Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: LNCRNA–MRNA COMPETING ENDOGENOUS RNA NETWORK IN IR-HEPG2 CELLS AMELIORATED BY APBBR DECREASING ROS LEVELS: A SYSTEMATIC ANALYSIS
Review round: 1
Reviewer: 1

Output:
Basic reporting: English is not clear at all. There is no continuity between sentences. Very few literatures were cited. Poor description of aim.
Experimental design: Poorly designed experiments. Methods not fully described. Result section poorly written not clear.
Validity of the findings: no comments
Additional comments: 1. English is poorly written , not clear what authors want to say.
2. Author should describe aim in detail.
3. Figures are not properly labelled. Figures are very confusing and author should increase the resolution of figures
4. Introduction is very very small. Author should describe about ROS and what are the relationship between ROS and Diabetes?
5. why authors chose only HepG-2 cell lines, why not Huh7 cell lines?
6. Did the authors looked into total ROS? Phagolysosomal ROS? or Mitochondrial ROS?
7. Figure 1c is POORLY represented. what is the meaning of triangles and stars? what does model represent?
8. line 120 what is grpm?
9. why did the authors chose to add 10mg APBBR? Did the authors perform standard curve?
10. Author should take care while writing P value .


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: LNCRNA–MRNA COMPETING ENDOGENOUS RNA NETWORK IN IR-HEPG2 CELLS AMELIORATED BY APBBR DECREASING ROS LEVELS: A SYSTEMATIC ANALYSIS
Review round: 1
Reviewer: 2

Output:
Basic reporting: The study is overall well presented, though with several grammar mistakes and confusing statement. Introduction provided sufficient background information about the study. The structure  of the manuscript is fine. This article is self-contained with relevant results to hypotheses.
Experimental design: HepG2 IR cell model was used to generate the model. Then unbiased genome-wide RNA sequencing was used to investigate changes between groups. With the results, GO and
KEGG were then adopted to interpret the change. Venn analysis screened out candidate lncRNAs and target genes followed by construct interaction network of diﬀerentiated
lncRNA–miRNA–mRNA. The design is overall logic, with description sufficiet.
Validity of the findings: The idea of the study is good, with novelty. But was hust a preliminary exploration, still needs further molecular validation.
Additional comments: This article is overall well-designed which brings up an interesting question in discussing combined activities of the two potential antidiabetic ingredients, AP and BBR in ameliorating IR and efficacy in treating diabetes. But there're still some issues need to be explained as follows.
1. Validation reaults are needed to support the solidity of the study.
2. Interaction network of diﬀerentiated lncRNA–miRNA–mRNA needs further interpretation.
3. Sellection critiria of candidate lncRNAs and these target genes needs further concrete explaination.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: LNCRNA–MRNA COMPETING ENDOGENOUS RNA NETWORK IN IR-HEPG2 CELLS AMELIORATED BY APBBR DECREASING ROS LEVELS: A SYSTEMATIC ANALYSIS
Review round: 1
Reviewer: 3

Output:
Basic reporting: 1.	Manuscript has typographical errors in multiple places which need thorough checking. The letters”ff” is shown as box in all places. Kindly verify the font settings. Italicize  in vitro in line 370.
2.	Language and sentence construction needs refining to make sure the intended meaning is conveyed. Eg: Line 366 states “microorganisms react with cell macromolecules” but it should be “ROS reacts with..”
3.	Titles of sub headings in results section should be revised to indicate the results and not just the technique used. The first two sub headings of results section mentions just the technique used. The result obtained is not actually explained even in the first paragraph.
4.	Raw data submitted is not proper. (kindly refer general comments for detailed comments).
Experimental design: 1.	The research is original and has the potential to add significant knowledge upon further refinement.
2.	The aim of the manuscript is well framed but the experimental plan has introduced a bias in the selection of genes. This makes the conclusion biased too which need to be clarified by correcting the title of the manuscript, aim and conclusion accordingly. (kindly refer general comments for detailed comments).
Validity of the findings: 1.	Since the manuscript achieves identifying the target genes through pathway analysis and has not validated them, the discussion should clarify that it is in silico finding and in vitro/ in vivo validation is further needed when discussing about the pathway in figure-5.
2.	Previous reports with AP and BBR individually have reported to have anti tumor activity inducing cell death in multiple cancer systems. Therefore it is imperative to test their effect individually and in combination on proliferation/ cell survival of HepG2 control cells as well as model cells to see whether the increase in proliferation seen by the authors is specific to model cells.
3.	The glucose content is tested in only control and model cells and not with APBBR treatment. Also change in ROS in control cells upon APBBR is not tested. Adding these data will be more meaningful support the effect of the combination of these drugs in the concentration used in this study.
Additional comments: In the manuscript titled “Systematical analysis of lncRNA–mRNA competing endogenous RNA network on IR-hepG2 cells ameliorated by APBBR through decreasing ROS level”, the authors have attempted to understand the mehcanism of APBBR in regulaitng lncRNAs involved in regulating ROS pathway. Though the manuscript reveals the key lncRNAs and the ceRNA pathways regulated by APBBR to regulate ROS pathway in IR condition by pathway analysis, certain key points need to be addressed.

1.	Figure-4 represents comparative analysis between mRNA and lncRNAs does not add any significant information to the aim of this paper. Instead, comparison of mRNA and lncRNAs between control and model with and without APBBR treatment will add up information on the relationship between the ROS and RNA biogenesis in this context and the effect of APBBR if it alters.
2.	Line-344 states “24 miRNAs, 7lncRNAs and 3 mRNAs”, but line 741 states “30 miRNAs; Figure-5 shows 6 lncRNAs. Kindly verify these statements.
3.	In line-465, Is it “SOD” or “SCD” ?
4.	Line-120 states 100grpm. Centrifugation is performed according to xg or rpm calculation. Kindly clarify.
5.	Lines 340, 424 states candidates are selected based on relevance to ROS and IR. Therefore, there is a bias to see only the effect of APBBR on the relationship between ROS change in IR. Therefore the aim has to corrected accordingly. Moreover, how does this justify the statement in lines 336-337. Further, the analysis cannot be global pathway analysis in figure-5 when ROS pathway is selectively enriched.
6.	The lncRNAs shortlisted from venn diagram, (total of 7) are not seen in the lncRNA differential expression data given in supplementary file.
7.	The attached supplementary files does not represent the total list of lncRNAs obtained from analysis because it has only 100 lncRNAS in both the conditions and among them most of them does not have a significant P value. Only 1 in model vs control and 3 in APBBR vs model are significant (P < 0.05).


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: LNCRNA–MRNA COMPETING ENDOGENOUS RNA NETWORK IN IR-HEPG2 CELLS AMELIORATED BY APBBR DECREASING ROS LEVELS: A SYSTEMATIC ANALYSIS
Review round: 2
Reviewer: 1

Output:
Basic reporting: English is clear and Professional.
Experimental design: Primary research within the aims and scope of the journal. Research question well defined.
Validity of the findings: Conclusions are well stated and all data are provided
Additional comments: Thank you authors for revising the manuscript.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: LNCRNA–MRNA COMPETING ENDOGENOUS RNA NETWORK IN IR-HEPG2 CELLS AMELIORATED BY APBBR DECREASING ROS LEVELS: A SYSTEMATIC ANALYSIS
Review round: 2
Reviewer: 2

Output:
Basic reporting: Work is well presented.
Experimental design: The research is original and has the potential to add significant knowledge to the field.
Validity of the findings: The manuscript identifies the target genes through pathway analysis and can lead to future studies on validation..
Additional comments: 1. Kindly look at the lncRNA expression profile file updated as supplementary data and revisit the analysis. Presence of same lncRNA multiple times is acceptable but same lncRNA (SNHG6) is up regulated as well as down regulated (both significantly too). Kindly clarify the analysis method and make sure these anomalies are rectified.

2. As noted earlier, previous reports with AP and BBR individually have reported to have anti-proliferative activity inducing cell death in multiple cell lines including HepG2 cells. But here combination of both increases the proliferation inn HepG2 derived model cells. Therefore it is imperative to test their effect individually and in combination on proliferation/ cell survival of HepG2 control cells as well as model cells to see whether the increase in proliferation seen by the authors in this study is specific to model cells. This data is essential in two aspects. 1. whether AP and BBR have different functions when administered individually from being together. 2. whether the function of AP and BBR changes with context (control cell line and model cell line). So, doing this experiment is critical to this manuscript also.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: LNCRNA–MRNA COMPETING ENDOGENOUS RNA NETWORK IN IR-HEPG2 CELLS AMELIORATED BY APBBR DECREASING ROS LEVELS: A SYSTEMATIC ANALYSIS
Review round: 3
Reviewer: 1

Output:
Basic reporting: Work is well presented with references.
Experimental design: The research is original with methods explained in detail and has the potential to add significant knowledge to the field.
Validity of the findings: The manuscript identifies the target genes through pathway analysis and can lead to future studies on validation of the target genes.
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: SEASONAL VARIABILITY AND VERTICAL DISTRIBUTION OF AUTOTROPHIC AND HETEROTROPHIC PICOPLANKTON IN THE CENTRAL RED SEA
Review round: 1
Reviewer: 1

Output:
Basic reporting: Review report:
“Seasonal Variability and Vertical Distribution of Autotrophic and Heterotrophic Picoplankton in the Central Red Sea”

This study has investigated the vertical and seasonal variations of hydrological conditions and picoplankton communities in the central Red Sea, respectively.
Experimental design: Sampling plan in the present study is very good and the data set is also highly interesting. However, there are many repetitive descriptions and minor problems in the manuscript, I think the manuscript is needed to be compacted and revised. Overall, this manuscript is suggested to be published after aborative revisions. Specific comments are as follows:
Validity of the findings: The authors revealed that maximum cell abundance for each picoplankton group showed large differences in vertical distribution; while picoplankton abundances exhibited various patterns for seasonal variation. Consistent with previous observations, autotrophic picoplankton biomass in the upper waters accounted for the majority of total picoplankton biomass. The biomass of heterotrophic prokaryotes throughout the whole water column, however, were much higher than that of autotrophic picoplankton. Conclusively, the seasonal differences of picoplankton assemblages in the central Red Sea are not fundamentally different to higher latitude regions.
Additional comments: Comments to the Authors
Review report:
“Seasonal Variability and Vertical Distribution of Autotrophic and Heterotrophic Picoplankton in the Central Red Sea”
General comment:
(1)This study has investigated the vertical and seasonal variations of hydrological conditions and picoplankton communities in the central Red Sea, respectively. The authors revealed that maximum cell abundance for each picoplankton group showed large differences in vertical distribution; while picoplankton abundances exhibited various patterns for seasonal variation. Consistent with previous observations, autotrophic picoplankton biomass in the upper waters accounted for the majority of total picoplankton biomass. The biomass of heterotrophic prokaryotes throughout the whole water column, however, were much higher than that of autotrophic picoplankton. Conclusively, the seasonal differences of picoplankton assemblages in the central Red Sea are not fundamentally different to higher latitude regions.
(2) Sampling plan in the present study is very good and the data set is also highly interesting. However, there are many repetitive descriptions and minor problems in the manuscript, I think the manuscript is needed to be compacted and revised. Overall, this manuscript is suggested to be published after aborative revisions. Specific comments are as follows:
ABSTRACT:
(1)P22-23, please change “standing stocks and cellular characteristics” into “abundances and biomass”;
(2)P23, please delete the repetitive word “cyanobacteria”, or change “Prochlorococcus and Synechococcus” into “picocyanobacteria”;
(3)P27-29, I don't understand why the authors described the hydrological conditions starting at “The sea surface temperature ranged from.......” as one part of the abstract, and what the significance and correlation are between these sentence and the manuscript's aim in this part.
(4)Additionally, P29-45, these sentences are mainly repetitive descriptions of the results and some are redundant, please simplify.
(5)P50-52, please check English grammar
Key words:
(6)The authors should add the key words, which are important for readers to know more about this paper.
INTRODUCTION:
(7)P62, please change “cyanobacteria” into “picocyanobacteria”
(8)P109, please change “cellular characteristics” into “biomass”
MATERIALS AND METHODS:
(9)P129, 200 ml water samples? Is it enough for acquiring the size-fractionated Chl a?
(10)P141, 10% paraformaldehyde? Please check;
(11)P150, Bibliographic references should be added to support the application of SYBR Green II;
(12)P151, A recently published paper showed the detection of surface Prochlorococcus is a major challenge to even the most sensitive instruments (BD Influx with small particle detector; Ribeiro C G et al., 2016, Estimating microbial populations by flow cytometry: Comparison between instruments), and I’m not sure your instrument has a small particle detector, if not, please give full details in the Instrument Settings. Please refer to Wei et al., 2019, Dynamic responses of picophytoplankton to physicochemical variation in the eastern Indian Ocean.
(13)P159, I am confused that how the authors calculate this conversion factor 237 fg C μm–3, Please list the calculation formulas and references.
RESULTS:
(14)P177, Figures quality need to be improved, especially for the font format (all should be changed into Times New Roman). Please provide high resolution graphs;
(15)P178, Please delete the redundant word “sea”;
(16)P200, Please use seasonal interval, rather than days of year;
(17)P279, I don't understand the meaning of this sentence starting at “The stress level was relatively low, indicating a reliable distribution of samples in two arbitrary dimensions.” How do you assess the reliability based on stress level? Please explain and list bibliographic references.
(18)P281, Please list the original data of the correlation coefficient between NMDS scores and environmental variables, and please explain “r, r2 and p”
(19)P285-288, I don't understand what the authors would like to express through these sentences, is it correlation? If so, where is the correlation coefficient?
DISCUSSION:
(20)P293, Please list subheadings in the discussion section;
(21)P370, DIP is a key factors in affecting the distributions of picoplankton, but i am confused why the authors did not analyze the relationship between DIP and picoplankton abundance based on the NMDS analysis in the discussion section;
(22)P371, The authors indicated that the vertical distribution of picoplankton was most clearly affected by depth, and is related to gradients in environmental variables, for example light irradiation; however, I don't understand why the authors presented the relationship between picoplankton and light as per bibliographic references, instead of analyzing the field irradiance (PAR) acquired from SeaBird SB9 Plus or IDRONAUT 305 CTDs.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: SEASONAL VARIABILITY AND VERTICAL DISTRIBUTION OF AUTOTROPHIC AND HETEROTROPHIC PICOPLANKTON IN THE CENTRAL RED SEA
Review round: 1
Reviewer: 2

Output:
Basic reporting: The manuscript was very well written and the story, logic and results easy to follow.
However, I felt the first two paragraphs of the introduction were rather long and it took a long time to get to the third paragraph where reasoning for the study was first introduced. Suggest to make the first two paragraphs more concise, and highlight the gaps that are relevant to this study (i.e oligotrophic environment, high temperature and salinity compared to other regions, limited information of picoplankton in these types of environments). Then using those gaps, lead into the third paragraph to highlight what is known of picoplankton in the Red sea and why having an understanding of temporal changes in their abundance is important. I felt the link to upper food webs in the Red Sea was lacking – suggest to include more information on this (in a few sentences).
The structure of the manuscript conforms to PeerJ standards.
Raw data is supplied in the supplementary information.
Figures are well presented, labelled well and on the most part easy to understand. A few suggestions provided below to improve figures and their interpretation by readers.
Figure 3– suggest to have Synechococcus (LF and HF) on the same scale, and Speuks and Lpeuks on the same scale – to allow clear interpretation by the reader.
Figure 4 – Have D and E on the same scale.
Figure 6 – (cell ml-1) change to (cells ml-1)
Experimental design: The research was well defined. The way the research fills an identified knowledge gap could be made clearer, in the abstract, introduction and discussion. See above for comments on the intro in relation to this and expand on this briefly in abstract and further in discussion.
The periodic seasonal sampling provided for meaningful and provided for clear results. Measured parameters were valid for the study and explained well in the methods section.
The statistical analyses performed for the study were appropriate for the data, allowing for detection of differences in the picoplankton community between seasons and in the vertical water column where found. These results were well detailed and depicted.
Validity of the findings: The findings of the study are novel for the region of the Red Sea and expand on the increasing information available on picoplankton in the ocean. The trends were displayed well in figures and interpreted well in the manuscript. Discussion points and speculation and conclusions reached were for the most part, valid. Some discussion points were highlighted in the pdf version to either rework, condense or add more information. See pdf for this.
Additional comments: This study provides temporal and in situ vertical distribution information on picoplankton in the oligotrophic, high temperature and salinity waters of the Red Sea. Distributions were linked to environmental parameters, and showing light and nutrients to be clear drivers of the picoplankton community. This study fills a knowledge gap for the region of the Red Sea and what is known on the temporal and vertical picoplankton abundances and distributions.
In addition to the below review, please see also attached manuscript with edits/and suggestions to improve the manuscript.  Most suggested changes and additions are included in the pdf as comments and word edits.
In all this manuscript provides new data in relation to picoplankton in the Red Sea. The survey design well thought out and instigated, and all the data collected was relevant to the writing of the manuscript.  The manuscript was well written, clear and concise in most parts (the suggested changes/edits are indicated in the pdf). In all, with the suggested edits, I would recommend publication of this manuscript to PeerJ.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: SEASONAL VARIABILITY AND VERTICAL DISTRIBUTION OF AUTOTROPHIC AND HETEROTROPHIC PICOPLANKTON IN THE CENTRAL RED SEA
Review round: 1
Reviewer: 3

Output:
Basic reporting: The MS by Al-Otaibi et al (#39703) addresses the question of the seasonal variability and vertical distribution of autotrophic and heterotrophic picoplankton in the central Red Sea. It provides the first insight into temporal dynamics of ecologically relevant players.

The article is well written and the work presents an interesting dimension to a less studied marine ecosystem.
However, the introduction reads like a review of existing literature, including their own, rather than a structured argument for the study. This part needs significant improvement; else, it digresses the readership.

Some terminologies are not clear (e.g., “unicell”).
Important literature from recent work is also not referenced though it represents significant advancement to the functional molecular ecology of the Red Sea (Thompson et al. 2016. The ISME Journal 11, 138-151
; 2013. Ecology and Evolution 3). For instance, in line #95

In line#108, I would suggest re-phrase the permanently stratified statement, by qualifying with a specific depth. Stratification is defined by depth of the water column, and this changes considerably by season. Indeed, line#304–305 shows that the nutrient dynamics change in this site. So up to what depth is the Red Sea water (at the site) stratified?
Experimental design: Although the methods are well defined, with majority coming from the authors’ lab(s), it would help if a supplementary graphical figure were provided encompassing a guide to these approaches. At the moment it’s too verbose; and a figure would help navigate the experimental design better.
Validity of the findings: All data are provided and statistically sound.

In the abstract and line #298 please rephrase the word “700 m deep” to “700-m deep”; the former suggests that the sampling was done at 700 m!

In line#324, it should be pointed out that the two methods have different sensitivities; PCR is more sensitive; so that the oddity suggested is invalid. The subsequent line#330 only suggests differences in flow cytometer detection limits.

The line#331, the authors lay emphasis on the “lowest” abundance ever recorded. I think this is rather speculative since biomass in the ocean is dynamic, and can be low or higher depending on the season. So the values reported are only a steady-state situation at the time of sampling. To make the “lowest ever recorded” claim requires high-frequency sampling (s.f. line#437–438).
Additional comments: The MS is sound and the data provided is relevant for understanding ecosystem function of the changing pelagic global ocean. And studies coming from the Red Sea provide a basis for understanding the implications.
In sum, I recommend the acceptance of the MS, provided the minor issues are resolved.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: SEASONAL VARIABILITY AND VERTICAL DISTRIBUTION OF AUTOTROPHIC AND HETEROTROPHIC PICOPLANKTON IN THE CENTRAL RED SEA
Review round: 2
Reviewer: 1

Output:
Basic reporting: no
Experimental design: no
Validity of the findings: no
Additional comments: Keywords should not be abbreviated! As the authors have considered all comments and suggestions, I recommend this MS for publication. Congratulations!


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: PREVALENCE OF AND RELATED RISK FACTORS IN ORAL MUCOSA DISEASES AMONG RESIDENTS IN THE BAOSHAN DISTRICT OF SHANGHAI, CHINA
Review round: 1
Reviewer: 1

Output:
Basic reporting: The article fails to meet the PeerJ standards
English is poor
Experimental design: The study is not well designed to demonstrate the aims and scope.
Validity of the findings: Provided data are not robust, not statistically supported.
Additional comments: The authors describes the prevalence of OMDs and related risk factors, in Shangai.
The study is not well designed and linguistic and conceptual limits do not raccomand the article publication in the present form.

INTRODUCTION

“… occur in the oral mucosa and soft tissues”
please specify the differences between oral mucosa and soft tissues.

“… and are related to general health”
 not all the OMDs are related to general health. Traumatic lesions, for example, are not related to general health.

“…The etiology is unknown…” . Of what?

“…the course of disease is difficult to cure, easy to relapse, and is closely related to systemic diseases and physical and mental”.
 Convulsionary phrase. Physical and mental what? Are you describing a specific disease or all the OMDs?

“OLP is the most common clinical OPMDs”
 why have you specified “clinical”?

Please, cite the most common meta-analytic studies about the OLP rate of transformation in OSCC.

“Oral leukoplakia (OLK) is the most important OPMDs”:
why you defined OLK “important“ ?

Poor prognosis of OPMDs and the condition of multiple and recurrent cancers can cause great physical and mental pain to patients.
Poor prognosis of OPMD why? Please cite the references about physical and mental pain.

Early diagnosis of OPMDs with high risk of cancer is of great significance for the prevention of oral malignant tumors (McCullough et al., 2010; Amagasa et al., 2011).”
In my opinion, early diagnosis shlould be referred to all OPMDs, not only to OPMDs with high risk of cancer.

“In this study, the epidemiological characteristics of oral mucosal diseases..”
OMDs.

“…for the prevention and treatment of oral mucosal diseases.”
OMDs.

M&M
The sample size calculation is missing
Local ethical committee permission is missing in the text.
How the clinicians were calibrated?
Have you evaluated the inter-rater agreement? If yes, how?
“Our survey form was prepared according to the oral health assessment form of WHO (2013) (World Health Organization, 2013).”
Please cite a reference or the site address

Please describe how the patients were visited; how the lesions were scored or described, if biopsies were performed, were expert pathologists involved? Who confirmed the diagnosis?

RESULTS

“White collar person”
Please clarify
Please re-write results in a more appropriate way.

DISCUSSION
re-write according to results revisions.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: PREVALENCE OF AND RELATED RISK FACTORS IN ORAL MUCOSA DISEASES AMONG RESIDENTS IN THE BAOSHAN DISTRICT OF SHANGHAI, CHINA
Review round: 1
Reviewer: 2

Output:
Basic reporting: 1. According to the authors, almost 7% of the participants were lost to follow-up; did these subjects differ in terms of social and demographic characteristics from those who were evaluated in 2018?
2.	Figure 1, correct the word “make” with “male”. In the same Figure indicate significant differences between males and females.
3.	In Figure 2, please present data not in lines but in columns.
4.	In Figures 3 and 4 define the meaning of the asterisks.
Experimental design: How did the authors evaluate alcohol consumption and smoking? A definition should be provided in the methods section. The same stands for diagnosis of diabetes, hypertension, coronary heart disease and cerebrovascular disease.
Validity of the findings: The authors reported that they examined incidence of OMD during the 4-year period; however, no such information is provided and instead prevalence is reported.
Additional comments: This is an observational prospective study that examined the prevalence of oral mucosal diseases (OMDs) in residents in one district of Shanghai during the years 2014-2018.  The authors examined 653 residents aged from 17 to 92 years old. They found that the prevalence rate of OMDs was 9.04-9.56%. The most common OMDs were atrophic glossitis (1.84%), recurrent aphthous ulcer (RAU, 1.68%), burning month syndrome (BMS, 1.38%), oral lichen planus (OLP, 1.23%), and traumatic ulcers (1.23%). Tobacco and alcohol use and psychological factor in OMDs group were higher than the no-OMDs group. System disease including diabetes mellitus (DM) was relevant to OLP. They conclude that age, tobacco and alcohol use, and psychological factor correlated with the occurrence and development of OMDs and that OLP was closely related to DM.

Comments:
1.	According to the authors, almost 7% of the participants were lost to follow-up; did these subjects differ in terms of social and demographic characteristics from those who were evaluated in 2018?
2.	How did the authors evaluate alcohol consumption and smoking? A definition should be provided in the methods section. The same stands for diagnosis of diabetes, hypertension, coronary heart disease and cerebrovascular disease.
3.	Figure 1, correct the word “make” with “male”. In the same Figure indicate significant differences between males and females.
4.	In Figure 2, please present data not in lines but in columns.
5.	In Figures 3 and 4 define the meaning of the asterisks.
6.	The authors reported that they examined incidence of OMD during the 4-year period; however, no such information is provided and instead prevalence is reported.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: PREVALENCE OF AND RELATED RISK FACTORS IN ORAL MUCOSA DISEASES AMONG RESIDENTS IN THE BAOSHAN DISTRICT OF SHANGHAI, CHINA
Review round: 1
Reviewer: 3

Output:
Basic reporting: - English language and grammar use should be examined in the entire manuscript, including the tables
Experimental design: I have found one recent study reporting the prevalence of oral lesions in Shanghai, which is cited in the text and which included larger number of patients, but these patients were not followed-up after four years as the authors of this study did. This information from this article can be useful to the readers.
Please fill in, in the section Materials and Methods, how the participants were selected? How many inspectors examined the patients?
Validity of the findings: I have found one recent study reporting the prevalence of oral lesions in Shanghai, which is cited in the text and which included larger number of patients, but these patients were not followed-up after four years as the authors of this study did. This information from this article can be useful to the readers.

The first sentence in the "Conclusion section" should not begin with "Therefore", I suggest that the authors rephrase this sentence.
Additional comments: The study includes a large number of patients, and it is useful that the follow-up was made after four years to compare the data. After the suggested corrections and language correction, I think that the article can be published.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: PREVALENCE OF AND RELATED RISK FACTORS IN ORAL MUCOSA DISEASES AMONG RESIDENTS IN THE BAOSHAN DISTRICT OF SHANGHAI, CHINA
Review round: 2
Reviewer: 1

Output:
Basic reporting: The authors have made a great improvement in English language and grammar. The sentences are now clear, easy to read and supported by data obtained from the research.
Experimental design: Research questions are well defined. The methods are described with sufficient details and information. My previous comments have been responded in the text.
Validity of the findings: The data are statistically sound and encouraged with the results from the literature. Conclusion is now well stated, reformulated and clear.
Additional comments: Dear authors, you have made significant improvement in structure and language. The limitation of the study is sample size, which you have pointed out in the text.The strength of your study is a four-year follow up of the patients, which is useful for comparing data.
I have noticed one small mistake in line 242, please correct this: "Our study showed that the prevalence of OMDs in patients who smoke, drink and experience anxiety was higher than in those who were healthy".
I recommend that, after this correction, the article should be accepted for publication.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: PROGRESS OF RESEARCH INTO CIRCULAR RNAS IN URINARY NEOPLASMS
Review round: 1
Reviewer: 1

Output:
Basic reporting: No comments
Experimental design: No comments
Validity of the findings: No comments
Additional comments: In this manuscript, Wan and colleagues reviewed the current knowledge of circRNAs in bladder cancer, renal cancer, and prostate cancer. The authors also discussed circRNAs as therapeutic targets for the treatment of these diseases. Overall, the review is novel and interesting. However, I have a few minor comments to improve the manuscript.
Comments:
1.	Figure legends need to be rewritten for a better understanding of the figures.
2.	Figure 1; The circRNA function has been very well discussed in many reviews. Please remove the circRNA function from this figure.
3.	Figure 2; All transcript starts with Exon 1, please edit the figure accordingly and put another exon at the end. Additionally, the vast majority of circRNAs start and end in the middle exons. The circRNA function panel in Fig 1 can be placed in the place of the middle panel in Fig 2.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: PROGRESS OF RESEARCH INTO CIRCULAR RNAS IN URINARY NEOPLASMS
Review round: 1
Reviewer: 2

Output:
Basic reporting: In this review, author summarized the role of circ-RNA in urinary neoplasms. The article has good logicality and the narration is fluent.
Experimental design: 1.In this article, author choosed bladder cancer, renal cancer, and prostate cancer. Are the the include all types of urinary neoplasms or occupy most of urinary neoplasms? Please explain the relationship between these three kinds of tumors and urethral tumors to make convenient for readers without medical background.
Validity of the findings: 2.There are some inconsistent abbreviations such as “CircRNA or circRNA”, Anticancer or anticancer? (line 238), and mir or miR? (line 285).
3.Plesas properly introduce the naming rules of CicrRNA as I feel the name of circRNA is confused.
4.In line 200, there is a instance about circHIPK3, the author side “Silencing circHIPK3 can significantly inhibit the growth of human cells ” and in line 206 the author side “Overexpression of circHIPK3 effectively inhibited migration, 207 invasion, and angiogenesis of bladder cancer cells in vitro and suppressed bladder cancer growth 208 and metastasis in vivo”. it seems there is contradiction between this sentences. If there is different results about circHIPK3 in different study? Please interpret and discuss it.
5.The sentece “Recent studies showed that dysregulation of circHIPK3 expression correlated with occurrence and progression of human disease (Cao et al., 2018；Yu et al., 2018)” line202-203 should be put ahead to make the narrative more logical.
6.Please add the “q-PCR” abbreviation behind “Quantitative Real-Time Polymerase Chain Reaction” (line 213). Most readers are more familiar with q-PCR.
7.Line 214, author has mentioned “circRNA-000285 was down-regulated in bladder cancer tissues, cell lines and serum of bladder cancer patients”, the said “ it was also significantly down-regulated in bladder cancer serum samples” again (line 215). It was duplicate of serum.
8.Line 252, “CircFNDC3B was.....” if there should be “is”?
9.Line 197, in general understanding, miRNA can inhibit target gene expression, here the author side “CircRNAs function as sponges of miRNAs to down-regulate target gene expression and inhibit progression of bladder cancer (Fig2)”. So how circRNA sponges miRNA and further down-regulated target gene expression?
10.There are some sentence shuld be split, for instance in line 243, the author said “A recent study suggested that circUBXN7 was significantly down-regulated in BC tissues compared with matched non-tumor tissues, and the expression of circUBXN7 was related to the pathological stage, grade and poor prognosis of bladder cancer positively, further studies found that circUBXN7 could directly bind to miR-1247-3p, and reversed the oncogenic effects induced by miR-1247-3p”. the sentence is too long, and further studies...should be another new sentence. Similar problems occur many times.
Additional comments: 11.If the each circRNA and instances could be summerized in table, it will convenient for readers to remember and summarize.
12.Last but not least, in general, most part of the text is simply narrate, there is few of valuable discussion and author's own thoughts. Pleases discuss further, for example, but not limited to what is the appropriate concentration of circRNA treatment in examples involved, which is a problem of concern of readers, and what should be paid attention to in circRNA studing? And what are the biggest advantages or obstacles in circRNA studing field in author's point of view?


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: RESTORED FRESHWATER FLOW AND ESTUARINE BENTHIC COMMUNITIES IN THE NORTHERN GULF OF MEXICO: RESEARCH TRENDS AND FUTURE NEEDS
Review round: 1
Reviewer: 1

Output:
Basic reporting: There appears to be proposals to divert river flow to deliver sediment downstream to rebuild wetland habitats, and this study provides a review of the potential effects on benthic communities.  This is well justified but should mention the many studies that describe wetland loss rates that have already happened.  As written, the first paragraph makes it appear that it is a relative SLR issue alone, but I thought it was due to scouring effects of the dykes and levees along the Mississippi River and this has been going on for a very long time (how long?).

The study also borders on being of local interest only, and it should probably be broadened a bit to make of interest to a wider audience.
Experimental design: The authors have done a good job of thinking through all the potential confounding factors (such as salinity change, food-web alterations, and habitat alterations) and demonstrating how each might cause unanticipated consequences.

The one thing that needs more attention is the “estuary signature” issue.  What appears to be contradictory results are simply differences among estuaries because of antecedent conditions,  long-term average estuary conditions, or residence times.  An estuary where the salinity is low (<5 psu) does not change much when a lot of water is added, but and estuary where salinity is high (>25) changes a lot when water is added.  Also the relative volumes of the water flow and the receiving waters is a critical metric.  A bay that is small and water age is short, responds very differently from a bay that is large and the water age is long.  This means that you have to be careful not to make broad sweeping conclusions, that might in fact only reflect a specific type of system.
Validity of the findings: The paper is unique and tackles a problem that is not often studied, so I think it is important.  Also, there will be a lot of focus on restoring Gulf of Mexico habitats over the next 30 years because of the restore funding made available by the Deepwater Horizon settlement, so the review is timely.

While I agree that the literature reviewed is appropriate, I think there is a lot more literature from Mobile Bay, AL, and the Sacramento and San Joaquin River Delta area in CA that are relevant.  This is a tough one because no review that is manuscript in length can cover everything, I do think there are some lessons from CA that are useful because the flow volumes there are also large like the MS River volumes.

The findings and conclusions are sound, but I do think that the finding should be tempered by what I call the estuary-signature issue (described above and below).
Additional comments: The reference list and citations within the text need a thorough review, there are many inconsistencies.  And, there needs to be a check for missing references.  Some specific comments are below:

L32: “results … are optimistic” doesn’t make sense. Plans can be optimistic. Better revise this sentence.
L34: Abstracts are better when written in the third person.
L41-44:  An abstract should end with the significance of the findings.  While I agree with the sentiments expressed in the last two sentences, they are not conclusions of this study.
L106: there is a ton of benthic stuff published on Mobile Bay too, which should be relevant to a review, particularly by Gary Gaston, and Chet Rackocinski.  There is a ton of work on meiofauna from John Fleeger and his students in the LA bays and marshes.
L195: I think this reference should be Palmer et al. or Palmer, Montagna, and Kalke.
L220, 222, 252, 258, and many more: VanDiggelen and Montagna?
L400-402:  Needs a little tweaking.  While it is true that systems with high flow volumes (like the MS River) wash Chl downstream, systems with lower flow volumes (like some of the TX estuaries) can stimulate Chl, and you see positive correlation with flow.  Point is that you can get different responses in different kinds of systems depending on the overall volumes of flow and the receiving bay.  Thus a better indicator than flow rate is turn-over or residence time of the water.
L477: Interesting section, but stuff about seagrass response is a bit surprising.  Which seagrass species increase in which salinity range?  Most seagrass species prefer high salinity and marine conditions, and high flow rates decrease seagrass cover.  One exception is Vallisneria, which likes salinities in the range of 5 psu or so. There is a lot of literature from the west coast of FL on this, particularly by Peter Doering.
L554:  Again, it depends on the system and antecedent conditions.  In estuaries where the average salinity is low (~ 10-15) then floods kill oysters because salinities go near zero.  But in estuaries where average salinity is high (~25-30) then floods enhance oysters because salinities go to their optimal range around 18.  There are tons of papers on this from the Gulf, particularly Apalachicola Bay in FL, Copano, San Antonio, and Galveston Bays in TX, and Breton Sound, LA.  BTW, this explains why there is no conflict between Turner (Estuaries and Coasts 29:345-352, 2006) and Buzan et al. (Estuaries and Coasts 32:206-212, 2009).  You would be doing the world a favor by pointing this out.
L566: I think this is the same story as above.  Just be careful here.
L604: Do you mean “… response to sediment flux caused by freshwater flow diversions..”?  Or the other way around “…response to salinity change caused by freshwater flow diversion to deliver sediment to the…”?
L611-615: Again, I think it is misleading to make blanket statements without considering antecedent conditions, or a change in the average conditions.
L641: replace since with because.
L675: can you provide a link to this report?
L 691: out of order.
L752: caps?
L765: incomplete reference
L771: caps?
L813-814: punctuation


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: RESTORED FRESHWATER FLOW AND ESTUARINE BENTHIC COMMUNITIES IN THE NORTHERN GULF OF MEXICO: RESEARCH TRENDS AND FUTURE NEEDS
Review round: 1
Reviewer: 2

Output:
Basic reporting: The review has a clear and important purpose, will be of interest to many researchers, and is appropriate for this journal.

I think the introduction needs some work:
1.	I suggest reorganizing to lay out all of the expected effects of the diversions at the beginning then discuss the potential impacts of each in the sections. As written, the paper seems very long and it’s not clear what is coming next. There are nice transition sentences between sections, but I think it would be better to lay out the outline clearly in a bit more detail at the beginning and remove or shorten the transitions.
2.	The explanation of the diversions in the system is confusing and needs clarification and some more detail. I suggest modifying figure 1 to specify where the water goes from each of these diversions with arrows and also include information about how much water is diverted at each one (maybe visualized as arrow size in the figure). I’m not totally clear on the difference between the existing “freshwater” diversions and proposed “sediment” diversions (line 66), more explanation here would be helpful.
Experimental design: The literature review seems fairly thorough to me, although I had a few minor points:
1.	Lines 330-335 this is an oversimplification and not necessarily accurate. See classic work by Sanders in Buzzards Bay.
2.	Line 409 ref needed here

The review is organized well into sections that make sense, but I recommend some reorganization to put more of the predicted effects of the diversions at the beginning and focus in the later sections on how these predicted effects will affect benthic communities (see above).

Figure 2 does not seem necessary.
Validity of the findings: The conclusions and points for future research seem good to me. The authors have compiled a lot of useful information and have written a nice synthesis, but I think the paper would really benefit from a well-conceived conceptual diagram to summarize these findings. Figure 3 is sort of confusing and not particularly informative, and the two tables contain an overwhelming amount of information. A really nice diagram that clearly conveys the major effects of freshwater diversions on benthic communities would be widely used in teaching and research (at least, I would like to have a good diagram on this for my teaching!). I recognize that developing really good conceptual diagrams is challenging, but I strongly encourage the authors to spend some time on this.
Additional comments: This manuscript is really interesting and generally well written but does seem a little long and somewhat wordy in places, I recommend editing to make it a little more concise.

Minor points:
Lines 269-271 awkward sentence
Lines 307-309 these numbers aren’t comparable, need to have the same units.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: RESTORED FRESHWATER FLOW AND ESTUARINE BENTHIC COMMUNITIES IN THE NORTHERN GULF OF MEXICO: RESEARCH TRENDS AND FUTURE NEEDS
Review round: 2
Reviewer: 1

Output:
Basic reporting: The authors have done a good job of responding to all suggestions, and this section is now good.
Experimental design: The authors have done a good job of responding to all suggestions, and this section is now good.
Validity of the findings: The authors have done a good job of responding to all suggestions, and this section is now good.
Additional comments: L 176: Meiofauna in estuaries are usually defined as <0.5 mm and > 0.063 mm. There are hundreds of references on this, but using one of the books by Olav Giere is best.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: RESTORED FRESHWATER FLOW AND ESTUARINE BENTHIC COMMUNITIES IN THE NORTHERN GULF OF MEXICO: RESEARCH TRENDS AND FUTURE NEEDS
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors have done a nice job of addressing my comments. Figure 1 is much better. I still have a few concerns about Figure 3 – most importantly, it has red and green arrows that will not be distinguishable by someone who is color-blind or even when printed on a black and white printer, the colors need to be changed and ideally distinguishable by line type as well as color. Why will increased sedimentation increase primary production? The figure doesn’t really match the text. Consider adding arrows for unknown effects – the text discusses potential but unknown effects on benthic community structure, diversity.
Experimental design: no comment
Validity of the findings: no comment
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: TRANSCRIPTOMIC AND PROTEOMIC PROFILES OF II YOU 838 (ORYZA SATIVA) PROVIDE INSIGHTS INTO HEAT STRESS TOLERANCE IN HYBRID RICE
Review round: 1
Reviewer: 1

Output:
Basic reporting: More background about the mechanism of heat-tolerance in rice.
Experimental design: No comment.
Validity of the findings: No comment.
Additional comments: Wang et al described a genome-wide transcriptome and proteome analysis of hybrid rice. Their work identified the potential role of a complicated regulatory network in heat tolerance of II YOU 838, including HSF-Hsp, photosynthesis and oxidation-reduction. The experiments are well designed and the manuscript is well organized. However, there are several points I feel concerned.

Major points
1)	Proteome data were used in combined analysis with transcriptome data, which also provided key evidences. Hence, the title should be improved.
2)	The introduction section is too weak. I failed to gain a whole picture of the mechanism of heat-tolerance in rice or even other plants from this section.
3)	The authors described the results in an illogical order. For example, DEGs encoding TFs were described, followed by those encoding PALs, GSTs, and Hsps and so on in line 185-197. Why?
4)	They speculated that HSF-Hsp might be important for heat tolerance in II8, and explained a lot of their evidences. However, too little information was given in the figures.
5)	Some references are missed.

Minor points
1)	Line 35: ‘help to’.
2)	Line 44-46: References are needed.
3)	Line 60-62: References are needed.
4)	Line 70: Confused. I think they want to say the overlook of early responses of heat shock in previous studies.
5)	Line 83: ‘Sichuan’.
6)	Line 113: Please check the reference.
7)	Line 129: ’ACTIN1’.
8)	Line 150-157: The authors described the flag leaf phenotype and identified II8 to be more tolerance to heat stress. Is there any physiological evidence?
9)	Line 176: What does they mean by over-dominant genes?
10)	Line 184: I feel it is not so interesting.
11)	Line 260 and 262: What does the WRKY family mean? The whole family in rice? Or DEGs belonging to WRKY?
12)	Line 260-262: Which WRKY? Is it included in the DEGs?
13)	Line 277: ‘than in’.
14)	Line 290-298: Which RNA samples were used? Are they identical to those for RNA-seq? Why?
15)	Line 353-356: Those two sentences should be appeared in Introduction section.
16)	Fig 3: The cluster name and number of DEGs of each cluster should be given in the figure. The order of each plot should be identical to the appearance order in the text.
17)	Fig 4: The word size is too small.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: TRANSCRIPTOMIC AND PROTEOMIC PROFILES OF II YOU 838 (ORYZA SATIVA) PROVIDE INSIGHTS INTO HEAT STRESS TOLERANCE IN HYBRID RICE
Review round: 1
Reviewer: 2

Output:
Basic reporting: The current MS is on comparative transcriptomics and proteomics analysis of heat resistant hybrid rice and their parent lines.  Given the current and alarming problem of global warming, the aim of this study is very significant.
1.	The title of this MS is too conclusive while the results and discussion are not directed towards that.
2.	There are few typos (e.g. line 48: nighttime should be night time), please go through the text again.
3.	The introduction is not very detailed and you are citing almost all of the references more than 5 years old. While there is a number of new reports on rice and increasing temperature.
Experimental design: 1.	Please provide in details about planting materials and growth conditions. From the current methods, it’s hard to understand how you started your planting material. Is it from plates to the growth chamber or directly sown in field and later transferred to growth chamber?
2.	“Heading stage plants were transferred to growth chamber” Please also mention in terms of days after sowing/plating.
3.	At which stage tissue were collected? Please also mention in terms of days after transfer to the growth chamber.
4.	We know that most of the genes are regulated by circadian rhythm, so it is also important to mention the time of tissue collection.
5.	The color resolution of Fig 1A is very poor. It will be good if you provide pics from 0 hr to 120 hrs, this will help us to understand the dynamic changes under heat stress.
6.	Table 1 and 2, should go-to supplement. You may pick the top 10 candidates from each table and make one table instead of long two different tables.
7.	Starting from the title of this MS and several places in the text, ‘mechanisms’ is the word of choice, but I didn’t see any single experiment/ data which is directed towards this. At least at the end, a model figure may be helpful which is very much missing.
Validity of the findings: Based on only RNA-seq and proteomics analysis, it is very hard to come to any conclusive picture of the problem. It is now highly recommended to verify the results of transcriptome/proteome by at least picking one/two candidates and go for further characterization.
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: TRANSCRIPTOMIC AND PROTEOMIC PROFILES OF II YOU 838 (ORYZA SATIVA) PROVIDE INSIGHTS INTO HEAT STRESS TOLERANCE IN HYBRID RICE
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: This is a resubmission with significant changes according to the reviewers' suggestions. After reading the revision, I am satisfied by the changes the authors made in this revision. The revision addressed all of concerns and, as I can see from the responses to the reviewers' comments, also addressed most, if not all, concerns and questions raised by other reviewers. I think this revision has significantly improved the quality of the paper.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: TRANSCRIPTOMIC AND PROTEOMIC PROFILES OF II YOU 838 (ORYZA SATIVA) PROVIDE INSIGHTS INTO HEAT STRESS TOLERANCE IN HYBRID RICE
Review round: 2
Reviewer: 2

Output:
Basic reporting: Based on earlier suggestion and review, authors improved this MS very significantly and responded to all the queries.
Experimental design: Improved and upto the mark  now.
Validity of the findings: This revised MS is improved. All the findings were discussed in details with relevant citation.
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: MOLECULAR CHARACTERIZATION OF TWO RECOMBINANT ISOLATES OF TELOSMA MOSAIC VIRUS INFECTING PASSIFLORA EDULIS FROM FUJIAN PROVINCE IN CHINA
Review round: 1
Reviewer: 1

Output:
Basic reporting: This manuscript reports on the complete genome sequences of two Telosma mosaic virus isolates isolated from Passiflora edulis plants in China, and evidence of recombination within each genome. The authors also propose that isolate PasFru, previously proposed as representing a novel species, be accepted as an isolate of Telosma mosaic virus.

Minor grammatical errors are prevalent throughout the manuscript, and I suggest the authors employ a good editing service to correct these.

Some specific points are given below:
L 39-41 It is documented that passion fruits are susceptible to infection of more than 25 different viruses (Baker et al.  2011), in which several different potyviruses have been observed worldwide.
Please delete or clarify the phrase following the comma.
L43. Provide a reference for this statement and the one in lines 54-55.
L44. Write the full name of the virus species (in italics). ‘Telosma mosaic virus is a species of the genus Potyvirus. TeMV has a positive-sense ssRNA…
L51. Which plant host was it reported from in China?
L57. Change Potyvirus species to Potyvirus genus, or a new species of potyvirus
L58-60. Please clarify this sentence. Name the Vietnamese isolate.
Experimental design: L72. Clarify what you mean by ‘randomly collected’. Were they chosen based on symptoms? Please describe the context of the infected plants: commercial orchard, home garden, feral plants etc

L71 How certain are the authors that these symptoms were induced by TeMV infection? Could other viruses be present. Were transmission experiments done to healthy passiflora or other plants? If not, please explain why not.

Line 124-125. Change 5 to five
L129. Clarify what is meant by ‘As an additional check to clarify sequence accuracy, the viral genome sequences were repeated at least three times.’

Table S1. I am uncertain how five sets of primers were sufficient to sequence the entire genome. Each amplicon would have to be >2 Kb, and to sequence each amplicon in both directions would require several other sets of primers. This section is not well -described, but it should be.
Validity of the findings: L182 remove ‘more than’ and provide numbers for each comparison.

L196. Provide the statistical evidence for recombination in this section.

L204. The Potyviridae is not the largest family of plant viruses. I would like to advise that the first small paragraph not be a repeat of the introduction, as it currently stands, but rather a one or two sentence summary of the aims and results of the study.  Along the lines of ‘The complete genomes of two isolates of TeMV were fully sequenced from passion fruit plants in China. We provided for the first time evidence that intra-species recombination has occurred…” Then go on to discuss implications of your findings in terms of evolution of this species, and speculate on how this may influence pathogenicity, transmission etc, as you have done from line 212.

The paragraph from 217-228 should come after the discussion on recombination.

Table 1A. Please provide amino acid identities too for full or partial ORF too.

Fig 1A Wuyishan appears to be color-enhanced. I suggest deleting it and retaining the image Fuzhou if this represents typical symptoms. Another option is to remove these images and provide a thorough description.

L213 Provide a reference for this statement.
L216. A reference required on risks of virus accumulations in vegetatively-propagated plants.
Additional comments: The final paragraph of the Discussion is weak. Perhaps point out some of the weaknesses of the current study (only two isolates, only one host species sampled, only one location sampled, the inherent limitations of RT-PCR-based sequencing, etc) and where further studies could focus.

Your main finding is essentially two complete genomes of isolates of Telosma mosaic virus. Isolates of this species have been provided by other previously, so I suggest you place greater emphasis on the recombination finding and its implications.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: MOLECULAR CHARACTERIZATION OF TWO RECOMBINANT ISOLATES OF TELOSMA MOSAIC VIRUS INFECTING PASSIFLORA EDULIS FROM FUJIAN PROVINCE IN CHINA
Review round: 1
Reviewer: 2

Output:
Basic reporting: no comment'
Experimental design: no comment'
Validity of the findings: no comment'
Additional comments: In this study, authors analyzed the complete genome sequence of two TeMV isolates, Fuzhou and Wuyishan and identified the recombination breakpoints  within the CI and NIb genes of the Fuzhou isolate, also within the P1 gene of the Wuyishan isolate for the first time. There some problems should be
corrected befored pubilication.
1. The title "in china" is too large to cover you contents. because the authors only analyzed the samples collected from Fujian. so please change into Fujian.
2. in materials and methods, line 83, "RNA extraction and reverse transcriptase polymerase chain reaction (RT-PCR)", but the content afterward did not contained the RT-PCR. you should combined this part with the part of "Molecular detection of virus".
3. line 157, the results of Indirect-ELISA were not showed in the part of results. you should add the results or delete the methods in the revised manuscript.
4. TeMV-infected P. edulis showed severe symptoms, such as mosaic and distorted leaves, mosaic skin on green fruit and decreased fruit size. but the picture in figuer 1 was not typical.
5. there is a blank between numbers and unites. such as line 161. you should check it throughout the article.
6. please delete the from passion fruit in line 72.
7. please  add is between  it and consumed in line 36.
8 in fact, Chen et al identified Telosma mosaic virus infection in Passiflora edulis and analyzed its impact on phytochemical contents. you shuold cite the article.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: MOLECULAR CHARACTERIZATION OF TWO RECOMBINANT ISOLATES OF TELOSMA MOSAIC VIRUS INFECTING PASSIFLORA EDULIS FROM FUJIAN PROVINCE IN CHINA
Review round: 1
Reviewer: 3

Output:
Basic reporting: In general the manuscript has been written with professional english. As some typos can still be found, another round of proofreading could improve the presentations. For example, in the abstract on row 27 - phylogenetic indicate (phylogenetic analysis indicates?). Also TeMV isolate PasFr is abbreviated in the abstract ParFru.
Experimental design: This reserach pertains to biological sciences.  The aim of the research was to understand the nature of the viruses affecting the yield and quality of passion fruits in orchards in Fuijan province in China. The viruses within the symptomatic passion fruit plants were identified as potyviruses and by sequencing to be isolates of Telosma mosaic virus (TeMV). Therefore, the third aims was to provide more sequence information for taxonomic decisions concerning the TeMV isolates.
After initial screening of the plant samples with universal potyvirus antiserum in an indirect ELISA test, those that were regarded as positive were subjected to further analysis. The methods how the full-length sequences were obtained as well as those of phylogenetic and recombination analyses have been described in sufficient detail. To my understanding the investigations were conducted to a high technical standard. For example, seven different programs were used to determine the possible areas of recombination within Fuzhou and Wuyishan isolates and the criteria for recombination event was set as follows: event had to be supported by four of the programs with a p-value less than 10-6.
Validity of the findings: The manuscript reports sequences of two novel Telosma mosaic virus isolates. The sequences indicate that these two isolates have typical potyviral sequences.  It was found that there are two regions of recombinations within these RNA sequences.

The sequences of the two novel TeMV isolates show that according to species demarcation criteria  (the complete ORF are <76% nucleotide identity and <82% amino acid identity) they are TeMV isolates as is also PasFr. The thresholds for species demarcation using nucleotide identity values for the individual coding regions range from 58% for the P1 coding region to 74–78% for other regions. For the coat protein, the optimal species demarcation criterion is 76–77% nucleotide and 80% amino acid identity (Adams et al., 2005b). The authors suggest that all sequenced TeMV isolated should be considered as one potyvirus species. Except the high variation in P1 gene of Hanoi isolate this statement is well supported by the sequences.
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: MOLECULAR CHARACTERIZATION OF TWO RECOMBINANT ISOLATES OF TELOSMA MOSAIC VIRUS INFECTING PASSIFLORA EDULIS FROM FUJIAN PROVINCE IN CHINA
Review round: 2
Reviewer: 1

Output:
Basic reporting: Acceptable
Experimental design: Acceptable
Validity of the findings: Acceptable
Additional comments: I have read the rebuttal and the manuscript and I am satisfied that the authors have made a thorough job of amending the manuscript. I feel that it can be accepted for publication, with only minor editorial amendments required


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: MOLECULAR CHARACTERIZATION OF TWO RECOMBINANT ISOLATES OF TELOSMA MOSAIC VIRUS INFECTING PASSIFLORA EDULIS FROM FUJIAN PROVINCE IN CHINA
Review round: 2
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: In the revised manuscript, authors have revised the article as suggested by the reviewer. We agree with the publication of the article.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: MOLECULAR CHARACTERIZATION OF TWO RECOMBINANT ISOLATES OF TELOSMA MOSAIC VIRUS INFECTING PASSIFLORA EDULIS FROM FUJIAN PROVINCE IN CHINA
Review round: 2
Reviewer: 3

Output:
Basic reporting: -
Experimental design: -
Validity of the findings: -
Additional comments: The revised version of the manuscript ”Molecular characterization of two recombinant isolates of telosma mosaic virus infecting Passiflora edulis from Fujian Province in China (#41501) has answered most of the reviewer’s comments. I still spotted few corrections, which could be considered:
-	Introduction , row 56: only one complete TeMV isolate
-	Materials and methods of cDNA synthesis and PCR: giving the volumes how much RNA/DNA and primers were pipetted into the reactions does not give an idea of the real amounts of these. Please, provide mass or volume + concentration of them.
-	Although the sentence on rows 129-130 has been reformulated, it still could be made more clear: was the whole sequencing process repeated three times? Did you start from new RNA isolation, new cDNA synthesis or from the PCRs – how independent were the sequenced samples from each other?
-	Row 164: Please, give the Genebank number for the TeMV genome sequence that was used here for comparison.
-	Row 165-166: I think the results show that the symptomatic trees were infected by TeMV, but it is not clear whether the symptoms were caused by this virus.
-	Row 174: Is the ribosomal frameshift signal G2A6 required for frameshift if its origin is transcriptional slippage?
-	Figure 1 legend: The legend still tells that it shows symptoms in P. edulis infected with Fuzhou and Wuyishan isolates. Only one is left in revised Fig. 1 , which one?


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: LONG NON-CODING RNA POLYMORPHISMS ON 8Q24 ARE ASSOCIATED WITH THE PROGNOSIS OF GASTRIC CANCER IN A CHINESE POPULATION
Review round: 1
Reviewer: 1

Output:
Basic reporting: In introduction section, the authors should clarify the therapy strategies of gastric cancer to emphasize the importance of the issue.
Experimental design: No comment.
Validity of the findings: 1.In my opinion, the Fig.S1 should make a swap for Fig.2 to highlight the findings.
2. Type 1 error of multiple testing should be corrected.
Additional comments: This study shows some interesting findings regarding the prognostic biomarker signature for gastric cancer. The major issue is correlation between lncRNA SNPs and GC prognosis, the authors should emphasize the associated findings. In discussion section, at line 276-278, the prediction role of rs12682421 and rs1562430 should be discuss, and provide more information about correlation between therapy approaches and genetic background.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: LONG NON-CODING RNA POLYMORPHISMS ON 8Q24 ARE ASSOCIATED WITH THE PROGNOSIS OF GASTRIC CANCER IN A CHINESE POPULATION
Review round: 1
Reviewer: 2

Output:
Basic reporting: Language is good and article is well organized and structured.
Experimental design: Study was done appropriate larger sample size.  Research question, hypothesis and objectives were properly provided.
Validity of the findings: SNPs were well analyzed by using appropriate stats tool.
Additional comments: Overall good study as done on larger sample size and able to justify the hypothesis and objectives taken with proper results and discussion.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: LONG NON-CODING RNA POLYMORPHISMS ON 8Q24 ARE ASSOCIATED WITH THE PROGNOSIS OF GASTRIC CANCER IN A CHINESE POPULATION
Review round: 1
Reviewer: 3

Output:
Basic reporting: This study discusses the association between Inc-RNA polymorphisms and gastric cancer prognosis in a Chinese cohort. The manuscript is clear and unambiguous. Statistical analysis is comprehensively applied to clinical and experimental data. A few minor concerns and questions regarding the context are listed as following:

1. Line 107 and 108: Does “different human” mean different individuals or different races?

2. Since eight SNPs were analyzed in the same cohort, has linkage disequilibrium be considered in this study? If some of them are associated, influences from other loci need to be considered when analyzing the association between one SNP and GC risk or prognosis.

3. In Table 2, MSTs between different genotypes are not that significant, unfortunately. Even for rs12682421, the log-rank p-value is 0.03 without adjustment. Since statistical analysis involves multiple simultaneous statistical tests in this study, I highly recommend multiple test corrections to avoid type I error. It seems that rs12682421 has the most significant association with GC prognosis in Table 2. Have you further analysis which genotype has the closest relationship with GC survival, or which allele indicate better or worse prognosis?

4. More than two-thirds of references are before 2015, and only 10 references are published in recent 3 years. For innovation points, it’s better to introduce and discuss more recent works and publications.
Experimental design: It's already involved in basic reporting.
Validity of the findings: It's already involved in basic reporting.
Additional comments: It's already involved in basic reporting.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: LONG NON-CODING RNA POLYMORPHISMS ON 8Q24 ARE ASSOCIATED WITH THE PROGNOSIS OF GASTRIC CANCER IN A CHINESE POPULATION
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: no comment


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: LONG NON-CODING RNA POLYMORPHISMS ON 8Q24 ARE ASSOCIATED WITH THE PROGNOSIS OF GASTRIC CANCER IN A CHINESE POPULATION
Review round: 2
Reviewer: 2

Output:
Basic reporting: Many thanks to the authors' responses. I don't have any new questions now.
Experimental design: No new comment.
Validity of the findings: No new comment.
Additional comments: No new comment.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: THE COMPLETE MITOGENOME OF ARION VULGARIS MOQUIN-TANDON, 1855 (GASTROPODA: STYLOMMATOPHORA): MITOCHONDRIAL GENOME ARCHITECTURE, EVOLUTION AND PHYLOGENETIC CONSIDERATIONS WITHIN STYLOMMATOPHORA
Review round: 1
Reviewer: 1

Output:
Basic reporting: The authors indicate that accession number from GenBank is pending. If everything is correct, you get the number in less than a week (usually 48h). You shouldn’t submit the manuscript without the number because is one of the first quality reports that check if there are anything wrong with the data.
Experimental design: No comment
Validity of the findings: In general, I find the legends poor. Legends must be understandable by themselves. For some of them is necessary look into the main text or make interpretations (e.g. Fig. 5; Tables 1, 5 and 6).
On the other hand, I did not find the legends for the supplementary Figures S2, S3 and S4. Without legends I can’t say many things but, many clades were not supported… (Fig S2 & S4: Bootstrap support values? Lower than 70; Fig. S3: BPP ? lower than 0.95). Also in the Fig 4., at least the family Helicoidea is not supported (0.82 BPP) but in the text is indicated that was recovered with high support.
Additional comments: Please find all my comments in the pdf file attached.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: THE COMPLETE MITOGENOME OF ARION VULGARIS MOQUIN-TANDON, 1855 (GASTROPODA: STYLOMMATOPHORA): MITOCHONDRIAL GENOME ARCHITECTURE, EVOLUTION AND PHYLOGENETIC CONSIDERATIONS WITHIN STYLOMMATOPHORA
Review round: 1
Reviewer: 2

Output:
Basic reporting: The manuscript meet the standards for publication.
Experimental design: The research question is well described but should be limited to the evolution of the stylommatophoran group. All the data analyses were well performed and the methods appropriate to their goals.
Validity of the findings: The authors have robust conclusions about the evolution of the taxonomic group and contribute to the understanding of natural selection over the mitogenome.
Additional comments: The manuscript describes evolution of the stylommatophoran group and the mitogenome architecture and selection. The authors sometimes describe and discuss the Arion vulgaris mitogenome, and sometimes the evolution of the entire taxonomic group. This is confusing and the fact they have sequenced the A. vulgaris mitogenome is a plus but not the main strength of the manuscript. I suggest limiting the entire manuscript to the phylogenetic reconstruction, selection and architecture of stylommatophorans. Therefore, I suggest change the title, the introduction is very informative about the diversification and evolution of the taxonomic group, but it should eliminate details about A. vulgaris, and add more the context of the natural selection over the mitogenome since it is only addressed in the objectives.

Lines 251-331: This three first subtitles of the Results and Discussion are very descriptive. Reduce significantly these sections. Most of this data are shown in tables at supplementary material but the caption could be more detail with a few more explanation and pointing at the tables the most important values. Sometimes the authors compare the Arion vulgaris mitogenome with all other species, and sometimes it does the comparison among all species (A. vulgaris as one of the species). Please limit to the second comparison.

The authors found three different tree topologies, but the authors describe the tree with higher support as the most reliable. The discussion between the tree found and the other studies are very important, but it is confusing here (lines 344-351). The authors should also discuss why those differences between their findings and the other studies (few or different markers, different phylogenetic reconstruction methods…).

The results are very relevant because they highlight the importance of eliminating saturated substitutions to perform phylogenetic reconstruction analyzes. In this regard, I think it is important to emphasize results such as:
1) phylogenies constructed with ML (Fig. S3) and BI (Fig S4) without eliminating substitutions and saturated genes share the same topology and place members of two different families as sister species (Succineoidea and Orthalicoidea)
2) When the phylogenies are constructed without the substitutions and saturated genes, the position of the species of the Succineoidea and Orthalicoidea family is recovered.  ML places Polygyroidea within the Helicoid clade, but with a low node support (S2), while BI (Fig. 4) recovers the position of the Polygyroidea family.

402-404: This phrase is a bit confusing. It can be written more clearly.

438-439: The MEME and aBSREL methods evaluate the existence of episodic diversifying selection, that is, the selection arises sporadically within one or some lineages. However, FUBAR evaluates the existence of pervasive selection. In this sense, it is not correct to say that everyone suggests episodic diversifying selection. You could use only "diversifying selection" (Chek this in the abstract, lines 44-45).

Other minor reviews:
30-33: These two phrases are not necessary
Line 152: How did you obtain the mitogenome reads from the whole-genome reads?
Line 347: I am not clear what do you mean in this phrase, after “However”.
Figure 1 could be at supplementary. It is not the goal of the manuscript.
Line 386: Complex to write about the “diversification of Arion species” since it has been evaluated only two species.
Line 406: Eliminate “.”


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: THE COMPLETE MITOGENOME OF ARION VULGARIS MOQUIN-TANDON, 1855 (GASTROPODA: STYLOMMATOPHORA): MITOCHONDRIAL GENOME ARCHITECTURE, EVOLUTION AND PHYLOGENETIC CONSIDERATIONS WITHIN STYLOMMATOPHORA
Review round: 2
Reviewer: 1

Output:
Basic reporting: I think the authors made an excellent work with the revision of the manuscript. The authors answer and correct all the comments proposed by the reviewers in a clearly way. However, I have a minor consideration that should be corrected before accepting the ms. In one of the responses to the Reviewer 1, the authors say that they modified the text to indicate that the Helicoidea superfamily is not statistically supported but, I still can read in the abstract that the monophyly of all superfamilies is well supported. This should be removed from the abstract.
I hope my comments are clear and somehow helpful.
Experimental design: The goals of the work are well defined and all the analyses were correctly performed.
Validity of the findings: The conclusions of this manuscript are strong according to the results and will help in understand the evolutionary history of the stylommatophoran.
Additional comments: No comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: RETROSPECTIVE STUDY: CLINICOPATHOLOGICAL FEATURES AND PROGNOSIS OF IDIOPATHIC MEMBRANOUS NEPHROPATHY WITH SERONEGATIVE ANTI-PHOSPHOLIPASE A2 RECEPTOR ANTIBODY
Review round: 1
Reviewer: 1

Output:
Basic reporting: Below some suggestions:

- Overall, the article includes sufficient background and the role of anti-PLA2R antibodies is extensively debated and appropriately referenced. . However, the Introduction fails to discuss the rational of the PLA2R antigen assessment. Then, the Authors should also remark on this topic into this section.

- The current phrasing is sometime redundant and the general structure of the article should be revised. In brief, to improve the readability of the text, the Authors should simplify and rewrite some sentences. For instance,

-	Line 76 and 77: “titer level” could be replaced with “titer” or “level”.
-	Line from 85 to 91: the brief description of the study aim and design should include only general information to make the message clearer. Let me give you an example on how to rewrite this paragraph: “In this study, we performed a two-step evaluation: firstly, we retrospectively compared clinical and pathological features of anti-PLA2R negative (PLA2R-) with anti-PLA2R positive (PLA2R+) subjects; then, we evaluated the prognostic value of PLA2R negative result using a longitudinal design and analysis.”
-	Line 105: the clinical and laboratory data should be organized in a more logical way. For example, “General demographic (age, gender) and clinical (duration of disease, systolic and diastolic blood pressure, etc.) records were collected. Laboratory data included general tests (…) and specific biomarkers of renal function and disease activity (e.g. urinary protein excretion (g/day), serum creatinine (mg/dL), etc…)”.
-	Line 112: antiphospholipid enzyme A2 receptor (PLA2R) antibody should be removed as this biomarker is extensively described in the next paragraph.
-	Line 117: the sentence “The eGFR was calculated based on the MDRD formula” should move in the previous paragraph in the part of the text where the specific biomarkers are listed.
-	Line 151: Statistical method paragraph can be simplified and also needs some language revision; line 152: M(1/4,3/4) should be replaced with median and 25°/75° percentiles.

Furthermore, below some typing error to be revised:
-	Line 110:  "macroglobulin" should be replaced with "microglobulin".
-	Line 165: “Result” should be replaced with “Results”.
-	Line 312: “PRUE A HILL” should be replaced with “Hill”.
-	Line 373: “study” should be replaced with “studies”.
-	Line 402: “REFERENCE” should be replaced with “REFERENCES”.

Furthermore, PeerJ standards do not require numbered subsections and the titles of the paragraphs in Materials and Methods should be included or replaced with more appropriate ones to make the message straightforward. On the other hands, the subsections in Results sound redundant; my suggestion is to write the results in a single paragraph.
For instance (these are just suggestions):
-	Line 103: “Research method” is redundant.
-	Line 104: “Clinical and laboratory data collection”
-	Line 114: “Anti-PLA2R detection”
-	Line 119: “PLA2R antigen detection”
-	Line 124: “Renal biopsy”
-	Line 142: “Outcomes in followed up patients”
Experimental design: - The description of the methods needs some minor revision. In particular, the paragraph including the description of the study subjects (line 93) should also include the diagnostic criteria for iMN with some more detail in renal biopsy characteristics. This description should be included before the exclusion criteria (line 96).

- Statistical method (line 154): the Authors stated that they used SNK test to compare two groups. Are they sure? This test is usually performed for comparing three or more sample means. Furthermore, logrank test should be included in this paragraph.
Validity of the findings: - The Authors should clarify the total number of the enrolled patients. In fact, at line 166 they stated that 229 patients with iMN were retrospectively collected, including 59 and 119 PLA2R negative and positive patients, respectively. However, 59 plus 119 equals to 178. Then, what about the remaining 51 subjects?

- The statistical results that are included in parentheses should be integrated including the value of statistical test, the degree of freedom when requested  and the right value of p-value (not p<0.05). For example, “(chi2=…, df=…, p=…)” or (KW=…, p=…). This is for line 170,172,175, etc.

- In tables 6 and 7, confidence intevals of B coefficients or of Exp(B) should be reported.
Additional comments: No additional comments


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: RETROSPECTIVE STUDY: CLINICOPATHOLOGICAL FEATURES AND PROGNOSIS OF IDIOPATHIC MEMBRANOUS NEPHROPATHY WITH SERONEGATIVE ANTI-PHOSPHOLIPASE A2 RECEPTOR ANTIBODY
Review round: 1
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: Dr. Guo et al. measured serum PLA2R Ab by using EUROIMMUN ELISA as well as staining for PLA2R Ag and IgG4. They found that seronegative for PLA2R Ab IMN patients showed milder disease and better renal prognosis. They claimed that renal pathological staining for PLA2R is important for IMN patients especially when serum PLA2R Ab was negative. The findings are clinically important. However, I still have several concerns.

1. Title
Clinicopathological features and prognosis of idiopathic membranous nephropathy with
negative anti-phospholipase A2 receptor antibody

This title may mislead the readers. To be precise, the title should be modified as follows:
“Clinicopathological features and prognosis of idiopathic membranous nephropathy with
seronegative anti-phospholipase A2 receptor antibody”

2. Lines 40~41 in ABSTRACT:
Otherwise, the PLA2R antigen-positive rate of 43 patients in the PLA2R-group was 62.79%.

I do not understand what “Otherwise” means in this sentence.
Moreover, the PLA2R antigen-positive should exist at least in low level in normal kidney podocyte as shown by Beck et al. (N Engl J Med. 2009 Jul 2;361(1):11-21. doi: 10.1056/NEJMoa0810457.) Therefore, “the PLA2R antigen-positive rate” should be replaced by some other phrases such as “the PLA2R antigen-positive staining rate,” or “the rate of granular staining for PLA2R antigen.

3. Line 301, DISCUSSION
This study showed that 43 of 162 patients with IMN were negative for anti-PLA2R antibodies,

This sentence should be modified as follows:
This study showed that 43 of 162 patients with IMN were negative for anti-PLA2R antibodies in the sera,

Authors should be more carful in describing these critical points.

4. Line 303, DISCUSSION
The anti-PLA2R antibody in the serum is negative, but PLA2R antigen in the kidney
tissue is positive.

Again, I do not agree with this sentence, because PLA2R antigen in the kidney tissue should always be positive at least in a low level. This sentence should be, “The anti-PLA2R antibody in the serum is negative, but PLA2R antibody is positive in the kidney tissue.”

5. Figure 2
Pictures of immunohistochemistry is not very convincing. The authors should show better photos with stronger stanning. Pictures with higher magnifications are also needed.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: RETROSPECTIVE STUDY: CLINICOPATHOLOGICAL FEATURES AND PROGNOSIS OF IDIOPATHIC MEMBRANOUS NEPHROPATHY WITH SERONEGATIVE ANTI-PHOSPHOLIPASE A2 RECEPTOR ANTIBODY
Review round: 1
Reviewer: 3

Output:
Basic reporting: The paper is of interest however the literature reference should include all the papers about the topic.
There are few typing errors, the English style should be revised.
Experimental design: The authors should refer to the shared definition of complete remission.

It is not clear when the PLA2R-antibodies have been tested, the authors hypothesized that in the negative group ' The patient's condition is in a stable state, and there is currently no immune activity in the body'. Are all the PLA2r tests performed at the time of the biopsy?

Since the authors are defining the complete remission as urine protein<0,3g/day and normal kidney function, the difference in the treatment group  (more patients are treated with cyclosporine in the positive group) and the chronic pathological lesions at the diagnosis could be a bias.
Validity of the findings: the design of the study is influencing the validity of the findings
Additional comments: The paper is of interest and it is analyzing the difference among the PLA2R positive and negative iMN subgroups. However the differences in the baseline characteristics could had influenced the outcomes.


Instruction: You are one of the reviewers, your task is to write a review for the article. You will be given the title of the article, the number of the round in which the article is located, and your order among the reviewers.

Input:
Title: RETROSPECTIVE STUDY: CLINICOPATHOLOGICAL FEATURES AND PROGNOSIS OF IDIOPATHIC MEMBRANOUS NEPHROPATHY WITH SERONEGATIVE ANTI-PHOSPHOLIPASE A2 RECEPTOR ANTIBODY
Review round: 2
Reviewer: 1

Output:
Basic reporting: Please, add some minor revision to statistical methods. Actually, the term "abnormal distribution" is unusual. Furthermore, I disagree with this sentence “and a P value <0.01 was considered notably statistically significant”. Indeed, in statistics the strength of an association is stated by odds ratio or risk ratio, etc... Conversely, a lower p-value does not mean a greater probability of the association.
Below some suggestions:

Descriptive statistics were used to calculate mean and standard deviation for quantitative variables with normal distributions, median and percentiles for non-normal distributions and percentage for categorical variables.  The comparisons between independent groups were performed by t-test, non-parametric tests and Chi-squared for continuous or categorical variable, respectively. Correlation between several parameters was expressed as Spearman rank coefficient of correlation. Patient and renal survival probabilities were estimated by the Kaplan-Meier method. The relationships of the covariates to patient and renal survival were evaluated by univariate analysis with the log-rank test and by multivariate analysis with the Cox proportional hazards model; the Harrel C statistic was used for verification of the risk factors confirmed by the Cox proportional hazards model. A Cox analysis of risk factors was performed in combination with clinical significance. A p-value < 0.05 was considered statistically significant.
Statistical analyses were performed using IBM SPSS Statistics for Windows, version 19.0 (IBM Corp., Armonk, N.Y., USA).
Experimental design: I agree with the revised version
Validity of the findings: I agree with the revised version
Additional comments: I thank the Authors for their effort in revising the manuscript. The current version improved a lot the structure and clarity of the manuscript. I finally ask them to add some minor revision into the statistical method section as suggested above.