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 RULE-BASED INSENSITIVITY EFFECT: A SYSTEMATIC REVIEW
Review round: 1
Reviewer: 2

Output:
Basic reporting: This study was well reported. The language used was clear and unambiguous throughout. The Introduction was adequate in providing background/context. The literature was well referenced and relevant in that focused on rule-governed behaviour and the theoretical background to this. The structure / layout of the paper conformed to ‘PeerJ’ standards, and to the norms for Psychology.  Figures/tables were relevant, good quality, well labelled and described.
Experimental design: This was a review paper which is within the scope of the journal. The research questions were well defined, relevant and meaningful and it was clearly stated how the review would fill what was identified as a knowledge gap. The review was rigorously conducted to a high technical standard. Methods were thorough and were clearly described with sufficient detail and information to replicate.
Validity of the findings: The impact of the findings was adequately discussed with respect to all outcomes. All relevant data/results were provided. Data seemed robust, based on statistically sound analyses. Conclusions were well stated, linked to the original research question and limited to supporting results.
Additional comments: A well conducted and reported piece of work.

Just a few minor details for correction:

Introduction
L49-52
‘Under such circumstances…instructions’
Why is ‘you’ (i.e., the reader) referenced here? Instead of talking about what ‘you’ might do, the authors should continue to refer only to the groups of pts in the example.
L59
Capital ‘H’ for ‘Holmes’
L99
‘That is, studies that used convenience samples…’
This is a sentence fragment. Amend.


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 RULE-BASED INSENSITIVITY EFFECT: A SYSTEMATIC REVIEW
Review round: 1
Reviewer: 3

Output:
Basic reporting: Clear and unambiguous professional English is used throughout. I highlight below a small number of typos/suggestions that might improve this:
line 31 healthy -> healthily
line 59 and 474 Barnes-holmes -> Barnes-Holmes
line 138 “the proportion of women it included” -> “the ratio of males:females”
line 382 tarantula’s -> tarantulas

All other aspects addressed.
Experimental design: Under Information Sources and Search Strategy:
I am assuming that alternative spellings of behavior (i.e. behaviour) were automatically searched by default? Although this may seem a trivial point to raise, I note that the authors explicitly state that, for example, “instruction following” and “instruction-following” were entered as distinct search terms; so if the search algorithms did not automatically search for the other, hyphenated variant when the first was entered, the same might also be true for alternate spellings of behavior.

Under Quantitative Synthesis: Vote Counting
This may just be due to my own failing, but I cannot work out how the vote counting method applied led to the inclusion of 11 studies in the quantitative synthesis as detailed in the Prisma diagram. Was it because the other 10 studies did not report effect sizes or similar outcome measures? So the studies that were deemed "Unclear" were not included? It would be useful to clarify this by putting a number to it in the main text as well as in the diagram.
Validity of the findings: For those studies where information such as "Presence of experimenter" was deemed to be unclear, might it be beneficial to contact the corresponding author of the studies, where possible, to obtain this information?
Additional comments: This is an interesting, timely and necessary paper. My one major suggestion for improvement before publication might be - the authors have identified as a limitation of the study that vote-counting does not provide information about the magnitude of the observed effects unlike the standard meta-analytic approach. The rationale for using this method is that not all studies provided information such as effect size. But would it not be worthwhile adopting the meta-analytic approach to obtain information about the magnitude of observed effects from those studies that did include this information?


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 RULE-BASED INSENSITIVITY EFFECT: A SYSTEMATIC REVIEW
Review round: 2
Reviewer: 1

Output:
Basic reporting: Good, no further comment.
Experimental design: Good, no further comment.
Validity of the findings: Good, no further comment.
Additional comments: Dear authors,

In my initial review I qualified my suggestions with "The feedback below I personally deem 'minor points' for you to take or leave as you see fit.". Despite this I see you have engaged with the feedback and made a number of changes. I feel like the changes made have improved the manuscript, so kudos to you. Also kudos for being interested in making changes even when it is qualified that they are not perceived as a necessary 'requirement'. This suggests to me that you are passionate about your work and interested in presenting it in the best possible way that you can, it is a nice thing to see.

Congratulations on your paper, and all the best for the future,
Shane L. Rogers


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: ANALYSIS OF PROGNOSTIC GENES IN THE TUMOR MICROENVIRONMENT OF LUNG ADENOCARCINOMA
Review round: 1
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: In this study, authors used bioinformatics to screen nine prognosis-related genes associated with the LUAD tumor microenvironment. However, the selected key genes need to do validation using Western blot or IHC staining in their collected cancer samples with paitients' prognosis, not just the data from datasets or website.Otherwise, the reliability of the results is not strong.


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: ANALYSIS OF PROGNOSTIC GENES IN THE TUMOR MICROENVIRONMENT OF LUNG ADENOCARCINOMA
Review round: 1
Reviewer: 2

Output:
Basic reporting: In this manuscript, authors found nine prognosis-related genes associated with immune cells/stromal cells in LUAD using the ESTIMATE algorithm. Although the authors emphasized that the new biomarkers associated with immune cells/stromal cells played an important role in the prognosis of the LUAD, some contents are not fully abundant and controversial.
In terms of basic reporting, there is a problem that needs to be revised.In Line 110, the abbreviation ”logFC” lacked its full name.Other content basically meets the requirements.
Experimental design: With regard to the experimental design, the following content still needs to be added.
1.The standard and definition of the cutoff by which both the stromal scores and the immune scores were grouped should be provided in the full manuscript.
2.The results of univariate Cox regression mentioned in Line175-176 should be provided as supplementary material.
Validity of the findings: This manuscript is novel, reporting the new biomarkers based on the immune cells/stromal cells in LUAD using the ESTIMATE algorithm. However, the following results still needs to be modified.
1. In Line 35-37, it was mentioned that immune scores and stromal scores are significantly associated with the survival time. However, the results showed in the Line 154-155 and Figure 1E, didn’t indicated that there was a significant association between stromal scores and overall survival (p = 0.179). If the stromal scores didn’t significantly affect the prognosis in LUAD, is it accurate and necessary to conduct further research on it?
2. Were the immune scores and stromal scores the independent prognostic factors in LUAD? More information should be provided.
3. In Line 156-164, GSEA was performed to investigate mechanisms contributing to both the high immune and stromal scores. However, there was only a series of figures in the Figure 2, which wasn’t explicitly stated that the analysis is based on which score groups.
4. Because both the GSEA and DAVID analysis were performed using the GO analysis and KEGG pathway enrichment, consistency between the two results is inevitable. Thus, it is unknown whether DAVID analysis could actually verify the results in GSEA.
5. There were three GEO database for verification. However, the venn diagram showing  prognosis-related genes based on GSE11969, GSE50081, GSE37745 and TCGA cross-validation was lacked. Please explain why only two database was chosen to cross-valid the TCGA datasets in Fig 6 A&B. Furthermore, the Kaplan–Meier survival analysis in Fig 6 suggested that the 9 genes might be the prognosis-related factors rather than independent ones. Further results should be provided.
Additional comments: See 'Validity of the findings' for details.


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: ANALYSIS OF PROGNOSTIC GENES IN THE TUMOR MICROENVIRONMENT OF LUNG ADENOCARCINOMA
Review round: 1
Reviewer: 3

Output:
Basic reporting: The authors have conducted an extensive study on the TME of LUAD. The manuscript was well written, with informative figures and tables and thorough results. The English language used is clear. The literature is well referenced and the conclusions based on the results are generally sound, however, citing some studies in the Introduction and Discussion sections would be beneficial and strengthen the manuscript.

In some instances, some changes should be taken into account to add consistency to the text:
1)	Line 19-20, authors should write the identification of different prognostic genes in TME.
2)	Line 30-31, How many DEGs were used to construct PPI.
3)	Line 40, Which nine genes were found, please input the name of these genes.
4)	Line 49-50, Eighty-five percent of lung cancers are non-small cell lung......., references should be included.
5)	Line 59-60, Please clarify the sentence.
6)	Line 183, replace “value” with “associated”.
7)	In figure1A-D, please mention the statistical threshold in legend and please mention the statistical threshold in all legends of figures.
8)	In figure 1E, please clearly indicate the meaning of all different lines in survival curve.
9)	In figure 3C-D, title of circle should be more clear. Title of circle is confusing.
10)	 In figure 6C, clearly indicate the meaning of all different lines in survival curve because there are many line and it is confusing.
11)	The legends of every figure should be more descriptive, clear, and cosistent with the diagram.
Experimental design: Databases and analyses used were generally adequate to reach the objectives, however, some suggestions should be taken into account for the robustness of this study:
1)	Line 94, the website should be mentioned.
2)	Line 95-96, the database number should be provided.
3)	Line 180-181, the name of some important genes should be given.
4)	In Introduction, add some text with references indicating that stromal genes are associated with the poor survival of patients in different cancers, including lung cancer.
5)	Because stroma encompasses many type of cells, to improve the quality of the manuscript, I suggest the authors to search the GEO database on stroma of LUAD and validate the expression and prognostic value of genes.
6)	The authors can identify the prognostic hub genes from PPI networks which may improve the quality of this study.
7)	In figure 5A, provide the significant p values for each GO.
Validity of the findings: To prove the validity of the findings, the authors should search the databases on single stroma or immune cells of lung cancer to identify which part of the stromal compartments or immune cells the prognostic nine genes are associated with.
Additional comments: The findings of this study are potentially useful for establishing appropriate management and treatment of lung cancer. The conclusions could be improved with a more detailed discussion of the background and a more cautious interpretation of results.


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: ANALYSIS OF PROGNOSTIC GENES IN THE TUMOR MICROENVIRONMENT OF LUNG ADENOCARCINOMA
Review round: 1
Reviewer: 4

Output:
Basic reporting: There were so many grammar mistakes, so please edit the manuscript by a native English speaker.
Experimental design: The DEGs in high immune and stromal score group from the TCGA database should be provided in the supplementary files.
Validity of the findings: The prognostic accuracy of immune and stromal score should also be validated using cases from the GEO database. You just analyzed the intersect genes between cases from the GEO and TCGA databases, it was not the validation of the findings from the TCGA database.
Additional comments: 1. Too many categories of p-value in Table 1, I think just p<0.05* and 0.01** are enough.
2. A prognostic model should be constructed based on the DEGs, which can be identified through LASSO regression.


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: ANALYSIS OF PROGNOSTIC GENES IN THE TUMOR MICROENVIRONMENT OF LUNG ADENOCARCINOMA
Review round: 2
Reviewer: 1

Output:
Basic reporting: There were so many grammar mistakes, so please edit the manuscript by a native English speaker. Such as “In addition to tumor cells, stromal cells, immune cells, and tumor-associated normal epithelium…” in line 65.
Experimental design: Please figure out which parameters were analyzed with student’s t-test and one-way statistics and which statistical software was used.
Validity of the findings: Just analyze the distribution of DEGs included in both immune and stromal score group in three GEO datasets.
Additional comments: 1. Too many categories of p-value in Table 1, I think just three decimal places of p-value are enough.


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: PLASTID GENOMICS OF NICOTIANA (SOLANACEAE): INSIGHTS INTO MOLECULAR EVOLUTION, POSITIVE SELECTION AND THE ORIGIN OF THE MATERNAL GENOME OF AZTEC TOBACCO (NICOTIANA RUSTICA)
Review round: 1
Reviewer: 1

Output:
Basic reporting: The authors perform a study of the plastidial genome of different Nicotiana species, centered on Nicotiana rustica (aztec tobacco). Although the Discussion section is well written, the Introduction and the Results could benefit from a more extended language revision. In more than one case, a sentence was hard to understand or contained errors.
In the Introduction some of the needed citations are either outdated or missing, which results in incorrect dates reported for certain species. Most importantly, there is a missing point that should be addressed: Paternal chloroplast transmission has been observed in Nicotiana species before, under certain stress conditions or reproduction systems. Since Nicotiana is one of few species where this is known it should be mentioned in the text.

Specific comments

41-43: It should be clear for any reader that, besides the maternal parent who is hereby identified, there is a candidate paternal parent (N. undulata) (Sierro et al, 2018 https://doi.org/10.1186/s12864-018-5241-5 ). This point is reported in the Discussion (4.3) but not in the introduction or abstract.

69-70: The smoking tobacco hybridization date and the Suaveolentes hybridization date are currently placed at 0.4 and 5 million years ago, respectively (Clarkson et al., 2017 https://doi.org/10.1007/s00606-017-1416-9 , Schiavinato et al., 2020 https://doi.org/10.1111/tpj.14648 ).

72: “amphidiploidy” (correct: amphidiploid) is used wrongly. N. tabacum cannot be considered an amphi-diploid because it does not contain two entirely conserved diploid genomes within its nucleus, as it would be in the moment of hybridization (Lim et al., 2007 https://doi.org/10.1111/j.1469-8137.2007.02121.x ). Hence, it should be referred to as a “hybrid” or as an “allopolyploid”.

73-74: Not only N. tabacum, but also N. benthamiana is used as model organism, perhaps even more, and comprehensive resources exist for N. benthamiana as well (Goodin et al, 2008 https://doi.org/10.1094/MPMI-21-8-1015 , Bally et al 2018 https://doi.org/10.1146/annurev-phyto-080417-050141 , Schiavinato et al, 2019, https://doi.org/10.1186/s12864-019-5960-2).

92: Paternal inheritance of chloroplast DNA was observed also in Nicotiana under certain conditions of stress or reproduction ( Medgyesy et al, 1986 https://doi.org/10.1007/BF00425497 , Avni et al, 1991 https://doi.org/10.1007/BF00269859 ). Although this doesn't affect the claim that maternal inheritance is to be expected, it should be addressed in the paper.

154: The species name S. dulcamara comes out here for the first time, but it is not clear why it was used. Although it might be clear for the authors, it has to be at least referred to in the methods as well (e.g. “a species from the nightshades used as control”) and a reference should be added where the data were obtained from. I believe that they used it because some of the authors already published the chloroplast sequence of this species (Amiryousefi et al., 2018 https://doi.org/10.1371/journal.pone.0196069 ). Also, the name should be written entirely since it's the first appearance (Solanum dulcamara). This issue is reiterated at line 268, where S. dulcamara is intrudoced as a reference species for the Ka/Ks ratio calculation.

255-256: “The endpoint of the Solanaceae JLA is characteristically located upstream of the rps19 and downstream of the trnH-GUG.” The sentence is copy-pasted from a previous publication of some of the authors (Amiryousefi et al., 2018 https://doi.org/10.1371/journal.pone.0196069 ). Despite that, the JLA term is not defined or referenced, so the reader must rely on personal knowledge to understand it. According to Meng et al (2019) (https://doi.org/10.1371/journal.pone.0211340 ) it is a known chloroplast marker. Although this is common knowledge in the field of plastid genomics, it should be clarified in the text (the previous publication does not report details on it either).

372-375: “The size range of LSC, SSC and IR varies between the plastid genomes of species that advances to alterations...” -- the point expressed by the authors is unclear, please rephrase.

499-500: “N. rustica and in fact all Nicotiana tetraploids, except species included in section Suaveolentes, originated from a doubling of the diploid chromosome for the genus”. This sentence is unclear. The authors do not specify to which chromosome they are referring. In each Nicotiana hybrid, the doubling of the genome (not just one chromosome) happened through hybridization between different Nicotiana species. This is true for section Suaveolentes as well (Kelly et al, 2013 https://doi.org/10.1111/j.1558-5646.2012.01748.x ; Clarkson et al, 2017 https://doi.org/10.1007/s00606-017-1416-9 ; Bally et al 2018 https://doi.org/10.1146/annurev-phyto-080417-050141 ). Another work (Schiavinato et al., 2020 https://doi.org/10.1111/tpj.14648 ) even shows that the lineage of Nicotiana section Suaveolentes is now fully resolved. I believe that it was not available at the time this paper was written; however, the other ones were. Overall, this sentence should be rewritten adjusting the content and including the provided citations.

549-550: “further data is required to elucidate the phylogenetic relationship among these two species”. This sentence can be expanded. The work of Schiavinato et al., 2020 https://doi.org/10.1111/tpj.14648 showed how very large collections of phylogenetic trees can overpower the limitations of using a small set of genes. In fact, previous studies on Nicotiana tetraploid species ( Clarkson et al, 2017 https://doi.org/10.1007/s00606-017-1416-9 ) could not perfectly resolve the lineage of section Suaveolentes (i.e. the oldest Nicotiana hybrids). This was likely due to insufficient signal due to excessive sequence divergence.

Readability and Grammar

28-29: sentence is unclear. From a grammar standpoint, “tobacco plants” refers to Solanaceae, while the authors probably wanted to refer to the Nicotiana genus.

28: “are a group” refers to the Nicotiana genus, hence “is a group”. The authors probably referred to “tobacco plants”. The sentence should be reorganized in terms of grammar.

33: showed “the” typical.

80: specify “Proteins” e.g.  “Proteins contained therein”.

102: “transplastomic” should be plural (transplastomics).

151: “substitution” should be plural (substitutions).

168+337: The headings in Methods and Results include the word “phylogenomic” but throughout the paragraph it is used as “phylogenetic”. The latter is probably more accurate, since only the chloroplast genome is analysed.

174-177: To increase readability, a supplementary table would be recommended instead of a list of genes.

177: “a matrix was used” instead of “we used a matrix” (according to the recommended grammar for methods).

200: “Six biogeographical areas were defined” instead of “we defined six biogeographical areas” (according to the recommended grammar for methods).

222-223: The “x” that follows each coverage value means “cross product” (or vectorial product). It is commonly used when two parents of a hybrid are described together, to signify that the hybrid is the product of those. In the context of coverage, an “x” (the letter) should be used.

224: “was highest” instead of “were highest”.

237: “was encoded” instead of “were encoded”, as it refers to percentage (singular).

377: “which has” instead of “which have”.

378: “the rps19 gene” (missing “the”).

569: Author name “Abdullah” without firstname/surname correct?
Experimental design: The Materials and Methods did not include crucial information such as program parameters that would enable other scientists to reproduce the analyses. Please check all programs mentioned in the Methods section if the information given in the text is sufficient to reproduce the results.

Specific comments

114-115: The authors should specify which bwa subprogram was used (i.e. “mem”, “aln” , “fastmap” or “bwasw”, as the result can vary greatly. In fact, given that long queries (contigs) were mapped the alignment strategy should take into account the expected mismatches between contigs and the reference used. This is true especially because the reference chloroplast genome is not from the same species, hence some divergence is expected.

116: missing Geneious parameters

118: missing GeSeq and CPGAVAS2 parameters

119: “manually inspected and curated” please expand with explanation of the strategy used for curation.

121: missing Aragorn parameters

122: missing OGDRAW parameters

124: as for lines 114-115, in this case short reads are used and therefore a different mapping strategy was likely used but is not described

136: missing IRScope parameters

239: “Relative synonyms codon usage (RSCU)” is introduced in the text but not explained. The reader can only rely on personal knowledge to understand this term, since no reference is provided. One reference could be Sharp and Li (1987) (https://doi.org/10.1093/nar/15.3.1281) but the authors should clarify which codon usage bias model they used.

270-274: The reference values indicated for Ka/Ks ratios are somewhat arbitrary (0.5 and 4). As reported in the Discussion, Ka/Ks < 1 means purifying selection while Ka/Ks > 1 means positive selection (Ka/Ks = 1 being the neutral case). When reporting the results, it would be more informative to report the number of genes whose ratio is above, below or equal to 1. In addition to that, the whole sentence could benefit from rearrangement to make it clearer, for example: line 273-274 say “whereas genes rpoC1, atpB, rpoA, ndhD had Ka/Ks ratio more than 4 species”. It is not clear from the sentence whether 4 is the number of species or the Ka/Ks value (until the Supplementary Table S6 is consulted). Later in the paragraph (line 278) the correct ω reference values are reported. More in general, if a rationale is used to choose 0.5 and 4 as reference values, it should be explained in the text.
Validity of the findings: Newly generated/assembled sequence data should be made available in a public database (e.g. NCBI GenBank).
Additional comments: In the Discussion, the authors first address the different structures of plastidial genomes found between the analysed Nicotiana species. Specifically, they show that a series of loci are more variable than others that are commonly used as markers. Hence, the more variable loci could be used as well. This conclusion is interesting and based on convincing information.
They later show results on molecular evolution of plastidial genes, highlighting positive selection in multiple ones. They conduct the study with the right tools and come to interesting conclusions. Specifically, they show how positive selection of plastidial genes is often overlooked, and parallel their results to the ones obtained for more than a hundred grass species. The Discussion of these results is particularly well-written.
Finally, they analyse the phylogenetic relationships that defined the tetraploid hybrid Nicotiana rustica. The discussion of these results requires some rearrangements. As pointed out in the comments above, it is unclear what the authors mean when referring to section Suaveolentes and it could potentially be a wrong claim.


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: PLASTID GENOMICS OF NICOTIANA (SOLANACEAE): INSIGHTS INTO MOLECULAR EVOLUTION, POSITIVE SELECTION AND THE ORIGIN OF THE MATERNAL GENOME OF AZTEC TOBACCO (NICOTIANA RUSTICA)
Review round: 1
Reviewer: 2

Output:
Basic reporting: Piont 1. English must be thoroughly revised.

Point 2. Overall manuscript is used word plastome, chloroplast genome, and plastid genome in a mixtures, so you should be consistent. Likewise, unify the words "ψ" and "pseudogene".

Point 3. It would be better to provide candidate primer sequences or multiple alignment sequences for hotspot regions.

Point 4. Manuscript is exist many irrelevant references and duplicates sentences.
Experimental design: Point 1. Briefly explain why you mainly targeted 5 species.
Validity of the findings: Point 1. Ka, Ks, and Ka/Ks values may be more suitable to average value after cross-correlate comparison, rather than comparison with a reference.

Point 2. Figure 4 to 6 seem to like to show as a single figure, or trun it over to supplementary figure.

Point 3.In abstract, N. rustica was the common ancestor of N. paniculata and N. knightiana. However, both N. rustica and N. knightiana was constructed a sister group in figure 8 and 9. Please explain it more clearly.
Additional comments: Line 78. It would better "furthermore" than "while"

Lines 80-81. It would better "Most proteins are functioned for photosynthesis along with" than "Proteins are used not only for photosynthesis but also for".

Line 85. It would better "typically" than "typical".

Line 86. It would better "which are consist of" than "with".

Lines 88-90. Does it mean that structural modifications oucur frequently?

Line 91. It would better "have been known a maternal inheritance" than "have a uniparental maternal inheritance".

Line 92. It would better "reported" than "recorded".

Line 95. It would better "took advantage of" than "exploited".

Lines 100-103. There are duplicated above, change the location of the paragraph and delete the duplication.

Line 111. Change from "Nicotiana knightiana L." to "N. knightiana".

Lines 114-116. BWA is mapping program for reference sequence, not a program for conig selection. Did you used for a reference mappping? Is this right, contents should be modified accordingly.

Lines 116-117. You should provided the parameters used for de novo assembly in more detail.

Line 117. It would better "Gene annotation was conducted" than "The genome sequence was annotated".

Line 118. It would better "After draft (or automatical) annotation ?" than "Following de novo annotation"

Line 119. Explain in more detail about manually inspected and curated.

Line 121. You should provided the parameters of Aragorn.

Line 121. drawn with -> drawn by

Line 123. determined -> calculated

Line 123. Explain the "mapping all reads" correctly. Is it raw reads or trimmed reads?

Lines 135-136. The expansion and contraction of inverted repeats and their border positions -> Structural border of chloroplast genome

Line 136. ten selected Nicotiana species -> 10 Nicotiana species

Line 142. Microsatellites repeats  -> Microsatellites

Line 142. detected -> identified

Lines 151-152. It looks like an unnecessary sentence.

Line 177. For phylogenetic analysis -> For phylogenetic analysis, (added comma)

Line 195. As you mentioned 10 million generations, is this meant MCMC chain-length? If correct, it should be modified.

Line 218. I thought "species" would be better to delete.

Line 218. assembled and the lengths of these plastid genomes were: -> completely assembled those genome size as follows:

Lines 222-226. It seems better to write the size and GC contents of each structure rather than average coverage.

Line 227. De novo assembled Nicotiana plastid genomes had 133 unique genes, whereas -> Nicotiana plastid genomes harbored 133 unique genes, of those

Line 254. Add to reference paper of IRscope

Lines 294-296. Is this sentence meant to investigate the dispersed repeat? If this is right, write to purpose of analysis in more datail.

Line 338. What is mean of "reconstructed"?

Line 339. Add to number of concatenated protein-coding genes.

Lines 376-377. Nicotiana tabacum -> N. tabacum
Nicotiana tomentosiformis -> N. tomentosiformis

Line 387. Specify to the exact number of species, not "all the species".

Line 393. Using without abbreviation of Ts/Tv, or paraphrasing to Ka/Ks.

Line 411. polymorphic regions -> polymorphism

Lines 418-434. Those paragraphs are look like the introduction.

Line 437. It would better "neutral selection" than "natural evolution".
You are previously wrote a positive selection, so you should be used "negative selection" than "purifying selection".

Line 485. Is this a typo? clpP1 -> clpP

Line 487. I thought "a recent study by " would be better to delete.

Lines 488-489. Following by "This might ~", what did you think so?

Lines 508-510. It is not good "However, our results should be regarded as tentative ~ as below" for discussion. Sentence should be replaced.


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: PLASTID GENOMICS OF NICOTIANA (SOLANACEAE): INSIGHTS INTO MOLECULAR EVOLUTION, POSITIVE SELECTION AND THE ORIGIN OF THE MATERNAL GENOME OF AZTEC TOBACCO (NICOTIANA RUSTICA)
Review round: 2
Reviewer: 1

Output:
Basic reporting: see "general comments"
Experimental design: see "general comments"
Validity of the findings: see "general comments"
Additional comments: I have difficulties to find the modifications since the text has heavily changed overall, and only a small fraction of changes is highlighted in the “grid” version. Can the authors please copy the new or modified sentence(s) along with their answers below each comment to facilitate a second review of the manuscript. Specifying line numbers would be helpful, too. Thanks.


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: OUTSTANDING PERFORMANCE OF AN INVASIVE ALIEN TREE BISCHOFIA JAVANICA RELATIVE TO NATIVE TREE SPECIES AND IMPLICATIONS FOR MANAGEMENT OF INSULAR PRIMARY FORESTS
Review round: 1
Reviewer: 1

Output:
Basic reporting: This study aims to understand the mechanisms of Bischofia javanica invade into the primary forest in Haha-jima Island, Japan. The English used in the manuscript is easy to understand, and introduction of the study is also clear. One concern is the definition of invasive species. A study in a nearby island, Taiwan, showed a primary forest on limestone was dominated by both Pisonia umbellifera and Bischofia javanica (Lin et al., 2017). Therefore, can the growing pattern of the Bischofia javanica considered as a northward expansion of the territory of the species, rather than invasive? If this expansion is a cause of natural climate change, such as global warming, is it really necessary to eradicate the species? How can we justify invasion when considering the regional flora, as Bischofia javanica is actually widely distributed in the east and southeast Asia, including Japan. Therefore, it is vital to define the definition of invasive at the introduction of the manuscript but also acknowledge that the species is actually widely distributed in the neighbourhood region.

The crown width index is not clearly defined. I think it is necessary to explain the rationale of the authors to use the index in the method section. For example, what the ecological meaning of the index is, and what a high number of the index indicates. Is the index necessary to indicate crown width, can it imply something else, such as coexistence potential? As the ecological meaning is not clear, it may be easier for the readers if the authors use a straight forward name of the index (e.g., covered stem per canopy tree?). However, again, what is the ecological meaning if more stems were covered under the crown of a species? Does this really correlate with crown width?

In Fig.4, 5, and 6, similar to the previous comment, the use of ‘above’ and ‘below’ is not clear. Please use a straight forward term, e.g., ‘covered by’ ‘be covered’. Also, in Fig 5 and 6, please clearly indicate which ones are the canopy species, and which ones are the understorey species in the figure legends.
Experimental design: The growth of large trees for one cm would have a different meaning in the total quantity of biomass compared to that of small trees. The authors need to justify why did they choose to use absolute growth rate, rather than the relative growth rate in the method section.

In Fig. 2, it seems to be the changes in density. As there are two kinds of growth, one is density changes and the other is diameter growth, it is better to clarify the terms used in the study.

Line 154 did the authors studied seedlings? In the method section, they only mentioned a survey of trees with DBH ≥ 10 cm in 2006 in line 115. What is the definition of seedlings in this study?

Line 179 to 183 how did the authors calculate the mortality rate? Please clarify in the method. There are several calculating methods, please see Kohyama et al. (2017).
Validity of the findings: In Fig.8 it is not clear why there are only two points of census data, but can have a prediction for two separate plots. If one point indicates the 1987 census and the other indicates the 2006 census, there should be four points in order to predict the patterns for two separate plots. Please explain.
Additional comments: Line 125 ‘……a map of individual trees created……’ revise the sentence as ‘ a tree-by-tree map drawn’

Line 266 the ecological meaning of this index is not clear.

Kohyama, T.S., Kohyama, T.I., Sheil, D., 2017. Definition and estimation of vital rates from repeated censuses: Choices, comparisons and bias corrections focusing on trees. Methods in Ecology and Evolution. 9, 809–821.

Lin, Y.-C., Comita, L.S., Johnson, D.J., Chen, M.R., Wu, S.H., 2017. Biotic vs. abiotic drivers of seedling persistence in a tropical karst forest. J. Veg. Sci. 28, 206-217.


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: OUTSTANDING PERFORMANCE OF AN INVASIVE ALIEN TREE BISCHOFIA JAVANICA RELATIVE TO NATIVE TREE SPECIES AND IMPLICATIONS FOR MANAGEMENT OF INSULAR PRIMARY FORESTS
Review round: 1
Reviewer: 2

Output:
Basic reporting: This is a very good paper that provides robust data, analysis and interpretation to show how an alien tree species is able to take advantage of a major disturbance to assume dominance of a biodiverse forest with important implications for biodiversity conservation.

I found the paper to be well conceived, well written, well referenced. In all, a very useful contribution to the growing literature on biological invasions in forests and alien tree invasions.
Experimental design: The study took advantage of a natural event and thus uses a natural experiment - obviously it would have been better to have replicates etc, but that was not possible. Overall, I think that the way that data were collected, analysed and interpreted is both novel and adequate to arrive at the conclusions that they did.
Validity of the findings: Although several studies have reported on the major impacts of invasive trees on islands (these are adequately referenced in the paper), this one makes especially interesting (and very worrying) new observations.
Additional comments: Minor specific suggestions:

line 34 - suggest replacing "invasive tree" with "tree invasions" (the latter term is more widely used)
line 46 - this species is currently known as Morella faya
lines 300-301 - The authors may want to consult the framework of Downy & Richardson (2016) [Downey, P.O. & Richardson, D.M.  (2016). Alien plant invasions and native plant extinctions: a six-threshold framework AoB Plants 8: plw047; doi: 10.1093/aobpla/plw047] when discussing how the impacts reported in this study could results in more dramatic impacts in terms of biodiversity loss over time.
line 355 - author name = Higgins
Figures 2-8 - Link to abbreviated names - I suggest that the full names and abbreviated names are given in Table 1- readers should not need to consult online appendices to get the full names. In all figures I suggest that the focal species (Bischofia javanica) be indicated in a different shading to make it stand out.
Table 1 - the terms "indigenous" and "alien" need to be explained here - indigenous/alien to which (bio)geographical region?. Bischofia javanica should be highlighted to make it stand out clearly.


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: OUTSTANDING PERFORMANCE OF AN INVASIVE ALIEN TREE BISCHOFIA JAVANICA RELATIVE TO NATIVE TREE SPECIES AND IMPLICATIONS FOR MANAGEMENT OF INSULAR PRIMARY FORESTS
Review round: 1
Reviewer: 3

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: In the manuscript, authors compared population dynamics (stem growth, survival and population changes) between an invasive tree, B. javanica and native tree species in primary native forests in an oceanic island to evaluate processes of its invasion and expansion. In addition, authors constructed logistic regression model using long-term census data to predict future expansion of B. javanica. Clarifying invasion processes of invasive trees to native forests and predict future invasion is very important to conduct effective conservation actions, especially, oceanic island ecosystems. Therefore, it is my opinion that this article warrants publication with major revision. There are several criticisms in this manuscript, but these could be remedied.

General comments
In this study, authors suggested that shading by canopy of B. javanica can inhibit growth of understory trees of native species. However, authors did not measure light environments directly. Therefore, discussions about effects of canopy of B. javanica on understory trees would be speculation. Authors should revise them.

I can not judge whether prediction of expansion based on the logistic model is reliable or not. This model is based only on data in 1987 and 2006. Are there direct or indirect evidences that changes in stem density and BA in this period is common in the forests and will continue in the future?

Overall, descriptions of hypotheses, predictions, measurements and statistical analyses are insufficient. I think that the four components and their correspondence should be descripted clearly. For example, correlations between annual diameter growth and population in Results (L194-198) is not descripted in Statistical analyses.

Specific comments
Line 28
“inhibit” is inappropriate expression because direct investigation about inhibition of B. javanica to native trees are not conducted.

L38-41, L45-47
These sentences are not necessary because it is likely that effects of B. javanica in this study are direct competitive effects for light, which is not ecosystem engineering.

L140-144
What is explanatory and responsible variables?

L177-183
Statistical analyses about mortality or survival among tree species (at least between B. javanica and dominant species) are necessary. For example, it can be analyzed using by GLM that responsible variable is dead or alive of individual stems (binomial error) and explanatory variable is tree species.

L184-192
Statistical analyses about stem density among tree species (at least between B. javanica and dominant species) are necessary. For example, it can be analyzed using by GLM that responsible variable is numbers of stem (Poisson or negative binomial error) and explanatory variable is tree species.

L194-198
The information is insufficient to show that whether values of B. javanica is deviated from those of other species These results should be also shown by scatter diagram.

L206-208
“inhibit” is inappropriate expression because direct investigation about inhibition of B. javanica to native trees are not conducted.

L232-234
An increase of population size depends not only on growth and survival but also on recruitment. Discussion about recruitment is also necessary.

L234-235：なぜ？　今回の台風に対する反応はあくまで相対的な値では
In this study, discussions about responses to typhoon damages are based on comparisons between B. javanica and native species. This can not suggest that native species do not adapt to typhoon damage. Are absolute growth rates of native species in this study less than those in other regions?

L250-251
Are there any evidences that B. javanica is still in an early stage of invasion?


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: OUTSTANDING PERFORMANCE OF AN INVASIVE ALIEN TREE BISCHOFIA JAVANICA RELATIVE TO NATIVE TREE SPECIES AND IMPLICATIONS FOR MANAGEMENT OF INSULAR PRIMARY FORESTS
Review round: 2
Reviewer: 1

Output:
Basic reporting: I have studied the response of the authors to my previous review and am satisfied that all my concerns were adequately dealt with.

I also read the full paper and believe that it is improved overall and that it makes an important contribution to the literature on tree invasions.
Experimental design: Sound and appropriate
Validity of the findings: Good
Additional comments: I am happy with the responses to my comments and suggestions.


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: WHONDRS-GUI: A WEB APPLICATION FOR GLOBAL SURVEY OF SURFACE WATER METABOLITES
Review round: 1
Reviewer: 1

Output:
Basic reporting: The figures appear to be screenshots of various pages of the WHONDRS-GUI from within RStudio. They contain ill-defined edges consistent with screenshots. Two of the figures still show the breadcrumb bar, which is not appropriate for a publication-quality figure. Lastly, the screenshots are not of sufficient resolution for publication. Thus, I recommend remaking these figures in an appropriate manner for publication prior to Acceptance.
Experimental design: The methods for generating the web application are described in sufficient detail. I was able to download the data and code and launch the web application locally. Note that I received errors when running the app locally and as such was unable to view the data within the web application. However, I was able to access the data via the Shiny server without issue.
Validity of the findings: No comment.
Additional comments: I commend the authors for their well-developed web application. In addition, the manuscript is clearly written in professional, concise, and unambiguous language. As noted below, the weakness is in the presentation of the figures and in the lack of a clearly defined way to report bug issues with local instances of the web application, which should be improved upon before Acceptance.
1.	Your figures need improvement to meet the standard of publication quality. Specifically, the figures appear to simply be screenshots of the Rstudio window with the WHONDRS-GUI running, resulting in low resolution images with ill-defined edges (i.e., you can clearly see the edges of background windows in the screenshots) and features that are not relevant to the image, such as the breadcrumb bar in Figures 1 and 3. It is also not clear what the inclusion of the scroll bar on the right-hand side of Figures 1 and 3 accomplishes in conveying information to the reader.
2.	I thank the authors for providing the raw data and code, however the local instance of the web application resulted in errors when viewing the data in my browser. You should provide a clearly defined way of reporting bug issues to the code author(s). There was not an obvious way to do this through the ESS-DIVE archive, and there is no reference to a public repository (e.g., github) for the app code that would such built-in capabilities. Although the code is shared, this should be improved by providing end users with a way to report bugs with the code (preferably something more streamlined than simple email communication with the corresponding author, which I inferred as the only option for reporting this issue).


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: WHONDRS-GUI: A WEB APPLICATION FOR GLOBAL SURVEY OF SURFACE WATER METABOLITES
Review round: 1
Reviewer: 2

Output:
Basic reporting: Integration of different types of knowledge worldwide about physical, chemical and biological processes in surface waters (rivers) to allow better predictions of possible scenarios of environmental perturbations is an interesting topic and a need
Experimental design: In my opinion, the more difficult aspect of the proposal is probably the integration of surface water metabolites and biological parameters information (which is highly changeable and dependent on time scale), with water physical properties and processes. Synchronization of both type of parameters is not easy.

Can the authors give more detail about how this crucial aspect can be approached?
Validity of the findings: Good proposal, interesting but challenging. Important aspects are not covered yet.
Additional comments: An important aspect not considered in the proposal is what data analysis tools should be used for the integration of information and for the acquisition of new knowledge, interpretation and prediction.

In the technology offered by the authors, only the access to the different type of data bases is given. This aspect is of great interest, but it is only the first step for the goal enunciated at the beginning of the paper, i.e. the understanding of the effects of river perturbations (dam operations, discharge, floods, draughts…) on the biogeochemistry of the river water resources. This should be made more clear in 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: ANTIMICROBIAL STEWARDSHIP IN REMOTE PRIMARY HEALTHCARE ACROSS NORTHERN AUSTRALIA
Review round: 1
Reviewer: 1

Output:
Basic reporting: The authors sough to understand the antimicrobial use in remote primary healthcare settings in Northern Australia. This is an important study, given the rising burden of antimicrobial resistance, globally.

In general the paper is clearly written and easy to follow. However there are a few concerns regarding the basic reporting.
1. The use of the word "understanding" in the title is unnecessary as the authors did not measure this. This should be deleted
2. The authors inappropriately use certain words without definitions e.g. "episodes", clinical presentations, treating health professionals, broad spectrum and narrow spectrum etc. This is misleading. The authors should revise the manuscript and minimize the use of undefined terms or their misuse
3. The introduction, in particular does dont compare antimicrobial use with other studies/audits in Australia and outside Australia. There is need to do a thorough literature search to inform the need for the study
4. In general, it is not clear what the objectives of the study/audit were. Authors should state the primary objectives and secondary objectives. These seem to be avrying from the abstract, not indicated in the introduction, different in the methods, discussion and conclusions. There needs to be consistence.
5. The authors should clearly state the audit standards against which they were making comparisons. This is not mentioned any where!
6. There is duplication in reporting of results in the tables and figures. Kindly revise accordingly
Experimental design: (1) It is not clear what study design was implemented and the outome measures thereof. Although it is indicated as an audit (which is descriptive) the authors make several comparisons among the districts and other districts outside Northern Australia.
(2) The comparisons should be supported by valid statistical analysses such as ANOVA, t-test or Chi-square test or logistics regression
(3) results should be reported according to the objectives. gain if one objective is on the functionality of the tool, then appropriate tests should be done to test the construct validity and reliability of the tool in the context of Northern Australia.
(4) The authors should classify the antibiotics/antimicrobial according the agreed upon WHO/ATC classes and also quantify then according to WHO/ATC classes. This helps to copare results across countries and regions. Currently the even the pencilins are grouped differently and perhaps not well classified (e.g. Amoxicillin classified as a narrow spectrum antibiotic)
(5) The most challenging aspect of the manuscript is lack of clear objectives from the onset and throughout the sections
(6) There is need to define what remote is and describe these settings briefly. It is lao not clear why and how 5 clinics were chosen from each area and how many clinics are in each area. The inclusion exclusion criteria should be indicated, as well as the recruitment of patinets and how it was done!
(7) What was the software Stata used to analyse and why?
Validity of the findings: (1) The results should be present according to clearly defined objectives to guide clear reading of the manuscript

(2) The authors make alot of comparisons among districts, health professions, antimicrobial and regions outside Northern Australia which is not backed up by results or appropriate statistical analyses.  Audits never aim to compare with others but to compare with self.

(3) The use of the tool in remote settings has to be tested for reliability and validity for the results to be interpreted accurately

(4) Who/how determined the appropriateness of the prescription. This may introduce bias and the authors need to explain this clearly

(4) The authors need to provide thresholds for  all measurements , e.g. compliance, functionality of the tool, prescribing rates of antibiotics etc
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: ANTIMICROBIAL STEWARDSHIP IN REMOTE PRIMARY HEALTHCARE ACROSS NORTHERN AUSTRALIA
Review round: 1
Reviewer: 2

Output:
Basic reporting: The authors should be congratulated for undertaking an ambitious body of auditing and analysis to provide a much needed insight into antibiotic prescribing in remote Australia.  The following are recommendations for improving the article:

Background:
Given the international audience of this journal consideration should be given to providing more context regarding how the health system operates in Australia and in particular remote areas.  This may also help with untangling all the acronyms.Many readers will be surprised to hear about how remote these areas are, and how clinical services are delivered as a result - including the staff mix and outreach services.
Some extra information on what we know about levels of antibiotic use and resistance in remote Australia from other studies and surveillance systems would also be useful.
Experimental design: This study was well designed and ethically conducted to a high technical standard.

Methods:
A quick summary of NAPS and why GP rather than hospital NAPS was chosen as a source for modification should be provided, along with relevant references.
Therapeutic Guidelines needs a reference and some explanation - esp in regards to how these are recommended by accreditation standards.
The evaluation of the tool is only allocated a few lines 146-148;215-224.  In the discussion there is a focus in the paper on lack of documentation - but this really isn't an issue of the tool itself - more a challenge often faced in point prevalence surveys and AMS in general.  There is a wealth of really interesting information and feedback about the tool hidden in the supplementary appendix.  I suggest some of this is added into the main paper.

The presentation of results is clear, and in line with the stacked charts often used in this area.  I found Figure 3 a bit confusing as it is trying to combine two sets of results - by jurisdiction, and also by profession.  Consider splitting this into two parts or display like Figure 1 and 2 for consistency.
Validity of the findings: Discussion: Some of the most interesting findings in the table such as the % of patients who were Aboriginal & Torres Strait Islander, the difference in staffing profile between the jurisdictions, and the % of abx dispensed with micro results, are not discussed in enough detail (or at all). Were these results expected based on what we know about the settings?  A bit of extra context would be useful here, rather than just a focus on what is different between urban and remote areas.
Additional comments: Well done in pulling this together - with just a bit of extra background and some more discussion it will make the article more accessible to an international audience.


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: ANTIMICROBIAL STEWARDSHIP IN REMOTE PRIMARY HEALTHCARE ACROSS NORTHERN AUSTRALIA
Review round: 2
Reviewer: 1

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: The authors have carefully edited the paper to address previous reviewer concerns.  As a result the manuscript now reads very well, and provides important contextual information that is useful for readers not familiar with AMS in Australia.


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: SALIVARY PROTEOME OF A NEOTROPICAL PRIMATE: POTENTIAL ROLES IN HOST DEFENSE AND ORAL FOOD PERCEPTION
Review round: 1
Reviewer: 1

Output:
Basic reporting: The English needs a major edition
Sufficient literature background, being relevant for drawing the conclusions and discussing the results.
Figures and tables are ok.
Experimental design: It seems to be adequated, but some clarifications are needed, as I suggest in the comments to authors.
Technics abl to provide rigorous and relevant data
Validity of the findings: Valid, but the presentation and discussion should be revised, as suggested in the comments to the authors.
Additional comments: The manuscript presents interesting results, relating the saliva of a primate with diet. This was an interesting evolution from other articles where saliva of these animals was studied, but now adding information through proteomics approaches.
However, the manuscript has several major considerations that need to be addressed before it can be considered for publication. One of the major points is English, which needs to be edited, since it is difficulting the interpretation of some parts of the text. Moreover, introduction is too long, considering the type of information it contains. Some methodological aspects should also be added and results section reviewed. Concerning discussion, I add also some points that should be addressed, but some of them would be avoid if English was clear.
My point-to-point considerations:
Abstract
Line 39 - "and for oral food perception" instead of "and taste sensitivity". This because after the authors refer astringency, and this is not a taste sensation.
Line 54 - The lack of identification of proline-rich proteins may not mean a really lack in the presence of these proteins, but rather a failure in these to be identified by mass spectrometry following a digestion with trypsin. I would suggest not to highlight these proteins in abstract.

Introduction:
Line 62 - I don't think this is the right place to cite Shimada. This paper refers that some species have salivary tannin-binding proteins, which protect them from suffer the anti-nutritional and toxic effects of tannins. As the sentence is written it seems that this paper refers that saliva may help to recognize diet-toxins, in order to animals select... I would suggest to change the sentence, if the authors want to keep the reference.
Line 65 - "relates to" instead of "influence"

Line 78-81 - English needs to be edited. This is an example of sentence which concepts seem confuse, but this may be due to the English
Line 92 - What the authors really want to say with "over-accumulation"? Do they mean increased levels in response to astringency? Or higher levels in individuals responding with higher intensity to astringency? Probably this needs clarification.
Lines 95-98 - Another example of confusing sentence, that does not allow to understand well the concepts

Material and methods
Lines 154-155 - dimension of gels and % of acrilamide should be detailed.
Lines 157-158 - what was the composition of the CBBR-250 solution and the composition of the fixative solution used before staining? It is important to have this information, since these reagents have influence in to obtain, or not, the pink bands after destainning with acetic acid.

Results
Lines 256-257 - I would remove this sentence from this section, since thisis more discussion than results
Line 260 - The number of individuals for which these 13 protein bands were digested and subjected to LC MS-MS is not clear. Each of these 13 protein bands is a pol of the same band from all the animals, or did the authors run 13 bands * 14 individuals. This must be clarified.
Lines 317-332 - All this paragraph is more a discussion than results presentation. If, on one hand, I understand that the authors want to present these in results section, since they are listing the proteins identified, which are related with oral food perception, on the other hand, I think this is not the best way of presenting. I would suggest that the authors make a table where they can put a column for the proteins identifies, other column for the type of oral sensation that they relate with and other column with the references where the link between the slivary protein and that oral sensation has been reported.
Probably table 1 is already the type of table I a suggesting, so you can base the presentation of results in that and avoid all this description.

Discussion
Lines 340-341 - This sentence needs to be reviewed. As it is I cannot understand if the authors identified for the first time or if de Sousa-Parreira et al had identified before
Line 371 - Another sentence where correction is imperative to achieve rigour. As it is it appears that is specifically in the saliva of howlers that this protein has these functions. But the study tht is cited does not refer these animals.

Lines 381-382 - once more it appears that the cited study evaluated this for the howlers... Please correct the sentence
Lines 389-397 - Moreover, the preparation procedure, with centrifugation at 16000g and the analysis of supernatant result in loss of mucins in the precipitate
Lines 397-400 - I think the authors should not consider "strange" the absence of PRPs. The methodology used in this study does not allow us to expect to find these proteins. On one hand, the sample preparation, with centrifugation would remove potential PRPs complexes that could be formed by binding to food (polyphenols) constituents. Although no incubation was made in vitro, in the oral cavity saliva is in contact with food constituents and, in case of some degree of presence, it would be expected to be in the precipitate. Moreover, with digestion with trypsin it is not expected to identify PRPs by mass spectrometry easily, since they do not digest as it would be in theory, due to the prolines present. So, I think that the other types of possible explanations to the failure in identifying PRPs, or even the hypothesis of lacking in these animals makes not much sense.
Lines 413-416 - This sentence needs to be supported with references where these specific proteins have been observed to b linked with "negative" traits of foods, which I suppose the authors mean bitterness and astringency
Line 427 - I am not comfortable with saltiness being associated with fat and energy content... In humans, an indirect relationship with processed foods can be made, but in animals, with natural access to food it makes not so many sense. So, thinking in adaptative evolution of senses, I would avoid to make this relationship, at least without bibliographic support.

Line 441 - When the authors are stating that leafs have few energy, it makes no sense to me to refer that the presence of some salivary proteins would help to select the ones with more energy... I think the focus must b mainly concerning the need to avoid PSM. I am not stating that these proteins cannot help in other sensory processes, but since this manuscript does not have measured diet type, nor subjected the animals to different types of diets, the authors should focus with is most known from other studies and I think the potential relation between salivary proteins and PSMs is stronger that hypothesis with energy signaling in leafs.

Lines 444-445 - This hypothesis would benefit if supported for studies showing a relationship between cystatins and sweet food sensitivity

Lines 450 -451 - This was already stated in the previous paragraph. Please reorganize to have each of the different sensory/nutritional aspects of foods together
Lines 456-458 - This sentence, in this place, does not add value to the discussion, unless the authors refer that other defense mechanisms exist in humans (besides salivary proteins) and this can also be expected in monkeys. Even so, I think it is not clear to have this in sequence of the previous text.
Lines 459-462 - This sentence needs to be supported with references.

Line 467 - please remove this part of the sentence: “but did not identify these proteins”

Conclusions
Line 480 - As I referred before, I would prefer the authors to say "oral food perception" rather than "taste sensitivity", since they are discussing all the results with different types of sensations that can occur in mouth
Lines 486-487 - Since the approach used would not allow many conclusions about these proteins, I would opt by not referring them here or in abstract.


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: SALIVARY PROTEOME OF A NEOTROPICAL PRIMATE: POTENTIAL ROLES IN HOST DEFENSE AND ORAL FOOD PERCEPTION
Review round: 1
Reviewer: 2

Output:
Basic reporting: The paper was straight forward and easy to read for the most part. It could use the assistance of a language editor. Examples include but are not limited to line 63 "so that a nutritious non-toxins can be selected" and 66 "in a diversity of environment." Also there is some repetition eg. Lines 102-105 and 451-454 are almost identical.
Experimental design: This is not a hypothesis driven paper, it is descriptive in nature.  Samples were collected from darted monkeys and analyzed.
Validity of the findings: My major concern with the paper is that the authors have defined and interpreted the proteins they found by categorizing them based on the literature which is at best unsure.  For example, there is still quite a lot of debate about the role of some of these salivary proteins in taste and many are correlated with preference at best.  I strongly urge the authors to temper their interpretations of these protein classes. For example, something as simple as acknowledging the uncertainty of the interpretation would help.
An example, although my concerns are not limited to line 409 should read ".. that may allow them to be selective and discerning while feeding"

I am also concerned by the lack of PRPs in the results.  This suggests that a step in the identification of the proteins was not ideal for isolating and identifying the PRPs. It would be useful to have a bit more discussion about this issue.
Additional comments: This is a straightforward and well contained description of howler monkey saliva. I would caution the authors to tone down the interpretation of the proteins presence when the fields looking at those proteins are still in debate on the causal relationships between the proteins and the functions in many cases.


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: SALIVARY PROTEOME OF A NEOTROPICAL PRIMATE: POTENTIAL ROLES IN HOST DEFENSE AND ORAL FOOD PERCEPTION
Review round: 2
Reviewer: 1

Output:
Basic reporting: Corrected according suggestions.
Experimental design: OK
Validity of the findings: With the corrected version it is ok.
Additional comments: The authors were able to answer my concerns and the manuscript greatly improved. I consider it acceptable in its current form.
A very minor point, but that I think should be adressed is in the pargraph in lines 326 – 333, “human taste perception of fatty acids" can be replaced by “human taste perception of bitterness or fatty acids”.


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: SALIVARY PROTEOME OF A NEOTROPICAL PRIMATE: POTENTIAL ROLES IN HOST DEFENSE AND ORAL FOOD PERCEPTION
Review round: 2
Reviewer: 2

Output:
Basic reporting: Authors have addressed my concerns.
Experimental design: Clear and thoughtful
Validity of the findings: Underlying data are interesting and useful
Additional comments: The authors have addressed my concerns.


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: DESCRIPTION OF TWO NEW SPECIES OF THE GENUS HETEROCHELAMON TÜRKAY & DAI, 1997 (CRUSTACEA: DECAPODA: BRACHYURA: POTAMIDAE), FROM SOUTHERN CHINA
Review round: 1
Reviewer: 1

Output:
Basic reporting: The language still needs some degree of elaboration, as I remarked directly on the main text file in PDF format.
Reference citations are sufficient.
Article structure, as well as figures and table, are in good condition. Sequence data is shared.
Main objective of this paper is to describe two new species of the potamid freshwater crab genus Heterochelamon. Recognition of the two new species seems to be supported by both morphological and molecular evidence.
Experimental design: The manuscript is the resubmission after my two-times reviews. I do not repeat the same report.
Validity of the findings: Discovery of two new species of freshwater crabs contribute the biodiversity research on the globe.
Molecular data seems to be sufficient. Morphological descriptions require minor reexamination, as remarked on the main text file.
As noted above, the recognition of new species seems to be justified. Discussion on the zoogeography contains some speculation, but clearly identified as such, acceptable.
Additional comments: I could normally communicate with the manuscript after resubmission with two-times review.
Species comparison could be expanded to mention potential relationship of the new species to other congeneric species. Four species are available for molecular phylogenetic analysis.
For more detailed comments and edits, please see the main text file remarked.
I know that drafting manuscript of a scientific article in foreign language is always challenging for non-native speakers, but we can not avoid it for normal communication in our community.


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: DESCRIPTION OF TWO NEW SPECIES OF THE GENUS HETEROCHELAMON TÜRKAY & DAI, 1997 (CRUSTACEA: DECAPODA: BRACHYURA: POTAMIDAE), FROM SOUTHERN CHINA
Review round: 1
Reviewer: 2

Output:
Basic reporting: .
Experimental design: .
Validity of the findings: .
Additional comments: See attachment


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: AN OVERVIEW OF BIOMASS CONVERSION: EXPLORING NEW OPPORTUNITIES
Review round: 1
Reviewer: 1

Output:
Basic reporting: This paper intended to overview the plant biomass processing methods and intend to explore the possibilities of new methods and enzymes to be used in biomass recyclization. But the structure and logic of the whole manuscript is not very clear,  and the authors should have thought more deeply and provide more own perspective and important conclusions.
Experimental design: no comment
Validity of the findings: no comment
Additional comments: This paper intended to overview the plant biomass processing methods and intend to explore the possibilities of new methods and enzymes to be used in biomass recyclization. But the structure and logic of the whole manuscript is not very clear,  and the authors should have thought more deeply and provide more own perspective and important conclusions.
1.	Line 22-24, actually, lots of work has been done in the modification of enzymes and alter the function of enzymes.
2.	Your introduction needs more detail.
3.	Line 390-408, Enzyme modification, in this part, the author should review the progress on enzyme modification, especially advances in methods, great progress have been made in recent years.
4.	The references should be arranged in alphabetical order.


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: AN OVERVIEW OF BIOMASS CONVERSION: EXPLORING NEW OPPORTUNITIES
Review round: 1
Reviewer: 2

Output:
Basic reporting: Must be improved - see comments for suggestions. Notably, the structure of the manuscript lacks coherence and the figure has no strong contribution to the goal of this review.

Literature references are not sufficient for lines before Line 109.
Experimental design: no comment.
Validity of the findings: no comment.
Additional comments: The manuscript intends to review "the results of plant biomass processing methods", including pretreatment methods (2 pages), enzymes for biomass processing (1.5 pages), and optimization of enzymes (computational modeling for 3 pages and experimental confirmation for 0.5 pages). The basic concepts might be useful, however they are marred by poor presentation. The focus of the manuscript seems to be shifted to computation modeling later on without enough rationals.

Line 31. Can the authors provide more recent data?
Line 51. What's the significance of mentioning "Hydrolysis of the ...... molecules?
Line 58. Lack of coherence: The authors mentioned the hydrolysis of hemicelluloses takes place under milder condition. However, the next sentence goes to the hydrolysis conditions for cellulose and lost track of hemicellulose conditions.
Line 64. The sentence is the same with the previous one.
Line 69-72. What's the significance of mentioning "pectin"? It was never mentioned again later on. If this is part of the introduction, the authors should focus on the topics that are useful for main results/discussion.
Line 31-109. Lack of literature supports.
Line 113. check grammar.
Line 130. Add reference.
Line 131. What does "this purpose" refer to?
Line 135. "Modified micro fibrillated cellulose was used" for what purpose?
Line 137. "changed the surface character" of which component?
Line 135-143. The paragraph before and after this seem to be talking about pre-treatment. However, these lines seem to be talking about modification? Should move this paragraph to somewhere else.
Line 144-146. Why is this sentence relevant to the topic and the context?
Line 150-153. Why is this sentence relevant to the topic and the context?
Line 157-159. "...elasticity..." Why is this sentence relevant to the topic and the context?
Line 160. "....the reduction" of which component?
Line 163. Why is this sentence relevant to the topic and the context?
LIne 164-170. this paragraph seems to be sentences of information pasted together with no connection to each other.
Line 171-173. Why is this sentence relevant to the topic and the context?
Line 187-189. This paragraph seems to be talking about modification? but this sentence is not about modification. It does not go well with the context.
Line 197-200. It's important to state what other researcher has done. But the authors provided methods instead of results, showing no relevance to the context or the manuscript.
Line 207. Why immobilize? This sentence might go better with the next paragraph
Line 219-221. Maybe it's better to lead the paragraph with this sentence.
Line 234. "by enzymes..." Please specify which enzymes.
Line 258. reference.
Line 264-265. Why is this sentence relevant to the topic and the context?
Line 281-281. This sentence is a repeat of previous sentence.
Line 289-291. Why is this sentence relevant to the topic and the context? What results did the reference show?
Line 303. Why is this figure relevant to the manuscript?
Line 306-309. Why is this relevant to the topic and the context?
Line 342-347. Why is this knowledge relevant to the topic?
Line 352. "...broader space..." what does this imply and why is this relevant to the topic?
Line 370. "To examine the linker function..." should this be moved up to Line 354 so it goes together with other "linker" topic?
Line 402. "may affect the critical properties of enzymes" how? and why is this relevant to the topic?


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: AN OVERVIEW OF BIOMASS CONVERSION: EXPLORING NEW OPPORTUNITIES
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: The coherence of the manuscript was much improved! The introduction is sufficient and the rational of the study is clear. The authors' rebuttal provides some interesting aspects for the significance of "modification of enzymes using molecular modeling methods": "There are very few articles on the latter...All this is possible using special molecular modeling methods... 50 new articles, most of which are from the last two years". Incorporating the rebuttal into main manuscript might help stress the importance and point out the fast evolving nature of this area of research.


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: ROLE OF METHYLTRANSFERASE-LIKE ENZYME 3 AND METHYLTRANSFERASE-LIKE ENZYME 14 IN UROLOGICAL CANCERS
Review round: 1
Reviewer: 1

Output:
Basic reporting: Needs improvement of English.
Experimental design: Needs more recent references to relevant works, specifically on the same topic.
Validity of the findings: Figures and table are helpful for the reader.
Additional comments: In this review the authors summarize evidence on m6A-related proteins METTL3 and METTL14 on urological cancers. I have some suggestions for improving the manuscript:

-Some gramatical errors and sentences merit review: eg. “When METTL3 is high expression”, please rephrase. Sentence “These results suggest that although METTL3 and METTL14 show different expression and regulation mechanism in urological cancers” makes no sense, it is not complete. The same with “Similar to METTL3, METTL14 are more predisposed to mutation or CNV” and “Low METTL14 and PTEN expression show shorter OS” – the patients show mutations or poorer survival, not the proteins, please rephrase. Please change “style” for “type” when referring to the histological types of the various cancers. Prostate cancer is abbreviated, but then the abbreviation is not always used after the first mention. I advise authors to carefully review the written English for these details.

-The authors lack reference to some recent reviews. Including works on the exact same topic, i.e., m6A modifications on Urological Tumors, including METTL3 and METTL14. I suggest adding “The Emerging Role of Epitranscriptomics in Cancer: Focus on Urological Tumors, PMID: 30428628” to the discussion.

-The authors decide to focus on urological cancer, but leave out testicular tumors, which is unfortunate given the insightful parallelism between the impact of m6A during development and the emergence of germ cell tumors, which would be interesting for the reader. I suggest adding this briefly to the review, namely discussing very recent works on this topic, which can substantiate the impact of m6A in urological cancer: “m6A RNA modification and its writer/reader VIRMA/YTHDF3 in testicular germ cell tumors: a role in seminoma phenotype maintenance,  PMID: 30866959” and also “N6-Methyladenosine detected in RNA of testicular germ cell tumors is controlled by METTL3, ALKBH5, YTHDC1/F1/F2, and HNRNPC as writers, erasers, and readers, PMID: 30903744”.

Authors are also missing a recent complete work on prostate cancer (“VIRMA-Dependent N6-Methyladenosine Modifications Regulate the Expression of Long Non-Coding RNAs CCAT1 and CCAT2 in Prostate Cancer, PMID 32218194”. Since the authors present a review article specifically directed to urological cancer in a recent expanding field, I advise authors to be complete in their literature search and include/discuss all works available on m6A-related proteins, to discuss briefly and give the reader a broad overview, and only then give focus to METTL3/METTL14.


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: ROLE OF METHYLTRANSFERASE-LIKE ENZYME 3 AND METHYLTRANSFERASE-LIKE ENZYME 14 IN UROLOGICAL CANCERS
Review round: 1
Reviewer: 2

Output:
Basic reporting: The manuscript，“Role of methyltransferase-like enzyme 3 and methyltransferase-like enzyme 14 of N6- methyladenosine in the urological cancers” submitted by Zijia Tao and coworkers, describes METTL3 and METTL14 expression in urological cancers. They found a potential possibility for using m6A as a new therapeutic target in urological cancer.
Experimental design: No comment
Validity of the findings: Conclusions are well stated.
Additional comments: This manuscript was well-written and presented in a clear and logical fashion.


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: ROLE OF METHYLTRANSFERASE-LIKE ENZYME 3 AND METHYLTRANSFERASE-LIKE ENZYME 14 IN UROLOGICAL CANCERS
Review round: 1
Reviewer: 3

Output:
Basic reporting: The authors have done a good job in assimilating the literature knowledge into this review. However, it might be important for all readers to know what is urological cancer and its types in the "Introduction", which is not well-written. Please include how this review is going to advance the field in the form of significance of this review.

There are few grammatical English language error.
Experimental design: The authors managed to categorize well but this has led to redundancy of many points throughout with proper references.
Validity of the findings: Need to add significance of this review in the existing field.
Additional comments: 1. Line 52 “living entities” can be replaced with “living organisms”
2. Line 149-150: meaning is not clear
3. Line 151-157: This sentence is very generalized for all cancers, might not be needed here
4. The authors could use the appropriate inhibitory pathway arrow instead of the yellow arrow.


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: ROLE OF METHYLTRANSFERASE-LIKE ENZYME 3 AND METHYLTRANSFERASE-LIKE ENZYME 14 IN UROLOGICAL CANCERS
Review round: 2
Reviewer: 1

Output:
Basic reporting: No further comments.
Experimental design: No further comments.
Validity of the findings: No further comments.
Additional comments: No further 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: ROLE OF METHYLTRANSFERASE-LIKE ENZYME 3 AND METHYLTRANSFERASE-LIKE ENZYME 14 IN UROLOGICAL CANCERS
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors have thoroughly worked and improved upon the previous remarks made. However, there are few points below which I think will help to make the work more accurate.
1.	English language throughout the text is very convoluted with too many jargons and gene symbols, that are explained nowhere, which off-puts readers and leads to confusion than convincing the stated facts. Language clearity will enable the authors to keep the review be well cited.
2.	Fig3, I guess the authors wanted to write “less reports of study with METTL14 in prostate cancer” not METTL3
3.	Please be consistent with the terminologies like ONCOGENE and TUMOR SUPPRESSOR which should be uniform in text and figures and tables. Avoid writing tumor promoting and anti-oncogenic, they are incorrect.
Experimental design: It is well investigated study, however, the authors should also included TCGA urological cancer datasets.
Validity of the findings: Please check the figure legend of Fig 3.
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: SCHOOL HEALTH ASSESSMENT TOOLS: A SYSTEMATIC REVIEW OF MEASUREMENT IN PRIMARY SCHOOLS
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript is written in clear professional English.
References and background are sufficiently provided.
The manuscript adopts a professional article structure, with relevant (but improvable) results.
Results include the definitions of the different psychometrical properties (i.e. internal consistency, measurement error, etc...). I would move the definitions in the Methods section.
Experimental design: The manuscript focuses on the psychometric properties of the instruments and only superficially depicts and analyses the instruments constructs and their practical usability in the clinical or research practice.
The Authors should: 1) better justify why the psychometrical / statistical evaluation is important in the background section; 2) perform a more detailed analysis of the content of the instruments and reprise it in the discussion.
Validity of the findings: In a manuscript that evaluates instruments, the reader would expect to find implementation issues in the discussion.
The discussion section lacks of implication for the clinical or research practice. For example, what instruments should be used? Do you reccomend it? I would say that the answer to this question should include more than an evaluation of the validation methodology.
Additional comments: The third table is redundant, it could be converted in plain text. Conversely, the search algorithm (lines 143-160) could be reported in a table.


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: SCHOOL HEALTH ASSESSMENT TOOLS: A SYSTEMATIC REVIEW OF MEASUREMENT IN PRIMARY SCHOOLS
Review round: 1
Reviewer: 2

Output:
Basic reporting: Thank you for the opportunity to review your manuscript! The authors address a critical issue regarding school health assessment and how the work fits into the broaden the knowledge of school health promotion. Major relevant literature has been appropriately referenced.

Other suggestions:
Title: Shouldn’t only the first alphabet of the first word be capitalized?
WHO Health-Promoting Schools Framework and WHO health-promoting components were mentioned in the article. If they present the same concept, I suggest authors to maintain consistency throughout the article.
Table 1. Please list studies reviewed in chronological order; use the correct format for Table 1 title.
Several grammar errors were identified. Please correct them throughout the manuscript. For example, line 305.
Citations in the references should follow the guideline and format provided by the journal.
Experimental design: I hope the following suggestions will help improve the quality of the study.
In the methods section, some information needs further clarifications.
Criteria for selection (2), the instruments should measure the WHO health-promoting components (at least four of the eight components). Authors introduced several models suggesting various components of school health. I wonder why the WHO health-promoting components were used? What are those eight components proposed by WHO health-promoting? I suggest authors to address them in the literature review. Also, what is the rationale of at least four of eight components should be met? Please explain. Shouldn’t those WHO health-promoting components be used as terms other than “school health” to search for additional potential articles?
Criteria for selection (4), please help me understand the rationale of the focus on primary school students? Why were middle and high schools excluded? If primary school was chosen,  I suggest that authors improve the description in literature review to provide justification for your study.
The term “evaluation” was used in the search (line 151). It should be added to line 148.
Validity of the findings: If authors can clarify the issues mentioned in Experimental design section, the findings of the study will make more sense.

Results:
Please make sure that the description and numbers of articles described in the Study Selection section aligns with Figure 1.
Additional comments: Thank you for the opportunity to review your manuscript! The authors address a critical issue regarding school health assessment and how the work fits into the broaden the knowledge of school health promotion. Major relevant literature has been appropriately referenced. I hope the following suggestions will help improve the quality of the study.

In the methods section, some information needs further clarifications.
Criteria for selection (2), the instruments should measure the WHO health-promoting components (at least four of the eight components). Authors introduced several models suggesting various components of school health. I wonder why the WHO health-promoting components were used? What are those eight components proposed by WHO health-promoting? I suggest authors to address them in the literature review. Also, what is the rationale of at least four of eight components should be met? Please explain. Shouldn’t those WHO health-promoting components be used as terms other than “school health” to search for additional potential articles?
Criteria for selection (4), please help me understand the rationale of the focus on primary school students? Why were middle and high schools excluded? If primary school was chosen,  I suggest that authors improve the description in literature review to provide justification for your study.
The term “evaluation” was used in the search (line 151). It should be added to line 148.

Results:
Please make sure that the description and numbers of articles described in the Study Selection section aligns with Figure 1.

Other suggestions:
Title: Shouldn’t only the first alphabet of the first word be capitalized?
WHO Health-Promoting Schools Framework and WHO health-promoting components were mentioned in the article. If they present the same concept, I suggest authors to maintain consistency throughout the article.
Table 1. Please list studies reviewed in chronological order; use the correct format for Table 1 title.
Several grammar errors were identified. Please correct them throughout the manuscript. For example, line 305.
Citations in the references should follow the guideline and format provided by the journal.


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: SCHOOL HEALTH ASSESSMENT TOOLS: A SYSTEMATIC REVIEW OF MEASUREMENT IN PRIMARY SCHOOLS
Review round: 2
Reviewer: 1

Output:
Basic reporting: No comment
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: IDENTIFICATION OF KEY GENES OF HUMAN BONE MARROW STROMAL CELLS ADIPOGENESIS AT AN EARLY STAGE
Review round: 1
Reviewer: 1

Output:
Basic reporting: The content of this paper is thought to be scientific and straightforward. They performed the experiments based on the previous research.
Experimental design: Using the downloaded GEO database, they performed various analysis such as DDEGs, KEGG pathway, and PPI network analysis. Finally, they confirmed the results obtained by the analysis described above in vivo OVX model mouse. The experimental strategy is simple and the obtained results are informative.
Validity of the findings: They used the data that have already uploaded to the gene profiling data base. That is why  I feel the novelty of this manuscript is at average level. However, Their analysis sounds interesting for especially the researchers in the field of mesenchymal cell biology.
Additional comments: In this manuscript, Chen et al., investigated the intrinsic molecular pathway and factors involved in adipogenesis of bone marrow stromal cells. Using the downloaded GEO database, they performed various analysis such as DDEGs, KEGG pathway, and PPI network analysis. Finally, they confirmed the results obtained by the analysis described above in vivo OVX model mouse. The experimental strategy is simple and the obtained results are informative. Before it can be considered for publication, I would like to request some revisions or answers against the following points.

1.	In the introduction section (lane 72-73), the author described that “further investigations of …..and balance of osteogenic and adipogenic lineage commitment are needed.”
What the authors identified in this paper is the key genes of human BMSCs adipogenesis. Therefore, these sentences in the introduction section might give us the wrong impression that the authors also investigated key factors involved in the balance of osteogenic and adipogenic lineage commitment.
2.	Lane 207, “Fig. 4A-C” should be “Fig. 4A and B”.
3.	The authors identified many important genes that were significantly changed in this analysis. However, in vivo experiments, the authors checked the expression of only S1PR3, ACSL1, ZBTB16 and GPC3. Why did the authors choose these 4 genes? Selecting ACSL1 seems reasonable based on the data of GSEA enrichment analysis. How about the others?


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: IDENTIFICATION OF KEY GENES OF HUMAN BONE MARROW STROMAL CELLS ADIPOGENESIS AT AN EARLY STAGE
Review round: 1
Reviewer: 2

Output:
Basic reporting: In this manuscript, the authors used the existed datasets with gene expression during adipogenesis, and extrancted the differentially expressed genes. Those genes were further analyzed witn GO, KEGG, GSEA analysis and PPI network analysis. The diffential expression of some of designated genes were confirmed by cultured cells and OVX.
Those confirmed genes can have the potentiality of function in adipogenesis.

To be acceppted, following concerning to be solved.

1.
In Fig. 2, The red colored expression seems to be all saturated.
The color gradation should be shown in both of red and blue direction.
The value of relative expression should be shown in color guide.

2.
In Fig. 3, P-value for each GO term presented should also be shown similaly to Fig. 4.

3.
In main text line 206, "Fig. 4A-C" should be "Fig. 5A-C".

4.
In Fig. 5E, color gradation guide with the value should be shown.

5.
In Fig. 6, Since figures were too complecate, it is diffecult to understand the detailed network relationship.
Especially in Fig. 6B, nodes and edges should be presented more clearly.
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: IDENTIFICATION OF KEY GENES OF HUMAN BONE MARROW STROMAL CELLS ADIPOGENESIS AT AN EARLY STAGE
Review round: 2
Reviewer: 1

Output:
Basic reporting: No comment.
Experimental design: No comment.
Validity of the findings: No comment.
Additional comments: All points of the requests have been properly answered and corrected.
I agree to accept this manuscript to be published in this journal.