percentile (box) and the lowest/ highest data points (whiskers). ns, non-significant (t-test). Sample sizes are n = 6 NAFLD and n = 4 healthy, with 3-4 technical replicates per donor.",
    "diseases": "NAFLD"
  },
  {
    "caption": "(e) Box-whisker plots show percentages of inhibition on immune cells chemotaxis by treatment with anti-CXCL12 IgG (CXCL12 neutralizing antibody). Box-whisker plots indicate median (middle line), 25th, 75th percentile (box) and the lowest/ highest data points (whiskers). ns, non-significant (t-test). Sample sizes are n = 5 NAFLD and n = 3 healthy, with 3-4 technical replicates per donor.",
    "diseases": "NAFLD"
  },
  {
    "caption": "(g) Box-whisker plots of the numbers of circulating endothelial cells per million PBMCs in healthy (n = 6) and NAFLD subjects (n = 11). Box-whisker plots indicate median (middle line), 25th, 75th percentile (box) and the lowest/ highest data points (whiskers). ns, non-significant (t-test).",
    "diseases": "NAFLD"
  },
  {
    "caption": "(A) Immunofluorescence analysis of DSBs associated foci as marked by γH2AX in lung adenocarcinoma (A549) cells, cultured either in low glucose (5.5mM, left panel) or high glucose (30mM, right panel) for 5 days, then treated with etoposide (5µM for 60 minutes). The resolution of DNA-DSBs foci, as marked by γH2AX was monitored over 24 hours after drug treatment, CML (marked in green) served as induction control (scale 10µm). (B) Mean percentage of DSBs positive nuclei as evidenced by γH2AX positivity after pre-treatment of different reducing carbohydrates at 0, 3 or 24 hours. More than 400 cells were analyzed for each bar (mean ± SD, : p<0.01;: p<0.001). ",
    "diseases": "lung adenocarcinoma"
  },
  {
    "caption": "(A) Representative images of lungs for nuclei positive for the DNA-DSBs marker γH2AX, versus DAPI, in age-matched 3-, or 6- months control, versus STZ induced diabetic mice, as determined by immunofluorescence analysis (scale 10μm). (B) Mean percentage of nuclei positive for the DNA-DSBs marker γH2AX in lungs of age-matched control versus 6-month STZ induced diabetic mice, as determined by immunofluorescence analysis of lungs (mean ± SEM, :p<0.05;: p<0.01; : p<0.001; N=6). ",
    "diseases": "diabetic"
  },
  {
    "caption": "(C) Representative images of lungs from age-matched control versus 3 or 6-month STZ mice, stained for the peroxide linked oxidative stress marker DHR-123(in red), as determined by mean fluorescence intensity. Blue nuclear staining represents DAPI (Scale 10µm). (D) Quantitative analysis of respectively age-matched control versus 3 or 6-month STZ induced diabetic lungs for persistent DNA damage signaling associated inflammatory marker IL-6, as determined by mean fluorescence intensity of respective group lungs (mean ± SD; : p<0.01: p<0.001; N=6). ",
    "diseases": "diabetic"
  },
  {
    "caption": "(E) Representative images of lungs from age-matched controls, versus 3 or 6-month STZ induced diabetic mice. Sections stained for cellular senescence-associated β-galactosidase [β-Gal] as described in Methods and visualized by bright field and polarized light, the senescent areas are recognized by its bluish-green staining (Scale 40µm).",
    "diseases": "diabetic"
  },
  {
    "caption": "(A) Pressure-volume curves were determined using the FlexiVent system in age-matched control versus 3-month STZ induced diabetic mice. The curves represent group averages (mean ± SD; : p<0.05; N=5).",
    "diseases": "diabetic"
  },
  {
    "caption": "(B) Quantitative analysis of static pulmonary compliance in age-matched control versus 3 months STZ induced diabetic mice, as described in Figure 3a. The curves represent group averages (mean ± SD; : P<0.05, : p<0.01; N=5).",
    "diseases": "diabetic"
  },
  {
    "caption": "(C) Representative images of lungs from age (3- or 6- month) matched control versus STZ induced diabetic mice, stained for Masson's Trichrome stain, as described in Methods and visualized by bright field and polarized light, the accumulated ECM is recognized by its blue staining (Scale 40µm).",
    "diseases": "diabetic"
  },
  {
    "caption": "(D) Percentage total lung capacity of controls versus patients with diabetes. The dotted line represents the cut-off decided as per the guidelines of the European Respiratory Society (ERS) and American Thoracic Society (ATS), (mean ± SD, : p<0.05; triplicates from each Ncontrol=44, Ntype-1=35, Ntype-2=110). (E) Percentage forced vital capacity of lungs in controls versus patients with diabetes. The dotted line represents the cut-off decided as per the guidelines of ERS and ATS, (mean ± SD; : p<0.05; triplicates from each Ncontrol=44, Ntype-1=35, Ntype-2=110).",
    "diseases": "diabetes"
  },
  {
    "caption": "(F) Quantitative analysis of the NAD+/NADH ratio in lungs harvested from age-matched 3, or 6 months control, or STZ induced diabetic mice, after homogenization in extraction buffer (mean ± SD; : p<0.01, : p<0.001; N=5).",
    "diseases": "diabetic"
  },
  {
    "caption": "(G) Quantitative analysis of the NAD+/NADH ratio determined in serum from patients with diabetes, as described in methods (N=3; mean ± SD, : p<0.01, : p<0.001).",
    "diseases": "diabetes"
  },
  {
    "caption": "(A) Representative images of γH2AX positive nuclei in lungs of 6-month STZ induced diabetic mice, transduced with respective RAGE virions as described in Methods. The lungs were harvested 6-weeks after viral transduction. The empty vector served as control. Red represents γH2AX foci green cytoplasmic staining represents α-tubulin; blue nuclear staining represents DAPI (Scale 10µm). No primary antibody control served as a negative control (from control lung) of the staining.",
    "diseases": "diabetic"
  },
  {
    "caption": "(B) Mean percentage of nuclei positive for the DNA-DSBs marker γH2AX in transduced lungs of 6-month STZ diabetic mice as described in Figure 5a (mean ± SEM; : p<0.01; N=8).",
    "diseases": "diabetic"
  },
  {
    "caption": "(C) Representative images of lungs from 6-month STZ induced diabetic mice, transduced with respective RAGE virions as described in Methods. Lungs were stained for cellular senescence-associated β-galactosidase as described in Figure 5a and visualized by bright field and polarized light, where the accumulated senescent areas are recognized by its blue staining (Scale 40µm).",
    "diseases": "diabetic"
  },
  {
    "caption": "(D) Quantitative analysis of persistent DNA damage associated inflammatory marker IL-6, in transduced lungs from 6-month STZ-diabetic mice, as determined by mean fluorescence intensity of respective group lungs (mean ± SD,: p<0.05, : p<0.001; N=8).",
    "diseases": "diabetic"
  },
  {
    "caption": "(E) Quantitative analysis of Masson's Trichrome stain for lungs of 6-month STZ induced diabetic mice with respective RAGE virions as described in Figure 5F (mean ± SD, : p<0.001; N=8).",
    "diseases": "diabetic"
  },
  {
    "caption": "(G) Pressure-volume curves of diabetic and non-diabetic mice were determined using the FlexiVent system 6 weeks after transduction using respective the RAGE virions, as described in Figure 5a. The curves represent group averages (N=8). The lungs studied in Figure 5a, b, c and d are identical (mean ± SD; Vector alone vs. RAGE-EE; : p<0.05; N=8).",
    "diseases": "diabetic"
  },
  {
    "caption": "A: Relative expression of ELDR in OSCC patient samples compared to adjacent non-tumor tissues (N=20) analyzed by qRT-PCR. Technical triplicates were used from each sample. 18S rRNA was used as an internal control. Data were analyzed by Student's t test. Small bars indicate standard error (*, p<0.05, **, p<0.01; *** p<0.001).",
    "diseases": "OSCC"
  },
  {
    "caption": "B: OSCC grade wise upregulation of ELDR expression was noted in the patient samples (N=20). Correlation analysis showed signification positive correlation of ELDR expression with tumor grade (R2= 0.926, significant P value = 0.01). Pearson correlation coefficient and p value was calculated using socscistatistics.com. Well: well differentiated, Mod: moderately differentiated, Poor: poorly differentiated carcinoma. Data are represented as the mean ± SD,",
    "diseases": "carcinoma, OSCC"
  },
  {
    "caption": "C: Representative images of FISH analysis with an RNA probe of ELDR (red) and DAPI staining (blue) in formalin fixed paraffin embedded OSCC tissue. An unrelated probe was used as negative control. Magnification: 40X; inset magnification 100X and scale bar 10 µm.",
    "diseases": "OSCC"
  },
  {
    "caption": "D: Relative expression of ELDR in OSCC cell lines compared to normal oral keratinocytes (NOK) analyzed by qRT-PCR. 18S was used as internal control. Data were analyzed by Student's t test. Small bars indicate standard error (**, p<0.01; *** p<0.001). n = 4 biological replicates. Data are represented as the mean ± SD,",
    "diseases": "OSCC"
  },
  {
    "caption": "F: OSCC-PDX tissue was implanted subcutaneously into the flank of NSG mice. When the tumor volume reached >70 mm3, mice were divided into two groups. 10µg of siELDR or control oligoes were injected intratumorally as described above. Body weight was measured in control and siELDR treated mice. n=5 animal per group",
    "diseases": "OSCC"
  },
  {
    "caption": "G: Representative images of OSCC-PDX tumors in control and treatment groups.",
    "diseases": "OSCC"
  },
  {
    "caption": "I: ELDR knockdown was examined by analyzing expression of ELDR in treated OSCC-PDX tumors compared to the control tumors. 18S gene was used as internal control. n=5 animal per group and 3 technical replicates presented as the mean ± SD",
    "diseases": "OSCC"
  },
  {
    "caption": "H-K. BHLHE40  expression  in islets  from diabetic mice. BHLHE40   expression  was analyzed in ob/ob mouse islets   by qRT-PCR (n = 4 biological replicates; H) and  Western blotting  (I) and in db/db mouse islets   by Western blotting (J). Subcellular localization  of BHLHE40  in ob/ob mice islets   by immunohistochemical  analysis (K). Data information: Data are mean ± SEM; *p < 0.05, **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test. β-actin was used as a loading control. Scale bar, 100 μm.",
    "diseases": "db, diabetic, ob"
  },
  {
    "caption": "C, D.  Glucose tolerance test  of Ctrl:ob/ob  and βB40KO:ob/ob mice  (n = 9 mice  and n = 8 mice, respectively; 6 weeks old) (C) and AUC (D). Data information: Data are mean ± SEM; *p < 0.05 **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test.",
    "diseases": "ob"
  },
  {
    "caption": "E. Glucose-stimulated insulin  secretion in Ctrl:ob/ob  and βB40KO:ob/ob mice  (n = 9 mice  and n = 6 mice, respectively; 8 weeks old). F. Glucose-stimulated insulin  secretion in isolated islets   from Ctrl and βB40KO mice  after culture under 5% O2  for 24 hours (n = 8 biological replicates). Data information: Data are mean ± SEM; *p < 0.05 **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test.",
    "diseases": "ob"
  },
  {
    "caption": "I, J. Representative images of  pancreatic islets stained  for insulin  and glucagon  in Ctrl:ob/ob  and βB40KO:ob/ob mice  (12 weeks old) (I). The ratios of total islet  area to whole pancreas  area (%) are shown (n = 3 biological replicates; J). Data information: Data are mean ± SEM; *p < 0.05 **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test. Scale bar, 10 μm.",
    "diseases": "ob"
  },
  {
    "caption": "K, L. Representative images of pancreatic islets stained  for insulin, MAFA, and BHLHE40  in Ctrl:ob/ob  and βB40KO:ob/ob mice  (12 weeks old) (K). Fluorescence intensities of nuclear  and cytosolic MAFA  in K were quantified (n = 30 cells; L). Data information: Data are mean ± SEM; *p < 0.05 **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test. Scale bar, 10 μm.",
    "diseases": "ob"
  },
  {
    "caption": "M. qRT-PCR  of Mafa  and its target genes in Ctrl:ob/ob  and βB40KO:ob/ob mice  (n = 4 mice). Data information: Data are mean ± SEM; *p < 0.05 **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test.",
    "diseases": "ob"
  },
  {
    "caption": "(B) Non-supervised clustering heatmap plot indicates substantial clustering of transcripts from each tissue but not of transcripts from patients compared to controls. PD samples indicated in red.",
    "diseases": "PD"
  },
  {
    "caption": "(D) qPCR validation of TH levels in SN samples of PD and controls, normalized to beta-actin mRNA. T-test p*=0.025, Data presented as mean ± SD. n=18 for CT and 24 for PD.",
    "diseases": "PD"
  },
  {
    "caption": "(D) Heatmap of circRNA abundance, indicating significant tissue-based SN clustering, PD samples indicated in red.",
    "diseases": "PD"
  },
  {
    "caption": "(A) Total circRNAs detected in the SN, MTG and AMG of both PD and control donors, p*=0.02 p*=0.026 and p*=0.022 for comparison between PD and CT in SN, MTG and AMG. T-test for total SN vs MTG p*=2.27E-8 and SN vs AMG p*=5.86E-10. n=8 for Amygdala control, 15 for Amygdala PD, 8 for MTG control and 13 for MTG PD, 10 for SN control and 15 for SN PD. The box is drawn from Q1 to Q3 with a horizontal line drawn in the middle to denote the median and x marks the average. Whiskers mark minimum or maximum values. P value was calculated by T-test.",
    "diseases": "PD"
  },
  {
    "caption": "(B) Global editing levels in the 3 brain regions is based on the Alu editing index, representing the weighted average editing level across all expressed Alu sequences, Wilcoxon, corrected p*=0.038, 0.055 and 0.42 for Amygdala, MTG and SN. Wilcoxon test between the Alu editing index of control and PD samples.",
    "diseases": "PD"
  },
  {
    "caption": "(C) Global RNA editing levels based on the Alu editing index, studied only in Alu elements within circRNA exons and their flanking introns, in the 3 brain regions, for circRNAs corrected p*= 0.025 and 0.040 for the AMG and MTG and p=0.3 for SN. For flanking introns p*= 0.02 and 0.040 for AMG and MTG and p=0.34 for SN, Wilcoxon test. n=8 for Amygdala control, 15 for Amygdala PD, 8 for MTG control and 13 for MTG PD, 10 for SN control and 15 for SN PD. The box is drawn from Q1 to Q3 with a horizontal line drawn in the middle to denote the median and x marks the average. Whiskers mark minimum or maximum values.",
    "diseases": "PD"
  },
  {
    "caption": "(F,G) Correlations between circRNAs detected in each sample and the age of the control (green, correlation = 0.68, p-value = 0.032) and PD donors (blue, correlation = -0.14 p value = 0.62).",
    "diseases": "PD"
  },
  {
    "caption": "(H) Volcano plot of DE circRNAs in PD vs control tissues, red dots indicate statistically significant DE circRNAs according to FDR correction of Wald test (DEseq2 analysis). CircSLC8A1 is marked is red.",
    "diseases": "PD"
  },
  {
    "caption": "(B, C) CircSLC8A1 and linear SLC8A1 levels in the SN of control and PD brains, T-test p=0.025, p= 0.118 respectively.",
    "diseases": "PD"
  },
  {
    "caption": "(D) qPCR validations of circSLC8A1 and SLC8A1 mRNA changes in the SN, T-test p*=0.025. n=18 for CT and 24 for PD, x defines mean values.",
    "diseases": "PD"
  },
  {
    "caption": "(E) no difference in circSLC8A1 levels in females and males, T-test p=0.583 for control and p=0.262 for PD. n=15 females and 16 males. . The box is drawn from Q1 to Q3 with a horizontal line drawn in the middle to denote the median and x marks the average.",
    "diseases": "PD"
  },
  {
    "caption": "(F, G) CircSLC8A1 and linear SLC8A1 mRNA levels are correlated in control, R2=0.47 T-test p=0.0017 but not in PD samples, R2= 0.016, p>0.05. n=18 for CT and 23 for PD.",
    "diseases": "PD"
  },
  {
    "caption": "Luciferase-based imaging of drug response in Vegfr3Luc;Tyr:CreERT2;BrafV600E; Ptenflox/flox mice. Panels labeled as \"basal\" and \"induced\" correspond to the bioluminescence of animals prior and 5 weeks after administration of 4OH-tamoxifen (5 mM, topical administration, 3 consecutive days) for the induction of melanomas. (Right panels) Treatment with anti-PD-L1 antibody (αPD-L1; clone 10F.9G2, 3 weeks) or the corresponding control IgG (200 ug/dose, twice per week, 3 weeks); vemurafenib (Vem, 50 mg/Kg, oral once per day, 3 weeks) or BO-110 (BO, 0.8 mg/kg, twice per week, 3 weeks). Scale: p/s/cm2/sr (x106).",
    "diseases": "melanomas"
  },
  {
    "caption": "Relative mRNA levels of VEGFC  and VEGFD in the indicated melanoma cell lines 8 h after treatment with vehicle (V) or 0.5 µg/ml BO-110 (BO), as determined by qRT-PCR. Data correspond to the mean ± SD of 3 experiments. Statistical significance was determined by t-test.",
    "diseases": "melanoma"
  },
  {
    "caption": "Type I IFN mRNA induction (IFNA2 and IFNB1) in SK-Mel-147 melanoma cells treated for 16 h with the indicated amounts of BO-110 (in mg/ml). Data correspond to the mean ± SD of three experiments with three technical replicates normalized to vehicle control. Statistical significance was determined by ANOVA.",
    "diseases": "melanoma"
  },
  {
    "caption": "Heatmap depicting expression changes in interferon-related genes (GO:0034340) in SK-Mel-147 melanoma cells (left panel) and HLEC (right panel) treated with vehicle or 0.5 g/ml of BO-110 for 10 hours.  CD274, LAG3 and PDCD1 genes were also included as a reference.",
    "diseases": "melanoma"
  },
  {
    "caption": "IFNB1  mRNA induction analyzed by qPCR at the indicated times  after BO-110 treatment (0.5 µg/ml) of SK-Mel-147 melanoma cells or HLEC (left and right graphs, respectively). Data correspond to the mean ± SD of three experiments with three technical replicates normalized to vehicle control.",
    "diseases": "melanoma"
  },
  {
    "caption": "Quantification of the impact of  BO-110 as single agent or in the presence of the indicated blocking antibodies for type I interferon (IFNB1 or IFNAR1). Upper graphs show the effect of these agents on  MDK mRNA levels in SK-Mel-147 melanoma cells. Similar treatments were performed on HLEC for the analysis of VEGFR3  mRNA (middle graphs) and tube formation capacity (lower graphs). Data correspond to the mean ± SD of 3 biological replicates in triplicate.",
    "diseases": "melanoma"
  },
  {
    "caption": "Growth  of B16 melanoma xenografts in siblings of  Ifnar1+/+, Ifnar1+/- or Ifnar1-/- mice. Treatment started 10 days after tumor cell implantation. BO-110 was administered at 0.8 mg/kg, every third day for 2 weeks. N= 6 mice per condition. Graphs show the mean tumor size ± SD at each time point. Statistical significance was determined by Two-Way ANOVA.",
    "diseases": "melanoma"
  },
  {
    "caption": "B) Western blot  assays for the expression   level of TFAM  in ten HCC  cell lines, one normal liver cell line (LO2) and two non-tumor liver  tissues. The protein level  was quantified as ratios between  TFAM and GAPDH  (n = 3 independent experiments). Data information: Graphs show mean ± s.e.m., two-tailed unpaired t-test. **P < 0.01.",
    "diseases": "HCC"
  },
  {
    "caption": "(C) Western blot  and quantitative analysis for the expression  of TFAM  in HCC  cells with TFAM  stable knockdown and control cells (n = 3 independent experiments). shCtrl, control shRNA; shTFAM, shRNA against TFAM; EV, empty vector; TFAM, expression vector encoding TFAM. Data information: Graphs show mean ± s.e.m., two-tailed unpaired t-test. **P < 0.01.",
    "diseases": "HCC"
  },
  {
    "caption": "(D, E) Wound-healing migration assay (D) and Transwell migration and invasion assays (E) for HCC cells with treatment as indicated (n = 3 independent experiments). Scale bars, 100μm. Data information: Graphs show mean ± s.e.m., two-tailed unpaired t-test. **P < 0.01.",
    "diseases": "HCC"
  },
  {
    "caption": "(G) Representative H&E images of lung metastasis  in mice  used in (F). Scale bars, 100μm. (H, Number of metastatic nodules   per lung  (H) in mice  used in (F). Data information: Graphs show mean ± s.e.m., two-tailed unpaired t-test. **P < 0.01.",
    "diseases": "metastasis"
  },
  {
    "caption": "(C) Immunofluorescence  analysis of TFAM  and Phalloidin staining  in human HCC  cells from paired clinical samples (n=100). The 3D reconstruction of z-stacks from nuclear  region is showed in the right side. Red: LifeAct, Blue: DAPI, Green: TFAM. Scale bars, 20μm for microscopy images, 40μm for 3D reconstruction.",
    "diseases": "HCC"
  },
  {
    "caption": "(E) Representative H&E images of lung metastasis    in mice  used in (D). Scale bars, 100μm. (F and G) Number of metastatic nodules  per lung  in mice used in (F) and the incidence of lung metastasis   (G) in mice  used in (D). Data information: Graphs show mean ± s.e.m., two-tailed unpaired t-test. **P < 0.01.",
    "diseases": "metastasis"
  },
  {
    "caption": "F) Western blot assays for protein expression levels of metastasis   related gene in HCC  cells (n = 3 independent experiments) and tumor tissues from mice  (n =4 per group) with treatments as indicated. Data information: Graphs show mean ± s.e.m., two-tailed unpaired t-test. *P < 0.05; **P < 0.01.",
    "diseases": "HCC"
  },
  {
    "caption": "(H Western blot  assays levels of  FN1, ITGB3 in HCC  cells with treatment as indicated (n = 3 independent experiments). Data information: Graphs show mean ± s.e.m., two-tailed unpaired t-test. *P < 0.05; **P < 0.01.",
    "diseases": "HCC"
  },
  {
    "caption": "(A) Western blot analyses for the protein level of key regulators of actin  polymerization in the  cytoplasm and  nucleus  of HCC  cells with treatment as indicated. Tublin and  Lamin B1 were used as loading controls for the cytoplasm  and nucleus, respectively (n = 3 independent experiments).",
    "diseases": "HCC"
  },
  {
    "caption": "Representative IHC  images of mDia2 nuclear translocation  in human (E) HCC  tissues. NT, non-tumor liver  tissues, n=100; MT, metastatic  tumor tissues, n=58; NMT, non-metastatic tumor tissues n=42. Scale bars, 25μm. (F) Positive rates of mDia2  in nucleus  and cytoplasm  was calculated based on the IHC  assay in (E). Graphs show mean ± s.e.m. One-way ANOVA. **P < 0.01.",
    "diseases": "metastatic, HCC"
  },
  {
    "caption": "(D) Western blot analysis of anti-mDia2 IPs  and whole-cell lysates (WCL) derived from HCC  cells and mouse  tumor tissues (n = 3 independent experiments). NT, non-tumor liver  tissues; MT, metastatic  tumor tissues; NMT, non-metastatic  tumor tissues.",
    "diseases": "metastatic, HCC"
  },
  {
    "caption": "(H) Representative H&E images of lung metastasis   in mice  used in (G). Scale bars, 100μm. (I) Number of metastatic nodules  per lung  in mice  used in (G). Data information: Graphs show mean ± s.e.m., two-tailed unpaired t-test for , I). *P < 0.05; **P < 0.01.",
    "diseases": "metastasis"
  },
  {
    "caption": "(A) IHC  scores of TFAM  in 429 paired tissues from HCC patients. The relative expression  ratio of tumor to non-tumor was log2-transformed. T, tumor tissues; NT, non-tumor liver  tissues.",
    "diseases": "HCC"
  },
  {
    "caption": "(B) mRNA level of TFAM  in 50 HCC patients' paired tissues from TCGA database. The relative expression  ratio of tumor to non-tumor was log2-transformed.",
    "diseases": "HCC"
  },
  {
    "caption": "(C) Representative images of IHC staining  of TFAM  (top panel) and scores (bottom panel) in HCC  tumor tissues. One-way ANOVA. *P < 0.05; **P < 0.01. MT, metastatic  tumor tissues; NMT, non-metastatic  tumor tissues. Scale bars, 25μm. Boxes: first quartile to third quartile; Whiskers: minimum value to maximum value; Central band: median.",
    "diseases": "metastatic, HCC"
  },
  {
    "caption": "(D Kaplan-Meier  curves for overall survival  of HCC patients stratified by TFAM  expression. (F Kaplan-Meier  curves for overall survival  of HCC patients  stratified by nuclear F-actin positive rates.",
    "diseases": "HCC"
  },
  {
    "caption": "E) the recurrence  of HCC patients  stratified by TFAM  expression. G) the recurrence  of HCC patients  stratified by nuclear F-actin positive rates.",
    "diseases": "HCC"
  },
  {
    "caption": "(H) Representative images of IHC staining  of TFAM, FN1  and ITGB3 from two HCC patients. Scale bars, 25μm. (I) Spearman correlation analysis between the levels of TFAM  and FN1, IL-6, TGFB1 or ITGB3.",
    "diseases": "HCC"
  },
  {
    "caption": "(C-F) Kaplan-Meier survival plots comparing the survival probabilities (y-axes) as a function of time in days (x-axes) for proteins and cancer types shown in (A) and (B). (C) MYC/brain cancer (inactive = 71, neutral = 39, active = 67). (D) MYC/liver cancer (inactive = 58, neutral = 59, active = 40). (E) MAP3K8/renal cancer (neutral = 95, active = 7). (F) PRKCA/renal cancer (inactive = 3, neutral = 92, active = 7). The log-rank P-values are shown in the plots.",
    "diseases": "brain cancer, renal cancer, liver cancer"
  },
  {
    "caption": "Increased apoptotic cell death in the skin of ORAS patient III.2. Serial sections of normal skin (top panels) and a skin biopsy from patient III.2 taken at an inflammatory flare (bottom panels) were immunostained for cleaved caspase-3 (centre panels) or analysed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay (right panels). Arrowheads indicate cleaved caspase-3-positive mesenchymal cells. None \u2028of these markers were present in the healthy control skin. H&E, haematoxylin and eosin. Boxes in H&E panels indicate the areas magnified in the cleaved caspase-3 and TUNEL panels. Scale bars, 100 μm. \u2028Data are representative of stained sections from three healthy controls and one biopsy from ORAS patient III.2.",
    "diseases": "ORAS"
  },
  {
    "caption": "Analysis of the blood cell chimerism in patient III.2 after HSCT. Short terminal repeat (STR) analysis was used to determine the percentage of donor cells in peripheral blood. Arrow indicates point of relapse.",
    "diseases": "chimerism"
  },
  {
    "caption": "Photograph of patient III.2 at age ~10 years at an episode of inflammation caused by delayed etanercept administration. Arrows indicate the erythematous subcutaneous nodules (panniculitis).",
    "diseases": "inflammation, panniculitis"
  },
  {
    "caption": "Human whole blood transcriptomic signatures for timepoint across the two observed phases of natural CHIKV infection. Expression was measured with RNA-seq and quantified at the transcript level, with all models of differential expression adjusting for patient age and gender as covariates. For all panels, 42 patients were sampled at 2 timepoints, each with 2 technical replicates; q values are Benjamini-Hochberg adjusted P values from a moderated paired t-test under the mixed effects model. A, volcano plot of differentially expressed host transcripts between acute- and convalescent-phase samples, with negative log10-scaled q values on the Y axis, and the fitted β coefficient for each transcript (corresponding to modeled log2 fold change) on the X axis. Transcripts to the right of the vertical dashed line were comparatively upregulated in acute-phase samples, while transcripts to the left were upregulated during the convalescent phase. Transcripts that pass FDR < 0.05 and fold change > 2 are colored salmon and turquoise for acute-associated and convalescent-associated transcripts, respectively. Top transcripts by q value or fold change are individually labeled by their corresponding gene symbol.",
    "diseases": "CHIKV"
  },
  {
    "caption": "Human whole blood transcriptomic signatures for timepoint across the two observed phases of natural CHIKV infection. Expression was measured with RNA-seq and quantified at the transcript level, with all models of differential expression adjusting for patient age and gender as covariates. For all panels, 42 patients were sampled at 2 timepoints, each with 2 technical replicates; q values are Benjamini-Hochberg adjusted P values from a moderated paired t-test under the mixed effects model. B, heatmap of expression in units of Z-scores per transcript for the top 50 differentially expressed host transcripts between acute and convalescent phase samples. Clinical variables are depicted for all samples across the top of the heatmap; convalescent post symptom onset anti-CHIKV antibody titer and viral titer (which was measured during the acute phase) are both in units of log10 dilutions. Hierarchical clustering (using complete linkage) was applied to both samples (X axis) and transcripts (Y axis). Two major clusters of samples (largely separating acute and convalescent samples) are highlighted.",
    "diseases": "CHIKV"
  },
  {
    "caption": "Human whole blood transcriptomic signatures for CHIKV viral titer at the acute phase of natural CHIKV infection. Expression was measured with RNA-seq and quantified at the transcript level, with all models of differential expression adjusting for patient age and gender as covariates. For all panels, 42 patients were sampled at 2 timepoints, each with 2 technical replicates; q values are Benjamini-Hochberg adjusted P values from a moderated paired t-test under the mixed effects model. C, volcano plot as in A but for differentially expressed host transcripts between samples with higher and lower CHIKV viral titer. Transcripts to the right of the vertical dashed line are associated with higher viral titer, while transcripts to the left are associated with lower viral titer. Transcripts significant at FDR < 0.05 are colored red.",
    "diseases": "CHIKV"
  },
  {
    "caption": "Human whole blood transcriptomic signatures for symptom severity, across the two observed phases of natural CHIKV infection. Expression was measured with RNA-seq and quantified at the transcript level, with all models of differential expression adjusting for patient age and gender as covariates. For all panels, 42 patients were sampled at 2 timepoints, each with 2 technical replicates; q values are Benjamini-Hochberg adjusted P values from a moderated paired t-test under the mixed effects model. volcano plot for differentially expressed host transcripts between patients with more severe and less severe acute-phase symptoms. Transcripts to the right of the vertical dashed line were comparatively upregulated in more severe cases, while transcripts to the left were upregulated in less severe cases.",
    "diseases": "CHIKV"
  },
  {
    "caption": "Human whole blood transcriptomic signatures for symptom severity across the two observed phases of natural CHIKV infection. Expression was measured with RNA-seq and quantified at the transcript level, with all models of differential expression adjusting for patient age and gender as covariates. For all panels, 42 patients were sampled at 2 timepoints, each with 2 technical replicates; q values are Benjamini-Hochberg adjusted P values from a moderated paired t-test under the mixed effects model. heatmap of expression for 20 differentially expressed host transcripts (all significant at FDR < 0.05) under a model that includes a severity-timepoint interaction. Transcripts have been filtered to those differentially expressed between the timepoints in more severe cases but not in less severe cases.",
    "diseases": "CHIKV"
  },
  {
    "caption": "Human whole blood transcriptomic signatures for convalescent (15d post-symptom onset) anti-CHIKV antibody (Ab) titer across the two observed phases of natural CHIKV infection. Expression was measured with RNA-seq and quantified at the transcript level, with all models of differential expression adjusting for patient age and gender as covariates. For all panels, 42 patients were sampled at 2 timepoints, each with 2 technical replicates; q values are Benjamini-Hochberg adjusted P values from a moderated paired t-test under the mixed effects model. F, volcano plot for differentially expressed host transcripts between patients with higher and lower convalescent (15d post symptom onset) anti-CHIKV antibody (Ab) titers. Transcripts to the right of the vertical dashed line were comparatively upregulated in patients with a higher convalescent anti-CHIKV antibody titer, while transcripts to the left were upregulated in patients with a lower convalescent anti-CHIKV antibody titer.",
    "diseases": "CHIKV"
  },
  {
    "caption": "(C) T2-weighted MR images in coronal  plane show abscess formation in the  left  lower  pulmonary lobe   (upper panel) and in  spleen  and   left axilla (lower panel).",
    "diseases": "abscess"
  },
  {
    "caption": "(A) Volcano plot shows genes where RNA reads are statistically significant under- or over-expressed in 5 RIRCD affected individuals versus 6 controls resulted from DESeq2 analysis. Decreased genes are represented in red, the up-regulated ones are in green while blue dots highlight most outlying genes (defined by absolute (log2(fold change) + log10(padj))>10).Genes that were not statistically significant are represented in black. Grey and black gene names indicate top 30% of the most dysregulated genes with a highlight on ones involved in metabolism.",
    "diseases": "RIRCD"
  },
  {
    "caption": "(D) Relevant functional changes in gene expression showing the major genes that return to baseline or contribute to the recovery in RIRCD patients. The data depicted is between the affected and recovered biopsies of the same patient (F6/1M).",
    "diseases": "RIRCD"
  },
  {
    "caption": "(E) Comparative proteome profiling of proteins that are significantly under- or over-expressed in RIRCD affected versus control individuals (p-Anova <0.05-statistically significant - horizontal line). Proteins which are decreased are represented in red while the up-regulated ones are in green while proteins that did not reach statistical significance threshold are marked in black. Vertical lines are delimiting the regulated proteins resulted from the proteomics analysis (the cut-off values were determined based on the 2× standard deviation and the normal distribution from all identified protein's log2 ratio in which the bell curve is symmetric around the mean, therefore, an average log2 ratio of a protein which <−2.2 or > 0.98 was considered as regulated).",
    "diseases": "RIRCD"
  },
  {
    "caption": "(F) Transcriptomic pathways related to ATFs and ISR changed in affected patients compared to controls (RIRCD n=5; controls n=6) and in recovered muscle compared to affected muscle (n=1, affected and recovered muscle was collected from the same individual and was analysed using 4 technical replicates) and schematic representation of the metabolic pathways impacted in patient muscle (bottom, right panel).",
    "diseases": "RIRCD"
  },
  {
    "caption": "(A) Patient n= 4 (F7/7F-healthy carrier, F7/2M-RIRCD, F7/5F-healthy carrier, F7/1M-RIRCD without a clear second mutation) and control fibroblasts (n=2) were grown for 12 days in media containing 0.02 mM cysteine and 5% dialyzed FBS. Proteins belonging to mitochondrial complexes (NDUFA9-Complex I, SDHA-Complex II, MTCO1-Complex IV and MTCO2-Complex IV) were analysed via Western Blotting. VCL was used as a loading control and the densitometry analysis was done based on the mitochondrial proteinTOM20. (B) Densitometry analysis of proteins from (A) showing no significant changes in OXPHOS proteins upon glutamine/ glutamic acid depletion. Control bar represents an average of the two control fibroblast lines employed (F008 and F154). ",
    "diseases": "RIRCD"
  },
  {
    "caption": "(C) Patient (F7/7F-healthy carrier, F7/2M-RIRCD, F7/5F-healthy carrier, F7/1M-RIRCD without a clear second mutation) and control fibroblasts were grown for 12 days in media with no added glutamine or glutamic acid and 5% dialyzed FBS. Cells were lysed and the above mentioned mitochondrial proteins were checked via Immunoblotting. VCL was used as a loading control while the densitometry analysis (D) was done based on the mitochondrial proteinTOM20. Control bar represents an average of the two control fibroblast lines employed (F008 and F154). Although we could observe significant changes upon cysteine depletion in all conditions, the phenotype was exacerbated in the digenic fibroblasts compared to the controls.",
    "diseases": "RIRCD"
  },
  {
    "caption": "F. The concentration of FGF21  in serum. Control, N=18; POI, N=20; Boxplot, central band stands for median, boxes stand for 50% of the data, whiskers stand for min or max of the data G. The concentration of GDF15  in serum. Control, N=14; POI, N=9; Boxplot, central band stands for median, boxes stand for 50% of the data, whiskers stand for min or max of the data. Data information: Error bars stand for SEM of biological repeats. The p value was calculated by two-tailed t-test with 2-way ANOVA correction.",
    "diseases": "POI"
  },
  {
    "caption": "A-B. Elevation of serum ceramide  in POI patients  from the Fudan Cohort or the Shandong Cohort. Left, the relative abundance of total ceramide; right, the relative abundance of ceramide  with specific acyl chain. A. N=18; B. N=10; Truncated violin plot, central band stands for median, dotted lines stand for the upper quartile or the lower quartile of the data; Data information: The p value was calculated by two-tailed t-test with 2-way ANOVA correction.",
    "diseases": "POI"
  },
  {
    "caption": "H, I. Wnt inhibition reduces the expression of HR and FA pathway genes in a RNF43-mutant pancreatic cancer patient-derived xenograft and AsPC-1 cells. (H) Pancreatic canc­er PDX with G371fs RNF43 mutation treated with vehicle or ETC-159 (30 mg/kg) for 21 days were analysed for changes in the expression of the indicated genes measured by qRT-PCR. Each data point represents an individual tumor. The horizontal lines represent mean of 3 tumors/group. (I) AsPC-1 cells were seeded in low adherence plates, treated with DMSO or ETC-159 (100 nM) for 72 hours and the expression of indicated genes was measured by qRT-PCR.",
    "diseases": "Pancreatic canc­er, pancreatic cancer"
  },
  {
    "caption": " E, F. G007-LK and olaparib synergistically inhibit the growth of COLO320HSR colorectal cancer cells with APC mutation. COLO320HSR cells were plated at a low density and treated with G007-LK, olaparib or the combination of the two inhibitors at an equivalent dose as described in Figure 1A. (E) Representative image from two independent experiments is shown. (F) The Combination Index (CI) values of olaparib and G007-LK calculated from two independent experiments using the Chou-Talalay CompuSyn software ",
    "diseases": "colorectal cancer"
  },
  {
    "caption": "H-K. Expression of MYBL2 is downregulated upon ETC-159 or G007-LK treatment in multiple Wnt-high tumors. Expression of MYBL2 in AsPC-1 xenograft tumors and colorectal cancer PDX (as measured by RNA-seq) or in pancreatic cancer PDX with RNF43 mutation (measured by qRT-PCR) is reduced with ETC-159 treatment. G007-LK reduces MYBL2 expression in COL320HSR cells (measured by qRT-PCR). p-values were calculated with Mann-Whitney U test. Each data point represents an individual tumor or replicate. n = 4-6 samples/group. The horizontal lines represent median of 4-6 replicates with the upper and the lower edges of the boxes representing the 75th and the 25th percentile of the data respectively and the whiskers representing 1.5x interquartile range.",
    "diseases": "colorectal cancer, pancreatic cancer"
  },
  {
    "caption": "Immunohistochemical staining of sections of small intestine from C57BL/6J mice for DNA repair proteins shows that the expression of BRCA1, FANCD2 and RAD51 was high in the crypts (Wnt high compartment) whereas the villi did not show any staining. Small intestinal adenomas from APCmin/+ mice displayed positive nuclear immunostaining for HR and FA pathway proteins BRCA1, FANCD2 and RAD51. The bottom panels are higher magnification images of the areas marked in the top panels.",
    "diseases": "adenomas"
  },
  {
    "caption": "A Heatmap showing the unsupervised consensus clustering of TCGA melanomas (n=445: 356 metastases and 89 primary melanomas). The identified clusters are indicated below the heatmap: cluster 1 (n=55, red), cluster 2 (n=304, blue) and cluster 3 (n=86, green). Type of melanoma samples (primary or metastatic) and of metastatic site (subcutaneous, lymph node or distant) within each cluster are indicated below and above the heatmap, respectively. B Heatmap showing the unsupervised consensus clustering of TCGA primary melanomas (n=89) using the 1,000 most variable expressed genes in the same dataset. The identified signature clearly divides the TCGA dataset in two groups: Primary-A (n=34, red) and Primary-B (n=55, pink), as indicated. ",
    "diseases": "melanoma, melanomas"
  },
  {
    "caption": "C Boxplots showing the distributions of the normalized rank-sums of the up-regulated (left panel) and down-regulated (right panel) genes in the identified signature. Down-regulated genes in Primary-B melanomas better discriminate the two groups of primary melanoma samples (p=5.9e-15, Wilcoxon rank-sum test). Median, minimum, maximum, 25th, 75th whiskers of ranksum distribution are shown.",
    "diseases": "melanoma, melanomas"
  },
  {
    "caption": "A Box and whiskers (from 5th to 95th percentile) plots depicting TINCR RNA levels in the TCGA SKCM RNA-seq dataset of melanoma samples. TINCR expression is higher in Primary A melanomas, and its reduction in Primary-B melanomas and all groups of metastatic samples is statistically significant (Mann-Whitney test, **p< 0.01). Median, minimum, maximum, 25th, 75th whiskers of expression values are shown.",
    "diseases": "melanoma, melanomas, SKCM"
  },
  {
    "caption": "B Scatter-plot showing correlation between the expression of TINCR RNA and normalized rank-sums s of the down-regulated (upper panel) and up-regulated (lower panel) genes in the primary melanoma signature. TINCR expression strongly correlates (Spearman's correlation coefficient of 0.79, Spearman rank p-value: **p<0.01) with the expression of the down-regulated genes.",
    "diseases": "melanoma"
  },
  {
    "caption": "C Dot plot showing qRT-PCR analysis of TINCR expression in primary (8) and metastatic (8) melanoma samples from surgical specimens or patient-derived xenografts (4 primary and 8 metastatic PDXs). TINCR RNA levels relative to the L32P housekeeping gene are shown. Paired primary and metastasis PDXs are marked with an asterisk. The difference between primary and metastatic samples is significant (Mann-Whitney test, **p< 0.01). Median, minimum, maximum, 25th, 75th whiskers of expression values are shown.",
    "diseases": "melanoma"
  },
  {
    "caption": "(a) AAV-hACE2 mice were treated with saline and challenged with SARS-CoV-2 (8 × 104 PFU) for 5 days. Lung tissue sections were stained with DAPI (blue), anti-MPO antibody (green), anti-citrullinated histone H3 (Cit-H3) antibody (red), anti-CD42b antibody (yellow) and anti-CD31 antibody (gray). yellow arrow: NETs (DNA+Gr-1+MPO+Cit-H3+); red arrow: immunothrombosis (NETs + thrombus (CD42b+)), Scale bar is 100 μm.",
    "diseases": "immunothrombosis"
  },
  {
    "caption": "b & c) For prophylactic treatment, CLEC2.Fc (or vehicle) was given at 1 h before virus challenge; for therapeutic treatment, CLEC2.Fc was given at 8 hours post-infection. The area of NET (colocalization area of MPO and Cit-H3) (b) and immunothrombosis (colocalization area of Cit-H3 and CD42b) (c) were measured using MetaMorph software. Data are mean ± SEM from two independent experiments (saline: n=3 for 3 d.p.i., n=4 for 5 d.p.i.; isotype: n=3 for 3 d.p.i., n=4 for 5 d.p.i.; prophylactic treatment of CLEC2.Fc treatment: n=5 for 3 d.p.i. and 5 d.p.i.; therapeutic treatment of CLEC2.Fc: n=3 for 3 d.p.i. and 5 d.p.i.). *p <0.05, **p < 0.01 (Two-way ANOVA).",
    "diseases": "immunothrombosis"
  },
  {
    "caption": "Impact of TMPRSS2 on S levels. D. TMPRSS2 decreases S surface levels, measured by flow cytometry. 293T cells were transfected with S plasmid, with or without TMPRSS2, and analyzed 18h later. Murine polyclonal anti-S antibodies, one serum from a convalescent COVID-19 patient (sera n°111), and two monoclonal antibodies (anti-S1 and anti-S2) were tested. Data are representative of three independent experiments.",
    "diseases": "COVID-19"
  },
  {
    "caption": "Representative H&E images of human lung tissues from normal background and bronchiolitis obliterans (BO) with progressive fibrosis.",
    "diseases": "BO, bronchiolitis obliterans, fibrosis"
  },
  {
    "caption": "Representative IF images showing the expressions of nuclear YAP, DATP cell marker CLDN4, and AT1 cell marker AQP5 in the airways of normal background (top) and BO (bottom) human lungs. CLDN4 (white), AQP5 (red), YAP (green), and DAPI (blue). Of note, a flattened airway layer in BO lungs. Scale bars, 100μm.",
    "diseases": "BO"
  },
  {
    "caption": "Representative IF images showing the expressions of secretory cell marker CC10 and mTORC1 activation marker p-S6 in the airways of normal background (top) and BO (bottom) human lungs. CC10 (green), p-S6 (white), and DAPI (blue). Scale bars, 100μm.",
    "diseases": "BO"
  },
  {
    "caption": "Representative IF images showing the expression of nuclear YAP, ATF4, and AQP5 in the airways of normal background (top) and BO (bottom) human lungs. YAP (green), ATF4 (white), AQP5 (red), and DAPI (blue). Of note, co-expressions of nuclear YAP, nuclear ATF4, and AQP5 in the airways of BO lungs. Scale bars, 100μm.",
    "diseases": "BO"
  },
  {
    "caption": "Representative IF images showing the expression of p-S6 (white) in the airway cells losing CC10 (green) expression of BO human lungs. Scale bars, 100μm.",
    "diseases": "BO"
  },
  {
    "caption": "(D) Representative images of Nissl staining of Gpr56 null and Gpr56 S4 E16.5 neocortex. Arrows indicate cortical ectopias that are shown in insets. (E) Quantification of ectopia size per section. (F) The distribution of ectopia from rostral to caudal cortex.",
    "diseases": "ectopia, cortical ectopias"
  },
  {
    "caption": "(A, B) NDST3 protein levels relative to β-tubulin in B lymphocytes derived from healthy controls and C9orf72-linked ALS patients, as examined by immunoblotting  (n = 3 biologically independent samples, **P = 0.0026). Data information: Error bars represent ± standard deviation.",
    "diseases": "ALS"
  },
  {
    "caption": "(C-F) The protein levels of NDST3 relative to GAPDH (D) (**P = 0.0013), Ac-α-tubulin relative to total α-tubulin (E) (*P = 0.0379), and total α-tubulin relative to GAPDH (F) (P = 0.5700), as examined by immunoblotting, in spinal cord tissues from healthy controls and C9orf72-linked ALS patients (n = 4 biologically independent samples in the control group and n = 5 biologically independent samples in the  ALS patient group). Data information: Error bars represent ± standard deviation.",
    "diseases": "ALS"
  },
  {
    "caption": "(A) Immunoblot analysis of phosphorylated Smad2 (P-Smad2) and PMEPA1 (high and low exposures displayed) in MB patient sample lysates from different groups: WNT (blue), SHH (red), Group 3 (yellow) or Group 4 (green). β-actin was used as a loading control. Relative quantification of P-Smad2 signal to β-actin (P-S2/β-Actin) and total Smad2 (P-S2/Tot-S2) are indicated below the blots.",
    "diseases": "MB"
  },
  {
    "caption": "(B) Boxplots summarizing the expression of INHBB, TGFB1 and TGFB3 ligands of the TGFβ/Activin pathway in the different groups of MB (blue WNT, red SHH, yellow Group 3 and green Group 4) and in fetal and adult cerebellum (grey) in the dataset of \"Data ref: Cavalli et al, 2017\". Wilcoxon rank-sum tests were performed to determine p-values for panel B. p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.",
    "diseases": "MB"
  },
  {
    "caption": "(C) Immunoblot analysis of phosphorylated Smad2 (P-Smad2) in non-Group 3 (blue) and Group 3 (yellow) MB cell lines on the left panel. The level of total Smad2 (Smad2) was assessed and β-actin was used as a loading control. On the right panel, relative level of P-Smad2 (P-S2) were quantified to total β-actin. The p-values were determined by unpaired t-test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Bars represent the mean ± SD. Number of replicates is n≥3.",
    "diseases": "MB"
  },
  {
    "caption": "(D) RT-qPCR were performed on RNA extracted from non-Group 3 (blue) and Group 3 (yellow) MB cell lines to compare expression levels of INHBB (left) and TGFB3 (right). The p-values were determined by unpaired t-test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Bars represent the mean ± SD. Number of replicates is n≥3.",
    "diseases": "MB"
  },
  {
    "caption": "The level of phosphorylated Smad2 (P-Smad2) and total Smad2 (Smad2) was assessed by immunoblotting and β-actin was used as a loading control. Lower bar graphs show WB quantification of P-Smad2 (P-S2) normalized to β-actin. (A) Activation of the pathway was assessed in non-Group 3 (blue) and Group 3 (yellow) MB cell lines in response to TGFβ or ActivinB stimulation for 1h.",
    "diseases": "MB"
  },
  {
    "caption": "The level of phosphorylated Smad2 (P-Smad2) and total Smad2 (Smad2) was assessed by immunoblotting and β-actin was used as a loading control. Lower bar graphs show WB quantification of P-Smad2 (P-S2) normalized to β-actin. (C) Conditioned media experiments were performed on the HDMB03 MB cell line. Phosphorylation of Smad2 was analyzed by immunoblot upon treatment with either non conditioned media (NCM), media conditioned with HDMB03 cells (CM-HDMB03) or media conditioned with 1603MED cells (CM-1603). Pre-incubation with blocking antibody against ActivinB (Ab α-ActB) or vehicule (PBS) was performed before HDMB03 cell-line treatment as indicated. Relative level of P-Smad2 (P-S2) were quantified to β-actin (below). The p-values were determined by unpaired t-test. *p < 0.05, **p < 0.01, ***p < 0.001. Bars represent the mean ± SD. Number of replicates is n≥3.",
    "diseases": "MB"
  },
  {
    "caption": "(A) Ranking of top genes whose expression is correlated with INHBB in Group 3 MB patient samples. Spearman's rank correlation coefficient ρ and p-value are indicated. The p-values were determined by Spearman rank correlation test *p < 0.05, **p < 0.01, ***p < 0.001.",
    "diseases": "MB"
  },
  {
    "caption": "(B) Boxplots representing PMEPA1 expression levels in the different MB groups (WNT in blue, SHH in red, Group 3 in yellow and Group 4 in green) and in fetal and adult cerebellum (grey) in the dataset \" Data ref: Cavalli et al, 2017\". Only p-values corresponding to comparisons between Group 3 and the other groups are indicated. The p-values were determined by Wilcoxon rank-sum test *p < 0.05, **p < 0.01, ***p < 0.001.",
    "diseases": "MB"
  },
  {
    "caption": "(C) Scatter plot of INHBB and PMEPA1 gene expression levels in all MB groups. Colored dots represent each patient samples and colors represent the MB groups (WNT in blue, SHH in red, Group 3 in yellow and Group 4 in green). The p-values were determined by Spearman rank correlation test *p < 0.05, **p < 0.01, ***p < 0.001.",
    "diseases": "MB"
  },
  {
    "caption": "(A) Immunoblot analysis of phosphorylated Smad2 (P-Smad2) in Group 3 MB cell lines and PDXs. The level of total Smad2 (Smad2) was assessed and β-actin was used as a loading control. Quantification of P-Smad2 (P-S2) to β-actin are shown on right panel. Right (A) panels represent the relative quantification of P-Smad2 normalized to β-actin. Bars represent the mean ± SD. Number of replicates is n≥3.",
    "diseases": "MB"
  },
  {
    "caption": "(B) Expression of INHBB in Group 3 MB cell lines and PDXs relative to HDMB03 (set at 1) by RT-qPCR. Bars represent the mean ± SD. Number of replicates is n≥3.",
    "diseases": "MB"
  },
  {
    "caption": "(D) Conditioned media experiments were performed on HDMB03 MB cell line. Phosphorylation of Smad2 (P-Smad2) was analyzed by immunoblot upon treatment with either non-conditioned media (NCM), media conditioned with HDMB03 cells (CM-HDMB03) or media conditioned on PDX4 cells (CM-PDX4). Pre-incubation with blocking antibody against ActivinB (Ab α-ActB) or with vehicle was performed before HDMB03 cell-line treatment as indicated. lower panels represent the relative quantification of P-Smad2 normalized to β-actin. The p-values were determined by unpaired t-test. *p < 0.05, **p < 0.01, ***p < 0.001. Bars represent the mean ± SD. Number of replicates is n≥3.",
    "diseases": "MB"
  },
  {
    "caption": "(D) Boxplots representing the expression level of INHBB, PMEPA1, MYC and NRL in the different MB subtypes, as defined in Cavalli et al. (Cavalli et al., 2017). Only p-values corresponding to comparisons between Group 3 subtypes are indicated. Patient samples are colored by subtypes as indicated. (E) Scatter plot of INHBB and PMEPA1, expression levels in Group 3 patient samples. Colored dots represent each patient sample and colors represent the group 3 MB subtypes (α in yellow, β in brown and δ in orange). Wilcoxon rank-sum tests were performed for panel D. Spearman's rank correlation coefficient ρ and p-value are indicated on panel E. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001. Bars represent the mean ± SD. Number of replicates is n≥3.",
    "diseases": "MB"
  }
]