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: COMPUTED TOMOGRAPHY ELUCIDATES ONTOGENY WITHIN THE BASAL THERAPSID CLADE BIARMOSUCHIA
Review round: 1
Reviewer: 2

Output:
Basic reporting: no comment (see below)
Experimental design: no comment (see below)
Validity of the findings: no comment (see below)
Additional comments: The manuscript entitled “Computerized tomography elucidates ontogeny within the basal therapsid clade Biarmosuchia and compels revision of the genus Lemurosaurus Broom, 1949” provides relevant information and novel aspects on the hypothetical ontogeny of members of the clade Biarmosuchia. However, as the study deals with a number of closely related specimens that do not represent the same species, some of the aspects discussed need to be emphasized more as hypothetical. In general, I consider the manuscript worthy of publication, but the points listed below should be carefully considered and address for a revised version.

General points:
•	Make sure to be consistent in your language for example with regards to the use of specimen numbers, e.g. RC55 vs. RC 55
•	The description is sometimes a bit too generalized or includes rather common knowledge, e.g. in line 385 that “The dentary is the largest and anterior-most bone of the lower jaw…” or line 423 “The articular is the posterior-most bone of the lower jaw…“, which is essentially the case in all tetrapods. Maybe check the description and delete these unnecessary sections.
•	The authors could add comparisons relevant for identification,  i.e. the diagnostic characters and features for Biarmosuchia, Burnetiamorpha and or the specimens currently assigned to Lemurosaurus.
•	For the description of CGP MJF 22 there could be additional figures especially highlighting areas and features that are described in the text as revealed by CT scans, such as the separation of the parietal  (line 517f) as well as for the palatal view (line 553f, vomer). Additional figures of the CT scanned area would clearly add to the understanding of that individual specimen, as the presented Figure (Fig 8) is not showing several features clearly. The outline drawings atop of the photographs are covering described sutures or characteristics.
•	References should be checked as some taxon names are not in italics (Line 1237  Simoliophis, Line 1266  Thrinaxodon liorhinus, Line 1343 Anteosaurus magnificus, Line 1405  Australopithecus robustus, Line1417  Eustreptospondylus oxoniensis, Line1469  Thrinaxodon liorhinus)
•	The Discussion is partitioned into 8 subsections, which are listed in the following with selected comments, that I would like to see considered:
1.	Orbit size – as far as I remember this has already been discussed in detail by Sidor and colleagues, I think in the Hopson Festschrift, please check and potentially expand or modify the discussion accordingly
2.	Tooth replacement – while potentially relevant, this aspects seems somehwhat far-fetched to support the juvenile status of a specimen, as this certainly needs to be considered in a phylogenetic framework, which is thus far lacking in the frame work of this study. If possibly, please add a more quantitative analysis this!
3.	Cranial bosses and pachyostosis – again, while this is a valid point, this also is an aspect that cannot be considered by itself, like orbit size for instance as you argue yourself. The lack of bosses and pachyostosis could simply reflect or more basal phylogenetic position of the respective taxon and hence, only a proper ontogenetic series of a single species could enlighten this aspect
4.	Radial vasculature pattern – I’m somewhat skeptical about your sample size here and the lack of information for some specimens, but yes I agree that this is a valid point
5.	Braincase and bony labyrinth ossification – valid point, but again should not be considered on its own but in combination with all other characters (including orbital size!)
6.	Fusion of the preparietals and internal parietal sutures – in this section you should certainly include the recent publication by Marilao et al. 2020 (see below)
7.	A hypothetical biarmosuchian ontogenetic series – this section is probably the most speculative and problematic, as it does not necessarily seem intuitive to reconstruct an ontogenetic sequence from closely related but distinct species within a higher clade. However, as it is phrased “hypothetical”, it should also be treated as such and sometimes  it could phrased more carefully rather than certain.
8.	Taxonomic revision of Lemurosaurus Broom, 1949 – overall, this very relevant section almost disappears in comparison to the more detailed description of the rather undiagnostic other specimens above. Maybe the manuscript could be modified to put this specimen in focus rather than having in listed and named in this very brief section

Minor corrections

Line 110: change to “… Burnetiamorpha indet., because… ”
Line 223 and 446: change to “gen. et sp. indet.”
Line 246: change to “anterior end”
Line 272: change to “disappears”
Line 297: change to “vertically”
Line 298: change to “squamosal”
Line 340: delete second “could not”
Line 387: “ten” instead of “10” since you should be consistent in one sentence, where you lateron mention “five”; and change to “… on the right ramus…”
Line 454: change to “well preserved”
Line 473: change to: “The lacrimal is a quadrangular bone, forming most of…”
Line 475: delete on “.”
Line 591: change to “anteromedial”
Line 922: change to “orbits” and “lengths”
Line 951: change to “tooth replacement”
Line 968: change to “linked”
Line 1005: change to “Estemmenosuchus”
Line 1046: change to “well ossified”
Line 1061: in this context you should cite and potentially discuss: Marilao et al. 2020 Histology of the preparietal: a neomorphic cranial element in dicynodont therapsids https://doi.org/10.1080/02724634.2020.1770775
Line 1089: I don’t really see how this reference to paired parietals in Dinosauria being indicative of juveniles is relevant in this regard, maybe simply stick to references to more closely related taxa unless it has broader evolutionary implications that you would like to address
Line 1121: change to “…reliable juvenile characters on their own…”
Line 1156: something is missing in this sentence, maybe “… lower jaw that was described …”
Line 1178: change to “well-developed”


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: COMPUTED TOMOGRAPHY ELUCIDATES ONTOGENY WITHIN THE BASAL THERAPSID CLADE BIARMOSUCHIA
Review round: 1
Reviewer: 3

Output:
Basic reporting: The paper gets into very difficult philosophical territory: to what extent can morphological variation be attributed to ontogeny vs. phylogeny? I could imagine some reviewers taking a strong position within either of these camps, especially in regard to Lemurosaurus and the validity of the proposed Peterotherium (formerly referred to Lemurosaurus by Sidor & Welman, 2003). A parallel debate rages in the realm of dinosaur paleontology regarding the nature of cranial ornamentation in pachycephalosaurs (Horner & Goodwin, 2009) and ceratopsians (Scanella & al., 2014). Nevertheless, it’s important that these debates take place in the public sphere so that future paleontologists can investigate these hypotheses with new data. So I would like to see this published in some form and would recommend “Acceptance with Minor Revision,” pending that the authors take a more conservative position instead of splitting BP/1/816 and NMQR 1702 and/or erecting new taxa (unless those new taxa have clear autoapomorphies).

Maybe one such approach could be to: Propose the ontogenetic hypothesis (i.e., Fig. 23)—accepting that there is some ambiguity in the taxonomic assignments (I am okay, for example, with the referral of Rubidgina to Burnetiamorpha indet.)—but DO NOT go so far as to erect a new taxon for NMQR 1702 until more specimens and a more complete ontogenetic sequence comes to light. A more conservative approach would be especially merited for now since there is no accompanying phylogenetic analysis in the paper.

My gut reaction is that this paper is too ambitious and draws too many conclusions with too little data. Also, since skull size alone is not a consistent indicator of age or sexual maturity in many tetrapods, and neither is suture closure (Bailleul & al., 2016), then it is still possible that the smaller BP/1/816 and the larger NMQR 1702 could still fall within a shared ontogenetic sequence (maybe one was better fed or lived during more equitable conditions, or their size was density-dependent or sex-specific like modern alligators) calling into question the authors’ decision to split these specimens which were, incidentally, co-existing entities in the context of the Cistecephalus assemblage. The variation could be evaluated in the future with more varieties of specimens at different sizes and with histologic ontogenetic staging (Griffin & Nesbitt, 2016).
Experimental design: See above
Validity of the findings: See above
Additional comments: See above


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

Input:
Title: COMPUTED TOMOGRAPHY ELUCIDATES ONTOGENY WITHIN THE BASAL THERAPSID CLADE BIARMOSUCHIA
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: I have gone through the manuscript again in detail and carefully read the detailed authors' repsponse to the queries of all three reviewers and from my perspective all points have been addressed to my satsifaction and I have n0othing to add at this point. Hence, I recommend publication of this manuscript in PeerJ.


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: SPONGES OF WESTERN MEDITERRANEAN SEAMOUNTS: NEW GENERA, NEW SPECIES AND NEW RECORDS
Review round: 1
Reviewer: 1

Output:
Basic reporting: There are a number of spelling and grammatical errors which can be confusing. I have provided suggestions for improvement in my review but encourage the authors to seek assistance from a native English speaker to review the article prior to re-submission. Technically, the manuscript is sound and comprehensive.

There are a few missing references from the reference list. I suggest the authors carefully cross-check between in-text and the reference list. Otherwise, the references are sufficient in providing the necessary background information.

Figures and tables are well presented.
Experimental design: The study is taxonomy/ biodiversity focused and descriptive. The research question is well defined and technical approach sound.
Validity of the findings: The findings are novel and important towards building fundamental understanding of sponge diversity on seamounts in the Mediterranean.
Additional comments: A lot of work has gone into this study, to identify the diversity and also to describe new species of sponges that are found on seamounts. Technically, I find little fault with the study, however, I do encourage the authors to thoroughly review and correct any critical grammatical errors contained. I have provided comments as annotation to the pdf copy of the manuscript for careful consideration.


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: SPONGES OF WESTERN MEDITERRANEAN SEAMOUNTS: NEW GENERA, NEW SPECIES AND NEW RECORDS
Review round: 1
Reviewer: 2

Output:
Basic reporting: The paper reports the original results of important and extensive surveys performed on the seamounts off the Balearic Islands which are of remarkable importance. The study of the seamounts is particularly interesting for a better knowledge of the mesophotic zone sponge fauna. There is still a gap of knowledge of deep habitats and the present research contributes to fill it. The involved ecological and biogeographical aspects have been considered.
Authors are certainly more familiar with genetics and phylogeny than with sponge taxonomy, biogeography and so on. They do not always use the current terminology about sponge morphology, spicules, skeleton and character description. Several publications as the thesaurus of sponge morphology or the sponge guides may help them and I invite to consult them during the MS revision. I have corrected the manuscript – spending a lot of time and with a considerable effort – and all my notes and comments are reported on the pdf file. The English language requires a careful revision. I have made several corrections on the MS where the meaning was unclear or mistakes were evident, but this is not my task nor am I a mother tongue reviewer.
The introduction is complete and detailed and the structure of the paper conforms to the rules of the Journal.
Figures are exhaustive and of good quality. The notes on the MS help to make clearer the legends both of figures and tables.
The number of tables in my opinion is excessive (especially as to those regarding single species) but this depends on the policy of the Journal about the space to allow for each submitted paper. As to the position of the tables I would prefer to have them placed within the text and not at the end of the MS but this one also is and editorial choice.
References are adequate and correct. The insertion of a few more citations is suggested with notes on the manuscript.
Experimental design: Sampling was correctly performed and specimens were studied with modern techniques and adequate facilities which are well described in the method paragraph. Sponge taxonomy is the main topic of the study but phylogenetic aspects are treated in detail.
Validity of the findings: The erection of new species is justified and they are correctly described taking into account  the genetic aspects. Probably also the choice of attributing two of them to a new genus is correct. The skeletal characters of the new genus are clearly described but the images illustrating them are not fully convincing. If possible they should be replaced with better ones or integrated with a drawing.
The choice of the name Pseudoaplysina for the new genus on the basis of a mere morphological and far from univocal likeness - in my opinion - has to be rejected. The genus Aplysina has nothing to do with the new one and the use of this name is misleading.
I have no suggestions about the choice of the new name but I recommend being cautious also when using the term pseudo. This should be a motivated choice suggesting the idea of “false” in relation to a valid term of comparison.
Additional comments: I invite you to read carefully the pdf file reporting corrections and suggestions and to follow it during the revision of the MS


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: SPONGES OF WESTERN MEDITERRANEAN SEAMOUNTS: NEW GENERA, NEW SPECIES AND NEW RECORDS
Review round: 1
Reviewer: 3

Output:
Basic reporting: In line with yours standards
Experimental design: Very good
Validity of the findings: Very good
Additional comments: Dear Editor and authors,
the manuscript titled "Sponges of Western Mediterranean seamounts: new genera, new species and new records" is a beautiful work, well written (although I am not a native speaker). The manuscript describes the biodiversity of sponges of some seamounts of the Mediterranean Sea with the description of a new genus and new sponges. Despite the scientific value of this work, I would like to propose some points that I do not agree with the authors (in the word of the manuscript that I have attached there are the details).
My opinion is that this MS can be accepted after medium review.
1.	Abstract “Background”, Authors should write more than just “are poorly explorer”!
2.	“Results”, Some data are not true, for example distribution of P. vansoesti (see word MS file);
3.	INDEX: In my opinion it makes no sense!
4.	Introduction. Some sentences are followed by quotations that are now a bit dated! The names of the species that are inserted should always be checked and updated according to the systematic. Whenever a species is cited for the first time, the authors and the year must be entered (not in italics);
5.	Materials and methods. Ok, just a few minor changes;
6.	Results. Errors in the subgenera, lack of the authors of the species;
7.	Systematic. The name “Pseudoaplysina” for the new genus, in my opinion is that this name is beautiful but very misleading, having nothing to do with the genus Aplysina, the external morphology cannot be used in this sense! However, if you zoom in on the photo, the surface is completely different from that of Aplysina. In my opinion, the name of the genus should be changed. Very good descriptions and rest; the description of the skeleton would go before the spicules; I would divide "Taxonomic remarks" and "Molecular remarks". We come to the description of the well-known species like some Phakellia species (see text), you have done a good job, but the descriptions of these species are already well done in other works and the images of the spicules, in my opinion it is an unnecessary repetition, I would leave only the part of the distribution and ecology.
Heteroxya mediterranea sp. nov. I'm sorry but this species cannot be considered valid, the authors themselves write " the COI sequence is identical to two others …", if no other molecular evidence is found, perhaps with other markers, this species must be eliminated from the manuscript.
Rhabdobaris implicata, Haliclona (Soestella) fimbriata, Petrosia (Strongylophora) vansoesti, Petrosia (Petrosia) raphida and Hemiastrella elongata other species known and already described very well; in my opinion descriptions are superfluous.
8.	Discussion. Everything that I have marked in red must be rewritten for me. It is absolutely not true that classical taxonomy should be replaced with genetics, the latter has made huge mistakes over the years! They should be used together, but it's still nice and above all scientifically correct to be able to create new species without genetics!
9.	Figures and tables: Ok, apart from the little things marked in the MS file.


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

Input:
Title: SPONGES OF WESTERN MEDITERRANEAN SEAMOUNTS: NEW GENERA, NEW SPECIES AND NEW RECORDS
Review round: 2
Reviewer: 1

Output:
Basic reporting: already commented in the first revision
Experimental design: already commented in the first revision
Validity of the findings: already commented in the first revision
Additional comments: already commented in the first revision


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: MEASURING WALKING IMPAIRMENT IN PATIENTS WITH INTERMITTENT CLAUDICATION: PSYCHOMETRIC PROPERTIES OF THE WALKING ESTIMATED-LIMITATION CALCULATED BY HISTORY (WELCH) QUESTIONNAIRE
Review round: 1
Reviewer: 1

Output:
Basic reporting: 1) A dataset has been submitted with the article, however it is largely incomprehensible. The file should be edited so that it is much easier to interpret/navigate/use.
2) It would be useful to indicate somewhere in the abstract that the sample consisted of intermittent claudication patients specifically.
3) Line 51: define PROM in full at first use
4) Table 3 title: “exercise intervention group (n = 994)” – is this n-value correct? It seems too large and not in keeping with the n-values included in the table itself.
5) P177: “inevitable” – seems an odd choice of word since I don’t think it is inevitable. How about replacing with “required” or “necessary”?
6) References 7 and 12 are the same.
Experimental design: 1) Line 65: The WELCH is listed as a secondary outcome measure on the clinicaltrials.gov registration but not in the BMJOpen protocol paper; why was it not included in the latter?
2) Line 68: The sample of 2042 doesn’t match with the sample size mentioned on the registration page (1982) or protocol paper (1760). Please explain the discrepancy. I presume that it’s something to with needing to enrol 2042 to end up with enough people also completing baseline (1759).
3) Line 73-74: Please can you explain the data collection people in more detail as this will aid the interpretation of feasibility (e.g. rate of missing data). You say the participants received a battery of paper questionnaires. Was this handed to them in-person or mailed out to them? They return by mail but was a pre-paid envelope used for this? What support, if any, could the participants access with completing the questionnaires? What processes did the trial use for minimising missing data? E.g. were reminders sent to people who didn’t respond, could an investigator chase missing data via telephone?
4) Line 80-81: The original authors of the WELCH are French, so I’m wondering what the translation process was when creating the German version, e.g. who was involved and how rigorous was the process to ensure appropriate wording? This is referred to in the discussion but should probably also be clarified in the methods. The discussion indicates that the questionnaire was translated and back-translated – can the authors verify this as it would help address the first limitation in the discussion? Please also state in the text that the German version used can be viewed as a supplementary file.
5) Line 110-111: The COSMIN standards set does not appear as a supplementary file as indicated on these lines.
6) Line 114-117, 123, 127, 132, 136: Where do the thresholds used for assessing feasibility, floor and ceiling effects, test-retest reliability, validity, and responsiveness come from? Are they completely arbitrary or can you justify and add supporting references? Please also clarify if these thresholds were specified a priori or after the data had been observerd/inspected.
7) Line 118-119: For test-retest reliability, 72 PAD patients completed the WELCH twice within a 2-week period around the 12-month follow-up point in the RCT. Did your ethics approval cover the repeat assessment here? There’s no mention of it in the trial registration or protocol paper.
Validity of the findings: 1) Table 1: Can you provide any data on PAD status, e.g. ABI or proportion of patients in Fontaine IIa and IIb?
2) Line 189-190: “Test-retest reliability has not yet been tested for the WELCH” – this is not true. It was definitely tested in Ouedraogo et al. (2013) and Cucato et al. (2016). Please revise this section of the discussion accordingly.
3) Results: please add summary statistics for the total WELCH score at baseline and follow-up. You only show the mean (SD) change score.
4) Line 215-216: “… it is likely that changes in walking distance are not well captured by the WELCH” – I’m not sure I agree with this and it seems like speculation. It is OK to speculate, but it should be identified as such. Inspection of table 2 suggests that it’s a combination of changes across all four items that would contribute to a change in the total score. Items 1-3 ask about the continuous duration achievable at different walking speeds. Wouldn’t an increased ability to walk for a longer duration reflect an increased ability to walk a greater distance?
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: MEASURING WALKING IMPAIRMENT IN PATIENTS WITH INTERMITTENT CLAUDICATION: PSYCHOMETRIC PROPERTIES OF THE WALKING ESTIMATED-LIMITATION CALCULATED BY HISTORY (WELCH) QUESTIONNAIRE
Review round: 1
Reviewer: 2

Output:
Basic reporting: Rezvani and colleagues perform a psychometric analysis of the German version of the « walking estimated calculated by history (WELCH) questionnaire in a rather large. The study aimed at analyzing various (feasibility, test-retest reliability, construct validity (i.e. convergent, divergent and known-group validity), and sensitivity to changes properties in comparison to other existing tools (i.e.: VascuQoL, GAD-7 and WIQ). Although not detailed in the method section, according to the data file provided for review, patients in the follow up group seem to results from two different populations including both patients completing the questionnaire twice without apparent therapeutic intervention (Routineversorgung : routine treatment)  and patients that underwent an intensive rehabilitation program teGeCoach that seems an active telemonitored intermittent walking exercise.
The authors should be congratulated for the quality of the writing and organization of the paper. The goal of the study is original and adds to the existing literature.
Experimental design: The goal of the study is original and adds to the existing literature and seems to me in the general scope of the journal for medical and health sciences.
Validity of the findings: I would strongly recommend that the two populations should be described in a new table after table 1. I completely agree with the authors that the questionnaires may be analyzed for the whole group of 1759 included patients at baseline and/or 1279 at twelve months, when the aim is to analyze feasibility, test-retest reliability, construct validity. Nevertheless, I do believe that analyzing separately these two subgroups would provide some additional useful information to the paper.

Indeed, in studying changes in scores, the variability in score differences (M12-M0) has mathematically variability for each toll that is twice the variability of the toll against a control gold standard (as could be a 6 min walking tests or treadmill). Thereby the coefficient of correlation of the linear regression analysis of the score differences is as expected quite low because of the high residuals that would be expected for each tool against a standard. It seems to me that the conclusion that the authors made that the WELCH is relatively insensitive to changes as compare to the WIQ could be strengthened by comparing the area under ROC curve of each of the two tolls in determining if patients where actively treated or not. Indeed, lacking a gold standard, the toll that have the higher area is expected to be the best one for estimating changes in case of active treatment.
Additional comments: No further 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: MEASURING WALKING IMPAIRMENT IN PATIENTS WITH INTERMITTENT CLAUDICATION: PSYCHOMETRIC PROPERTIES OF THE WALKING ESTIMATED-LIMITATION CALCULATED BY HISTORY (WELCH) QUESTIONNAIRE
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: I think that the authors have responded well to the comments raised in the initial review. The manuscript appears to have been strengthened and will be a useful addition to the evidence base.


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: MEASURING WALKING IMPAIRMENT IN PATIENTS WITH INTERMITTENT CLAUDICATION: PSYCHOMETRIC PROPERTIES OF THE WALKING ESTIMATED-LIMITATION CALCULATED BY HISTORY (WELCH) QUESTIONNAIRE
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors have performed an extensive revision of the initial manuscript accounting for the suggestions atht were made by the editor and the two reviewers and improved their manuscript significantly
Experimental design: The study and experimental design is clear and well defined and fills the technical and ethical standard.
Validity of the findings: I have no further comments
Additional comments: Thank you for the careful correction of your manuscript and for the interesting results that you show. I look forward for future evaluation such as long term follow up...
Minor point :
Just a a doubt at line 246 that the sentence may start with a number (this might be changed at editing)


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: CAMOSTAT MESILATE INHIBITS PRO-INFLAMMATORY CYTOKINE SECRETION AND IMPROVES CELL VIABILITY BY REGULATING MFGE8 AND HMGN1 IN LIPOPOLYSACCHARIDE-STIMULATED DF-1 CHICKEN EMBRYO FIBROBLASTS
Review round: 1
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: In summary
The authors reported that camostat mesilate inhibited IL-6 and TNF-α from DF-1 cells, as well as improved cell viability induced by LPS in vitro. They tried mass spectrometry to study the mechanism of camostat mesilate. They found MFGE8 and HMGN1 participated in IL-6 and TNF-α production and cell viability which regulated by camostat mesilate in DF-1 cells, and further confirmed them by using their siRNA.
The finding is based on in vitro data, it is interesting, but evidence is limited.
Specific points:
1.	What is DF-1? You should specify this cell in manuscript and change the title.
2.	It should be shown full name of MFGE8 and HMGN1 in abstract.
3.	Figure 1. It should be mentioned statistic methods and numbers of samples you used in figure legend. Did you try different time points and concentration of CM?
4.	Figure 2 and 3, I suggest you combine them, and should add your hypothesis about the results, especially related with your finding. In the legend, you should also specify the full name of DLE, DL, etc.
5.	Figure 4, the concentration of LPS used here was so high, why did you choose this concentration? What is statistic method and numbers of samples you used?
6.	Row 165-178, you should mention your MS data first, and then to clarify them. For MS data, people usually used western blot to confirm them, why did you choose RT-PCR?
7.	Figure 5, you said si-HMGN1#2 was used for further experiment (Row 186), but in Figure 5C,D,E, you used si-HMGN1#1, which one is correct? Your current data were not enough to support your conclusion, controls (LPS alone, CM alone) should be added here. To support your hypothesis, it is better to use western blot to see the protein levels of MFGE8 and HMGN1 after treated with CM.
8.	The English language should be improved to ensure that an international audience can clearly understand your text.


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: CAMOSTAT MESILATE INHIBITS PRO-INFLAMMATORY CYTOKINE SECRETION AND IMPROVES CELL VIABILITY BY REGULATING MFGE8 AND HMGN1 IN LIPOPOLYSACCHARIDE-STIMULATED DF-1 CHICKEN EMBRYO FIBROBLASTS
Review round: 1
Reviewer: 2

Output:
Basic reporting: The authors have tested a known inhibitor of TMPRSS2 Camostat mesylate in chicken fibroblasts treated with LPS and illustrated that pro-inflammatory and cytokine secretion is decreased and the drug improves cell viability by regulating MFGE8 and HMGN1 in lipopolysaccharide stimulated DF-1 fibroblasts. The data is interesting but preliminary. The choice of fibroblast cell lines for this study is intriguing since they are not the main immune responders.
Experimental design: Specific comments
Provide specific references that chicken fibroblasts undergo TLR4 mediated signaling in response to LPS or bacteria. None of the references cited are of avian origin.
The TNF and IL6 ELISA kit specifications are not provided. These are necessary since the readers will want to know if the kits recognize chicken proteins.
Validity of the findings: In Fig 1C, there is not a drastic cell viability change in cells treated with LPS. Ideally a dose response to LPS and subsequent rescue by dosage of CM should be shown. The manuscript does mention the concentration of LPS was used in all assays. How did they determine this? Also, to assess pro inflammation and cell injury, more markers are needed.
What are the fold changes of the differentially expressed proteins selected for further analysis? Mention in the results. Also describe the functions of these proteins in the results itself.
In the qPCR, dose response to LPS/CM and also different time points for the RNA levels should be shown to convince the readers that these small changes are significant. This is a critical flaw. If antibodies are available, protein levels should be shown.
The characterization of SiRNAs can be removed to the supplementals.
Dose response is needed for Fig 5 to generate any conclusions that the authors put forward. The effect of LPS stimulation might be reversed after 72 hrs in some of these experiments.
If the target of CM is known, then how do the authors correlate the effects on these proteins? Discuss. It is easier to test these hypothesis on a human fibroblast cell line and another relevant cell line THP1 for eg; to show that these effects are true. Western blots can be easily performed in human cell lines with specific antibodies available.
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: CAMOSTAT MESILATE INHIBITS PRO-INFLAMMATORY CYTOKINE SECRETION AND IMPROVES CELL VIABILITY BY REGULATING MFGE8 AND HMGN1 IN LIPOPOLYSACCHARIDE-STIMULATED DF-1 CHICKEN EMBRYO FIBROBLASTS
Review round: 1
Reviewer: 3

Output:
Basic reporting: The reporting is clear with some minor errors in the flow of the paper. The edits have been mentioned in the pdf. The literature use is accurate and the data is shown clearly to support the hypothesis
Experimental design: The experiments have been designed to support the hypothesis as well as to support the results obtained from the proteomic analysis obtained by the author using TMT.
Validity of the findings: The data have been validated in biological replicates and the supporting data  adds to more robust underlying data which supports the findings reported in the manuscript
Additional comments: The authors have put together a relevant piece of work. The data is clearly shown and represented in the manuscript. There are some basic comments and concerns that have been addressed in the attached pdf.


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

Input:
Title: CAMOSTAT MESILATE INHIBITS PRO-INFLAMMATORY CYTOKINE SECRETION AND IMPROVES CELL VIABILITY BY REGULATING MFGE8 AND HMGN1 IN LIPOPOLYSACCHARIDE-STIMULATED DF-1 CHICKEN EMBRYO FIBROBLASTS
Review round: 2
Reviewer: 1

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


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

Input:
Title: CAMOSTAT MESILATE INHIBITS PRO-INFLAMMATORY CYTOKINE SECRETION AND IMPROVES CELL VIABILITY BY REGULATING MFGE8 AND HMGN1 IN LIPOPOLYSACCHARIDE-STIMULATED DF-1 CHICKEN EMBRYO FIBROBLASTS
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors have updated the manuscript based on the suggestions from the editor as well as the reviewers
Experimental design: The design has been updated
Validity of the findings: The manuscript is now focused and has significant clarity
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: FACTORS INFLUENCING INTENTION TO INTERVENE IN ELDER ABUSE AMONG NURSING STUDENTS
Review round: 1
Reviewer: 1

Output:
Basic reporting: This manuscript reports on a study attempting a Factors Influencing Intention to Intervene in Elder 2 Abuse among Nursing Students. In this respect I applaud the authors for their worthwhile undertaking which reflects a recent spate of research in Korea.
The article is written in a clear and unambiguous way and literature references is enough provided. The article keeps a suitable structure, figures and tables. The literature is connected with the objectives of the research.
However, I would like to make some suggestions to the authors. For example, the authors include the term elderly along the article, but this term is generally considered ageist and stereotyped because it does not take into consideration the heterogeneity of older people which increases with age, for this reason I highly recommend use “older people” or “older adults”. Moreover, it is recommended not use like keywords terms included in the title. In addition, they use the term gender, but I am not sure whether they talk about a social variable (gender) or a biological variable (sex). Maybe they may think about it.
Experimental design: The article define the research questions and they are relevant and meaningful because of it is a knowledge gap about this topic in their geographical context. It seems that the investigation has been conducted rigorously. Although I would like to know more about the sample recruitment method.
As regards the measures, the usual procedure to describe them is to begin with sociodemographic data and after that the other variables.
I would like to know why they adapt two tools developed previously for child abuse to suit with older people. There are some tools that assess elder abuse attitudes for example but they do not used them and maybe for these reason the Cronbach´s alfa is .68.
Validity of the findings: It seems that the results are important because their novelty in their geographical context and they have benefit to literature in this field.
Although I am curious about why they collect some variables, included in table 1, but after that, they do not used them in order to analyze their relationship with the other variables. I think these results could be pretty interesting to future intervention programs.
Furthermore, they include the exact p value when generally the right way is p> o < .01 or .05.
Finally, although the discussion and conclusion section are rather well stated, on the one hand, it would be desirable to make deeply inferences about the controversy between their results and the literature. On the other hand the authors points out general alternatives but it seems like other articles that tackle with this topic. I highly recommended offer more specific practical purposes. I am very interested in the practical application of these results and the contributions to the field. I encourage to authors to include more information about it.
Overall, although I find the study´s findings very valuable, the paper needs more work in order to be of a suitable standard for publication to improve its significance and to increase its appeal or impact on the broader scientific readership in the field. The aim of these comments is only to improve the quality of the article.
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: FACTORS INFLUENCING INTENTION TO INTERVENE IN ELDER ABUSE AMONG NURSING STUDENTS
Review round: 1
Reviewer: 2

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: This research aims to describe the factors influencing the intention to intervene in elder abuse in nursing students. Elder abuse is a very relevant topic. Unfortunately, there is a lack of training in sociosanitary professionals. Assessing nursing students is of special interest to develop specific education programs and guidelines focused on elder abuse prevention and promotion of good practices/care towards older people in long-term care.

The literature review is well-developed and referenced. The methodology is conducted correctly and in enough detail to replicate. Results are well described, statistically sound, including tables that help to follow the main results. Finally, both the discussion and the conclusions are well-stated from the results.

I suggest addressing some minor issues to improve the manuscript.

1. In the introduction, it is clear the importance of evaluating elder abuse in nursing students. However, previous literature on nursing students´ attitudes, perceptions and elder abuse associated factors are not described. The authors state that few studies address this issue, and that's the relevance of developing this study. However, it would be convenient to include previous articles developed although they are only a few.

2. The results show that nursing students are more able to detect physical abuse. Considering this, you suggest developing training in also other types of abuse, which is correct. I would also discuss further in the discussion section the importance of training nursing students on implicit types of abuse since it seems they detect better explicit types. For example, infantilization (infantilized communication, not empowering older people, etc) is a type of violence towards older adults very related to negative stereotypes and most professionals are not conscious they can be disrespecting and emotionally hurting the older adult. Universities and educational courses could also work on negative stereotypes towards older people, empowerment, recognition of their dignity, etc, in order to prevent elder abuse.

3. The English language can be understood clearly but some sentences could be improved. I include two examples below. However, I would review the complete text.
- “The intention to intervene in elder abuse was the perception of elder abuse (r=.26, p=.005), legal 215 and institutional knowledge (r=.54, p=.046), attitude (r=.121, p=.004), and there was a 216 significant positive correlation”. (lines 214-216). I would replace it with “The intention to intervene showed a significant positive correlation with the perception of elder abuse (r=.26, p=.005), legal 215 and institutional knowledge (r=.54, p=.046) and attitude (r=.121, p=.004).”
- "The descriptive research design was conducted by completed the questionnaires to 182 nursing students." Reformulate 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: FACTORS INFLUENCING INTENTION TO INTERVENE IN ELDER ABUSE AMONG NURSING STUDENTS
Review round: 1
Reviewer: 3

Output:
Basic reporting: The English language needs improvement to ensure readability by an international audience. The following lines include examples of where language needs revision: 47-52, 60, 65, 67, 72, 79, 93-94, 155-156, 214, 269-270, 272-273, 274, 287-288, 295-296. I recommend the authors use an editor or colleague who is proficient in English to review the wording.

The introduction and background need to more clearly indicate the gap in evidence that this study addresses. The authors do a good job addressing an increase in elder abuse, nurses' need to report abuse and factors associated with medical providers intention to intervene. However, the authors are missing evidence that explains and connects this healthcare issue with nursing education. For example, the statement on line 74 regarding research with nursing students is not supported by evidence. I am unclear why the authors chose to address nursing education instead of nurses based on this review of literature. Lines 250-252 with supportive literature would be useful to include in the background section to substantiate the need for this study.

Examination or description of the coursework that students take in nursing programs would be useful to explain what content students are regulated to receive by agencies that have oversight for nursing education.

Thank you for including Tables 1 and 2. Please include more content to clarify these tables. For example, in Table 1, explain to what "differences in intention of intervening" refers. The use of the word 'difference' appears to suggest differences within the sample and the statistics reported do not support an evaluation of differences between participants. The authors could simply name this table as 'sample characteristics'. Further, clarify variable names in Table 1. For example, explain to what 'need for education' refers. Data analysis could be improved by including confidence intervals for results in Table 2.

Tables 3 and 4 are thoroughly done.

Thank you for providing raw data. However, supplemental files need more descriptive metadata identifiers to be inclusive of international audiences.
Experimental design: This paper reports an original research study within the aims and scope of the journal. Elder abuse is an important public health issue.

The authors indicate an increase in elder abuse and the need to address this issue among healthcare providers. The author could provide more evidence to justify the need to address education of nurses and nursing students regarding elder abuse. For example, the connection made by the authors between fewer reported cases of abuse and lower perceptions, intention or knowledge regarding elder abuse among nurses needs to be substantiated more clearly with evidence.

Authors did a thorough job explaining the use of factors on lines 67-70 to substantiate why these were included as predictors and an outcome variable.

Authors need to provide more detail about the methods to allow replication of this study. Specifically, the authors need to explain how students were recruited and data was collected. Authors needs to explain how coercion of students was minimized. For example, explaining the relationship of the authors to the students would be useful to explain how students voluntarily agreed to participate and if faculty were connected to the research study.

Explanation if the Crohnbach alpha values for each instrument were acceptable would increase validity of the use of these instruments in this study.

The sample needs to be described to be inclusive of international audiences. For example, on line 189, 'the fourth grade' refers to individuals 9 to 10 years of age in the United States. Further, levels of degree preparation need to be described in a way that is inclusive of international audiences.
Validity of the findings: Thank you for providing raw data. However, supplemental files need more descriptive metadata identifiers to be inclusive of international audiences. I have no comment about this data for this reason.

Authors do a thorough job of comparing the study findings to other evidence on lines 255-264.

Wording on lines 269-277 could more clearly supported by the data from the study. For example, authors could explain how nursing students do not take care of elderly (line 270). Perhaps the authors mean that students do not have as much experience taking care of elderly. Additionally on line 272, authors could state that participants indicated that of all types of abuse, physical abuse was rated as the most severe and explain what 'most severe' means.

The conclusions on lines 292-305 appear to overreach the results. The study results suggest that certain factors are associated with intention to address situations of elder abuse. The link between intention to intervene and actual intervention in situations is not clearly substantiated by evidence. Authors could indicate that these factors were associated with intention in this study and further exploration between intention and behavior needs to be established.
Additional comments: Thank you for addressing an important public health issue. The authors' most important issue is to improve the English language in the paper and in the tables. The next important issue is adding evidence to support the rationale for this study. The next most important issue is to add detail to the methods section. A final point would be to provide resources for the reader would add to this paper. For example, the authors provide examples of resources for more information about abuse, reporting standards, and case studies or simulation exercises that could increase reader proficiency in addressing this issue.

I hope this review is helpful. This is an important issue and I hope you will continue this work. Thank you for inviting me to review this paper.


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: FACTORS INFLUENCING INTENTION TO INTERVENE IN ELDER ABUSE AMONG NURSING STUDENTS
Review round: 2
Reviewer: 1

Output:
Basic reporting: I would like to thank to the authors for the revision of the article.
The term elder abuse is correct, only in this circusntance elder could be used because it is the consensuous term to refer abuse towards older people.
Experimental design: The authors make the changes requested.
Validity of the findings: The authors make the changes requested.
Additional comments: The authors make the changes requested.


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: FACTORS INFLUENCING INTENTION TO INTERVENE IN ELDER ABUSE AMONG NURSING STUDENTS
Review round: 2
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: I do think that my concerns have been addressed in this version. The methodology is sound and offers interesting findings. Having done the changes suggested, I believe that this important piece of research is ready for the next stage of the publishing process.
Thank you for your work!


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

Input:
Title: RECOMMENDED NITROGEN RATES AND THE VERIFICATION OF EFFECTS BASED ON LEAF SPAD READINGS OF RICE
Review round: 1
Reviewer: 1

Output:
Basic reporting: need native English

the idea is clear, and the authors follow the constructions of the journal

the hypotheses is clear

the authors need to folow this article
A comparison between different chlorophyl lcontent meters under nutrient deficiency
conditions  .  Kalaji et al 2017  Journal of Plant Nutrition 2017, VOL. 40, NO. 7, 1024–1034
Experimental design: Two field trials comprising of seven nitrogen (N) rates (0, 45, 90, 135, 180, 225 and 270 kg N  ha-1) were conducted in 2019 (two different fields in the same area with same planting pattern),  using a randomized complete block design with three replicates
Validity of the findings: All underlying data have been provided; they are robust, statistically sound, & controlled
Conclusions are well stated, linked to original research question
Additional comments: the author need to follow (Kalaji et al 2017)
A comparison between different chlorophyl lcontent meters under nutrient deficiency
conditions  .    Journal of Plant Nutrition 2017, VOL. 40, NO. 7, 1024–1034

need improve your discussion part ,
answer the question (what is relationship between N and chlorophyll content

do you think it will give you same results and stress conditions?
can you compare your result with normal chlorophyll measurements?


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: RECOMMENDED NITROGEN RATES AND THE VERIFICATION OF EFFECTS BASED ON LEAF SPAD READINGS OF RICE
Review round: 1
Reviewer: 2

Output:
Basic reporting: Eglish level is poor and should be consalted with native speaker . Authors discribe the problem of N -fertilization only from one side. They see only the problem of over fertilizatision but they didn't saw that very often problem of insufficient fertilization which cause a problem of N deficiency
Experimental design: There is lack of information about kind of soil the experimental sites was localised there is no information  about vegetation period characteristic and
Validity of the findings: All invetigation which authors done based on single basic method . There is suggest to compare gained results with some references methods. The authors did not provide information on the number of leaves in the sample for measurment
Additional comments: Rewrite the text using the suggestion in the review to improve qality of 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: RECOMMENDED NITROGEN RATES AND THE VERIFICATION OF EFFECTS BASED ON LEAF SPAD READINGS OF RICE
Review round: 2
Reviewer: 1

Output:
Basic reporting: Using SPAD method, Easy to handle, reliable, high-efficiency, and environmentally friendly method to diagnose
plant nitrogen (N) status , predict grain yield and optimize N management is essential in
modern rice production systems
Experimental design: Original primary research within Scope of
the journal. Research question well defined, relevant
& meaningful. It is stated how the research fills an identified knowledge gap.
Methods described with sufficient detail &
information to replicate.
Validity of the findings: novality is poor

he must compare with normal analysis to chlorophyll or Nitrogen
 to see what is difference between his method and normal method
Additional comments: i asked you to compare between normal analysis and SPAD even with previous studies


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

Input:
Title: RECOMMENDED NITROGEN RATES AND THE VERIFICATION OF EFFECTS BASED ON LEAF SPAD READINGS OF RICE
Review round: 2
Reviewer: 2

Output:
Basic reporting: Language was improve and I don't see any mistakes, Literature was replenished with suggested possitions. Authors corect the manuscript with all sugested areas
Experimental design: Experiment design is better described than it was previously. Rsearch and statistical methods were now corectly described . Methods were descibed with sufficient details and information.
Validity of the findings: Conclusions are well stated, linked to original research question. Gained results are interesting for local perspective
Additional comments: Good job .  In my opininion I can accept the  manuscript and all changes which were done by authors


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: RECOMMENDED NITROGEN RATES AND THE VERIFICATION OF EFFECTS BASED ON LEAF SPAD READINGS OF RICE
Review round: 3
Reviewer: 1

Output:
Basic reporting: The article "Recommended nitrogen rates and the verification of effects based on leaf SPAD readings of rice" is an interesting article, which can be accepted after considering following comments

1) line 54  "SPAD may reflect the plant leaves’ N status and is simple, quick, reliable, and harmless" Please explain SPAD more clearly.

2) Line 109 Please write the name of SPAD producer, company name, city, country.

3) Line 115 please indicate the years

4) Use Fig. or Figure - please check journal suggestion

5) Figure 2 legend is wrong "Temperature and precipitation during the rice-growing stage" please correct it

6) Xiong et al. (2015; https://doi.org/10.1038/srep13389) has shown that SPAD-based leaf nitrogen estimation is impacted by environmental factors and crop leaf characteristics, how the authors considered this issue please specify.

7) Manuscript can be further benefitted by following references
"https://doi.org/10.1626/pps.17.81"
Experimental design: No comments
Validity of the findings: SPAD meter is for a long time use for nitrogen estimation with some limitations please specify how your work is different, and not just a confirmatory work?
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: PREVALENCE AND CHARACTERIZATION OF EXTENDED-SPECTRUM Β-LACTAMASE-PRODUCING ESCHERICHIA COLI AND KLEBSIELLA PNEUMONIAE ISOLATED FROM RAW VEGETABLES RETAILED IN SOUTHERN THAILAND
Review round: 1
Reviewer: 1

Output:
Basic reporting: Language:
The English language was clear. Some suggested changes were made in the manuscript.
Literature references, sufficient field background/context provided:
Abstract, results section: In line 32 of the abstract additional information is needed as indicated in the comments box in the manuscript: The title of the manuscript mentioned prevalence of ESBL producing Escherichia coli and Klebsiella pneumoniae. In the first section of the results the following statement was made: ESBL-producing E. coli and K. pneumoniae isolates were found in 14 of the 305 samples obtained from seven out of ten types of vegetables (4.6% of the total). It is important to incorporate information on prevalence in the vegetables, before describing the genes screened for in the abstract.

Introduction:
•	In the abstract broad-spectrum ampicillin and extended-spectrum cephalosporin resistance of clinical isolates of E. coli and K. pneumoniae were mentioned specifically. The author tested isolate resistance to ampicillin which is a broad-spectrum antibiotic, cephalosporins, carbapenems, tetracycline and aminoglycosides. Some background information on the importance of ampicillin resistance of E. coli and K. pneumoniae should be included in the introduction.

•	Some background information regarding the specific genes screened for is lacking in the introduction.

•	In lines 54 and 57 references should be added as indicated with track changes in the text in the introduction.
•	Line 57-58 some detail of the organisms i.e. E. coli and K. pneumoniae should be mentioned and not only generally referring to microbes to clarify the focus and provide more context for performing the study.

Professional article structure, figures, tables:
Table 3: The origin of the samples not written in the English alphabet. Please correct.
Table 3: The heading mentions Eric-PCR primers, however these were included in the manuscript text and are not listed in the table.

Self contained with relevant results to hypothesis:
The manuscript form a distinct unit of research question to be addressed, results obtained and discussed.
Experimental design: Original primary research within the Aims and Scope of the journal:
The manuscript focuses on isolation, identification and characterisation of potential human pathogenic bacteria, specifically ESBL producing E. coli and K. pneumoniae and therefore fits into Biological/Environmental and potentially Health Sciences which are in the scope of the journal.
Research question well defined, relevant & meaningful. It I stated how research fills and identified knowledge gap.
The motivation for the study, goals, the knowledge gap to be filled and the contribution to existing knowledge were clearly articulated.
Rigorous investigation performed to a high technical & ethical standard.
Some suggestions were made regarding the methodology used in this study.
Methods described with sufficient detail & information to replicate.
•	In line 78 please change the heading Bacteria identification process and ESBL-producing bacteria isolation to reflect the specific organisms targeted.

•	In line 84 please include information how the colonies were purified.

•	In line 98 add the reference details.

•	In line 11 add the original reference for the Kirby-Bauer test.

•	In line 118 add the reference.

•	In line 124: Title changed. See track changes in the manuscript.

•	In line129 please describe how the concentration of the DNA was determined and what was the range of concentrations used for PCR analysis. Also how was the DNA template concentration dependant on the primers used?

•	In line 130 and in Table 1 please add reference/s for the primers used in PCR analysis to screen for and identify the ESBL encoding genes.
Validity of the findings: In Table 2 the heading states common edible vegetables from a market. This is confusing as in the Material and Methods two markets were described.

Is it not a summary of the vegetables and ESBL prevalence in both markets as reflected in Table 3? If that is the case the heading has to be corrected.

As indicated previously, please write origin details in Table 3 using the English alphabet.

Please refer to the track changes in the results and discussion section of the manuscript as there are a number of questions/changes.
Additional comments: It is highly recommended that the authors determine the variants of the amplicons sequenced to confirm and discuss the identities of the genes detected which will add significant value to the results obtained during the study and comparison to results reported in other studies.  It certainly is a worthwhile study to report, but after substantial revision.

This can be performed by subjecting amplicon sequences of the ESBL genes to BLAST nucleotide search analysis to identify the antimicrobial resistance genes and variants.


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: PREVALENCE AND CHARACTERIZATION OF EXTENDED-SPECTRUM Β-LACTAMASE-PRODUCING ESCHERICHIA COLI AND KLEBSIELLA PNEUMONIAE ISOLATED FROM RAW VEGETABLES RETAILED IN SOUTHERN THAILAND
Review round: 1
Reviewer: 2

Output:
Basic reporting: English - it is clear

Literature - ok

Article structure - ok

Hypothesis - well-stated and relevant
Experimental design: Experimental design - ok for the study

Research question - clearly defined and important

Methodology - for what was done it is ok
Validity of the findings: The findings are valid.

My only suggestion is that what is missing is whole-genome sequencing (WGS). It would be important to understand the level of genomic variation, genotypes, and global picture of AMR and other putative properties based on pan-genomic analysis. I would even suggest that the population structure analysis of the isolates (using genomic data) be done in the context of freely available genomes of the same species deposited on NCBI, by specifically picking representative genomes from ST (sequence types) from different environments. This is just a suggestion. Also, I would use WGS with more than just one isolate from each plate and try to pick more colonies to maximize the chances of capturing different variants. I think it is important to get WGS data to link genotypes to phenotypes at a higher level of genotypic resolution than what is provided now.
Additional comments: I think the work is important and has implications for food safety. But in my view, it can maximize its reach by using WGS.


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: PREVALENCE AND CHARACTERIZATION OF EXTENDED-SPECTRUM Β-LACTAMASE-PRODUCING ESCHERICHIA COLI AND KLEBSIELLA PNEUMONIAE ISOLATED FROM RAW VEGETABLES RETAILED IN SOUTHERN THAILAND
Review round: 1
Reviewer: 3

Output:
Basic reporting: The manuscript is clear and easy to follow. Methods and Results are described thoroughly, although there are some places where additional might be useful.
Experimental design: The experimental approaches are well defined.
Validity of the findings: The manuscript described a meaningful assessment of the ESBL-producing E.coli and K.pseumonae presence in raw vegetables in Thailand, which is of significant value to public health and food safety. All data are presented in a clear manner, and well supported the conclusions.
Additional comments: The manuscript described a thorough characterization of extended spectrum beta-lactamase producing Klebsiella and E.coli in raw vegetables in local markets in Thailand. The research presented in this manuscript is scientifically sound, and the conclusions are well supported by the data. There are, however, some minor issues that I hope the authors can address before this manuscript can be accepted for publication in PeerJ.

Line 122, 333, 337, 339 etc.: please make sure gene names are italicized throughout the manuscript

It would be useful to include in the introduction the structures of the antibiotic classes used in this study, and the phylogenetic relationship of the b-lactamase genes characterized, as well as their targets on the b-lactam structures.

Figure 1:
I suggest the authors to include more description of the experiment in the figure legends.

Figure 2: It is important to clarify how the dendrogram was constructed (from ERIC-PCR patterns), and how ERIC-PCR pattern is representative of the phylogenetic relationship between the isolates. Therefore, I would like to state again that the authors should clarify the relationship between the b-lactamase genes in this study.

Does the presence of multiple drug resistance in these isolates suggest anything about the possibility of horizontal gene transfer among them, given that they are isolated from the very same location/sample? Can the authors elaborate more on this?

E. coli and Klebsiella are human pathogens and not natural plant colonizers. Can the authors discuss a source of contamination on the raw vegetables collected from the local market?

Table 4: the title should be corrected as “Antimicrobial susceptibility test in E.coli and K.pneumoniae”, as prior this test, it was unknown whether these isolates are resistant to an extended spectrum of b-lactam.


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: PREVALENCE AND CHARACTERIZATION OF EXTENDED-SPECTRUM Β-LACTAMASE-PRODUCING ESCHERICHIA COLI AND KLEBSIELLA PNEUMONIAE ISOLATED FROM RAW VEGETABLES RETAILED IN SOUTHERN THAILAND
Review round: 2
Reviewer: 1

Output:
Basic reporting: The language and structure of the article are clear after revisions were made.
Experimental design: I have no comments here.
Validity of the findings: I understand the funding argument posed to guard against doing WGS for this study. I empathize with the author in all honesty. I truly do.

But after doing such a nice study in attempting to isolate important AMR bacteria that has consequences for Public Health, the work necessitates WGS.

If you examine the discussion, the authors would like to compare what you have in light of the population structure of these isolates and those associated with humans or other sources. In my view, that cannot be done with the data you have.

Examine these two paragraphs:

"The prevalence of E. coli and K. pneumoniae isolates was demonstrated by the range of different strains determined using phylogenetic tree analysis. ESBL-producing bacteria may, therefore, be involved in spread to community, thereby causing infectious diseases.

Conclusions
As per our findings, it was determined that retail vegetables at local markets in Nakhon Si Thammarat may be reservoirs for the spread of ESBL-producing E. coli and K. pneumoniae. This may lead to antibiotic resistance through food chain transmission if consumer hygiene is poor."

If you had WGS and analyzed these data in the context of other genomes deposited on NCBI coming from humans and other sources, these statements would carry enough weight to provide a hypothesis or even a prediction. Because I believe this work is relevant for Public Health, WGS is crucial here.
Additional comments: I respect the work done by the authors. I think this work has the potential to be even stronger by WGS of the isolates acquired in the study, and a population-based analysis in light of other clinical and environmental isolates.


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: IMPORTANCE OF EXPERIMENTAL INFORMATION (METADATA) FOR ARCHIVED SEQUENCE DATA: CASE OF SPECIFIC GENE BIAS DUE TO LAG TIME BETWEEN SAMPLE HARVEST AND RNA PROTECTION IN RNA SEQUENCING
Review round: 1
Reviewer: 1

Output:
Basic reporting: The english used, while clear, is very verbose so sentences can be challenging to understand. You may wish to consider reviewing the general language used to improve it's readability

e.g

lines 18-21

Huge amounts of data produced by high-throughput sequencing technologies have been submitted into the Sequence Read Archive (SRA) for reuse by repository users. However, it may not be possible to clarify the validity of the sequence data without metadata containing experiment-specific information.

would be clearly written as

Large volumes of high-throughput sequencing data have been submitted to the Sequencing Read Archive (SRA). The lack of experimental metadata associated with the data makes reuse and understanding data quality very difficult.

Line 47 there is no citation for the SRA such as https://doi.org/10.1093/nar/gkq1019

Line 59  For example, this author has observed that the time taken to process the same number of RNA samples was 15 min for one technician and 60 min for another technician in the same laboratory;

This is an anecdotal assertion without any support. It would be good to see this sentence strengthened with evidence or soften to a general trend
Experimental design: The experimental design is strong for the hypothesis being tested, that longer RNAseq processing times lead to changes in the observed gene expression profiles, especially for genes linked to apotosis

The authors should consider if they could share their protocol more widely, in a structure which is easier to reproduce via service such as protocols.io

https://www.protocols.io/
Validity of the findings: This paper identifies a clear challenge with the public sequences databases and proposes an experiment to identify the scale and nature of the challenge.

The way the results are presented in the paper make it difficult to see how large the difference is when lag time is considered and the fact the authors added cultivation time to this experiment to has somewhat clouded the results.

It would be good to see the authors think about focusing some of their consideration on a single cultivation time and assessing differences just in processing time in more detail to give greater evidence for their core assertion that processing time has a strong impact on the gene expression profiles derived. Figure 3 either adding an extra panel or a different visualisation might help here.
Additional comments: Line 150 there is a distinct lack of metadata associated with the data submission to DDBJ DRA006016 which given the assertion of the paper that such metadata is required to reanalyse data seems like a significant oversight

The authors don't demonstrate any awareness of existing metadata standards for RNAseq data such as the MINISEQE recommendations from the Functional Genomics Data Society, the ENCODE standards or the Livestock standards from the Functional Annotation of Animal Genomes consortium

http://fged.org/site_media/pdf/MINSEQE_1.0.pdf
https://genome.ucsc.edu/ENCODE/protocols/dataStandards/ENCODE_RNAseq_Standards_V1.0.pdf
https://www.ncbi.nlm.nih.gov/pubmed/30311252

The recommendations in the discussion section lack specificity starting on line 261 the authors propose better metadata with submissions without stating what variables should be provided and what type of data each of those variables should contain.

The authors correctly identify that without a specific standard it can be difficult to compare between studies and researchers only tend to submit variables which they think are important but don't talk about possible solutions through systems like the standards described above or the checklist system that the ENA has implemented with this to help with this problem https://www.ebi.ac.uk/ena/submit/checklists

The authors assert that protocols reported via video are easier to reproduce that text protocols without providing any evidence of that assertion or any commentary about if text protocols can be improved themselves if an author would struggle to produce and upload a video protocol.

I cannot recommend this paper for publication in its current state. The problem it identifies is real and the experiment chosen can be used to demonstrate why one particular RNAseq processing variable is important but the paper is lacking any discussion of previous attempts to try and address this challenge not do they even follow their own recommendations and provide such detail in their own DDBJ data submission.

thank you

Laura Clarke, EMBL-EBI


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: IMPORTANCE OF EXPERIMENTAL INFORMATION (METADATA) FOR ARCHIVED SEQUENCE DATA: CASE OF SPECIFIC GENE BIAS DUE TO LAG TIME BETWEEN SAMPLE HARVEST AND RNA PROTECTION IN RNA SEQUENCING
Review round: 1
Reviewer: 2

Output:
Basic reporting: Overall the quality of English and reporting is very good. That said, I think there
are a number of points that need to be clarified before this paper can be accepted for
publication. I want to stress that this is not a matter of extra work, simply clarification.

Specifically it's not clear in figures 3 and 4 what correlations (or other measure) are being used. Are the correlations over the
technical replicates? Are they over the day by day data (as opposed to the different times between gathering the RNA samples)?

With respect to figure 5 the focus is on showing genes that are DE between different RNA gathering times but surely it is more
interesting to ask what genes are DE between days of measurement and then to see if that pattern is borne out between different
measuring times?

Finally, the focus on genes related to apoptosis seems arbitrary - there needs to be some motivation why this is being examined in
detail.
Experimental design: The overall experimental design is sound though I note the above comments on reporting and what is being computed should be noted here.
Validity of the findings: Overall the findings are valid, though I note the points above in the reporting section.
Additional comments: I think some clarifications need to be made here but it's nothing that can't be fixed.


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: INFLUENCE OF TIED-RIDGE WITH BIOCHAR AMENDMENT ON RUNOFF, SEDIMENT LOSSES, AND ALFALFA YIELD IN NORTHWESTERN CHINA
Review round: 1
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: The study investigated how tied-ridge with biochar amendment improved soil characteristics and alfalfa yield in a specific area I china. The findings of the research were positive and significant. The quality of the work is of an acceptable standard. Some comments to improve the work are given below
1.	Line 60, kindly include the botanical name of alfalfa at first mention.
2.	Line 133-135, this need not appear in the introduction.
3.	Line 142-145, to help readers appreciate the significance of the research more, it would be beneficial to include a map of the study area.
4.	Line 162, if available, please give the product name of this biodegradable film. This could assist in cases where the experiments need to be replicated.
5.	No details on biochar source, properties, and application technique, and quantity were presented in the methods section. In fact, there was no mention of the word ‘biochar' in this section. That is quite odd.
6.	Line 277, 296, 339, 353, 356, 373, kindly avoid the use of personal pronouns like ‘we’ and ‘our’.
7.	The manuscript should be thoroughly spell-checked and grammar-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: INFLUENCE OF TIED-RIDGE WITH BIOCHAR AMENDMENT ON RUNOFF, SEDIMENT LOSSES, AND ALFALFA YIELD IN NORTHWESTERN CHINA
Review round: 1
Reviewer: 2

Output:
Basic reporting: The English language needs to be improved to ensure that an international audience can clearly understand your text. Some examples where the language could be improved include lines 97 and 372. I suggest you have a proficient English colleague and familiar with the subject matter, reviews your manuscript, or use grammar checking tools.
One example can be described as lines 222 and 238, in which short sentences can be managed in tables.

Figure 2 and Figure 5 do not have high resolution to identify the contents. It is recommended to revise the figures.
Experimental design: The experimental design is well organized, which demonstrated consistency with other authors' findings. It can also be of help if authors provide findings in disagreement from the literature if applicable.
Validity of the findings: The findings are valid, well compared with other results from the 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: INFLUENCE OF TIED-RIDGE WITH BIOCHAR AMENDMENT ON RUNOFF, SEDIMENT LOSSES, AND ALFALFA YIELD IN NORTHWESTERN CHINA
Review round: 1
Reviewer: 3

Output:
Basic reporting: No comment.
Experimental design: No comment
Validity of the findings: No comment
Additional comments: This is a well written, clear and concise manuscript. The overall conclusions of the study are not novel, but the methodology is proper and the quality and amount of results, as well as their analysis is adequate. The study is interestring and the manuscript is worth of publication.

1 - Introduction: The agronomic benefits from the biochar addition to soil are widely acknowledge. However, biochar addition to soil can also present possible detriments to soil health. Such possible detriments should be referred by the authors. For example, the long-term effects of biochar application on soil including its fate in different soil types and management practices still need to be explored, such as influencing soil hydrophobicity and increasing soil sorption capacity of trace contaminants and contamination of aquifers. See Solaiman, Z.M. and Anawar, H.M. 2015. Application of Biochars for Soil Constraints: Challenges and Solutions. Pedosphere 25(5), 631–638. https://doi.org/10.1016/S1002-0160(15)30044-8;

2 - A figure of the location of the study area should be added.

3 - L156: "(3 tillage systems x 2 mulching materials + flat planting (FP) as control)" This is not well explained. This gives 7 plots. What do you mean with mulching materials? Biochar and no biochar, or biochar and the plastic? Be clearer.

4 - Figure 1: Figure 1 is not clear. What do the up and down arrows (on the left of the terms soil moisture, fodder yield and so on) mean? Represent the preferential direction of runoff and the slope gradient in the plots. Identify the biochar, the plastic mulch as well as the areas with the ridges, furrows and the lines with the crops and so on. The figure should be explanatory by itself.

5 - Equation 4: Capital W in Wsediment. Equation 5: It should be a capital P for precipitation. L227: Define WUE. Equation 6: Capital RE for runoff efficiency. Equation 10: Rectify the â symbol.

6 - The biochar characteristics and properties are not mentioned in the methodology. Also, the authors always refer the biochar application as mulching. Mulching is the biochar and the biodegradable film. In the title the authors refer biochar amendment. However, in the methodology, it seems that the authors forgot the main purpose of the article: study the influence of biochar amendment.

7 - L257-258: "The annual precipitation averaged 385.3 mm over 46 years, as rainfalls from May to August were higher than in the 46-years monthly record." What is the purpose of this information? And why a figure (Figure 2) detailing this? Is this important for this study?

8 - The authors should first introduce a Figure and then analyse it.

9 - Consider only "Conclusions" instead of "Conclusions and recommendations". The main reason is that the recommendations part is almost non-existent. Remove the numerical values from the conclusions. The authors already presented a lot of numerical values and percentages in the results. For the conclusions, it is only important to know if one treatment is better than other and at what.

10 - Figures 3-5 have very poor quality.


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

Input:
Title: INFLUENCE OF TIED-RIDGE WITH BIOCHAR AMENDMENT ON RUNOFF, SEDIMENT LOSSES, AND ALFALFA YIELD IN NORTHWESTERN CHINA
Review round: 2
Reviewer: 1

Output:
Basic reporting: OK
Experimental design: OK
Validity of the findings: OK
Additional comments: The paper is now acceptable for publication.


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

Input:
Title: INFLUENCE OF TIED-RIDGE WITH BIOCHAR AMENDMENT ON RUNOFF, SEDIMENT LOSSES, AND ALFALFA YIELD IN NORTHWESTERN CHINA
Review round: 2
Reviewer: 2

Output:
Basic reporting: Please correct line 136 by removing "to" in "can to". And please double-check for punctuations such as commas, for example, in line 436, before "according to."
Experimental design: The experimental results support research questions by investigating the knowledge gap with the help of a literature review.
Validity of the findings: Conclusions based on the data, which are robust and statistically sound, are acceptable.
Additional comments: No additional comments


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

Input:
Title: EXPERIENCES OF INTERNATIONAL MEDICAL STUDENTS ENROLLED IN CHINESE MEDICAL INSTITUTIONS TOWARDS ONLINE TEACHING DURING THE COVID-19 PANDEMIC
Review round: 1
Reviewer: 1

Output:
Basic reporting: The English writing could be improved. Somethings are not clear or need clarification.

There is sufficient field backround given.

I'm not sure that raw data is shared but it has a professional article structure.

The study states aims and these should be brought up again at the end.

I would like to know more about the themes and subthemes that you had as this does not appear in enough detail. I was expecting a figure about this but there was not one.
Experimental design: Research question pretty well defined but needs to be followed up in the discussion. It states how the article will fill a research gap. Investigation is performed to a good standard and ethical standard.

Methods need a bit more about the process of thematic analysis.
Validity of the findings: Describes how the article is novel. Data is quite robust and statistically sound.
Conclusions could link to the aims of the research more.
Additional comments: This is an interesting study. I have suggested some changes that may improve the work.
Sometimes the language flows and sometimes it doesn't flow very well ie the abstract is very well written but the introduction about Covid 19 etc is not as well written and could be more concise. Thank you for the opportunity to read your work.


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

Input:
Title: EXPERIENCES OF INTERNATIONAL MEDICAL STUDENTS ENROLLED IN CHINESE MEDICAL INSTITUTIONS TOWARDS ONLINE TEACHING DURING THE COVID-19 PANDEMIC
Review round: 1
Reviewer: 2

Output:
Basic reporting: 1. It seems that word "responses" is not needed in the title.
Experimental design: 1. Ln 135 "1107 IMS were recruited randomly studying in Chinese medical institutions."
Could you please explain in more details what random means, how very the respondents picked? From how many institutions were the students recruited?
2. Ln 143 questionnaire was in English I would suggest you state this fact.
Validity of the findings: Ln 328. It would be useful to give a short description of "Osmosis and BiteMedicine".
Lns 336.-338. "Some countries may have been disproportionately represented with more significant numbers of responses, such as Pakistan, possibly skewing outcomes because of sample bias compared to Tanzania" - are there any data or reference how IMS are from which country. If it is speculation, it should be identified as such.
Additional comments: A nice article on an interesting topic. It surely will be useful to improve online teaching.


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: EXPERIENCES OF INTERNATIONAL MEDICAL STUDENTS ENROLLED IN CHINESE MEDICAL INSTITUTIONS TOWARDS ONLINE TEACHING DURING THE COVID-19 PANDEMIC
Review round: 2
Reviewer: 1

Output:
Basic reporting: English is MUCH improved. I can't fault it.
References provided.
Professional article structure.
Experimental design: No issues
Validity of the findings: No issues
Additional comments: I think this is ready for publication. The only thing I would say is there is a number like 456 thousand
and I would write 456,000 rather than use the word thousand - but extremely minor.


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: EXPERIENCES OF INTERNATIONAL MEDICAL STUDENTS ENROLLED IN CHINESE MEDICAL INSTITUTIONS TOWARDS ONLINE TEACHING DURING THE COVID-19 PANDEMIC
Review round: 2
Reviewer: 2

Output:
Basic reporting: The language has been significantly improved.
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: ENTEROAGGREGATIVE ESCHERICHIA COLI IS ASSOCIATED WITH ANTIBIOTIC RESISTANCE AND URINARY TRACT INFECTION SYMPTOMATOLOGY
Review round: 1
Reviewer: 1

Output:
Basic reporting: No comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Among bacterial species involved in UTIs, uropthogenic Escherichia coli (UPEC) is the most common. Antimicrobial resistance in UPEC and spreading MDR UPEC in recent decades is a clinical problem. Increasing frequency of MDR UPEC result in excessive use of broad-spectrum antibiotics such as fluoroquinolones, cephalosporins and aminoglycosides. Antimicrobial resistance among UPEC is increasing in many countries and shows time- and area-related variability.
This manuscript can be published in Peer J but minor revision is necessary:
1. Line 47: Instead 105 CFU should be ≥105CFU
2. Line 116: Please state which cards dedicated to Vitek2 have been used to identify bacteria, determine antibiotic susceptibility and detect resistance mechanisms.
3. Instead “strains” should be “isolates”. Change “strain” to “isolate”, please correct this throughout the manuscript.
4. Line 174: Change  “Phylogenetic grouping …. “ to “Phylogenetic groups and presence of EAEC isolates among UPEC”
5. Line 182: Change “Pathotypes and population characteristics”  to “Occurrence of UPEC and UPEC/ EAEC in patients with different clinical symptoms and demographic characteristics”
6. Line 198: Change “Virulence genes …..” to “Occurrence of virulence genes in EAEC and UPEC isolated  from asymptomatic and symptomatic patients”.
Line 216: Change “susceptibility pattern” to “resistance”.


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: ENTEROAGGREGATIVE ESCHERICHIA COLI IS ASSOCIATED WITH ANTIBIOTIC RESISTANCE AND URINARY TRACT INFECTION SYMPTOMATOLOGY
Review round: 1
Reviewer: 2

Output:
Basic reporting: this manuscript is clear and unambiguous.  data are appropriate as presented.  figures and tables are OK.  English is good.
Experimental design: The question is well-defined and the is rigorous.  However, there are some gaps that should be addressed, e.g. what is the frequency of the reported genes in fecal E. coli isolates?
Validity of the findings: The findings appear valid but the reservations below.
Additional comments: This is a useful contribution to the field.  but i have some criticisms the response to which will strengthen teh paper.

1. although EAEC genes appear to be prevalent (surprisingly so), it would make a more powerful case for their association with UTI if their frequencies among fecal strains in teh same human population were known.  i doubt they could be as high as among the urinary isolates, but this is a critical point for the ms.

2. AggR controls expression of both aatA and aap genes.  therefore, one would expect that there would be a high degree of correspondence among the genes.   Indeed, presence of aap or aatA without aggR would suggest that the former loci would be silent, and therefore not clinically relevant (unless another regulator were at play). Moreover, the Aat apparatus was initially reported to be the transporter of the aap gene produce dispersin, so they should also be linked (in theory).   the authors should report the combinations of genes - perhaps a supplemental table of the 100 isolates showing all their genotypes would be helpful for the circumspect reader.

3. Table 4.  i'm not sure what the p values represent.

4. line 188: "no", rather than "none"


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: IN SILICO PREDICTIONS OF PROTEIN INTERACTIONS BETWEEN ZIKA VIRUS AND HUMAN HOST
Review round: 1
Reviewer: 1

Output:
Basic reporting: The literature review is not sufficient. Only clinical background on Zika virus is presented. No review of the vast literature on protein protein interaction prediction, including prediction of Zika-human protein protein interactions is provided.

The images provided are of poor quality. Figure 3 is a "hairball" with little to no information provided by this image.

Figure 4 is an automatically retrieved image, which at best could be used in the supplement.
Experimental design: Computational methodology relies on adequate reference to prior work. If the same task has been carried out before, the authors must recreate the the prior work as to allow the side by side comparison of the new results. Otherwise, there is no way of evaluating if the current work constitutes an improvement over prior existing work.

The research question is not well defined. We are many years past predicting host-pathogen interactions if there are no major conclusions derived from the predictions or the methodology shows any novelty.

In its current form, it is impossible to conclude if the current work fills an actual knowledge gap.
Validity of the findings: The choice of the negative dataset is not well justified and researched. There are other approaches that previous PPI prediction work has considered and these should at least be referenced, with a justification for why the chosen approach is superior. Currently, it appears arbitrary why the Eid et al paper was chosen.

The Go-term enrichment yielded very generic pathways, such as ErbBx signaling, complement, NFkappa B, PI3K-AKt signaling and phosphatidylinostiol signaling, ubiquitin etc. These are not specific and it is not clear what we learn from finding the respective proteins over-represented in the interactome.

There is essentially no conclusion in this paper.
Additional comments: Here is an experimental determination of PPI large scale involving Zika - this is the minimum paper I would expect to see cited:

Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms of Dengue and Zika Virus Pathogenesis.
Shah PS, Link N, Jang GM, Sharp PP, Zhu T, Swaney DL, Johnson JR, Von Dollen J, Ramage HR, Satkamp L, Newton B, Hüttenhain R, Petit MJ, Baum T, Everitt A, Laufman O, Tassetto M, Shales M, Stevenson E, Iglesias GN, Shokat L, Tripathi S, Balasubramaniam V, Webb LG, Aguirre S, Willsey AJ, Garcia-Sastre A, Pollard KS, Cherry S, Gamarnik AV, Marazzi I, Taunton J, Fernandez-Sesma A, Bellen HJ, Andino R, Krogan NJ.
Cell. 2018 Dec 13;175(7):1931-1945.e18. doi: 10.1016/j.cell.2018.11.028.
PMID: 30550790

There are many many other papers that are relevant that you should look at, some example are listed below:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747333/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742907/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102568/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474419/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783930/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736651/