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

Input:
Title: A QUANTITATIVE COMPARISON OF TOWED-CAMERA AND DIVER-CAMERA TRANSECTS FOR MONITORING CORAL REEFS
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript is very well presented and is easy to read and follow. I do provide some suggestions and recommendations list below.

Much of the introduction mentions costs involved with survey methods but there is no mention about the difference in costs of running diver survey verses a towed video survey. I would suggest, maybe in the discussion, having a few lines that state a towed video system cost $xx and cost $xx to survey xx sites versus $xx dollars for a diver survey. If there is a significant cost difference this could help a perspective reader decided what method is appropriate etc. I have seen some method comparisons papers provide a table that includes cost of unit, number of people required for survey, cost a days survey etc. Could you even provide a decision tree / flow chat for the discussion/conclusion?
Experimental design: -	My main question around the study design and statistical analysis is around the dreaded pseudo-replication. I can see two potential issues of pseuda-replicaiton and wonder what the authors think or if it should be addressed. Neither of these are deal breakers, especially as the objective is to compare two methods. However, I still think they should be consider?
o	The first, including method as a fixed factor in the PERMANOVA? I understand they have included the interaction between method and habitat etc. However, PERMANOVA assumes independence of all samples. Is a sample from towed video is taken from the exact same location as a diver survey surely, they are not independent? Therefore, the risk of type 1/2 error is a concern? I would have thought doing 2 separate PERMANOVAs, one for each method, and testing to see if the results are within x% of each other and therefore able to make the same inference regardless of the method?
o	The second, having individual transects going end to end ie. 5 transects in a 250m site? I know this is a commonly use method but it also doesn’t necessarily make it correct. A review of the Victorian Marine Park monitoring program found this level of pseudo-replication was an issue and had to change the methodology. Has this been tested? Does transect or site need to be considered as a random factor to account for spatial correlation?
-	Line 314 you mention that differences between methods varied with habitat? Is this true variability or could this be due to a low sample size? Is it worth doing a power analysis to see if both methods have the ability to detect change?
Validity of the findings: No comment
Additional comments: Minor comments
-	Line 32-33 - this sentence is confusing I would suggest rewording.
-	Line 34 - percent cover of what?
-	Line 43 – I would like to see a concluding sentence in the abstract. Something along the lines of a recommendation i.e we recommend towed video can replace diver survey if a monitoring program is focussed on….. At the moment I am left wondering what the authors are recommending until the very end of the discussion. I always suggest never leave the reader hanging.
-	Line 50 – this doesn’t just apply to conservation planning, it also applies to spatial management, impact assessment, fisheries management, oil and gas exploration etc.
-	Line 62 – how are the data comprimise?
-	Line 65 – Ongoing discussion about what?
-	Lines 62 and 65 don’t really link the paragraphs. I would almost remove the opening sentence on Line 65.
-	Line 70 – Technical advances also allow for an increase in replication, greater sample size = (sometimes) greater abilitiy to detect change = greater statistical power.
-	Line 75 – you can also add it provides a permanent record.
-	Line 77 – This could be a useful reference: https://www.frontiersin.org/articles/10.3389/fmars.2019.00134/full
-	Line 74-79 – Have you seen the NESP Field Manuals? It would be worth making reference to this collection of field manuals/ SOPs as they were design to ensure that there are standardised method to allow for detection of change, reproducibility, comparability etc etc. Most importantly there is a Towed Video, ROV, AUV chapter.
-	Line 82- I don’t think this is true? Towed video/cameras/ROV have been used in monitoring programs for decades. I have been using these technologies for 20 years now! What I think has changed is that they are now more affordable, more options, more accessible to the average researcher / low budget projects etc.
-	Line 125-126 – Slight rewording to improve reading, suggest “… and due to their isolation and conservation protection they have not experience many….
-	Line 162 – include the megapixels and sensor size given that you mention this for the towed video system.
-	Line 275 – Why did you fit a model with a Poisson, ZIP or negative binomial distribution that would account for what I assume is zero inflation? Are these species of interest? Often it is the less common rare species that are the most important for detecting changing in a monitoring program? Are they worth including?
-	Line 304 – I would also include the standard error after the mean.
-	Line 370 – Can I suggest a closing sentence along the lines of towed video is comparable to diver surveys…. Could be used to replace diver surveys etc. Once again as the reader I am left hanging till the conclusions to know what you would recommend.
-	Discussion in general, so is camera quality that is most important? Do we need to test multiple camera brands, types, lighting etc to find a more suitable towed video camera?
-	Line 423 – This more future suggestion comment that you may already be aware of, in the past I have use a camera – boat offset to geo-locate the photo with the GPS track. I bit of simple Pythagoras theorem, length of cable out + depth and you can calculate how far the camera is behind the GPS.
-	Conclusions, I’m still hang to know if towed video could replace diver surveys. The results suggest it depends on many factors. If I was a funding body or a manager I want to know that after 10 years of monitoring can I swap to towed video and get usable comparable data? This is why I think a decision try would be useful?
-	Figure 3 – Can I suggest changing a method symbol to circle or square or even open. Having opposite triangles with so many sample is hard for the reader to disentangle the patterns, especially when a color scale is involved.


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

Input:
Title: A QUANTITATIVE COMPARISON OF TOWED-CAMERA AND DIVER-CAMERA TRANSECTS FOR MONITORING CORAL REEFS
Review round: 1
Reviewer: 2

Output:
Basic reporting: Interesting contribution. Well written manuscript with an elegant data analysis statistical approach.
Experimental design: Methods: presented with logical, well designed statistical design. Thorough Results and the Discussion.
Validity of the findings: Although the Structure for Motion/Photogrammetry survey techniques are revolutionizing coral reef monitoring, it will not be long before technology replaces swinging divers by towed-camera systems able to follow the bottom contour. This manuscript provides a baseline for future forthcoming protocol updates and technology advancement.
Additional comments: Cresswell et al. A quantitative comparison of towed-camera and diver-camera transects for monitoring coral reefs

General comments:
Interesting contribution. Well written manuscript with an elegant data analysis statistical approach. As authors indicate, with limited budgets, increasing operational costs, and limited staff, remote sensing techniques have rapidly gained traction among coral reef monitoring programs worldwide. Although the work presented in this is not particularly innovative, its scientific merit and dissemination power are worth publication.
Methods: presented with logical, well designed statistical design. Thorough Results and the Discussion. Although the Structure for Motion/Photogrammetry survey techniques are revolutionizing coral reef monitoring, it will not be long before technology replaces swinging divers by towed-camera systems able to follow the bottom contour. This manuscript provides a baseline for future forthcoming protocol updates and technology advancement.

Just a few comments section by section:

Methods:

Lines 124-132: Seems to me that this is unnecessary detail, much of which is irrelevant to the objectives of the MS. I suggest authors limit the site description to the location of the reefs.

Line 135: “Sites were stratified by habitat: ‘forereef slope’ …. ‘reef crest’. Seems to me these habitat names are self-explanatory and do not necessitate the added description.

Lines 140-149:  Streamline…. “Based on the prevailing conditions, general surveys were prioritized during slack tides. Winds below 20kn and swell less than 1 m. All survey activities were permitted accordingly”.

-What was the area of each image photographed by divers and towed-camera; was the area compatible?

Line 200-201: How did select fixed points? Arbitrarily/stratified? Why only 5 points per image? Did you experiment with different number of points on the TDC images? An increase in the number of points could potentially increase the accuracy and eliminate a portion of the unidentified due to image blur?

Line 269: Zuur et al 2010 absent in References

Line 236: In my experience, cover data generally does not necessitate transformation; and on occasions, PERMANOVA results can vary depending whether transformation is applied or not. Did authors explored this issue?

Figures and Tables
Table 4B, D- Nice graph, but not particularly intuitive to read.


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: DESIGN AND EVALUATION OF A SIMULATED WOUND MANAGEMENT COURSE FOR POSTGRADUATE YEAR ONE SURGERY RESIDENTS
Review round: 1
Reviewer: 1

Output:
Basic reporting: Overall this article meets all standards. I do think that there may be room to define specific surgical jargon that is used throughout the article. Since this journal is not specifically targeting surgeons as a audience but rather has a broader audience there may need definitions provided as to what is meant by some of the terms used (i.e. dumbbell, dog ear treatment, spindle resection, etc...).
Also reference used to articulate the claim that clinical interventions could result in adverse effects on the skin, deep soft tissues ..with an average incidence of 2.6% needs to be updated. The citation used is from 1999.
Experimental design: Meets standards.
Define Peyton's four-step approach.
Validity of the findings: Please explain the use of Chi-square test and Mann-Whitney test.
would like p values and test use for baseline test provided in table 3
Missing information in figure 4 to be able to understand it. Please include what * means? Also p values needed.
Table 4 needs notes so that one can understand what *, triangles mean as subscripts. Also appears that the analyses were done at the group level, but this analysis seems to be more appropriately done with paired tests, specifically ANOVA. I am also not completely clear on what the percentages are ... are the percentage of participants who were successful? Based on the narration the outcome was suture numbers and +/- dog ear approach... but this does not seem to be reflected in the table outside of a %. Also how was decreased incision tension measured? This does not seem clearly measured in terms of a percent. Narration does not match well information provided in the table. Please revisit.
Additional comments: Thank you for your submission. This is an interesting study of importance to the field.  There are however some issues with methods used for analysis as well as some of the jargon that needs addressing. It is possible that the methodological an be addressed for a successful publication, but give the fact that this was a retrospective study it is unclear if this is possible. I have left other comments in the sections above. Thank you for your submission and work on this important topic.  I am not sure you really established that what you presented as study findings are evidence of mastery of suturing. It is possible that they are, but you need to more clearly set this up / speak to how they do.
I think the second paragraph of the discussion belongs in the background section. The description of the low tech simulation used included in the in the discussion belongs in the methods section.


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: DESIGN AND EVALUATION OF A SIMULATED WOUND MANAGEMENT COURSE FOR POSTGRADUATE YEAR ONE SURGERY RESIDENTS
Review round: 1
Reviewer: 2

Output:
Basic reporting: The paper is well written and clear for readers.  Those relevant literatures are cited properly to support the key message.
Experimental design: The study used the quasi-experimental design to compare the impact of the training course for wound management.  It is not ideal but fits the real-world nature of program development for the course. The study outcome is well defined and relevant for clinical practices. But this study also didn't address the outcomes of Kirkpatrick model level 3 and 4 for clinical impact which is common weakness for many similar simulation studies.
Validity of the findings: The study results are presented well and showed the impact as expected. Due the limitation of study design, not sure the results will add more evidences of existing literate related to the topic. As many well-designed clinical trials have shown the post impact of simulation training in various specialty and programs.    E.g., 2011 JAMA Systematic Review by Cook. https://pubmed.ncbi.nlm.nih.gov/21900138/

Do you know how many surgical procedures those learners did during those 7 months period before assessment?  How do you know final performance variation is solely due to difference teaching methods and not due to exposure real clinical practice.  This might need to be addressed in the discussion section.
Additional comments: Instead of using the parallel study flow chat, I would suggest to replace Figure 1 with flowchart to demonstrate longitudinal nature of the study design to reduce the confusion.

If you have any survey data from the learners about those courses will be very beneficial to support your conclusion.

The 1-3 paragraph of discussion section could be reduced with more concise language.


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: DESIGN AND EVALUATION OF A SIMULATED WOUND MANAGEMENT COURSE FOR POSTGRADUATE YEAR ONE SURGERY RESIDENTS
Review round: 1
Reviewer: 3

Output:
Basic reporting: I find the basic reporting of the study to be very descriptive and realistic. It made
me feel that I had a good understanding of what kind of simulation training course was being conducted. I feel that most of the time, the authors has prepared this manuscript targeting to a more broad audience (rather than the Chinese medical education scholars).

The authors provided descriptive illustration towards the "traditional" way of surgical wound management course training for the residents, and how the new wound management course was being designed and implemented (although it was being mentioned mostly in the supplement material).

Nevertheless, I encourage the authors to consider the way the study is being reported regarding the following issues.

1. In Lines 128 - 133, it will be good to anchor this part with the designated objectives in your description, so that it can clearly represent the element of Mastery Learning. You could state that details see supplement.

2. Regarding Performance Assessment (Lines 143 - 159), are the residents allowed to practice and retake the exam (with the same MPS) if they did not pass the test?

3. How exactly is the MPS being determined? Could you provide a bit more information on that since it is an important element of ML.

4. Certain minor language errors identified, such as "carefully" in Line 57, a typo in Line 159 "toutcome".
Experimental design: This novel experiment is within the scope of the PeerJ Journal. Given the study is a quasi-experiment study, I understand that it would be difficult to control certain variables

I believe that this paper adds to the current literature in best practices in wound management towards surgical training, which few prior reports have been made public, especially those that have certain degree of alignment with the Mastery Learning (ML) Model in current medical education literature.

I am glad to see that the authors obtained IRB approval regarding the study. Just a quick question, do the authors have consents from the participating residents? Whether it's oral or written consent?
Validity of the findings: No comment.
Additional comments: No additional comments


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

Input:
Title: DESIGN AND EVALUATION OF A SIMULATED WOUND MANAGEMENT COURSE FOR POSTGRADUATE YEAR ONE SURGERY RESIDENTS
Review round: 2
Reviewer: 1

Output:
Basic reporting: No more comments.
Experimental design: No more comments.
Validity of the findings: No more comments.
Additional comments: Thank you for make modifications for those suggestions. The manuscript is great improved. Good work!


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: DESIGN AND EVALUATION OF A SIMULATED WOUND MANAGEMENT COURSE FOR POSTGRADUATE YEAR ONE SURGERY RESIDENTS
Review round: 2
Reviewer: 2

Output:
Basic reporting: After proofreading as suggested, the manuscript is now more friendly to read towards international audience. Also it is good to see the authors have updated the references for the background session.
Experimental design: The authors have included the part regarding obtaining oral consent towards the residences.
Validity of the findings: no comment
Additional comments: Although the study, by its nature is not actually a mastery learning study, but the results of the study do support the idea towards shifting towards mastery learning do provide better learning outcomes. Given the significance of the study results, I believe that this manuscript is okay to be published, in hope to raise better attention internationally towards simulatio-based mastery learning model in procedural-based training.


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: STABILITY OF HEPATITIS B VIRUS PREGENOMIC RNA IN PLASMA SPECIMENS UNDER VARIOUS TEMPERATURES AND STORAGE CONDITIONS
Review round: 1
Reviewer: 1

Output:
Basic reporting: In the introduction section, the authors described the background information on serum HBV RNA. However, the molecular nature of serum HBV RNA is still under fierce debate. The authors are advised to update their knowledge with newer publications. Several references are recommended below:
PMID:  33079954, 30282709, 30362148

In my opinion, it is best not to restrict serum circulating HBV RNA as pgRNA as there are plenty of evidence against this assertion.
Experimental design: The overall design of this study is acceptable. However, the authors have explored very limited area in the stability of this biomarker.

In addition to two days of room temperature storage. There should also be investigation on the stability of serum HBV RNA after freeze-thaw cycles (-20℃ and -80℃) which is critical for the reliability of retrospective studies.

The authors should also put enough efforts in detailing the protocols for RNA extraction and quantification. The current form did not specify how the DNase I treatment was performed and inactivated, the exact product name and catalog number of Bio-Rad digital RT-PCR mix was not specified and how exactly the ddPCR was performed was largely unclear.
Validity of the findings: The findings and statistical analysis are valid.
Additional comments: The current manuscript should include more details on the ddPCR. The background of serum HBV RNA should also be updated. I advise that the authors should perform additional experiments on the stability of serum HBV RNA after more harsh conditions such as prolonged room temperature storage and freeze-thaw cycles in order to test the analytical limits of this novel biomarker.


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: STABILITY OF HEPATITIS B VIRUS PREGENOMIC RNA IN PLASMA SPECIMENS UNDER VARIOUS TEMPERATURES AND STORAGE CONDITIONS
Review round: 1
Reviewer: 2

Output:
Basic reporting: The manuscript entitled, Stability of hepatitis B virus pregenomic RNA in plasma specimens under various temperatures and storage conditions” describes how the pgRNA level differs regarding different storage conditions. This subject is important as pgRNA reflects viral replication activity and is valuable for monitoring the effect in patients receiving novel anti-HBV therapies. Nevertheless, different storage conditions were supposed to affect RNA levels and in consequence, interfere with the quantification results. This study demonstrated that HBV pgRNA is quite stable under different storage temperatures.
Experimental design: no comment
Validity of the findings: These findings are important but the authors should discuss more significant differences presented in Table 2.  The authors claim that pgRNA is stable at room temperature at least 48h after collection but these data clearly show that the difference in RNA level changes.
Additional comments: The manuscript entitled, Stability of hepatitis B virus pregenomic RNA in plasma specimens under various temperatures and storage conditions” describes how the pgRNA level differs regarding different storage conditions. This subject is important as pgRNA reflects viral replication activity and is valuable for monitoring the effect in patients receiving novel anti-HBV therapies. Nevertheless, different storage conditions were supposed to affect RNA levels and in consequence, interfere with the quantification results. This study demonstrated that HBV pgRNA is quite stable under different storage temperatures.

Minor comments:
1) These findings are important but the authors should discuss more significant differences presented in Table 2.  The authors claim that pgRNA is stable at room temperature at least 48h after collection but these data clearly show that the difference in RNA level changes.
2) How was the ddPCR lower detection limit calculated?
3) Table 1: what are A and B?


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: AGE AND GROWTH OF PALAEOLOXODON HUAIHOENSIS FROM PENGHU CHANNEL, TAIWAN: SIGNIFICANCE OF THEIR AGE DISTRIBUTION BASED ON FOSSILS
Review round: 1
Reviewer: 1

Output:
Basic reporting: This paper describes a large sample of teeth from Palaeoloxodon huaihoensis recovered from the Penghu Channel. The paper is well-written and researched. Included figures are clear and appropriate. Some minor points are listed below:

I found the tooth notation to be a bit unusual. Older literature tended to use superscript and subscript numbers to designate upper and lower teeth, respectively. Modern literature generally uses uppercase and lowercase letters (M3 vs. m3, dP4 vs. dp4), and I would suggest using this notation. Related, the measurement supplemental table uses another scheme that is not explained, but I think uses M3 vs. 3M. Again, I suggest uppercase vs. lowercase.

On Figure 3, I suggest adding a diagram showing how height was measured.

In Line 256, “Hot spring” should be “Hot Springs”.
Experimental design: The authors’ methods are observational, and well-described, including basic measurements, age determinations, and basic statistical analysis of the sample. Specific comments are below:

The authors develop a tooth aging scheme for Palaeoloxodon based on the methods of Laws 1966. However, because their sample does not include any young individuals, their Group I starts with 6 year olds. However, presumably younger Palaeoloxodon are known from somewhere. If the authors want to have their scheme widely adopted by other Palaeoloxodon workers, they may want to consider recalibrating their scheme to start at something like VI instead of I, to allow the younger ages to be designated at some future date.

Related to this, the age determination supplemental file attempts, in part, to show how the Palaeoloxodon groups compare to Laws groups. Unfortunately, I found this table very confusing and was not able to completely decipher it. I think this table needs a detailed description explaining it, but I was unable to find one.
Validity of the findings: The bulk of the discussion attempts to explain the sample’s predominance of older individuals in the sample, and the complete absence of very young individuals. The authors make a good case that this is not a sampling bias, and point out that this pattern is similar to that seen in mammoths at Hot Springs, even though the taphonomic settings are completely different.

From these observations, the authors suggest that the age distribution is due to environmental stress leading to intraspecific competition (they say “interspecific” in Line 260, but I think they meant “intraspecific”.) While this is a perfectly good hypothesis, I think it’s a bit of a reach. My impression is that this age distribution (rare young, middle-age and elderly dominated) is not that uncommon among proboscideans (see, for example, Saunders 1977 and Green and Hulbert 2005 on mastodons). It may well be possible (even probable) that there are a number of settings that could independently lead to this population structure. I suggest that the authors soften this conclusion and emphasize that they’re putting this forward as one hypothesis to explain this distribution.
Additional comments: The authors should be commended for publishing these rather obscure but important specimens, and making their data open access so that they can contribute to other studies.


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: AGE AND GROWTH OF PALAEOLOXODON HUAIHOENSIS FROM PENGHU CHANNEL, TAIWAN: SIGNIFICANCE OF THEIR AGE DISTRIBUTION BASED ON FOSSILS
Review round: 1
Reviewer: 2

Output:
Basic reporting: Overall this is a well-written article with a robust set of appropriate statistical analyses to address the proposed hypotheses. There are a few places, especially in the introduction, were there is some awkward wording and passive voice. I would like to see a better discussion of the Hot Spring comparative site. While I agree this is an appropriate assemblage to use in comparison, those not familiar with Hot Springs would be unable to infer some comparisons as is. Will the author's photographs be available or do museum collection permissions make that impossible? While the manuscript is sufficient as is, if possible to have images in supplementary material I would find that ideal. All analyses were well laid out and appropriate for testing the author's hypotheses. The author's examination of possible sources of bias was well done and presents a compelling argument.
Experimental design: comments concerning this were addressed in the previous section. Overall appropriate and well-done statistical analyses, that most certainly address interesting and unique study questions. This clear hypothesis to test, to discussion of results leaves me eager to see potential follow ups to this work.
Validity of the findings: Appropriate statistical analyses were used throughout. Clear explanations of both the reasoning behind selection of particular statistical methods and metrics, as well as well examined sources of possible bias.
Additional comments: While the content of your figures is appropriate and necessary in each case, many are somewhat difficult to read. Larger text, clearer symbols and colors, and additional in-figure labels and expanded figure captions would greatly improve the overall polish of this work.


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: TEMPORAL INVERSION OF THE ACID-BASE EQUILIBRIUM IN NEWBORNS: AN OBSERVATIONAL STUDY
Review round: 1
Reviewer: 1

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

In this manuscript, Dr. Mizutani Y and her colleagues conducted an observational study to investigate the relationship between the pH drift at birth and postnatal acid-base regulation within the first week of life in spontaneously breathing newborn infants. They founded that the higher blood pH on days 5-7 were significantly correlated with lower cord blood pH, greater gestational age, lower partial pressure of carbon dioxide and lower lactate level, with adjustment for sex and postnatal age.
This manuscript might bring a novel perspective for the treatment strategy of transition failure at birth and subsequent neurodevelopment impairments. However, to accept the manuscript, there are still concerns about description that the authors should correct or give additional comments on.

Major problems
1.	Study population
	Although you investigated it by using spontaneously breathing infants in the study, you study population included 43 infants with initially ventilated infants at birth. If you like to see the biological response to the pH drift from the physiological equilibrium, why didn't you exclude them and just focus on 153 non-ventilated infants?  Especially if you want to move on your next study based on the current study results, then you had better do so.
	According to the cord blood pH, the severity of general status of your study population did not seem to be less, because they were almost within normal ranges. Therefore, I am still thinking that it would be better to look at the same parameter in severe cases, as well, to clearly show the postnatal acid-base regulation in both normal and abnormal conditions.
2.	Rationale of investigating blood pH on d5-7
Could you please give some comments on the rationale of investigating blood pH especially on d5-7.
3.	Trend in pH from birth to d5-7
I am curious about the trends in pH from birth to d5-7, not just two point of pH, at birth and d5-7. To show the detail of biological response, those information might be more informative for understanding of biological response to the covert disruption of pH homeostasis at birth.

Minor problems
1.	How about Anion Gap in the blood gas analysis?
2.	As you’ve already noted in Discussion, pleases clarify the timing of taking blood gas sample of PCO2 and lactate, here in Abstract or Table3, too.
3.	In discussion, your bibliographic consideration looks great, but there seems to be too much speculation. You mention about an intracellular alkaline overshoot for severe acidosis, but in your study population, their pH did not seem to show any excess acidemia at birth or excess alkaline shift at d5-7.


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: TEMPORAL INVERSION OF THE ACID-BASE EQUILIBRIUM IN NEWBORNS: AN OBSERVATIONAL STUDY
Review round: 1
Reviewer: 2

Output:
Basic reporting: -	I recommend authors provide more details regarding the effect of pH drift on neurodevelopmental impairments in Line 64
-	Issue in line 72: dot and parenthesis are separated by a space.
-	Additional space in line 103 between “pH” and “on”
-	More information is required for how the multivariate model was developed in Line 107
-	Line 108: what is the correlation? Is it statistically significant?
-	Line 112: Again, information regarding the developed models is missing. It is necessary to clarify the details.
-	Table 1 is somewhat confusing specially for those working in a different field. For example, the values in the table have brackets/parenthesis in front of them without any description about what they mean. In addition, there are some variables reported with no unit, it is highly recommended to use “(-)” if the variable is dimensionless.
-	Line 127-148: All major findings are reported without in-depth explanation and the results are summarized in tables (Table 2 and 3). I highly recommend considering adding a better visualization as simple as a 2D graph instead of reporting numbers that are not easy to compare across different variables and conditions.
Experimental design: -	This study lacks a solid hypothesis about the processes and factors involved in blood pH regulation of newborns.
Validity of the findings: no comment
Additional comments: -	This is an interesting observation about blood pH regulation found to happen within the first week of life. However, I believe including graphical representation of the findings will enable readers to understand and digest this article easier. Moreover, a comprehensive discussion is necessary on the possible underlying processes that control the pH regulation during the first week of life. Finally, a detailed description on the models developed is missing that needs to be addresses.


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: TEMPORAL INVERSION OF THE ACID-BASE EQUILIBRIUM IN NEWBORNS: AN OBSERVATIONAL STUDY
Review round: 1
Reviewer: 3

Output:
Basic reporting: Cluttered, incoherent with no emphasis on the salient points. Too difficult to follow with no correlation to the clinical conditions of the babies categorised to the reasons they were admitted in the first place. These infants are not representative of the normal population unless their underlying conditions are clearly spelt out.
Experimental design: Flawed. These are not normal spontaneously breathing infants but were sick and on the road to recovery. Spontaneously breathing infants not mechanically ventilated do not equate healthy infants. I find it difficult to accept the conclusion when there was no mention at all about the underlying disease particularly any residual lung disease, the respiratory rate, temperature - these could impact on hyperventilation, low CO2 and therefore higher pH in the sicker infants initially who are recovering. These cannot be considered to represent the normal "over-correction" phenomenon claimed by the authors.
The authors need to specify what were the clinical conditions of these infants, the average respiratory rates and temperatures at the D5-7 sampling day.
As this was an observational study, all the other infants excluded should actually be included for their data to be analysed according their individual conditions.
Why were the 4 who received bicarbonate be excluded. We should look at these infants and examine why was bicarbonate required, which is seldom given nowadays anyway in neonatal care.
Validity of the findings: Without correlation with the underlying clinical conditions, the blood investigation results could not be interpreted sufficiently accurately. The conclusion also could not be validated and confirmed as such.
Additional comments: It is crucial that the clinical diagnosis of the 200 infants be spelt out clearly from the beginning, i.e.
what were they admitted for - severe lung disease, or no lung disease but suspected bacterial infection, feeding difficulties, asphyxia? etc.
Some of these infants were actually on respiratory support at D5-7, which will not represent the normal babies acid-base status as such.
The heterogeneity of this population makes it difficult for the conclusions to be drawn accurately.
Other information need to be spelt out includes : were the babies on intravenous fluid plus enteral feeds at D5-7. Were there babies who were receiving phototherapy, and what were their hydration status as such.
The voluminous metabolic data need to be correlated with the clinical status of the babies for accurate conclusions to be drawn.


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: TEMPORAL INVERSION OF THE ACID-BASE EQUILIBRIUM IN NEWBORNS: AN OBSERVATIONAL STUDY
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: Thank you for your revised manuscript entitled “Temporal inversion of the acid-base equilibrium in newborns: an observational study”
The revised manuscript shows much improvement. I appreciate your complete response to my comments and accept it.


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: BIOINFORMATICS ANALYSIS OF LARYNGEAL SQUAMOUS CELL CARCINOMA: SEEKING KEY CANDIDATE GENES AND PATHWAYS
Review round: 1
Reviewer: 1

Output:
Basic reporting: 1) Clear English used.
2) Raw data reference from GEO has been cited.
3) The authors have done a nice work on giving a background introduction of their research
4) Each of the results section is supplemented with articles as per standard
Experimental design: The research question is defined, but bioinformatics methods applied is not presented in details. Please see my comments below
1) While analyzing 2 available microarray dataset, how was the batch effect dealt with? Along with GEO2R methods used, could you please use other tools (such as combat) to apply the batch correction and see how differential expression is changed as compared to results presented

2) For the PPI network modules, how many genes were used for GO analysis.

3) Please explain the PPI methods in details in the method section

4) Legend in figure 3 is too small to read. Please increase the legend size
Validity of the findings: The experimental results support the hypothesis which authors are presenting. But bioinformatics methods used are not robust and needs more detailed analysis.
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: BIOINFORMATICS ANALYSIS OF LARYNGEAL SQUAMOUS CELL CARCINOMA: SEEKING KEY CANDIDATE GENES AND PATHWAYS
Review round: 1
Reviewer: 2

Output:
Basic reporting: 1. English need to be improve throughout the manuscript.
2. Most relevant references need to add.
Experimental design: Primary research are with in the Aims and scope of the journal.

Research question well defined.

Investigation need to be required more technologically sound.

 Methods are fine.
Validity of the findings: Impact is ok.

All the data included.

Conclusions are rightly stated.
Additional comments: Following concerns need to address before this manuscript gets published.
1. Over all English need to improve and most relevant references need to add.
2. All the figures size should be same.
3. Figure 2A text is not readable. Need to improve the figure.
4. Figure 3A text size is too small.
5. Figure 4 there is no statistical significance symbol but author mentioned P value<0.05 in the legend. Moreover its not clear that significance shown between which groups.
6. In Figure 5B, ratio calculation with beta actin is incorrect as per Y axis label. Moreover Panel A has 2 bands so author need to indicate which band is relevant. If considering thick band (upper) is the relevant band then its totally incorrect ratio calculation.


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: BIOINFORMATICS ANALYSIS OF LARYNGEAL SQUAMOUS CELL CARCINOMA: SEEKING KEY CANDIDATE GENES AND PATHWAYS
Review round: 1
Reviewer: 3

Output:
Basic reporting: The language can be made better
Experimental design: Solid. No issues.
Validity of the findings: Conclusions are well supported by the analysis. They authors have been very cautious.
Additional comments: This is a manuscript by Ma et al that looks at differentially expressed genes (DEGs) in Laryngeal squamous cell carcinoma (LSCC).   The authors find 235 DEGs, including 83 upregulated, 152 downregulated and 9 hub genes. This manuscript is a step forward in the framing of policies for LSCC diagnosis.  It is written in a very simple and easy to follow manner. The conclusions are supported by the analysis. This is one of the rare manuscripts that can be accepted as is at PeerJ- a few minor comments

1)	The figure legends should be expanded
2)	Please check for grammar


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: NATURAL RESOURCES TO CONTROL COVID-19: COULD LACTOFERRIN AMEND SARS-COV-2 INFECTIVITY?
Review round: 1
Reviewer: 1

Output:
Basic reporting: Editing of the manuscript would improve the presentation of the material. For instance, the opening sentence of the abstract is missing a verb. There are typographical errors in many places, such as line 142, line 231, line 233, and the figure captions, among others.

Figure 2 appears to be from a different article or re-worked from a different article. For instance, it references age and aging as well as "food stud" and a "Huge Gut Microbiota" even though neither "food stud" nor "Huge Gut Microbiota" are discussed within the text of the manuscript.

The abstract positions the manuscript as taking a look at the clinical use of LF for COVID-19, but the content focuses on basic cellular mechanisms and in vitro experiments with little attention give to clinical data.

As currently written, the manuscript organization is lacking. Several paragraphs are off topic  or out-of-place (lines - 155-165, 201-206, 231-232, among others). The addition of more section headings would be useful.

The conclusion section brings up new material that has not been covered in the body of the manuscript (lines 408-413).

The authors suggest that "specialists in food science and technology" (line 100) are an intended audience for this manuscript, but as written, this is not the case.
Experimental design: The authors describe their search terms and database use. However, it is stated that preprints were included, and as far as I am aware, the listed databases (pubmed, scopus, and web of knowledge) do not include preprints in their searches. Furthermore, the manuscript reviews studies of LF in the context of other coronaviruses (for example: lines 167-172ish), but the search terms do not include "coronavirus" without "COVID-19" or "SARS-CoV-2."  This evidence suggests that the terms and databases used are wider than currently presented in the methods.
Validity of the findings: The authors use COVID-19 and SARS-CoV-2 seemingly interchangeably whereas COVID-19 is the disease caused by the SARS-CoV-2 virus. This should be corrected throughout.

Statements such as, "breastfed children are mostly unaffected by COVID-19" must cite the relevant literature. For instance, this statement is flawed. All children, even those not breastfed, are mostly unaffected by COVID-19.

The statement that "the digestive system comes right the after[sic] respiratory system in infection" also must include a citation to the relevant literature.

Evidence from cell culture experiments does not make for a "readily translatable adjunctive therapy" especially when no attention is given to the dose of LF used in the in vitro experiments being described. Are the doses physiologically relevant? There is no discussion of this in the review article text or with figures 1 or 3.
Additional comments: While this manuscript covers a lot of literature, the current organizational structure and missing citations as well as limited search details severely limit my enthusiasm for this review.


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

Input:
Title: NATURAL RESOURCES TO CONTROL COVID-19: COULD LACTOFERRIN AMEND SARS-COV-2 INFECTIVITY?
Review round: 1
Reviewer: 2

Output:
Basic reporting: The paper of Mattar et al. highlights the recent in vitro and in vivo studies of lactoferrin against SARS-CoV-2 infection.
1. The paper lacks of several references, for example in the sentence (lines 63-66 and 77-78). In addition, some references are not recent.

2. The direct interaction between Lf and SARS-CoV-2 needs to be further discussed. In Campione et al. 2020b was reported a decrease in viral load on both Vero E6 and Caco-2 cell line after pre-incubation between Lf and the virus. In addition, in this study, molecular docking indicates a possible interaction between the human and bovine Lf and the spike protein

3. Please add and discuss the following papers: Salaris et al. 2021 doi: 10.3390/nu13020328; Hu et al. 2021 DOI: 10.1080/22221751.2021.1888660

4. Please, discuss the resolution of the symptoms of COVID-19 patients after Lf treatment compared.
5. Please, add the dose of lactoferrin used in clinical trial

 In conclusion section, add a suggestion for future clinical trials about the role of Lf against SARS-CoV-2
Experimental design: The authors should explain the results of the study design. "We selected articles that were most related to COVID-19, with priority being given to the articles that reported experimental data on the analysis of the LF-COVID-19 interactions that were not covered in previous reviews." Add a section "result" where reporting the found articles in a synthetic way.
Validity of the findings: no commen
Additional comments: The paper is well-written and highlights the newest applications of Lf in SARS-CoV2 and coronavirus.


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: ZEBRASHARE: A NEW VENUE FOR RAPID DISSEMINATION OF ZEBRAFISH MUTANT DATA
Review round: 1
Reviewer: 1

Output:
Basic reporting: The authors describe ZebraShare, an online submission system as part of ZFIN that allows researchers to upload information on mutant lines that may be of general interest to the community.  ZebraShare is currently live on ZFIN but no published details on how to submit information exists.  The authors describe the workflow for submitting information to ZFIN and the various fields that are to be completed in the ZebraShare workbook prior to submission.  The authors then provide five Case Studies of mutants that have been submitted to ZebraShare.  The manuscript is clearly written and there is adequate background provided for the Resource.
Experimental design: The experimental design focuses on the workflow of submitting phenotype and mutant information into ZebraShare.  The characterization of mutant data in their Case Studies is limited.  The inclusion of several Case Study mutants is unclear and no obvious relationship exists between the different mutants.   This particular manuscript focuses on a Resource (e.g. ZebraShare) rather than a specific hypothesis-driven research question.  As such, there is some concern that this may not fully fall within the Aims of the Journal.  While the analysis of the mutants following standard procedures the methods lacked adequate details (see below) related to the number of animals tested, whether techniques were performed on single embryos/larvae or pooled sample, and whether any statistical methods were conduced.
Validity of the findings: The benefits of ZebraShare to the zebrafish community include the dissemination of phenotypic information for mutants that may have limited benefit to the lab of origin.  Perhaps the biggest benefit will that mutants lacking phenotypes can be identified to avoid duplicating negative results by multiple labs. It is debatable whether investigators would submit alleles that have novel phenotypes rather than attempt to follow-up.  The workbook and submission process appears simple and straightforward.  The online submission process is currently active and self-explanatory.

The inclusion of the Case Study mutants is less persuasive.  These mutants have limited benefit to the labs of origin, but the inclusion of five different Case Studies is probably overkill.  The data supporting the mutant characterization could be enhanced by additional information related to identify n-values, biological and technical replicates, and total numbers of animals analyzed.
Additional comments: The manuscript provides a description of ZebraShare and offers a brief description of submission process and the information required in the workbook.  Both of these items are self-intuitive by looking at ZFIN and the workbook.  Due to the simplicity of the submission process, the current manuscript describes a resource rather than documenting hypothesis-based science.  One concern is that the submission process and workbook do not require detailed protocols and are rather self-explanatory.  Unlike websites that require multiple toggles or explanation of the input s, this is a basic upload of an Excel spreadsheet.  Dissemination of ZebraShare could occur over email announcements from ZFIN rather than publication here.  The inclusion of multiple mutants in their Case Studies is also questionable.  A single mutant would likely be sufficient.  It’s not clear if the focus of this manuscript is on ZebraShare or the various Case Studies that lack the anticipated phenotypes.  This detracts from the stated emphasis of the manuscript, which is explaining ZebraShare.

•	The Methods section lists multiple sections on mutagenesis that are redundant and consists of both Methods and Results, with more emphasis on Results.  It is not clear why the authors elect to say mutants were constructed as described in DeLaurier et al. and then proceed to give a lengthy description of mutagenesis results.  The authors do not provide vendor information on enzymes, kits, of any concentrations for mRNA, gRNA, Cas9 protein.  The text should be rewritten in an appropriate and concise format.
•	The number of animals or larvae examined for various experimental techniques should be specified for all experiments.  Statistical analysis, if necessary, should be performed.
•	Within the methods, authors are encouraged to specify whether analyses, such as sequencing or PCR, were performed on single embryos or larvae or from pooled animals.
•	The sentence in lines 247-249, “We do not intend to follow up with analysis of this defect, but this phenotype may be of interest to labs studying connective tissue in the head and face” is not relevant for this publication.  The focus of the current manuscript is intended to be on the purpose of ZebraShare and the types of mutants that can be submitted.
•	The choice of mutants included in this manuscript appear to have very little in common except their lack of utility to the authors.  The authors are encouraged to provide some background supporting the inclusion of these particular mutants in this manuscript. While the use of ZebraShare is promoted as a means to provide information on unpublished mutants, a single mutant example would be sufficient in the current manuscript.
•	Why did the authors elect to include five distinct Case Studies?  In particular, Case Study 2 details the lack of craniofacial phenotypes in two unrelated mutants, the ldlrap1a and kdm1a mutants.  It is not clear why the ldlrap1a mutant is included here at all. The human disease is hypercholerolemia.  It is not mentioned whether this results in craniofacial phenotypes in humans?  Why are the kdm1a mutants included with ldlrap1a in the Case Study here?  There does not appear to be any functional or disease-associated relationship between these two genes.  The authors would be encouraged to select a single mutant as an example of a ZebraShare submission.


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: ZEBRASHARE: A NEW VENUE FOR RAPID DISSEMINATION OF ZEBRAFISH MUTANT DATA
Review round: 1
Reviewer: 2

Output:
Basic reporting: No comment.
Experimental design: No comment.
Validity of the findings: No comment.
Additional comments: This study describes Zebrashare, a new resource hosted by Zfin that gives the opportunity for zebrafish investigators to share information about the mutant lines they have generated. Zebrashare was desperately needed and will without doubt be used extensively by the zebrafish community. Great study!


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

Input:
Title: ZEBRASHARE: A NEW VENUE FOR RAPID DISSEMINATION OF ZEBRAFISH MUTANT DATA
Review round: 1
Reviewer: 3

Output:
Basic reporting: The current submission by DeLaurier et al. is a clear, concise, and well-written manuscript with very minimal typographical errors which I will enumerate below. They provided sufficient literature and background. The figures are all of high quality, and I find that the decision trees are especially informative in simulating the thought processes before, during, and after submission to ZebraShare.

Lines 104-105, 117-118, 132-133: Even though the cas9 mRNA information was described in the cited paper from the same group (DeLaurier, Alvarez & Wiggins, 2019), readers would really appreciate if this information was explicitly mentioned here.

Lines 144-145, 162-163, 175-176: Same as above. A little bit of detail here would be appreciated by the readers.

Delete Lines 409-411: These were repeated from Lines 406-408.

Figure 3 Title: For consistency, change "zebrashare" to "ZebraShare".

Figure 4 Delete "." before "Wild type"

Figure 5 Legend, after "microns". Delete "<!--[endif]-->"
Experimental design: Given the numerous targeted zebrafish mutants being generated around the world  (including those generated via CRISPR-Cas techniques), there is a need to rapidly disseminate information on these mutants outside the confines of the traditional publication format. In this manuscript, the authors describe ZebraShare, a tool integrated within ZFIN, that fills this need. This new resource is relevant and a very useful tool for the whole zebrafish community. The authors had done an amazing job in defining the necessary information needed for each ZebraShare submission and in soliciting information on the validation of mutants. The mutants they described (case studies) in this manuscript are all appropriate, and they will help the readers and the zebrafish community in getting a sense of the many different kinds of mutants and the information that could be shared through ZebraShare.
Validity of the findings: The authors findings including the raw data provided are all robust and valid. Their conclusions are all well stated and are consistent with the case studies they presented.
Additional comments: Thank you for thinking about  ZebraShare and for implementing it within ZFIN. It would be a very useful resource to the zebrafish community.


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

Input:
Title: ZEBRASHARE: A NEW VENUE FOR RAPID DISSEMINATION OF ZEBRAFISH MUTANT DATA
Review round: 2
Reviewer: 1

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: The authors have made substantial revisions that have significantly improved the manuscript and address the prior concerns.  ZebraShare should be a useful resource for the community.


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

Input:
Title: ZEBRASHARE: A NEW VENUE FOR RAPID DISSEMINATION OF ZEBRAFISH MUTANT DATA
Review round: 2
Reviewer: 2

Output:
Basic reporting: This revised study describes Zebrashare, a new resource hosted by Zfin that gives the opportunity for zebrafish investigators to share information about the mutant lines they have generated. Zebrashare was desperately needed and will without doubt be used extensively by the zebrafish community.
Experimental design: The authors have added details in their description of their approaches and have included quantifications and statistics to the results. The focus on 4 different examples (instead of 7 in the original version) describing mutants with variable phenotype improves the manuscript and makes it easier to read.
Validity of the findings: The data presented  by the authors are clear and convincing.
Additional comments: This revised manuscript by DeLaurier et al., is well written and describes a new resource hosted by Zfin that was desperately needed by zebrafish investigators. It will give them the opportunity to share information about the mutant lines they have generated and possibly develop new collaborations.

This new version addresses the initial comments made by reviewers. I only spotted a few typos and minor details that need correction:
- line 143: please indicate the origin of Cas9 protein
- line 159: add the reference Parant el al., 2009 (Dev. Dyn) for describing HRMA
- line 116: write mMESSAGE instead of mMessenge
- line 155: replace with “we synthesized the Cas9 mRNA from ….”
- lines 284 and 319: add commas after last names in references
- line 347: add an “s” to “highlight”


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: ZEBRASHARE: A NEW VENUE FOR RAPID DISSEMINATION OF ZEBRAFISH MUTANT DATA
Review round: 2
Reviewer: 3

Output:
Basic reporting: The authors have addressed all my comments.
Experimental design: No comment.
Validity of the findings: No comment.
Additional comments: No additional comments


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

Input:
Title: GENOME-WIDE INVESTIGATION OF THE AP2/ERF SUPERFAMILY AND THEIR EXPRESSION UNDER SALT STRESS IN CHINESE WILLOW (SALIX MATSUDANA)
Review round: 1
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: In this study, the authors characterized of the AP2/ERF transcription factors gene family within tetraploid tree species, Salix matsudana. They analyzed the bioinformatic results of AP2/ERF gene family, including chromosomal location, conserved motif, phylogenetic tree, gene structure, gene number, syntenic analysis etc. Further, expression pattern of SmAP2/ERF genes under salt stress were screened to identify the salt-tolerant candidate genes in willow. Some concerns are listed below:

1. The author identified 364 AP2/ERF TFs genes in total, while they showed the expression patterns of 285 genes in figure 7, why? Actually, they screened 31 DEGs AP2/ERF TFs genes in response to the salt stress by RNA-seq, however, they further verified 14 genes by qRT-PCR, which was inconsistent. In addition, in my opinion, the author only need present the expression levels of 31 DEGs in fig.7, other information could be moved to the supplementary file. Finally, what the authors mean by writing Sample 1, Sample 1N, Sample 2, Sample 2N in figure 7? What’ s their relationship with ‘Yanjiang’ and ‘9901’.
2. For Figure 3, the phylogenetic tree was not that robust as showing low bootstrap values, I advise this figure could be moved to the supplementary file.
3. Line 226, Using TopHat2 software, the clean reads were mapped to the reference genome sequence of S. matsudana (Kim et al., 2013). This citation need be placed after to the TopHat2 software. Otherwise, readers would mistake it for the reference genome.
4. Where did the author deposit the clean data of RNA-seq.


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: GENOME-WIDE INVESTIGATION OF THE AP2/ERF SUPERFAMILY AND THEIR EXPRESSION UNDER SALT STRESS IN CHINESE WILLOW (SALIX MATSUDANA)
Review round: 1
Reviewer: 2

Output:
Basic reporting: Please double check the website (https://js-568garden.cn/?list_6/99.html) to make sure that data are available for public.
Experimental design: no comment
Validity of the findings: no comment
Additional comments: This manuscript concerns AP2/ERF gene family and their potential roles in salt stress in Salix matsudana, a tetraploid ornamental tree species. The manuscript was well organized, and the content was qualified for publication in PeerJ. Before the final acceptance, there are some minor errors require corrections, as listed below:
(1) Gene names should be in italic type (e.g. Line 98, Line 99, Line 101, Line 155, and ……);
(2) Species names should be in italic type (e.g. Line 133, Line 134, Line 155, and ……);
(3) Figure legend for Fig. 3B "Motif composition of tartary buckwheat AP2/ERF proteins" should be revised.
(4) More details are highlighted in the attached file.


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: GENOME-WIDE INVESTIGATION OF THE AP2/ERF SUPERFAMILY AND THEIR EXPRESSION UNDER SALT STRESS IN CHINESE WILLOW (SALIX MATSUDANA)
Review round: 1
Reviewer: 3

Output:
Basic reporting: The manuscript is an computacional analysis of AP2/ERF transcriptional factors in Salix matsudana compared to Salix purpurea and Populus trichocarpa also shows RNA expression of some genes related to salt tolerance in S. matsudana.
The work is well written, results are quite well shown and add knowledge to this tree species with importance in China.
Experimental design: I have some comments and questions to the authors:
Line 104: correct the word alfalfa
Line 114: Koidz should not be italic
Line 151: what is the meaning of "mimic RNA sequencing"
Line 164: please review the Pfam code (PF00847.16) and add the gathering cut-off value.

Line 171: why did your used SMART ? This tool also use Hidden Markov Model.

Line 179, for multiple sequence alignment and phylogenetic tree, did you used dataset of pfam or your "in-house Perl script method?  Could you mention, why they did not use the proteins selected by Pfam?.

Line 181: what was the criteria to select only the 48 AP2 domains of Arabidopsis and Populus, please, could you increase the citations of these works.

Line 190: the Salix matsudana genome is already assembled? and annotaded?, please if so, you could add the url.

Line 201: The citation should be just after TBtools.

Line 216: how the gene pairs were estimated for the nonsynonymous substitution rate (Ka) and Synonymous substitution rate (Ks)?, it was all vs all? are they paralogs?.

Line 218: I dont find the formula T = Ks/2λ in the Lynch study, and the The clock-like rate λ value for Populus, please review.

Line 228: the fragments per kilobase of transcript per million fragments mapped (FPKM) was estimated by your team? if yes, could you mention how it was calculated, if it was not you could you please add the citation.

Line 237: I would like to suggest to add the supplementary material with .domtblout information of hmmsacan, to make the search and the result of that search easier.

Line 244: The criteria used to cladificate the ERF and AP2 subfamilies, were according to the presence of the WLG and YLG elements respectively?, please clarify this point, including also the same criteria for RAVE and Soloist subgroups.

Line 248: Please change "Basing" to Based on

Line 299: The S4 supplementary data is missing. Also could you add the the bioinformatic tool reference used to determine FPKM?

Line 344: How to explain the large variations in the divergence times of the genes (Table S3), do you know if there were ploidization events in the species, do you consider that these data correlate with whole genome duplication?.

Line 399: The statement " Tetraploid Salix is valuable because they have higher tolerance to abiotic stress than their diploid relatives" is conclusion or you have a reference that confirm that?

Line 461: I would like to suggest adding a histogram, presenting the Ks / Ka or Ks vs frequency or density to better visualizing that result that I find interesting.

Line 474-478: Since the data indicated that the two diploid progenitors of Salix matsudana underwent hybridization and genome duplication not more than 10 Mya with only one gene family? I think it would be more appropriate to mention that apparently there were two large gene duplication events 8 and 36 Mya ago in the AP2 / ERF family.

Figure 1, please add the MEGA 7.0 citation
Figure 3, correct the word "members" . The protein length of figure b and c do not have the same scale, please check
Figure 7, please, clearly indicate the samples with the two conditions (before and after salt stress)
Validity of the findings: The results and discussion of this article add knowledge Salix species related to stress tolerance.
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: GENOME-WIDE INVESTIGATION OF THE AP2/ERF SUPERFAMILY AND THEIR EXPRESSION UNDER SALT STRESS IN CHINESE WILLOW (SALIX MATSUDANA)
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: The author have addressed most of the comments, however, For Figure 3, the author should use other method or software to perform the phylogenetic analysis, to make the tree 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: GENOME-WIDE INVESTIGATION OF THE AP2/ERF SUPERFAMILY AND THEIR EXPRESSION UNDER SALT STRESS IN CHINESE WILLOW (SALIX MATSUDANA)
Review round: 2
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: I consider the article was improved. There were some questions not answered from my previous review but the authors make changes in the manuscript.
Validity of the findings: no comment
Additional comments: The authors have improved the article.


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

Input:
Title: GENOME-WIDE INVESTIGATION OF THE AP2/ERF SUPERFAMILY AND THEIR EXPRESSION UNDER SALT STRESS IN CHINESE WILLOW (SALIX MATSUDANA)
Review round: 3
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: The authors have addressed all of my comments and I have no further suggestions.


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

Input:
Title: THE PREVALENCE OF FATIGUE AMONG CHINESE NURSING STUDENTS IN POST-COVID-19 ERA
Review round: 1
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: This is a meaningful survey on the prevalence of fatigue among Chinese nursing students. Before publication, I have several concerns as follows:
1. In line 123-128, the authors said "To lower the risk of contagion between
 students, the spring semester was postponed in all universities in China since early 2020. Further, all classroom teaching has been suspended, and replaced by online teaching and learning (Xinhuanet, 2020a, Xinhuanet, 2020b). Due to lockdown measures, outdoor/ physical activities were prohibited." Is this true in all areas of China? Or what's the period/areas when outdoor/ physical activities were prohibited?
2. Using the Questionnaire Star Application embedded in WeChat, how did the participants provide the written informed consent?
3.  A NRS was adopted to evaluate severity of pain (Haefeli and Elfering, 2006). What kind of pain was asked here? What is the relationship between pain and fatigue? The authors should introduce and discuss with more details.
4. How did the authors measured the economic loss, perceived economic status and perceived health status? Is there any criterion or tools for these?
5. In the univariate analyses, I see age (years) was significantly statistically different between the two groups. So is the variable age entered into the multiple binary logistic regression model? If yes, multicollinearity could exist between age and the year of study.
6. A total of 1,121 nursing students were consecutively invited to participate in this study; of whom, 1,070 met the study criteria and completed the assessment, yielding a response rate of 95.5%. Is that mean 51 of the invited nursing students did not match the criteria? Why they were lost?
 7. In the Discussion section, I don't suggest the authors to say "This was the first study that examined the prevalence of fatigue among nursing students in post-COVID-19 era". Its is hard to say the "first".
8. Actually Table 2 and Figure 1 showed the same results.
9. Typo in line 222: (OR=1.48, 95%CI=1.08-3.33, P=0.015; compared to low loss)).


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

Input:
Title: THE PREVALENCE OF FATIGUE AMONG CHINESE NURSING STUDENTS IN POST-COVID-19 ERA
Review round: 1
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: The authors aimed to examine the prevalence of fatigue and its association with QOL among nursing students during the post-COVID-19 era in China. It is qualified for PeerJ, while several issues should be addressed first.
1.	In the abstract, the authors declared “many nursing students were summoned to work in hospitals to compensate for the shortage of manpower”, however, as I know, few medical students were summoned to work in the COVID-19 outbreak. So, it would be better to give more information in the Introduction.
In the methods, was there any variables such as whether the students were summoned to work or not investigated? If yes, please give the information, if not, please give the reasons.

2.	In this study, five university nursing schools (locates in Beijing, Jilin, Lanzhou, and Wuhan) were investigated, these four cities are in the north or centre of China, they can’t represent the prevalence of China.

3.	How many students from Wuhan, was there any difference from other school?

4.	In the discussion, if no data supported the medical students served as volunteers in clinical settings, it can’t be conclude as the reasons of high levels of stress and anxiety at work.

5.	The English writing should be revised by a native speaker.


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

Input:
Title: THE PREVALENCE OF FATIGUE AMONG CHINESE NURSING STUDENTS IN POST-COVID-19 ERA
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: Thank the authors for considering my concerns and revised thea 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: THE PREVALENCE OF FATIGUE AMONG CHINESE NURSING STUDENTS IN POST-COVID-19 ERA
Review round: 2
Reviewer: 2

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: ASSESSMENT OF HAND FUNCTION IN WOMEN WITH LYMPHADENOPATHY AFTER RADICAL MASTECTOMY
Review round: 1
Reviewer: 1

Output:
Basic reporting: Thank you for conducting this study in the much needed area of function in women with breast cancer related lymphedema.  I hope that you find the comments and suggestions helpful.

There are some opportunities for improvement in flow and meaning in the introduction and methods, and correction of grammatical errors and use of punctuation here and there.

Introduction

1.  Line 37: No comma after patients.

2.  Lines 39-41: This sentence could be much clearer.  I suggest (if this still accurately reflects your meaning): The cancer registry program of twenty-five Population Based Cancer Registries (PBCRs) reports increasing trends for incidence and mortality of breast cancer in Indian women.

3. Lines 55-56: You wrote: “It is also seen that lymphedema cause restricted range of motion in the affected limb, reduced functional ability as well as physical disfigurement, pain, and skin problems.”  I suggest instead: “BCRL is also associated with restricted range of motion in the affected limb, reduced functional ability, as well as physical disfigurement, pain, and skin problems.”

4. Line 73:  change “done to assess” To “that evaluated”

5. Use person-first language:  Instead of “lymphedema patients”, say “in women with BCRL”

6. Once you use the acronym BCRL that first time, you should use that throughout… you don’t need to spell it out anymore, nor do you need to say lymphedema when referring to breast cancer related lymphedema; you can simply use BRCL.

7. Try to be more consistent with the use of patients, women, participants, and subjects. Where appropriate, use a consistent term for the women enrolled in your study.

8. Line 62-64: You wrote: “While most of the studies subjectively measure the hand function, there are few studies available that have measured objectively the hand function in patients with breast cancer related upper limb lymphedema.  I suggest a slight edit to: “While most studies have used subjective measures to evaluate hand function in women with BCRL, few studies have used objective measure of hand function.” I suggest moving the information about the reliability and validity of the tools used in this study to the methods section.

9. And then move lines 69-71 to the end of what is currently line 64.  I also suggest these edits to that sentence: You wrote: “It is important to assess hand grip strength and hand function, so that appropriate clinical assessment and intervention planning of lymphedema can be based on it.”  I suggest: “It is important to objectively assess hand grip strength and hand function so that appropriate and complete clinical assessment and intervention can be implemented to address any impairments or functional limitations”.

10. Lines 72-76: You wrote: “Objective assessment of hand function will give more clarity on the level of independence in performing functional activities of daily living comparatively better than subjective assessment of hand function, hence there is requirement of assessing hand functional activity objectively in patients with BCRL. This study evaluated the hand grip strength and hand functional activities in people with BCRL”.  I suggest modifying this last paragraph to explicitly state the study purpose or aim.  You also need to add that you’re comparing your findings to normative data. My suggestions:  The purpose of this study is to 1) evaluate the hand grip strength and hand functional activities using objective outcome measures in women with BCRL; and 2) to compare findings in women with BCRL to normative data.  In women with BCRL, objective assessment of hand function will provide greater clarity and precision regarding performance of functional activities of daily living than will subjective assessment alone, which will better guide clinical practice.

11. I also highly recommend you include a hypothesis statement in that last paragraph if you have one.  The study purpose and hypothesis are not clearly stated.  I’ve made some recommendations with reference to that. In addition, the current introduction does not mention normative data or comparison to that (which should be done in the purpose statement).  A hypothesis could be stated as such: “We hypothesize that grip strength and objectively measured hand function will be impaired in women with BCRL compared to normative data.”

Materials and Methods

1. Line 78: Change “It” to “This study”

2. Move the information regarding sample size to the Statistical Analysis section at the end of methods.

3. The word data is plural and should be followed by were or are, not was or is.

4. Add the information about reliability and validity of the outcomes to the appropriate section in methods.

5. Statistical Analysis section:  Move sample size estimate here.

Literature references, sufficient field background/context

1. The article includes sufficient introduction to breast cancer related lymphedema.  There are some areas that need to be developed and some references need to be checked and potentially updated.

2. Lines 42-43: You should use primary references here.  The reference you cite is for a different study – not an incidence study.

3. Lines 44-49: The reference you cite for this paragraph supports only the first sentence of the paragraph.  While the authors of the paper you cite do describe the finding in your second sentence, they are citing a different study. It would be best to cite the original, primary, source for your references whenever possible.

4. Line 51: You refer to 25% incidence of BCRL here, but earlier you say 5.5 to 56% incidence.  I suggest being consistent, or you could modify this sentence to say: “Women with BCRL may have impaired upper limb use during functional activities.” (and, of course, keep the citation)

5. There are two issues you need to address in terms of background and gaps in the literature:

You don’t talk about what normal grip strength or hand function is. You compare your data to normative data but never talk about the normative studies. You should add a discussion of what normal strength is in women in this age group (you can cite the studies that use the normative data you’ll be comparing too). Also relate those findings to the findings from other papers.  How much have the other studies found grip strength to be impaired in BCRL cases vs non-cases, or compared to normative data?  Consider adding this after line 58.

The paper would really benefit from a more detailed discussion of the BCRL literature on hand function to address these questions:  Of the studies that looks at patient reported outcomes of function, what did they show?  Of the studies that did look at objective measures of function, what did they use, and what did they show?  You write that “there are few studies available that have measured objectively the hand function in patients with breast cancer related upper limb lymphedema.”  (line 63).  Few implies that some were done.  If none were done, say “No studies have been identified that”.  If there are some, talk about their findings. The you can come back to that in your discussion to compare and contrast your findings to theirs.

6. At your current line 71, you have 4 references.  I’m not clear about the relevance of reference #16 here. (Rhee H, Yu J, Kim S. Influence of Compression Types on Hand Function: A Preliminary Investigation. Journal of Physical Therapy Science. 2011;23(3):477–80.)

Article structure, figures, tables:

The structure of the article conforms to the acceptable journal section format. Two tables are included.  I suggest the addition of a Participant Characteristic Table (as table 1 with changes to titles to Table and 3 as a result) with age, body mass index, hand dominance, side of BCRL, type of cancer treatment (surgery, radiation, therapy, chemotherapy), number of nodes removed, duration of BCRL, etc.).  This is important so that the reader knows who the participants were. The reader cannot generalize the results of this study to their own patients if they don’t know how similar they are. This speaks to the external validity of the study.

All appropriate raw (outcomes) data has been made available.
Experimental design: The paper fairly clearly defines a gap that the authors are trying to fill – the lack of assessment of hand function and grip strength using objective data.  Grip strength is most often assessed with objective measures (dynamometry) and has been reported in a number of studies.  However, the assessment of hand function using an objective tool is novel and has clinical value. However, there are some additional gaps that I’ve described above.

2. Line 90: Participant eligibility:  In exclusion criteria, what is meant by “recent” in terms of fracture or surgery?

3. Lines 91-92.  Delete and add below a subheading.  My suggestion:

Objective Measures

A hand dynamometer and pinch gauge/ pinch meter were used to measure power grip and precision grip strength and The Jebsen-Taylor hand function test (JTHFT) Tool Kit was used to assess hand function. Hand dynamometer and pinch gauge are valid instruments to assess grip strength.  (And add a citation for this   last sentence)

This study is a single group cross sectional study, comparing findings in women with BCRL to normative data.  The biggest issue that must be addresses is that there is no indication of how the normative data was derived, who they are, their age, etc.  The comparison is not valid without details about the sample from which this the normative data arose.

in the intro and methods, a discussion of normative data may need to be added.  Without knowledge of the normative data, the conclusions cannot be confirmed.
Validity of the findings: The outcome data looks good.  However, there are some threats to study validity that I hope can be addressed.

Internal validity is threatened by 1) unknown source of normative data, and 2) potential for confounding effects of unknown clinical and demographic characteristics, which were not reported.

External validity is threatened by sampling but more so by the fact that the sample is poorly described. In cross sectional designs, internal validity can be improved by attempting to control for confounders during the sampling process (inclusion and exclusion criteria). While external validity may be sacrificed for these tighter inclusion criteria, at least the study conclusions will be more trustworthy.  However, we don’t know much about the sample to see if there is an underlying issue with potential confounders. If all the women had chemotherapy induced neuropathy, for example, we can’t be sure that the association found (between BCRL and hand strength/function) is a true associations.

The data for the sample studied has been provided. Thank you. However, references for the normative data were not provided.

Clinical and demographic characteristics are poorly reported and are not controlled for.
In the discussion (lines 153-155), you state: “The overall time taken by the subjects for completion of tasks was 68.8 seconds for right hand dominant and 100.3 seconds for left hand dominant.”  Were all your participants right hand dominant?  If so, you need to very clearly state this where ever it’s needed.  Dominance is a potential confounder, and if you controlled for that during your sample selection, include that in your paper please (e.g., as an inclusion criteria). You do say that the BCRL has to be the dominant side, but not that it had to be right or left sided.  According to your data spreadsheet, you have both right and left affected (thus dominant) participants.

The conclusion should be modified slightly.  You state (line 174-177): The results of this study indicate a significant reduction of hand grip strength and hand function, resulting in reduction in functional activities in patients with BCRL. These impairments are amenable following an upper limb rehabilitation intervention. Based on the result of this study, physical rehabilitation is recommended in the management of BCRL.”  There are two concerns here.  1) You can’t say that the reduction in strength and function result in reduction in functional activities.  You didn’t test that.  I suggest removing “resulting in reduction in functional activities in patients with BCRL” from the sentence. 2) You also can’t say that the impairments are amenable to intervention and that based on your findings rehab is recommended because you didn’t test that either.  You can say that based on your findings you recommend that objective measures of grip strength and function be included in the assessment of women with BCRL to better guide clinical decision making and patient care, which may include impairment associated with hand strength and function.  You can use words like “our findings suggest”, or “we speculate that”…. Etc.

In addition, your paper needs a limitation sections, and directions for future research.
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: ASSESSMENT OF HAND FUNCTION IN WOMEN WITH LYMPHADENOPATHY AFTER RADICAL MASTECTOMY
Review round: 1
Reviewer: 2

Output:
Basic reporting: Article is written with clear and concise English. There were places where references were missing and those places are highlighted. A comment was made on the figure.
Experimental design: The research question is clear. The authors did a nice job with identifying the knowledge gap. A few comments are made to improve the methods section.
Validity of the findings: The study uses valid and reliable instruments for the assessments. The sample size is small and seems like a pilot study. This can be highlighted in the conclusion. Future studies would need to be done on a bigger sample to confirm findings. The data analysis is done appropriately and I have made a few suggestions for improvement.
Additional comments: This important study should be published with minor revisions as suggested.


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: ASSESSMENT OF HAND FUNCTION IN WOMEN WITH LYMPHADENOPATHY AFTER RADICAL MASTECTOMY
Review round: 2
Reviewer: 1

Output:
Basic reporting: Thank you for your attention to the suggested revisions!  The reporting is clear, the appropriate background literature has been discussed and references, the results and conclusions are consistent with the hypothesis. I like the addition of effect sizes as suggested by the other reviewer.
Experimental design: The hypothesis and study purpose are present and clear. The gap in the literature has now been addressed with the modifications.  Methods are clear.
Validity of the findings: Data has been provided. Analysis is clear. Conclusions are valid and not over-reaching.
Additional comments: The revisions were acceptable and well done.  I have one suggestion - rather than use the term "normative data" switch to "control group data" or healthy controls.  That's actually a more accurate reflection of what you did.  You didn't compare your BCRL group to "normative data" per se.  I tried to correct that in the annotated pdf.


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

Input:
Title: OUTCOMES OF HOSPITALIZED PATIENTS WITH COVID-19 ACCORDING TO LEVEL OF FRAILTY
Review round: 1
Reviewer: 1

Output:
Basic reporting: The authors carry out an adequate review of the bibliography for the introduction and part of the results, but they need to explore and discuss their information further. You need to improve figure 1 and review the final analysis of the study.
Experimental design: Method
The authors need to review the type of study, as it is not prospective.
The scale used in the study could be used as the authors put it in the study that is to say without evaluating the elderly and only by the medical records? Does the scale validation for Spanish from Spain indicate this? In the creation of the scale, the authors who created it refer that the scale can be used in this way?
Has the scale been validated for Spanish in Spain? especially the cutoff point? this information does not appear.
The authors need to better explain the instrument used, the extraction of information from medical records.
Validity of the findings: the results need to answer the objective of the study, the authors want to present important data but that in the course of these and the analyzes are lost, leaving aside its main outcome, which is fragility and not the survival of the elderly.
Results
Table 1 not only demographic data appear, but also clinical data (diseases), there is some information with a data that can direct the statistical significance of the category. Review the title of the table 1, it is not adequate according to the data it presents.
In Table 2, presentation of signs and symptoms it is not clear how the change in consciousness and behavior was assessed, making this information more clear.
In table 3, what does identified microorganism mean? Is related to what?
The information about heart disease that the authors refer does not appear in table 3, making this information clearer.
To improve the information in figure 1, it is not recommended to make a figure in 3D. Now, why do figure and not table? What do the authors want to present? The way the data is distributed the information is not adequately evidenced
This information is about what? “Lung disease: bacterial pneumonia, ARDS, pneumothorax, pleural effusion. Neurological disease: meningitis, seizures, stroke. Heart disease: congestive heart failure, myocarditis, pericarditis, endocarditis, arrhythmia, cardiac ischemia, cardiac arrest. Hematological disease: coagulation disorder, subsidiary anemia. Muscle disease: rhabdomyolysis. Digestive disease: digestive bleeding, pancreatitis, liver failure. Psychiatric disease: acute confusion syndrome, psychiatric complications. Infectious complications: infectious upon admission, bacteremia. Inflammatory disease: endocarditis, myocarditis, pericarditis, pancreatitis, meningitis”
Table 4 shows linear regression related to mortality, interesting information but which does not answer the objective of the study. In this sense, the dependent variable, frailty, was considered as independent, which leads to another study objective, to review this information.
Additional comments: Title
The title is in agreement with the objective of the study but not with the results. it is suggested to modify it or review the study results

Abstract
The authors need to improve the method, results and conclusion. It does not adequately answer the study objective. The descriptors used are adequate

Introduction
The researchers describe the situation that Spain experienced with the beginning of the pandemic of COVID-19; bring important data that must be rigorously evaluated, especially with the large number of elderly people who died from the disease or complications from the disease.
At present there is no standard definition of frailty syndrome, the authors bring a definition of it but is it the theoretical framework used in the research? I think they could bring the consensus of Morley's frailty that is widely used and the concept of the instrument used to identify frailty in the elderly in this study.
The authors describe the frailty scale in the introduction but that this should be in the method.
The next paragraph: “In addition, our research group has also considered the CFS as the best tool to use in this pandemic context because it is less time consuming and because ICU patients are often unable to meaningfully participate in frailty assessment” is a conclusion. The authors need to review its location within the text in the corresponding section.
The study needs a plausible justification for why it is important to do it.
The objective of the study is “to explore the clinical complications and prognosis of individuals with COVID-19 admitted to a third-level hospital and to assess the relationship between these complications and prognosis with frailty” but in the introduction, the authors do not write nothing about the complications and prognosis.

Discussion
The authors discuss data on elderly people who live in nursing homes but there is no way to raise this hypothesis because it is data that has not been presented, which can lead the discussion to error. The authors must also inform data on the number of elderly people who are dying in the world, there is already literature on the subject, review the discussion of sociodemographic data.
Contamination by COVID-19 leads to changes in the organism. The authors need to be careful when stating that "an episode of delirium in elderly and fragile patients should lead us to suspect COVID-19," since a deeper evaluation is important for this. It is recommended to revise the indicated paragraph.
The authors refer "in addition to confirming the relationship between frailty and mortality in patients with COVID-19, delirium behaved as a predictor of death in frail people" this result is interesting does not answer the objective of the study, review this information
In the course of the text, no hypothesis was presented, as if to affirm, as the researchers indicate, that the study hypothesis in which they refer that “the evident increase in the mortality rate among fragile patients supports the hypothesis of our study”. Likewise, the authors refer “Another possible cause could be related to the fact that people who are weaker and less likely to survive have a lower allocation of health resources than the subgroups with greater resistance to infection” but do not make the corresponding discussion, this could bring about a legal medical problem.
The authors do not present the limitations of the study

Conclusion
The conclusion does not answer the objective of the study. The following statement: "Higher frailty scores were associated with worse results and an increased mortality rate in ICU admissions" not identified among the results, it is suggested to review the information
What would be the recommendations? What would be the contribution of your work to the advancement of science and to the area of gerontology and geriatrics?

References
Suitable for the study