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: EFFECTS OF MATERNAL TAURINE SUPPLEMENTATION ON MATERNAL DIETARY INTAKE, PLASMA METABOLITES AND FETAL GROWTH AND DEVELOPMENT IN CAFETERIA DIET FED RATS
Review round: 1
Reviewer: 2

Output:
Basic reporting: Data and Figures/Tables:

Please can authors confirm that all data were tested for normality and the parametric statistical tests applied are therefore appropriate.

In methods it is stated that litters were culled to a max of 8 (4M/4F if possible). In results it states that litter sizes were comparable and male:female ratios unaffected so one would expect similar n’s across all groups in Figure 4 (offspring body weight). But n’s range from n=12-24. Can authors provide an explanation for this?

In methods it is also stated that at the end of lactation, mothers and three male and three female offspring from each litter were culled. Table 5 n numbers are inconsistent with this: there should be n=18 for male and female pups from the control group (based on n=6 control dams) and n=21 for the remaining experimental groups (based on n=7 dams). Furthermore, control females are n=24 which would mean 4 were culled per litter rather than 3. Can authors provide an explanation for this?

There are inconsistencies in reporting of data: Table 1 data is intake in g/day, therefore not normalised to body weight. However authors report taurine consumed in mg/g body weight/day (starting on line 214), which is normalised to body weight. Do the effects seen in Table 1 remain when body weight is entered into analyses as a covariate? Conversely, how are the estimated values for taurine consumption affected if not normalised to body weight? Authors should consider if it is appropriate to normalise these data to body weight.

Table 2 – organ weight is expressed as % of body weight. This seems inappropriate when there have been fluctuations in maternal body weight over the course of the study (e.g. CAFT dams were heavier pre-gestation, comparable during pregnancy, and then lighter during lactation). It is recommended these data are not expressed relative to body weight (as was done in their 2009 study).

On Figures 2 and 3 it would be helpful to indicate pre-gestation, gestation, and lactation.

Authors should check all figure legends explain what is meant by letters a/b/c (this information appears to be missing from figures 2, 3, and 4.
Experimental design: The research question and its relevance:

The relevance of the study in terms of its translatability is questionable. What is the rationale for giving taurine pre-pregnancy? Translating this in to human pregnancy would require obese women to take taurine supplements prior to conceiving, for which there would be inevitable issues with compliance. Women are more likely to take supplements once pregnant, therefore a more appropriate study would involve administering the taurine after mating. This point should be raised by authors in Discussion as a limitation of the study. Related to this, authors state that they aimed to examine whether taurine given with cafeteria diet during gestation and lactation exerts any protective effects. But, as mentioned, rats were given the diet +/- taurine for 8 weeks prior to mating. Therefore line 111 should be amended so that it reads ‘…examine whether taurine given with cafeteria diet prior to gestation, during gestation and lactation exerts any protective effects…’
In terms of protective effects, it is not clear what the authors expect taurine to protect against. In the abstract it is written: Maternal obesity may disrupt the developmental process of the fetus during gestation in rats. This study aimed to examine the effect of maternal cafeteria diet and/or taurine supplementation on maternal dietary intake (what is the rationale for this? Does taurine supplementation have the potential to affect appetite?), plasma metabolites, fetal growth and development. However, the design of the study has prevented a thorough assessment of fetal growth and development because most assessments were made at weaning rather than at the end of gestation. The cafeteria diet used in the current study is the same as first described by the same authors (Akyol et al) in 2009. In the 2009 study, fetal growth restriction was observed in the CAF-CAF diet. However, this phenotype was not reproduced in the current study. Authors fail to highlight in Discussion this discrepancy between their original study which observed growth restriction and their current study which did not observe any effect on birthweights.  Authors should draw comparisons where possible between the current findings and findings from the Akyol et al 2009 study in Discussion.

The aims of the study as outlined in the abstract and in Discussion (line 282) suggest that the focus is on fetal/offspring health, but a large proportion of the study relates to maternal metabolic health measured when pups were at weaning. It is unclear why this timepoint was chosen to assess maternal metabolic health. Can authors comment on the rationale and relevance to human pregnancy?
Validity of the findings: Authors refer to the cafeteria diet as a robust model of inducing dietary obesity in laboratory animals. But it is not confirmed if there was maternal obesity at the time of mating as a result of the cafeteria diet in their current study. CONT appear to be the heaviest at the time of mating (lines 224-225). Please can authors include a sentence that explicitly states if the cafeteria diet had led to obesity by the time of mating, thereby confirming this was a true model of maternal obesity.

How neonatal morbidity was calculated is unclear. Was it an average of litters? Was it relative to born litter size or relative to litter size after culling? Was it comparable across litters and between sexes, or was it skewed in any way? Can authors comment on how soon after birth the pups died? Did some die after culling to a maximum of 8 pups per litter? The answers to these questions are important for determining the validity of these data.
Additional comments: Minor comments:

Intro, lines 83-85. The sentence ‘The identification of obesity related complications during pregnancy and developing effective interventions as early as possible to prevent the development of obesity is vital’ does not make sense. How can an intervention prevent the development of obesity in an individual who is already obese? Do the authors mean to say development of complications?

Lines 109-100 state 'To date none of the studies have investigated the possible protective role of taurine within a maternal cafeteria diet model on pregnancy outcomes in rats'. However the Li et al 2013 study has, therefore this sentence should be removed or modified.

Authors should speculate in Discussion on how taurine supplementation could have exerted the positive effects (no maternal hyperleptinemia or increase in MDA) in the obese model if plasma taurine was not increased. Did authors make a direct comparison of plasma taurine between CAF and CAFT? The data suggest this is likely to show significantly higher taurine levels in CAFT.


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: EFFECTS OF MATERNAL TAURINE SUPPLEMENTATION ON MATERNAL DIETARY INTAKE, PLASMA METABOLITES AND FETAL GROWTH AND DEVELOPMENT IN CAFETERIA DIET FED RATS
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: Authors answer my questions and did appropiate corrections in the manuscript.

It is clear that new experiments should be carried out to understand the possible role of taurine on obesity


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: EFFECTS OF MATERNAL TAURINE SUPPLEMENTATION ON MATERNAL DIETARY INTAKE, PLASMA METABOLITES AND FETAL GROWTH AND DEVELOPMENT IN CAFETERIA DIET FED RATS
Review round: 2
Reviewer: 2

Output:
Basic reporting: Authors have thoroughly addressed all comments raised in my original review of this manuscript with the exception of the following minor point:
- Pre-gestation, gestation and lactation indicators need adding to Figure 3, as has been done for Figure 2.

Table 2 data is now presented as raw organ weight rather than as a % of body weight. For consistency, it is suggested that the data in Table 5 (offspring organ weight) is also presented as raw weight instead of as a % of body weight.
Experimental design: No comment.
Validity of the findings: No comment.
Additional comments: Thank you to the authors for thoroughly addressing all comments raised in my original review of this manuscript.


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

Input:
Title: NO SIGNIFICANT ASSOCIATION OF REPEATED MESSAGES WITH CHANGES IN HEALTH COMPLIANCE IN THE COVID-19 PANDEMIC: A REGISTERED REPORT ON THE EXTENDED PARALLEL PROCESS MODEL
Review round: 1
Reviewer: 1

Output:
Basic reporting: No comment
Experimental design: No comment.
Validity of the findings: No comment.
Additional comments: Yang et al. examined the effects of repetition on behavior intent to adhere to a health message, in the context of perceived threat and efficacy as operationalized in the EPP model. The authors performed SEM to extricate interactions between different variables on behavioral intent. Interestingly, they find no effect of either repetition or threat on behavioral intention. These null findings, in the context of the Covid19 pandemic, are important and worthy of highlighting. Why waste time and resources on repetition or, worse, inducing a negative state of mind (fear), if these efforts have no effect? My main criticism here is that these null findings are not highlighted enough.

Some minor issues:
1. Given there was a null finding concerning the repetition of the health message I recommend changing the title of the study.

2. Some confusion about lines 345-351. I think it is interesting to speculate on causes, but it may also be that threat is simply not an effective motivator relative to self or response efficacy. There must be considerable literature in this area.

3. Also, while you mention Tannenbaum et al.’s meta-analysis, it seems you omit their supporting result that repetition of fear message has no effect. https://psycnet.apa.org/doiLanding?doi=10.1037%2Fa0039729

4. In line 414, the tendency towards Typhoon Eye is a bit speculative as well, as those most effected by a tragedy may leave maladaptive responses –such as panic- for a later time, when the immediate danger subsides.

5. Finally, the manuscript is well written but I recommend a very thorough copy-edit to streamline the wording.


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: NO SIGNIFICANT ASSOCIATION OF REPEATED MESSAGES WITH CHANGES IN HEALTH COMPLIANCE IN THE COVID-19 PANDEMIC: A REGISTERED REPORT ON THE EXTENDED PARALLEL PROCESS MODEL
Review round: 1
Reviewer: 2

Output:
Basic reporting: a.	The authors tend to use “it” and “they” in reference to psychological constructs (like perceived threat on line 120). The authors should always label constructs instead of using pronouns so as to reduce confusion and aid reader comprehension.
b.	It is not clear what “(1.47%)” on line 24 is in reference to. I believe that the authors are trying to state the Japanese mortality rate, but I am not sure. It would be worthwhile for the authors to label this number more clearly for the readers.
c.	Lines 25-27 contain a confusingly worded sentence that ought to be revised, especially the phrase “achieved staged success.”
d.	The authors should include a citation in line 31 after they define “functional fear.”
e.	I cannot determine if line 38 should be revised so that it says “fear-appealing communication” or if “fear appealing communication” is the standard term from previous literature.
f.	Lines 43 – 46 report about the positive and the negative main effects of fear, but it is not clear what the terms “positive” and “negative” are in reference to. I felt like “positive main effect of fear on persuasion” may mean that fear increases persuasiveness, but positive and negative are too ambiguous of terms to know for sure. The authors should specifically report the results from the studies they’ve cited in lines 43 – 46 in order to aid reader comprehension.
g.	Line 47 contains the term “fear appeal,” but it seems to me that this should be revised to “fear-appealing communication.”
h.	Line 328 should be revised to say “When we applied this strategy the results showed . . .”
i.	The authors do a good job at highlighting the unique and specific contributions of their research.
j.	The authors do a good job of explaining the EPPM in the paragraph contained within lines 50 – 65.
k.	It is not clear if the authors mean to say that we are exposed to health proposals about COVID-19 multiple times per day or that people have been exposed to health proposals about COVID-19 at least once (lines 67-69).
l.	It is very helpful that the authors reported all results in reference to their stated hypotheses then discussed those results more specifically.
m.	I appreciated that the authors explicitly warned the reader about post-hoc exploratory analyses before discussing the results of those analyses (lines 295-302).
n.	The paragraphs between lines 337 – 357 provide an excellent set of explanations for the non-significant path between perceived threat and behavior intentions.
Experimental design: a.	The authors pose their hypotheses in lines 87 – 114 but then pose further hypotheses and/or research questions in lines 116 – 148. The authors may want to re-order the final part of their introduction so as to end with their hypotheses or label the final three paragraphs according to the research questions they include. At the moment, it feels as though the authors are posing additional research directions beyond the hypotheses they’ve already stated and I feel distracted from the important research hypotheses as I go into the next section.
b.	Lines 125 – 127 may be re-stating a hypothesis or may be posing a research question. The authors should either reference their hypothesis directly or explicitly pose a new research question.
c.	The authors do not explain why they chose to use the 24-72 hour delay between message exposures in this experiment. In light of their own discussion of previous research using different procedures (lines 364 – 373), it is necessary for the authors to explicitly defend their decision to use a 24-72 hour delay between message exposure for participants in this study instead of using previously successful procedures.
d.	The authors’ arguments for why they removed some participants prior to analyses are clear and sufficient.
e.	The authors do not report Cronbach’s alpha for their Risk Behavior Diagnosis Scale, but their reported analyses for convergent and discriminant validities are sufficient.
f.	The authors’ explanation for why they chose their particular message is clear and sufficient.
g.	The authors’ explanation for why they used their particular procedures is clear and sufficient.
h.	The authors report that Table 2 contains correlations among variables along with means and standard deviations, but values for means and standard deviations appear to be missing in Table 2. There is only one value per cell and I believe that these values are the correlations. The authors should make certain to add the means and standard deviations for each item or report them in a separate table.
Validity of the findings: a.	The authors do a good job of highlighting the important and relevant implications of their research.
b.	The authors suggest useful directions for future studies.
Additional comments: The authors have done a good job and I believe that this paper will be suitable after minor revisions.


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

Input:
Title: NO SIGNIFICANT ASSOCIATION OF REPEATED MESSAGES WITH CHANGES IN HEALTH COMPLIANCE IN THE COVID-19 PANDEMIC: A REGISTERED REPORT ON THE EXTENDED PARALLEL PROCESS MODEL
Review round: 1
Reviewer: 3

Output:
Basic reporting: OK, see General Comments
Experimental design: OK, see General Comments
Validity of the findings: Some issues, see General Comments
Additional comments: This is an interesting study, applying the EPPM in combination with a repetition of the behavior change message. Using the EPPM as well as introducing repetition within this framework are both commendable. I do have some issues with how the authors interpreted the EPPM and with their analyses. Those issues may be repairable.

The EPPM is a model predicting the effect of risk information on behavior, distinguishing between four predictors, combined in two predictors of intention. The way the authors present these four predictors in the hypotheses, as all having an independent influence on intention, is misleading. The essence of the all predictions of the EPPM lies in the interaction of those four concepts. For example, even if severity, susceptibility, response efficacy are positive and high, there would not be a behavior change when self-efficacy is low, et cetera. I think that it would help the reader when the authors or more explicit about the crucial role of the interaction among the predictors.

Related to that first issue, I cannot get a clear idea how the authors deal with these interactions in the SEM analysis. E.g. is perceived efficacy an outcome of the SEM or just the combination of those six questions?

The results are a nice demonstration of what the EPPM would predict: people don’t change as a result of threat or fear, but as a result of efficacy, especially self-efficacy, given that the threat is there anyway. The total lack of effect from repetition is obviously unexpected, but my interpretation is that the manipulation of repetition is rather weak.


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: NO SIGNIFICANT ASSOCIATION OF REPEATED MESSAGES WITH CHANGES IN HEALTH COMPLIANCE IN THE COVID-19 PANDEMIC: A REGISTERED REPORT ON THE EXTENDED PARALLEL PROCESS MODEL
Review round: 2
Reviewer: 1

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


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

Input:
Title: NO SIGNIFICANT ASSOCIATION OF REPEATED MESSAGES WITH CHANGES IN HEALTH COMPLIANCE IN THE COVID-19 PANDEMIC: A REGISTERED REPORT ON THE EXTENDED PARALLEL PROCESS MODEL
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors' revisions have adequately addressed all my concerns.
Experimental design: The authors' revisions have adequately satisfied all of my concerns.
Validity of the findings: The authors' revisions have adequately satisfied all of my concerns.
Additional comments: Thank you for your thoughtful and thorough revisions.


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

Input:
Title: NO SIGNIFICANT ASSOCIATION OF REPEATED MESSAGES WITH CHANGES IN HEALTH COMPLIANCE IN THE COVID-19 PANDEMIC: A REGISTERED REPORT ON THE EXTENDED PARALLEL PROCESS MODEL
Review round: 2
Reviewer: 3

Output:
Basic reporting: See general comments.
Experimental design: See general comments.
Validity of the findings: See general comments.
Additional comments: The authors have responded to my comments by repeating their earlier interpretation. That is fine with me, given that they explain carefully what they do and why.
There is one point that seems incorrect: “In any case, we prefer to think that threat has its own function even if not reflected in number because studies (Witte, 1992; Gore & Bracken, 2005) have shown that if individuals receive a no-threat and high-efficacy message, the message did not influence them, which is not predicted by the EPPM (380-382)”. I do not think that last remark is correct. There is more in life than threat, and if there were no other reason for behavior than no-threat, why would people do something? High self-efficacy alone is no reason for behavior.
We need research papers on COVID-19 preventive behaviors and we need them fast. Readers can check for themselves if they agree with the authors’ interpretation.


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: BITE FORCE ESTIMATES IN JUVENILE TYRANNOSAURUS REX BASED ON SIMULATED PUNCTURE MARKS
Review round: 1
Reviewer: 1

Output:
Basic reporting: Language is clear, and highly accessible: the authors even explain regression lines and confidence intervals in a caption. I suggest one additional reference (see "Validity of the findings).

The format can be improved slightly by distributing part of the discussion to the methods and results (lines 165-173). A brief take-home message about load rate sensitivity can be added to the discussion.
Experimental design: Excellent. It's unclear whether the printed cobalt model replicates denticles, which would presumably have an effect on the results.
Validity of the findings: Would denticles lower the necessary indentation forces? A discussion of the possibility is warranted.

Birds roll their heads vigorously with m. complexus and m. rectus capitis ventralis neck muscles, and broad-skulled T. rex would be notably good at it. A combination puppy dog tug-of-war and partial crocodilian death roll. Worth noting the possibility as a component of prey dismemberment by juvenile T. rex. A citation is suggested.
Additional comments: A refreshingly direct paper that will be influential for investigation of reptile feeding biomechanics. Interesting how Deinonychus and now juvenile T. rex show greater actualized bite forces than might be or have been expected from musculoskeletal simulations. It's intriguing to think about what we're missing in terms of muscle architecture and physiology.

Further comments and minor typo corrections are on the commented manuscript.


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

Input:
Title: BITE FORCE ESTIMATES IN JUVENILE TYRANNOSAURUS REX BASED ON SIMULATED PUNCTURE MARKS
Review round: 1
Reviewer: 2

Output:
Basic reporting: The article is well written, with very clear use of the English language throughout. The literature in general is well rounded, however I have suggested some additional references in the "Validity of Findings" section. The article is well structured, however the abstract is missing at least a "Discussion" section.
From a different perspective, the link found on line 135 presents a page stating "No media found".
A minor comment: the acronym MDA in line 53 has already been defined on line 46
Experimental design: I am very interested in the present study, and would even be interested in replicating some of the experiments myself, however I have some small concerns about certain elements of the experimental analogies presented. While I am sure that they can easily be cleared up, I think it is important that some additional details be presented so as to ensure the most transparent publication of results.

(1) The authors need to clarify how they know the bite marks observed (lines 73 - 75) are without a doubt attributable to Tyrannosaurus. While they cite previous studies that argued these marks to be product of this specific predator, the present text should also confirm this, even if through a simple summary of the previous studies in 3 or 4 lines. I personally struggle to see how bite marks from this time period can be confirmed to be product of a specific animal, so think the text would benefit from clarifying this point.

(2) The authors need to clarify why they used a cobalt chromium alloy. Is this material truly analogous with the hardness of enamel? I am not a dentist, and I doubt many readers would be as well, however I have worked with tooth marks. If any scientist would be interested in replicating these experiments, then some clarification on why the authors used this material is necessary. From my understanding, metal implants are used in dentistry because they are less susceptible to corrosion, but to what point is the use of metal going to be conditioning the results?

(3) In light of the previous point, the authors need to clarify throughout the text (especially in the abstract) that the material used was an alloy. The abstract simply states that cobalt was used, which is misleading. The use of the term "dental grade" may also be useful for clearing up some confusion as well.

(4) Information about whether the bone used in experiments had meat intact or not is missing. When we work with bite marks, we have to consider that these traces are accidentally produced, few animals go around purposefully leaving bite marks on bone. Tooth marks are created when the tooth eventually comes into contact with bone, and more often than not this is product of the animal eating. If meat is intact, this will surely cushion the impact of tooth to bone and effect the results. If the tooth mark was created directly on the bone without anything in between, this will surely distort results and overestimate the true force. Did the authors take this into consideration? If not, I think this is an important point to take into consideration in future research.

(5) the authors report mean force values, however do not appear to take into consideration the best practices of descriptive statistics (at least as the text reads). If the measurements are not normally distributed, and present outliers, then mean values are not the most reliable metrics to report. The authors should first check the nature of the distribution (e.g. via a Shapiro-Wilks test), and upon determining whether the distribution is Gaussian or not, either report the mean (for Gaussian) or median (for non-Gaussian) values. I also ask the authors to please report some measurement of deviation, for example the standard deviation (for Gaussian) or Median Absolute Deviation (for non-Gaussian) values. These steps are quite simple to take, and can be performed in base R using the shapiro.test( ), mean( ), median( ), sd( ), and mad( ) functions.
Validity of the findings: The study is very interesting, and as stated in previous sections I would be very interested in looking into replicating these experiments with my own samples. The discussion of the paper presents a wide array of different observations that are welcoming and insightful.

My only "query" or comment is that I'm not sure about the use of the term "puncture" in some cases. Especially in the case of the marks observed on the vertebra. In taphonomic analyses of Pleistocene and some Holocene sites, I would argue that the marks found on the vertebra of Fig. 2 are actually pits, not punctures. However this may be due to my lack of knowledge on pre-Pleistocene tooth mark analyses. Nevertheless, the majority of terminology describes a puncture to be a mark where the tooth directly penetrates the cortical surface, leaving more of a hole than an indentation. When the tooth does not penetrate the surface, but instead simply leaves an indentation, this is referred to as a tooth pit. This observation is based on the terminology presented by the following authors;

Binford, L.R. (1981) Bones: Ancient Men and Modern Myths. New York: Academic Press Inc.

Haynes, G. (1983) A guide for differentiating mammalian carnivore taxa responsible for gnaw damage to herbivore limb bones, Paleobiology. 9(2):164-172

Fernández-Jalvo, Y.; Andrews, P. (2016) Atlas of Taphonomic Identifications. The Netherlands: Springer.
Additional comments: No further comments


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

Input:
Title: BITE FORCE ESTIMATES IN JUVENILE TYRANNOSAURUS REX BASED ON SIMULATED PUNCTURE MARKS
Review round: 1
Reviewer: 3

Output:
Basic reporting: This manuscript calculates potential bite force in juvenile Tyrannosaurus rex by simulating known bite marks using mechanical indentation simulations. While bite force has been estimated across ontogeny within this group, previous studies have used alternate methods. The results presented here are slightly higher than the bite forces presented in the prior literature, and the authors frame their findings in terms of ecological niche partitioning across ontogenetic stages of the species.

The figures and table are all well-structured and presented, and all are critical to fully communicating the results of the study. The length is appropriate as well, and the quality of the writing is high. The only major omission of prior literature I noticed is probably related to its very recent publication. I think a discussion of its findings would strengthen the results:

Schroeder, Katlin, S. Kathleen Lyons, and Felisa A. Smith. "The influence of juvenile dinosaurs on community structure and diversity." Science 371.6532 (2021): 941-944.

(I also have a paper in press discussing similar eco-ontogenetic patterns in crocodyliforms coming out some time this month. I’d be happy to share it if the authors would like another point of comparison when discussing dietary niche transitions during growth and development.)

The general concept of the study is solid, with a few omissions I will discuss in more detail below. I think that a small amount of reorganization might provide clarity though. For example, the specific measurements of the tooth marks in the introduction (line 58) seem like details that should fall within the materials and methods. In the methods, only one speed of the indentations was mentioned (line 105), but in the discussion, multiple speeds are referenced (line 167). The varying speeds and why they were selection should be addressed in the methods. Similarly, the authors’ reasoning behind inclusion or exclusion of specific simulation runs is covered in the discussion (line 188), which seems like a subject that should be in the methods (such as near line 112). Many of the questions I had while reading would be cleared up with this slight restructuring.
Experimental design: This study largely follows the methods outlined in the Gignac et al (2010) paper. I did have a few questions about the experimental design that I think should be addressed in the text. Are there concerns that the structural integrity of the two bones were affected in later runs by breakage that occurred in earlier runs? Why were more bones/runs not used, especially in the higher speed indentations, whose n values are particularly low? Are the 17 runs presented in the Table the total number of simulations, or was there a first pass to remove runs where obvious movement of the specimen fouled the data? Could the authors include some kind of notation in Table 1 to show which were used in the total regression vs. the one that excluded incidences of breakage?

Also, in Figure 6, and the related sections of the results and discussion, what are the formulae of the regression lines? The results really need some metric of significance or goodness-of-fit of the regression line to the datapoints. The original paper by Gignac et al (2010) reports a linear formula and an R2 value for its regressions, both of which should be reported somewhere around line 120 and in the associated figure. The formula is mentioned in line 127, but I can’t find the actual results in the text. Also, starting on line 128, which of those results come from which of the two regressions’ formulae? Are they being averaged together? Perhaps reports both sets of predicted results and explicitly state which regression and formula were used in each.

In line 184, the authors are discussing some of their specific run results, but mention that the data are not shown. Why are they not shared? Perhaps exemplar graphs could be included, and then all of the runs appended to the manuscript for maximum transparency.
Validity of the findings: The results drawn from these simulations seem to align with previous estimates (though these are a little higher than those previously reported), but it is difficult to fully assess the validity of the results without the regression formulae and R2 values themselves.
Additional comments: I only a have a few, exceedingly minor comments that do not fit in the previous sections.

Does the company that provided the bones need to be named in the paper on line 97, or could they be placed in the acknowledgements? Also, I think that the hyphen needs to be removed from “in-tact”.

A quick skim through the citations revealed a couple of small typos: 1) Capitalize Eocene in line 308. Capitalize H in McHugh in line 327. The D in Deinonychus isn’t italicized in line 365.


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: AIR POLLUTANTS AND OUTPATIENT VISITS FOR INFLUENZA-LIKE ILLNESS IN BEIJING, CHINA
Review round: 1
Reviewer: 1

Output:
Basic reporting: More literature review is needed, especially for the scenario of doing this analysis.
Experimental design: One concern of this study was including only one hospital in the analysis, which might lead to selection bias.

Another issue is blured in this manuscript, on the one hand, the authors claimed that they want to examine whether air polluction can contribute to the transmission of enfluenza, on the other hand, the analysis actually examined the association between daily air pollution and outpatients for enfluenza. In some extent, this can be two different study questions.
Validity of the findings: The observed negative association on some lag days during some special period needed caution to make any conclusion. This can be due to the data quality, for example only one hospital data were used, and adjustment of potential confounding factors.
Additional comments: Is it possible to include more hospitals for the analysis to make the analysis more robust.


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: AIR POLLUTANTS AND OUTPATIENT VISITS FOR INFLUENZA-LIKE ILLNESS IN BEIJING, CHINA
Review round: 1
Reviewer: 2

Output:
Basic reporting: •	Criteria
o	Clear, unambiguous, professional English language used throughout.
o	Intro & background to show context. Literature well referenced & relevant.
o	Structure conforms to PeerJ standards, discipline norm, or improved for clarity.
o	Figures are relevant, high quality, well labelled & described.
o	Raw data supplied (see PeerJ policy).
•	Comments
o	The structure conforms to PeerJ standards and is logically organized.
o	The background can be strengthened by providing further rationale for the examination of the association between air pollution and influenza-like illness.
o	The figures are mostly high quality but can be better labelled and captioned. Some data which would benefit the audience should be added (please see detailed comments below).
o	Please review and revise work for irregularities in grammar and sentence structure.
o	Unsure if raw data have been provided in the submission.
Experimental design: •	Criteria
o	Original primary research within Scope of the journal.
o	Research question well defined, relevant & meaningful. It is stated how the research fills an identified knowledge gap.
o	Rigorous investigation performed to a high technical & ethical standard.
o	Methods described with sufficient detail & information to replicate.
•	Comments
o	Original primary research using administrative hospital data and environmental data.
o	The research can have meaningful knowledge and policy implications; however, it is more preliminary or exploratory than explanatory.
o	The authors are asked to specify or justify several methodological choices, such as the selected setting and time period for data extraction, the lag times, using single-pollutant model rather than a multi-pollutant. Further details are required to assess appropriateness of methods.
o	The methods are described with sufficient detail to replicate.
Validity of the findings: •	Criteria
o	Impact and novelty not assessed. Negative/inconclusive results accepted. Meaningful replication encouraged where rationale & benefit to literature is clearly stated.
o	All underlying data have been provided; they are robust, statistically sound, & controlled.
o	Speculation is welcome, but should be identified as such.
o	Conclusions are well stated, linked to original research question & limited to supporting results.
•	Comments
o	Similar studies have been conducted previously, as noted in the introduction and discussion, so the study is not entirely novel. However, the findings of different effects during the outbreak and non-outbreak seasons are of interest.
o	The reported results are statistically significant. However, non-significant results should also be reported when relevant to the research question (for example, at different lag times).
o	Conclusions are clearly stated and linked to the original research question.
Additional comments: 1.	Lines 57 and 58. Please express “less than” or “greater than” using words instead of the symbols. As well, please reword the sentence to clarify the DALYs; currently, it states PM exposure causes over 100 million DALYs, but I believe the authors mean that PM exposure causes a loss of over 100 million DALYs.

2.	Line 59. Please correct exposured to exposed.

3.	Line 60. Please correct the sentence to “high risks to their health” or “high health risks”.

4.	To strengthen the background, please clarify the explanation of why PM2.5 concentrations might be associated with or increase the risk of exposure to influenza. What is the hypothesized underlying pathway from exposure to disease? Further, on Line 79, the authors state it is necessary to confirm the effects of influenza outbreaks on ILI outpatient visits. I believe it is important to clarify and close the paragraph with the main research question (effect of PM concentration on ILI). The last sentence is succinct and clear.

5.	Lines 87 and 88. Why was this hospital and these dates chosen in particular?

6.	Line 89. As above, please use “less than 15 years old”.

7.	Lines 102 and 103. What constituted an outbreak period versus a non-outbreak period in this study?

8.	Line 111. Why might including dummy variables for days of the week help control for confounders? More broadly, how did the authors choose the co-variates in their model?

9.	Lines 112 to 113. Why did the authors choose the previous five days to control for lag effects?

10.	Line 134. What is meant by “gross pollution” here?

11.	Line 147. Why did the authors choose to use only a single-pollutant model and not a multi-pollutant model? Also, please consider including this information in the methods section.

12.	For Figure 3, please clarify the differences between the plots A and B, between plots C and D, and so on. The axes and exposure for each pair are the same, so it is unclear how the two plots differ. Would it be possible to also report the point estimates, CIs, and p-values in a table, so that exact estimates are available for readers?

13.	Line 175. Please clarify what is meant by “on the whole”.

14.	Line 200. It may be more clear to state that the exposure is associated with an increase in risk of the outcome, rather than vice versa.

15.	Line 209. Please clarify what is meant by “population specificities” and “a component of the complicated mixture”.

16.	Lines 214 and 217. Did any of the lag times used in previous studies inform your study methods and choice of lag time? Why or why not? This question is similar to point #9 about why one to five days was chosen. The authors note that an Australian study used ten days.

17.	Line 222. Interesting hypothesized mechanism. The authors suggest that the use of face masks is a mediator for the effect of air pollutants on ILI (good air quality -> less mask use -> higher ILI transmission)

18.	Line 229. Please express symbols such as > in words.

19.	Lines 241 to 244. The authors explain why children and elderly individuals might have lower exposure to air pollutants during an outbreak compared to middle-aged adults, but they do not explain why the association with ILI cases is less pronounced.

20.	The limitations paragraph includes important limitations but is short/not comprehensive. Another potential limitation is that the study uses an ecological design, which may limit the ability to control for potentially relevant confounders, such as individual-level demographic or socio-economic factors.

21.	The authors should also discuss suggestions for future research at the end of the discussion.

22.	Table 3. Why did the authors exclude the RRs for Lag3, 4 and 5?

23.	Figure 1. Please consider labelling the axes completely.


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: AIR POLLUTANTS AND OUTPATIENT VISITS FOR INFLUENZA-LIKE ILLNESS IN BEIJING, CHINA
Review round: 2
Reviewer: 1

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


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

Input:
Title: OPTIMIZED NITROGEN FERTILIZER APPLICATION STRATEGIES UNDER SUPPLEMENTARY IRRIGATION IMPROVED WINTER WHEAT (TRITICUM AESTIVUM L.) YIELD AND GRAIN PROTEIN YIELD
Review round: 1
Reviewer: 1

Output:
Basic reporting: English should improve by native person. Literature is ok. Hypothesis is OK.
Experimental design: Original primary research is within Aims and Scope of the journal.Research question is well defined.Methods are described with sufficient detail & information to replicate.
Validity of the findings: All underlying data have been provided; they are robust, statistically sound, & controlled.

Conclusions are well stated, linked to original research question & limited to supporting results.
Additional comments: English should improve by a native person. The paper suffers from a poor English structure throughout and cannot be published or reviewed properly in the current format. The manuscript requires a thorough proofread by a native person whose first language is English. The instances of the problem are numerous and this reviewer cannot individually mention them. It is the responsibility of the author(s) to present their work in an acceptable format. Unless the paper is in a reasonable format, it should not have been submitted.
2.    The novelty of the study needs to be highlighted compare to other similar studies.
3.    Discussion is weak. The discussion needs enhancement with real explanations not only agreements and disagreements. Authors should improve it by the demonstration of biochemical/physiological causes of obtained results. Instead of just justifying results, results should be interpreted, explained to appropriately elaborate inferences. Discussion seems to be poor, didn't give good explanations of the results obtained. I think that it must be really improved. Where possible please discuss potential mechanisms behind your observations. You should also expand the links with prior publications in the area, but try to be careful to not over-reach. For the latter, you should highlight potential areas of future study.
4.    The scientific background of the topic is poor. In "Introduction" and "Discussion", the authors should cite recent references between 2016-2020 from JCR journals (with impact factor) about recent achievements.
5.    A detailed "Conclusion" should be provided to state the final result that the authors have reached. Please note you only need to place your conclusion and not keep putting results, because these have already been presented in the manuscript.


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

Input:
Title: OPTIMIZED NITROGEN FERTILIZER APPLICATION STRATEGIES UNDER SUPPLEMENTARY IRRIGATION IMPROVED WINTER WHEAT (TRITICUM AESTIVUM L.) YIELD AND GRAIN PROTEIN YIELD
Review round: 1
Reviewer: 2

Output:
Basic reporting: Clear and unambiguous, professional English used throughout.
Literature references, sufficient field background provided.
Experimental design: This experiment is designed well, the data statistical analysis is ample.
Validity of the findings: All underlying data have been provided, they are robust, statistically sound.
The results are of great interest to the relative readers such as agronomy researchers, field management farmers.
Additional comments: The present MS reported that the results of field experiment conducted with five treatments including different nitrogen fertilizer rates under supplementary irrigation mode to examine the effects of split nitrogen application on grain and protein yields by improving nitrogen translocation, metabolic enzyme activity and grain nitrogen accumulation. The results showed that the use of split nitrogen fertilizer application at a ratio of 50%:50% basal-topdressing significantly increased nitrogen accumulation post-anthesis and nitrogen translocation to grains, increased flag leaves free amino acid levels, activity of nitrate reductase and glutamine synthetase, accumulation rate, active accumulation period, accumulation of 1000-grain nitrogen. The results of this research highlighted the important of this nitrogen application mode on improving grain yield and nitrogen yield together. The present reports add new information relative to their previous reports. Generally, this experiment is designed well, the data statistical analysis is ample, and its results are of great interest to the relative readers such as agronomy researchers, field management farmers. Thus, the paper is of worth to be published in the journal. However, a minor revision may be needed before it can be accepted.

1. I support to change the title to “Optimized nitrogen fertilizer application strategies under supplementary irrigation improved winter wheat (Triticum aestivum L.) yield and grain protein yield”.
2. Please introduce this variety, such as type, planting area, growth duration, general yield, and so on.
3. For the fertilizer application period, it will be better to make it more accurate, such as days after sowing.
4. Please, add more information about the climate for this region.
5. Line 183, please add the detail of this reference “zhang et al.,”
6. “2.3.2. N-metabolizing enzymes”, the measurements of NR and GS should be in different paragraphs.

Figure
Figure 1: I support “percipitation 2016-2017” should be changed to “2016-2017”, “precipitation 2017-2018” should be changed to “2017-2018”.
Table4: the legend of the color is confusing, meanwhile, the values on blue colors are negative, please check again.


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: OPTIMIZED NITROGEN FERTILIZER APPLICATION STRATEGIES UNDER SUPPLEMENTARY IRRIGATION IMPROVED WINTER WHEAT (TRITICUM AESTIVUM L.) YIELD AND GRAIN PROTEIN YIELD
Review round: 1
Reviewer: 3

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: A two-year field experiment was carried out to investigate optimization of the basal-top-dressing nitrogen ratio for improving winter wheat grain yield and protein yield. The topic is interesting and the findings can provide some new information for the assessment of winter wheat production. At the present pattern, however, there are some minor limitations need to be deal with before publishing.
Line 55-77, it is better to put these two paragraphs together in one paragraph.
Line 94, “covered an of was” should change into “covered area was”.
Line134, these formulas need add to the reference.
Line 183, “zhang et al” should add the published year.
Line 187, “DAA” should be “Days after anthesis (DAA)”, and then used the abbreviation.
Lines 245, "and there no" should be revised into “and there was no”.
Lines 257, deleted “an”.
Line 300, The authors used many abbreviations, which reduced the readability of the manuscript. I would recommend the abbreviations already accepted by the research community.
Figure 1, “Preciptation” should be “Precipitation”.
Figure 4, “Kg/ha” should be “kg/ha”.
Table 3, “R2” should be revised
Check the grammars throughout the whole text to make all the sentences clearer.


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: NICOTINE SMOKING IS ASSOCIATED WITH IMPAIRED COGNITIVE PERFORMANCE IN PAKISTANI YOUNG PEOPLE
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript is reasonably written and reads well. However, the literature review does not satisfactorily align with the topic. There are concerns about some of the articles cited to support the narrative in the manuscript. For example, line 110-112: the cited reference (Bueno, A., Carvalho, F. B., Gutierres, J. M., Lhamas, C., & Andrade, C. M.) refers to the effects of anabolic androgenic  steroids (not nicotine) on memory, anxiety, social interaction, acetylcholinestrase activity and oxidative stress in rats. This does not appear to be an appropriate citation for the point raised by the authors. The discussion fails to capture the current understanding on the cognitive enhancing effects of nicotine. Given that this is a controversial topic (cognitive enhancing effects of nicotine),it would be useful to briefly outline both sides of the argument. Furthermore, there is now evidence that the cognitive enhancing effects of nicotine differ on whether nicotine administration is acute or nonacute. (Heishman SJ, Kleykamp BA, Singleton EG. Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology (Berl). 2010;210(4):453–469)
Experimental design: The methods are reasonably described. However, in describing the study procedures, important details are left out. For example, were the smokers deprived or allowed to smoke up to and including the time of testing? It is not clear why only males were included in the study.  Sampling has not been described and it is unclear how participants were selected. Additionally, a description of the study settings is not adequately provided. The authors report that the study was conducted in the department of zoology at the University of Gujrat without highlighting relevance given than this is a human subjects study.
Validity of the findings: The conclusion appears not to be linked with the results. The study was conducted among male participants and the conclusion should reflect this and not generalize to young adults as presented in the conclusion section.
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: NICOTINE SMOKING IS ASSOCIATED WITH IMPAIRED COGNITIVE PERFORMANCE IN PAKISTANI YOUNG PEOPLE
Review round: 1
Reviewer: 2

Output:
Basic reporting: References cited in text are, in majority of instances, not matching the sentence they are cited in.
More detailed comments are provided below in General comments.
Experimental design: Authors need to precisely identify and state the knowledge gap and how this research fills that gap.
Methods are not described with sufficient detail (especially how sample was chosen, how investigated scores were calculated etc.).
Authors need to clarify certain ethical considerations.
More detailed comments are provided below in General comments.
Validity of the findings: Almost no demographic data are provided, either in the text of the manuscript or in the provided underlying data. Authors mentioned how they chose the groups so that they do not differ, e.g. in socioeconomic status - but failed to present this anywhere.
Conclusion and implications need to be rephrased in order to be limited to supporting results.
More detailed comments are provided below in General comments.
Additional comments: Line 75: Authors should consider rephrasing the first sentence so that it is more appropriate for a scientific manuscript.
Lines 75-76: The cited references are completely unrelated to the sentence where they are cited - Singh et al. study electronic cigarettes use and Xu et al. study ADHD trends. Please find an appropriate reference and cite it here.
Lines 76-77: Please check whether this information is provided in the cited reference.
Lines 77-78: Again, authors need to check whether this sentence is supported by the cited reference.
Lines 78-81: Please consult the WHO's Report on Global Tobacco Epidemic and cite the appropriate reference.
Line 79: Not just in developed countries, and authors state "more than 5 million deaths per year" globally - shouldn't it be more than 8 million deaths? Please use the most recent data throughout the paper.
General comment: Throughout the entire manuscript, authors need to double check and verify that they have appropriately used and cited the references in the appropriate place in the text, since there are many instances of the opposite being the case.
Line 91: Please add years, you have cited two papers by Benowitz in the list of references - which one is cited here?
Lines 92-94: Please add the appropriate reference.
Overall, it was difficult to check authors' claims since references cited in the text were in most cases completely unrelated to the sentence they are cited in.
Lines 115-116: Authors have cited one study, not studies. Further on, the authors need to specify the population which was included in the cited study.
Introduction: This section needs to give a better and more comprehensive overview on the current body of evidence in this area - description of previous studies and their findings is lacking. This is necessary for the authors to give an adequate explanation of the gap in knowledge their study is trying to address.
Introduction: Describe findings of previous similar studies by sex, to provide a rationale for including only males in the present study.
Line 123: Authors should finish the introduction with a description of the aim or aims of their study.
Lines 127-129: Describe the study population from which the sample is drawn. Specify inclusion and inclusion criteria. How were people recruited for this study?
Lines 129-130: How was a complete clinical history obtained? If a self-reported questionnaire was used - please attach an English version. If medical records of participants were checked to either verify or obtain this information - please state this.
Lines 130-131: Were there no further considerations regarding smokers, in terms of the intensity of smoking?
Lines 131-132: Please clarify what was considered as "never smoked regularly" among the participants in the non-smokers group - does this mean that some of the participants in the "nonsmokers" group could have smoked cigarettes too just not "regularly"?
Lines 133-134: How was the presence of these addictions determined?
Subjects: The study sample description is incomplete. How was the study sample size arrived at? Were groups of 50 smokers and 50 non-smokers large enough to detect a significant difference between them?
Line 138: Did the Institutional Review Board approve the waiver of written consent?
Lines 138-140: Please clarify the ethical considerations - currently, as this text reads, it is not clear whether the ethical approval was received prior to study's beginning?
Line 146: Readers of this article might benefit from a brief description of the CANTAB testing process.
Methods: Add explanations for the scoring of all used tests. For example, authors mention raw and standard score for PRM - this, as well as the scoring for other used tests needs to be explained and supported with appropriate references.
Lines 169-170: Please clarify how were clinical histories collected using the MMSE?
Lines 168-174: Table 1 needs to be cited in this paragraph. But more importantly, Table 1 is supposed to display demographic characteristics of participants - but only provides their sex (when the whole sample is compiled by males?) and age. Table 1 needs to be completely revised and detailed information of participants added to it. This way authors will display whether there really were no differences between the two groups other than their smoking status. Also, smoking habit of the smoking group needs to be presented in detail - was data collected on the smoking start age, duration of smoking, smoking intensity etc.?
Table 2: Indicate used test and p value at which significance was considered in the Table's footnote.
Lines 197-202: None of these studies included young adults - please expand this section by adding comparable studies in terms of the studied population.
Lines 207-209: How was socioeconomic status defined (what did it encompass) and how was it assessed in this study?
Lines 219-222: Results of the present and cited study are not completely similar. Namely, Meo et al. found statistically significantly higher CRT-% in the group of shisha smokers, while the present study found a significantly higher CRT-% in the group of non-smokers. Authors need to discuss these differences. They state in lines 222-223 that he subjects between these two studies differed - please give detail about these differences, since the other study included young men - what were the subjects differences which are mentioned here?
Lines 223-224: Is this sentence really appropriate, since authors have discussed a similar study in the same paragraph, even in previous sentences, a study which also demonstrated he cognitive effect of nicotine smoking using CRT parameters?
Lines 233-234: There are numerous limitations of this study, none of which have been explicitly stated here. Authors should go back to some of the comments given in the section methods, and address those appropriately and if not - add the demonstrated issues to the section limitations.
Lines 237-242: Please limit the conclusion to the findings of the present study and implications for practice based on the results of this study, particularly consider rephrasing the last two sentences so that they specifically correspond to the findings of this study, instead of being a general claim.


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

Input:
Title: NICOTINE SMOKING IS ASSOCIATED WITH IMPAIRED COGNITIVE PERFORMANCE IN PAKISTANI YOUNG PEOPLE
Review round: 2
Reviewer: 1

Output:
Basic reporting: Satisfactory
Experimental design: Acceptable
Validity of the findings: Acceptable
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: NICOTINE SMOKING IS ASSOCIATED WITH IMPAIRED COGNITIVE PERFORMANCE IN PAKISTANI YOUNG PEOPLE
Review round: 2
Reviewer: 2

Output:
Basic reporting: Please see comments below.
Experimental design: Please see comments below.
Validity of the findings: Please see comments below.
Additional comments: Thank you for the opportunity to review a revised version of this manuscript. The authors have made many changes and improved the manuscript. However, some questions still need to be addressed.

Lines 231-234: Please provide a reference for the better performance of CANTAB compared to other tests, which is mentioned here.
Aim in the section Introduction: If the intention when planning the study was to include only males, then please revise "Pakistani population" with a more specific description of the studied population.
In addition to the previous comment and in light of revisions made in the Methods section and Discussion, please consider clarifying whether study was planned from the beginning to be conducted only with males, or were there no such limitations but later it proved hard to recruit female participants? Since the questionnaire authors included in the rebuttal letter asked participants about gender, it seems they planned to include females too. Therefore, this needs to be stated as a limitation.
Lines 291-295: If interviewers used questionnaires based on which they collected data from participants face-to-face, please clarify that here when mentioning self-report and interview. Authors mention a questionnaire in their rebuttal letter, and they state they included a questionnaire - but this questionnaire does not cover any of the variables investigated here other than name, gender, age, education, economic status, employment and marital status.
Authors did not respond whether they looked further into the intensity of smoking, instead in their rebuttal letter they repeated the definition of smoking which they used. The question remains - were there no further analyses for smokers who smoked 5 cigarettes a day during the last year and smokers who, e.g., smoked 40 cigarettes a day? It needs to be noted as a limitation of this study if authors did not investigate the age when participants started smoking, duration and intensity of smoking.
In their rebuttal letter, authors state that non-smokers "Nonsmokers (the control group) had never smoked a cigarette in last 30 days." - please use the same definition in the manuscript. Was the same or similar definition used in similar articles? Not in cited paper by Xia et al. for example. What's the rationale behind this definition?
Rebuttal letter includes a response regarding sample size - but this was not incorporated in the manuscript. Were any calculations done based on the cited references of other studies?
Line 297: Please specify that each group consisted of 50 participants, so that it's clear that the entire sample comprised 100 participants.
Finally, please perform a final grammar and spelling check - for example there are instances of words like "Chines" etc.


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: NICOTINE SMOKING IS ASSOCIATED WITH IMPAIRED COGNITIVE PERFORMANCE IN PAKISTANI YOUNG PEOPLE
Review round: 3
Reviewer: 1

Output:
Basic reporting: Please see below.
Experimental design: Please see below.
Validity of the findings: Please see below.
Additional comments: Through the changes they made, authors have made their manuscript more coherent and clear.

English language of the text has been improved, but the authors should recheck the newly added sentences for the last revision, as there are a few instances of missing words (e.g. Lines 260-264), or for example - Line 140 - prevalence is higher not "more".

Important note: Please consider rephrasing the newly added sentence in section Limitations at Line 273 - so that it matches the text given in the Methods section in Lines 139-140 (the Methods text states your inability to include women in this study and the word unable should be underlined in Limitations too).


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: RELIABILITY OF HIP MUSCLE STRENGTH MEASURED IN PRINCIPAL AND INTERMEDIATE PLANES OF MOVEMENT
Review round: 1
Reviewer: 1

Output:
Basic reporting: This article meets basic reporting standards, apart from an apparent error between the images and caption of figure 2, which is highlighted in the specific comments to the authors below.
Experimental design: The experimental design standards have been adequately met.
Validity of the findings: Findings appear to be valid and clearly reported to a high standard.
Additional comments: •	Introduction
o	Lines 39-40: please clarify the aspects of athletic performance you are referring to (e.g. sprint performance, jump height etc.)

•	Methods
o	Lines 87-88: please clarify if the exclusion criteria of having prior hip surgery is just within the last three months or lifetime history, as it currently isn’t absolutely clear
o	Line 92: please clarify the rationale for allowing participants to complete their follow-up testing session within a range of 3 to 9 days after the initial session. There is potential that any muscle soreness resulting from the first session could still be present 3 days post the first, but this is unlikely at 9 days. Not a major criticism, but it needs to be addressed here in my opinion
o	Line 94: should the cycle ergometer resistance be reported in Watts rather than Newtons?
o	Line 96: please report the sample rate of the uniaxial load-cell in Hz
o	Line 102: please clarify if the submaximal familiarisation contractions were standardised (e.g. 50% of maximal effort) or was no instruction given apart from being sub-maximal?
o	Lines 112-114: please clarify why combined hip abduction and external rotation was not assessed? The response doesn’t need to be included in the paper, but I am curious as to why this combination was not included, given it is open prescribed as an exercise for people with hip pathology
o	Lines 128-130: please clarify if and how the strap position was standardised relevant to the distal shank (e.g. proximity to the malleoli) and thigh (e.g. proximity to the femoral condyles) as this has important implications for the subsequent torque calculation
o	Figure 2: the captions provided do not appear to match the lettering sequence of images in the figure. For example, the caption reads that A indicated hip abduction/adduction measures, but the images appear to be showing hip extension, which is references as C in the caption. Please correct this apparent error
o	Figure 2: the image of hip extension using the custom rig appears to show the line of pull of the load cell and in-series elements to be very different to what would be expected to be generated by the movement of hip extension. Please clarify if this is the actual position of testing, as this would likely result in the knee flexors being a large contributor. If this image is not truly reflective of the testing setup, please correct and take another image

•	Discussion
o	Lines 274-277: consider citing Askling et al. who used a similar position to your hip extension custom rig setup but to measure knee flexion with an externally fixed load cell https://pubmed.ncbi.nlm.nih.gov/16371489/ This is an important point you correctly mention, as it is likely the custom rig setup was more an assessment of hamstring strength compared to short hip extensor muscle (e.g. glue max, adductor magnus) strength
o	Line 289-290: consider citing Hickey et al. as an example of a study demonstrating the reliability of assessing knee flexor strength using load cells externally fixed to a squat rack https://pubmed.ncbi.nlm.nih.gov/29073840/


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: RELIABILITY OF HIP MUSCLE STRENGTH MEASURED IN PRINCIPAL AND INTERMEDIATE PLANES OF MOVEMENT
Review round: 1
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: Overall:
The current study assesses the reliability and validity of a custom dynamometer rig in customary planes and ‘intermediate’ planes. The manuscript is well written and provides thoughtful justification and discussion for exploring intermediate planes. I have a few suggestions for improvement listed below.
General comment:
The terms ‘planes’ and ‘directions’ are used interchangeably (e.g. line 54 & 73). Suggest chose one term (either planes or directions) and use throughout.
 Specific comments:
Introduction
Line 54 – the second part of this sentence require references for these statements made: “tasks performed in intermediate plates generate the highest levels of activation” and “testing strength in directions outside of principal planes is necessary to fully…”
Line 59 – suggest replace the word ‘Normalising’ with another to avoid confusion since normalize is usually used in regards to adjusting force measures on a dynamometer to a participants height and or weight.
Line 68 – not sure what ‘this’ refers to – the antecedent that the pronoun refers to is not clear, please revise.
Line 69 – ‘combined actions’ and ‘function’ is slightly vague and can be specified by replacing with ‘force’ and ‘strength’. Please consider this or revising to clarify.
Line 71 – ‘other devices’ is vague – please replace with a specific set of technology, like HHD? Or remove.
Line 73 – Suggest instead of giving an example of an intermediate plane, define what you mean by intermediate plane… this term needs an operational definition somewhere in the introduction.
Line 76 – It is not clear how the term ‘absolute’ is different from maximum… please describe the meaning of absolute here, or revise.
Line 80-82 – The last sentence of the introduction is not related to the hypotheses, instead it is more of a discussion item. Suggest moving to the Discussion section.
Methods
Line 90 – Twenty participants meet the minimum sample size requirement for ICC as reported by Walter, et al. STATISTICS IN MEDICINE, VOL. 17, 101-110 (1998), mentioning this would increase the internal validity of the study.
Line 147 – Suggest moving the sentence that starts on this line to the procedures section
Line 155 – The word ‘relative’ seems unnecessary, suggest remove.
Line 165 – since torque is force multiplied by a constant (moment arm length), why analyze reliability with both? It seems redundant. Please add justification for this or revise to only assess force or torque.
Line 168 – equation may be missing a parenthesis between MDD and x100
Results
Line 191-194 – It is difficult to understand the results of Bland Altman plots clearly with variables in parentheses. Suggest explicitly state the results, rather than using parentheses to imply.
Discussion
Line 212-215 – Suggest revising this sentence to remove repetition of results.
Line 233 – A potential discussion point would be to compare the intra-session ICC reported by Aramaki et al., 2016 to the intra-session ICC of this study… since more than two repetitions were collected, an intra-session ICC can be calculated, and would provide a better comparison between the current study and previous literature.
Line 264 – This sentence mentions that multiple studies report large discrepancies between force measured using a HHD and MDD – however only one study was cited. Please provide additional citations or revise sentence to remove plural.


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: RELIABILITY OF HIP MUSCLE STRENGTH MEASURED IN PRINCIPAL AND INTERMEDIATE PLANES OF MOVEMENT
Review round: 1
Reviewer: 3

Output:
Basic reporting: Article is missing multiple references that would improve the quality of the manuscript.

Article does not provide adequate rationale for the need for the study, specifically the multiplanar measures.

At times the manuscript reaches in its conclusions.
Experimental design: Methods in some places could use more clear and thorough explanations.

Not clear about the knowledge gap that the research fills.

Not clear if it followed established reliability study guidelines.
Validity of the findings: Multiple comparisons not completed due to methods being different in one test versus another. Assume that the agreement would have been very poor with these results included.

Speculation is at times taken too far towards a clinical population.
Additional comments: The purpose of this study was to evaluate the inter-session reliability of hip strength tested in the cardinal and intermediate planes using a load cell and Biodex. The use of a load cell has not received extensive research in hip strength testing so this is an important topic due to certain limitations of HHD. The manuscript is generally well written. However, there are a number of concerns that the authors should address prior to the manuscript being considered for publication.

General Comments:

One of the biggest criticisms of this paper was that the need to test hip strength in these intermediate planes was not well argued. Lines 67-70 do not provide a convincing argument as to why strength needs to be measured in a multi-planar manner. Measuring strength in this fashion does not allow a clinician to target certain muscles and therefore, all hip muscles would need to be targeted. Testing multiple muscles takes more time and effort but provides more specific information. This needs to be better argued and explained.

Throughout the text, strength, force, and torque are used interchangeably. Force and torque should be used when discussing these measures and strength should be discussed when talking about the general idea or construct. Adjust accordingly throughout.

The discussion (and even the introduction) leans too heavily on the hip pathology literature even though this study is in a healthy population. Many references to hip strength testing are not cited with really only Thorborg articles being discussed. The following articles and subsequent discussion of them would help to improve this manuscript substantially.

References to consider:
ABD reliability & other considerations-
Krause et al., 2007
Kelln et al., 2008
Kawaguchi JB, 2010
Bazett-Jones et al., 2011
Krause et al., 2014
Romero-Franco et al., 2016 (this is using a load cell as well so important to compare)
Bazett-Jones et al., 2017
Martins et al., 2017 (already cited by not discussed)
Bazett-Jones & Squier, 2020

IR & ER reliability-
Katoh 2009
Katoh & Uchida 2011
Hoglund et al., 2014
Martins et al., 2017 (suggested above)
Bazett-Jones & Squier, 2020 (suggested above)
Glaviano & Bazett-Jones 2021 (EMG study)

Hip extension position selection-
Krause et al., 2014 (as above)
Kindel & Challis, 2017
Bazett-Jones & Squier, 2020 (suggested above)

Specific Comments:

L36 – the conditions that are listed here are hip, not LE. Hip strength testing also applies to PFP and other knee pathologies as well as ankle sprains and instability. Throughout the manuscript, the authors limit the impact of this study by only concentrating on the population of hip pathologies.

L68 – please clarify what “this motion” is referring to.

L75 – aims should use force or torque, not strength.

L77 – same as previous comment. Also need to specific which action since some were excluded from this analysis.

L84 – Were GRRAS guidelines (Kottner 2011) followed?

L99 – how was the dominant leg defined?

L111 – abbreviation of MDD not used here. Used consistently throughout or not at all.

L117 – the inconsistent positions are a major limitation of this study. For varying measures of hip ABD, 3 different positions are used when standing could have been used for all.

L128 & L131 - a more specifically defined placement should be provided since this can influence the measurements.

L133 – Was the joint angle confirmed to be the same as the angle given on the Biodex? The problem with this is that the pad that is attached causes the angle of the device to be different than the angle of the joint.

L138 - Was the weight of the test limb used to correct for gravity of the custom rig as well? How does this influence the data? Are you able to compare MDD and custom rig even if they both were not corrected?

L148 – Measurement of the lever arm should be a procedure, not data processing. Move up and describe more thoroughly.

L151 – was only the highest force value used or was the highest torque value used as well?

L153 – what were the results of the normality test?

L154 - Number of outliers excluded should be reported in results so we know the impact it has on the data.

L173 – Strength = force or torque?

L183 – good and excellent reliability should be reported separately as was above for the custom rig.

L185 – Weren’t the custom rig results from the principal planes provided in the first sentence? This would then be conflicting with that. Please clarify.

L191 – since there are only 3 comparisons, it seems that they all could be listed here and the bias direction could be named more explicitly (e.g. towards greater flexion measured by MDD)

L193 - Please provide 95% CIs for the LOA so that we know the precision of these.

L2019-211 – This statement seems like a reach since the authors did not test set-up reliability or inter-tester reliability and still had large measurement error. Not to mention that it requires a large, custom rig.

L212-218 – MANY other studies that have investigated hip strength reliability that could be added here. See general comment.

L227 – This study only measured healthy individuals, not those with hip pathologies so this statement seems like a reach.

L240 - This has been done somewhat similarly in Lee et al 2014 (https://pubmed.ncbi.nlm.nih.gov/24560168/) and McBeth et al 2012 (https://pubmed.ncbi.nlm.nih.gov/22488226/). This might improve the discussion.

L241 – application to hip pathology understanding is a stretch for this study. Suggest toning down language.

L254 – The Casarelli reference only applies to hip pathology. There are other pathologies that this statement may or may not apply to as well. This statement is too broad in its current form. Revise or remove.

L293 - The ability and desire of clinicians to figure out hardware and software would be questioned, especially with limited time.

L294 – the inability to compare half of the measures between the MDD and the custom rig leaves a large hole in the results of this study. This is a major limitation that needs to be addressed.


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: RELIABILITY OF HIP MUSCLE STRENGTH MEASURED IN PRINCIPAL AND INTERMEDIATE PLANES OF MOVEMENT
Review round: 2
Reviewer: 1

Output:
Basic reporting: No comment.
Experimental design: No comment.
Validity of the findings: No comment.
Additional comments: Thank you to the authors for their considered responses to all of my previous comments. I am satisfied that they have adequately addressed all of my previous concerns, apart from one apparent referencing error in their in text response to my comment related to athletic performance. In their response to my comment they included an additional line addressing contribution of hip muscle strength to athletic performance and said they cited Prendergast et al., however, in the revised manuscript van Dyk et al. is cited, which does not appear to be the appropriate reference. As long as this minor error is corrected, I have no further comments and congratulate the authors on a thorough revised manuscript, which I believe warrants 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: RELIABILITY OF HIP MUSCLE STRENGTH MEASURED IN PRINCIPAL AND INTERMEDIATE PLANES OF MOVEMENT
Review round: 2
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: Thank you for considering my revisions. The manuscript has greatly improved.


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: RELIABILITY OF HIP MUSCLE STRENGTH MEASURED IN PRINCIPAL AND INTERMEDIATE PLANES OF MOVEMENT
Review round: 2
Reviewer: 3

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: The authors are commended on their much improved manuscript. All of my comments have been adequately addressed, except the introduction still seems to lack some justification. The "non-principle planes have never been measured" argument does not provide adequate justification, in my opinion . The third paragraph seems the least relevant (though I do appreciate the desire to have a clinical application). My suggestion is to write further about what Neumann 2010, Delp 1999, Dostal 1986, etc. have described as changing moment arms and/or length-tension, which can impact torques. When I think about the line of action for the posterior fibers of the glute med, as the hip is externally rotated (per your device and positions), the moment arm distance is increased and the muscle is shortened. How does the intermediate plane position impact the anatomical structures and mechanics of the hip? What is the rationale, from this specific perspective, for why testing in the intermediate planes would have any impact on the results? It seems like addressing this type of question that specifically provides a rationale for why differences might be found would be preferred over conjecture that these results are likely different from the primary planes just because the hip is complex and has 6DOF. However, if the editor feels that it is appropriate as is, I support his decision.


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: EFFECTS OF THIOUREA ON THE SKULL OF TRITURUS NEWTS DURING ONTOGENY
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript is incomplete, insofar as not enough basic information about the study system is included to rigorously interpret the data or results. See specific comments below.

Syntax of figure legends is awkward in places.
Experimental design: Certain basic information that would explain and justify the experimental design is missing:

94	Likely, but are there any empirical studies that document the TH profile during metamorphosis in these species?

100-101	Why use interspecific hybrids and not larvae of one species or the other? Is the fact that they are hybrids make us expect that they would respond differently than larvae of each species?

112-114	Need to describe basic features of this staging table that are most pertinent to this study. For example, what are the key skeletal features of stages of greatest interest here—50, 62, and metamorphosis? These questions are not answered in Table S1.

119-120	What bones are normally present at these stages, and at what stages do bones form between them?

132-133	What bones are normally present at these stages, and at what stage(s) do bones form between them?
Validity of the findings: Certain inferences made regarding the nature of thyroid hormone control of cranial ossification during metamorphosis in amphibians are not justified by the results provided here. A more nuanced discussion of these results in terms of what they do--and don't tell us--is needed. There is a vast literature that describes thyroid gland activity and the nature of thyroid hormone action on target tissues. Little of that literature is cited here.

251-253	While one can safely conclude that there is differential TH-sensitivity between early- and late-forming bones, evidence for the claim that “cranial bones are not TH-dependent” is weak, despite claims made in published studies cited here. Neither the fact that early-forming bones may not be inducible by exogenous TH, nor that application of thiourea fails to prevent their formation, is conclusive. In the former instance, exogenous TH may have been applied before the bone-forming sites are competent to respond to it, and in the latter instance TH produced before application of thiourea may be sufficient to promote bone development after the application. These subtle relationships have a bearing on the way that results of the present study are interpreted.

258-265	While technically it may be correct to say that, for the experimental protocol used here, “thiourea does not have significant impact on skull development during midlarval period,” and that “larval cranial development proceeds similarly regardless of different TH level,” these claims need not mean that TH is not mediating the ossification of early-forming bones as is implied by the sentence that follows: “The thyroid gland begins its activity at the late larval period and has the greatest influence on late-appearing bones.” The pervasive effects of TH on metamorphosis at all stages, and I believe the past demonstration that the thyroid gland is active at if not before early stages, contradict the published claim cited here.
Additional comments: Minor corrections:

49	No hyphen in “triiodothyronine”

54	add comma after “metamorphosis”

145-146	Only the A in Alcian should be capitalized. The b in blue, a in alizarin, and r in red should all be lowercase.

369-371	This paper is cited out of chronological order.

384, 387	Need to correct spelling of second author’s name, here and in text.

436-437	Delete “for analyzed bones”

440-441	Delete “for analyzed bones.” palatopterygoid is misspelled.

Figure 2	Explain circles and squares. What does “of Inertia” mean?

Figure 3	Explain orientation of deformation grids. Anterior? Posterior? Dorsal? Ventral?


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: EFFECTS OF THIOUREA ON THE SKULL OF TRITURUS NEWTS DURING ONTOGENY
Review round: 1
Reviewer: 2

Output:
Basic reporting: This manuscript describes experimental research into the influence of thyroid hormone deficiency on bone ossification and cranial morphology in developing Triturus newts. Thyroid hormones are well documented to have an important role in skeletal differentiation and morphogenesis in vertebrates and in amphibian metamorphosis, specifically. The influence of thyroid hormones on cranial bone appearance and ossification is well documented in Urodela (salamanders/newts); however, this study is the first study on skull shape in Urodela (based on information provided by the authors).

In order to evaluate the effect of thyroid hormone deficiency on skull development/shape, larval newts were exposed to a known disruptor of thyroid hormone synthesis, thiourea, which has previously been documented to alter thyroid hormone status, result in glandular hypertrophy, and processes dependent on thyroid hormones (e.g., metamorphosis in Anurans). The authors report on two experiments with which they were able to compare the effect of thyroid hormone deficiency (produced by exposure to two concentrations of thiourea) on cranial morphology during mid-larval and late larval development. Cleared and stained skull of skeletal whole-mounts were evaluated for presence and amount of ossification of skeletal elements with skull shape described/digitized using cranium landmarks.

1.1.	This manuscript is well written with detailed descriptions of the work conducted and clarity in structure. To the best of my knowledge, the analyses conducted are appropriate. However, there are aspects of the reporting, experimental design, and findings that need clarification and/or expansion in order to provide support for the conclusions made, as described below.

1.2.	The introduction provides a good overview of the importance of THs in vertebrate development; however, for the context of thyroid disruption, it is important to include details on the mode of action of thiourea and documented effects on circulating thyroid hormones, beyond the generalities described here.

     1.2.1. In the Intro, I recommended adding information on the mechanism by which  thiourea reduces THs – likely through inhibition of thyroperioxidase (TPO) enzyme activity, as suggested by the use of thiourea-type compounds included as reference chemicals for TPO in Wener et al. 2016
[Wegner S, Browne P, Dix D. Identifying reference chemicals for thyroid bioactivity screening. Reprod Toxicol. 2016 Oct;65:402-413. doi: 10.1016/j.reprotox.2016.08.016]

     1.2.2. Although thiourea is well documented as a model thyroid disruptor, details on documented reductions in circulating thyroid hormones from previous publications should be added to support the premise of this study. If possible, include reference to studies that documented reductions in T3 and/or T3 in amphibians – either in the Intro or the Discussion.

1.3.	It is unclear why interspecific crosses were used for this study. Would the expectation of effects be the same in both of these species?

1.4.	The figures and tables are relevant, well-described, and support the text of this manuscript.

1.5.	The raw data are provided for the ossification scores from both experiments. These data are easy to understand, and my only recommendations are to correct the typo on the ‘concentration’ heading and perhaps indicate the compound (‘thiourea’) in either the header or the entries for this field. I am not sure if it is possible to provide the raw data for the digitized cranium landmarks – but this information could be of interest to some.
Experimental design: 2.1.	It is not clear what the experimental unit is in these studies – the individual (at with scoring and landmarks were done) or the container (Line 129 indicates that there were 5 larvae per container). Please clarify the experimental unit, how many containers, and which were used for the statistical analysis. The sample sizes reported suggest that there were only 2-4 containers per treatment each with 5 larvae.

2.2.	It would be beneficial to expand upon the selection of concentrations of thiourea (Lines 123-124). I appreciate the citation for the concentration selection, but suggest expanding on the effects these concentrations had in the citation used (and possibly add other citations). Also, was thiourea dissolved in the same tap water as used for the controls?

2.3.	Please clarify which data were used for the PCA for variation in skull shape. Scores on presence and ossification level (described on Lines 163-165?) Cranium landmarks?

2.4.	This research was conducted under ethic standards following national permits and institutional approval, and in compliance with the European Directive 2010/63/EU. The described exposures meet the standards in the field, with some additional information that should be reported: details on exposure (described below in 3.2) and method of euthanasia. The research questions could only be addressed with these experiments, and the authors used the minimum number of organisms (perhaps fewer than would be recommended, as described above in 2.1).
Validity of the findings: 3.1.	The design of these experiments provided a good basis for addressing the question of effect of TH deficiency on skull development/shape, including controls and 2 treatment levels at two different developmental stages. However, it is challenging when development and/or metamorphosis is delayed and the treatments cannot include organisms that are staged-matched with the controls. The authors have recognized this challenge, but I recommend that further descriptions or information are needed to determine whether the differences in the study with late larval/metamorphic newts are due to actual changes in skull development/shape due to TH deficiency, or are the exposed organisms just delayed in development and have skull shapes similar to an earlier stage. If possible, perhaps it would be informative to compare the ossification scores and shape metrics of treated organisms to this same information from control organisms at multiple earlier stages.

3.2.	To improve confidence in the results reported, I suggest adding other details on the exposure. Specifically:
     3.2.1. What was the length of exposure for each of the studies? Did they differ greatly?
     3.2.2. What as the density per container by mass? And how did that differ between the two studies?
     3.2.3. What were the conditions in the containers? (Dissolved oxygen, pH, temperature, etc).
     3.2.4. Was there much mortality observed in either study? What about other growth effects?
Additional comments: 4.1.	Line 54: I suggest revising “secretion of TH” to more specific description of “TH synthesis and release to bloodstream increases” or “circulating TH increases”.

4.2.	Lines 54-56: Consider adding additional citations to support the pattern of TH through the metamorphic process. There are multiple studies with amphibians that would supplement the 2 citations already included, such as: Regard et al. 1978, Larras-Regard et al. 1981, Sternberg et al. 2011 (and many others).

Regard E, Taurog A, Nakashima T. Plasma thyroxine and triiodothyronine levels in spontaneously metamorphosing Rana catesbeiana tadpoles and in adult anuran amphibia. Endocrinology. 1978 Mar;102(3):674-84. doi: 10.1210/endo-102-3-674.

Larras-Regard E, Taurog A, Dorris M. Plasma T4 and T3 levels in Ambystoma tigrinum at various stages of metamorphosis. Gen Comp Endocrinol. 1981 Apr;43(4):443-50. doi: 10.1016/0016-6480(81)90228-8.

Sternberg RM, Thoemke KR, Korte JJ, Moen SM, Olson JM, Korte L, Tietge JE, Degitz SJ Jr. Control of pituitary thyroid-stimulating hormone synthesis and secretion by thyroid hormones during Xenopus metamorphosis. Gen Comp Endocrinol. 2011 Sep 15;173(3):428-37. doi: 10.1016/j.ygcen.2011.06.020.

4.3.	Lines 80-81: Were these studies on cranial osteology conducted in tadpoles (as mentioned in the first ½ of the sentence) or in other amphibian groups?

4.4.	Lines: 82-85: For the more general audience associated with this journal, it would be helpful to provide context for what are included in the Order: Urodela (salamanders/newts).

4.5.	Line 124: I suggest moving the details on the action of thiourea to the Intro (instead of including here in the Methods) – it would fit well with the sentence on lines 71-73. I also recommend adding the CASRN and/or Product ID from the thiourea obtained from Sigma, along with the reported purity of the lot received.

4.6.	Line 131: “They were sampled.” Euthanized with ??, preserved whole? Any tissues or blood collected?


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: EFFECTS OF THIOUREA ON THE SKULL OF TRITURUS NEWTS DURING ONTOGENY
Review round: 2
Reviewer: 1

Output:
Basic reporting: English grammar and syntax is still awkward in places in the text. Someone in the editorial process will need to fix.

Specific errors (line numbers in parentheses):
76	Delete comma after “agent”.
86	Change “as” to “a”.
118	treated is misspelled (“tread”).
330	Eagleson is misspelled (“Eagieson”) here and in Literature Cited.
402	Add “of the United States of America” after “Sciences”.
417	Capitalize first a of “alcian”.
426	Eagleson.
526	Insert space after “Lithobates”.

thiourea is misspelled (“tiourea”) in one of the Supplemental files (peerj-55888-skull_shape_raw_coordinate_stage_62.xlsx”).
Experimental design: In their response to reviewers, the authors provide a helpful explanation and justification of the use of hybrid larvae, but little of that text has made it into the revised manuscript (lines
123-127). I suggest inserting more of the explanation and justification into the manuscript to allay readers' concerns.
Validity of the findings: Problematic claims from the original draft have been removed or modified appropriately.
Additional comments: No additional comments