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: DRAMATIC IMPACT OF FUTURE CLIMATE CHANGE ON THE GENETIC DIVERSITY AND DISTRIBUTION OF ECOLOGICALLY RELEVANT WESTERN MEDITERRANEAN CAREX (CYPERACEAE)
Review round: 1
Reviewer: 1

Output:
Basic reporting: In this manuscript Benítez-Benítez et al. are doing a comprehensive population genetic study with a group of closely related taxa of Carex, In addition, the authors are modelling their niche and projecting them to several scenarios of climatic change; apart from estimating lost/gained areas, they are doing a worthy attempt to see how the levels of genetic diversity and the genetic structure may change at the end of this century with respect to the present. Both the studied species (Carex, a well-known group with cold affinities) and the studied area (the Mediterranean Basin, whose climate will be among the most affected in the light of climate change) are particularly suited for this kind of approximation.
The methodology, both for the genetic and niche modeling aspects, is generally correct, with well-performed analyses. It is a pity, however, that the authors are still using the climatic scenarios of the Fifth Report of the IPCC (2014) and, thus, have not attempted to use the most updated climatic scenarios of the Sixth Report of the IPCC (CMIP6), that are available at least since early 2021. While the RCPs have been recalculated, they are combined with different socioeconomic assumption, i.e., the SSP or “Shared Socioeconomic Pathways”.
The Discussion is interesting and presented in a logical manner, though perhaps a little bit long (the conservation part can be easily reduced a little bit). In general, I liked the paper and I recommend publication in PeerJ.

Some minor questions:
(1)	I suggest the authors to note that the estimation of ten genetic diversity and genetic structure under the scenario of climate change assumes no migration (i.e., that the populations outside the inferred potential distribution will be extinct and the populations inside will remain in the same place), which is an important limitation of this approximation (and should be acknowledged).
(2)	The estimation of the ecological niche using the PCA for the future (Suppl. Fig. 4) is also assuming that the populations of the three species will remain in the same place as they occur today, which is quite unrealistic.
(3)	Line 406: the authors use genetic data to infer the location of potential refugia, which is correct. The authors, however, could take advantage of the SDM and infer the location of climate refugia at the LGM and even for older periods. There are paleo-climatological data till the Pliocene in the PaleoClim database (http://www.paleoclim.org/) or in Oscillayers (https://onlinelibrary.wiley.com/doi/full/10.1111/geb.12979).
Experimental design: The experimental design is the usual in population genetics and ecological niche modelling. All used parameters and statistical tests are conventional and suitable for the present study.
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: DRAMATIC IMPACT OF FUTURE CLIMATE CHANGE ON THE GENETIC DIVERSITY AND DISTRIBUTION OF ECOLOGICALLY RELEVANT WESTERN MEDITERRANEAN CAREX (CYPERACEAE)
Review round: 1
Reviewer: 2

Output:
Basic reporting: In the present manuscript, Benítez-Benítez and collaborators analysed the genetic structure of two sister species within the genus Carex, C. panormitana and C. reuteriana, using AFLP data. After disentangling the genetic structure within the complex, they studied the ecological niche of both species and subordinate taxa at present but also projected to the future under different climatic scenarios. They show how not only the putative favourable areas will be reduced in the future, but also how genetic diversity will be reduced as a consequence of the loss of populations.
The manuscript is well written with a careful English grammar, it is also well structured, with the introduction following the same structure than the discussion, stating clear objectives and hypotheses. Figures and tables are clear and clearly show the obtained results, and relevant literature on the field of study is cited.
Experimental design: The authors performed a great variety of analyses using different approaches, which led to the obtaining of strong results. For example, six different algorithms were used for the species distribution modelling, future projections were performed under another six different general circulation models, etc. Thus, I think the methods are well implemented, and despite the lower resolution of the AFLP when compared to high throughput sequencing techniques, the authors obtained good resolution to adress their questions.
Validity of the findings: Results are well supported by the strong and complete methodology followed by the authors. Even in the title, authors said that the study species are ecologically relevant, which also makes this research of interest for the understanding of those ecosistems and the consequences of the global climate change on their evolution in the future. In the text, the relevance of the species is justified by the abundance of these species in some ecosystems. My concern is whether these species, besides the abundance in riparian ecosystems, can play a role on those ecosystems, in sense of relationships with other species. After reading the manuscript and especially the threat of the species by overgrazing, I am thinking about this species as a primary resource for herbivorous species, and some other sources of importance for the ecosystems.
In this sense, I would add more ecologically information to the manuscript, not only to the introduction but also discussing the importance and implication that have the species on their ecosystems, and the consequences of their putative extinction. With a bit more ecological focus of the manuscript, this can be of interest for a broader audience and will generalized the scope of the research to other species and not only the two under study.
Additional comments: I found this manuscript is suitable for publication in PeerJ after some minor revisions and corrections as I specified above, and after incorporating the following:

Abstract:
Line 26 – Add comma after “…probably endangered”

Keywords:
Most keywords are already in the title or the abstract. I would suggest including some new keywords related to the manuscript, avoiding those in the title and/or abstract, for a more efficient indexing of the manuscript once published.

Introduction:
Lines 113-115 - The conservation will depends on the scope of the assessment (E.g. if regional or global). Thus, its conservation status is NOT disputed, but conditioned to the range considered for the assessment of the given species. If you wish to assess this species from a global perspective, maybe you can compare different (but global) red list.

Materials and Methods:
Line 153 – Specify version for PAUP
Line 169 – Specify version for GeneAlEx

Results:
Line 278 – “Carex” instead “C.” at the beginning of a sentence.
Line 306 – “Carex” instead “C.” at the beginning of a sentence.

Discussion:
Line 369 – Comma after “…subspecies reuteriana”
Line 394 – “North of Africa” instead “North Africa”
Line 397 – Remove “to” at the beginning of this line.
Line 451 – Rewrite this line as follows for a clearer comprehension: “endemism (Sicilian-Tunisian vs. Sardinian populations, Fig. 2) could remain stable over time.”
Line 523 – Correct this sentence to “…there are also at least…”
Lines 524-525 – Do you have some evidence for this species or another Carex species for the favouring of vegetative reproduction by overgrazing? Or is the overgrazing just preventing from sexual reproduction by herbivory of flowering shoots? if the latter, the rate of vegetative reproduction would remain stable and is the sexual reproduction rate what is decreasing. In this case, maybe you could rephrase this sentence.


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: DRAMATIC IMPACT OF FUTURE CLIMATE CHANGE ON THE GENETIC DIVERSITY AND DISTRIBUTION OF ECOLOGICALLY RELEVANT WESTERN MEDITERRANEAN CAREX (CYPERACEAE)
Review round: 2
Reviewer: 1

Output:
Basic reporting: The authors have correctly addressed my concerns. So, I think that the ms. is now in good shape.
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: DRAMATIC IMPACT OF FUTURE CLIMATE CHANGE ON THE GENETIC DIVERSITY AND DISTRIBUTION OF ECOLOGICALLY RELEVANT WESTERN MEDITERRANEAN CAREX (CYPERACEAE)
Review round: 2
Reviewer: 2

Output:
Basic reporting: In the previously-submitted version of the manuscript I commented some minor corrections that authors should be prior the acceptance of this paper. In this reviewed version, they incorporated most comments and justified why some (only few) other comments I made are not relevant to be included in this manuscript, in most cases due to lack of information about the study species/complex.

Then, I think this manuscript could be accepted for publication in PeerJ as is.
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: GOAL ADJUSTMENT AND WELL-BEING AFTER AN ACQUIRED BRAIN INJURY: THE ROLE OF COGNITIVE FLEXIBILITY AND PERSONALITY TRAITS
Review round: 1
Reviewer: 1

Output:
Basic reporting: It is a well-structured written manuscript with a clear and unambiguous statement and relevant literature were included. The figures and tables were appropriately included. No major comment on the basic reporting.
Experimental design: The overall design of the study is appropriate, with sufficient data included. All the tools used were clearly mentioned and the details procedures were clearly described. However, there are a few comments regarding the design.

 Page 13, lines 183 – 184; I would suggest if the author could include one figure to illustrate the procedure.
Validity of the findings: The results were well reported and discussed. However, there are some issues with regards to the finding specifically in terms of the participants involved and maybe could be discussed:

Page  10, lines 114-115; Participants’ age ranged from 19 to 66 years. Looking at the wide range of the participant's age, I am afraid it might affect the overall finding. I would suggest a much more focused age group. Even though the author did not discuss this variable, but from the finding, it is clear that there is a correlation between age and cognitive problems in general. How do you see this variable in understanding your finding as age is known to affect cognitive ability and the rehabilitation process?

Page 10, lines 115-116; some of the participants were of unique characteristics such as having stroke and history of brain surgery. how do you see this dynamic influencing your result?
Additional comments: no additional comment


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

Input:
Title: GOAL ADJUSTMENT AND WELL-BEING AFTER AN ACQUIRED BRAIN INJURY: THE ROLE OF COGNITIVE FLEXIBILITY AND PERSONALITY TRAITS
Review round: 1
Reviewer: 2

Output:
Basic reporting: Needs small improvements.
Experimental design: Needs small improvements.
Validity of the findings: Findings are valid. Reporting needs small improvements.
Additional comments: Thanks for opportunity to review manuscript entitled ‘‘Goal adjustment and well-being after an acquired brain injury: the role of cognitive flexibility and personality traits’’ for Peerj Journal. The author/authors examined the association between goal adjustment and well-being among acquired brain injury individuals. The strength of the manuscript includes examining variables of interest in a  sample where such studies are scarce, very good use of English, Overall,  the article is generally very well written and deserves to be published in this journal. However, some minor revisions must be made before the publication of the article. Because my main philosophy  of reviewing a manuscript as reviewer and sometimes an editor to improve the manuscript and not punishing the authors, I provided very specific and detailed peer review of the manuscript to increase its quality and citation potential. I hope authors of the manuscript may benefit from my review. Minor revisions reported section by section with the page and line number and when possible with suggestions.
Minor Revisions
Title
1. Title, Page 4, Line Number, Not available: The title of manuscript must be revised for correctness.  The correct form of title is  ‘ ‘Goal adjustment and well-being after an acquired brain injury: The role of cognitive flexibility and personality traits’’.
Abstract
2. Abstract, Page 4, Line Number, Not available : ‘ ‘78 persons with an ABI completed a set of questionnaires.’’ Must be corrected. It is incorrect to use numbers at the beginning of sentence as per APA 7 rules. The correct form is ‘ ‘Seventy eight persons with an ABI completed a set of questionnaires.’’
3. Abstract, Page 4, Line Number, Not available : Please revise following sentence ‘ ‘Indicators of wellbeing were the European Brain Injury Questionnaire (EBIQ) and the Satisfaction with Life Scale (SWLS).’’ One revision may be that ‘ ‘Indicators of wellbeing were measured with the European Brain Injury Questionnaire (EBIQ) and the Satisfaction with Life Scale (SWLS).’’
4. Abstract, Page 4, Line Number, Not available : Authors must provide long name of the NEO-FFI (NEO Five-Factor Inventory) in its first use in Abstract. Moreover, authors must used statistical analyses to Method section of abstract.
5. Abstract, Page 4, Line Number, Not available : No need to following sentence in Abstract and must remove from the manuscript ‘ ‘…..i.e., goal disengagement and goal reengagement’’.
6. Keywords are completely missing in the manuscript and must be added.
Introduction
7. Introduction, Page 5, Line 4:    Please revise following sentence for correctness ‘ ‘Head traumata and stroke are main causes.’’ One revision may be that ‘ ‘Head trauma and stroke are main causes.’’ Moreover, This sentence is very assertive. Thus,  add a citation to this sentence.
8. Introduction, Page 5, Line 4-5: The citation/citations need for following sentence ‘ ‘Less common causes are anoxia, brain tumours, substance abuse and brain infections.’’
9. Introduction, Line 12-15: Following sentences are unrelated o content of manuscript and must remove from manuscript. ‘ ‘Nevertheless, accepting of the reality of the problem has been shown to improve the subjective quality of life (Van Bost, Van Damme & Crombez, 2017). Of importance, acceptance is not simply surrendering to an unwanted reality. It is ”recognizing the need to adapt to chronic illness while perceiving the ability to tolerate the unpredictable, uncontrollable nature of the disease and handle its adverse consequences” (Evers, 2001, p. 1027). Diller (2005) considers acceptance to be a marker of mental health and a desirable outcome of rehabilitation efforts.’’
10. Introduction General: Apart from above correction Introduction is very well written. I congratulate the authors. I really very much liked the section Line 24-47.
Method
11. Method, Page 9 Line, 103: 68 participants must be 78 participants.
12. Method, Page 9 Line, 107: participating centres must be participating centers.
13. Method, Page 9 Line, 114: M and SD must be italic.
14. Method, Page 9 Line, 117: SD must be italic.
15. Method, Page 9 Line, 118: M and SD must be italic.
16. Method, Page 9 Line, 120-123: Following sentences must move to Procedure section ‘ ‘Ethical approval was obtained from the Ethical Committee of the Faculty of Psychology and
Educational Sciences of the Ghent University (2012/66). Written informed consent was obtained from the participants. They also gave permission to the rehabilitation professional of the service to give information about demographics and illness characteristics to the researcher.’’
17. Method, Page 11, Line 155: Please revise following sentence for clarity ‘ ‘Cronbach’s α for the Acceptance-scale was .91’’ One revision may be that ‘ ‘Cronbach’s α for the Acceptance-scale was .91 in this study’’.
18. Method, Page 11, Line 156-158: Please revise following sentence ‘ ‘The Dutch version of the 5-item Satisfaction with Life Scale (Diener, Emmons, Larssen, & Griffin, 1983) measures judgements about global life satisfaction (e.g. “I am satisfied with my life”).’’ One revision may be that‘ ‘The Dutch version of the 5-item Satisfaction with Life Scale (Diener, Emmons, Larssen, & Griffin, 1983) was used to measure global life satisfaction (e.g. “I am satisfied with my life”).’’
19. Method, Page 11, Line 166-167: Please revise the following sentence. It is very difficult to understand ‘ ‘The psychometric properties are sufficient (Sopena, Dewar, Nannery, Teasdale, & Wilson, 2007). Van Bost, Van Damme, & Crombez (2017) made a Dutch translation.’’
20. Method, Page 11, Line 168: Please revise the following sentence ‘ ‘ …… which will also be used in this study’’ One revision may be that ‘ ‘…..which we used in this study’’.
21. Method, Page 11, Line 168: Authors must add Core’s internal consistency coefficient calculated in their study (Cronbach’s alpha). Moreover, authors must add possible scores for missing scales. For example Core.
22. Method, Page 11, Line 172: Please revise the following sentence ‘ ‘ …… or number (1-4).’’ One revision may be that ‘ or number in this test’’. I am not able to understand what authors want to mean with ‘‘(1-4)’’
23. Method, Page 13, Line 185: The reason why authors did not used the ICQ in their analyses are unclear and authors must give information about reasons. Moreover, ıf they did not used this scale, I think authors must completely remove from Measures section but not sure about this. The last decision related to this pertaining to editor.
24. Method, Page 13, Line 191: Please add such as after the demographic information the new form looks like this ‘ ‘…….demographic information such as time since injury, the expert ratings of the illness characteristics….’’
25. Method, Page 13, Line 193-194: Please revise the following sentences ‘ ‘Associations between those variables were examined using Pearson correlation coefficients.’’ A better writing may be that ‘ ‘We used Pearson’s product moment correlation analyses to examine strength and direction of linear association between study variables.’’ or ‘ ‘Pearson’s product moment correlation analyses were used to examine strength and direction of linear association between study variables.’’
26. Method, Page 13, Line 195: Please revise the following sentences ‘‘Two hierarchical multiple regression analyses were then conducted.’’ One revision may be that ‘ ‘Then, we conducted two separate two hierarchical multiple regression analyses.’’
27. Method, Analysis: Authors must change Analyses title as Statistical Analyses. Moreover, author must add brief information about assumption testing in regression and correlation analyses. For example, ‘ ‘Preliminary analyses conducted to ensure no major violation of assumptions of normality, linearity, homoscedasticity, and multicollinearity in the main analyses.’’ or ‘‘We performed preliminary analyses to ensure no major violation of assumptions of normality, linearity, homoscedasticity, and multicollinearity in the main analyses.’’ Homoscedasticity of variance in multiple regression, and homogeneity of variance in t-test is the same thing. Thus, writing one of them is enough. Some researchers unfamiliar with general linear models thinks they are different.
28. Method, Analysis: As a multivariate analyst, I can confidently say that unpaired t-tests are completely wrong if authors compared to  difference between the personality of this group of individuals with an ABI and that of the general population. The true analysis is one sample t-tests if standard deviation is unavailable. If standard deviation available for population one sample z-test must be used. However, standard deviation is an approximation in one sample z-test if sample size is no fairly large. Thus, one sample t-test is a better choose in most situations. Moreover, I calculated one sample t-test for randomly chosen variables from Table 2 and found similar results. authors may be wrongly reported their used analyses.
29. Method, Analysis: As a multivariate analyst, I think information/writing about hierarchical multiple regression analyses are very repetitive. Moreover, authors did not conduct two separate regression analyses, rather they used four separate regression analyses. Two for different goals , one for life satisfaction, and one for quality of life. Apart from above corrections, Method  section is well written.
Results
30. Results, General: Authors must report all findings with two decimal except for p value (three decimal) in the Tables.
31. Results, General: Authors must add Notes. Under the Tables before reporting significance levels.
32. Results, General: Authors must add commas between significance level under the tables.
33. Results, Table 2: Authors must add Cohen d effect size estimates after they are correcting the analyses.
34. Results, Table 3, Table 4: Authors must add semi-partial correlations to Table 3, and Table in the final model after the β final (standardized).
35. Results, Table 4: Abbreviations must be under the table in Table 4.
36. Results, General: Authors need to correct reporting all F change reporting. Add a space between to degrees of freedoms, and p value reporting  and change with delta.  Wrong: (F change (1,60) = 4.27, p=.043). True: (ΔF (1, 60) = 4.27, p = .043). Apart from above corrections, Result section is well written.
Discussion
37. Discussion, Page 16, Line 251-252: Authors must remove following sentence.  I think it is unnecessary. ‘ ‘as measured by the percentage perseverative errors on the WCST.’’.
38. Discussion, Page 16, Line 267: Authors must remove following sentence.  I think it is unnecessary. ‘ ‘i.c. cognitive flexibility,’’
39. . Discussion, Page 19, Line 324-128: Although I read six times fourth limitation , I am not able to understand what I have to conclude. Authors need to completely revise following part  ‘ ‘It is not possible to make strong statements based on a single test. The choice for the full version of the WCST prevented us to test for cognitive persisitence. Teubner-Rhodes et al. (2017) developed a measure of cognitive persistence based on the short version of the Wisconsin Card Sorting Test.’’
40. Discussion, Clinical Implications: Clinical implications are written for others who may benefit from research findings. Thus, as a writing tip don’ use any time we statement in this section otherwise very necessary. Always use such as mental health professionals, practitioner, researchers, clinicians, counselors, rehabilitation professionals. Thus, I strongly recommend to rewrite sentence with we in this section.
41. Discussion, General: Conclusion section and future studies is completely missing in this section. Author must add a paragraph after clinical implications section and must add a conclusion paragraph and recommendations for future studies.
42. Apart from above corrections, Discussion section is well written.


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: GOAL ADJUSTMENT AND WELL-BEING AFTER AN ACQUIRED BRAIN INJURY: THE ROLE OF COGNITIVE FLEXIBILITY AND PERSONALITY TRAITS
Review round: 1
Reviewer: 3

Output:
Basic reporting: Basic reporting is adequate.
Experimental design: Experimental design is adequate and true.
Validity of the findings: The findings are valid.
Additional comments: Thanks for giving me the opportunity to review the manuscript entitled ‘‘Goal adjustment and well-being after an acquired brain injury: the role of cognitive flexibility and personality traits’’ for Peerj Journal. The author/authors examined the association between goal adjustment and well-being among acquired brain injury individuals. The strength of the manuscript includes examining variables of interest in a sample where such studies are not common. Overall, the article is very well written and deserves to be published in this journal. However, some minor revisions must be made before the publication of the article. I hope authors of the manuscript may benefit from my review. Minor revisions reported section by section with the page and line number and when possible with suggestions.
Minor Revisions
Title
1. Title, Page 4, Line Number, Not available: The title of manuscript must be revised for correctness. The correct form of title is ‘‘Goal adjustment and well-being after an acquired brain injury: The role of cognitive flexibility and personality traits’’.
Abstract
2. Abstract, Page 4, Line Number, Not available : ‘ ‘78 persons with an ABI completed a set of questionnaires.’’ Should be changed as ‘ ‘Seventy eight persons with an ABI completed a set of questionnaires.’’ in terms of APA 7.

Introduction
3. Introduction, Page 5, Line 3:    Please add another sentence between first and second sentence. There is a sharp pass between them.  One revision may be that ‘ ‘Although there are various causes for it, traumata and stroke are main causes.’’

Method
4. Method, Page 9 Line, 103: 68 participants must be 78 participants.
5. Method, Page 9 Line, 107: participating centres must be participating centers.
6. Method, Page 9 Line, 114: M and SD must be italic.
7. Method, Page 9 Line, 117: SD must be italic.
8. Method, Page 9 Line, 118: M and SD must be italic.

Results
9. Results, General: Authors must report all findings with two decimal except for p value (three decimal) in the Tables.
10. Results, General: Authors must add Notes. Under the Tables before reporting significance levels.
11. Results, General: Authors must add commas between significance level under the tables.
12. Results, Line 227, F change should not be reported like.

Discussion
12. In discussion section implications might be strengthened for clinicians and researchers.

References
13. References, Please correct the uppercase letters for this reference ‘Brandtstädter, J., & Rothermund, K. (2002). The Life-Course Dynamics of Goal Pursuit and 349 Goal Adjustment: A Two-Process Framework. Developmental Review, 22(1), 117-150.

14. There are same mistakes through the reference list. İt should be checked.


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: GOAL ADJUSTMENT AND WELL-BEING AFTER AN ACQUIRED BRAIN INJURY: THE ROLE OF COGNITIVE FLEXIBILITY AND PERSONALITY TRAITS
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: all the comments and suggestions have been taken into consideration and improvements to the manuscript have been made.


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: GOAL ADJUSTMENT AND WELL-BEING AFTER AN ACQUIRED BRAIN INJURY: THE ROLE OF COGNITIVE FLEXIBILITY AND PERSONALITY TRAITS
Review round: 2
Reviewer: 2

Output:
Basic reporting: The manuscript is  clear and unambiguous, professional English used throughout.
Experimental design: Rigorous investigation performed to a high technical & ethical standard.
Validity of the findings: All underlying data have been provided; they are robust, statistically sound, & controlled.
Additional comments: Thanks for opportunity review revised manuscript entitled  ‘‘Goal adjustment and well-being after an acquired brain injury: the role of cognitive flexibility and personality traits’’. I would like the thanks to authors. They make a good job for improving  quality of their manuscript. Authors revised the manuscript as I requested with  a good will. In this form, Introduction reflects very well the previous studies and study aim, Method section and Result section is correct, and Discussion section adequately synthesis to previous study findings and current study results. Overall, I have no further comment regarding to manuscript. I congratulate to authors and wish them success on their future endeavors.


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: GOAL ADJUSTMENT AND WELL-BEING AFTER AN ACQUIRED BRAIN INJURY: THE ROLE OF COGNITIVE FLEXIBILITY AND PERSONALITY TRAITS
Review round: 2
Reviewer: 3

Output:
Basic reporting: It is suitable.
Experimental design: It is suitable.
Validity of the findings: The validity of the findings is correct.
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: SEAMENS’ SIGN: A NOVEL ELECTROCARDIOGRAM PREDICTION TOOL FOR LEFT VENTRICULAR HYPERTROPHY
Review round: 1
Reviewer: 1

Output:
Basic reporting: Academic reporting of cases is generally reserved for bedside case presentations (usually not mentioned in the standard textbooks) do not catch enough attention to warrant publication. This article is definitely not one such.
Experimental design: no comment
Validity of the findings: Any possible impact of this novel clinical finding is hard to predict as it depebds upon post it might find in every-day work. However, the method of presentation is clear and straightforward enough to permit replication.
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: SEAMENS’ SIGN: A NOVEL ELECTROCARDIOGRAM PREDICTION TOOL FOR LEFT VENTRICULAR HYPERTROPHY
Review round: 1
Reviewer: 2

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: Well prepared, clear and effectively structured 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: SEAMENS’ SIGN: A NOVEL ELECTROCARDIOGRAM PREDICTION TOOL FOR LEFT VENTRICULAR HYPERTROPHY
Review round: 1
Reviewer: 3

Output:
Basic reporting: 1. Dr. Walker and colleagues  developed a novel, quick, easy to use ECG screening criterion (Seamens’ Sign) for LVH. This new criterion was defined as the presence of QRS complexes touching or overlapping in two contiguous precordial leads.  When compared to both the Sokolow-Lyon criteria and the Cornell criterion for men, Seamens’ Sign is noninferior in ruling in LVH on ECG. Additionally, Seamens’ Sign has higher inter-rater agreement compared to both Sokolow-Lyon criteria as well as the Cornell criteria for men and women.
2. The English writing is well.
3. The literature reviews are comprehensive.
4. Raw data were shared.
Experimental design: 1. The study design was acceptable.
2. In the methods, the authors reported a high prevalence of echocardiographic LVH "35%", but did not mention the quantitative definition for echocardiographic LVH, possibly leading to a bias.
3. There were no baseline profiles of the patients, i.e. hypertension which might limit the applications.
4. I would like to see the correlations between various ECG criteria and Seamens sign for LVH. For instance, what are the consistency rates between Sokolow-Lyon (+) and Seamens sign (+) as well as Sokolow-Lyon (-) and Seamens sign (-)..... And what are the additional advantages of Seamens sign on the other ECG criteria for echocardiographic LVH?
Validity of the findings: 1. The sensitivity and specificity using Sokolow-Lyon and Cornell ECG-based criteria were close to prior studies.
2. The PPV and NPV were low, limiting the applications.
Additional comments: In the current ECG machine, there are automatic interpretation software for LVH interpretation according to various ECG criteria, which could be helpful to the physicians and the utilization of Seamens signs might be limited.


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: SEAMENS’ SIGN: A NOVEL ELECTROCARDIOGRAM PREDICTION TOOL FOR LEFT VENTRICULAR HYPERTROPHY
Review round: 1
Reviewer: 4

Output:
Basic reporting: At first, this appeared as a decently written manuscript that would
find its way quite easily. ¸Unfortunately, I distinctly remembered that I have read this paper before.
Experimental design: -
Validity of the findings: -
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: SEAMENS’ SIGN: A NOVEL ELECTROCARDIOGRAM PREDICTION TOOL FOR LEFT VENTRICULAR HYPERTROPHY
Review round: 2
Reviewer: 1

Output:
Basic reporting: When I reviewed the original of this paper. I detected a huge amount of previously published materials published elsewhere by the same group of authors.  It was not clearly said that it was not a peer-reviwed material, which was ok to submit. So, my criticism is chiefly to the journal. The authors' work seems fit for the publication.
Experimental design: The authors' work seems fit for the publication.
Validity of the findings: The authors' work seems fit for the publication.
Additional comments: The authors' work seems fit for the publication.


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

Input:
Title: SEAMENS’ SIGN: A NOVEL ELECTROCARDIOGRAM PREDICTION TOOL FOR LEFT VENTRICULAR HYPERTROPHY
Review round: 2
Reviewer: 2

Output:
Basic reporting: As prior comments
Experimental design: As prior comments
Validity of the findings: As prior comments.
Additional comments: In the authors' response, they stated their paper strengths and limitations below, please adding these statements in the revised manuscript.

The correlations between the various ECG criteria were not calculated during this study, as it was planned for a future study of the Seamens’ Sign. With regards to this study though, given that the ECG criteria to evaluate LVH yield qualitative results, we believe that the comparison of the sensitivities and specificities is adequate since the various test methods are calculated for each patient against the TTE for each individual patient, which was defined as the gold standard in our manuscript.


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

Input:
Title: SEAMENS’ SIGN: A NOVEL ELECTROCARDIOGRAM PREDICTION TOOL FOR LEFT VENTRICULAR HYPERTROPHY
Review round: 2
Reviewer: 3

Output:
Basic reporting: I feel this submission is acceptable
Experimental design: I feel this submission is acceptable
Validity of the findings: I feel this submission is acceptable
Additional comments: I feel this submission is acceptable


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: SEAMENS’ SIGN: A NOVEL ELECTROCARDIOGRAM PREDICTION TOOL FOR LEFT VENTRICULAR HYPERTROPHY
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: SEAMENS’ SIGN: A NOVEL ELECTROCARDIOGRAM PREDICTION TOOL FOR LEFT VENTRICULAR HYPERTROPHY
Review round: 3
Reviewer: 2

Output:
Basic reporting: The paper is acceptable at current version.
Experimental design: The paper is acceptable at current version.
Validity of the findings: The paper is acceptable at current version.
Additional comments: The paper is acceptable at current version.


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: SEAMENS’ SIGN: A NOVEL ELECTROCARDIOGRAM PREDICTION TOOL FOR LEFT VENTRICULAR HYPERTROPHY
Review round: 3
Reviewer: 3

Output:
Basic reporting: I had no suggestions previously.
Experimental design: I had no suggestions previously.
Validity of the findings: I had no suggestions previously.
Additional comments: I had no suggestions previously.


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: GLOMERULAR FILTRATION RATE CORRELATION AND AGREEMENT BETWEEN COMMON PREDICTIVE EQUATIONS AND STANDARD 24-HOUR URINARY CREATININE CLEARANCE IN MEDICAL CRITICALLY ILL PATIENTS
Review round: 1
Reviewer: 1

Output:
Basic reporting: Thank you for the invitation to review this manuscript. This is an interesting piece of work. However, there are several limitations in the manuscripts which I believe should be considered before making any decision on this submission.

1. The abstract section of the manuscript has more details on the study rationale and methods. The authors provided very limited results in this section. I suggest including more numerical results rather than descriptive statements i.e. correlation coefficients between equations, demographics of patients, etc.

2. The conclusion section in the abstract is quite general, and does not represent the main findings from the results. The conclusion should be according to the results of this study rather than a general statement. These statements can be adjusted after conclusive remarks.

3. Authors have well explained the rationale of this study but did not provide any information on the previous studies conducted on the same topic. It's obvious that the current study is not the first one in this field, authors need to provide the reference from previous studies and explain the justification that why this study is needed in the presence of other studies.
Experimental design: The methodology section is very brief and dispersed. Authors may follow the following headings to re-construct this section; ethics, study location, study population with inclusion and exclusion criteria, data collection, operational definitions, normal laboratory values used to classify morbid conditions in this study, primary outcome variables, and statistical analysis. I appreciate that the authors have presented most of this information but it would be more convenient for readers to understand the methods divided into various sections.
The sample size estimation must be provided under a separate heading with the name of the equation used for such estimation.
 The level of correlation should be explained in the statistical analysis section. i.e. the cut-off values used in the classification of correlation coefficients
There is a lack of information on how baseline serum creatinine was estimated among patients. Since the baseline values are important for GFR estimation, the authors did not discuss the impact of over-and under-estimation of baseline Serum creatinine on the findings of this study.
Validity of the findings: The findings of this study are well presented in the form of tables and figures. However, the discussion section needs the attention of the authors.  There is a need to discuss the impact of cystatin-based equations on the findings. Do authors provide a hypothesis that GFR based on the UCrCl method may be equal, higher, or lower than what is estimated with cystatin-based equations? I think the authors should also consider the low sample size as a potential limitation of this study. Since authors have carried out vigorous inferential tests on the data, a large sample size may result in variable findings. Please discuss the same in the limitation section.
Again, the conclusion section is quite general, authors should state the major results in this section followed by directions for future research and recommendations for practice.
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: GLOMERULAR FILTRATION RATE CORRELATION AND AGREEMENT BETWEEN COMMON PREDICTIVE EQUATIONS AND STANDARD 24-HOUR URINARY CREATININE CLEARANCE IN MEDICAL CRITICALLY ILL PATIENTS
Review round: 1
Reviewer: 2

Output:
Basic reporting: Thanks for asking me to review this study. Wongpraphairot et al. attempted to compare the four commonly used equations for estimation of GFR among critically ill patients with respect to UCrCl. I agreed with the authors that these equations primarily originated from other populations without involving critically ill patients. There is a need to explain that in the presence of a large volume of studies (given below) where the use of these equations is discouraged, why this study is needed, and what new information is being produced through the analysis in this study.

https://pubmed.ncbi.nlm.nih.gov/34055406/

https://jintensivecare.biomedcentral.com/articles/10.1186/2052-0492-2-31

https://academic.oup.com/ndt/article/25/1/102/1909271

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2731708

https://link.springer.com/article/10.1007/s40262-018-0636-7

https://journals.sagepub.com/doi/pdf/10.1177/0310057X1804600107

I agree that there is a need for more data and the authors may have used these grounds to conduct this study. But what new information is brought up through this study is not clear to me.
Experimental design: The methodology and study design are sound in this study. However, the method section requires more clarification, particularly the terms used throughout the manuscript. For example, low- and normal-UCrCl groups should be defined in the method section.
Since this study is conducted on a cohort from a previously initiated trial, there is a need to briefly describe the primary cohort from which patients` data were extracted.
There is no information on the confounding adjustment in the statistical analysis section, the CrCl and GFR are also confounded by various factors which the authors have already discussed in the discussion section. Were these factors adjusted in the correlation analysis?
Validity of the findings: Discussion section: Authors have quoted the statement "It also should be noted that the correlation between UCrCl and eGFR from predictive equations was poor and had a large bias and poor repeatability in several critical care settings, either for medical or surgical patients----------------------"

However, in their results, they explained that "We performed a correlation analysis for UCrCl and eGFR from four commonly used predictive 188 equations using the Spearman rank correlation coefficient. All eGFR values from the predictive 189 equations showed a good correlation. Nevertheless, the MDRD-6 equation had the strongest correlation with the standard UCrCl method, with a correlation coefficient of 0.76".... There is a need to explain the deviations
Additional comments: Can I assume that the authors are trying to convince the use UCrCl method instead of these four equations in critically ill patients?


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: GLOMERULAR FILTRATION RATE CORRELATION AND AGREEMENT BETWEEN COMMON PREDICTIVE EQUATIONS AND STANDARD 24-HOUR URINARY CREATININE CLEARANCE IN MEDICAL CRITICALLY ILL PATIENTS
Review round: 1
Reviewer: 3

Output:
Basic reporting: The language should be clearer and there is still way to improve
Experimental design: 1)	The author should stress the basis of using 24-hour Urinary Creatinine Clearance in the setting of acute kidney injury in the introduction.
2)	It is best to include patients' urine volume among these clinically ill patients and their baseline kidney problem or eGFR. Other vital signs are essential too.
3)	The definition of a more stable patient admitted to ICU should be clearly defined as the definition of the targeted cohort is very important for the reliability of the results (In methodology).
Validity of the findings: 1)	Regarding the discussion, what other literature suggested the best formula for the critically ill patient? Compare authors finding with other published literature.
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: GLOMERULAR FILTRATION RATE CORRELATION AND AGREEMENT BETWEEN COMMON PREDICTIVE EQUATIONS AND STANDARD 24-HOUR URINARY CREATININE CLEARANCE IN MEDICAL CRITICALLY ILL PATIENTS
Review round: 2
Reviewer: 1

Output:
Basic reporting: I have no more concerns on this submission.
Experimental design: I have no more concerns on this submission.
Validity of the findings: I have no more concerns on this submission.
Additional comments: I have no more concerns on this submission.


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

Input:
Title: GLOMERULAR FILTRATION RATE CORRELATION AND AGREEMENT BETWEEN COMMON PREDICTIVE EQUATIONS AND STANDARD 24-HOUR URINARY CREATININE CLEARANCE IN MEDICAL CRITICALLY ILL PATIENTS
Review round: 2
Reviewer: 2

Output:
Basic reporting: Authors had addressed all the relevant comments and made necessary modifications in the manuscript clearly.
Experimental design: Authors had addressed all the relevant comments and made necessary modifications in the manuscript clearly. Although i still feel that current research does not fill knowledge gap as already so much work has been done on renal function estimating equations and urine creatinine clearance
Validity of the findings: In the revised manuscript, authors have added study rationale and significance.
Additional comments: Overall authors have addressed all the comments in the revised version of manuscript.


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

Input:
Title: QUALITY ASSESSMENT OF A SERUM AND XENOFREE MEDIUM FOR THE EXPANSION OF HUMAN GMP-GRADE MESENCHYMAL STROMAL CELLS
Review round: 1
Reviewer: 1

Output:
Basic reporting: The background of the figures (Fig5.d) demonstrating adipogenic differentiation is too dark and blue. It would be better to increase the intensity of illumination to get images with lighter background.
Experimental design: The work described in the manuscript of Martinaude et al. entitled “Quality assessment of a serum and xenofree medium for the expansion of human GMP-grade mesenchymal stromal cells” (#56142) is not novel. The authors perform experiments that have been recommended by the ISCT and published earlier. The manufacturer of this GMP medium (Milteny Biotech: MSC-Brew GMP Medium) have tested this product as described on the homepage. I agree that validation of a newly introduced serum and xenofree culture medium/bag in their stem cell production facility is absolutely necessary but this is of limited scientific value.
For demonstration of the immunosuppressive property of these clinical grade MSCs in co-culture with THP-1 cells, the authors measure the decrease in the amount of the pro-inflammatory cytokine TNFalpha. This experiment alone is not the most adequate choice, especially if the authors show only ratio and no absolute numbers. The TNFalpha absolute values in this case could be very low anyways (Fig6.).
In the MSC-THP-1 co-culture experimental setting, it would be much better to demonstrate the parallel increase of factors that consequently reduce inflammation (e.g.  PGE2, IL-10) and provide absolute concentrations as well.
Furthermore, one should consider other type of experiments (inhibition of T cell proliferation). Functional in vitro tests should be relevant for later clinical use of the particular MSC product. The authors do not provide information on the future clinical use of the cells.
Validity of the findings: I have concerns about the high percentage of positivity with the CD146 marker (Fig4.a) that supposed to stain a subpopulation of MSCs as published by multiple groups earlier.  The authors discuss this phenomenon as known in dental pulp MSCs cultured with serum and xenofree medium, but here they use MSCs from bone marrow and adipose tissue and they also have high CD146 positivity (30-95%) in their reference culture with alphaMEM medium and human concentrate platelet lysate.
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: QUALITY ASSESSMENT OF A SERUM AND XENOFREE MEDIUM FOR THE EXPANSION OF HUMAN GMP-GRADE MESENCHYMAL STROMAL CELLS
Review round: 1
Reviewer: 2

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: The manuscript provides an interesting comparison of platelet lysate versus SXFM cultured MSCs. Since, SXFMs will be needed for the commercial production of MSCs, the present study is relevant for the advancement of the field. However, the methods, results, and discussion section require some major revisions before the manuscript can be accepted.

Introduction:
The introduction is adequate, but there are a few minor issues
•	Line 90: What is the significance of specifically mentioning psoralen in the sentence?
•	Line 93: The following sentence does not make good sense: ‘Finally, hCPL release criteria that have been recently proposed may be challenging for small structure and encouraging alternative products’

Methods:
•	Figure 1 greatly helps in understanding the structure of the study. Although there is some ambiguity in the methods section that should be corrected.
•	Multipotency assay: The text does not mention if hCPL or SXFM were added to the differentiation media. Moreover, it is mentioned that FBS was added to both the differentiation media. Please explain why?
•	Immunomodulatory assay: not clearly mentioned at what step hCPL or SXFM was added in the experiment.
•	Statistics: Ln 237, where were the non-inferiority analyses applied?

Results:
•	Figure 2: Please provide images of the whole plate for CFU assay showing multiple colonies, in addition to the zoomed-in images of a single colony in 2A. That will help in visualizing the difference in number, size, and density of the colonies, as mentioned in the results.
•	Figure 3: Statistical results should be presented; the level of negative markers seems variable between CPL and SXFM and could be significantly different. Please also explain how the authors decided that less than 5% positive cells for a maker is considered lack of expression (Ln 274). The figure legends states that 'N=2-6', is that a typographic error?
•	Figure 4: Can the authors quantitatively compare the differentiation of cells in the 2 media (probably by quantify the stains?), if not please discus this limitation.

Discussion
Please discus the limitations of the present study and the future directions required to further validate the clinical utility of the SXFM under investigation.

Supplemental data
Explain the content of the supplemental data in the manuscript text or remove it. In its current form the supplemental does not make much sense.

Minor corrections:
•	Ln 147: Replace ‘on the it’ with 'on them'
•	Ln 172: centrifuged
•	Ln 177: analyses
•	Ln 217: should it be 0.2 and 1 x 10^6 cells/mL?
•	Ln 343: immunomodulation
•	Ln 344: 4 X 10^6 cells


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: QUALITY ASSESSMENT OF A SERUM AND XENOFREE MEDIUM FOR THE EXPANSION OF HUMAN GMP-GRADE MESENCHYMAL STROMAL CELLS
Review round: 2
Reviewer: 1

Output:
Basic reporting: Manuscript 56142-2:
I accept the responses to my comments and modifications made by the authors.
Experimental design: N/A
Validity of the findings: N/A
Additional comments: No 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: IL-4/IL-13 AXIS AS THERAPEUTIC TARGETS IN ALLERGIC RHINITIS AND ASTHMA
Review round: 1
Reviewer: 1

Output:
Basic reporting: Yes the review if of broad and cross-disciplinary interest. The topic and content discussed in this manuscript is within the scope of the journal

oThe role of IL-4/IL-13 in allergic response has not been reviewed. This manuscript provides novel insights and informative summaries of recent development in this field. From a quick pubmed search, another IL-4 / IL-13 review (published on Cells in 2021) that might be of interest describes their involvement on inflammatory arthritis with a specific focus on RA. (Link: https://pubmed.ncbi.nlm.nih.gov/34831223/) It would be interesting to compare and contrast some of the pathophysiological pathways in AR/asthma and RA as IL-4/IL-13’s involvement in inflammatory arthritis is well-studied.

The Introduction provided concise context on the pathophysiology of AR and asthma as well as the involvement of IL-4 and IL-13 in this process. However, it failed to mention what is missing / unknown in this field that this manuscript can provide valuable insights on. It would be great if the authors can provide their opinions on where the future research should focus on to better enhance our understanding of the Il-4/IL-13 signaling pathways, as well as clinical research into AR and asthma. The transition from describing the signaling pathways to therapeutic antibodies targeting IL-4/IL-13 is very abrupt. It would be great if the authors can add a few sentences on why IL-4 and IL-13 have been used as therapeutic target for AR and asthma to better establish this link.
Experimental design: Yes the survey methodology is consistent with a comprehensive and unbiased coverage of the subject.

The authors did a great job sourcing / citing relevant publications. The summary table of clinical studies targeting IL-4/IL-13 for AR and asthma is very helpful.

The organization and subsections are also appropriate. The manuscript is structured and presented in a reader friendly manner.
Validity of the findings: Overall comments: the authors provided very good descriptions and summaries of clinical studies targeting the IL-4/IL-13 axis for AR and asthma. The authors included studies with both positive and negative results on the therapeutic potential of IL-4/IL-13 targeted agents. However, the authors spent a lot of texts summarizing the past / recent clinical studies targeting IL-4/IL-13, but the descriptions on the biochemical and cellular pathways regulated by IL-4 and IL-13 are disproportionally limited. Figure 1 provides great illustration on the complex signaling pathway, but it would be great if the authors can elaborate more on the involvement of IL-4/IL-13 in AR and asthma.

Row 122-124 "IL-4Rα/13Rα1 high-affinity heterodimer receptor has the ability to bind both IL-4 and IL-13, which clarifies the similarity of their biological functions in the development of allergic responses."
This is an overstatement. Just because the IL-4Ra/13Ra1 heterodimer receptor has the ability to bind both IL-4 and IL-13, it is not sufficient to draw the conclusions that IL-4 and IL-13 has similar biological functions during allergic responses.The authors should provide additional literature to support this statement or additional rationales / evidences to demonstrate that IL-4 and IL-13 truly play similar functions in allergic responses

The Conclusion section is week and contains statements that are not accurate. Specifically, the authors only mentioned the clinical success of dupilumab in AR/asthma but neglected the many trials with negative / inconclusive results. It would be better if the authors can provide an unbiased and less rosy view on the clinical outlook of IL-4/IL-13 targeted therapeutics. Given the various trial results, it would also be worth discussing what might have caused the different outcomes and potential hypothesis on the limitations of only targeting the IL-4/IL-13 axis
Additional comments: N/A


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

Input:
Title: IL-4/IL-13 AXIS AS THERAPEUTIC TARGETS IN ALLERGIC RHINITIS AND ASTHMA
Review round: 1
Reviewer: 2

Output:
Basic reporting: The paper is well structured and written, with clear objectives. The topic is an important subject.
Experimental design: This review is organized logically into coherent paragraphs/subsections.
Validity of the findings: In this manuscript, there are well-developed and supported arguments that meet the goals set out in the Introduction, and the authors also discuss the future directions in in AR and asthma.
Additional comments: In this review, the authors demonstrated that the type II cytokines IL-4 and IL-13 play an important role in the pathogenesis of allergic rhinitis and asthma. The authors also discussed the biological characteristics of IL-4 and IL-13, their signaling pathways, and therapeutic monoclonal antibodies targeting each cytokine as well as their receptors in both AR and asthma. Then the authors suggested that the pleiotropic roles of IL-4 and IL-13 in orchestrating Th2 responses in AR and asthma patients indicate that dual IL-4/IL-13 blockade is a promising therapeutic strategy for both diseases. However, there are several concerns that the authors need to address/clarify further and validate the current conclusions.

1.	The authors need to add more epidemiological information in the introduction such as how many people do AR and asthma affect, and the fatality rate.
2.	I suggest removing T cell, eosinophil, basophil, neutrophil, monocyte, RANTES, and MUC5AC in the Figure. It's not very appropriate to put them in a nucleus.
3.	The authors show that the IL-4/IL-13 signaling pathway plays an important role in both AR and asthma, and those therapeutic antibodies against each cytokine have emerged as promising targeted therapies for AR and asthma. It is recommended that briefly introduce the role of other factors in this signaling pathway in asthma. such as STAT6, JAK3, or Arg-1.
4.	I suggest the authors divide the figure shown in the manuscript into two figures, one summarizing the IL-4/IL-13 signaling pathway and the other summarizing potential cellular effects of IL-4 and IL-13 on inflammatory and structural cells in asthma.


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: IL-4/IL-13 AXIS AS THERAPEUTIC TARGETS IN ALLERGIC RHINITIS AND ASTHMA
Review round: 2
Reviewer: 1

Output:
Basic reporting: The authors have significantly improved this review manuscript with the additional information on clinical significance of IL-4/IL-13 pathway, IL-4/IL-13's involvement in the inflammatory response of AR and RA. The new figure 2 is a great summary of IL-4/IL-13 signaling pathway's multiple functions.

I would like to applaud the authors for doing a great job at writing this insightful review manuscript on IL-4/IL-13 and driving the field forward.
Experimental design: N/A
Validity of the findings: N/A
Additional comments: N/A


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

Input:
Title: IL-4/IL-13 AXIS AS THERAPEUTIC TARGETS IN ALLERGIC RHINITIS AND ASTHMA
Review round: 2
Reviewer: 2

Output:
Basic reporting: The paper is well structured and written, with clear objectives.
Experimental design: The paper is technically sound.
Validity of the findings: The paper contributes some new ideas.
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: UDP-GLUCOSE PYROPHOSPHORYLASE: GENOME-WIDE IDENTIFICATION, EXPRESSION AND FUNCTIONAL ANALYSES IN GOSSYPIUM HIRSUTUM
Review round: 1
Reviewer: 1

Output:
Basic reporting: In this manuscript, the authors identified 66 UGP genes in four cultivated cotton species. For the widely-cultivated Gossypium hirsutum, a total of 19 genes were found. The transcriptome data and qRT-PCR results showed that six genes from G. hirsutum were highly expressed in 15-DPA fiber. Furthermore, the authors studied their potential function in fiber development with different sorts and different gradients of phytohormones by ovule culture assays. They found that low IAA and GA3 concentrations promoted the development of ovules and fiber clusters, and the expressions of all six UGP genes were increased to different degrees in the 15 DPA fibers from ovule culture. These results provide insights into some of the UGP genes that may influence cotton fiber development. However, some changes are needed to improve the quality of this manuscript.
1.	Please revise the abstract because of large proportion about the UGP family from four cotton species. Or the title of this manuscript should be revised to “UDP-glucose pyrophosphorylase: genome-wide identification, expression and function analyses in cotton” or other better title the authors think.
2.	L139, L153: the sentences need to be rewritten.
3.	In the Methods, part of the description in lines 177-187 is too similar to another paper (UDP-Glucose Dehydrogenases: Identification, Expression, and Function Analyses in Upland Cotton (Gossypium hirsutum), Tingting jia, 2020).
4.	In the Result, 3.2 developmental is improper. The title can be revised to “Evolutional analysis of UGP gene family”. 3.3 subpopulation should be subgroup.
5.	L 228: their is redundant.
6.	L233-L236: Please carefully check the sentences.
7.	Fig.8B and Fig.9 are lack of the statistical significance analyses.
8.	In the Conclusion, the author restates the main results. Please rewrite the conclusion.
9.	land cotton should be upland cotton. Conventionally, L145 “BP” should be bp. L288 “p<0.05” should be P<0.05. G. arboretum should be revised to G. arboreum.
10.	There were numerous typos and grammatical problems in the text that would require thorough English editing prior to the formal publication.
Experimental design: no comment
Validity of the findings: no comment
Additional comments: no comment


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

Input:
Title: UDP-GLUCOSE PYROPHOSPHORYLASE: GENOME-WIDE IDENTIFICATION, EXPRESSION AND FUNCTIONAL ANALYSES IN GOSSYPIUM HIRSUTUM
Review round: 1
Reviewer: 2

Output:
Basic reporting: In this study, a total of 66 UDP-glucose pyrophosphorylase (UGP) (EC 2.7.7.9) genes were identified from the genomes of four cotton species. The analysis of its evolutionary relationship, gene structure, and expression provides a basis for further studies on the function of UGP genes in cotton development. The manuscript can be considered for publishing in Peer J after moderate revision.

Some sentences are very confusing and lots of grammar mistakes need to be fixed.
Line 97, the round brackets should not be italic.
Line 122, “G. arboretum” should be “G. arboreum”.
Line 139-141 should be adjusted.
Line 153 is not a complete sentence.
Line 154-160. The sentence is too long and confused.
……
The English language should be improved to ensure that an international audience can clearly understand your text. I suggest authors have a colleague who is proficient in English and familiar with the subject matter review your manuscript, or contact a professional editing service.

The format of references should be adjusted according to the Journal’s requirement, e.g., some Journals’ names are in full name, whereas some others are in abbreviation; Lattin name of species should be italic.

Lattin name in the legend of Figure 1 should be italic. The legend of Figure 2 should be more explicit.

In the tables, “table 1” should be “Table 1”, et al. Gene names in Tables should be italic.
Experimental design: The novelty and experimental design of the manuscript is fine.
Validity of the findings: The authors validate the evolution and expression of the UGP gene family in cotton.
Additional comments: no comment.


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

Input:
Title: UDP-GLUCOSE PYROPHOSPHORYLASE: GENOME-WIDE IDENTIFICATION, EXPRESSION AND FUNCTIONAL ANALYSES IN GOSSYPIUM HIRSUTUM
Review round: 1
Reviewer: 3

Output:
Basic reporting: The language should be improved since some statements were quite confused, for example, the UGP genes in some species such as Arabidopsis has been reported, but what you describe in your article is' A total of 81 UGP genes were identified in seven species' (line 192) or ‘we identified 81 UGP genes in seven different species’ (line 297).
Experimental design: Statistical analysis need to be shown in all figures and the methods for data analysis should be supplemented in ‘Materials and Method’.
Validity of the findings: no comment
Additional comments: I found that the phylogenetic tree was quite different from the previous report (Wang et al, Plant Cell Reports, 2011). In previous study, the UGP genes were divided into five subfamilies in cotton, which was inconsistent with this manuscript, the authors should explain that, or at least, discuss it.

The figure legends are not detailed enough. The ordinate title was missing in figure 9.


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: RISK FACTORS FOR FALLS IN COMMUNITY-DWELLING OLDER PEOPLE WITH MILD COGNITIVE IMPAIRMENT: A PROSPECTIVE ONE-YEAR STUDY
Review round: 1
Reviewer: 1

Output:
Basic reporting: In the abstract, the sentence “..no cognitive factors associated with falls..” needs to be clarified. Perhaps it would be best to say “ no measures of cognitive function”.  In the introduction the term “ do not affect daily life function” needs to be clarified. Perhaps to activities of daily living, if this is accurate.  There is a notation of “enter method” noted on line 228 of the statistical analysis section. Perhaps this was left over after a review or edit. In Table 1, what medications are included in the Psychotropic medication category? If this includes the other medications listed then then numbers don’t add up. Medication use should be describe further in the methods. What were the psychotropic medications that predicted fall? Antidepressants?
What are the psychotropic agents here? Antidepressants, antianxiety, stimulants, antipsychotic agents and mood stabilizers, benzodiazepines, barbituates, etc.
Experimental design: Unclear why participants who walk with a walking aid were excluded here. This should be explained. Why adjust for only age and sex ? Why not also include specific medication use and educational level for example. Medication use should be describe further in the methods
Validity of the findings: No comment
Additional comments: The authors need to clarify which medications were in the category of psychotropic medication use. It is not clear if this included sedative hypnotics, antianxiety, antipsychotic agents and antidepressants. If this is the case, the numbers don’t add up to a total of 19 non-faller group and 27 in the faller group. Should adjustments have been made for antidepressents whose given that numbers was significantly higher in the faller group.  Is this what was driving the observed association between  MCI and falls. Use of antipsychotic agents is associated with cognitive impairment. Were these agents excluded under the psychotropic agent category. Patients on psychotropic agents may screen positive for MCI due to medication use.


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: RISK FACTORS FOR FALLS IN COMMUNITY-DWELLING OLDER PEOPLE WITH MILD COGNITIVE IMPAIRMENT: A PROSPECTIVE ONE-YEAR STUDY
Review round: 1
Reviewer: 2

Output:
Basic reporting: 1. Early review in the aspect of vision (visual acuity and visual contrast sensitivity) could be useful as compared to introducing in Discussion section. Perhaps consider a paragraph before Page 8 Line 91.

2. Page 8 Line 94: Balance or postural sway could be introduced to complement the various factors of falls.

3. Consider using “poor visual contrast sensitivity” instead of poor vision.

4. Abstract Conclusion: “… so require consideration in fall prevention programs for this population.” The authors can consider “… so these factors could be carefully considered in fall prevention programs for this population.”
Experimental design: 5. Page 14 Line 221: It is unclear how the 3 SD allocation was determined.

6. Page 14 Line 231: It is unclear to me why median is used as a cut-off for the Melbourne Edge Test.
Validity of the findings: 7. My main concern is the interpretation of findings, specifically Table 2, “Postural sway”. The odds ratio is 1, or approximates very closely to 1, which can be statistically significant but not clinically meaningful. Thus, potentially inappropriate to proceed with dichotomisation of the continuous data.
Huak, C. Y. (2009). Are you a p-value worshipper?. European Journal of Dentistry, 3(03), 161-164.

8. Understandably, a study cited by the authors (Taylor et al. 2017) has already identified postural sway as a modifiable risk factor of future falls. The use of sway area may not consider directional sway (anteroposterior and mediolateral) differences of individuals who may utilise different sway strategy. There are other studies that the authors could consider, which could also enhance the discussion in the authors’ postural sway discussion.
Johansson, J., Nordström, A., Gustafson, Y., Westling, G., & Nordström, P. (2017). Increased postural sway during quiet stance as a risk factor for prospective falls in community-dwelling elderly individuals. Age and ageing, 46(6), 964-970.
Kwok, B. C., Clark, R. A., & Pua, Y. H. (2015). Novel use of the Wii Balance Board to prospectively predict falls in community-dwelling older adults. Clinical biomechanics, 30(5), 481-484.
Maki, B. E., Holliday, P. J., & Topper, A. K. (1994). A prospective study of postural balance and risk of falling in an ambulatory and independent elderly population. Journal of gerontology, 49(2), M72-M84.
Mignardot, J. B., Beauchet, O., Annweiler, C., Cornu, C., & Deschamps, T. (2014). Postural sway, falls, and cognitive status: a cross-sectional study among older adults. Journal of Alzheimer's Disease, 41(2), 431-439.
Additional comments: The author presented a good study aim and methods to address the research gaps. I have provided some suggestions and hope that they could help to enhance your team's manuscript.


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

Input:
Title: RISK FACTORS FOR FALLS IN COMMUNITY-DWELLING OLDER PEOPLE WITH MILD COGNITIVE IMPAIRMENT: A PROSPECTIVE ONE-YEAR STUDY
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: The authors made considerable efforts to improve the manuscript and have sufficiently addressed my 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: VIRGIN AND UV-WEATHERED POLYAMIDE MICROPLASTICS POSED NO EFFECT ON THE SURVIVAL AND REPRODUCTION OF DAPHNIA MAGNA
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript is clearly written with supporting contextualizing references. The results are relevant despite the absence of effects. Negative results are extremely important to assess MPs toxicity.
Experimental design: The research question is well defined and the methods are adequate by following guidelines. All technical aspects are correct and detailed.
Validity of the findings: The findings point to no toxicity of PA MPs. Negative results are also very important for MPs toxicity and the authors present sufficient evidence from the literature supporting their results.
Additional comments: In my opinion, the manuscript is well written and has the potential to be published in this journal.


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: VIRGIN AND UV-WEATHERED POLYAMIDE MICROPLASTICS POSED NO EFFECT ON THE SURVIVAL AND REPRODUCTION OF DAPHNIA MAGNA
Review round: 1
Reviewer: 2

Output:
Basic reporting: This manuscript deals with the new experimental data on the effects of various forms of polyamide microplastics to Daphnia magna survival and reproduction. Its content is clear. The manuscript is clearly written, the introduction yields sufficient background and is followed by research hypotheses, and the literature is adequately cited. English is clear and professional.
Experimental design: The experimental scheme is extremely simple. It includes the exposure of daphnids to virgin and UV-weathered polyamide microplastics at various concentrations of MP with or without the surfactant, in the close to natural conditions. Methods are described fully enough, just some details should be corrected (see general comments below).
Validity of the findings: The findings of the authors proved the importance of investigations on versatile effects of microplastics to aquatic biota. The observations were carried out properly, and the data are presented with adequate statistical analysis. Conclusions are reasonable and summarize the output of this study.
Additional comments: Table 1 can be placed in Supplemental materials because its data were not presented/discussed either in Results or Discussion parts of the ms.

Minor comments:
L. 28 (widely used plastic material). It can be omitted. Cf Line 19-20: "one of the commonly used MP worldwide."
L. 87 Change (Khosrovyan & Kahru (2021) to (Khosrovyan & Kahru, 2021).
L. 141. “In total, 6 experiments…” When looking into the Supplemental file, it is obvious that there were 6 treatments each performed within 2 (independent) experiments. Please correct.
L. 140–142. This paragraph should be joined with the above one.
L. 214 etc. Use the same spelling: “UV-weathering” throughout the text.
L. 283. Change (categories 1-… to (categories I-…
L. 335. Change ‘throughput’ to ‘throughout’.


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: AUTOMATIC DETECTION OF THE PARASITE TRYPANOSOMA CRUZI IN BLOOD SMEARS USING A MACHINE LEARNING APPROACH APPLIED TO MOBILE PHONE IMAGES
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript is clearly written and adequately exposes the study problem, however, it does present some lines that require a revision of the English language (eg lines 38-39, 78). The arguments presented are supported by specialized and updated references, however, some editorial observations are noted in the text (eg lines 38-39, 261-264, among others). The methodological approach and the results are adequately presented in images and tables that allow a better understanding to the reader.
Experimental design: The proposal of the work is to use the camera of a mobile phone to acquire the images and their subsequent analysis for the recognition of trypanosomes. The massive use of this electronic device can be used for different and varied purposes, such as this research. The methodological approach described was clear and would allow its replication without problem, although I consider that too many characteristics of the parasite were considered that could affect its results, such as the different categories that they established for the comparison of the performance of the algorithm (body, kinetoplast, body and kinetoplast, body and nucleus, and T. cruzi), although in the end the authors recognized it. The authors are advised to explore other variables in the treatment of the blood to improve its staining and recognition of the parasite (lines 339-341). Statistical analyzes were supported by pertinent literature. The manuscript is in the appropriate range for the objectives and interest of the journal
Validity of the findings: It is necessary for the authors to reinforce their arguments for the application of their results, since there are other algorithms and proposals that have shown better performance in the recognition of the parasite. For example, explain where your findings are located and how they can be applied. Otherwise, the results found appear to be irrelevant.
The discussion is well oriented based on the existing knowledge on the subject, and has a good self-criticism in the results. Recommendations are made to the authors for potential publications with a greater quantity and diversity of images.
Additional comments: The generation of knowledge through new approaches will always be welcome, in such a way that it allows to propose or design better strategies to solve different social problems, such as in this case, the diagnosis of Chagas disease. In this context, this manuscript fulfills this function in the generation of potentially applicable knowledge.


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: AUTOMATIC DETECTION OF THE PARASITE TRYPANOSOMA CRUZI IN BLOOD SMEARS USING A MACHINE LEARNING APPROACH APPLIED TO MOBILE PHONE IMAGES
Review round: 1
Reviewer: 2

Output:
Basic reporting: This work describes an approach to automatically count trypanosomes in blood smear images, captured using a mobile phone, as a quick and accessible method of detecting infection. As identificaton of parasites in a blood smear is the gold standard for diagnosis this is a simple but valuable tool.

Overall the paper is suitably structured and presented. It is readable and seems to cite literature well. There is one major problem with the text:

Use of "dpi" to describe resolution does not make sense. How are standard print resolutions related at all to image pixel sizes in the microscopy system? Resolution is also probably not the correct term, this presumably refers to pixel size rather than the resolving power of the optical system.
Please list instead the relevant parameters about 1) the typical scale of the images in question, in units of micrometres per pixel, and 2) the dimensions of the images in question, in units of pixels or micrometres. The overall optical system should also be described, particularly objective lens magnification and numerical aperture, any additional magnification (eyepiece or camera mount) and the physical pixel size in the cameras used/referred to. That allows calculation of actual resolving power. Only then can the mobile phone images really be compared to dedicated microscope camera images.
This affects many places in the text, line 43, 49, 99, 102, 109, etc. etc.

I found it hard to understand much of the detail around the actual images going into the study due to this poor description - this needs to be corrected carefully. Overall, I get the impression that image pixel is probably not the limiting factor at all - but a combination of contrast and actual resolution in comparison to using a much larger and more expensive microscope and dedicated camera.

Paragraph starting line 237:
This is the first description of the images that makes sense. Note again, "resolution" in microscopy systems normally refers to the resolving power (the objective type is not specified, but for a 100x oil immersion objective resolution is ~0.2um). 2.835 pixels/um is the image's scale.
Experimental design: Paragraph starting 343:
I'd particularly like to see performance of your method on images captured by a dedicated microscope camera rather than a mobile phone - that would be the 'gold standard' for comparison to this approach.

Paragraph starting 254:
Does perceptual lightness for thresholding help with thresholding the image?
How can classes 1) and 3) occur - kinetoplast or nucleus without a cell body? I found this description unclear. Surely this reflects a limitation of the original intensity thresholding?
It seems that the limiting factor in this approach will be this intensity thresholding, although overall the method seems to works.

Paragraph starting 305:
The miss-clasification of leukocytes seems like a serious limitation, especially as leukocyte number can be affected by many different conditions. Could they be included as a category for the training to allow them to be positively identified rather than a false positive?
Validity of the findings: I suspect the classification is probably quite over-fitted to the specific parameters of the combination of this particular sample preparation and the particular combination of mobile phone and microscope. It seems to have only been tested with one microscope and camera, and one sample? Performance on some number of different samples, prepared on different days, by different researchers and then tested on different microscopes with different mobile phone cameras should really be tested to convince me that this tool could actually be used by other research groups.

The results shown from this dataset appear robust. However, this does not mean this tool is robust. As such, currently it is an interesting proof-of-concept, but there is not evidence that it is a usable tool - the discussion should reflect this.
Additional comments: Paragraph starting line 237:
Is there such a thing as an uncompressed JPEG? I thought the chroma data is always downsampled and the storage of the frequency domain representation of the luminance is always at least a little compressed.

Paragraph starting 283:
It is unclear what execution this time refers to. Training or classification? Indicating that it is (presumably) a purely CPU workload would be useful.

Paragraph starting 305:
Issues with out-of-focus false negatives could likely be solved by cropping the field of view. Is the 'out-of-focus' referred to here truly focus problems, is it an issue with focal plane planarity? or chromatic aberration?

Paragraph starting 353:
As Plasmodium is an intracellular parasite, in comparison to the extracellular blood stage of T. cruzi, this comparison doesn't seem 'fair' - some consideration of the differing biology is needed.

Paragraph starting 361:
It is still unclear to me what the limiting factor of the mobile device camera is here. It is presumably not actually resolution of the microscope

Overall comments:
Overall this is a potentially valuable study. The ability to automatically quantify cruzi parasitaemia using a mobile phone and a standard portable 'student'-type microscope is a genuinely useful approach. As I indicate above, I have significant concerns that it would be a useable tool, but stands as an interesting proof-of-concept.

I must note that I find the overall approach a little surprising. Surely an advanced object detection algorithm like YOLO (https://pjreddie.com/darknet/yolo/) could perform significantly better? However, this does not invalidate the results shown.


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: AUTOMATIC DETECTION OF THE PARASITE TRYPANOSOMA CRUZI IN BLOOD SMEARS USING A MACHINE LEARNING APPROACH APPLIED TO MOBILE PHONE IMAGES
Review round: 1
Reviewer: 3

Output:
Basic reporting: In general, applications of machine learning to biomedical problems are always welcome and, this article proposes a method on this line. However, I think that the paper needs reworking to clarify the main ideas. For instance, it is not clear how the classifier is used with six classes. SVM is not a multi-class classifier therefore, you should report which of the known strategies to deal with this was used in this work. An illustration with the pipeline of the whole algorithm/method would be welcome.

In Figure 1, the ROC curve is hard to read.
Experimental design: According to the paper, the feature extraction was performed over the segmented image. This to me, seems to be very inefficient since the segmentation algorithm is a very simple one and for sure there must be plenty of inaccurately segmented parasites. Doing manual segmentation of the kinetoplast and nucleus and the feature extraction would be a much better idea.

You mention that PCA was performed and only the principal K components were used for training. What is the value of K?

In the object classification section, you should introduce your classes and no later. On the contrary, the paragraph in this section is incomprehensible.

The manual labeling section is not clear. You describe that manually by a point-and-click event you are labeling the nucleus and kinetoplast of each parasite. Therefore, you are not finding the centroid of each region of interest (ROI), nor creating a bounding box around them, nor labeling each pixel of the ROIs. What is the point to have an almost randomly selected coordinated inside each ROI?

I also don’t understand what you mean by the field-of-view identifier, the pointed object
(Nucleus or kinetoplast). (Lines 250 to 253)

Then, you introduce 6 different classes. First, I don’t see the point in doing that because you only have features for the kinetoplast and nucleus. Therefore, it is natural to wonder how you are representing the other four classes.

In line 283, you mention “We observed a performance gain after feature selection”. Are you referring to gains (reduction) in processing time? Is this processing time only for PCA or the whole algorithm? Later you will state that PCA reduction did not work together with the classifier. Then, why give times of something that did not work?

Then you report your classification results, showing that PCA did not help at all. Since you did not report the number of PCA components used (the value of K) it is difficult to comment about that.

The same comment applies to the definition of your classes. Why use so many if you only want to detect the parasite? Introducing many classes makes the classifier struggle and the paper difficult to read.

The problems you are reporting with respect to objects of similar color are expected. Including color in the features maybe not be a good idea. The stain may vary due to many reasons and therefore the algorithm is prone to errors.
Validity of the findings: My other main concern is that the reported results are below some published works. I guess this is because a simple method such as SVM was used and no other techniques such as Adaboost, neural networks and so on that may boost the results. It seems then that the only novelty here is the use of low-resolution images.
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: AUTOMATIC DETECTION OF THE PARASITE TRYPANOSOMA CRUZI IN BLOOD SMEARS USING A MACHINE LEARNING APPROACH APPLIED TO MOBILE PHONE IMAGES
Review round: 1
Reviewer: 4

Output:
Basic reporting: Tables and figures must be resized so that they fall on the same page with the title (empty pages should be avoided).
Experimental design: In this paper, the authors present classification results of T. cruzi trypomastigotes in low-resolution images (72 dpi) using SVM based algorithm for the detection. To correctly categorize a candidate parasite, the proposed method needed the selection of a non-fixed threshold value involving segmentation before classification. Images were converted to CIEL*a*b* color space, and the objects of interest were segmented with the adaptive (local) threshold technique. Whereas for the classification they marked the position of each nucleus and kinetoplast of the trypomastigotes found in the image and constructed 6 classes: 1) kinetoplast; 2) kinetoplast with cell body; 3) nucleus; 4) nucleus with cell body; 5) T. cruzi; 6) unknown.
The model was capable of recognizing the parasites in the training set with 91.4% and 91.7% accuracy and sensitivity, respectively, and with a sensitivity of 89.6% in a set of test set data.

The overall work has a lot of question marks:
1) The authors claim that the model works on low-resolution images (72 dpi) where we don't see a comparison with the existing models where the data is collected as high-resolution. For such data sets, the authors can try their model and show the comparison with the existing models. The other way around, the authors can use the existing machine learning models on the newly collected data set and apply them by resetting the train and validation set. In this way, the authors can claim that the model they provide is better for low-resolution images.
The authors can use for such comparison already cited works (such as Uc-Cetin work ) or the work of other works which are not cited such as

da Silva Pereira, Andr´e, Alexandre dos Santos Pyrrho, Daniel Figueiredo Vanzan, Leonardo Oliveira Mazza, and Jos´e Gabriel RC Gomes. ”Deep Convolutional Neural Network applied to Chagas Disease Parasitemia Assessment.”Congresso Brasileiro de Inteligˆencia Computacional, January 2020 , DOI:10.21528/CBIC2019-119

2) I see that the authors adaptive (local) threshold technique. This technique will lead to noise sensitivity. Did the authors take this into account? If so would be good to be further explained.  The proposed method needs a better description with sufficient detail on all the other image processing techniques and their parameters limitation.

3) The features generation of 6 classes is confusing. Why the authors wouldn't use a binary classifier for automated T. cruzi detection? I am afraid such a classification leads to an increase in the accuracy shown in the paper.

4) Górriz et al., 2018 is not found as reference.

Considering the above-mentioned comments I recommend the authors resubmit the paper with a major revision.
Validity of the findings: To be considered in case the authors answer the comments in the Experimental design.
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: AUTOMATIC DETECTION OF THE PARASITE TRYPANOSOMA CRUZI IN BLOOD SMEARS USING A MACHINE LEARNING APPROACH APPLIED TO MOBILE PHONE IMAGES
Review round: 2
Reviewer: 1

Output:
Basic reporting: I agree with the corrections made by the authors
Experimental design: The authors adequately addressed the observations made
Validity of the findings: The authors adequately addressed the observations made
Additional comments: I recommend that the authors continue to improve their device to achieve a contribution that can be applied to the human population


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: AUTOMATIC DETECTION OF THE PARASITE TRYPANOSOMA CRUZI IN BLOOD SMEARS USING A MACHINE LEARNING APPROACH APPLIED TO MOBILE PHONE IMAGES
Review round: 2
Reviewer: 2

Output:
Basic reporting: In my opinion, this article is not ready for publication yet. It is promising but some improvements need to be done.

There are some issues that I describe below.
Experimental design: The adaptive thresholding segmentation process is so simple that it is practically impossible to segment the whole parasite body. In Table 1, we can see that you ended up with only 111 T. Cruzi parasites in the training set and 23 in the test set. Meanwhile, the kinetoplast, nucleus, and unknown classes have a size in the order of thousands. Your dataset is quite unbalanced. Therefore, you either upgrade your segmentation method, use a manual segmentation method (at least for training) or apply any technique to deal with an unbalanced dataset (such as image augmentation).

Again, seems to me that the output of the segmentation algorithm forced you to go for six classes when you really should aim for two. Too many classes should be avoided when doing binary segmentation even more in unbalanced sets. Otherwise, the performance of the classification algorithm gets decimated.

Let me insist that I do not see the need to present the PCA and CFS algorithms since they did not improve the classification results. I suggest removing them and just mentioning in the manuscript that they were tested but delivered bad results.

The output from the SVM classification algorithm may be improved by using techniques such as ensemble methods. I encourage the authors to explore this possibility.
Validity of the findings: The performance of your proposal is far from close to one of the other techniques already published. The argument that this method is suitable for low-resolution images and the others not, is from my perspective, weak to say the least.
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: AUTOMATIC DETECTION OF THE PARASITE TRYPANOSOMA CRUZI IN BLOOD SMEARS USING A MACHINE LEARNING APPROACH APPLIED TO MOBILE PHONE IMAGES
Review round: 2
Reviewer: 3

Output:
Basic reporting: The revised version is acceptable for publication.
Experimental design: Fully valid.
Validity of the findings: Acceptable.
Additional comments: No additional comments