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: ADAPTIVE DIVERGENCE, NEUTRAL PANMIXIA, AND ALGAL SYMBIONT POPULATION STRUCTURE IN THE TEMPERATE CORAL ASTRANGIA POCULATA ALONG THE MID-ATLANTIC UNITED STATES
Review round: 1
Reviewer: 2

Output:
Basic reporting: This article is clearly presented, and well organised. It is clearly written.
Experimental design: This article presents original results on the genetic structure of a temperate scleractinian coral and its associated dinoflagellate symbiont in two locations of western Atlantic. The research question is meaningful. The data come from mRNA sequencing which was initially performed for an experimental study of thermotolerance. The results are based on an analysis of potentially selected loci, on differentiation tests and Fst estimates, and on multivariate analyses.

The results are interesting, but their interpretation is limited by the quite low final number of SNPs retained in the study, especially for the symbiont. This is a problem for the search of potentially selected alleles, and this point should be in the discussion: is it really meaningful to test for outlier loci with only 68 SNPs? The study is also based on the comparison of only two populations which also limits the conclusion about local adaptation, and replicates would be useful. I understand this is not possible for the present study, but this point should be discussed as well.
Validity of the findings: From a methodological point of view, the authors tested for outlier loci in their dataset. I wonder if this analysis can be biased for dinoflagellates considering their life cycle and ploidy ? For the outlier analyses there was no filtering to keep one SNP per locus : why ? We can see on line 357 that nine coral contigs contained more than one outlier : I wonder if this could have modified the analysis. More generally, in the SNP filtering the authors did not retain SNPs which were not in Hardy-Weinberg equilibrium : but for dinoflagellate, do we expect panmixia ? For the outlier SNPs, both for coral and symbionts, do they correspond to non-synonymous mutations ? And I think that analyses of outlier loci should include several different methods to check the robustness of the results.
Regarding the coral samples, it would be necessary to indicate if putative clones were detected in the dataset (as this can bias the study of genetic structure). Apart from the genetic structure, the authors could give some estimates of genetic diversity such as expected heterozygosity. For this coral dataset, an analysis of genetic structure (with the software STRUCTURE or another similar method) would be interesting to estimate levels of admixture in individuals. There is also an interesting result of differentiation among white and brown coral morphs in Rhode Island (see Fst and PCA), but this is not discussed. More generally the white / brown differentiation is not discussed here, whereas this dataset is a very good opportunity to study this polymorphism.
Additional comments: Abstract :
"In the symbiont, the two putatively adaptive loci…" (there are only two candidate loci, right?)

Introduction :
line 69 : factors instead of forces
line 78 : some organisms or all organisms ?
line 94 : as drivers
lines 95-97 : maybe give some species names
lines 99-100 : you could check the litterature on the thermotolerance of Mediterranean octocorals for example
line 103 : at the beginning of the sentence, write the full genus name
line 109 : give some numbers
line 119 : five weeks in aquarium right ?
line 121 is similar to line 101

Materials and methods :
lines 130-134 : were brown and white colonies sampled exactly at the same site and in the same ecological conditions ?
line 132 : samples sizes are already given on line 130
line 140 : is there a possibility to collect colonies issued from asexual propagation ?
lines 174-181 : what about light and food ? Did you use the same conditions for white and brown colonies ?
line 194: the experiment was a short stress, but the sampling lasted 1 h  40 min after the experiment : please explain this (e.g. what were the first and last samples?).
lines 254 – 255 : do the numbers refer to the number of species in the different databases ?
line 263 : this filtering seems logical, but then you can’t test here if there was some signals of dinoflagellate sequences in white morphs ?
line 296 : what is the meaning of "h" in your Hardy-Weinberg filtering ?
lines 300-302 : give a brief explanation about how this method works. Why didn’t you filter for on SNP par locus here ?
 And it would be necessary to test other methods to detect loci under selection
line 303 : in table 3 you mention low and high outliers : please explain here.

Results :
line 330 : by "sites" do you mean bp ? (because vcf files usually refer to variant sites)
lines 332-333 : recall here what are the two and four populations analyzes (and use plural for populations)
lines 344-345 :it would be interesting to analyse other axes in PCA (this can be in supplementary material)
line 353 : " a total of 19 sites were used" : because you test later if there are some outliers, you can’t say here that they are neutral
line 353-354 : indicate that the two outliers were not on the same contig (deduced from supplementary material but this should be mentioned here). And you could nevertheless do an Fst analysis on this SNPs.

Discussion :
line 388 (see also line 407) : you did not describe patterns of connectivity here but patterns of genetic differentiation. For the dinoflagellate, the genetic differentiation could also be driven by drift of different genotypes inside colonies which could lead to genetic differentiation among populations. This could also be driven by selection of different genotypes even if this was not detected by your outlier analysis because of a low number of SNPs.
line 419 : Sinularia is an octocoral
line 421 : I would suggest octocoral rather than soft coral
line 449 : "connected and isolated" ? I don’t understand
line 465 : what about the larval duration for the other species mentioned above ?
line 475-476 : please explain how environmental differences could drive divergence in neutral loci.
line 482 : "the metapopulation could be able" rather than "was able"
line 493 : "similar differences" : similar to what ?
lines 501-502 : for this kind of analysis it is also important to consider and discuss the possibility of false positives.
line 518 : response to which stress then ? You just mentioned copper. And you also mentioned a gene putatively involved in variation in symbiont density (so maybe not only coral response).
lines 529-533 : it would be important to analyze more loci to get more confidence in outlier analysis

Conclusion
line 542 : why do you not discuss this ?

References : check the bibliography format. For example some references use abbreviated journal name, and some others use full name


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: ADAPTIVE DIVERGENCE, NEUTRAL PANMIXIA, AND ALGAL SYMBIONT POPULATION STRUCTURE IN THE TEMPERATE CORAL ASTRANGIA POCULATA ALONG THE MID-ATLANTIC UNITED STATES
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: This is the second time I review (Reviewer #1 in the previous round) the manuscript entitled “Adaptive divergence, neutral panmixia, and algal symbiont population structure in the temperate coral Astrangia poculata along the Mid-Atlantic United States” by Aichelman and Barshis.

First of all, I would like to acknowledge the impressive work made by the Authors during the revision.They addressed and clarified most of the topics raised from the first version of the MS and I believe the manuscript has significantly improved.

I thus recommend the manuscript for acceptance.


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: MACHINE LEARNING PREDICTION OF MOTOR RESPONSE AFTER DEEP BRAIN STIMULATION IN PARKINSON’S DISEASE—PROOF OF PRINCIPLE IN A RETROSPECTIVE COHORT
Review round: 1
Reviewer: 1

Output:
Basic reporting: 176 ‘can be interpret easily’: typo.

Figure 3B: please use different colours (lowerright corner is unreadable).

Table 1: legend is incomplete.
Experimental design: See below.
Validity of the findings: See below.
Additional comments: Habets and colleagues describe an interesting study on a machine learning based prediction model to model success after DBS surgery (or rather: failure of DBS surgery). Their use of an advanced modelling approach is commended, as well as their use of preoperative clinical features to enhance the generalizability. The authors rightly state that this model is a proof-of-concept and should not be interpreted as a ‘final model’ for clinical practice.
There are however, several limitations with regard to insufficient information on variable-importance, a small sample size which is (incorrectly) stated to be overcome through cross-validation, and lack of external validation whereas more cohorts with these data are available.

73. “… limited or no improvement of motor disability”: do you intend motor fluctuations or severity of motor symptoms?

100-102 “To add value… clinical decisions”: you correctly state that challenging cases should be improved rather than valid decisions. However, given that you intend to develop a generic model the case-mix you require should resemble the case-mix from the actual population in order to prevent overfitting / underfitting.

111-113 “We included all… on-stimulation condition”. How many patients were initially considered (i.e. underwent STN DBS in the given time period) and how many patients were excluded for the mentioned reasons?

114-115: Was this study approved in the absence of informed consent, or was formal evaluation waived given the retrospective nature?

117-123: Please provide a list with the exact tests that were incorporated in the model (‘categorical, and letter tests’ are relatively vaguely descripted).

150-151: The reason for labelling a patient as a ‘strong responder’ in case of MCID improvement in any of the three domains can be understood, however if a patient improves in one domain and deteriorates in the two others this label may be subject for debate.

172-173: Using this approach (i.e. cross-validation) the test-set remains relatively small and you run the risk of testing on outliers. I agree with the merits of this approach (definitely better than split-sample validation) but the limitations should be discussed as well.

173: ‘predictive variables or confounders’: please remove the word ‘confounders’, there are no confounders in prediction modelling (as opposed to causal research).

176 ‘can be interpret easily’: typo.

221 “63 out of 90 patients were categorized as strong responders”. See earlier comment, please consider at least reporting the MCID improvements per domain separately as well rather than joined together.

231 Why choose 0.24 as a threshold? Even if the argumentation holds true, are you confident that this threshold would hold up in a prospective study of large sample size and therefore should be utilized in clinical practice?

Discussion:
I do find the discussion to be somewhat overoptimistic of the actual performance. It states that in 78% of cases the predicted class would be correct, however there are more outcomes relevant to PD care than just the UPDRS-classes (e.g. quality-of-life, satisfaction with surgery etc.). Moreover, the sample-size is by far too small to make any definitive claims on its utility. Although the authors have stressed this in the final paragraphs of the discussion, I would appreciate some more elaboration on the 'next required steps' before this research can proceed to clinical implementation.

279-285: see previous comments: there is no such thing as confounding variables in prediction modelling.

286-289: with such a small sample size: overfitting is still an issue. I do agree that cross-validation circumvents this issue, but definitely not entirely and the statement that cross-validation ‘decreases restriction due to sample-size’ is untrue. Moreover, cross-validation certainly does not prevent selection-bias as this is inherent to your study-design. An option is to provide ROC curves per cross-validation run to assess the dispersity of results (although this may not be very visually attractive).
Why was external validation not performed? There are a lot more similar cohorts available with which to increase your sample size and overcome several of the limitations mentioned in your discussion.

A rather large limitation of this study is that this model is based only on those patients that have been selected for surgery. Cases on which there is ‘preoperative’ doubt may or may not have been rejected for surgery and therefore there is a large likelihood of those patients being underrepresented in the training-set, thereby reducing its validity in a clinical setting.

Figure 3B: please use different colours (lowerright corner is unreadable).

Figure 3C: please provide exact numbers rather than visualization.

Table 1: legend is incomplete.


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: MACHINE LEARNING PREDICTION OF MOTOR RESPONSE AFTER DEEP BRAIN STIMULATION IN PARKINSON’S DISEASE—PROOF OF PRINCIPLE IN A RETROSPECTIVE COHORT
Review round: 1
Reviewer: 2

Output:
Basic reporting: The basic reporting is excellent:

The submission is ‘self-contained,’ represents an appropriate ‘unit of publication’, and includes all results relevant to the hypothesis.
Coherent bodies of work are not inappropriately subdivided merely to increase publication count.
Experimental design: The experimental design is conceptualised and conducted very well:

This is original primary research within the Aims and Scope of the journal. The Research question is clear, relevant, timely and meaningful. It is stated how research fills an identified knowledge gap.
The investigation is conducted rigorously and to a high technical standard. The research is conducted in conformity with the prevailing ethical standards in the field.
Methods described with great detail. The raw data is provided to replicate the results.
Validity of the findings: The validity of the findings is excellent:

The raw data is provided to replicate the results. The benefit to literature is clearly stated.
All underlying data have been provided; they are robust, statistically sound, and controlled.
Conclusions are well stated, linked to original research question & limited to supporting results.
Additional comments: In this is a proof-of-principle study in 90 patients with Parkinson’s disease Habets et al. implement a machine learning logistic regression prediction model of “weak” and “strong” response to bilateral subthalamic stimulation. The model input parameters include a wide range of preoperative variables. Not abiding to the “rule-of-ten” is feasible because the authors use this machine learning prediction with a 10-fold cross-validation. The model predicts weak responders with a good C-statistic (0.88) and has 78% diagnostic accuracy.
This is a timely study by an experienced group, the statistical approach is sound and the primary research question of preoperative prediction of postoperative motor DBS outcomes is of key clinical importance. Overall, the authors have done an excellent job in explaining the advantages of the implemented machine learning logistic regression prediction model as opposed to the traditional univariate approach implement in a number of earlier studies.
Minor points:
-	In 4 patients the motor improvement was predicted to be strong but was observed in truth to be weak. It is understandable to include only preoperative clinical parameters for the model. However, the authors may add that STN targeting was confirmed (e.g. based on postoperative imaging or intraoperative electrophysiology – at least in these 4 patients) so that it is clear that there were no lead misplacements which could account for false predictions in these 4 patients.
-	The preoperative motor response was quantified by subtracting UPDRS-III ON – UPDRS-III OFF. Other studies have often used a ratio and reported the % improvement. Could the authors explain why they preferred a subtraction?
-	Line 329 and 330: the term neuropsychological functioning is very broad and may be specified (executive functions).
-	Line 332: higher preoperative QoL-scores predict larger QoL postoperative improvement


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: MACHINE LEARNING PREDICTION OF MOTOR RESPONSE AFTER DEEP BRAIN STIMULATION IN PARKINSON’S DISEASE—PROOF OF PRINCIPLE IN A RETROSPECTIVE COHORT
Review round: 2
Reviewer: 1

Output:
Basic reporting: I have no further comments.
Experimental design: I have no further comments.
Validity of the findings: I have no further comments.
Additional comments: I have no further comments.


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

Input:
Title: MACHINE LEARNING PREDICTION OF MOTOR RESPONSE AFTER DEEP BRAIN STIMULATION IN PARKINSON’S DISEASE—PROOF OF PRINCIPLE IN A RETROSPECTIVE COHORT
Review round: 2
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: This is the first revision of a proof-of-principle study on machine learning logistic regression prediction model of “weak” and “strong” response to bilateral subthalamic stimulation in 90 patients with Parkinson’s disease. The authors did a good job in implementing the most reviewer comments and the manuscript has improved.


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

Input:
Title: STEM CELL IMAGING THROUGH CONVOLUTIONAL NEURAL NETWORKS: CURRENT ISSUES AND FUTURE DIRECTIONS IN ARTIFICIAL INTELLIGENCE TECHNOLOGY
Review round: 1
Reviewer: 1

Output:
Basic reporting: Review of Manuscript: #49552 entitled ‘Stem Cells imaging through Artificial Intelligence
Technology: Current issues and future directions’ by Ramakrishna and colleagues.

Dear The Editor

The above manuscript by Ramakrishna and colleagues is a review manuscript describing the role of artificial intelligence technology in stem cell imaging. The discovery of stem cells opened many doors in medicine in terms of treatment of many diseases and conditions with no cure at present. The use of stem cells in medicine is however hampered by the great heterogeneity observed and also their functional study. Whilst great work has been done in stem cell research more is required before they reach their full potential in their application in medicine. This review manuscript argues that artificial intelligence can be used to study stem cells better than currently is. For example, development of automated instrument for analysis of iPSC colony is fundamental to the use of stem cells. This review manuscript is an attempt by the authors to present an overview of artificial intelligence and its role in biomedical field and associated stem cells-based therapy and research.

Overall the manuscript requires major changes before it is ready for publication. Most importantly, a native English speaking person must edit the manuscript before re-submission as there are many errors, including simple mistakes such as singular and plural mistakes.

Specific Points
1.	Whilst the Abstract mention that the manuscript will discuss the use of artificial intelligence in stem cell-based therapy, the manuscript contains minimal information on stem cell based therapy and the use of AI in this field.
2.	Lines 42-43. The definition of stem cell given is wrong. As given, it implies a cell can become terminally differentiated whilst at the same time it can self-renew. This is wrong. A stem cell can divide into two daughter cells with one cell undergoing terminal differentiation whilst the other one maintains self-renewal properties.
3.	Lines 113 -132. The selection of articles and other materials used in the construction of the manuscript must be given in a Figure form. Add inclusion and exclusion criteria to the Figure as well.
4.	Lines 162 onwards. Sections for Machine learning and Deep learning require more than one Figure. The authors must illustrate what they are describing in these sections.
5.	Lines 247- Sections on ‘CNN and Medical Analysis’ and ‘CNN in Cell Biology’ is missing key publications. The following references must be added to these sections.
PMID: 32416778
PMID: 32213531
PMID: 32061286
PMID: 31367025
PMID: 30617339
PMID: 31592719
PMID: 31313972
PMID: 32602650
Experimental design: Review of Manuscript: #49552 entitled ‘Stem Cells imaging through Artificial Intelligence
Technology: Current issues and future directions’ by Ramakrishna and colleagues.

Dear The Editor

The above manuscript by Ramakrishna and colleagues is a review manuscript describing the role of artificial intelligence technology in stem cell imaging. The discovery of stem cells opened many doors in medicine in terms of treatment of many diseases and conditions with no cure at present. The use of stem cells in medicine is however hampered by the great heterogeneity observed and also their functional study. Whilst great work has been done in stem cell research more is required before they reach their full potential in their application in medicine. This review manuscript argues that artificial intelligence can be used to study stem cells better than currently is. For example, development of automated instrument for analysis of iPSC colony is fundamental to the use of stem cells. This review manuscript is an attempt by the authors to present an overview of artificial intelligence and its role in biomedical field and associated stem cells-based therapy and research.

Overall the manuscript requires major changes before it is ready for publication. Most importantly, a native English speaking person must edit the manuscript before re-submission as there are many errors, including simple mistakes such as singular and plural mistakes.

Specific Points
1.	Whilst the Abstract mention that the manuscript will discuss the use of artificial intelligence in stem cell-based therapy, the manuscript contains minimal information on stem cell based therapy and the use of AI in this field.
2.	Lines 42-43. The definition of stem cell given is wrong. As given, it implies a cell can become terminally differentiated whilst at the same time it can self-renew. This is wrong. A stem cell can divide into two daughter cells with one cell undergoing terminal differentiation whilst the other one maintains self-renewal properties.
3.	Lines 113 -132. The selection of articles and other materials used in the construction of the manuscript must be given in a Figure form. Add inclusion and exclusion criteria to the Figure as well.
4.	Lines 162 onwards. Sections for Machine learning and Deep learning require more than one Figure. The authors must illustrate what they are describing in these sections.
5.	Lines 247- Sections on ‘CNN and Medical Analysis’ and ‘CNN in Cell Biology’ is missing key publications. The following references must be added to these sections.
PMID: 32416778
PMID: 32213531
PMID: 32061286
PMID: 31367025
PMID: 30617339
PMID: 31592719
PMID: 31313972
PMID: 32602650
Validity of the findings: No comment
Additional comments: Review of Manuscript: #49552 entitled ‘Stem Cells imaging through Artificial Intelligence
Technology: Current issues and future directions’ by Ramakrishna and colleagues.

Dear The Editor

The above manuscript by Ramakrishna and colleagues is a review manuscript describing the role of artificial intelligence technology in stem cell imaging. The discovery of stem cells opened many doors in medicine in terms of treatment of many diseases and conditions with no cure at present. The use of stem cells in medicine is however hampered by the great heterogeneity observed and also their functional study. Whilst great work has been done in stem cell research more is required before they reach their full potential in their application in medicine. This review manuscript argues that artificial intelligence can be used to study stem cells better than currently is. For example, development of automated instrument for analysis of iPSC colony is fundamental to the use of stem cells. This review manuscript is an attempt by the authors to present an overview of artificial intelligence and its role in biomedical field and associated stem cells-based therapy and research.

Overall the manuscript requires major changes before it is ready for publication. Most importantly, a native English speaking person must edit the manuscript before re-submission as there are many errors, including simple mistakes such as singular and plural mistakes.

Specific Points
1.	Whilst the Abstract mention that the manuscript will discuss the use of artificial intelligence in stem cell-based therapy, the manuscript contains minimal information on stem cell based therapy and the use of AI in this field.
2.	Lines 42-43. The definition of stem cell given is wrong. As given, it implies a cell can become terminally differentiated whilst at the same time it can self-renew. This is wrong. A stem cell can divide into two daughter cells with one cell undergoing terminal differentiation whilst the other one maintains self-renewal properties.
3.	Lines 113 -132. The selection of articles and other materials used in the construction of the manuscript must be given in a Figure form. Add inclusion and exclusion criteria to the Figure as well.
4.	Lines 162 onwards. Sections for Machine learning and Deep learning require more than one Figure. The authors must illustrate what they are describing in these sections.
5.	Lines 247- Sections on ‘CNN and Medical Analysis’ and ‘CNN in Cell Biology’ is missing key publications. The following references must be added to these sections.
PMID: 32416778
PMID: 32213531
PMID: 32061286
PMID: 31367025
PMID: 30617339
PMID: 31592719
PMID: 31313972
PMID: 32602650


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: STEM CELL IMAGING THROUGH CONVOLUTIONAL NEURAL NETWORKS: CURRENT ISSUES AND FUTURE DIRECTIONS IN ARTIFICIAL INTELLIGENCE TECHNOLOGY
Review round: 1
Reviewer: 2

Output:
Basic reporting: Ramakrishna et al reviewed the potential applications of AI in the stem cell field. This review manuscripts aims to go over the literature that focused two broad fields, although it is hard to tell real differences between applications of AI in other cell types. Anyhow, this review is novel, and there was an intention to write it as a systematic review, and it is presented in that way. However, it lacks the solid criteria needed to consider as one of them, and hence this format is misleading. Moreover, it is unclear why this review was written. Although I perfectly understand the potential uses of AI in the stem cell field, this is not clearly stated in this review. It is definitively vague in this matters.
Experimental design: As I said, the review is presented as a systematic review, and the authors did an excellent job in collecting the few papers in the field. However, information is not presented as the interested reader would expect. Overall, it is not clear what information a stem cell researcher would be able to take out from a review like this. For example, figure 1 is correct. It shows a diagram of a CNN, but there is no legend that extensively explains what this is about, nor it is explained in the text. It is really uninformative in this way.
Validity of the findings: Overall, the review lacks deepness. It is a shallow review of what Ai can do in stem cells. Many times, the text does not flow into any conclusion, and frequently the reader is taken from one subject to another without any reasonable connection. A few examples are lines 171 (no explanation what are these three fields), lines 184 to 187 (what these accomplishment really mean), the section CNN in medical analysis (it is non informative for this review), etc. Moreover, most interesting details for a stem cell biologist are not fully explained. For example, the whole paragraph from line 297 to 310. Perhaps this is one of the most important paragraph in this manuscript, but unfortunately does not describes in details the main findings of these papers, as well as makes some comments about U-Nets, which only adds confusion. I appreciate that the authors also cited our work, which I don't think it was fully understood. We showed an extremely example of detecting stem cell differentiation, but most interesting, incredible fast and cheap. These findings are not discussed and we believe that they are of paramount importance for stem cell biologists. Finally, the field of stem cells is too wide, from EC to haematopoietic stem cells. However, they are extremely different, from biology to medical applications. I think that this distinction should be clear.
Additional comments: Unfortunately, I believe the authors did not fill the expectations of a potential reader for this manuscript. I think that there is a strong potential for this review, but it essentially needs to be rewritten. Some major questions for the stem cell field would remain without answers if this manuscript is published in this format.


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: STEM CELL IMAGING THROUGH CONVOLUTIONAL NEURAL NETWORKS: CURRENT ISSUES AND FUTURE DIRECTIONS IN ARTIFICIAL INTELLIGENCE TECHNOLOGY
Review round: 2
Reviewer: 1

Output:
Basic reporting: The manuscript reads very well now. After going through several times, English language is good for publication. References have been added and is adequate.
Experimental design: The structure of the Review has been adjusted and is good. A Figure has been added to the Survey Methodology, making it clear and understandable to readers.
Validity of the findings: Conclusions drawn by the authors appear plausible and applicable. The authors did a good job of addressing the issues l raised in the previous review.
Additional comments: The review is good for publication now


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: KINEMATIC EFFECTS OF THE CIRCLE WITH AND WITHOUT RIDER IN WALKING HORSES
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript requires further work to improve the clarity and written English.
Experimental design: This study is original research and within Scope of the journal. The research question is not well deﬁned, although relevant. It is not well stated how the research ﬁlls an identiﬁed knowledge gap. Methods require further detail.
Validity of the findings: Findings are valid. All underlying data have been provided. Please see general comments in relation to more detailed feedback.
Additional comments: The background section of the abstract is too short. There needs to be a better explanation of the reason for performing this study.
Line 20: curved, not bent
Line 27: laterally on cannons is vague. Fore and hindlimbs? Is this in brushing boots? If so, state.
Line 28: Was this split for a full stride using the left or the right hindlimb?
Line 29: extracted?
Line 30-31: It is not clear what step and cannon (limb) variables actually are.
The results section is too long and does not highlight well the key results from this study. There is a need to tie these into the reasons for performing this study better.
The conclusion is not very strong. Once key results are highlighted better the conclusion needs to provide a more justified reason for studying circles at walk. It that the only conclusion coming from this work? Why? What findings indicate that more research on circles will be useful?
Line 57-58: This results in that the….poor grammar. This results in out of phase movement of the fore- and hindquarters.
Line 60-61: ‘Even if the walk is slow, the movement pattern is complex.’ I am not sure what this statement is saying. Is a fast walk pattern not similarly complex then?
Liner 61-63: Would it not be better to just describe the motion of the saddle in walk, instead of comparing to trot.
Line 64: The rider does not maintain a four-beat rhythm, the horse does. Please reword.
The first paragraph needs additional references. Also, I assume that all of these descriptions are in a straight line?
Paragraph 2 contains no references. Also, what is important in relation to studying the horse-rider interaction during walking. Yes, the horse may be asked to bend to the left or right by the rider, but what is ‘important’ about this?
Line 75-83: This is a better paragraph showing what has already been found during turning at walk in horses. But is leads me to wonder…so what? What does this mean? What is important about it? Why study the walk during turning further if we already know this?
The aim has no mention of the difference between ridden and in hand turning. Why only hindlimb steps? The second statement is just about measurements. You need to justify why we need to know this and also you need to include hypotheses. The aim is also quite vague.
Line 93: for not since
Line 95: Can you be more specific. Lameness scale scores?
What type of horses/riders? What level? Dressage or not?
Line 104: Age range of riders, not specific ages.
Line 105: For not since
Lines 112-113: Please provide more specific anatomical detail in relation to sensor placement. If the cannon sensors were in brushing boots this should be stated, together with whether they were attached to all four limbs. Cannon’s is also rather layman language. Please improve.
Line 113: Sign convention should be clearly stated in a new sentence.
Line 116: I don’t understand what this relates to. (other IMU-recorded data not used in the study)
Line 118-121: Where was the camera placed when recording in a straight line? Also if the sensors were tapped before putting them on the horse I assume you continued recording throughout the time that they were placed on the horse? Why on a stool? Why not placed on the horse and then tapped?
Line 127: Are AE and HE researchers?
How many days did each horse perform the tests? I assume this is because some riders rode more than 1 horse? Perhaps a table describing this in more detail would be useful.
I am finding the description of ridden/lunged/left/right confusing. From what you have written I assume they were all led and lunged first, then ridden afterwards. If they were lunged first to the left, then they were ridden first to the right? Is this what you mean? Why?
Why did you decide to use minimal contact between the horse and rider? I expected that you might have investigated the difference in ridden and unridden conditions where the rider rode normally. By not doing this, I expect you are just looking at the effect of the rider sitting on the horse (so essentially not much more than a mass increase), rather than the horse-rider interaction? This should come through in the aims and hypotheses much more clearly.
Line 148: Did you assess the straight line data for L/R symmetry? I can see the logic in splitting using the inside hind on a circle, but if the L/R data was not symmetrical (and you didn’t assess the horses quantitatively for soundness), then you may be introducing errors due to asymmetry when splitting the circle data.
Line 152-163: It is not clear or justified as to why you have chosen these variables, why they are split in the way you have split them and why you have constrained certain data. You may need to include some graphical evidence or at least a better justification for doing this. S1 appears for the first time here. I think you used croup previously?
I have to say that reading the statistical analysis gives me the impression that you have thrown everything into the model with the justification that this is exploratory, even though some studies have already investigated walk kinematics. The statistics should map to the aims and hypotheses of the study more clearly and the reasons for your modelling should be better justified.
Line 213: What is a trial?
Line 214: were not was
Figures and tables should be in the order they first appear in text.
Line 228: 39.3%*2>87.6%, figures first row of Table 5 what does this mean?
When stating significance in text please include p values as a minimum.
Please be consistent when reporting vertical excursion. Either mm or m, but not both.
Line 262-270: It is not clear whether all of these results are significant.
There is quite a large amount of text, tables and diagrams illustrating the results. I would suggest you include just the highlights in the text and allow the tables and figures to report the majority of these findings. There should not be excessive duplication.
The discussion should begin with a summary of the study, highlighting any main findings and stating whether the hypotheses may be accepted or rejected. Please include.
The discussion should not be merely a comparison of your data to other studies. It should focus on what is important about your findings. You need to critique other studies in relation to the difference in walk kinematics in a straight line and on a circle, what are the differences? How does this relate to other studies? Why are they different? Different equipment, methods, horses etc. It is not about presenting values from other studies and just comparing them to yours. It is more about why you have found what you have found. Also, do not split by measurement variables. Split by conditions (i.e. ridden/unridden, straight/circle) and compare the ‘whole horse’, for example when you have a change in max protraction in the forelimb, how does this influence the vertical displacement of the withers and why would a rider being on top influence that? The later sections are improved, but mainly focus on what the differences are between your data and other studies and not why these differences are likely to have occurred and what that means in the wider context of the equestrian world (i.e. for riders, for lameness evaluations etc).
Table 2: The legend for this table does not match all of the data? You have included ROM estimates? This is not detailed in the legend. Also, your min and max estimates and ROM for pro-retraction seem to be much smaller than pro-retraction values recorded in walk?
Table 3&4: What does 1 and 0 mean? What comparisons are the colours indicating? Define non-significant. Why are some of the squares blank?
Figure 2: The arrows on the diagram are not always in the right place and appear to be sketched. Please improve the quality of this figure and label the axes for angles on one side and vertical displacements on the other. Include units.
Table 5: The colour scheme seems to indicate the same colours between comparisons for all data? Do you need to state here that values with no colour are not significant. i.e. there is no difference between the unridden and ridden condition when the cells are not coloured.
Figure 3: Please graph the ridden, unridden and straight conditions on the same graph for that limb. S1 and withers data can be graphed separately. Also, this should be inner and outer, not left and right.
Figure 4: As for Figure 3. In addition, include inner and outer fore. Inner and outer hind.


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: KINEMATIC EFFECTS OF THE CIRCLE WITH AND WITHOUT RIDER IN WALKING HORSES
Review round: 1
Reviewer: 2

Output:
Basic reporting: The manuscript requires a revision to improve manuscript.
Experimental design: The research question and hypothesis are not well defined, although relevant. Methods and Discussion are require further detail.
Validity of the findings: Finding are valid.
Additional comments: thank you for the interesting information. However, it need to re-write to academic writing.
According to this study show many data, I would recommend make it compact and pick the data that
answer your hypothesis. Please select the importance information and present in graph or table
which should clear and simple. I commend the author which should be improved before acceptance.
1. Line 4 Agneta Egenvall 1
,* what is refer to, if it mean Corresponding Authors : you should
to change to Agneta Egenvall 1
*, and put the * infront of Corresponding Authors
2. Abbreviation Line 28 at the Abstract: ROM, It would be good for reader to understand please
give full name if it at the first page or first time in the paragraph. Example; range of motion
(ROM)
3. Abbreviation Line 43, 44 what is the S1?
4. Abbreviation Line 80 what is the EMG refer to?
5. Abbreviation Line 95 a veterinarian (AE), Is it necessary?
6. Abbreviation Line 127,139 AE, HE, AB Is it necessary? Do you what show a veterinarian(AE)
is the author of the study and also the lameness examiner, rider and video recorder ? How is
importance?
7. Abbreviation Line166 what is Proc MIXED?
8. Line170 What do you mean the rider*horse?
9. Abbreviation Line171 What is pdiff?
10. Line 183 What do you refer to: horse*rider*exercise?
11. Line 195 what do you refer to: horse*rider*horse side?
12. Please check the reference style in the Introduction and Discussion. There are variety of
reference example at Line 63 (Byström et al., 2010), Line75 Chateau, Degueurce &
Denoix (2005) Line79 Wakeling et al. (2006)
13. Please use words in consistency
Example: Line 85 Forehand / Wither / forelimb? , Line 86: Hind quarters/ hind limb? Line88
Croup/ S1 / Sacrum ?
14. Please make Objective of this study is clearer. How many objective of this study?
15. For Materials and methods : Line95 This study use subjective lameness examination by a
veterinarian. Do you think only a veterinarian can be bias? It has been reported in previews
study from Keegan. Why don’t you use Objective tool for lameness examination because in
this study you used inertial measurement units (IMU) to measure? Do you think lameness
horse might give you difference results?
16. For Materials and methods : Line 108 ( Table1)
It would be useful for the reader if you show the detail weight of saddle plus weight of rider
rather than Duration with the owners (I guess relation of that horse and the owner).
17. For Materials and methods: Line 108 (Table1) Breed of horse in this study. Do you think
difference breed or difference activity is might have difference of character to walk? Type of
small horse: Do you think the size of horse might affect with the results?
18. For Materials and methods: Equipment Line 112 Inertial measurement units (IMU)
(https://x-io.co.uk/ngimu/), Line 118 video-recorded (Sony FDR-AX53), Line 140
(Matlab version 2019b, The MathWorks® Inc., Natick, MA, USA) , The details of
these equipments should give more details for example IMU: What is the company,
program version have been used. The details should declare conflict of interest, support. The
details should be at additional part after reference section. Please check with the Journal
format. For each Tool will give difference value. It would be better if this study classify the
main parameters that obtained from which tool. ROM in degree, Vertical translation of the
wither and croup in mm. and give interpretation why is minus in degree.
19. For Materials and methods: Study design Line123 Do you think speed of walk might be effect
to ROM in the circle and straight-line? How do you control speed?
20. For Materials and methods: Study design Line123 Do you think natural walk and active walk
during longing and ridding might be effect with ROM?
21. Statistical analysis: Do you use only descriptive analysis and present in percentage?
22. Results Line 213, Refer to the study design each horse had 6 conditions: straight –line with
and without ridden, Left circle with and without ridden, Right circle with and without ridden.
In Total (10 horses) should be 60 Trials. Why in the results show 14 trails? How comes of
this number?
23. Results Line 211-331, after report the descriptive results of the horses and riders should
report in order what have done in the study design. Especially the data that fit with the
objective. For example, the data focused on vertical translation of the withers and the
croup, and ROM, minima, maxima and their timing for sagittal cannon angles in walk,
approximating limb protraction and retraction.
24. Results Line 212-221 why the range of stride of each condition was variety, especially
minimal range of stride? Do you think is that a good represent of your study?
25. Results Line 223 Academic writing need content in text of each new paragraph then refer to
Table or figure. This need to re-write “Tables 3 and 4 show model results that are further
explained below”.
26. Results Line 211-331 and Discussion Line 333-501 Need grammatical prove, Repetition, too
much additional information in the sentence.
Example: Line 337,339 Our results, Our
Line:354 was 36% for straight line (0.92+(-15.38)+50 [because of step adjustment]).
Line: 428-429 the outer hind limb differed from straight (earlier protraction and retraction),
while it was the inner forelimb that changed (earlier protraction).
Line: 440 increased first vertical force peak for the (same) forelimb in early stance
Line: 449 In the current study there was, however, no significant differences
Line 498-499 We recommend use of high-speed video for detailed studies of withers vertical
excursion in ridden horses. We also note that
27. Table and Figure
Table2. Title of this table is too long and it need to separate data into 2 tables
Table3. Title of this table is too long and too much explanation. What is the meaning of BTb
Colum? What is CompC
refer to ?
Table4. The subtitle in Variable Colum are duplicate. Please check Timing of maximum
retraction (percent of stride), It should be Maximum and Minimum
Figure 1 . Show a green sensor on the right forelimb which is not correlate with the text Line
113 that laterally on the cannons of all four limbs. It can make reader confuse.
Figure 2. I would expect to see how is the trend vertical movement of wither of each trial
compare with and without ridden
Figure 3. Is it croup or Sacrum or S1 vertical position? From the graph picture I got the
information that the horse without ridden movement sacrum more freely than ridden
condition is it the thing that you would like to represent?
Figure 4. Is this graph compare trend of outer and inner limb in circle ? Why straight line still
have outer and inner, How comes?
Line 235 what is the Figures S1-S3 that refer to? Where is it?
28. Conclusion: What is the take home massage for reader? From your study what is the impact
for sport rider, veterinarian and owner?


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: KINEMATIC EFFECTS OF THE CIRCLE WITH AND WITHOUT RIDER IN WALKING HORSES
Review round: 2
Reviewer: 1

Output:
Basic reporting: Much improved. Just a few small changes suggested.
Experimental design: No comment
Validity of the findings: No comment
Additional comments: Abstract Conclusion. Overall the outer hind limb had greater ROM in pro-retraction,
‘and with a rider also the forelimb.’ Is this ….and there was an increase in pro-retraction ROM for the outer forelimb with a rider.
Line 73: these events coincide
Line 82: gait is missing
Line 128: angular ROM of the cannon bones
Line 546 and others: toe-on? Do you mean landing or foot strike?
Line 597: might be because riders
Line 612: disrupted the biphasic vertical motion pattern of the forehand (the withers)
Line 639: evaluated not evacuated
Line 652: extraction not evacuation


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 TREND OF CARDIORESPIRATORY ENDURANCE IN URBAN CATALAN HIGH SCHOOL STUDENTS OVER A 20 YEAR PERIOD
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript text presents some introduction points that can be improved.The general write structure is correct. My specific suggestions are described in the attached file.
Experimental design: The objectives of the research need to be rewritten according a cross-sectional trend study. The main lack in this research is that authors affirm that is a longitudinal study and they present a cross sectional analysis.
Validity of the findings: Line 191- The main inconsistency of the study is revealed in the statistical analysis. The authors call the research of "longitudinal", however, they use an adequate test for independent samples, that is, groups with different people. This is what seems to happen. Thus, I suggest that the authors change the design of the longitudinal, for a trend study,a comparison of cross-sectional data over 20 years. The dataset confirm this hypothesis.
According this, The way of writing in all results (line 207) is compromised whereas the data of the study point to a comparison of different subjects. Perhaps the study is a mixed cohort. however, it is not longitudinal. I suggest not saying "increase" or "reduction", we must to say the X CRE value was greater or less than year Y. This is because they are not the same subjects, there is no effect of time and neither maturation, and nor physical activity effects in the present sample.
Additional comments: Thank you very much for the opportunity to evaluate your research. It is an interesting study because it has a greater sample of different years, with important changes in cardiorespiratory fitness. However, some methodologic adjustments are needed. I hope the contributions are relevant to improvements in the general presentation of research.


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

Input:
Title: TEMPORAL TREND OF CARDIORESPIRATORY ENDURANCE IN URBAN CATALAN HIGH SCHOOL STUDENTS OVER A 20 YEAR PERIOD
Review round: 1
Reviewer: 2

Output:
Basic reporting: I think the paper is very interesting and is about very important children's and adolescents' health indicators. In fact, cardiorespiratory fitness is one of the most important physical fitness components that needs to be highlighted over physical education classes and in several sports and activities for the youth population. In my opinion, your paper showed the necessity of several approaches that aim to prevent and treat several diseases by physical activity since early in life.

These results are very important and need to be considered as a public health policy.
Further, I really like the references that you have used, as well as, the manuscript is very well written, congrats.

I suggest some basic review. I hope you can be able to provide:
1. I suggest you to better present your results.
2. I suggest you change your conclusion over the abstract. Please, what do you think you could really suggest considering your main results? I really like your general conclusion, however in my opinion you could highlight more your results.
3. Please could you discuss a little more you results?
Experimental design: 1. I suggest you improve the description of the sample selection. How have you chosen these samples of adolescents? Did you invite all schools?

2. Please, could you include a better presentation of your figure and table?

3. Please, could you include a legend bellow the figure and table?

4. Please, I suggest you include more information about your sample characteristics such as weight, height, BMI, mean age. Moreover, if you have some information about the schools. It is very important for us to understand the sample characteristics. Thank you.
Validity of the findings: Please, could you deeply present how you proceeding to select your sample?
It is a representative sample?

I suggest you to included several considerations about the limitation of your study. For example, there are several variables that you could include as a covariate? Is this a representative sample? Despite we can be able to understand what is happening among this population, how is our limitation when we do the inference of your results?
Additional comments: Please, over the background and the discussion topics I  suggest you add the importance of the relationship between physical fitness with all other health indicators such as mental health, bone health, cognition, etc.

Again, please could explore the approaches that should be highlighted considering the great necessity of improving youth physical fitness?


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 TREND OF CARDIORESPIRATORY ENDURANCE IN URBAN CATALAN HIGH SCHOOL STUDENTS OVER A 20 YEAR PERIOD
Review round: 1
Reviewer: 3

Output:
Basic reporting: This is an interesting topic and has been discussed in the literature. Regarding the manuscript, it was possible to identify some strengths and points to be improved.

Strengths:
- The topic is relevant and evidence is needed.
- There is a practical implication for the results of the present study.

Points to be improved:
- In the background, despite being well referenced, I suggest a reorganization of ideas to better contextualize the theme and present the aim of the study. For example: start talking about physical activity and how it impacts physical fitness, after decreasing physical fitness over the years and how it impacts the health of children and adolescents. Then justify the investigation of the theme and present the objective.
Experimental design: - The objective is presented for the first time in the methods (it is important to add in the background and standardize since the aim presented in the abstract, in the methods, and in the discussion are different).
- On lines 157-158 the term "physical teacher" is correct?
- When you talk about schools, you use the term "several schools". But how was it selected? What about adolescents? Sample for convenience, voluntary? It is necessary to specify.
- It is necessary to include a sample calculation.
- Finally, the major methodological issue is in the design of the study. As I understand it, they are not the same adolescents over time. Thus, it cannot be considered a longitudinal study. I believe it is a red transversal trend.
Validity of the findings: - In the results, it is important to include more information for the sample characterization (and not the population), even if it is not the aim of the study. Just knowing how many boys and how many girls and describing CRF averages, are not enough to describe the sample.
- In the discussion, the authors should be more specific to answer the study aim and address the main results.  I find the idea of speculation interesting, but it is important not to shift the focus so far from the results found in the study.
- There are methodological issues that compromise the conclusions. It is necessary to review mainly the study design and to include the sample size calculation.
Additional comments: - I would also suggest that extra information be removed from the figures’ and tables' titles (it could be described in the legend or in the text that advertises the figures/tables).
- With regard to English, it is necessary to revise. Standardize the terms teenagers and adolescents (I suggest for adolescents) and correct the word "behavior"


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 TREND OF CARDIORESPIRATORY ENDURANCE IN URBAN CATALAN HIGH SCHOOL STUDENTS OVER A 20 YEAR PERIOD
Review round: 2
Reviewer: 1

Output:
Basic reporting: Thank you once again for the opportunity to revise this manuscript.
The authors were concerned with improving the work through suggestions, which greatly increased the quality of the article.
Experimental design: The authors answered methodological questions.
Validity of the findings: The authors answered the validity of the findings questions.
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: BEHAVIOURAL PATTERNS OF FREE ROAMING WILD BOAR IN A SPATIOTEMPORAL CONTEXT
Review round: 1
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: Two major concerns about the experimental design: i) only one study area and sampling season, and ii) the frequency estimated by each behavior could be biased due to movement related questions (see comments to authors for further details).
Validity of the findings: no comment
Additional comments: The manuscript is focused in the description of the wild boar behavior s, and their frequency and spatio-temporal patterns, in a natural population. The interest in wild boar is nowadays increasing in Europe mostly due to its role in growing conflicts with human activities, such as those linked to shared diseases (e.g., African swine fever) and agricultural damages, among others. However, even when the topic is relevant and timely, I have some major concerns that should be addressed in a new version of the manuscript.

i) One is in relation to the sampling design just focused on a single population and only one sampling season. In my opinion this is not the best design to describe the ethogram of a species since at least some additional localities would be needed and, ideally, a full year should have been monitored. Some of these drawbacks were discussed in the previous version, but all of them should be considered to tone-down some sentences describing the aims (Line 86) and gain precision when interpreting results in the new version of the manuscript.

ii) A major concern is related with the comparison among behaviors' frequency. Some authors have pointed that detectability of behavior from camera traps can be biased and slow movements can be underrepresented (e.g. foraging) and overrepresented others (e.g. locomotion) (e.g. Rowcliffe et al., 2016 – Remote Sensing in Ecology and Conservation 2: 84-94; Caravaggi et al., 2020 – Conservation Science and Practice e239). Likely, this fact is affecting the results reported here, since behaviors involving faster movements were those with higher rates in video captures (e.g., locomotion > olfactory > vigilance > foraging behaviors). The authors should try to weight the frequency of each behavior by the probability of detection that should be related with the relative speed of one beahviour to the others. Likely the picture that the authors can draw from weighted frequencies could be different to that reported now (see also lines 263-264).

iii) Even when the authors clearly stated that information from cameras placed at non-random points were not considered in the statistical models (but see below), they did not provide detailed information about the frequencies of each behavior at random vs non-random sampling points. I suggest including this information in order to complete the description of the spatio-temporal patterns in the behaviors. Likely some of the behaviors were only detected in non-random points or were more frequently detected in that points. At this respect, line 208 suggests that non-random cameras were just used to describe salt ingestion, right? If I am right, this is a relevant result meaning that random points are enough to describe the main behaviors and therefore monitoring aggregation points is not needed at least when the aim is more qualitative (behaviors’ description) than quantitative (estimating frequency of each behavior). Thus, comparative information between random vs non-random points is needed to enlarge discussion at this respect.

iv) Some discussion is lacked in relation to the results usefulness for implementing control strategies in the wild. This is announced in the abstract and in the introduction and, therefore, is expected to find further discussion at this respect. I recommend highlighting the applied component of their results in a new version of the manuscript.

Other considerations:

Lines 114-115. Authors described the minimum distance between cameras but information providing the effective distance is lacked. In relation to distance, it is probable that data from closer cameras can infringe the independence assumption of the observations. Can the authors provide information about the real distance among cameras? Was independence among observations tested or controlled in the statistical analysis? For this purpose, hierarchical models accounting for spatial autocorrelation can be an alternative to GAM (see for instance hSDM R package).

Lines 126-127. The effective area of detection for wild boar is quite small (see Hofmeester al. 2016 – Remote Sensing in Ecology and Conservation 3, 81-89) and it is not easily enlarged by locating cameras at higher heights. However, the camera height can drive differences in species detection depending of their size. Therefore, smaller individuals would be detected in low cameras in relation to tall (90cm height!) ones. Have authors observed some difference at this respect between age classes recorded at random and non-random points?

Line 136. More details about habitat characterization around cameras should be provided. For instance, what buffer size was considered to describe main species and cover? Since these are predictor variables in the models it is needed to provide a complete description of the procedure to obtain them.

Line 166. How were cameras operativity monitored? All cameras at the end of the experiment were operative (i.e. correctly positioned, with batteries, space in memory cards and taking pictures both at day and night)?

Line 168. Description of formula is not complete. It should be revised.

Line 199. Authors stated that locomotion was detected in 52% of video clips (number of video clips at random points 645). However, in supplementary material N=732 is reported for the locomotion model. Only the information at random points was actually used in the model?

Line 212. I am not sure if authors can refer to preferred habitats given their analytical framework. In my opinion to talk about avoided and preferred it is needed to account for habitat availability in the study area. Other case, results should be interpreted in terms of higher/lower frequency of video captures in relation to the habitat category used as reference in the statistical test.

Table 2. Decimal symbols should be dots. In addition, authors can include the difference obtained from Tukey's poshoc test in order to provide information about what is the behavior more frequent in the pair wise comparisons.


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: BEHAVIOURAL PATTERNS OF FREE ROAMING WILD BOAR IN A SPATIOTEMPORAL CONTEXT
Review round: 1
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: Your experimental design seem fine to me. I only have some minor points about the way of introducing the statistical approaches in the M&M section. In the attached pdf you will find some recommendations.
Validity of the findings: no comment
Additional comments: Dear Dana and Olivier,
I have found your work well written, timely and interesting.
My only concern is the lack of management implications in the discussion section. In fact, your started underlining the need of behavioural information for population management issues in the introduction section but later, in the discussion, you did not provide any kind of management implication or recommendation to alleviate the human-wildlife conflict caused by this wild pigs.
As you stated in the introduction section, wild boars are getting more and more common in urban areas (Castillo et al. 2019. Science of the Total Environment. 615: 282-288), cussing human conflicts. To my understanding, your behavioural recordings will help to minimize such  conflicts, for example, minimizing the accumulation of garbage during periods when wild boars are actively looking for food. I believe you will find much more management implications that will be welcome by the readers and in turn will increase the impact of your research.

I hope that my comments will be useful for your investigation


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: BEHAVIOURAL PATTERNS OF FREE ROAMING WILD BOAR IN A SPATIOTEMPORAL CONTEXT
Review round: 2
Reviewer: 1

Output:
Basic reporting: See comments for the authors
Experimental design: See comments for the authors
Validity of the findings: See comments for the authors
Additional comments: I acknowledge the efforts to accommodate some of my previous comments in the new version of the manuscript. In my opinion it now reads more clearly and can be more easily understood with the additional details included. However, some of the -major- methodological questions raised in the previous revision were not adequately handled:
1)	The comparison among behaviours’ frequency without taking into account that faster behaviours have higher probability to contact with cameras and therefore to be overrepresented in the trapping rates is, at least, risky. Authors acknowledged this fact in the discussion as a potential explanation of their results, but they did not provide consistent reasons to do not consider it in the analyses. In my opinion, data obtained in this study allow to compare temporal trend within a given behaviour but comparisons in terms of frequency among behaviours should be cautiously considered.
2)	The spatial autocorrelation in their data can bias the results in the statistical analyses (e.g. Sollmann 2018 – African Journal of Ecology 56, 740-749). Even when there are not overlap in the detection zones, the rates obtained by a given camera are expected to be closed to that obtained by its neighbors than to that for more far ones (i.e. spatial autocorrelation). I think that, at least, authors can test for spatial autocorrelation in the model residuals; if significant autocorrelation persists in the residuals then authors likely should move to another statistical framework accounting for spatial autocorrelation (e.g. hSDM or R-INLA R packages can be suitable options).


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: BEHAVIOURAL PATTERNS OF FREE ROAMING WILD BOAR IN A SPATIOTEMPORAL CONTEXT
Review round: 2
Reviewer: 2

Output:
Basic reporting: --
Experimental design: --
Validity of the findings: --
Additional comments: Congratulations


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

Input:
Title: TROPICAL PEATLANDS AND THEIR CONSERVATION ARE IMPORTANT IN THE CONTEXT OF COVID-19 AND POTENTIAL FUTURE (ZOONOTIC) DISEASE PANDEMICS
Review round: 1
Reviewer: 1

Output:
Basic reporting: - The topics covered in the article are of great interest in the current and future scenario;

- Abstract, line 63: I suggest: “many potential vertebrate and invertebrate vectors”;

- Introduction: The introduction is well structured and the objectives of the review are well defined;

- Figure 1: Please, remove the Earth illustration from the center of the virus. This is unnecessary. I also suggest connecting the green box “increased biodiversity loss” (cause) with the box “increased human-wildlife contact” (consequence);

- This is a cross-disciplinary review within the scope of the journal.

- The article is written in good English;

- The revised literature is updated.
Experimental design: - The methodology is interesting (it looks “sincere” and consistent) and adequately described. In brief, the methodology is well structured for a review article;

- Table S1: The authors state “non-zoonotic diseases (e.g. flu)”. Flu is not a good example since some authors consider flu a zoonotic disease (usually human influenza strains is derived from non-human animals). Please, change to another example to avoid confusion;

- Table S2: Okay;

-  Sources are adequately cited and the text is organized logically.
Validity of the findings: - Although the article often has very opinionated parts, references were used appropriately;

- The text is drafted in an appropriate manner and respecting a logical structure;

- Figures 2-6: Okay;

- Lines 864-869 (conclusion section): I suggest removing or modifying it for a more "pragmatic" paragraph. This final paragraph is full of expressions like "we hope". The authors must not forget that this is not an opinion article, but a review article, and therefore the final paragraph should represent the main conclusions about the works that have been reviewed throughout the text.
Additional comments: - Regarding the topic “Are Tropical Peatlands a Potential Source Habitat for Disease Pandemics?”: I suggest to include a paragraph (maybe second paragraph, after line 200) discussing the risk of spillover events associated with human contact with bushmeat and wildlife in forest environments;

- Lines 285-286: Please, remove “It is therefore possible – and indeed we hope – that many of the concerns raised here will never be realised in the context of this pandemic.” This sentence is speculative;

- Line 843: Please, correct “Wijedasa & al., 2017”.


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: TROPICAL PEATLANDS AND THEIR CONSERVATION ARE IMPORTANT IN THE CONTEXT OF COVID-19 AND POTENTIAL FUTURE (ZOONOTIC) DISEASE PANDEMICS
Review round: 1
Reviewer: 2

Output:
Basic reporting: This review presents broad and cross-disciplinary interests that fall within the scope of the journal. The authors present recent and very important issues that are indeed accessible to researchers of different areas of knowledge. Besides, the authors raised important and current concerns. The Introduction section is clear. However, I strongly suggest some recommendations to better align the Introduction with the text body with the proposal, such as outlined as follows:

# The present paper raised very important questions regarding the impacts of the current global scenario caused by Covid-19 pandemic. The authors indeed show the importance to keep the existing conservation strategies in peatland areas at this moment and elegantly expose the likely consequences of a halt in investments in training scientists, people education, and conservatory demands along with the need of economic improvements to avoid community crisis. However, the paper is not really focused on direct links between Covid-19 and tropical peatlands. Considering this, the conclusion and introduction should be constructed into the environmental health of peatland areas (and its communities' livelihoods) and their connected concerns in times of pandemics instead of a direct consequence of the pandemics or risk for EID. Of note, these last issues should appear as they are in the text, but the reader should be aware of the actual discussions raised through the text.

# Regarding the title, some adjustments could be make it more suitable to the text body. Recalling the comments above and the elegant issues raised mainly in the sections "Economy and Livelihoods", "Food Security and Land Conflicts", and "Unequal Community Impacts", I encourage the authors to reformulate the review title, raising a different call similar as "COVID-19 AND TROPICAL PEATLAND AREAS: LESSONS ABOUT VULNERABLE COMMUNITIES, CONSERVATION STRATEGIES, AND RESEARCH THREATS IN TIMES OF PANDEMIC".
Experimental design: The review content is within the Aims and Scope of the Journal and the authors did present adequate investigation with high technical and ethical standards. The methods used by the authors are descriptive and did present sufficient and detailed information to be confirmed or replicated (obviously considering the possible changes in the scenario outlined in the time of writing). The information provided did present a comprehensive and unbiased coverage along with an important and neglected issue in the context of the current global scenario. The references were adequately chosen and cited. Nevertheless, I have some recommendations regarding the paragraphs and subsections as follows:

# Within the topic "Public Health", from line 344 to line 350, there is a brief discussion regarding different pathogens and infections. This is an important and likely neglected issue, especially considering peatland communities and Sars-CoV-2. Considering this, it would be interesting to introduce a paragraph raising the possible co-infections and their complications to such communities in vulnerable areas. The paragraph should answer questions such as: Is there such a relevant co-infection risk in peatlands communities? How severe this risk would be? What are the most common infections that could represent complications for people affected by Covid-19? What are the strategies to manage such risks?

# In the "Public Health" section, from line 352, there is a discussion more related to environmental aspects than public health per se. I suggest including a topic named "Environmental Aspects" in which the text from lines 352 to 381 could be replaced. Alternatively, the authors could rename the topic to "Public Health and Environmental Aspects". Also, despite the great information provided in this section, it would be adequate to provide or briefly cite the alternatives to deal with the problems stated (similar to the strategies suggested for food security in lines 482-485 in the topic "Food Security and Land Conflicts").

# Considering that 'land conflicts are one of the most important and complicated problems in land-use management in many communities with large peatland areas, affecting a large number of people', this issue deserves a separate topic with a more profound discussion and evaluation. Besides, considering the specific interest of this review, the Covid-19 pandemic should be addressed in the context of land conflicts in a perspective of how it would make communities more vulnerable to the disease and, again, authors may present strategies to avoid or minimize such effects.

# Authors should be congratulated for including the topic "Unequal Community Impacts". Moreover, this is a very important and still neglected aspect of the impacts of Covid-19 pandemic in overall aspects. Raising this issue greatly increases the coverage and insight of the review work carried out, adding unprecedented value to the article and to the Journal. Of note, a more profound discussion about how women on peatland communities are differently affected by the pandemic should be included. Finally, I suggest change the section title to "Impacts of Unequal Communities and Gender Bias".

# The topic "Research, Training, and Education" is pretty welcome. Over-funding focused only on Covid-19 research is quite dangerous indeed and the authors elegantly provide examples of the consequences of short and long-term replacement of resources directed only to Sars-CoV-2 research in detriment of other scientific areas. To better finish this, it would be wonderful if authors suggest strategies to better assist the remote peatland areas with adequate technology such as internet support, remote censoring, and all the needs for the viability of future (without physical contact) researches and collaborations worldwide. Such strategies, once previously presented, could be recalled in line 646 of the topic "Conservation and Restoration".

# Line 695: "How Might COVID-19 Impact Future Tropical Peatland Conservation and Sustainable Management, and What Knock-on Effects Might This Have on the COVID-19 and Possible Future Pandemics?" is quite a long title. Please consider separating it in two 'title questions' and adequate the text to respond to each one of them, to better highlight each of the questions addressed.

# Recommendations and Conclusion could be separated sections. Also, even presenting recommendations at the end of the article, I reinforce to include or cite the possible solutions just after a problem is presented in the text body.

# Line 826: online communications/ technological resources for distance communication are recalled. Please make it an additional item in the recommendations section.
Validity of the findings: This review presents an important perspective, which considers various logistical aspects of both research and access to vulnerable populations in peatland areas so that they have adequate assistance. Still, the economic and environmental aspects revisited, in parallel with social issues of paramount importance, raise issues that, although urgent, are still neglected. However, the issue of the risk of emergence of infectious diseases and a direct link with Covid-19 are aspects presented in a secondary way throughout the text, thus some changes must be made in the Introduction and Abstract of the article, as outlined previously. I reiterate that such changes do not make the article less relevant. It is a question of adequacy with the ideas outlined in the text that, indeed, in some points are affected by the pandemic or that raise the discussion about EID. Finally, the conclusion is adequate and quite complete and presents strategies for mitigating the problems presented.
Additional comments: Dear Author(s),

I must congratulate you on the initiative in writing a paper addressing the conservation of peatland areas and the impacts that these strategies may suffer in the current pandemic scenario. This is a very important perspective, which considers various logistical aspects of both research and access to vulnerable populations so that they have adequate assistance. Still, the economic and environmental aspects revisited, in parallel with social issues of paramount importance, raise issues that, although urgent, are still neglected. This is the overview I get from reading your manuscript. The risk of emergence of infectious diseases and a direct link with Covid-19 are aspects presented in a secondary way throughout the text, thus some changes must be made in the Introduction and Abstract of the article. I reiterate that such changes do not make the article less relevant. It is a question of adequacy with the ideas outlined in the text that, indeed, in some points are affected by the pandemic or that raise the discussion about EID.

# It sounds redundant when the authors use the term "emergence" and the abbreviation EID together. I  suggest revising this throughout the text, with abstract as a starting point.

# Line 682: once transmission of Sars-CoV-2 from humans to other primates is mentioned, please use the term 'spillover'. Once the authors decide to not explain this term previously, it would be interesting to emphasize its meaning at this moment.


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: TROPICAL PEATLANDS AND THEIR CONSERVATION ARE IMPORTANT IN THE CONTEXT OF COVID-19 AND POTENTIAL FUTURE (ZOONOTIC) DISEASE PANDEMICS
Review round: 2
Reviewer: 1

Output:
Basic reporting: No comments additional to those already presented in the first revision of the manuscript. The current revised version of the article is suitable for publication.
Experimental design: No comments additional to those already presented in the first revision of the manuscript. The current revised version of the article is suitable for publication.
Validity of the findings: No comments additional to those already presented in the first revision of the manuscript. The current revised version of the article is suitable for publication.
Additional comments: The authors responded to the reviewers appropriately. The modifications made were sufficient to allow the publication of 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: TROPICAL PEATLANDS AND THEIR CONSERVATION ARE IMPORTANT IN THE CONTEXT OF COVID-19 AND POTENTIAL FUTURE (ZOONOTIC) DISEASE PANDEMICS
Review round: 2
Reviewer: 2

Output:
Basic reporting: # After the modifications made by the authors, the title of the manuscript and the text body are now properly aligned.

# The modification made on the manuscript title had an excellent result, as well as it maintained the originality and identity of the group of authors.

# In view of the uncertainties related to possible complications in the cases of COVID-19
 and occurrence of co-infections, the changes made in relation to this discussion are pretty adequate.

# In full agreement with the changes in “Public Health and Potential Combined Impacts from Haze Pollution” as well as the modifications in the new “Land Conflicts” sub-heading.

# The modification in the sub-heading “Unequal Community and Gender Impacts” deserves congratulations: it is a necessary topic with the potential to stimulate this same discussion in future articles from different areas.

# Changes made in "Conservation and Restoration" are sufficient.

# The shortened title of the sub-heading “How Might COVID-19 Impact Future Tropical Peatland Conservation, and What Repercussions Might This Have in Relation to Disease Pandemics?” is now much better and with more fluid reading.

# Thanks for adding more possible solutions to issues raised within the body text and for reinforcing the issue about online communications/ technological resources for distance communication in the recommendations section.
Experimental design: I have no additional or new declarations regarding the Study Design.
Validity of the findings: The author's responses are pretty convincing. I have no additional suggestions.
Additional comments: Thanks to the authors for accepting the small changes as well. Again, I congratulate the entire team for this beautiful review work and I thank the Editor and the Journal for the opportunity to contribute.


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: USE AND EFFECTIVENESS OF DAPAGLIFLOZIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A MULTICENTER RETROSPECTIVE STUDY IN TAIWAN
Review round: 1
Reviewer: 1

Output:
Basic reporting: In this manuscript, Jung-Fu Chen and colleagues evaluated the use and short-term effectiveness of dapagliflozin, the first‐in‐class SGLT-2 inhibitor in Taiwan since 2016, under routine clinical practice conditions. Major strengths of the study include the large sample size (1960 diabetic patients) with nationwide distribution and the assessment of baseline predictors of clinical response.

1.	I would suggest the Authors to update the reference list of real-world evidences on SGLT-2 inhibitors with:
Mirabelli M, Chiefari E, Caroleo P, Vero R, Brunetti FS, Corigliano DM, Arcidiacono B, Foti DP, Puccio L, Brunetti A. Long-Term Effectiveness and Safety of SGLT-2 Inhibitors in an Italian Cohort of Patients with Type 2 Diabetes Mellitus. J Diabetes Res. 2019 Nov 4; 2019:3971060. doi: 10.1155/2019/3971060.
Also, epidemiological trends of diabetes mellitus in Taiwan should be integrated and updated with the most recent International Diabetes Federation (IDF) and 2019 Diabetes Atlas references.

2.	Scatter Plots in Figure 3 are not easy and intuitive to read. I suggest the use of conditional colors and larger fonts, other than a presentation of panels ordered from A to C (and not the current B, A, C).

3.	The “LEAD” acronym of this multicentric retrospective study should be explained in the introduction section, with the meaning of terms it refers to. The LEAD abbreviation could be mistaken for a well-known clinical trial program assessing the efficacy of GLP1-RA Liraglutide.

4.	Table 1: the mean values of SPB and DBP should be illustrated in two separate rows.

5.	Given its importance, Table S1 should be inserted as an ordinary table and not in supplementary materials.

6.	I would recommend English editing to improve readability of the manuscript and solve minor grammar issues.
Experimental design: This real-world study adheres to high ethical standards and research integrity principles. However, I would rise some concerns about clarity in the Methods section.
1.	It should be described how patient data were retrospectively collected and unified in a single database. Was it an automated procedure or were data extracted manually from the original medical records? The first option would have secured a higher degree of uniformity in the collection and analysis of data from multiple diabetes centers, thereby representing a strength point of this study.

2.	The statistical software used for the analysis should be specified.

3.	The exclusion criteria for participant eligibility are not clear. In particular, the phrase “patients undergoing treatment with other investigational drugs concurrently during the retrospective data collection period” appears confusing. Were you excluding patients concurrently treated with other novel antidiabetic agents (e.g. GLP1 RA) or patients generally involved in clinical trials independently of diabetes?

4.	The methods section should include how missing data were handled for the statistical analysis.

The influence of dapagliflozin dosage (5 mg vs 10 mg) on glycemic and weight control has not been assessed. It would be an interesting point, given that the higher dose of dapagliflozin was not routinely administered in this study.
Validity of the findings: This real-world study on dapagliflozin effectiveness in Taiwanese patients covers a central topic in Diabetology, and so Health Sciences. However, given the interesting results, the Discussion section could be much richer.

1.	I would suggest the Authors to discuss the paradoxical negative influence on dapagliflozin response by a dual combination therapy (Table S1, OR 0.6). It cannot be excluded that the adjunct of dapagliflozin on distinct dual combination therapy options (e.g. met+sulfonylurea, met+acarbose, met+ insulin etc) may affect its effectiveness.  For example, Mirabelli et al. evidenced that the SGLT2 inhibitor-sulfonylurea combination therapy has a negative impact on weight control in owerweight/obese diabetic patients.

2.	Although the primary outcome of this study is the effectiveness of dapagliflozin, the finding of a high rate of treatment interruption within 6 months of follow-up (400 patients, 20.4%) should be better detailed in the Results section and properly discussed. The “intolerance” term suggests genitourinary side effects in most cases. However, given the high prevalence of nephropathy in this study population (34.6%, Table 1) the risk of dapagliflozin-induced kidney injury is also conceivable, together with a loss in glycemic efficacy for a glycosuric agent. Also, how many patients shifted from dapagliflozin to different antidiabetic regimens due to “inadequate HbA1c control”?
Additional comments: The study is interesting and well executed, however, greater clarity in the methods description is required, together with the addition of dapagliflozin dosage in the regression logistic model to predict a positive glycemic response. Also, the discussion section should explore the study findings outlined above.


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: USE AND EFFECTIVENESS OF DAPAGLIFLOZIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A MULTICENTER RETROSPECTIVE STUDY IN TAIWAN
Review round: 1
Reviewer: 2

Output:
Basic reporting: Chen et al. conducted a multicentre retrospective study to examine the effectiveness of dapagliflozin on cardiovascular risk factors in Taiwan. It studied 1960 people with type 2 diabetes (52% men; mean age 58 years, HbA1c 8.8%, BMI 28 kg/m2) who were initiated with or switched to dapagliflozin. At baseline, 8% and 35% had prior coronary artery disease and nephropathy, respectively. Raw data were shared.

A major pitfall in the present study was lack of a control group. The effects of dapagliflozin were in line with existing literature, which was also stated in the Discussion.

Other major comments are as follows:
1.	Line 89: Please clarify what did LEAD mean.

4.	Discussion:
a)	Need more details of the study limitations.
b)	A few references that can be useful throughout the manuscript:
https://pubmed.ncbi.nlm.nih.gov/29852973/
https://pubmed.ncbi.nlm.nih.gov/31416989/
https://pubmed.ncbi.nlm.nih.gov/31902326/
https://pubmed.ncbi.nlm.nih.gov/27866701/
Experimental design: 2.	Statistical analysis:
a)	How did the authors handle missing data including a loss to follow-up and drug non-adherence? The results shown in Table 2 were per-protocol analysis. Would this introduce bias?
Validity of the findings: 3.	Results:
a)	Given 90% of people were treated with metformin at baseline, did the authors compare the effects of using dapagliflozin as 2nd and 3rd line therapy, as well as in different dual, triple or >3 drug combinations?
b)	Lines 158-160: What was the proportion of drug initiation/switch in primary and secondary prevention groups?
c)	Lines 181-184: Were the baseline characteristics similar between people who received add-on therapy versus switching therapy?
d)	Safety and non-adherence data are important and should be reported.
e)	Table 1: What were the proportions of people with or without cardiovascular disease/nephropathy treated with dapagliflozin at baseline? Did they show similar effectiveness?
f)	Table S1: Did the authors report the logistic regression results of other cardiovascular risk factors e.g. body weight?
g)	Figure S3: The majority of results showed a greater response in people with worse glycemic control. However, the change in body weight in people with HbA1c >10% was less than those with better glycemic control. What could be the possible reasons?
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: USE AND EFFECTIVENESS OF DAPAGLIFLOZIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A MULTICENTER RETROSPECTIVE STUDY IN TAIWAN
Review round: 2
Reviewer: 1

Output:
Basic reporting: The manuscript has been improved, addressing this reviewer’s comments with careful attention. There is only a minor point that should still require Authors’ consideration.

Please provide these novel subgroup analyses, evaluating the real-world effects of dapagliflozin dosage (5mg vs 10 mg) on HbA1c and body weight, to the reader as a supplementary figure, with differences (p values) among subgroups at 3 and 6 months.
Subgroup stratification by dapagliflozin dosage should be cited in material and methods, and findings should be shown and briefly discussed in the appropriate manuscript sections, taking into account that a dose-dependent reduction in body weight with dapagliflozin has been demonstrated in Chinese patients under placebo-controlled trial conditions.

(Cai X. et al. The Association Between the Dosage of SGLT2 Inhibitor and Weight Reduction in Type 2 Diabetes Patients: A Meta‐Analysis. Obesity (Silver Spring). 2018 Jan;26(1):70-80. doi: 10.1002/oby.22066 ).
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: USE AND EFFECTIVENESS OF DAPAGLIFLOZIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A MULTICENTER RETROSPECTIVE STUDY IN TAIWAN
Review round: 2
Reviewer: 2

Output:
Basic reporting: Thank you for the revision.

A few comments:
Line 87-92: Current professional guidelines recommend the use of glucose-lowering drugs based on compelling indications while HbA1c is an important tool in glycemic monitoring. Suggest rephrase.

Line 244-245 and throughout the manuscript, tables and figures: Odds ratios and 95% confidence intervals in 2 decimal points and P-values in 3 decimal points would have provided sufficient precision.
Experimental design: Line 157-171: The authors should state that only patients with complete data at baseline, month 3 and month 6 were included. Information on the handling of missing data is required either being described in the Statistical Analysis section or in a supplementary table.
Validity of the findings: Line 71-72 and Line 230: Please clarify the definitions of “improvement in HbA1c” and “simultaneous reduction in HbA1c and body weight”. Readers need to know if these improvements were clinically meaningful e.g. the proportion of patients with at least 0.5% or 1% HbA1c reduction; at least 3% weight loss. Based on these, we can know the characteristics and medication profiles of patients who had a very good response to dapagliflozin. Fig 3 only provided crude visualization.

Response to Comment 3 of Reviewer 2: The 2 bar charts showing the effectiveness of dapagliflozin on HbA1c and body weight by different combination therapy did report some useful data. This reviewer opined that the results should be reported.

Study limitations:
-	As mentioned in the previous review, the authors should discuss the limitation related to a lack of comparison arm and thus, the reported effect sizes might not reflect the true differences.
-	The inability to analyse by primary and secondary prevention groups.
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: USE AND EFFECTIVENESS OF DAPAGLIFLOZIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A MULTICENTER RETROSPECTIVE STUDY IN TAIWAN
Review round: 3
Reviewer: 1

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


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

Input:
Title: USE AND EFFECTIVENESS OF DAPAGLIFLOZIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A MULTICENTER RETROSPECTIVE STUDY IN TAIWAN
Review round: 3
Reviewer: 2

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: Thank you for the revision. I have no further comments.