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: EXPLAINING DETECTION HETEROGENEITY WITH FINITE MIXTURE AND NON-EUCLIDEAN MOVEMENT IN SPATIALLY EXPLICIT CAPTURE-RECAPTURE MODELS
Review round: 1
Reviewer: 3

Output:
Basic reporting: This article has a colid presentation. I was very impressed by the breadth of literature references ranging from SCR-cost modeling to statistical nuances of model selection, etc. The authors are clearly well-read on these topics. The language is clear (though I note some areas for improvement). The tables and figures are also solid. The results do a fair job of matching the hypothesis. One area of improvement would be reframing aspects of the findings in terms of generally applicable recommendations. I discuss this more within the additional comments, which I hope is helpful!
Experimental design: The framework of the article is straightforward: exploring the applicability of a variety of common modeling approaches on a very impressive SCR dataset and comparing and contrasting estimates across approaches. The research gap that is addressed is about if non-Euclidean models (and finite-mixture models) should be used in instances where there is little to no expectation of landscape resistance from some aspect of the habitat. This is a fair question, and the authors explore the question with a solid dataset. Again, the SCR dataset is very impressive, and the authors clearly allocated a lot of computational effort to this project. The methods were sufficient most of the time. However, the authors should focus on double-checking how the details of their modeling approach align with standard recommendations from SCR modeling (related to spatial trap configuration, state-space modeling methods, and inclusion of a behavioral response), as it appeared there might be some inconsistencies, which I expanded upon within the additional comments.
Validity of the findings: There were doi references to the SCR dataset, and spatial covariates were referenced, as well. The study clearly uses a large dataset for an empirical investigation of a topic that has been studied with simulation studies as well as most often smaller empirical datasets, so it's interesting to see an application of ecological distance modeling here.
Additional comments: My most important (more major) comments are on lines:
1) L196
2) L195-196, L212, and L214
3) L300
4) L456

All comments:

Abstract

L17 - Here you are referencing multiple sources of heterogeneity, so consider rewording to: These types of heterogeneity can cause bias…”

L21 - Between these two sentences, it would be helpful to have a sentence that briefly describes the goal of this study.

L24 - This is an interesting result, but at this point in the Abstract we have no context as to why finite mixture models were used. That context isn’t provided until L28.

L24 - It’s unclear what “scale” is really referring to here. The resolution of the covariates? The size of the study area?

L30 - The real key to estimating landscape connectivity is in the number of spatial recaptures, not captures per individual, and it could be helpful to reframe that here. I expand on this in my later comments.

L31 - This sounds rather circular. Consider instead saying: “In our study areas, where we expected that landscape features do not seriously constrain movements,…”. Also, it’s unclear if “our study areas” refers to all 52 study areas or some subset of them.

L32 - From investigations of this issue, there is a recommendation of the maximum resolution of a landscape covariate, and it should be 0.5-1x the SCR spatial scale of detection parameter. It could be helpful to frame this sentence in reference to the standard recommendation. I expand on this in my later comments.

L36 - This sentence is rather long and becomes slightly confusing, especially what “it” is referring to in this last line. Consider rephrasing.

Introduction

L81 - Unclear what is meant by a dataset needing to have reliable application. Clarification would be very helpful.

L85 - This sentence is confusing, I think you’re trying to say it’s easier to model heterogeneity when you know the underlying cause of it, but the way the sentence is currently phrased doesn’t get that point across easily.

L112 - I think what you’re trying to say here is that the approach has significant potential, not that it’s potentially significant, is that correct?

L113 - Jumping into how ecological distance is calculated is jarring. Consider stepping back and fleshing out what is meant by ecological distance. From there, you could go into why it’s useful (which you discuss already, in that is more interpretable).

L135 - Typo: dropped the “s” on “corridor”

L137 - Typo: extra “s” on “model”

L132-L140 - After reading this paragraph several times, I’m not quite sure what point you’re trying to make. It seems like you might be using the jaguars as a counterexample for a hypothetical case of not knowing what structures movement. But the setup for that leads the reader to expect an example of the opposite. Consider revisiting this paragraph.

Methods

L173 - This seems like a diverse conifer community, with conifers of different canopy structures and resulting penetrability to large animals. Could this create any heterogeneity in movement?

L196 - This is a baited sampling design, which could lead to a behavioral response (i.e., “trap happiness”), but it appears the models used did not account for this. Can you expand on this choice in the text? See Augustine et al. (2014) for example.

L195-L196 - No mention here of trap design relative to standard recommendations. Is this trap spacing equivalent to the standard recommendation of ~2x the spatial scale of detection? SCR is very sensitive to adequate sampling design, so this must be addressed directly. Also, was it a grid of 40-45 traps (with all inter-trap distances equivalent), or a more heterogeneous design? A figure of some of the designs could be helpful.

L203 - 204 - Can you provide information on what effect this “discarding” might have on SCR estimates? Or should it be completely random such that all it does is lowers the detection intercept (g0)?

L212 - The resolution of the integration mesh should be equivalent to ~0.5-1x the spatial scale of detection, and the buffer should be ~3x the spatial scale of detection. As with trap spacing, you should reference standard recommendations here. This is all discussed in the Royle et al. book Spatial Capture-Recapture.

L214 - At this point, you have stated:
- Trap spacing of 1.5km, implying a sigma of 0.75km
- Integration grid of 1km resolution, implying a sigma of 1-2km
- State-space buffer of 15km, implying a sigma of 3km
These values appear to not match up with standard recommendations. If the traps are set according to standard recommendations, then the integration grid should be 0.375-0.75km in resolution, and the state-space buffer should be 2.25 km. This needs to be addressed — how did you choose the values for these three design components? What is the biological justification? I did not see estimates of sigma in the text for comparison, either.

L280 - To what is “the coarser scale described above” referring? Perhaps you mean “described below”, in the next section: Spatial resolution.

L292 - I could be misremembering, but I believe that alpha2 values of zero should be ok, and a value of zero just makes the scaling of Euclidean distance to ecological distance equal to 1, such that they’re equivalent. Further, if you don’t allow for zero-valued cost values, then how do you estimate negative cost values (e.g., a covariate class that relatively amplifies movement)? For example… cost(step1, step2) = (exp(alpha2*z(step1)) + exp(alpha2*z(step2)))/2 … cost = (exp(0*1) + exp(0*1))/2 … 1 + 1 / 2 = 1. So, in this way, the alpha2 parameter is converted to a cost, and (as you noted) the inverse of cost is connectivity.

L300 - It could be more generally applicable if you tested resolutions relative to sigma values, rather than arbitrary ones (e.g., 1-quarter sigma, 1-half sigma, 1-sigma, vs. 60, 120, 240, 520, 960).

Results

L328 - Please define “movements between traps” specifically.

L351-352 -  Resolving the scale issue for the design relative to sigma should make it more clear what covariate resolutions should be useful to test, and it could be that the resolution you were testing at was far smaller than necessary (recommendation is 0.5-1x sigma), which would be bumping up your computation time substantially. Also, given that the other design components suggest a sigma of around 0.75-1 km, the 15km buffer is likely far more than necessary, which would also dramatically increase computation time.

L372 - It would be helpful to streamline terminology. Overall, you use: non-Euclidean distance, ecological distance, cost, and landscape resistance. Most of these are fitting in the way they are used, but pointing out their relative meaning would be very helpful for the reader.

Discussion

L388 - “…would account for *otherwise* unmodelled detection heterogeneity…” might be better.

L389 - It seems like this sentence should be emphasizing that you expect non-Euclidean models to detect heterogeneity even where it might not be obvious (no dramatic structure), is that correct? Consider revisiting this sentence to rephrase it.

L396 - Focusing on movement recaptures is preferred over detections per individual since the former is more informative about movement and the ability to estimate alpha2.

L404 - “Contrary to past applications” I’m not sure exactly the point that you’re making here. Are you arguing that the listed past applications should not have used non-Euclidean models? Or that non-Euclidean models should not be used outside of situations where you have a good expectation of an important spatial covariate (as the listed examples did have)?

Conclusions

L456 - I noted that the emphasis should be on movement/spatial recaptures in L396, and it seems you’ve recognized that here. Making that point and shifting emphasis in that way throughout the paper would be very helpful since movement recaptures are the most important data for estimating how movement is affected by landscape structure.

Tables & Figures

Table 2 - Is “movement model” referring to what spatial covariate was used to estimate cost? If so, consider saying “spatial covariate” instead. Also, it would be helpful to clarify what the values in the table represent exactly.

Figure 1 - Plotting out the locations is helpful, but it doesn’t appear that there is much broad-scale spatial structure to density estimates or RSE. Perhaps there might be a better way to represent this?

References:

Augustine, B. C., Tredick, C. A., & Bonner, S. J. (2014). Accounting for behavioural response to capture when estimating population size from hair snare studies with missing data. Methods in Ecology and Evolution, 5(11), 1154-1161.


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: EXPLAINING DETECTION HETEROGENEITY WITH FINITE MIXTURE AND NON-EUCLIDEAN MOVEMENT IN SPATIALLY EXPLICIT CAPTURE-RECAPTURE MODELS
Review round: 2
Reviewer: 1

Output:
Basic reporting: Well written, good literature review, tables and figures relevant, and hypotheses addressed.
Experimental design: Experimental design sufficient and rigorous analysis of results.  Methods well described.
Validity of the findings: Conclusions well stated and not outside the scope of their analysis and data.
Additional comments: The paper “Explaining detection heterogeneity with finite mixture and non-Euclidean movement in spatially explicit capture-recapture models” by Marrotte et al. is an analysis of finite mixture, non-mixture, and non-Euclidean distance (non-ED) models to address individual heterogeneity in detection rates of black bears in Ontario.  I previously reviewed this manuscript and now comment on the revision.

L41.  “Data” is plural (change to “data are available”).
L45.  Really a nice introduction.
L84.  I am not sure what the conventions are for this journal but this list of citations is not chronological nor alphabetical.
L204.  By “scale of female movements” do you mean σ?  Please define.
L516.  I think it is important to point out that factors other than movement can cause individual capture heterogeneity that the non-Euclidean models do not assess.  Bears commonly approach hair traps but do not go in them; I think that some animals innately avoid entering traps and the non-Euclidean models will not identify those individuals.  However, the finite mixture models might.  I realize that random effects models are outside the scope of your paper but individual random effect models show promise for accounting for individual heterogeneity in non-SCR capture-recapture models (White, G. C., and E. G. Cooch.  2017.  Population abundance estimation with heterogeneous encounter probabilities using numerical integration.  Journal of Wildlife Management 81P:322–336.).  This has not been incorporated into maximum likelihood SCR models yet but that might make a good recommendation.
As an aside, I have found that finite mixture models are often affected by a few outlier observations.  A very large σ can often be associated with some large movements from a few individuals and re-running the model without those outlier captures can reveal whether they are the source for one of the mixtures.  I suspect that your very small estimates of σ might be due to multiple captures of individuals at only 1 trap, maybe because a trap is isolated from the others.  You might try removing a few of those repeat captures at single traps to see how much the mixtures are affected.  It could be that the mixture models are performing as they should and the problem is with study design.

In general, I am satisfied with how you addressed my concerns expressed in my earlier review.


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: EXPLAINING DETECTION HETEROGENEITY WITH FINITE MIXTURE AND NON-EUCLIDEAN MOVEMENT IN SPATIALLY EXPLICIT CAPTURE-RECAPTURE MODELS
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors substantially revised the manuscript for clarity. All else has remained satisfactory.
Experimental design: The design itself has remained the same, though the justification is seriously improved, and the design is solid.
Validity of the findings: The presentation of the findings is now more precise, and this is a meaningful contribution.
Additional comments: I'm satisfied with the authors' responses to my comments. Below, I elaborate on this regarding particularly important comments. Line number references correspond to those in the rebuttal document. I'm not requiring the authors to respond to these four points; the comments are just meant to clarify.

- The miscommunication between myself and the authors (on many points) was not that I ignored differences between sexes, but that it was not clear what the sigma value was for either sex based on what was written in the manuscript. That information should have been conspicuous. I see that the authors have included that information now explicitly (<1km for females, <2km for males).

- The reference to the Royle et al. book was simply a citation of this recommendation in the literature (a standard practice). I was not implying it need be cited in their manuscript.

- My comment on line L212 included a typo, apologies: the state-space buffer of 15 km should imply a sigma of 5km, not 3km (simple reversal). But, my point remained valid as I had explained it initially (SS buffer >= 3 x sigma, typically).

- In general response to my L212 comments: Again, sigma values for the sexes were not included obviously in the main text, and back-calculating them from design choices suggested incongruity that would have been, at the very least, confusing for the reader. I'm satisfied with the response from the authors and the additional information they included in the manuscript.


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

Input:
Title: MICROPLASTIC POLLUTION AT QILIANYU, THE LARGEST GREEN SEA TURTLE NESTING GROUNDS IN THE NORTHERN SOUTH CHINA SEA
Review round: 1
Reviewer: 1

Output:
Basic reporting: English was good but could be tightened up--I have provided edits to improve this. Everything else meets standards
Experimental design: no comment
Validity of the findings: no comment
Additional comments: This paper studies the plastic pollution of Qilianyu, China, an important nesting ground of the green sea turtle. This paper not only quantifies the plastic pollution at nesting grounds, but also highlights the potential problems and provides suggestions of solutions.

The basic reporting, experimental design, and validity of findings meet the standards of the journal.

The study is straightforward and solidly done. The only suggestions I have are of the text. The text could be tighter (cutting out a some unnecessary text), and explanations need to be more clear. i have included a pdf with edit suggestions. Please look at the attached file 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: MICROPLASTIC POLLUTION AT QILIANYU, THE LARGEST GREEN SEA TURTLE NESTING GROUNDS IN THE NORTHERN SOUTH CHINA SEA
Review round: 1
Reviewer: 2

Output:
Basic reporting: Abstract: Consider changing the terminology you use to refer to plastic types. What you call plastic blocks are more commonly referred to as fragments. There is also a difference between a microbead and a pellet (also called nurdle, or pre production pellet). I cant tell what the item in figure S1 box e is, because there is no size included. But refer to [Lusher, Amy L., et al. "Is it or isn't it: the importance of visual classification in microplastic characterization." Applied spectroscopy 74.9 (2020): 1139-1153.] for their classification of microplastics. It can be important to differentiate between microbead and pellets because they come from very different sources in the environment.

Line 160: Figure S1- what are the size of these plastic pieces? Please tell us how large each of the red boxes are, or include a ruler or some other measurement.

Line 193: Insert “due to” after the word likely. “This is likely due to the small population of the islands, implying that it is less severely affected by land-sourced plastic litter.

Line 222: This would be a good place to mention the density of the polymers youre seeing on the beach- PP, PE, PS, that are all less dense than seawater and thus float. Reference Brignac, Kayla C., et al. "Marine debris polymers on main Hawaiian Island beaches, sea surface, and seafloor." Environmental science & technology 53.21 (2019): 12218-12226.

Figure S3 and S4: Were larger items found on the beach included in this study? For example, Figure S4 shows a bottle pump that is fragmenting into smaller pieces and Figure S3 shows plastic bottles and a large piece of Styrofoam. Were these included or is it only microplastics?

Original data- thank you for providing the raw data, this is very important! However, in the second table, Column D, the sign is wrong. It currently says <1-2, which I take to mean pieces less than one up to 2. I believe it should be >1-2, meaning greater than 1 to 2. You also need units, is this mm? or cm?

Figure 1: Add abbreviation for each sampling site so the next figure is easier to understand. Example: North Island (NI)

Figure 3 - 5- I cannot tell the difference between the solid circle and the solid diamond. Can you please change one to help differentiate them? There also appears to be an * in some of the box plots, what are these?

Figures 3-5: clarify that the n = 18 is referring to the number of beaches.

Figure 7: Again, the <20-40 cm is misleading to me.
Experimental design: Line 101: What was the density of the sodium chloride solution?

Line 104: What was the density of the sodium iodide solution?

Line 119: What libraries specifically were used? Commercial or in-house library? How many polymers are in this library?

Line 128: Where are the results from the procedural blanks? Were any microplastics found in the blanks?
Validity of the findings: No Comment
Additional comments: Overall, this is a great paper providing baseline data of microplastic concentrations on a sea turtle nesting beach. Some basic reporting data is missing (units on graphs, density of separation solutions, etc), but otherwise is well written. It is important to provide additional information on how spectral analyses were conducted. Your spectra identification of polymers is only as good as the libraries you are searching through. Additional checking should be done manually to ensure correct identification.


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: MICROPLASTIC POLLUTION AT QILIANYU, THE LARGEST GREEN SEA TURTLE NESTING GROUNDS IN THE NORTHERN SOUTH CHINA SEA
Review round: 1
Reviewer: 3

Output:
Basic reporting: The authors explore the topic of microplastic interactions with sea turtle hatchings. Microplastics are an emergent pollutant that has widespread effects. This is an interesting topic worth examining. Overall the manuscript is straightforward and well written. However there are some portions which require clarification and referencing. The differentiation between results and discussion have to be more distinct.
Experimental design: no comment
Validity of the findings: Multiple references are missing throughout the manuscript, especially in the discussion
Additional comments: I have a few specific comments:

Line 20- what was the percentage of white particles? Kindly include percentage.

Line 39- references missing

Line 46- abrupt introduction to sea turtles, which species are you looking at? Would be better to give a short introduction to the sea turtle before describing their characteristics.

Line 53-54- reference missing

Line 56- reference missing

Line 57- the explanation using osmosis is unclear. Osmosis usually involves water. Kindly clarify.

Line 100- Can the authors provide measurement units in terms of microplastics/kg of sand? What was the weight of the sand?

Lines 146-149- should shift to discussion.

Lines 155-157- also shift to discussion

Section 3.4- The multiple values reported in the sentences should be tabulated for easier reading.

Lines 192-193- kindly substantiate the statement. Maybe the authors can consider adding a table with the comparison of microplastics with other neighbouring regions.

Lines 209,211- missing references

Line 220- it is difficult to confirm that the microplastics originated from those countries as no specific experiment was conducted


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: MEASURING THE DEVELOPMENTAL FUNCTION OF PEER REVIEW: A MULTI-DIMENSIONAL, CROSS-DISCIPLINARY ANALYSIS OF PEER REVIEW REPORTS FROM 740 ACADEMIC JOURNALS
Review round: 1
Reviewer: 1

Output:
Basic reporting: In general, it is a well-written paper that analyzes a large set of data. The research on the topic is growing and the authors should enhance the introduction including some other studies in order to present the existing literature in detail. The findings coming from studies on the attitudes of the reviewers, their focus concerning different parts of the manuscripts, the influence of anonymity/openness of the review on the review reports, the accelerated peer review during the pandemic and the influence on the reports, the external vs internal reviewers and their review reports, etc should be cited.
Experimental design: The study methods are well explained and sufficient details are provided.
Validity of the findings: I am not an expert in statistics. However, the conclusion is well stated deriving from the results.
Additional comments: Since the screening of the paper is the task of the editors/academic editors during the initial screen and before assigning reviewers, the major task of the Reviewers is to provide constructive feedback. Therefore the first sentence in the abstract is confusing.

A new term "developmental" in this area is introduced. 70-75 Authors mention that it refers to measuring the standards and practices of the review reports. It should be explicitly explained in the introduction what the term developmental contains.

Line 235-242
It seems like the impact factor of the journal does not affect the quality/development of the review reports. There are exceptions among SSE journals as well as journals in Physical and natural sciences. Not sure if this can support the conclusion that "the highest impact factor journals, in general, showed higher developmental standards of their review reports''. Table 11 for instance. Q3 and Q2 journals are positioned pretty high as well.  For instance line 295-303 confirms that additional time does not affect the thoroughness of the reports.

243-246
Is the quality/constructiveness of the review reports the reason or the only reason for the delay in submitting a review report? Does it look like a fast and bold conclusion?? Many other factors usually affect the speed of the reviewers.

258-263
HMS and LS seem like a significant proportion of the journals that do not conform with the conclusion? Can this question the conclusion?

264-271
It refers to which parts of the paper reviewers value the most. It seems the results are in line with some recent studies focused only on this topic.

If funding is received a statement would be necessary.


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: MEASURING THE DEVELOPMENTAL FUNCTION OF PEER REVIEW: A MULTI-DIMENSIONAL, CROSS-DISCIPLINARY ANALYSIS OF PEER REVIEW REPORTS FROM 740 ACADEMIC JOURNALS
Review round: 1
Reviewer: 2

Output:
Basic reporting: 1. There are several inconsistencies in language and writing.
2. The citations are not in the proper format.
Experimental design: 1. More details are required on how information is extracted from peer reviews based on the 14 dimensions. What kind of techniques did you use to automatically extract the review statements that fall under those 14 developmental functions?
2. Need to define developmental functions elaborately.
Validity of the findings: 1. Findings are interesting. It would be better that each finding is organized in sub-sections and then explained with data.
Additional comments: Nice large-scale study. Appreciate the efforts. The authors should consider making the data public for further research by the community. Also, the authors should cite some recent datasets on peer review analysis.


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: MEASURING THE DEVELOPMENTAL FUNCTION OF PEER REVIEW: A MULTI-DIMENSIONAL, CROSS-DISCIPLINARY ANALYSIS OF PEER REVIEW REPORTS FROM 740 ACADEMIC JOURNALS
Review round: 1
Reviewer: 3

Output:
Basic reporting: .
Experimental design: .
Validity of the findings: .
Additional comments: The paper is interesting, but lacks enough detail for the reader to really understand what is done. Therefore, several things need to be clarified.

General:
The claim in the beginning that peer review is the guarantee of trust in science seems overstated. Why would the opinion of two or three colleagues have such a weight. I guess this is just what many scientists believe, but I would guess that replication is the only guarantee. Of course the quality of peer review is important where peer review is decisive – as in acceptance of papers or selection of grants. However, at the same time, a lot of selection is not peer review at all. Grant selection panels are not peers, and in publication decisions, much is not peer review but desk decisions by editors or editorial staff.

Lacking details about the analysis:
•	Line 94: how was this cleaning of the texts done?
•	The test of the dimensions of Arcadia and the adaptation of the dimensions need more details of how it was done.
•	Line 136-150: the description is very brief, and would not allow anybody to replicate the study. May be the details could be in an annex.
•	Same holds for the description of the term selection (lines 151-157) and the dictionary building
•	The resulting development score, is it based on the numbers of terms, or on the shares of terms?
•	Section on ‘seniority’: how was the matching of the authors and scopus done on such a large scale.
•	Also the disambiguation of reviewers <-> scopus. How was that done?
•	Isn’t Cronbach alpha influenced by the number of items? If so, do the values of about 0.8 or higher say much, given the huge number of items?

Issues related to the findings
•	Standards derived are derived from the data -> why would the empirical average be the correct one, and not e.g. the median?
•	Figure 1 needs explanation on how to read it
•	The tables with the statistical analysis (T10, T12, T13, T14) should give more details. For example, it is unclear what type of analyses are represented by the tables.

Issues related to the discussion
•	Lines 291-294: what means ‘robust’ if it is not the same as ‘shared’? Could it also be shared and permissive?
•	The discussion sections contains bivariate relations. Given the number of cases (reviews), a multivariate analysis would have been useful, and may show that some relations disappear after introducing relevant covariates.
•	The discussion about the limitations is not very convincing, as many of the issues raised there seem not much related to the analysis in this paper. For example, why would one expect that a non-binary gender classification would influence the results at all? And, another example (line 368): “these editorial practices (of fast decisions) can influence - even if indirectly - the development of manuscripts in that drawing a straight line between quality screening and developmental function of peer review can be difficult Cowley (2015)”. One would like to read how this would influence the analysis, in order to assess the relevance of the analysis.

Some smaller issues
•	Please put the Titles of the tables ABOVE the tables, and the titles of the figures BELOW the figures (this is the standard way of doing it)
•	All areas of research: LS, PS, HMS, and SSE. -> Please add in the beginning of the paper what the abbreviations mean. This is now only done at page 8.
•	Line 249: The reviewers OBTAINED a score?
•	Line 264: Begin of the sentence is lacking
•	Lines 287-291: sentence difficult to read due to the chaotic placement of the references.
•	Line 337 and Line 346 both start with ‘Second’.


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: MEASURING THE DEVELOPMENTAL FUNCTION OF PEER REVIEW: A MULTI-DIMENSIONAL, CROSS-DISCIPLINARY ANALYSIS OF PEER REVIEW REPORTS FROM 740 ACADEMIC JOURNALS
Review round: 2
Reviewer: 1

Output:
Basic reporting: I agree with the current version.
However, in the discussion part is stated that women have shown more developmental tendencies in their reports BUT only in some areas. However, in the abstract is stated that this is "in general". The same for some other demographic factors.
Experimental design: Ok
Validity of the findings: ok
Additional comments: no


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: STORAGE MEDIA AND RNA EXTRACTION APPROACHES SUBSTANTIALLY INFLUENCE THE RECOVERY AND INTEGRITY OF LIVESTOCK FECAL MICROBIAL RNA
Review round: 1
Reviewer: 1

Output:
Basic reporting: The study by Koorakula et al. aims at assessing and comparing the impact of different storage and extraction methods for the isolation of microbial RNA from fecal samples. The study is clear and concise, with an adequate experimental design for the intended objective. However, the observations and conclusions reached are limited and do not seem to contribute to the existing knowledge on the field.
Although few studies have been dedicated to comparing RNA extraction methods exclusively, many of the statements in Koorakula et al. have already been reported in other studies (doi.org/10.3389/fmicb.2021.588025, doi.org/10.1186/1471-2180-12-158).
Experimental design: The extraction of sufficient and good-quality RNA is essential for metagenomic studies, and finding the best extraction protocol for each sample type is a question every research group has to explore.
The experimental design in this study is overall adequate for the intended objective. However, the conclusions reached have already been suggested in other articles.
Validity of the findings: The notion that RNA extraction kits and sample origin impact the quality and quantity of recovered RNA has already been addressed in metagenomic reports.
However, the effort done in this study would benefit from additional exploration of the RNA obtained with the different methods.
For example, performing a qPCR to determine the amount of host RNA remaining in the sample. This is a very important question when intending to analyze metagenomic data
Additional comments: The study is well designed and answers the proposed objective.
Consider exploring further the characteristics of the RNA obtained by the different methods to add value to the observations and conclusions. For example, exploring the amount of host RNA or if the perceived proportion of any taxa changed would greatly benefit the study.
Also, when mentioning the amount of RNA recovered, mention the total amount in ng, not only the concentration (ng/µL), and specify the quantification method you are referring to.


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: STORAGE MEDIA AND RNA EXTRACTION APPROACHES SUBSTANTIALLY INFLUENCE THE RECOVERY AND INTEGRITY OF LIVESTOCK FECAL MICROBIAL RNA
Review round: 1
Reviewer: 2

Output:
Basic reporting: The manuscript by Koorakula et al, aimed to determine the impact of sample storage and RNA extraction on the recovery of high-quality RNA.
Experimental design: The experimental design lacks samples, the authors only collect 1 pig sample and 8 chicken sample that were pooled by animal to perform further analysis. It is not clear why they call it fecal samples when they were collected from the distal part of the large intestine. The description of sample collection is not appropriate. Usually, samples used for RNA extraction should be collected and stored directly after slaughtering without moving them to the laboratory and proceeding with the storage.
The authors only share the minimum information about RNA concentration and integrity. It is missing information regarding 260/280 and 260/230 rations. In the supplementary table, we see values for RNA yield but no idea if they were measure with qubit or nanodrop.
Validity of the findings: This study lacks a critical experiment that would answer the question, is this RNA good enough to perform downstream analysis, is it sufficient to run a qPCR or RNA-seq? This should be answered here to prove their conclusions regarding the kit of choice.
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: STORAGE MEDIA AND RNA EXTRACTION APPROACHES SUBSTANTIALLY INFLUENCE THE RECOVERY AND INTEGRITY OF LIVESTOCK FECAL MICROBIAL RNA
Review round: 1
Reviewer: 3

Output:
Basic reporting: The authors have compared the efficiency of RNA recovery and integrity for four storage conditions (2 media X 2 temperatures-length) of primary samples of pig and chicken feces followed by RNA extraction using one of four commercial kits.

The writing is generally clear enough to ensure that an international audience can understand the text. However, I have noted a number of errors in structure, especially in the Conclusion section, comma usage and of choice of prepositions (e.g. in, for), some of which I have detailed bellow. I suggest the text should be revised by someone proficient in the English language for improvement.

The submission is «self-contained». The structure of the article conforms to the journal’s standard. Figures are relevant, of sufficient resolution and appropriately labeled. Raw data is provided.

Specific comments / corrections

Lines 31- 35. I suggest reordering the sentences to follow chronology:
« Fecal samples from pig and chicken were collected from conventional
slaughterhouses. Two different storage buffers were used at two different storage
temperatures. Extraction of total RNA was done using four different commercially
available kits and RNA integrity/quality and concentration were measured using a
Bioanalyzer 2100 system with RNA 6000 Nano kit (Agilent). »

Line 51. I suggest replacing by «… broken down through enzyme production by the animal host, and in …»

Line 54. I suggest replacing by «… in terms of taxonomy and phylogeny..»

Line 55-56. I suggest replacing by «… subunit gene, of which either the full length or its hypervariable regions are targeted for sequencing and used for taxonomic classification.»

Line 57-58. I find using the terms « Whole genome shotgun sequencing » may be confusing as « whole genome sequencing » generally refers to sequencing of a bacterial isolate genome, while « shotgun » as in « shotgun metagenomic sequencing » refers to sequencing all the DNA present in a primary sample. Therefore, I suggest using « shotgun metagenomic sequencing ».

Line 74. I suggest replacing by «… actually active in a given context..»

Line 89. I suggest using «next generation sequencing» instead of NGS as it was not previously defined and is only used once in the whole manuscript.

Line 93. …matrices…

Line 95 … are performed on fecal samples…

Line 96 … to as ZM) used in two storage conditions (overnight at 4C or 2 weeks at -80C), and in combination with…

Line 105. « Fecal sample from a 180 days old pig »

Line 109. I am not sure what is meant by « the respective gut digesta ». If there is only one pig sample, how was it pooled? If I interpret right the authors writing, I suggest the following modification instead of the sentence found in lines 107-112: «…transported to the laboratory. Samples from the digesta in the distal part of the large intestine, herein referred to as feces, were gathered. The pig fecal sample, as well as the pooled fecal chicken samples, were homogenized and then transferred...»

Line 116. Add references to support «the freezing period was considered of minor importance» statement.

Line 194. «followed by a» is duplicated.

Line 211-212. «…stored in RL for two weeks at -80C and extracted with the MN kit….»

Line 226. Why is « pig feces samples » plural if there was only one (n=1, line 105)?

Line 235. «…storage in ZM buffer… and extraction using the ZY kit…»

Line 238. Kit, singular

Line 243. «…storage in RL…»

Line 245-248. Poor English, please rephrase.

Line 250. Capital U in «Unlike»

Line 255. «… we compared…»; «storage media, temperature and length, as well as..»

Line 257. «…Our findings...»

Lines 257-260. Poor English, please rephrase.

Lines 263-264. I suggest specifying the scope of this statement. I do not think it is realistic that all the people doing microbiome studies worldwide use the same sample storage and extraction method, but I totally agree with the authors that results can only be compared when the samples were processed using exactly the same methods and conditions.

Lines 272-279. Did Reck et al. use the same methods as the authors? Compare their findings with those of this study.

Lines 283-284. Again, compared the findings of these previously published studies with your findings.

Lines 286-291. Extend the chicken focus to include pigs.

Lines 291-293. Rephrase: microbiome profiles were not investigated in this study.

Line 295. What about the pig gut microbiota?

Line 299. Capital W in «We»
Experimental design: This work fits within the Aims and Scope of the journal. The research question is well defined, relevant and meaningful. A knowledge gap is filled. However, the methods should be described with more clarity. Specifically, in lines 119-171, the only adjustments made to the manufacturer’s protocols were the use of 150 mg of samples and the volume of the elution buffet? Then, lines 134-171 are only summaries of the manufacturer’s protocols steps? The level of details provided for each methods varies. Were the bead beating conditions for each methods determined by the manufacturers? To ensure a good comprehension for the reader, I suggest revising this section to put clearly forward what were (all) the adjustments made for each method, and aim at providing equivalent levels of details for each method.
The details of the samples (lines 137 – 140) should be in the « RNA extraction » section as it applies to all the extraction methods. Moreover, the granularity provided should include the two animal types.

Line 174. If I understand right, there was a total of 96 individual extractions, not 48:
 2 animal types X 2 stabilization reagent X 2 storage conditions X 4 extraction methods X triplicates = 96 extractions

The authors work provides important stepping stones for studies involving metatranscriptomics of livestock feces, but I am finding the experimental set up a bit thin. First, I find the inclusion of only one pig sample  (line 105) very limited. It is hardly representative of what can be encountered in pig fecal samples that can vary substantially depending on the animal age, health status, diet and husbandry practices. Second, I suggest either rephrasing or additional experiments to support the conclusions/statements found in lines 264-266, « This is very important as the possible effect of these technological measures is high relative to the actual biological heterogeneity to be described in the microbiome studies. », line 299 «affects the results and therefore their possible biological interpretation» and line 303 «reliable microbial RNA extraction».  Although purity ratios are important indicators of sample quality, the best indicator of DNA or RNA quality is functionality in the downstream application of interest. RNA Integrity as observed by RIN is one thing, but an assay showing the actual quantification/sequencing of targets of interest would consolidate the work. I am suggesting assays of qRT-PCR targeting a number of genes (e.g. 3, one of which could be the 16S rRNA gene, others could be target genes known to be present and expressed at different levels in the studied microbiome). Results of all, or a selected subsets, of the RNA preparations could be compared to extrapolate on the storage & extraction methods robustness.
Validity of the findings: The underlying data have been provided. They appear robust and statistically sound.
Some conclusions are overstepping the limits of the supporting results, see the additional experiments I am proposing in the «Experimental design» section of my review.
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: STORAGE MEDIA AND RNA EXTRACTION APPROACHES SUBSTANTIALLY INFLUENCE THE RECOVERY AND INTEGRITY OF LIVESTOCK FECAL MICROBIAL RNA
Review round: 2
Reviewer: 1

Output:
Basic reporting: The authors have improved the manuscript by addressing the reviewer's concerns. However, the manuscript needs a broader discussion about their observations and rationale for this study, contrasting them with previous studies. These will define the study better for the readers.
Experimental design: The experimental design in this study is overall adequate for the intended objective. In addition, the authors included the suggested qPCR experiments providing a better notion about the RNA quality. Please, include these observations in the discussion section and mention the relevance of these results for someone who wants to perform high throughput sequencing techniques such as RNA-seq
Validity of the findings: I understand the author's rationale that most studies have been performed to research human and environmental samples, and these findings cannot be directly transferred to the animal microbiota. Thus, consider including a paragraph in the discussion section on whether or not these results can be transferred to livestock animals other than chicken and swine. Furthermore, expand the comparison between this study's observations and the results observed in humans. These can help clarify the relevance of the study.
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: STORAGE MEDIA AND RNA EXTRACTION APPROACHES SUBSTANTIALLY INFLUENCE THE RECOVERY AND INTEGRITY OF LIVESTOCK FECAL MICROBIAL RNA
Review round: 3
Reviewer: 1

Output:
Basic reporting: The authors have improved the manuscript by addressing the reviewer's concerns. They have enriched the discussion including key observations.
Experimental design: The experimental design is clear and adequate for the intended objective
Validity of the findings: The authors have enriched the discussion and conclusions supporting the results.
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: ONLINE E-LEARNING DURING THE COVID-19 LOCKDOWN IN TRINIDAD AND TOBAGO: PREVALENCE AND ASSOCIATED FACTORS WITH OCULAR COMPLAINTS AMONG SCHOOLCHILDREN AGED 11–19 YEARS
Review round: 1
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: I have reviewed the article and this article was aimed to determine the prevalence and factors associated with ocular complaints among school children aged 11-19 years during the COVID-19. Over 75% of students reported ocular complaints about online learning. Though the topic has been studied before, I still think this manuscript could add useful information to CVS in the Covid-19 pandemic.

I have a few questions or suggestions, and I suggest a minor review.

1. CVS has over 10 symptoms, so why did you choose only 5 ocular complaints?

2. Sample selection should be stated in detail. For example, how could you select seven schools from Trinidad's seven districts? Did students selected deliberately exaggerate the symptoms because they knew the aim of this study?

3. How could you distinguish the CVS symptom from symptoms from other ocular diseases? According to methods, students with other ocular diseases did not be excluded from the study.

4. The majority of participants were citizens of T&T (n=421, 96.8%), and it should be made clear the minority of them.

5. Another strength of this study was that the schoolchildren in this study were given adequate time to respond to the items voluntarily, and it is improbable that they completed the questions rapidly. The mean time students spent filling out questionnaires should be stated to prove this strength.


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: ONLINE E-LEARNING DURING THE COVID-19 LOCKDOWN IN TRINIDAD AND TOBAGO: PREVALENCE AND ASSOCIATED FACTORS WITH OCULAR COMPLAINTS AMONG SCHOOLCHILDREN AGED 11–19 YEARS
Review round: 1
Reviewer: 2

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: This is an interesting study aimed at evaluating the prevalence and associated factors with ocular complaints among schoolchildren aged 11-19 years with online e-learning during the COVID-19 lockdown in Trinidad and Tobago. Thank you very much for the opportunity of reviewing this article that greatly adds to the scientific body of knowledge. I congratulate the authors for the work performed. Hereunder, a few minor comments that could help the readers in the understanding of the article and its background are presented:

In the abstract:
I recommend the authors to include:
- Number of subjects that responded to the questionnaire
- “Mean age of children was (include the mean age ± standard deviation here)”.
- Add “self-reported”, in Results: “The prevalence of self-reported headache …”

Strengths and Limitations section:
- It seems that ambient illumination was not considered. Please, include it as a limitation.

References:
There are two duplicate references:
- Lines 570-576: Portello, J. K., Rosenfield, M., Bababekova, Y. Estrada, J. M., & Leon, A. (2012). Please, leave only one of both.
Lines 595-600: Usgaonkar, U., Shet Parkar, S. R., & Shetty, A. (2021). Please, leave only one of both.

Minor changes:
-	Lines 218-219, two lines that should be from the same paragraph are divided. Please, unify it.
-	Lines 316, 333, 382. Remove the initial “J” before the citation “Portello”.
-	In the title of Figure 2 it is written “Figure 3”.
-	The results presented in Table 4 are not clear. Please, present it with “more 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: ONLINE E-LEARNING DURING THE COVID-19 LOCKDOWN IN TRINIDAD AND TOBAGO: PREVALENCE AND ASSOCIATED FACTORS WITH OCULAR COMPLAINTS AMONG SCHOOLCHILDREN AGED 11–19 YEARS
Review round: 1
Reviewer: 3

Output:
Basic reporting: The manuscript entitled "Online e-learning during the COVID-19 Lockdown in Trinidad and Tobago: Prevalence and Factors Associated with Ocular complaints among schoolchildren aged 11-19 years" aims to analyze the Computer Vision Syndrome -related symptoms during online learning in Trinidad and Tobago.
In my opinion, this manuscript is very interesting and it contributes to the knowledge of CVS.
Experimental design: Some comments:
- Since the data were collected for 4 months, do the authors think that the results may have any bias between participants? I understand that the time that participants spent at home significantly increase the symptoms.
- In my opinion, the manuscript is too long and some parts are unnecessary. Together with some minor spelling mistakes that need to be correct, it could be shortened (especially “data analysis”, and the tables, only the variables statistically significant could be shown and delete the rest of information).
- It would be interesting to include the questionnaire used for the data compilation as an appendix, because it is not clear.
- I understand that the authors only asked whether the participants suffered from these 5 symptoms. According to the definition of CVS, there are more ocular and visual symptoms related to the increased use of electronic devices. Moreover, it is difficult to analyze these symptoms without any information of the severity of them. It would be interesting for further studies to take this into account.
Validity of the findings: The results support the conclusion.
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: ONLINE E-LEARNING DURING THE COVID-19 LOCKDOWN IN TRINIDAD AND TOBAGO: PREVALENCE AND ASSOCIATED FACTORS WITH OCULAR COMPLAINTS AMONG SCHOOLCHILDREN AGED 11–19 YEARS
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: I have reviewed the revised article and I think the authors answered questions and revised the manuscript seriously. Thus, I suggest an acceptance.

Though I suggest an acceptance, I still have an important suggestion. A minor review may be needed before acceptance.

The suggestion is as follows:

1. According to methods, students with ocular diseases other than nearsightedness, farsightedness, and astigmatism were excluded in this study, which is inappropriate from my view for these ocular diseases may be risk factors of ocular complaints. In addition, students with some ocular diseases, such as dry eye, allergic conjunctivitis, should be excluded from this study, because these diseases indeed have ocular symptoms and could be affected by seasons or other factors. This is a big limitation of this study, which should raise concerns of authors.


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: ONLINE E-LEARNING DURING THE COVID-19 LOCKDOWN IN TRINIDAD AND TOBAGO: PREVALENCE AND ASSOCIATED FACTORS WITH OCULAR COMPLAINTS AMONG SCHOOLCHILDREN AGED 11–19 YEARS
Review round: 2
Reviewer: 2

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: The authors have performed a good job with the modifications performed in the revised version of the manuscript.
It is an interesting article that, in a simple way, brings knowledge to the subject treated. Congratulations to the authors for transmitting science and highlighting the importance of ocular complaints from digital devices for online learning.


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: CELL DIVISION CYCLE ASSOCIATED 2 (CDCA2) UPREGULATION PROMOTES THE PROGRESSION OF HEPATOCELLULAR CARCINOMA IN A P53-DEPENDANT MANNER
Review round: 1
Reviewer: 1

Output:
Basic reporting: This study aims to determine the role of cell division cycle associated 2 (CDCA2) in hepatocellular carcinoma (HCC) and its underlying molecular mechanism. The background is sufficient. The English need some revision. The figures, tables and images are of high quality. It is self-contained with relevant results regarding the hypothesis.
Experimental design: The scientific method is rigorous, the objectives are clear, it is well explained and justified, the experimental procedures are modern and sound, the experimental design is appropriate, replicates were included, they selected appropriate controls, and the results are interesting. The figures and images are of high quality, and they do not seem to be manipulated.
Validity of the findings: This study revealed elevated expression of CDCA2 in HCC, possibly because of p53 dysregulation, which was associated with worse prognosis of patients. They confirmed the oncogenic role of CDCA2 in HCC in vitro and revealed some of the underlying molecular mechanisms. This study indicated the potential value of CDCA2 as a future target for the treatment of HCC. Conclusion are clear and discussed properly.
Additional comments: 1. The title must be corrected to: “Cell division cycle associated 2 (CDCA2) upregulation promotes the progression of hepatocellular carcinoma in a p53-dependent manner”
2. In Abstract. Instead of: “...had been demonstrated in several cancer types, however its involvement…” I suggest: “...have been demonstrated in several cancer types, however their involvement...”
3. In Abstract. Instead of: “…and using TCGA datasets.” I suggest: “…and using the Cancer Genome Atlas (TCGA) database.
4. In Introduction, line 72: “We report…”
5. In RNA extraction and real time PCR (qRT-PCR), line 103: “The mRNA expression levels of the target genes were compared by 2−ΔΔCt” I did not find this result in the Figures or Tables.
6. In line 235: I did not grasp the difference between Figure 1I with Figure 2G. Both seem related to measures of knockdown efficiency.
7. In Discussion, ¿What does OSCC stand for?
8. In Discussion, line 383: omit “were”
9. In Discussion, line 396: “CDCA2 might have a synergetic effect with mut-p53 in 397 inducing EMT and cell migration.” I do not see from what result(s) it is inferred a synergistic effect. Beside mut-p53 was reported for endocrine carcinomas. ¿Can it be extrapolated to hepatocellular carcinoma?


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: CELL DIVISION CYCLE ASSOCIATED 2 (CDCA2) UPREGULATION PROMOTES THE PROGRESSION OF HEPATOCELLULAR CARCINOMA IN A P53-DEPENDANT MANNER
Review round: 1
Reviewer: 2

Output:
Basic reporting: This paper presented a study about mut-p53-induced upregulation of CDCA2 expression promotes the progression of hepatocellular carcinoma. It's a topic of interest in the related areas, the bioinformatic-analysis and experiments are proper and comprehensive. But the paper requires some improvement before acceptance.

Line 234, the authors declare that shCDCA2-3 has the best knock-down efficiency according to Figure 1I. However, Figure 1I shows that CDCA2 protein level of Huh7-sh CDCA2-3 is the most similar to Huh7-shNC, which means shCDCA2-3 has the least knock-down efficiency.

There are some mistakes in this manuscript:
1.	Line 211 and title in Table 1, “CDCD2” should be corrected as “CDCA2”.
2.	Line 230, “L02 cell lines” should be corrected as “L02 cell line”.
3.	Line 273-277, the spelling of “Cdk” should be capitalized as “CDK”. Several nonstandard spelling issues distribute in the whole text.
4.	The legend of Figure 2(A) is obviously wrong.

The English writing should be improved.
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: CELL DIVISION CYCLE ASSOCIATED 2 (CDCA2) UPREGULATION PROMOTES THE PROGRESSION OF HEPATOCELLULAR CARCINOMA IN A P53-DEPENDANT MANNER
Review round: 1
Reviewer: 3

Output:
Basic reporting: In the title is using the word "mannar" it is probably a mistyping
check the word it is probably refering to "manner"
I suggest to check grammar in some lines that could be improved. i.e. 274,275 lines: "and found that the expression of CDCA2"  it could be better to use "and found that CDCA2 expression". Some parts in the text could be improved.
Experimental design: a) p21 primers sequence is not making correct aligment it is nonspecific, can you check the sequences. It is probably just a typping error.
It is missing one nucleotide in the reverse, Forward is 20 nucleotides and reverse 19, current sequence is not maching with p21 gene
b) Why did you choose to use 2 different test to compare ratios? which criterium did you use to choose?
Validity of the findings: no comment.
Additional comments: Results concerning figure 1.-
In line 234,235
It is stated that shCDCA2-3 have the best efficiency but western blot shows the opposite it is very necessary to clarify this
since it is used for subsequent studies.

Results concerning table 1
Important issue to check:
In line 213 it is stated that high expression is related to older age but table 1 percentajes do not match
it is showed 106 samples = 32.6 % (low)  and 83 samples = 67.4% (high)
in this case table 1 shows the opposite people <= 60 shows higher expression

Results concerning figure 2
Is it already know that E-cadherine is absent in SK-Hep1 cells? could you give a source of that information?
or why is it absent in your experiment?

Results concerning figure 4
why did you choose to show in C 20 uM for HepG2 instead of 50 uM? according to letter D 50 is the best concentration


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: ASSOCIATION BETWEEN FIBRINOGEN/ALBUMIN RATIO AND SEVERITY OF CORONARY ARTERY CALCIFICATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A RETROSPECTIVE STUDY
Review round: 1
Reviewer: 1

Output:
Basic reporting: The paper design should be revised according to the journal format.
The language should be redacted by a native speaker.
Experimental design: The patient selection criteria for tomographic scans should be clarified.
Validity of the findings: Findings are interesting and valuable. However, the methodological rules should be clarified.
Additional comments: Dear Authors,
I read your manuscript entitled “Association between fibrinogen/albumin ratio and severity of coronary artery calcification in patients with chronic kidney disease” meticulously. The overall idea is good and the methodology is well established. However, some points should be improved before publication as follows:
- How can you decide to make a multislice coronary computed tomography scan for a CKD patient? Is it routine for all CKD patients in your clinic? Cardiac tomography is a minimally invasive method that includes radiation and can give good results when necessary. However, it is not recommended for every patient for routine check-up purposes. There are certain standards recommended by guidelines such as AHA and ACC to decide beforehand. Please clarify your patient selection criteria.
- Did you detect any contrast-induced nephropathy in non-hemodialysis patients?
-Discussion section should be presented with a separated subheading and it should start with a descriptive sentence that indicates the novelty of your findings and a brief explanation of your main findings.
- The discussion should be improved with previous studies that focused on the relationship between coronary artery disease and FAR levels. For instance, “The relationship between fibrinogen to albumin ratio and severity of coronary artery disease in patients with STEMI. Am J Emerg Med. 2016 Jun;34(6):1037-42. doi: 10.1016/j.ajem.2016.03.003.”
- What are the limitations of the study? Please explain with a subheading.
- The manuscript should be revised according to journal rules described in instructions to authors


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: ASSOCIATION BETWEEN FIBRINOGEN/ALBUMIN RATIO AND SEVERITY OF CORONARY ARTERY CALCIFICATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A RETROSPECTIVE STUDY
Review round: 1
Reviewer: 2

Output:
Basic reporting: Dear Authors,
I read your manuscript with great interest. The topic is interesting. There are some major essential points that should be revised before publication:
- Do not start with a numeric to the sentence. If you want to give a number at the beginning of sentence, please use the word phrase. E.g. please phrase two hundred and eighteen rather than ‘218’.
- The language should be revised by a native speaker for immersive reading.
- The mechanism of action should be explained. The hypothesis must be based on a focus. As is known, low albumin has been associated with hyperinflammation and hypercoagulability. On the other hand, increased fibrinogen was associated with fibrinolytic and haemorheological factors. Studies conducted in this context have focused on the fact that the fibrinogen/albumin ratio may be a more effective marker in determining the clinical status in cardiovascular events*.
*Karahan O, Yavuz C, Kankilic N, Demirtas S, Tezcan O, Caliskan A, Mavitas B. Simple blood tests as predictive markers of disease severity and clinical condition in patients with venous insufficiency. Blood Coagul Fibrinolysis. 2016;27(6):684-90. doi: 10.1097/MBC.0000000000000478.
Concentrate on this point and explain your hypothesis.
- The parts of text should be designed with following subheadings:  Introduction, Material and Method, Results, Discussion, Conclusion, and Limitations
Experimental design: no experiment
Validity of the findings: Good and qualified
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: ASSOCIATION BETWEEN FIBRINOGEN/ALBUMIN RATIO AND SEVERITY OF CORONARY ARTERY CALCIFICATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A RETROSPECTIVE STUDY
Review round: 1
Reviewer: 3

Output:
Basic reporting: Thank you for the invitation to review the manuscript. This manuscript is of interest but lacks originality and novelty in many aspects.

Abstract: This section should describe the information on the study methods i.e., study design, population, etc. The conclusion section of the abstract is quite vague requiring further modification by considering the primary objectives of the study.

Introduction: The rationale of the study is not clearly illustrated in the manuscript. Authors should discuss the availability of any other study in China and other countries estimating the association between FAR and calcification in CKD patients. If such studies exist, both in China and internationally, authors should focus on the point that why this study is needed in the presence of available data. Moreover, the discussion section should be strengthened by the implications of the study findings in the current practice and research.

Methods: the methodology of the section is quite vague and simple. Authors should follow the following headings in the method section. These headings include; ethics, study site, patients with inclusion and exclusion criteria, operational definitions, diagnostic methods, data collection along with storage and anonymity of data, and statistical analysis with defined variables along specific interferential methods used in the analysis.

Results: Authors are using the word trial throughout the manuscript. I don't think that this retrospective design could be a trial analysis. I will suggest omitting this word. Authors should describe the name of the test under each table. If the author used one-way ANOVA to differentiate between three classes of FAR, then the post-hoc analysis is missing. I will suggest having Tukey`s analysis or non-parametric analysis for the more than 2 by 2 table. Authors should also put the univariate analysis for logistic regression. It is important to describe the reason that why some specific variables were selected for logistic regression (are they selected based on the chi-square analysis or clinical plausibility, or previously reported). Which univariate p-value was served to transfer the variables into multivariate analysis? ROC curve analysis for the logistic model will make the more robust risk prediction model and will help the readers to see the accuracy of the model.

Discussion: This section lacks the considerable essence of scientific writing. Authors should focus on the comparison of their findings with the previously published data rather than describing the physiological mechanism of the factors. Authors should discuss the clinical plausibility and possible mechanism of risk factors of CAC should relate them with other studies conducted elsewhere. The authors did not adjust the confounders in all analyses and I am afraid that their findings may not be generalized in other settings. The limitation section missing, as this study is accompanied by serious limitations.
The conclusion of the manuscript is not explicit and does not provide directions to clinicians and researchers.

Important: This manuscript requires English Editing from a Native English Speaker.
Experimental design: This study design is poor, considering the above-mentioned comments.
Validity of the findings: Validity of the findings is markedly affected by the small sample size and impact of confounders during the analysis.
Additional comments: Dear Editor, This manuscript requires English Editing from a Native English Speaker.


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: ASSOCIATION BETWEEN FIBRINOGEN/ALBUMIN RATIO AND SEVERITY OF CORONARY ARTERY CALCIFICATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A RETROSPECTIVE STUDY
Review round: 2
Reviewer: 1

Output:
Basic reporting: It is ok in current version
Experimental design: The authors made satisfactory changes which was suggested
Validity of the findings: Good and clear
Additional comments: The subheadings of discussion should be designed according to journal format. In its current version seems as a Review. Please remove FAR CVD and others which are not necessary


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: ASSOCIATION BETWEEN FIBRINOGEN/ALBUMIN RATIO AND SEVERITY OF CORONARY ARTERY CALCIFICATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A RETROSPECTIVE STUDY
Review round: 2
Reviewer: 2

Output:
Basic reporting: The language was revised successfully
Experimental design: Methodology was clarified
Validity of the findings: The presentation of findings is acceptable
Additional comments: In previous check I suggest to authors improve their paper with mechanism of action which clarify the possible action of FAR. Authors claimed that they improve the discussion part with discussion of a report "Simple blood tests as predictive markers of disease severity and clinical condition in patients with venous insufficiency. Blood Coagul Fibrinolysis. 2016 Sep;27(6):684-90." presented by Karahan et al. However, I can not see this part in revised manuscript (Also in reference part the mentioned article does not cited). I suggest again add a part discuss possible mechinism of action. For, instance according to my knowledge "Fibrinogen is a thrombin-coagulable glycoprotein occurring in the blood of vertebrates. This marker is getting higher amounts in thrombotic processes. By the way, albumin is an acute phase reactant and also it regulates the oncotic pressure. Lower levels may be related to increased thrombotic tendency. So, a higher FAR value can be associated with increased thromboembolic disorders". Please, create these kind of hyposthesis and discuss in the view of your findings.


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: ASSOCIATION BETWEEN FIBRINOGEN/ALBUMIN RATIO AND SEVERITY OF CORONARY ARTERY CALCIFICATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A RETROSPECTIVE STUDY
Review round: 2
Reviewer: 3

Output:
Basic reporting: The authors have addressed my suggestions. I have no more concerns.
Experimental design: The authors have addressed my suggestions. I have no more concerns.
Validity of the findings: The authors have addressed my suggestions. I have no more concerns.
Additional comments: The authors have addressed my suggestions. I have no more 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: DETERMINATION OF MUSCLE STRENGTH AND FUNCTION IN PLESIOSAUR LIMBS: FINITE ELEMENT STRUCTURAL ANALYSES OF CRYPTOCLIDUS EURYMERUS HUMERUS AND FEMUR
Review round: 1
Reviewer: 1

Output:
Basic reporting: See my overall review comments.
Experimental design: See my overall review comments.
Validity of the findings: See my overall review comments.
Additional comments: Review of plesiosaur paper by Krahl et al.

As noted in my email to the editors, I am afraid that there are very large sections in the paper on which I am unqualified to comment. I therefore restrict my review to a few general questions, mainly related to the biomechanics/FEA aspects of the paper.

Overall this appears to be an impressive piece of work, but unfortunately somewhat inaccessible to someone with my background, at least in the context of the time available to undertake a review.

I list them below, line by line.

LL123-125. I am surprised that you do not include Muscutt et al in the this list of references. The paper clearly discusses the different possible propulsion modes.

L139 - flapped would be a better word then beaten.

L160 - I think you could add a bit more here about the way that the correct motion of the hind flippers relative to the vortices shed by the fore-flippers  can actually enhance performance.

L199 Fluctuatingly is not the best word here, indeed I am not suer it is in the English dictionary.

LL200 et seq. The sheer density of references here obscure meaning and make it difficult for the reader. Do you really need so many?

L203 - I don’t understand the use of the word subordinately in this context. I have not reviewed all the references given, but my reading of Figure 3 in Biewener & Dial is that the highest strains are in compression, but the authors say that “Shear strains produced by torsion averaged 1.5 times the longitudinal components of strain…”. The values of the strains are only really meaningful if related to the ultimate strength of the material, and it is well established that the tensile strength of bone is not much more than half the value in compression. Torsional strength is also much lower than the compressive value. Thus in pigeons at least, the torsional strains are the critical ones in terms of closeness to material failure.
I therefore do not understand why the authors have focussed on compressive strains.

L210 I do not understand the phrase “By reducing the bending moment, biological lightweight structures may evolve.” More explanation of the mechanism is needed please.

L230-233 The references here are In german, so inaccessible to me. However, I do think the authors would have no trouble in finding papers in the wider aerodynamics/fluid dynamics literature on flapping foil propulsion that show clearly that efficient flapping propulsion requires the foil to move in both heave and pitch. This has been know for many years and is not at all novel.

L240 et seq. The approach of using a physical model is very gratifying to someone of my generation, but was it really the right approach in these days of computer simulation packages such as OpenSim, MDA models such as GaitSym? I think that a few words about this should be included. They have the great advantage that it is much easier to run sensitivity analyses at the tough of a mouse, rather than have to spend ages fiddling with bits of string. It is also well know that the thickness of cartilage has a big effect on joint mobility, so more discussion about what appears to have been some what arbitrary use of styrofoam would be beneficial.

L339 et seq. The text refers to the bone tissue being segmented out, but Figure 7 and the STL files provided only appear to describe the surface of the bone, not the internal structure. What data was used for the internal structure - wall thickness etc? In the absence of this information, it is hard to comment on the validity of the FEA analysis.

L355 In contrast to other statements that are supported by an overabundance of references, the value for E used in the FEA is simply stated with no justification or discussion. The value of E is fundamental to the results of and FEA analysis, so needs to be selected with care. A value of 12GPa could be considered low (see Currey’s book Bones for exampleTable 4.3 wherein many values are in excess of 20GPa.)

L384 - another word I do not recognise: angulated. Angled?

L763 et seq. I think that power and efficiency are being confused here. A very powerful downstroke may produce a lot of thrust, but if the flow regime is non-optimal (eg Strouhal number) than the efficiency may be low. This is unequivocally the case, for example, when birds are taking off.

L879 - why is a homogenous compressive stress distribution chosen as the defining variable. What about tensile or shear, both orientations of lesser ultimate strength in bone?

L891 I have not been able to follow all the detailed anatomical discussions in the paper, so cannot understand the very last statement. At the very least, perhaps the text could refer the reader to the relevant part of the mass of detail?

On the basis of my comments with regards L339, 355, 879 and 891, I have to admit to not being able to form a view on the validity of the findings. Clearly a huge amount of work has gone into the study, so it may be fine, but I think it needs to be explained better for the non-specialist reader.


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: DETERMINATION OF MUSCLE STRENGTH AND FUNCTION IN PLESIOSAUR LIMBS: FINITE ELEMENT STRUCTURAL ANALYSES OF CRYPTOCLIDUS EURYMERUS HUMERUS AND FEMUR
Review round: 1
Reviewer: 2

Output:
Basic reporting: The submitted manuscript describes the biomechanical study of the fore- and hindflippers of the plesiosaur Cryptoclidus in a mostly clear and professional way. Sufficient background and context is provided in the introduction and referred to in the discussion section as well. The overall structure is logical and most of the individual sections are sufficiently detailed.
 I have made some smaller edit and comments (mostly regarding language and clarity) directly in the attached PDF.
Experimental design: The research question is well-defined and clear. The experimental design is described in detail for the physical setup to calculate muscle orientation and attachments. However, the setup of the FEAs is very short and a lot of the relevant steps and underlying assumptions have been omitted.

 While the analogue model setup and the approach to obtain muscle lines and attachment angles is clearly described, no details are given on how muscle forces were obtained from the FEAs. "Forces of each humerus and femur muscle were approximated stochastically" and this seems to follow the approach outlined in Sverdlova and Witzel, 2010). In the referred study, in-vivo measurements were used to guide the initial muscle setup. Based on this initial analysis the loading regimes were refined to obtain a tension-free condition. If the same approach was used here, which initial force values or expected reaction forces were assumed and based on which assumptions (approximate muscle cross-section area, body size, etc.)? Further, was the iterative refinement done manually or automated? In both cases, what were the criteria used to guide the refinement? I would expect that there are countless permutations for ca. 20 muscles and some constraining criteria were likely applied.
It would be really helpful to outline the stochastical refinement approach in more detail and list the initial assumptions. I know that this could be gleaned from the referenced publications but having the information available will considerably increase the readability.

Secondly, it would be useful to have a figure showing the muscle attachments. I understand that this is provided in the first author's PhD thesis and is being prepared as a separate publication. However, it is impossible to get a good understanding of the insertions/origins from figures 1-5. I don't expect a full explanation and justification for every single muscle reconstructions as in the PhD thesis, but a figure with the mapped attachments (also in the thesis) is necessary here.

Thirdly, in the load case setup, explicit assumptions are made regarding the rotation of the humerus and femur along the long axis. The justification is provided in a referenced publication, but some brief explanation would be helpful here as well (in particular, considering that the referenced paper seems to be very niche and realistically inaccessible). Are other rotational settings possible or likely as well? What about rotation around the articulation on a horizontal plane?
Validity of the findings: The results are interesting and sound. In particular, the measured changes in muscle length are useful and a versatile approach to constrain hypothesised muscle reconstructions. Similar approaches have been used in other studies and mostly using digital methods, but the analogue approach offers a workable alternative solution.
 The presentation of the results is sometimes a bit sparse.
 - Figs. 2-5 are very busy and difficult to digest. A figure with some schematics illustrating the muscle vectors for the three tested scenarios would be very useful. I don't expect that all views are replicated from the photographs but the authors may consider a few simplified diagrams.

 Figure 6: I assume the numbers refer to specific muscles but a key explaining this is missing.

 Figure 7: Why are the FEA contour plots for the different scenarios superimposed? Space should not be a constraint with the journal and separate plots for upstroke and downstroke would be good to understand the differences in the stress regime for the different positions. The results for the muscle forces are based on the stress regime so having the separate plots would/should show the differences.
Additional comments: Overall, this is an interesting and useful study to provide new support for the often-discussed swimming style of plesiosaurs. The methodological approach is sound, but the readability is often hampered by the lack of detail. Underlying assumptions and explanations are often reduced to references to other (non-peer-reviewed) publications. Providing the respective information will make the manuscript fully self-contained and increase readability.
I have opted for major revisions to allow for sufficient time to implement the suggested changes.


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: DETERMINATION OF MUSCLE STRENGTH AND FUNCTION IN PLESIOSAUR LIMBS: FINITE ELEMENT STRUCTURAL ANALYSES OF CRYPTOCLIDUS EURYMERUS HUMERUS AND FEMUR
Review round: 1
Reviewer: 3

Output:
Basic reporting: The use of English is uneven and improvable in the Results and Discussion parts of the manuscript. However, some unusual phrases are delightfully direct and clear, and I urge the authors to keep them. Some punctuation is correct but can be changed to English conventions (quotes, decimal points).

The manuscript's references and structure (both technical and conceptual) are excellent.
Experimental design: The study integrates two exciting approaches: full-size physical models and FE structural analysis. The physical articulation of the flippers with thread-based muscle paths is a superbly tangible and direct stage of muscle reconstruction. FESA-based optimization towards a compressive stress regime is spectacularly innovative for refining inferences of both anatomy and function, which is the major research question of the paper. The authors accounted for cartilage at proximal articulations.
Validity of the findings: The findings are rigorous and exciting. I suggest additional citation of the successes of FESA for functional morphology, including substantiated predictions of anatomy in living animals. I'm a huge fan of the method, and more evidence will further promote understanding in the community.

The conclusions are up to PeerJ standards.
Additional comments: The biggest improvements to the manuscript will be clarification of the figures. The photographic images are welcome, but the lines of action and labeling are cluttered, hard to see, or minimal. Currently these figures show the basic physical results, but the muscles will be more obvious if the threads are traced over with color-coded lines, with colors representing different muscles. The muscle reconstructions are the most substantial results in the paper, and Cryptoclidus deserves more visually bold and clear visualizations.

I would prefer more FESA figures, but understand that the emphasis is on muscle reconstructions.

Substantial suggestions and edits are on the commented manuscript. An often-repeated request is to spell out lines of action (LOA) more often, the first time it's used in a paragraph and in figure captions. Make the text as easy as possible for a reader to understand at a glance anywhere in the manuscript, without looking around for definitions of acronyms.


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: QUERCETIN PREVENTS CHRONIC KIDNEY DISEASE ON MESANGIAL CELLS MODEL BY REGULATING INFLAMMATION, OXIDATIVE STRESS, AND TGF-Β1/SMADS PATHWAY
Review round: 1
Reviewer: 1

Output:
Basic reporting: The Introduction needs more detail. Specifically, I suggest that the authors need to improve the description regarding the role of Quercitin in CKD to provide more justification for your study, referring to a recent study “Quercetin Treatment Improves Renal Function and Protects the Kidney in a Rat Model of Adenine-Induced Chronic Kidney Disease” by Hu Yang et al. 2018. Moreover, it could be interesting that the authors deepened the theme of CDK; an interesting and recent paper regarding this could be “The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia–Reperfusion” by  Giovanna Casili et al., 2021.
The English language should be improved to ensure that an international audience can clearly understand the text. I suggest to contact a professional editing service to improve English language.
Experimental design: The authors performed a rigorous investigation. The methods were described with sufficient detail and information to replicate.
Validity of the findings: Conclusions are well stated, linked to original research question and limited to supporting results.
Additional comments: Conclusions are well stated, linked to original research question and limited to supporting 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: QUERCETIN PREVENTS CHRONIC KIDNEY DISEASE ON MESANGIAL CELLS MODEL BY REGULATING INFLAMMATION, OXIDATIVE STRESS, AND TGF-Β1/SMADS PATHWAY
Review round: 1
Reviewer: 2

Output:
Basic reporting: See the additional comments.
Experimental design: See the additional comments.
Validity of the findings: See the additional comments.
Additional comments: In this work, the authors demonstrated Quercetin prevents chronic kidney disease on mesangial cells model through regulating inflammation and TGF-β1/Smad pathway. Several suggestions are made as follows to improve the quality of the manuscript.
1.	Title is not suitable. Please change title to “Quercetin prevents chronic kidney disease on mesangial cells model through regulating inflammation and TGF-β1/Smad pathway”.
2.	Natural products or traditional Chinese medicine in Chinese herbal compound prescription and isolated compounds has been applied to treatment of CKD through regulating various molecular mechanisms including inflammation and oxidative stress, TGF-β1/Smad, Wnt/β-catenin pathway reported by many publications such as Trends Pharmacol Sci 2018,39(11):937-952; Front Pharmacol 2021,12:655372; Med Res Rev 2020,40(1):54-78. Please summarize pharmacological effects of natural products or traditional Chinese medicine in the introduction section to improve manuscript.
3.	Chemicals and Reagents should be provided in this section. Please include both the manufacturer's name and location (including city, state, and country) for specialized equipment and reagents throughout the manuscript.
4.
5.	TCM or natural products against CKD by TGF-β1/Smad pathway have been widely reported by several publications, such as Br J Pharmacol 2018,175(13):2689-2708; J Agric Food Chem 2018,66(8):1828-1842; Phytomedicine 2021,93:153774; Phytomedicine 2018,50:50-60; Free Radic Biol Med 2019,134:484-497. Please compare them with quercetin discuss them in the discussion section.
6.	TCM or natural products against fibrosis by regulating inflammation and oxidative stress have been widely reported by several publications, such as; Front Med 2021,8:747922; Frontiers Pharmacol 2021,12:800522; Front Pharmacol 2021,12:774414; Phytomedicine 2020,79:153352; Front Pharmacol 2021,12:630210. Several the latest reviews have summarized the application of natural products in renal injury. Please compare them with quercetin discuss them in the discussion section.
7.	Scale bar should be provided in Figure 5.
8.	The text must be extensively revised by a native English speaker.


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: QUERCETIN PREVENTS CHRONIC KIDNEY DISEASE ON MESANGIAL CELLS MODEL BY REGULATING INFLAMMATION, OXIDATIVE STRESS, AND TGF-Β1/SMADS PATHWAY
Review round: 2
Reviewer: 1

Output:
Basic reporting: Basic reporting is good.
Experimental design: Experimental design is good.
Validity of the findings: Experimental design is good.
Additional comments: The authors have improved the manuscript, so I suggest the manuscript should be accepted for publication.


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

Input:
Title: WITHASOMNIFEROL C, A NEW POTENTIAL SARS-COV-2 MAIN PROTEASE INHIBITOR FROM THE WITHANIA SOMNIFERA PLANT PROPOSED BY IN SILICO APPROACHES
Review round: 1
Reviewer: 1

Output:
Basic reporting: 1- pg 5, line 25. In the word "com-pounds" remove the hyphen.
2- pg 6, line 39. Please, remove the hyphen from the word "pa-tients".
3- pg 7, line 82. The word "in silico" must to be in italics.
4- pg 7, line 105. The word "Solanaceae" must to be in italics.
5- pg 7, line 115. Why did the authors cited the "NSP15"? Please, check if it is correct.
6- pg 9, line 167. Please, remove the hyphen from the word "hydro-gens".
7- pg 10, lines 202 and 208. In the word "mth", need the "th" to be overwritten?
8- pg 12, line 281. In the word "150th", need the "th" to be overwritten? Please, check it in all text.
9- pg 12, line 282. It is missing a space between the words "MM-PBSAbinding".
10- pg 12, line 302. Please, remove the hyphen from the word "phytocom-pounds". And check it in all text to find other words with typos.
Experimental design: 1- pg 8, lines 154-155. Please, indicate the force field used to optimize the molecules.
2- pg 12, lines 313-314. Please, add a comment about the docking results from the cited molecules. Is the data founded by the authors similar to the literature?
3- pg 27. Figure 2. Please, improve the quality of the figure 2. It is not possible to read the amino acids residues names and the interactions legend.
4- pg13, lines 332-334. Please, explain better why molecules with a poor BBB penetration are good drug candidates? Taking into account the neuroinvasive ability of SARS-CoV-2 (doi 10.1084/jem.20202135), please, comment the data.
Validity of the findings: no comment
Additional comments: no comment