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: ECOMORPHOSPACE OCCUPATION OF LARGE HERBIVOROUS DINOSAURS FROM LATE JURASSIC THROUGH TO LATE CRETACEOUS TIME IN NORTH AMERICA
Review round: 1
Reviewer: 3

Output:
Basic reporting: OK
Experimental design: OK
Validity of the findings: OK
Additional comments: Review, “Ecomorphospace occupation of large herbivorous dinosaurs from Late Jurassic through to Late Cretaceous time in North America” by Taia Wyenberg-Henzler

“competitive replacement of sauropods by hadrosauroids”

I’m happy to recommend this paper for publication but have a few suggestions for the author, made on a take-it-or-leave-it basis. If you think they’re good ideas, feel free, if not, do as you like.
My first instinct in reading this paper is that “oh of course it can’t be competitive displacement.” The diplodocoids and stegosaurs are diverse in the late Jurassic and completely disappear in the earliest Cretaceous, which strongly implies a major extinction near the J-K boundary and opportunistic replacement by other clades. I may be biased by studying mass extinction, but in my mind the record here reminds me of Paleocene mammals and dinosaurs- we don’t even need to discuss whether there’s competitive displacement, because there’s no evidence these taxa ever met. I guess my take is that displacement/opportunistic replacement is best tested by looking at the temporal distribution of the taxa, rather than morphology- no temporal overlap, no competition.
Anyway, maybe I’m wrong, but in that light, I think it might be better to focus the study slightly differently? Assuming there’s opportunistic replacement rather than competitive displacement, how do megaherbivores change over time: how do they compare in terms of morphospace overlap, but also overall morphospace occupation? Are these communities functioning similarly or differently from the Jurassic to the Cretaceous?
My sense of the data is that
(1)	there’s a distinct shift, which is likely due to both (i) different ways of solving the same or similar problems (e.g. sauropod gastric mills versus hadrosaur dental batteries) but also (ii) the groups solving different problems (lots of huge high feeders versus lots of smaller low feeders);
(2)	Not only is there a shift in what the dinosaurs are doing, the Cretaceous ones just do a wider range of stuff.
Anyway, in my mind it might make more sense to focus more on these angles.
With respect to the analyses. I’m not a primarily a specialist in morphometrics, which limits my ability to comment in great detail on the methods; others might be able to comment more usefully. Overall it looks fine, but a couple of thoughts.
Morphometrics is tricky in part because not all variation is necessarily functionally significant. For example, the casque of an oviraptorid or a Parasaurolophus will increase the skull disparity of their clades but these things are probably signaling about sexual selection, rather than feeding.
So one approach is to focus on a couple variables of known functional significance. Friedman’s rather elegant paper on fish extinction in PNAS does this- rather than focusing on lots of different variables he takes two- overall size (using mandible height*width as a proxy for size) and mechanical advantage (ratio of mandible length to the distance between the cotyle and the coronoid process). You’ve got that data so it might be fairly easy to use that approach?
My point is not to say “you’re doing it wrong” but it can be informative to measure things in different ways. If different approaches to measuring something give you broadly similar results, you’re probably onto something- rather than quibbling about the best way to analyze data (which statisticians can and will do forever) your results can be considered more robust if measuring things in different ways yields broadly congruent results. For example, if you measured the birds of the Amazon either in terms of number of species, number of families, skull disparity, size disparity, dietary preferences, or even range of colors, they’re going to be far more diverse than those of Alberta. So we can feel very confident there’s really high bird diversity there, it’s not an artifact resulting from the choice of what we measure.
Another easy approach to examine some of these problems might just be to compare overall size of these animals? The Benson et al. data would give you either mass and/or femur length and you could just plot the mass distributions of these creatures? Body mass is an interesting thing to study because it is correlated with so many differerent variables- locomotion, lifespan, reproductive strategy. Big animals are different from small animals in lots of ways, so when you see a wide range of sizes represented (or not) that tells you something about overall diversity. Similarly, overlap or lack thereof may tell you something. This would be quick-and-easy but I think could nicely complement the skull data and make the paper stronger.
NL


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: ECOMORPHOSPACE OCCUPATION OF LARGE HERBIVOROUS DINOSAURS FROM LATE JURASSIC THROUGH TO LATE CRETACEOUS TIME IN NORTH AMERICA
Review round: 2
Reviewer: 1

Output:
Basic reporting: The author has sufficiently addressed my comments on the first draft.
Experimental design: The author has sufficiently addressed my comments on the first draft.
Validity of the findings: The author has sufficiently addressed my comments on the first draft.
Additional comments: The author has sufficiently addressed my comments on the first draft.


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: ECOMORPHOSPACE OCCUPATION OF LARGE HERBIVOROUS DINOSAURS FROM LATE JURASSIC THROUGH TO LATE CRETACEOUS TIME IN NORTH AMERICA
Review round: 2
Reviewer: 2

Output:
Basic reporting: The revised manuscript improves upon what I had already regarded as a quite good study. The language is clear and professional. The graphics and tables include all the information necessary to evaluate the statistical analyses conducted. And while the paper represents just a part of the author's ongoing research in dinosaur paleoecology, it is self-contained with a specific set of hypotheses to test, and a presentation and interpretation of said tests (and their limitations).
Experimental design: The author is explicit in their choice of measurements to study, and methods to use (or in some cases, not to use: for instance, they make clear the reasons for their decision not to use pPCA-style analyses.)

The hypotheses being examined are clearly stated, and the conditions under which they would be supported or rejected specified.
Validity of the findings: The conclusions stem reasonably from the statistics and plots. Equally important, the author explicitly states the limitations of the data and analyses, and areas in which future studies might clarify issues which are still ambiguous.
Additional comments: It is my opinion that this research will represent a significant foundation upon which future studies of dinosaurian paleoecological studies might be built.


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: A MODEL OF MULTIPLE TUMOR MARKER FOR LYMPH NODE METASTASIS ASSESSMENT IN COLORECTAL CANCER: A RETROSPECTIVE STUDY
Review round: 1
Reviewer: 1

Output:
Basic reporting: Line 68 - 69: a very brief description of how those previously developed prediction nomograms perform, what they lack and how the authors propose to fill the gap would be helpful here.

Line197 -199: It would help readers if all the ROC plots could be in the same place. For example, moving Sig S4 plots to combine with Fig3.

Line 206: for the nomograms, and all the results in general, why are some figures chosen to be put in the main figure whereas others were in the supplementary? It would be much helpful if the authors could explain the logic and rationale and comparisons between models.
Experimental design: Line 206: despite nomogram being commonly used to visualize models, I recommend authors give basic guidance on how to read a nomogram. What does the length of each variable indicate, how to calculate total points. These could be explained in the legends, methods, or result section.

Line 207: again how do the authors interpret results from the calibration belt? It would be very helpful for authors to very briefly guide readers, who may not be experts in the immediate field to interpret the plots. It would be good to not assume readers understand all the statistical terminology and plots.

Line 235: for discussion, can the authors explain why LASSO regression was chosen for feature selection and model building in the first place? Why is Lasso the most suitable tool for identifying multiple markers?
Validity of the findings: Line 228, I would like to see a brief comparison of this new model the author developed with previous models referenced in the introduction.

Line248: When the authors made the claim that their model showed better performance than the clinical features model in the previous study, they did not show results from the previous study. Thus this conclusion is unjustified as-is.

Line 257-258: Please explain why the regression nomogram is more convenient and accessible by comparison.
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: A MODEL OF MULTIPLE TUMOR MARKER FOR LYMPH NODE METASTASIS ASSESSMENT IN COLORECTAL CANCER: A RETROSPECTIVE STUDY
Review round: 1
Reviewer: 2

Output:
Basic reporting: Authors proposed a new nomogram for lymph node metastasis assessment in colorectal cancer. They used LASSO algorithm to select patterns, and then combining them in a logistic regression model. The methodology seems to be adequate but, to further process the manuscript, there are issues in material and methods that must be clarify.
Experimental design: I have some concerns:
- Authors used an external validation cohort to asses the predictive abliity of their model, this is the most appropriate process to validate a model, but then it is not understood why they have divided the original database in percentage 7:3, a 10-fold cross-validation should be the best way to internally validated their prediction model. Choosing cutoff points using the 70% of database, and training the multivariate model with the rest 30% would have been understandable but it is not the procedure that the authors have followed
- Authors declare that "Logistic regression analysis was used to assess the effect of each tumor marker on CRC metastasis in the primary cohort, and the cutoff values of each tumor marker were obtained." This point must be clarify, it is not clear if they used the youden index to define a dichotomic variable for each marker, and this categorical variables (as appears in Table 1) are used in the multivariate model, or you are using the cutoff as a continuous variable in the prediction. In a case you used a dichotomic variable, as it seems in the nomogram, you must define these new variables as categorical CAmarker or similar, to an easy interpretation of the results. In any case, to dichotimize markers provides you a more adjusted predictions to the development cohort, but rest a general applicability of the model in different populations.
- In the results authors provide information about AUC, sensitivity and specificity. I suppose that sens and spec are estimated on the max Youden index. It is important to specify this in material and methods, and also to provide the cutoff point. Authors must verified that the Youden cutoff point of the models are in the range of values where the net benefit is superior in the decision curve.
Validity of the findings: The conclusions are derived from a complete validation process based on discrimination, calibration and clinical utlity, thus, avoiding the issues that authors must clarify about the experimental design, their conclusions are valid.
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: A MODEL OF MULTIPLE TUMOR MARKER FOR LYMPH NODE METASTASIS ASSESSMENT IN COLORECTAL CANCER: A RETROSPECTIVE STUDY
Review round: 2
Reviewer: 1

Output:
Basic reporting: All my concerns have been amended by the authors.
Experimental design: All my concerns have been amended by the authors.
Validity of the findings: All my concerns have been amended by the authors.
Additional comments: No comment


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

Input:
Title: THE EFFECT OF THE COVID-19 PANDEMIC ON HEALTH CARE WORKERS’ ANXIETY LEVELS: A META-ANALYSIS
Review round: 1
Reviewer: 1

Output:
Basic reporting: The following major issues were identified in this manuscript
- Method of selection is not well documented
Experimental design: - Statistical method is without necessary details to allow replicability of the work, you need to explain the statistical method in further details. You need to use other statistical tests to support the study findings or to disprove them.
Validity of the findings: - Heterogeneity might be a factor in the result and should be acknowledged
Additional comments: - Introduction and discussion are not well constructed and need to cite recent literature.


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

Input:
Title: THE EFFECT OF THE COVID-19 PANDEMIC ON HEALTH CARE WORKERS’ ANXIETY LEVELS: A META-ANALYSIS
Review round: 1
Reviewer: 2

Output:
Basic reporting: #1.1 Generally, the authors should follow and report in line with an updated PRISMA 2020 version.
-	Page MJ, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29;372:n71.

#1.2 Please provide a Table that summarizes the characteristics of the included studies such as country or geographical region based on WHO/World Bank income groups, study design, data collection, measurement tools, diagnostic cut-off that used for anxiety assessment, number of participants, mean age, the proportion of female, marriage status, working position (frontline vs. second-line), type of hospital (primary, secondary, tertiary), professional role (physicians, nurse, others).

#1.3 To shed light on the impact findings with regard to the prevalence of mental health problems during the COVID-19 pandemic, under the “Discussion” section, I advocate the authors should be discussed in terms of the hospital preparedness and resilience capability (e.g., hospital safety, hospital emerging disease leadership and cooperation, hospital emerging disease plan, emergency stockpiles and logistics management, and emergency staff and capability) to confront during the situation of disasters or public health infectious events.

Moreover, comprehensive discussion and compare the findings to other populations that facing the COVID-19 pandemic would be interest for readers as well as the scientific community as follows:
-	What We Have Learned from Two Decades of Epidemics and Pandemics: A Systematic Review and Meta-Analysis of the Psychological Burden of Frontline Healthcare Workers. Psychother Psychosom. 2021;90(3):178-190.
-	Global prevalence of mental health issues among the general population during the coronavirus disease-2019 pandemic: a systematic review and meta-analysis. Sci Rep. 2021 May 13;11(1):10173.
-	Prevalence of mental health problems among children and adolescents during the COVID-19 pandemic: A systematic review and meta-analysis. J Affect Disord. 2021 Oct 1;293:78-89.

#1.4 For statistical reporting, the I2 index should be expressed along with the 95% CI through the main text and figures.

#1.5 Table 1 Subgroup analyses, should be reported along with the P for interaction and the number of participants included.
Experimental design: #2.1 The search strategies should be updated to identify all available evidence in the recent year, they need to be included in this analysis. Also, key electronic databases including Embase, PsycInfo, and gray literature should be included.
Validity of the findings: #3.1. Under “Statistical Analysis”, the statistical approach for pooled effect estimates was not clear. Specifically, the random-effects model was performed based on a normal distribution or account for the effects of studies with extreme (small or large prevalence estimates), in which the normal approximation procedures often break down.

Theoretically, based on the broad definition of the methodological approach across the included studies as well as the disparities between countries that may affect the prevalence of anxiety, I recommended the authors perform a meta-analysis with appropriate methods which dealing with proportions close to or at the margins before pooling the effect estimates. Using the binomial distribution to model the within-study variability or by allowing Freeman-Turkey double arcsine transformation to stabilize the variances has been suggested.

#3.2. To shed light on the impact findings, under the “Statistical Analysis” section, both methodological and statistical heterogeneity should be comprehensively explored. I advocate the authors to performed subgroup analysis and meta-regression based on country or WHO regions with respect to the key characteristics of the included studies or major factors that may affect the preparedness to COVID-19 infection or associated with the classification of being anxiety (e.g., the proportion of female, working position [frontline vs. second-line], type of hospital [primary, secondary, or tertiary], professional role [physicians, nurse, or others], study design [cross-sectional, cohort, longitudinal survey], data collection [online survey, telephone, or paper-based survey], measurement tool [GAD-7, BDI-Anxiety, HADS, or DASS-21, etc.] and diagnostic cut-off).

Moreover, subgroup analysis and meta-regression according to the disparities between countries in terms of the poverty impacts of COVID‑19, preparedness of countries to respond, and economic vulnerabilities that impact the prevalence of anxiety should also be performed (e.g., the COVID-19-government response stringency index during the survey, the preparedness of countries in terms of hospital beds per 10,000 people, World Bank Countries by income groups, Human development groups, etc.).
Additional comments: No additional comments


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

Input:
Title: THE EFFECT OF THE COVID-19 PANDEMIC ON HEALTH CARE WORKERS’ ANXIETY LEVELS: A META-ANALYSIS
Review round: 2
Reviewer: 1

Output:
Basic reporting: The English language used is clear. The structure of the article complies with the PRISMA guidelines. Raw data has been provided.

Comment 1 - The introductory section could be implemented by explaining more clearly which topic was covered in the literature considered for the subgroup "unrelated COVID-19". It would be appropriate to indicate why the authors chose this topic for comparison and not literature from previous outbreaks, which might represent stress situations similar to that due to COVID but on a smaller scale. perhaps the authors' intention was to compare anxiety levels with different situations, to highlight the actual pandemic from COVID-19?

Comment 2 - The figures are relevant and of high quality, but I suggest improving the labels and changing the PRISMA checklist to the updated version (2020) found at http://prisma-statement.org/PRISMAStatement/Checklist.
Experimental design: The research question was relevant and meaningful. The research was well executed, in line with PRISMA guidelines.

Comment 3 - The methods were described with sufficient detail and information to replicate the study. However, I urge the authors to clarify what is stated in the commentary on the introductory section, as only by reading the exclusion criteria (specifically 4 - publications about other outbreaks) does the focus of the unrelated COVID-19 articles become clear.
Validity of the findings: The results are clearly reported, and the discussion appears comprehensive.

Comment 4 - I would suggest that the authors also comment briefly in this section on the choice not to compare the results of the COVID-19 studies with a subset of studies on other epidemics, and to specify what the studies in the unrelated COVID-19 subgroup were about.
Additional comments: Thank you for the opportunity to review this work.  The study is interesting and deals with an important issue. The paper is generally clear and complete. I understand the long work done, in the study and in the paper, however some minor revisions and explanations of the authors are necessary (please see Comment 1, 2, 3, 4).


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

Input:
Title: THE EFFECT OF THE COVID-19 PANDEMIC ON HEALTH CARE WORKERS’ ANXIETY LEVELS: A META-ANALYSIS
Review round: 2
Reviewer: 2

Output:
Basic reporting: This is an important study in an under-researched area of the world. The literature addressed is described accurately so far as I can see. The method seems to have been followed faithfully and the authors were well-positioned to conduct the analysis. The material is interesting, and the topic is relevant. However, some areas need clarifications:
- Describe more deeply the rationale for the review in the context of what is already known. What is the study's biggest contribution? The contribution should be clearly stated in the background.
Experimental design: - Specify the date when each source was last searched or consulted.
- State the process that will be used for selecting studies through each phase of the review (that is, screening, eligibility and inclusion in meta-analysis).
- How do you deal with missing outcome data? The researchers will contact and request first authors through electronic mails to provide missing outcome data, perform sensitivity analysis to assess the robustness of meta-analytic results, and discuss the potential impact of missing data on the review findings. Do you use any one of the several statistical approaches for dealing with missing outcome data?
- Please provide more information about how you perform sensitivity analysis to reflect the extent to which the meta-analytical results and conclusions are altered as a result of changes in the analysis approach.
- After performing meta-analysis, the researchers should be computing prediction interval to reflect the variation of outcomes of anxiety in different settings, including the direction of evidence in future studies.
- Please report the software package(s) used.
Validity of the findings: - The discussion section should be reorganized because they are poor. I believe there should be better integration of the results with the existing literature. Discuss the generalisability (external validity) of the study results. Also, discuss both the direction and magnitude of any potential bias.
- The recommendations for practice/research/education/management should have been approached in greater depth.
Additional comments: The manuscript will serve a broad audience of students, researchers, and practitioners, however, the manuscript needs to be carefully and attentively proofread because some sentences are awkwardly constructed, punctuation is deficient, and therefore reading is occasionally difficult to follow. The English of this manuscript should be reviewed by a fluent 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: THE EFFECT OF THE COVID-19 PANDEMIC ON HEALTH CARE WORKERS’ ANXIETY LEVELS: A META-ANALYSIS
Review round: 3
Reviewer: 1

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: Thank you for the opportunity to review this work again.  The paper is generally clear and complete the authors have improved the quality of the manuscript, taking into account my 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: THE EFFECT OF THE COVID-19 PANDEMIC ON HEALTH CARE WORKERS’ ANXIETY LEVELS: A META-ANALYSIS
Review round: 3
Reviewer: 2

Output:
Basic reporting: The material is interesting and the topic is relevant.
Experimental design: Methods well described.
Validity of the findings: The conclusions are well stated and linked with the research question.
Additional comments: I believe that the review carried out has greatly improved the quality of the study. Also, I do think that the author(s) addresses the broad questions, appropriately which were asked. Congratulations!


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

Input:
Title: DIEL GENE EXPRESSION IMPROVES SOFTWARE PREDICTION OF CYANOBACTERIAL OPERONS
Review round: 1
Reviewer: 1

Output:
Basic reporting: 1. On line 16, please remove "Add your abstract here."
2. The font size and face is different before line 34 and after line 35. Please check that you have the same formatting throughout the paper.
3. Throughout the paper, for e.g. lines 73, 97, 122, Supplemental Table 1 title and legend, I found that you have mistakenly specified "48 classifiers" instead of "44 classifiers". Please check the number of classifiers.
4. Figure 1 seems to be duplicated.
5. In peerj-65502-HellerTable1.docx, the author should correct the number of classifiers used i.e. 44 instead of 48. It also has a typo "Supplemental Table ZZZ2" instead of "Supplemental Table 2".
6. There is no need of peerj-65502-HellerSupplTable2.docx as it only contains "Supplemental Table 2" which is already presented in peerj-65502-HellerTable1.docx.

Overall, I found the paper easy to understand and found no grammatical or spelling errors.
Experimental design: The classifier design was well explained and applied. The proposed algorithm i.e. Logistic Model Tree was specified clearly, and the positive as well as the negative control sets were appropriately chosen. The number of features and timepoints selected to test the classifier seem to be significantly reasonable. Proper normalizations were applied to the gene expression data before classification. Impressively, 44 additional classifiers were tested and the proposed classifier seems to outperform each of them in both negative and positive test datasets.

Additionally, the author was mindful in warning that the classifier may required re-evaluation with other microorganisms and that organisms with little diel variation may perform poorly.
Validity of the findings: The result tables and figures seem to be sound but I could not open peerj-65502-HellerSupplementalCodeAndInstructions.jar on my mac. Does the author have instructions on how to view the contents of the jar file? Alternatively, does the author have the code published elsewhere, for instance Github?
Additional comments: Overall, I found the concept presented by the author simple yet effective in predicting correct operons and assigning functions to unknown genes. I foresee this model being useful to many working with Cyanobacteria and related microorganisms.


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: DIEL GENE EXPRESSION IMPROVES SOFTWARE PREDICTION OF CYANOBACTERIAL OPERONS
Review round: 1
Reviewer: 2

Output:
Basic reporting: Minor grammar comment - in general numbers are written out if they are less than 10 or if they begin a sentence.  I do not know if PeerJ adheres to these conventions, but this is what I have seen in most texts.

Ref 31 is posted as being from Zenodo instead of the original journal.  It’s okay to put the doi from Zenodo but the journal should be “American Journal of Advanced Research”.

Throughout the text some operons are described as having “both DNA strands present.” This language may be confusing for some readers.  I suggest using something like “genes within the same predicted operon are present on opposite strands, so these genes are likely not in the same operon.”

Just a general comment – it looks like Table 1 accidentally got submitted as supplementary material since it was not included as one of the primary files.
Experimental design: Please explain why the distance between genes was not taken into account for a pair of genes to be counted as an operon.  There can be genes on the same strand without any intervening genes but they are too far apart to be considered part of the same operon.

Please explain for the positive training set selection why only one gene in the operon needed to express diel variation for the operon to be counted as a true positive. If genes in an operon are expected to have similar expression signatures, shouldn’t this be a requirement for the true positives?

The statistic of P(false +) does not add much to the analysis.  I suggest removing this statistic or using a traditional statistic.  The reasoning for the cutoff of a 0.51 score is enough.
Validity of the findings: The author checked the predictions by making sure that the genes were on the same strand, same contig, and no intervening genes. However, the distance between the genes also still needs to be checked - even if a pair of genes satisfies these three requirements they still might be too far apart to be on the same operon.  One way to find the typical distance between genes in an operon for a specific organism is to take all of the true positives and make a distribution of the distances between genes in the operons. Then the predictions can be evaluated with this distribution.
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: DIEL GENE EXPRESSION IMPROVES SOFTWARE PREDICTION OF CYANOBACTERIAL OPERONS
Review round: 2
Reviewer: 1

Output:
Basic reporting: All proposed changes have been addressed. Thank you
Experimental design: N/A
Validity of the findings: N/A
Additional comments: N/A


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: DIEL GENE EXPRESSION IMPROVES SOFTWARE PREDICTION OF CYANOBACTERIAL OPERONS
Review round: 2
Reviewer: 2

Output:
Basic reporting: Throughout the text, machine learning should be lower case.

Table 1: Do the “?”s mean that a gene function was not able to be classified?  Please change to “No predicted function”
Experimental design: Regarding the number of genes in an operon that have diel expression variation for the priors, it looks like in the text it still needs to be changed to reflect this in the methods.  Dr. Heller changed the number of priors in the text but did not change lines 85 and 86 to reflect the change to requiring all genes have diel expression variation.
Validity of the findings: I thank Dr. Heller for the effort to do the gene distance analysis of the operons.  Please include a sentence in the methods stating that a gene distance analysis of the priors did not fit a gaussian distribution, making gene distance difficult to include in the operon prediction. Even though it did not lead to a contribution to the methods, I think it is worth mentioning the effort and it is informative for the reader.
Additional comments: After the above comments are addressed I can recommend this manuscript 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: TIMES AND PARTNERS ARE A-CHANGIN’: RELATIONSHIPS BETWEEN DECLINING FOOD ABUNDANCE, BREEDING SUCCESS, AND DIVORCE IN A MONOGAMOUS SEABIRD SPECIES
Review round: 1
Reviewer: 1

Output:
Basic reporting: There are minor grammatical errors which I have tried to address
Experimental design: No comment
Validity of the findings: There are a few parts of the discussion that would benefit from being expanded to widen the scope.
Additional comments: I really enjoyed reading this article. I think it is novel and interesting and well analysed and reported.  While it looks like a lot of comments they are minor edits to the grammar, suggested rephrasing and request for clarifications
Title – I am definitely not a fan of puns in titles but I appreciate why some people are.  However, here comes the sun is in no way related to your work so I suggest you remove it or think of a more suitable replacement
Line 12 – this first sentence is very, very broad and a bit vague.  I think you could make this a bit more focused on life history perhaps? Or reproduction?
Line 14 – I would rephrase to read “ at the population and individual level”
Line 19-20 – I would have thought this should be in the past tense?
Line 22 – is this always the case? If not how often would be helpful here
Line 30 – resilient to environmental change?
Line 32 – I would rephrase to be “Normally seabirds divide parental care between the pair” or something like this? It is a bit clunky as it is and is missing an apostrophe
Line 33 – why must they foraging simultaneously when there is food depletion? If there are on an egg or a chick they can not? I don’t really understand this sentence. They can leave the offspring unattended once it reaches a certain age? I can’t imagine they would leave a tiny chick or an egg? Maybe you could rephrase this to cover the idea that when food is scarce they are more likely to leave a younger chick or the chick earlier to obtain sufficient food?
Line 36 -I would state that this is for colonial breeders – or birds that nest in tight colonies. If they are in loose colonies or burrow nesters this would not be true.
Line 40 – why would this affect pair reunion? Because failure would do? I think it is the word therefore that is a bit confusing here. I would just say that this reduction in breeding performance can then affect pair reunion
Line 44 – you say 80% of birds are monogamous then they have diverse mating systems? Isn’t this contradictory? Do you mean the extent of true monogamy varies because 80% of spp are socially monogamous?
Line 47 – given you look at individual level variation would this be a good place to mention this variation too?
Line 50 – so do you include widowhood in divorce? By saying even it suggests you do but true divorce does not include instances where one partner dies
Line 56 – you can have biparental care without social monogamy….maybe “and the associated social monogamy”
Line 62 – this is quite vague – a random event. What about if a better partner comes along? Birds can upgrade their partner even if they haven’t failed. For example for a younger partner or one in better condition. I think you be a bit more thorough in this part.
Line 65 -  but not only conditions right?
Line 67 – but this is true for life time reproductive success but for a time lag of 1 this is a little simplistic.
Line 95 – typo
Line 97 – why are you repeating why gannets divorce?
Line 115 – was this from observations?
Line 173 – what does number of complete pairs monitored mean? Is this the pair retention? That would seem very low
Line 189 – delete does
Line 199 – for bivariate time series comparisons – do you mean pairwise comparisons between two variables? For people less familiar with these techniques an extra line here could be helpful
Line 223 – “individual was”
Line 233 –“showed substantial”
Line 237 – “were very different”
Line 239 – “was” , “accounted” – needs to be past tense throughout the results
Line 243 – I would personally drop “VAR model diagnostics” as this is in the methods
-	What does it mean given the lack of an inverse relationship? This would also be good to state
-	I would redefine the variables where the equation is shown
-	I think it would be better not to use abbreviations in table 2
Line 247 – is it worth including these results here or explain them a bit here?
Line 262 – 263 – this sentence doesn’t really make sense - rephrase?
Line 266 – what is a lost category?
Line 249 – I don’t think therefore is the right word here. Is this sentence describing the pattern from the result in the one before? If so then I would say “these analyses showed” or something explicit
Line 252 – what is an impulse? I would explain again here
Line 257 – delete does
Line 258 - delete both the
Line 281 – I would reiterate the hypothesis here
Line 282 – longer than what
Line 283 – biomass of mackeral?
Line 287 – biomass
Line 288 – has shown….were related
Line 293 – see comments in the intro – they always leave it unattended eventually so I think you need to be more specific here
Line 300 -this review
Line 301 – Otherwise should be However…estimates of divorce rates
Line 302 – vary
Line 312 - figured is not the right word here
Line 314 – the rate of divorce – I don’t think that occurance is the figure given here
Line 316 – actually? Do you mean than now?
Line 317 – I would rephrase as “High concentrations of DDT were another extrinsic factor….”
Line 322 – does not permit “us” to …
Line 324 – should be present tense
Line 326 – part-time partnerships is not a standard term – do you mean
low monogamy? Or birds that are only together when they breed and not during winter?
Line 326 – Northern gannets are a migratory species … (it is not obvious if you don’t know about gannets!)
Line 329 – but do waterfowl go onto land in the winter? If gannets stay at sea all winter is it likely that they meet their partners at sea? Seems unlikely
-	What does one and three pairs mean?
Line 321- Why would selection favour the effort of finding you partner at sea?
Line 335 – there is no difference detected…
-	This whole sentence is a bit muddled – why does leaving at the same time and females coming back later suggest the same thing? The final sentence could be better phrased – do you mean that decisions on divorce occur at the breeding ground?
Line 356 – change succeed to support to just support
Line 359 – here you show in another very closely related spp that divorce does not follow breeding failure.  I think in the discussion it would be good to explore why this may be in some seabirds. I think in very long lived spp where pair experience predicts fitness the cost of divorce is high and so you would expect divorce to come at a higher cost.  In order to extend the findings beyond that of this population, I think it would be nice to explore why the patterns are so mixed in seabirds. I also think it would be good to chat about how predictable or high quality the environment – if there is just one bad year would divorce be adaptive?


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: TIMES AND PARTNERS ARE A-CHANGIN’: RELATIONSHIPS BETWEEN DECLINING FOOD ABUNDANCE, BREEDING SUCCESS, AND DIVORCE IN A MONOGAMOUS SEABIRD SPECIES
Review round: 1
Reviewer: 2

Output:
Basic reporting: In general, I found the manuscript entitled “Here comes the sun: divorce in a seabird species increases breeding success during low food abundance” to be an interesting examination of how a widely-accepted concept (low breeding success leads to divorce in long-lived seabirds) operates in practice. In particular, I appreciated the extension of the analysis to include data on prey abundance, allowing for a more complete picture of how the lack of prey availability may directly lead to breeding failure, and, by extension, mate switching. I did have several thoughts about the analysis and the narrative, which I outline here, but I think that after revisions the study will make a worthwhile contribution to the literature on the topic. The style and grammar of the written text could be improved a bit by some copy-editing, but it was understandable throughout.
Experimental design: There was one aspect of the analysis caused me to think quite a bit, and I’m not sure I ultimately came up with a good answer: each of the time series fed into the Granger-causality tests was first detrended. I am not very familiar with Granger-causality, but that seemed like an appropriate step, because of the requirement that each series be stationary. However, as I considered an individual gannet’s mate choice from a biological perspective, I wasn’t sure if a bird would be capable of reacting to detrended prey or breeding success patterns—would not a gannet’s breeding success to react to the absolute prey abundance, and then a mate choice decision to react to the actual breeding success in prior years? However, I do see the value in removing any existing long-term trends, which could be the result of many other factors: for example, both breeding success and divorce rate could be decreasing as a result of some third, unknown factor also subjected to long-term trends. So, I found myself doubting whether an analysis that relies on detrended time series would be appropriate for this question. I wonder if the authors could help explain (either in the methods or discussion) exactly why the process of detrending the data is necessary, and perhaps discuss the ramifications of doing so in the interpretation of the results.

I may be mistaken, but I assume that the lag of 2-years found between mackerel SSB and breeding success (Table 3) should be interpreted such that breeding success is lower 2 years after a drop in mackerel stocks, correct? If so, I found that to be very counter-intuitive given my naked-eye interpretation of Fig 2, in which the most obvious pattern appears to be that breeding success dramatically declines in the year immediately following major declines in mackerel SSB. I suspect that a stronger 2-year lag may be the result of running the analyses on detrended data, and perhaps even a change in the feeding ecology of the gannets after the apparent crash in mackerel stocks in 2011. The authors do discuss the gannet diet briefly in the discussion, but any information about how breeding success increased so dramatically following the dramatic decline in 2012 would be helpful. Given that the time series seems to be so dominated by a large crash in mackerel abundance in the early period, and then a disassociation between mackerel and breeding success in the later period, is the Granger-test approach well-suited to these data? Some explanation for that counter-intuitive result may be useful for the reader in the results or discussion.
Validity of the findings: I found the individual results and model of partnership status, including Fig 3, to be the most compelling part of the argument. Those results told a very clear story about the difference in repairing after partner-loss and divorce. I also found the separation of the discussion into the “when” and “why” sections to be very effective.
Additional comments: My main suggestions for revisions are to further examine the ramifications of some of the methods associated with the Granger-causality tests, as described above, and to explain why those results seem to provide a counterintuitive lag between mackerel SSB and breeding success. Without more expertise on the Granger approach I cannot say whether changes to the analytical method are warranted, but I do feel that there should at least be some additional explanation for other readers who, like me, are unfamiliar with such methods.

Some minor edits to consider as well:

L108: Is it possible that the focus on peripheral areas of the colony influenced the rate of divorce? It is often suggested (for some species at least) that young/inexperienced birds may inhabit these areas, where breeding success is lower than near the center of a colony. That being said, I believe that actual empirical evidence for it may be quite rare (though, perhaps some work on Adélie Penguins may have discussed it?) If so, it is possible that the breeding success and rate of divorce observed here may not be representative of the entire colony.

The paragraph beginning on L79 seems to be making several loosely-related points about gannet biology in the region, and it is difficult to follow the narrative thread. A reorganization of the paragraph, perhaps splitting it into one paragraph on feeding ecology/prey and another paragraph on why it is a good model for studying divorce, may help.

L121: Does the section on sex determination need that much detail? Perhaps simply citing Griffiths et al. 1998 allows the rest of the paragraph to be much shorter? On the other hand, these details may be useful to some readers, so it may be better to keep them in, as long as the manuscript is not too long.

During the description of the Granger-causality methods, there were several terms used (such as “stationary”, “impulse”, and “shocks”) that may hold different connotations for most seabird biologists. In general, the section was fairly good at explaining the methods to a lay audience, but some additional explanation for the concepts in L194-210 may be helpful.

L211: It was not clear to be at first what “annual means” referred to, and why these methods were being employed. Perhaps an additional sentence at the beginning of this paragraph explaining how these methods connect to the rest of the methods would help.

Equation 1: I was unsure of the purpose of the various asterisks.

L374: The conclusions section isn’t really a summary, as it adds more relevant discussion—I would simply remove the ‘Conclusions’ header, or perhaps move some of the material out of this section and into another part of the discussion.


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

Input:
Title: TIMES AND PARTNERS ARE A-CHANGIN’: RELATIONSHIPS BETWEEN DECLINING FOOD ABUNDANCE, BREEDING SUCCESS, AND DIVORCE IN A MONOGAMOUS SEABIRD SPECIES
Review round: 1
Reviewer: 3

Output:
Basic reporting: This is a really interesting premise and a clear gap in the literature. The authors have identified a colony with comparably high divorce rates to the broader biogeographical range and use this to study the causes and consequences of divorce in the framework of an adaptive strategy. The paper is generally well written. There were some sentences that were hard to follow and others where parts seemed to be juxtaposed, and I have highlighted/corrected these in the attached annotated PDF.

Figures were very well presented and easy to follow, with really nice iconography to aid interpretation about pairs that stayed together and divorced. I did find the associated data difficult to use to replicate findings. Divorce rate data in particular did not identify the years that observations occurred in (just year t, t-1, t+1 etc). While that could be used with the provided code to run an analysis, there is no way of checking the underlying data to understand which years corresponded to poor food or breeding success. Perhaps providing raw data here would be a good idea, identifying nests and partners?
Experimental design: This is clearly original research that falls within the remit of the journal. The research questions could be better defined, for example, whether you expect a positive or negative relationship between variables rather than just a relationship.
Methods could do with some clarification to aid understanding and replication, but it is generally easy to follow and quite obvious that a significant amount of work has gone into field data collection for which the authors should be rightly proud.
Unfortunately I am unfamiliar with the analysis approach taken (I'm far more familiar with the use of Hidden Markov models for time series analysis that can be correlated with environmental variables), so can't really comment on the appropriateness of this. from the methods, it seems to be appropriate in terms of accounting for temporal autocorrelation and identifying time lags, but I can't really comment on the mechanics of the analysis.
Validity of the findings: this is probably where I had the greatest issue. While it is a very interesting study and there are clear results, I'm not convinced that the results are properly reflected in the paper title or conclusions. The paper suggests that poor food availability with a season leads to low breeding success and that this is caused by both parents having to forage and chicks being killed by aggressive neighbours. It ignores the fact that if both parents need to forage, that they may be maintaining their own body condition and chicks are simply not getting enough food to meet requirements. Perhaps the authors could support this with information on the weights or condition of chicks found dead in the colony?
Following poor breeding success as a result of low food availability, pairs are more likely to divorce. While they did show a convincing 1 year time lag between breeding success and divorce, there was no relationship between food and breeding success within seasons, in fact there was a 2 year time lag that seems to have been interpreted as demonstrating a link between food and breeding success that just doesn't make biological sense. I'm also unsure how the model accounted for the apparent increase in food conditions following a poor year, particularly for those pairs that remained together following a poor food season and breeding failure. Obviously if nests fail due to poor food availability in one year, if conditions are better the following year, breeding success should be higher across the board and not just on those pairs that divorced? And this may differ to those birds that were successful in the poor food year, but possibly unsuccessful the following year - perhaps there is some carry-over effect?  I was expecting a basic comparison of breeding success between failed nests that stayed together and failed nests that divorced in the year following breeding failure to disentangle increased food availability in years following divorce from the effect of divorce. This may be where my lack of expertise in the statistical approach lets me down, but I imagine other readers would have similar questions, so if this is accounted for in the model, perhaps this needs to be better explained.
Additional comments: I have provided a number of additional comments etc on the attached annotated manuscript PDF.


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: TIMES AND PARTNERS ARE A-CHANGIN’: RELATIONSHIPS BETWEEN DECLINING FOOD ABUNDANCE, BREEDING SUCCESS, AND DIVORCE IN A MONOGAMOUS SEABIRD SPECIES
Review round: 2
Reviewer: 1

Output:
Basic reporting: The authors have done a great job addressing my comments and I have no further comments
Experimental design: The authors have done a great job addressing my comments and I have no further comments
Validity of the findings: The authors have done a great job addressing my comments and I have no further comments
Additional comments: The authors have done a great job addressing my comments and I have no further comments


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

Input:
Title: QUANTITATIVE TRAIT LOCI MAPPING AND CANDIDATE GENE ANALYSIS OF STOMA-RELATED TRAITS IN WHEAT (TRITICUM AESTIVUM L.) GLUMES
Review round: 1
Reviewer: 1

Output:
Basic reporting: English writing is clear, background is enough, references is proper, the structure and figures, tables are good.Figure 3 and 4 may be integrated as one figure.
Experimental design: 1.	Because that stomata openness is subjected to environmental changes (such as water, N, K fertilizers, etc.), and 150 lines should have genetically different in response to environmental changes. Please add proper discussion. Additionally, please present the data about the environmental condition, such as temperature, soil and leaf water content, irrigation management.
2.	Is LOD value setting different for different traits? Why selected the 2.5? Was the mean of performance value of traits across the two years used for QTL location, or only one year for location? Please clarify. How about the effects of environmental factors on QTL locations?
Validity of the findings: The study mapped QTLs for stomatal length, stomatal width, stomatal density, potential conductance index of stomata, stomatal area, and stomatal relative area were measured in different parts of wheat glumes from a doubled haploid (DH) population and their parents, and provide the genetic understanding on wheat stomata.
What difference on trait performance and QTLs among different parts of wheat glumes? Please specify clearly and discuss in the discussion section.
In Result section “Expression analyses of candidate genes”: the study only found candidate genes but surely identified genes, therefore, for me, it is not appropriate to present the analysis based the previous reported data set. If necessary, the related results may be referred to in the discussion. So, the related statement in Abstract should be deleted.
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: QUANTITATIVE TRAIT LOCI MAPPING AND CANDIDATE GENE ANALYSIS OF STOMA-RELATED TRAITS IN WHEAT (TRITICUM AESTIVUM L.) GLUMES
Review round: 1
Reviewer: 2

Output:
Basic reporting: 1. The manuscript is easy to understand, though some minor English errors were identified.
2. Research background and references are well organised.
3. Structure of the manuscript is within the standard.
Experimental design: 1. Experimental design is reasonable.
2. SInce the manuscript focused on stomata from wheat glumes, the materials and method well suit the research purpose.
Validity of the findings: Yes. The QTL from the base of the glume is significant with a reasonable LOD value, suggesting the high contributions of these QTL to the studied stomatal traits.
Conclusions are well stated, discussed. There is not much QTL studied in stomatal using a large population.
Additional comments: I think this is a well-written manuscript only focusing on stomatal traits. This work requires a large amount of labour work and patience in data collection and analysis, especially when dealing with a DH population. As one of the reviewers, I appreciate the work done by these authors. However, since this work only focused on stomatal traits that involved no research on abiotic stresses, it is hard to say these QTL has a very close link to abiotic stress (as such of drought, salinity). Moreover, I endorse the confirmation of the candidate genes using the public database. However, it might be better if an RT-PCR could be also performed using representative lines to test the candidate genes.


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: QUANTITATIVE TRAIT LOCI MAPPING AND CANDIDATE GENE ANALYSIS OF STOMA-RELATED TRAITS IN WHEAT (TRITICUM AESTIVUM L.) GLUMES
Review round: 2
Reviewer: 1

Output:
Basic reporting: Since this is the revised version based on the comments from the reviewers, I have no further comments.
Experimental design: Since this is the revised version based on the comments from the reviewers,  I have no further comments.
Validity of the findings: Since this is the revised version based on the comments from the reviewers,  I have no further comments.
Additional comments: Since this is the revised version based on the comments from the reviewers,  I have no further comments.


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

Input:
Title: THE ASSOCIATION BETWEEN GEOGRAPHIC INFORMATION SYSTEM-BASED NEIGHBORHOOD BUILT ENVIRONMENTAL FACTORS AND ACCELEROMETER-DERIVED LIGHT-INTENSITY PHYSICAL ACTIVITY ACROSS THE LIFESPAN: A CROSS-SECTIONAL STUDY
Review round: 1
Reviewer: 1

Output:
Basic reporting: Authors reported on a very interesting study on neighborhood built environmental (BE) factors and accelerometer-derived light-intensity physical activity (LPA). The manuscript is generally well written, and the rationale, objectives and methodology are clearly presented. The article adds to the currently scarce literature regarding accelerometer LPA outcome-GIS  BE factors.  The study objectives are promising and important for the field of health promotion.  Also, investigating moderation between different age groups is an important step forward from the existing literature. Although I applaud the reasoning, objectives and the general quality/clarity of the manuscript, I have some major methodological concerns and other issues that the authors need to address before I can accept the manuscript for publication.

Abstract
•	Authors should consider changing the word “correlates” to “association” in the first line of the background section of the abstract
•	Authors should be specific with what they mean by “A small but significant association was observed between residential density” in the results section of the introduction. Is it a positive or negative association? Please clarify
•	I am a little bit confused with the statement “demonstrating that every decrease of 1000
dwellings per surface buffer was associated with a two-minute increase in LPA”. Is the Unit of LPA in minutes? Authors should please clarify.

•	Is the interpretation of the beta coefficient correct in the first line of the result section in the abstract? “A small but significant association was observed between residential density (500 m
buffer) and LPA in the total sample (B=-0.002; SE=0.0001; p=0.04), demonstrating that every
decrease of 1000 dwellings per surface buffer was associated with a two minute increase in LPA.”  If the beta coefficient is negative, the interpretation is that for every 1-unit increase in the predictor variable (i.e , residential density ),the outcome variable(i.e.LPA) will decrease by the beta coefficient value. Based on this, I was expecting the authors to write “……..demonstrating that every increase of 1000 dwellings per surface buffer was associated with a two minute decrease in LPA” Can the authors clarify this?

•	Authors should mention the number of days the accelerator/GPS was worn in the methods section of the Abstract
Background
•	[line 58] Please provide a citation
•	Can the authors maybe provide some more background on the importance of the different moderating variables analyzed ( i.e.age group-adults, adolescents,-etc) in relation to BE-LPA association . A paragraph will be Okay
•	[line 67] please provide a citation
•	The rational for examining the five BE should mentioned in the background section. Why did the authors choose to examine entropy index? Why did the authors choose to examine residential density and not other BE factors such as water bodies? At least the reader should be given a background on how each of the five BE factors are important to LPA.
Experimental design: Participants and procedure
•	Authors should consider changing the sub heading title “Participants and procedure” to something along the lines of “Study participant selection procedure”
•	[line 112] how was “low” and high walkability defined? The authors need to explain the criteria for “low” and “high” walkability. The same applies to the SES variable. What was the criteria for selecting a neighborhood as low or high SES?  The authors need to clarify
•	Authors should consider including a flowchart to summarize the participant selection process (The number of participants that were dropped or excluded at each stage) . This flowchart can be put in the appendix

 Outcome variable: LPA

•	Were the accelerometers equipped with GPS? If yes authors did not provide any details regarding raw GPS data processing. Was there malfunctioning due to signal quality when exposed to different environments? How did you deal with that? How about signal loss indoor? Did it occur? If you are limited in pages, at least an appendix or consort diagram of N numbers needs to be provided. Without knowing these details, it is tough to evaluate the quality of GPS data before aligning with accelerometer by timestamps.
•	When was data collected? Did they have lots of non-wearing hours?
•	The authors fail to mention the number of bouts they used for their accelerometer processing. Did they use a 5-min bout, 10-min bout? Please clarify
•	Transparency and quality of the spatial and statistical analyses can be improved by providing the reader with a flowchart, depicting compliance and loss of data in each step of the analytical process. The authors should provide information summarizing data loss at each step of the accelerometer data
•	There are doubts for readers about the level at which data are in the end analyzed. Overall you need to clarify what is the unit of analysis. Was the data analyzed at 60 -second epoch collected by the accelerometer? Was the data cumulated to 1 minute? All these need to be spelled out clearly in the methods section
•	It is not clear if the authors applied a point-based method to access cumulative exposure and examine its cross-sectional associations with LPA outcomes. Authors should clarify if they used a point by point base approached and mention the limitations that come with it in the discussion section.

Predictor variables: GIS-based neighborhood built environmental factors
•	Why did you select these 5 GIS-based neighborhoods built environmental factors? In other words, why they made the BE set but not others? Were they examined most frequently by previous studies? Were they related to LPA outcomes for certain reasons? The rationale should be provided.
•	Why were 500 m and 1000 m (1 km) around the home addresses of all participants selected? Are these arbitrary or are there specific reasons. Authors need to justify their reasoning for selecting these buffer radii.
•	Authors fail to go into details on the methodologies used to derived BE-factors. Please elaborate and explain the data-extraction from GIS-registries. What were the data sources? What software was used to perform your GIS operations? All of this information are missing in the methods section.

•	What was the logical reasoning for restricting your analysis to points within your 500 or 1000 buffer radius? Why ignore GPS points that fall out the home buffer. Light intensity physical activity may also occur outside the selected buffer radii. If the authors are restricting to only points that fall within the buffers, they are not using the full dataset over the 7 day period.
•	Authors should consider as a form of sensitivity analysis, perform the same analysis but this time using only points that fall outside the buffer radius. They can then compare the results to the results of the points that fall inside the buffer radii.
•	Authors should consider adding a table to illustrate the BE factor assessment method / operationability and data sources similar to table 1 of Troped et al 2010 . This will make it easier for non-spatial readers to grasp how your GIS BE factors were derived.
•	It is not clear how the authors merged or linked the accelerometer data to the  GIS built environmental factors. Authors need to explain into detail how they went about this process. At what unit or level was this done. Authors should please clarify how this linkage was performed. Was a GPS point linked to the closest built environment factor? Was there a spatial join? Please clarify
•	At what level was the analysis performed?  Did the authors apply a point-based method to access cumulative BE factor and use that to examine its cross-sectional associations with LPA outcome in the seven days.?  Authors need to clarify this in their writeup. If this was their approach its limitation must be discussed in the discussion section.
Validity of the findings: •	Authors are encouraged to revisit their rationale (and potentially also their methodology) about conceptualizing environmental factors and elaborate in the discussion-section on this concept.
•	Authors should consider reporting the output as per IQR increase
•	Transparency and quality of the spatial and statistical analyses can be improved by providing the reader with a flowchart, depicting compliance and loss of data in each step of step of the analytical process.
•	I would like to see more policy implication of your results
Table 1
•	Authors should consider not reporting the range of the age in the first row of the  age  variable. Just report the mean and SD

Table 2
•	please add a foot note explaining what variables were included in the single predictor and multiple predictor models
•	Authors should report the confidence intervals in addition to the p-values
Table 3
Authors should add footnotes to table 3
-explaining to the reader how the  the what variables were included in the Chi2 (df) for interaction effect
- at what alpha level( eg, <0.05)? is the p-value significant. Please make sure to include this in the table

overall, tables need to be reformatted for easier reading and clarity. Please add foot notes to all your tables where appropriate
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: THE ASSOCIATION BETWEEN GEOGRAPHIC INFORMATION SYSTEM-BASED NEIGHBORHOOD BUILT ENVIRONMENTAL FACTORS AND ACCELEROMETER-DERIVED LIGHT-INTENSITY PHYSICAL ACTIVITY ACROSS THE LIFESPAN: A CROSS-SECTIONAL STUDY
Review round: 1
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: Thank you for the opportunity to review the paper on accelerometer-based light-intensity physical activity, with the strength of incorporating three cohort databases. This is an important paper looking at the GIS-based environmental correlates of light-intensity physical activity. The findings can offer some insights into the target population at risk of physical activity promotion. To improve the paper, I have several comments for the authors to consider, as follows -

1.	The paper would be improved by a better justification for the need to investigate the moderating effect of age in the Introduction section. There is a comprehensive massive transport system in Belgium, so the mobility may not that limited to adolescents and older adults although they could not drive cars. Additionally, the authors can consider driver license or access to public transport as a confounding factor in the models if such information is available.

2.	In the single-predictor models, residential density within 500 meters was not associated with light-intensity physical activity; however, it became significantly associated with light-intensity physical activity in the multiple-predictor models, after adjusting for other confounding factors. This significant association between residential density and light-intensity physical activity needs to be interpreted in caution.


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

Input:
Title: THE ASSOCIATION BETWEEN GEOGRAPHIC INFORMATION SYSTEM-BASED NEIGHBORHOOD BUILT ENVIRONMENTAL FACTORS AND ACCELEROMETER-DERIVED LIGHT-INTENSITY PHYSICAL ACTIVITY ACROSS THE LIFESPAN: A CROSS-SECTIONAL STUDY
Review round: 1
Reviewer: 3

Output:
Basic reporting: I would suggest the authors to explore more on the literature that support why additional study utilizing accelerometer accessed LPA is needed. Please check all recent published manuscripts.
While the authors do a good job of highlighting pre-existing work as it relates to built environmental factors and LPA, as well as the potential modification effect of age, it would be helpful to more clearly emphasize why the authors are interested in examining the relationship/moderation (beyond the fact that it has never been done before). Specifically, self-reported walking date focus on walk, while accelerometer assessed LPA might include all kinds of activity fall into the cut-off points. How comparable are the current results versus previous studies (line 249, gardening, cooking and etc.)? In addition, effect of age may not have been examined in one paper, but different manuscripts using the same data source may have explored the association between different age groups. (e.g., https://ijbnpa.biomedcentral.com/articles/10.1186/s12966-019-0886-2)
Experimental design: Another suggestion was to explore MVPA, LPA, SED and sleep (compositional data analysis through isometric log-ratio) at the same time. As the authors already mentioned in the discussion, it is necessary to explore different PA intensity while considering their association within 24 hours window. Looking at LPA alone didn’t tell the whole story, hence limited the depth of the current study.
Validity of the findings: The strength mentioned are not very convincing. Regarding the age group, it is good intention to study age differences on the association, the sample size difference should not be ignored. Also, it would be hard for policy maker to accommodate different needs across different age groups within same neighborhood, additional thoughts should be put into the discussion. Line 271-273, several studies have examined associations between built environmental factors and accelerometer measured PA (BI Chen et. al., 2019; D Salvo et. al., 2011; AK Solbraa et. al., 2018; PJ Troped et. al., 2010 to name a few). In addition, self-reported measure does have its limit, but accelerometer measure (on waist) also has its limitations on accuracy and tracking activities such as weight-lifting, casual bike riding and etc. where movements on the waist are hard to detect and track.
Additional comments: 1.	Line 104-105, any potential participants in both BEPAS and BEPAS Seniors study? Any impact on the result?
2.	Line 136, since different accelerometers were used, any calibration/adjustment on the data to make results comparable?
3.	Line 144, please provide more details on Freedson and Evenson cut-off points, and why authors choose to use each on specific age groups (add ref).
4.	Line 154, any data on average age in the area? Might want to add as control/covariates when exploring age groups.


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

Input:
Title: THE ASSOCIATION BETWEEN GEOGRAPHIC INFORMATION SYSTEM-BASED NEIGHBORHOOD BUILT ENVIRONMENTAL FACTORS AND ACCELEROMETER-DERIVED LIGHT-INTENSITY PHYSICAL ACTIVITY ACROSS THE LIFESPAN: A CROSS-SECTIONAL STUDY
Review round: 2
Reviewer: 1

Output:
Basic reporting: Authors have addressed all my concerns adequately
Experimental design: Authors have addressed all my concerns adequately
Validity of the findings: Authors have addressed all my concerns adequately
Additional comments: Authors have addressed all my concerns adequately


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

Input:
Title: THE ASSOCIATION BETWEEN GEOGRAPHIC INFORMATION SYSTEM-BASED NEIGHBORHOOD BUILT ENVIRONMENTAL FACTORS AND ACCELEROMETER-DERIVED LIGHT-INTENSITY PHYSICAL ACTIVITY ACROSS THE LIFESPAN: A CROSS-SECTIONAL STUDY
Review round: 2
Reviewer: 2

Output:
Basic reporting: I thank the authors for responding to each of my comments. The revised paper has been greatly improved by clarifying the rationale of the investigation into the potential moderation effect and providing more details of the Methods and Discussion section.
Experimental design: The selection of participants was clearer after adding a flow chart. The only concern is that more than half of the adolescents were excluded (i.e., 150 included in the analysis out of 373 enrolled in the study), which has been added to the revised paper as a limitation. I have no further comments on the Method section.
Validity of the findings: The results of this study showed no strong association between environmental attributes and light-intensity physical activity, with only one plausible association of 500-m residential density with light-intensity physical activity after adjusting for sociodemographic characteristics. It is suitable to focus on the importance of taking 24-hour behaviours into account in future research, as the authors have done, rather than focus on the plausible 'negative' associations observed in the Discussion section. I have no further comments.
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: THE REGULATION OF HSACIRC_004413 PROMOTES PROLIFERATION AND DRUG RESISTANCE OF GASTRIC CANCER CELLS BY ACTING AS A COMPETING ENDOGENOUS RNA FOR MIR-145-5P
Review round: 1
Reviewer: 1

Output:
Basic reporting: The English used in this article is clear and technically correct. It would be advisable to check punctuation marks, as well as when capitalised and lowercase words are used throughout the text.
The references are correct. In line 317, the reference should keep the same format as the rest.
The estructure conforms to Peer J standards.
Figures are relevant and well labelled.
Some of the original supplementary information is in Chinese.
The hypothesis is relevant.
Experimental design: Some methodological aspects should be further elaborated in the manuscript to facilitate the understanding of the work.
Validity of the findings: The authors make a single conclusion from their work, but without showing its scientific relevance in the conclusion section.
Additional comments: Your introduction needs more detail.
You should update the treatment options for gastric cancer patients (ASCO Annual Meeting 2021) and explain that 5-Fu still has an important role in the treatment of gastric cancer patients today, so your research is clinically relevant.
In the introduction, regarding cicrRNA, I suggest that you improve the description of what it is and how it acts. You should provide more justification for your study (specifically, you should expand upon the knowledge about cicrRNA and drug resistance and gastric cancer).
In Line 51: made a gastric cancer cell line from SGC-7901 and not from MKN-45. You should explain the reason for your choice.
In the Results section:
1.	After normalization, a total of 4,496 circRNA targets were found in SGC-7901 and 31 distinct circRNAs were selected because their expression. It would be good to explain it in more detail.
2.	Hsacirc-004413 was highly expressed in 5-Fu resistant SGC-7901-5-Fu cells. In this experiment you used SGC-7901, SGC-7901-5-Fu and MKN-45 line cells. It would be advisable to explain why the MKN-45 cell line was used. As well, it would be very important for you to detail why you chose hsacirc-004413 and not another circRNA.
3.	Line 167 should be in bold.
4.	It should better explain the relationship between hsacirc-004413 and miR-145-5p and
5.	It should better explain the relationship between hsacirc-004413 and miR-145-5p and how it arrives at the hypothesis that the resistance of hsacirc-004413 to 5-Fu may occur though the adsorption of miR-145-5p (Lines 178-181).

The Discussion is very extensive and some results do not appear in the results section, for example:
- Lines 203-208: hsacirc_004413 was compared with hsacirc_0004650.
- Lines 226-236: although this is discussed in more detail in the appendix, discussing this in the results section would make it easier to understand the importance of miR-145 in this context.

The relevance of the only conclusion of this work should be explained.


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

Input:
Title: THE REGULATION OF HSACIRC_004413 PROMOTES PROLIFERATION AND DRUG RESISTANCE OF GASTRIC CANCER CELLS BY ACTING AS A COMPETING ENDOGENOUS RNA FOR MIR-145-5P
Review round: 1
Reviewer: 2

Output:
Basic reporting: The idea of paper is well thought and data make justice to the Hypothesis.
The literature reported in MS is sufficient for the project.  MS overall need better use of professional English language. I recommend to improve the language of result and discussion section. The article followed the professional structure although figure legends were not well written.
Experimental design: The experimental design of MS was comprehensive and well structure. It covered the scope of journal and finding mechanism of 5FU resistance in GC. The identification of miR-145-5p and circRNA was explained well for readers. The validation work was done with sound technical knowledge.
Validity of the findings: The work is novel for readers especially MS is very relevant to find 5FU resistance mechanism.
Additional comments: I strongly recommend to submit article with improve language and figure legend quality.


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

Input:
Title: THE REGULATION OF HSACIRC_004413 PROMOTES PROLIFERATION AND DRUG RESISTANCE OF GASTRIC CANCER CELLS BY ACTING AS A COMPETING ENDOGENOUS RNA FOR MIR-145-5P
Review round: 2
Reviewer: 1

Output:
Basic reporting: The MS is improved from last submission.
Experimental design: The experimental design is rational and well plananed.
Validity of the findings: The findings will add to development of future treatment strategy
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: ANTAGONISTIC CO-CONTRACTION CAN MINIMIZE MUSCULAR EFFORT IN SYSTEMS WITH UNCERTAINTY
Review round: 1
Reviewer: 1

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment.
Additional comments: This manuscript presents the results of a simulation study that demonstrates co-activation can be energy-optimal, particularly in noisy environments. This is a very important result, as it is often assumed that coactivation is sub-optimal. The authors' approach towards investigating whether co-contraction can be energy-optimal in noisy environments is well-thought-out, with several sub-studies included investigating the potential contributors to co-contraction being energy-optimal. Where the manuscript can be improved is the better motivate and describe some of the methodological choices, including the use of forward shooting methods and a simple inverted pendulum model.

Major Comments:
1) Although I agree that energy minimization is important for many of the behaviors we do on a day-to-day basis, the authors should be careful about overstating the importance of energy minimization for everything that we do (e.g., lines 46-47, lines 58-59, lines 291-294). Although tasks such as walking have likely evolved to be energy optimal, energy-optimality is not necessarily true of all tasks (e.g., novel task, sudden loss of balance, etc.). Moreover, while energy may be the main component being minimized in some tasks for healthy adults, this is not necessarily the case for impaired individuals who may be co-optimizing with other things (such as balance, pain, etc.). To be clear, I agree that energy minimization is important and that the results of this study demonstrate that co-activation can be energy optimal. But I advise the authors to tamper down some of the wording regarding energy minimization being the only thing that is important.

2) The motivation for the forward shooting approach combined with the simple inverted pendulum is confusing to me. Specifically:
a) The purpose of this paragraph starting on line 66 is to motivate the stochastic optimal control methods used in this study to effectively study the energy-optimality of co-contraction in noisy systems/environments. Several commonly used methods of optimal control are introduced, and their limitations are described. It is unclear as written if the linearized system approach mentioned in this paragraph would allow for the introduction of noise and it’s just the linearity that is “bad”, or if this method also suffers from being unable to include noise. [moderate/major]
b) The purpose of this paragraph starting on line 77 is to introduce the current methods for stochastic optimal control, including one recently developed by the authors using direct collocation. The authors’ direct collocation method overcomes the time-consuming limitations of previous approaches. However, the authors state that their new method does not scale well to models with a large number of degrees of freedom. Why is this? And why would forward shooting overcome this limitation? Could the authors somehow present a comparison of how large/difficult the problem becomes for each of these methods to motivate why forward shooting is the better approach? Finally, if the reason for shifting to forward shooting is because of the direct collocation approach becoming intractable when models have many degrees of freedom – why examine a single degree of freedom model in the current study?

3) One of the things I really like about this study is the different investigations towards showing co-activation is energy optimal for various reasons. However:
a) It is unclear by the end of the Introduction exactly what is being done in this study and how they related back to the hypothesis that co-contraction is energy optimal in a nonlinear system with uncertainty. The authors should consider re-writing this paragraph to more clearly describe the different “experiments” being done in this study, their predictions on what will happen in each of the experiments, and how these predictions would support the overall hypothesis.
b) There are a lot of different simulation “experiments” being run, but the purpose of each of them, how they are set up, etc. is hard to follow due to the organization of this section. The “Approach” section would be much easier to follow if it was split into sub-sections, similar to how the “Results” section is split up. For example, sub-headings could include: 1) Effect of co-contraction on effort, 2) Effect of task precision and co-activation, 3) Effect of neural time delay on co-contraction, 4) Effect of excitation-activation delay on co-contraction.
c) Related to point 3b above, there are also many different variables that are being tuned in each of the simulation “experiments”. It would be very helpful to have a table that summarizes for each “experiment: what variables are fixed and which ones are allowed to vary (and by how much).

4) Some methodological choices are unclear:
a) The authors state that they repeated each problem with 3 random seeds to account for variation due to the variability of the problem. What was done with the results of these 3 different repeats per problem? Were they averaged? Was the minimum of the three taken as the result? Or…?
b) It’s not clear why comparing the trajectories of the optimal simulations (lines 170-173) was only done for the neural time delay and muscle activation time investigations.
c) How were the weights of the objective function (Jscone) determined? And what effect might different weights have on the results of this study?
d) For the effect of adding neural time delay, why was the range 5-25ms chosen? For the effect of muscle activation delay, why was the range of 0.01-0.09 chosen? Were there any biological reasons for these choices? (line 166 + line 176)

5) The argument regarding potential changes in the elderly makes sense (Lines 317-319), but I would like to see it supported by data. What did deviation in the inverted pendulum look like with versus without the feedforward control? Did it deviate less, was the slope different, was the variability of movement different, etc.? In addition, Lines 331-334 regarding how max isometric force may affect co-contraction may also be a good argument for what might change in older adults and thus may be better suited to be included with the discussion about potential changes in the elderly.

Minor Comments:
- Introduction (lines 62-65): The introduction of the neural time delay as another reason for co-contraction is oddly worded and a little hard to follow. Perhaps the beginning of this sentence could be stated more clearly and better integrated with the next sentence.
- Methods (page 6): It would be helpful to more clearly denote in the manuscript that equation 1 is the “feedforward + feedback” controller and eq2 is the “feedback only” controller
- Methods (line 132): The motivation for why “noise” was added as perturbations at the base of the pendulum needs to be motivated
- Methods (line 157)”: “a perturbation amplitude of 100 Nm” means “a maximum perturbation amplitude of 100 Nm” right?
- Results: What is “experiment 1”, “experiment 2”, etc.? The authors should be consistent throughout the manuscript in how they refer to each set of optimizations.
- Discussion (lines 360-361): Towards the end of the Discussion section there is a sentence that states: “but the combination of proactive and reactive control requires less effort than only reactive control”. I really like this sentence. However, this may be the first time “proactive” and “reactive” are used together to describe feedforward and feedback control. These terms should be defined and used earlier.


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: ANTAGONISTIC CO-CONTRACTION CAN MINIMIZE MUSCULAR EFFORT IN SYSTEMS WITH UNCERTAINTY
Review round: 1
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: The authors investigated the role of co-contraction when stabilizing one joint with an antagonist muscle pair in a simulation environment. It was found that when optimizing a cost function that penalizes movement effort, the model with a feedback controller also predicts co-contraction even it is not necessary for task achievement. My comments are listed below.

Major:
Eqs 8-10: Cost function is the sum of muscle activation, positional error and success. This is the authors’ definition of “effort”. The ratio parameters were determined quite arbitrarily (100, 10, 100 in Eqs. 9&10). Since three components of the cost function have different units with different ratios, it is difficult to interpret the balance among the three. How are these ratios determined and how optimization results depend on them?

In current design (Eq.1), co-contraction simply makes the plant stiff at its current position – even when this position deviates from the neutral position. So, I doubt if co-contraction can contribute to stabilization around the neutral position. An alternative design could be that the co-contraction always works around a certain equilibrium position (e.g., the neutral position in the case of this study) which the plant is attracted to.

The two feedback gains were also optimized. The author would need a comparison between with and without feedforward control when the two gains for feedback control are the same: first find the optimal feedback gains for the model with pure feedback control. Then add the feedforward controller and run the optimization with the same feedback gains. Would the cost be smaller in this case?

Neural delay has a maximal value of 25ms. It is not clear how this could be related to real physiological system. The values are within the range of fast feedback loops in the neural system (i.e., spinal level). Does the result have any implication about higher-level feedback control (with neural delay > 50ms)?

Minor:
Eq. 2, why was the feedforward control set to 0.01 instead of 0? E.g., in Fig.2 the feedforward signal starts at 0.

Line 136: Was there a particular reason why the authors did not simulate the gravity? Gravitational torque can cause a fall when exceeding muscle torques.

What is the rational to investigate different time delays and activation constant? Would this also imply some kinds of impaired control in patients with movement disorders?

Line 104: It is better to use effort than energy, to be consistent with the text.

Lines 261-262:  Would larger feedback gains be sufficient to perform the task without co-contraction, even when MTU were (also a typo in text) not strong enough?


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

Input:
Title: ANTAGONISTIC CO-CONTRACTION CAN MINIMIZE MUSCULAR EFFORT IN SYSTEMS WITH UNCERTAINTY
Review round: 2
Reviewer: 1

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: The authors have sufficiently responded to my prior critiques.


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: ANTAGONISTIC CO-CONTRACTION CAN MINIMIZE MUSCULAR EFFORT IN SYSTEMS WITH UNCERTAINTY
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 addressed my comments in a satisfactory way and I believe that the manuscript has been much improved. I have only one further suggestion:
Eqs. 9 and 10: please also indicate ''...=0, if otherwise''.


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: ALLEVIATION OF DROUGHT STRESS BY ROOT-APPLIED THIOUREA IS RELATED TO ELEVATED PHOTOSYNTHETIC PIGMENTS, OSMOPROTECTANTS, ANTIOXIDANT ENZYMES, AND TUBERS YIELD AND SUPPRESSED OXIDATIVE STRESS IN POTATOES CULTIVARS
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript is well-written
Experimental design: The experimental design is fine and methods are well described. However, authors have to clarify few issues as indicated in the general comments
Validity of the findings: The data are technically sound and conclusion is well stated.
Additional comments: General comments:
The manuscript entitled “Alleviation of drought stress by root-applied thiourea is related to elevated photosynthetic pigments, osmoprotectants, antioxidant enzymes, and tubers yield and suppressed oxidative stress in potato “ described the effect of thiourea application on growth and yield of potato under drought stress by assessing morpho-physiological and biochemical traits. Moreover, authors have demonstrated that thiourea application enhances antioxidant levels thereby reduces H2O2 and MDA level during drought stress in two potato genotypes. The finding of this study is very interesting and important for the readers from related field. In my opinion, the MS should be accepted for publication after addressing few important issues.

Specific comments:

Materials and methods
The authors considered 65% field capacity is drought stress. Is it true? Usually less than 60% field capacity is considered as light drought stress. Authors have to give references to justify that the moisture level is low enough too classified as light or moderate drought stress.

Additionally, author’s mentioned that seedlings were treated with rooting media of thiourea application (0.5 & 0.75 mM) at the vegetative stage. The question is how much thiourea solution was applied?

Authors have to mention the temperature and duration of drying of the potato samples for getting dry weight.

Results
The authors logically represented the data however the authors have not showed any images of plants for example how potato plants looks after 15 and 30 days of drought stress and how thiourea treatment recovers severity of drought phenotype?
Figure 2, 3, and 4 should be improved. In few cases, letter and standard error bar is overlapping. Letters should be plotted at the upper side of the standard error. It would be nice if the authors produces color bar graph.

Discussion
Few mistakes were found in using the abbreviations. Please carefully use the abbreviated name of ROS detoxifying enzymes.

Further recommendation
It would be pretty interesting and worth reading for the related readers if authors could produce a flow/process diagram on thiourea -mediated drought tolerance mechanism in potato based on the findings of the present study.


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: ALLEVIATION OF DROUGHT STRESS BY ROOT-APPLIED THIOUREA IS RELATED TO ELEVATED PHOTOSYNTHETIC PIGMENTS, OSMOPROTECTANTS, ANTIOXIDANT ENZYMES, AND TUBERS YIELD AND SUPPRESSED OXIDATIVE STRESS IN POTATOES CULTIVARS
Review round: 1
Reviewer: 2

Output:
Basic reporting: Authors must recognize what is thiourea in terms of environmental sustainability, not a favorable item.

Use of term:
Line 106: germination is not correct, sprouting or budding

Figure legend should be more compact and abbreviation shall be placed at other part of r legend legibility stand alone. descriptive to be more self-explanatory.

Reference section should be proof-read carefully. No sufficient citation info.
Line 476, 481, 498, 622: NO volume and pages or doi
Line 525 and 574: Style does not match with other citation
Experimental design: Overall, the data assessment itself looks neatly done on statistical approach using the correlation matrices for PCA.
However, more  assessment can be made such with ontology mapping, could make it clear to conclude what authors aimed at.

Line 103: Authors mention "potato cultivars" SH-5 and FD73-110. What are they? The local varieties or breeding lines? How they are different in traits and pedigree. varietal genetic information is valid to analyze the data and lead to conclusion. Why they were chosen? Could it be with more varieties?
Validity of the findings: Authors claimed that there is positive effect for the environmental stresses in suing the direct observation of the use of the thiourea. But in looking practicality of how is the thiourea, it would not help agricultural practice. Thiourea can be high toxic and could be environmental toxin. Cyanamide could be processed from thiourea within human body if it is in-taken.
Hardly to see practicality, and while authors indicated their ethical screening, it would not be ethical in conducting research with negative value of chemical substances.
Additional comments: Experiment itself is done resonably, but the use of thiourea is dead end, and would not be practical for supporting abiotic stress.