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: EFFECT OF SHOOTING EXPERIENCE ON EXECUTIVE FUNCTION: DIFFERENCES BETWEEN EXPERTS AND NOVICES
Review round: 2
Reviewer: 2

Output:
Basic reporting: See the general comments
Experimental design: See the general comments
Validity of the findings: See the general comments
Additional comments: I think that the manuscript has considerably improved and I acknowledge that the authors have done a good job in taking care of the suggestions made by the reviewers. However, a few more issues need to be addressed before this manuscript moving toward publication.

1. The ages of participants seem to vary as a function of groups. This concern may be mitigated if the authors could include this factor in analyses as covariates. This concern is also worthy to be mentioned in the limitation section.

2. One major concern is that the conclusion regarding neural efficiency made here was not supported by the data, given the lack of brain measures in this study. Perhaps addressing the difference in domain-general cognitive functions may be more appropriate here.

3. It is suggested to provide the rationale for the design of ISI of the flanker task. Is this fact important for the investigation of expertise level here? Please clarify.

4. The factor of ISI should have three levels, please correct.

5. Finally, the major novel conclusion of this study, unfortunately, does not appear to be conclusively supported by the statistical evidence. To elaborate, given the lack of three-factors interactions, the simple main effects of group comparisons for each ISI in each trial type were not allowed. This issue should be carefully addressed because the weak statistical support for it is highly problematic.


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: EFFECT OF SHOOTING EXPERIENCE ON EXECUTIVE FUNCTION: DIFFERENCES BETWEEN EXPERTS AND NOVICES
Review round: 3
Reviewer: 1

Output:
Basic reporting: Given there's no evidence supporting the neural efficiency hypothesis, it is hard to connect all the points raised by the authors in this manuscript. Furthermore, after proofreading and the first revision, the quality of writing was expected to be improved extensively. However, many typos and abbreviations are not corrected.
Experimental design: no comment
Validity of the findings: In the introduction, there are four paragraphs talking about the relationship between motor behavior and executive function. However, when looking into the discussion, the tone was set to relate the results to the neural efficiency hypothesis. This contradiction is confusing. Hence, the inference in the direction of the effect experience on neural activity is relatively weak, as the dependent variables in this study did not provide the support to correlate the motor behavior (Flanker test) and executive function or neural efficiency (neural activity).
Additional comments: The results section is ambiguous. Besides listing the significant differences, the authors are recommended to point out the directions, e.g., the control group showed lower ACC than the novice group.


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: EFFECT OF SHOOTING EXPERIENCE ON EXECUTIVE FUNCTION: DIFFERENCES BETWEEN EXPERTS AND NOVICES
Review round: 3
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: This reviewer appreciates the effort for the revision by the authors. I only have few minor issues that needs to be addressed before this manuscript moving toward publication.

1. In abstract, please explicitly indicate the main findings rather than just mentioning the group differences.

2. Please create a table showing all the statistical results for the ANCOVA tests. In this version, the authors did not report the statistical findings for the covariates.

3. The headings for the tables are incorrect. Please carefully check any potential mistakes.


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: EFFECT OF SHOOTING EXPERIENCE ON EXECUTIVE FUNCTION: DIFFERENCES BETWEEN EXPERTS AND NOVICES
Review round: 4
Reviewer: 1

Output:
Basic reporting: The authors have done a great job of updating and revising the manuscript with a more informative and meaningful addition to the literature.

However, there are amendments that the authors are encouraged to revise to elevate the overall contribution of the paper to this research field.

General:
1.	Abstract. In the conclusions, what do the authors mean precisely concerning “plasticity” in the current manuscript? In the sense of a cross-sectional study, how did the authors measure the shooters’ plasticity?
2.	Terminology. Please be cautious regarding the difference between exercise and motor skills. One specific term used in this manuscript is particularly confusing, namely, exercise. For example, on line 12, the authors described the effects of open and closed exercise and their possible links to the executive function. However, this manuscript focused on the different experience on the motor skill, specifically, shooting, and its relation to the executive function. The authors are recommended to be clearer to use motor skills instead of exercise as the definition is not the same.
Experimental design: Please see the general comments below
Validity of the findings: Please see the general comments below
Additional comments: Specific comments:
1.	Line 22. It might be nice to have a concluded statement here to finalize the studies mentioned above.
2.	Line 23-33. Two disconcert concepts are listed in this paragraph. Line 23-31 is addressing the relationship between closed skill sports and the importance of executive function. However, line 31-33 is recommended serving as the title sentence of this paragraph as it might increase the reading flow of the readers.
3.	Line 43. Self-repression. Please justify this term and may be a good idea to cite the article that supports this statement.
4.	Line 45. Closed skill sport? The authors seem not clear to differentiate the concepts between exercise and sport. A precise proofread is recommended for the entire manuscript.
5.	Line 45, the final paragraph in the introduction. The reader might wonder what prompted the authors to run this experiment as there is no research question was addressed.
6.	Line 48. Regarding the Flanker task, the author might want to clarify what mental factors or constructs the Flanker task can measure and the rationale of using the Flanker task in the current study.
7.	Line 62. Athletes. Do the authors mean novice shooters here?
8.	Line 136. Please specify the significance of the main effect here.
9.	Line 154. It might be better to start discussing the results of RTs in another paragraph to improve the overall readability of this paragraph.
10.	Line 161. Do the authors mean “faster” response speed here?
11.	Line 168. The authors claim in advance that two years of clay pigeon training is good enough to make the shooters from a novice to a professional shooter. Nevertheless, when conducted this experiment, the average training year of the novice group was 3.39 years. How do the authors persuade the readers that this was a well-controlled experiment?
12.	Line 172. The authors try to discuss “again” the results of accuracy in this study. Would it be a good idea to move this part into the previous part (Line 146) to make the discussion session more streamlined?
13.	Line 176. Please check the citation of Wang et al. (2013). Again, it should be closed or open skilled sports. Not exercise.
14.	Line 185. How do the authors define the “plasticity” in this study? Have the authors measured the plasticity in this manuscript?


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

Input:
Title: EFFECT OF SHOOTING EXPERIENCE ON EXECUTIVE FUNCTION: DIFFERENCES BETWEEN EXPERTS AND NOVICES
Review round: 4
Reviewer: 2

Output:
Basic reporting: See the general comment.
Experimental design: See the general comment.
Validity of the findings: See the general comment.
Additional comments: The manuscript has been improved significantly. I only have some minor comments for further improving the manuscript.

1.The conclusion should be revised to be in line with the findings. I believe this study could not examine the characteristics of sports because only one type of sport was examined.

2.The English writing could be improved in order to enhance its readability of the manuscript.

3.Please correct the reference format.


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

Input:
Title: EFFECT OF SHOOTING EXPERIENCE ON EXECUTIVE FUNCTION: DIFFERENCES BETWEEN EXPERTS AND NOVICES
Review round: 5
Reviewer: 1

Output:
Basic reporting: After the revision, I have no further questions regarding the manuscript. There's one minor issue that the authors might want to revise is the in-text citation. For instance, line 13 (Tsai and Wang, 2015). The authors may want to check the format of in-text citations throughout the manuscript.
Experimental design: The experimental design is now clear and well-addressed.
Validity of the findings: No further questions regarding the findings.
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: GROUND BEETLES (COLEOPTERA; CARABIDAE) AS AN INDICATOR OF ONGOING CHANGES IN FOREST HABITATS DUE TO INCREASED WATER RETENTION
Review round: 1
Reviewer: 1

Output:
Basic reporting: Title
The title is clear and properly reflect the content.
Abstract and key words
The abstract is suitable and basically good.
Line 17 I think that the aim of your study is not "to try" but just "to assess". Please improve it.
Line 17-20 This sentence is definitely too long. Please divide it. It will make the goal more understandable and transparent.
Line 20-21 Sentence need the language improvements.
Line 24 Remove "observed". Please avoid redundant sentence structure or words.
Introduction
The introduction is comprehensive, but needs some corrections and explanations. Moreover in the title of the paper you use " ground beetle (Coleoptera; Carabidae) as an indicator...", please develop this thread in more detail in the introduction.
Line 52-54 Please do the language improvements of this sentence.
Line 60 I propose to add some reference to confirm this statement.
Line 61-65 Too long sentence. Please divide it.
Line 67 Remove "to try", it is not a scientific statement. Use just "evaluate..."
Discussion and Conclusions
Discussion is interesting and all-embracing.
References
Literature is well-chosen, but only three articles are from the last three years. Can you add more recent references? It will also emphasize that your research is current.
Table 2 There is "zone". Please clarify it and be consistent throughout the text.
Table 3. Please do not double Carabid/Carabidae in table caption.
Figure 2 Please remove the grid lines from the chart. Figure 2 a- axis signature should be "species richness", b- abundance. It should be the same as in the figure caption. The style of figure 2c differs slightly from a and b.
Figure 3 Please remove the grid lines from the chart. Please sign the axes on figure A, B and C.
Figure 4. Please sign the axes on figure A, B and C. Add the meaning of the abbreviations to the figure caption.
Experimental design: Material and Methods
Line 75-79 Once again, too long sentence.
Line 79 "Object" is not appropriate term. Maybe please use for example "study site"
Line 85-88 What does it mean "sphere". It's a strange term, rather rarely used. For me it looks like transect of five pitfall traps...or three habitats (A, B, C).
Line 94-95 Use English name in brackets.
Line 102 "and" should be remove, use comma.
Line 112 Here you use transect, and it is good expression. Use the same term throughout your work. I think the term sphere is misleading.
Line 121 "During the capture of beetles..." this is not good English expression. Please improve it.
Line 152 It should be GLM, not GML. Did you check the distribution of variables. You don't mention it in Data analysis.
Line 157 Why you used the Morisita's measure of similarity, not e.g. Bray-Curtis?
Line 161 I am not sure that PCA is appropriate analysis. Principal components analysis is a variable-reduction technique that shares many similarities to exploratory factor analysis. Its aim is to reduce a larger set of variables into a smaller set of 'artificial' variables, called 'principal components', which account for most of the variance in the original variables. In your case I propose to use RDA analysis (Redundancy analysis with Monte Carlo permutation test) because it is a method to extract and summarize the variation in a set of response variables that can be explained by a set of explanatory variables.
Line 167 "species classified as belonging to..." , please delete "classified as".
Line 178 Remove "once"
Line 194-198 Too long sentence
Line 219 What percentage of variance do the axes describe? As above I think the RDA analysis would be appropriate here not PCA.
Validity of the findings: no comment
Additional comments: The manuscript is concerned with the analyse the impact of the land drainage measures implemented under the framework of the above program on assemblages of ground beetles. This is very interesting study which try to assess the changes in Carabid community under land drainage works. The study was conducted in 2009, 2012 and 2013 in area formerly used for farming and then afforested and turfed. The authors choose two study sites differed by moisture conditions and distance form the retention water reservoirs. Ground beetles were collected in from three transects of pitfall traps set in study site I and three in study site II. I think this study is interesting and it is important to know the shift in ground beetle species diversity in such conditions especially in case of protection of rare and valuable species. However there are some obscurity. My recommendation for the current submission is to Minor revision. A list of comments with line numbers is given below.


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: GROUND BEETLES (COLEOPTERA; CARABIDAE) AS AN INDICATOR OF ONGOING CHANGES IN FOREST HABITATS DUE TO INCREASED WATER RETENTION
Review round: 1
Reviewer: 2

Output:
Basic reporting: The work is, unfortunately, written in very inadequate English, with several important terms erroneously used (e.g. for feeding type or trophic group, the word "trophy" is used) that leaves the reader grasping for meaning.
The conceptual background is murky, and there is considerable confusion about water retention (which is not drainage), as well as what exactly carabids will indicate in this context. The aims of the work are not clear.
As there are no specific hypotheses, results are not well structured, and the impression is that the authors themselves are unsure what precisely their findings mean? This leads to very simple and qualitative statements, like the presence of ca. 30% of the regional fauna, the appearance of moisture-preferring species, stb.
Diversity analysis is restricted to a very simple and indequate method.
Overall, these do not convince the reader that there is much new in this work.
Experimental design: There is no real repetition here - only one setup is studied, and the trapping effort is decidedly modest (15 traps). Strange terminology makes me a bit unsure about important details (e.g. what is "sphere"?)
The research question is not well defined, it seems like merely a "let's see what happened" type.
The diversity evaluation is very superficial, and there is no test about the completeness of the study - for example, by species accumulation curves, or an estimation of the number of species present.
The claimed information gap is only the scarce studies of peatlands of the study region. No justification is given why does this matter?
Validity of the findings: Not a big study with insufficient replication. This undermines the validity.
No well-formulated research questions, thus "results" leave the reader uninterested, and makes difficult to draw meaningful conclusions. In fact, those are very non-specific and qualitative. Imprecise and erroneous terminology adds to the confusion (re. drainage vs. water retention).
Additional comments: This work aimed to examine the changes in carabid assemblages triggered by the establishment of a water retention scheme. Unfortunately, the language is so bad that in many places, the reader has to guess the intended meaning. You will have to ask for help from a colleague with a better command of English.
You use the term community vs. assemblage as if they were equivalent. I suggest that your study concerns a taxonomic group and not an ecological one, so I'd use assemblage throughout. The correct term then would be "ground beetle assemblage/s" or "carabid assemblage/s".
Your trapping intensity is not high - at minimum, you have to prove its completeness by the use of a species-accumulation curve. Diversity evaluation is very primitive - use the scheme suggested by Henderson & Southwood's Ecological methods (2016, Wiley).
You also have to think about indication - what do you want to indicate and which parameters of the carabid assemblage would indicate that? This is not mentioned nor elaborated.


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: GROUND BEETLES (COLEOPTERA; CARABIDAE) AS AN INDICATOR OF ONGOING CHANGES IN FOREST HABITATS DUE TO INCREASED WATER RETENTION
Review round: 1
Reviewer: 3

Output:
Basic reporting: The manuscript is written in good English. The introduction provides with a sufficient overview of the scientific background of the paper with well-chosen references. The structure of the manuscript is according to the instructions given by PeerJ.

All table and figures are relevant for the paper and the figures are of good graphical quality. However, the captions of figs. 2 and 4 have to be improved. In the caption to fig. 2 lacks the information what is shown by the error bars. Did you calculate standard deviation or standard error? This is an important information. The letters “a”, “b, and “c’ should be in capitals as in the figure itself. Please add also the unit for MIB, which is mg. In the caption to fig. 4 it would be helpful for the reader to add at least a reference to the methods with respect to the abbreviations of the ecological groups.

According to the PeerJ policy the raw data are provided with the manuscript.
Experimental design: The manuscript is based on original primary research, which falls into the general scope of the journal. The basic purpose of the study is well defined (lines 66-69), but the authors might formulate some expectations (research hypotheses). Which kind of changes in carabid assemblages are expected? Which differences regarding the changes are expected between the different studied spheres?

The research was carried out accurately according to standards in the research on ground beetles (Carabidae).

The methods description should be improved. Information about the basic samples used in statistical analyses is missing. The authors mention that there were 15 traps in each object (5 per transect = sphere), which were emptied every 14 days. However, it is not clear if the material from the14-day-intervals were later pooled for each trap and if each trap was used as sample. Unfortunately the supplemental files “…raw_data.csv” and “…Statistical_data.csv” also give no precise information concerning this matter. The file, “Statistica_data.csv” contains several lines with data for each trap in each year (for example nine for the year 2009). Thus, I assume that these are nine 14-day-intervals. However, this should be indicated in the file. The file “…raw_data.csv”, however, shows only 5 columns for zone A in 2009. I assume that this are the data for the individual traps pooled. Instead of using “A”, “B”, etc. in this table I propose to use the respective trap numbers. From the file “…Statistical_data.csv” I would conclude that each 14-day-interval was used as basic sample in the statistics, but from fig. 4 I would conclude that the pooled data were used. Therefore, it has to be precisely described in the methods which basic samples were used for which statistical analysis.

I also suggest to provide more details regarding the PCA analysis (lines 159-162). Why was a linear method (PCA) selected instead of an unimodal method (CA)? Which settings (for example regarding data transformation) were used in the analyses?
Validity of the findings: The manuscript deals with an interesting and important topic. The authors accentuate with indication of reference that studies on entomofauna inhabiting areas submitted to land drainage programs are rare, hence underlining the importance of the research for a wider audience. The underlaying data seem to be robust and statistically sound. However, as mentioned above, I recommend some improvements in the supplemental files.

Results are described accurately, but I like to encourage the authors to rethink the description of the results of the PCA (lines 219-229). Even if I agree with the general trends formulated by the authors, the results are complex and not all assemblages of the respective years follow the described trends entirely. Therefore, I recommend to emphasize that the results have more tendency character. I propose also to emphasize the MIB indicator, since there is a clear tendency that assemblages from 2009 are characterized by lower MIB values, what is in accordance with the dominating of large zoophages after the retention project, as stated by the authors.

The results are discussed in a though-out manner taking into account an adequate number of references.

The conclusions formulated by the author are well stated. One or two sentences regarding possibilities of practical application of the results might be added.
Additional comments: Line 43: Probably it should be “mentioned” instead of “maintained”. Please check.

Line 55: The reference “Kosewska et al., 2015” is not included in the reference list. Instead, there is a reference “Kosewska & Nietupski, 2015”. Please specify.

Line 146: Has to be “Pacuła” instead of “Pacuk”.

Line 524: Please add information when the website was accessed.

Line 525: The reference “Zabrocka-Kostrubiec, 2008” should be shifted to the end of the reference list.


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: GROUND BEETLES (COLEOPTERA; CARABIDAE) AS AN INDICATOR OF ONGOING CHANGES IN FOREST HABITATS DUE TO INCREASED WATER RETENTION
Review round: 2
Reviewer: 1

Output:
Basic reporting: All my comments have been adressed.
One note: I found a small literal erros in the reference Igondová & Majzlan, 2015 (line 241 is "Igondová" and line 432 is "Igondowá" please improve it.
Experimental design: All my comments have been adressed.
Validity of the findings: All my comments have been adressed.
Additional comments: Thank the Authors for revising the manuscript. All my comments have been taken into account, so my recommendation for the current submission is to accept to 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: GROUND BEETLES (COLEOPTERA; CARABIDAE) AS AN INDICATOR OF ONGOING CHANGES IN FOREST HABITATS DUE TO INCREASED WATER RETENTION
Review round: 2
Reviewer: 2

Output:
Basic reporting: Formal flaws of the earlier version of the manuscript are corrected in the revised version. Due to the adding of research hypotheses the goals of the study are more clear now. The replacement of the PCA by an RDA clearly improves the manuscript.
Experimental design: The research design still could be better explained in the methods. The authors state in the response to my review that “each trap was treated as a replication. This information has been added to the manuscript text”. However, I cannot find this information in the revised manuscript! If I understand well, each trap as a replication was used for GLM analysis (Table 2), mean values of species richness, abundance and MIB (Figure 2), NMDS (Figure 4) and RDA (Figure 5). The authors should clearly state it. On the other hand, if I understand well, for calculation of species numbers, individual numbers and Shannon Diversity (Table 3) and for the species accumulation curves (Figure 3) the data of the five traps of each transect were pooled. This should be also stated in the text.
Validity of the findings: Instead of two somewhat differing supporting files, the authors provide now with one file, which shows in a sufficient manner the full set of raw data.
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: INTEGRATED JERK AS AN INDICATOR OF AFFINITY FOR ARTIFICIAL AGENT KINEMATICS: LAPTOP AND VIRTUAL REALITY EXPERIMENTS INVOLVING INDEX FINGER MOTION DURING TWO-DIGIT GRASPING
Review round: 1
Reviewer: 1

Output:
Basic reporting: This manuscript describes preference in the perception of motion rendered on a robotic hand. The scientific approach is valid but the quality falls short of usual standards, and is not sufficient to support the claims of the title and abstract.
Experimental design: - The two experiments, screen and VR, don’t test the same context, and the authors didn’t take into consideration that they shouldn’t be compared directly without discussing these differences. In particular, the n is different but the authors claim it is not an issue (as small n yield false negative and here we have only positive results) yet don’t mention it when making claims about the differences between real screen and VR (p12, l48). This aspect (how is the motion presented?) is not informative for the main argument of the paper regarding motion preference and almost invalidates the other results.
Validity of the findings: - Most important, claiming a preferences in kinematics for artificial agents on the basis of a single experiment with a very simple action (grasp, but mostly transport cf point 1), on one robotic hand with a sample of 22 subjects and 9 kinematics is simply insufficient nowadays, where, in particular for behavioral studies, tens of participants undergo a large number of conditions in order to support the conclusion. In the present case, for example, are particularly missing a larger number of different kinematics in a second experiment, a larger sample to adequately assess inter individual variance, a replication with other robots and actions, a direct comparison with the same actions performed by a human hand with the kinematics of a human hand manipulated along the same dimensions to demonstrate the effect is specific to the robotic hand or simply a feature of the normal action perception system that generalizes to artificial agent. These are just a few examples of the comparisons that would be required to support convincingly the main argument of the manuscript.
Additional comments: This manuscript describes preference in the perception of motion rendered on a robotic hand. The scientific approach is valid but the quality falls short of usual standards, and is not sufficient to support the claims of the title and abstract.

- The article talks about kinematics of grasp, but the three markers are on the index finger and none on the thumb, so it is already a degraded recording of a grasp (transport? index flexion?), and not a two-digit grasping as claimed in the title.

- The two experiments, screen and VR, don’t test the same context, and the authors didn’t take into consideration that they shouldn’t be compared directly without discussing these differences. In particular, the n is different but the authors claim it is not an issue (as small n yield false negative and here we have only positive results) yet don’t mention it when making claims about the differences between real screen and VR (p12, l48). This aspect (how is the motion presented?) is not informative for the main argument of the paper regarding motion preference and almost invalidates the other results.

- The explanations of the differences in results in Table 2 are not convincing. Actually, the RESULTS of Table 2 are not the same as in the previous version of the manuscript I reviewed, which is VERY puzzling:
Current:
Bvs.A 0.7 78726
Bvs.C 0.1 0.0
Previous:
C vs. B 0.7 78726
A vs. B 0.1 0

- Most important, claiming a preferences in kinematics for artificial agents on the basis of a single experiment with a very simple action (grasp, but mostly transport cf point 1), on one robotic hand with a sample of 22 subjects and 9 kinematics is simply insufficient nowadays, where, in particular for behavioral studies, tens of participants undergo a large number of conditions in order to support the conclusion. In the present case, for example, are particularly missing a larger number of different kinematics in a second experiment, a larger sample to adequately assess inter individual variance, a replication with other robots and actions, a direct comparison with the same actions performed by a human hand with the kinematics of a human hand manipulated along the same dimensions to demonstrate the effect is specific to the robotic hand or simply a feature of the normal action perception system that generalizes to artificial agent. These are just a few examples of the comparisons that would be required to support convincingly the main argument of the manuscript.


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

Input:
Title: INTEGRATED JERK AS AN INDICATOR OF AFFINITY FOR ARTIFICIAL AGENT KINEMATICS: LAPTOP AND VIRTUAL REALITY EXPERIMENTS INVOLVING INDEX FINGER MOTION DURING TWO-DIGIT GRASPING
Review round: 1
Reviewer: 2

Output:
Basic reporting: Introduction
The introduction is generally clear and concise. I think there should be more background information about what jerk is and how it is related to human movement (e.g. what is the normal profile for humans compared to robots).

Towards the end of the experiment, please provide an overview of all the experiments (e.g. that you first collect kinematic information, add this to an animation based on a recorded robot model…..etc). Also, more rationale needs to be added for experiment 3, which seems to cover perspective and embodiment. This will enable the reader to more easily process the methods section.

References to some materials are missing (states (see §)) and some of the figures are not referenced in the text
Experimental design: The study is within the scope of the journal.
The research question is well defined and relevant - this is an unexplored area and i like the quantitative and detailed approach the authors use.

Methods
The layout of the methods and analysis is unclear. My questions below could probably be answered if the methods were structured so that each experiment is presented separately, followed by a general discussion.  For example:
Experiment 1: methods, analysis, results, brief discussion
Experiment 2: methods (making use of exp 1 data), analysis, results, brief discussion. Make it clearer that kinematics were added to an animation of the hackberry robot
Experiment 3: methods, analysis, results, brief discussion

Equipment – this states that there were four main devices, but there are actually five

Experiment 1 – how is the data used? The rationale for this needs to be clearer and the use of the kinematics could be added to experiment 2 methods (developing the stimuli). How were those specific kinematics chosen?
Experiment 2 – indicate that the stimulus was robotic looking (based on the hackberry model)
Experiment 3 – it is not clear when or why the participants would move the hand stimuli. How are they stopped from moving them during each trial?  Overall, there needs to be more description of the procedure and rationale for this experiment.
Validity of the findings: Results
Experiment 2 and 3 – please add statistics for correlations (r/p values)

Discussion
Comparing laptop and VR experiments. The following lines need to be backed up in the results section. The linear trend/correlation is mentioned for the laptop experiment but not for the VR experiment . Please document these differences statistically in the results (and /or descriptively).

“but the VR experiment showed that minimum jerk was not preferred to slightly jerkier, human like kinematics (figures 8 and 9). First, whereas the preference pattern appeared to be approximately linear, or v-shaped for the laptop experiment (figure 8), the pattern was sigmoidal, or s-shaped in the VR experiment (figure 9). “

This sentence does not make sense:
“In the experiment, subjects rated prosthetic hands with human skin texture as more eery than all of: mechanically exposed robot hands, prosthetic hands with human skin texture, and actual human hands.”

Please provide a little more discussion around the potential use of the findings (for robotics/prosthetic or neuroscience research). The authors briefly mention previous findings that have used different appearances, but a more detailed discussion on how appearance and kinematics might interact would be valuable.
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: INTEGRATED JERK AS AN INDICATOR OF AFFINITY FOR ARTIFICIAL AGENT KINEMATICS: LAPTOP AND VIRTUAL REALITY EXPERIMENTS INVOLVING INDEX FINGER MOTION DURING TWO-DIGIT GRASPING
Review round: 2
Reviewer: 1

Output:
Basic reporting: The authors have answered my comments
Experimental design: The authors have answered my comments
Validity of the findings: The authors have answered my comments
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: ASSESSING THE PROGNOSTIC SCORES FOR THE PREDICTION OF THE MORTALITY OF PATIENTS WITH ACUTE-ON-CHRONIC LIVER FAILURE: A RETROSPECTIVE STUDY
Review round: 1
Reviewer: 1

Output:
Basic reporting: The article is well-written in English language, although there are some minor erratum along the text that should be corrected in a further revised version.
Experimental design: The study is well designed and address the hypothesis. However,  I think it would be interesting to perform an additional analysis to find the optimal cut-off point of each ROC curve.

In table 3 authors already present a cut-off point, but it is not mentioned along the manuscript if this is the optimal cut-off point based on the Youden's index. If so, authors should mention it in the methodology section. If not, I would recommend to calculate the "optimal cut-off point" where both sensitivity and specificity maximize using the above mentioned Youden index.
Validity of the findings: No comment.
Additional comments: This is an interesting study that compares the predictive and discriminative power of several scores in acute-on-chronic liver failure patients.

In addition to my previous comments (correct some minor erratum throughout the manuscript and calculate the optimal cut-off point for each ROC curve), I would recommend authors to summarize the main findings in the section "Predictive ability for 28-day, 3-month and 6-month mortality in ACLF patients." As authors state, these findings are shown in Table 3, so I recommend to write only the main findings in order to facilitate the reading.

Despite these minor issues, I think this is a great and interesting 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: ASSESSING THE PROGNOSTIC SCORES FOR THE PREDICTION OF THE MORTALITY OF PATIENTS WITH ACUTE-ON-CHRONIC LIVER FAILURE: A RETROSPECTIVE STUDY
Review round: 1
Reviewer: 2

Output:
Basic reporting: No comment
Experimental design: - line 179,180 and table, liver failure, and encephalopathy were mentioned separately as causes of death at 6 months. You can possibly combine them as liver-related mortality and subgroup causes.
- Do you have reasons for loss of follow up?
Validity of the findings: -line 272, you mentioned patients required treatment for bleeding oesophageal and gastric varices. Do you have data on the type of variceal bleed and treatment modality?
- For a single-centre study, the conclusion is too strong to generalize results to whole China.
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: ASSESSING THE PROGNOSTIC SCORES FOR THE PREDICTION OF THE MORTALITY OF PATIENTS WITH ACUTE-ON-CHRONIC LIVER FAILURE: A RETROSPECTIVE STUDY
Review round: 1
Reviewer: 3

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: The authors present a retrospective study for assessing the prognostic scores for the prediction of the mortality of patients with acute-on-chronic liver failure. There are major points that need to be addressed:
1. It is important to have a validation cohort to validate the performance.
2. The results are written unclear. For example, the authors don't need to write any AUC values for every scores. They could be explained by only a table or figure and with some text description.
3. How did the authors define normal distribution and abnormal distribution?
4. ROC curve and AUC had been used in previous works in biomedical such as PMID: 31921391, PMID: 31277574, and https://doi.org/10.1016/j.neucom.2019.09.070. Therefore, the authors are suggested to refer more works in this description.
5. It is important to have some comparisons to the previous works on the same problem.
6. The ROC curves should be presented together with AUC values (i.e. Fig. 2)


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: ASSESSING THE PROGNOSTIC SCORES FOR THE PREDICTION OF THE MORTALITY OF PATIENTS WITH ACUTE-ON-CHRONIC LIVER FAILURE: A RETROSPECTIVE STUDY
Review round: 2
Reviewer: 1

Output:
Basic reporting: The article is well-written, and authors have made an effort and corrected the erratum detected in the prior version.

However, there are some minor issues to be corrected:

Line 110: "The MELD: 3.8×log (bilirubin) +9.6×log(creatinine) +11.2×log (INR)+6.43 (reference 8)."

It seems this sentence is incomplete. I would rewrite it as "The MELD formula was: ..."

Line 111: please, correct "below" instead of "bellow"

Line 147: There are 102 patients in this study.

I think this sentence should be in past tense: "There were 102 patients in this study."

Line 271: "The predicting value of the CTP, MELD-Na, and MELD scores in ACLF is not complete prefect because indicators reflecting systemic inflammation and organ failure is lacking."

I would suggest: "The predicting value of the CTP, MELD-Na, and MELD scores in ACLF is not completely perfect because indicators reflecting systemic inflammation and organ failure is lacking."

Nonetheless, as aforementioned, the article is well-written and references are relevant. Tables and figures summarize the main findings and are completely understandable.
Experimental design: The authors have included the information about the Youden index in the methods section, as requested. However, I would suggest to reference this work:

Youden, W.J. (1950). «Index for rating diagnostic tests». Cancer 3: 32-35 (PMID:15405679)

Apart from this suggestion, I have no further comments. The study question is well defined and addressed, and methodology is sufficiently explained.
Validity of the findings: I have no suggestions nor comments regarding the validity of findings. Conclusions are well defined and answer the research question based on the findings, and the clinical relevance of these findings is notable.
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: ESTIMATING THE IMPACT OF MOBILITY PATTERNS ON COVID-19 INFECTION RATES IN 11 EUROPEAN COUNTRIES
Review round: 1
Reviewer: 1

Output:
Basic reporting: In the section of Introduction, Wuhan is city not province in China, please correct it.
The writing of the manuscript is professional and experimental design is reasonable and interesting. Interpretation of data supports the hypothesis and discussion of data  provides significant value to future epidemiologists to conduct research on the epidemic of COVID19.
Experimental design: The experimental design is logical and provides valuable reference for future research on epidemics.
Validity of the findings: The current findings are quite interesting and consistent with the current strategies to curtail the COVID-19 pandemic disease.
Additional comments: The current research is quite interesting with logical design and preferable result interpretation.


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

Input:
Title: ESTIMATING THE IMPACT OF MOBILITY PATTERNS ON COVID-19 INFECTION RATES IN 11 EUROPEAN COUNTRIES
Review round: 1
Reviewer: 2

Output:
Basic reporting: The paper suffers from many typos and inconsistencies in the formulae, which make the flow of the paper difficult to follow. Often, the impression is that the paper has been written too quickly. For example:

line 100: should use l_(k,t,m)
line 109: R_0 should be replaced why R_(0,m)
line 109: the Gaussian distribution also have a variance parameter. where is it?
line 130 and following: pi_m should depend on t as well
line 134: the construction that leads to this parameterization of the gamma distribution is not clear at all.
line 141:the cumulative number of deaths has not been defined so far. it comes afterwards, but in a different form
line 136: the logic underlying the discretisation step should be clarified
Experimental design: The model has the merit of introducing mobility data as predictors of the reproduction rate and, consequently, of the number of cases and number of deaths.

It suggests to do so using a Bayesian model, trying to extend the Imperial College London work which does not allows for a differential impact of mobility on R_0 among different countries.

The aim is valid but the methods employed to reach that aim are, in my opinion, weak. First of all, the logical flow of the model does not allow its interpretability. The authors should first explain the infection model, then the reproduction rate (depending on mobility) and finally the death model.

Instead, the reproduction rate model is introduced first, with  very a strong assumption on the baseline R_0: that is assumed constant across countries and time. This assumptions imply no effects pf public health policies different from mobility restrictions (unrealistic); no effect of testing and health procedures, different in each country, and so on..

The infection model is then very cumbersome, starting with a Negative Binomial for the number of deaths (why not Poisson? it is not explained) , to a sequence of Gamma distributions which are convoluted in an unclear way, for the infection - to death part.
The number of cases follow a renewal process which depend on R_0 and on a gamma distribution for the incubation time which is , once more, constant in time and space: another unrealistic assumption.

In addition, all assumed distributions, and their parameterisations, are described without explanations, and without any intuition on why they are so.

Finally, the MCMC computations are described in a rather obscure way. For example: why eight chains were run? why to use only the Gelman and Rubin to detect convergence? as here the parameter distribution to be approximate is multivariate and not univariate.
Validity of the findings: The main finding (that grocery and pharmacy mobility explain 97% of the reduction of R_0) is very strong, and should be checked against a better, and clearer model, as described above.

Also the authors should compare their model with a SIR based model, that allows for the introduction of covariates, and allows for estimates to vary over time, as the health system of each country goes through different stress (and testing procedures) phases. See e.g. the Poisson autoregressive models developed by some authors to model covid-19 contagion (Agosto et al., 2020)

The paper has a robustness section, but it appears very limited, considered the amount of assumptions made by the authors.

Also, being the paper Bayesian, there is no attempt to show the posterior distribution of R_0 and the posterior distribution over the model space, which would give a better explanation of "the importance of each mobility data".
Additional comments: The paper deals with an important problem. The proposed methods should be better formulated, in a simpler and clearer way, also comparing the model not only with the Imperial College paper, but with the range of papers available to model covid-19 contagion.

To understand the proposal, the authors should pay much attention to the mathematical formulation, and specify each assumption and their rationale, as exemplified by my comments above

In particular, the authors should develop the model in the logical-statistical order of the variables: contagion model, R_0 model, contagion to death model.

The Bayesian approach should either be abandoned or stretched to a complete framework that includes the presentation of variable importance in terms of posterior probabilities of the different models (and features). Also convergence of the posterior distribution must be better 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: ESTIMATING THE IMPACT OF MOBILITY PATTERNS ON COVID-19 INFECTION RATES IN 11 EUROPEAN COUNTRIES
Review round: 1
Reviewer: 3

Output:
Basic reporting: The language is clear, and the author has also used enough references. The figures are also clear.
Experimental design: The author built a model to predict the epidemic to help the government making decisions based on the feedback of the model.
The authors are concerned that the COVID-19 will further spread upon the lifting of the restrictions around the world. Therefore, they are motivated to build the model to understand and predict.
They evaluated the problem of the current model and gave their modification to the model by addressing the effects of cultural and sociological differences.
They showed that 3-week forecast of their model has a smaller error for government to analyze if NPI are working.
Their model is trained from 30 days, which has enough dataset.
The only concern for this model is there are some assumptions that are made by the author, it would be great if the author can spend 1-2 sentence to explain the assumption.
Validity of the findings: They also validated the model using the 3-week data available and fit the data with the model to compare with ICL model.
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: ESTIMATING THE IMPACT OF MOBILITY PATTERNS ON COVID-19 INFECTION RATES IN 11 EUROPEAN COUNTRIES
Review round: 2
Reviewer: 1

Output:
Basic reporting: The paper is fine now
Experimental design: The paper is fine now
Validity of the findings: The paper is almost fine. The authors should include at least one reference on SIR models and their extension. I suggest Agosto, Giudici. (2020) A predictive model for COVID-19 dynamics. Risks. https://doi.org/10.3390/risks8030077
Additional comments: The authors took into account my suggestions in their revision. They should include at least one paper reference for Sir models as I suggested 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: ESTIMATING THE IMPACT OF MOBILITY PATTERNS ON COVID-19 INFECTION RATES IN 11 EUROPEAN COUNTRIES
Review round: 2
Reviewer: 2

Output:
Basic reporting: The author sucessfully addressed the questions in the precious review. There are some minor points here:
PDF file, line 67-68, ‘Likely, different regions respond differently to the same NPIs, why it is vital to consider the effect of NPIs country wise’, this sentence does not read smooth.
Line 144-145: ‘The impact on R0 is assumed to be almost instantaneous, with an effect that decreases quickly with time, why a narrow gamma distribution was chosen’, this sentence does not read smooth

Line 230-231: ‘The R0 estimates are uncertain in the beginning of the epidemic when cases are few, why they are smoothed using one-week averages’ doesn’t read smooth

In table 2, last row, ‘Average absolute ror’ should be ‘Average absolute error’
Experimental design: The experiment design was reasonable.
Validity of the findings: The author validated the findings by using the model independently from the case data.
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: INTEGRATED ANALYSIS OF THE TRANSCRIPTOME-WIDE M6A METHYLOME IN PREECLAMPSIA AND HEALTHY CONTROL PLACENTAS
Review round: 1
Reviewer: 1

Output:
Basic reporting: The hypothesis that “to speculate that deregulation of m6A modification may also be
associated with PE” is acceptable. But Taniguchi et al. have been already published the role of m6A in PE (Taniguchi et al. PMID: 31914637. FASEB J. 2020 Jan;34(1):494-512. doi: 10.1096/fj.201900619RR.). The authors should refer this article.
Experimental design: The number of subjects is small. The authors should validate their results as adding validation subjects and examine protein levels of the genes which differentially expressed m6A peak in PE.
Validity of the findings: The functional meanings of m6A modifications is differed by its site in transcript and by which m6A reader that recognize m6A modifications bind on those sites. Hence, the authors should provide annotations of m6A peak regions in Table 3 such as 5’UTR, the beginning, the middle, and the last part of CDS, and 3’UTR.

The authors should provide not only the top 20 differentially expressed m6A peaks in PE but also whole differentially expressed m6A peaks data as supplementary data.

In conclusion, “the m6A RNA methylation landscape; reveal the potential functions of this methylation in the regulation of RNA metabolism” is based on results. However, “various biological processes in PE that may provide promising therapeutic targets for the prevention and treatment of PE.” is a rough conclusion, because it is unclear whether the modifications by methylation enhance protein levels or not. As mentioned above, authors should check changes in protein levels of differentially methylated transcripts.
Additional comments: In the present manuscript entitled “Integrated analysis of the transcriptome-wide m6A
methylome in preeclampsia and healthy control placentas”, Wang et al. explored placental molecular pathology of preeclampsia (PE) by introducing MeRIP-Seq. It revealed that PE accompanied post-transcriptional changes in several genes with modifying adenosine to N6-mehyladenosine or vice versa in their transcripts. These results suggest potential function of m6A modification in incidence of PE. However, there are some critical points as follows.

Major comments
1.	The sample size in this study is too small to conclude. In addition, the eventual m6A modification’s effects on gene expression is unknown. It is published that HSPA1A transcript increased m6A modifications at 5’ UTR during heat shock stress and which augment protein translation (Zhou et al. PMID: 26458103. Nature 2015 Oct 22;526(7574):591-4). Therefore, the authors should validate their results in protein levels as adding samples. Further, the authors should show the position of peak summit and in which transcript region (5’UTR, the beginning, the middle, and the last part of CDS, and 3’UTR) is located in peak region in table 3.
2.	The effects of methylation on transcripts fate depends on which m6A reader protein binds to m6A sites. The authors should also show the expression levels of m6A readers, writers, and erasers in each group from RNA-Seq results.
3.	Is there any contents in showing the m6A peak changes for each chromosome in Fig 3D? Are there significant differences compared to expression changes?
4.	Which genes were included in hyper-methylated and down-regulated, and hypo-methylated and up-regulated?
5.	The authors should provide mean and SD of m6A peaks height in each region of each group in addition to fold changes as for significantly different m6A peaks between PE and control.
6.	PE subjects delivered larger babies than normal subjects. It differs from the sample characters in Taniguchi et al.’s report. When did PE subjects in this study develop PE?

Minor comments
1.	Line 95. Was the mRNA mixed from the three different sites of placenta from an identical subject for MeRIP-Seq?
2.	Which version of Ensembl reference genome were referred for mapping?
3.	The authors fragmented RNA into 100-nt fragments for M6A-RIP. But sequencing was performed on pair-end 300 cycles protocol. It means one fragment was read twice from both directions. The authors should use single-end sequence data for mapping and peak detection.
4.	Line 207. Which value was adapted for cut off in filtering significant enrichment in GO analysis?
5.	Fig 3B and F. Which software did authors use for plot?
6.	“P” is missing in the title of Figure 3 and 4 for “preeclampsia”.


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: INTEGRATED ANALYSIS OF THE TRANSCRIPTOME-WIDE M6A METHYLOME IN PREECLAMPSIA AND HEALTHY CONTROL PLACENTAS
Review round: 1
Reviewer: 2

Output:
Basic reporting: no comment
Experimental design: Strengths:
Research questions is clearly defined with an identified knowledge gap.

Reasonable biological replicates and comparison groups included in the study.

Weaknesses:
Lack of orthogonal validation of sequencing results is a major weakness.
Validity of the findings: Weaknesses:
Key information/data, such as sequencing depth and sequencing data availability, are missing.

There are not validations for the sequencing results, which makes it difficult to evaluate the robustness of the analysis data and related biological interpretation.
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: INTEGRATED ANALYSIS OF THE TRANSCRIPTOME-WIDE M6A METHYLOME IN PREECLAMPSIA AND HEALTHY CONTROL PLACENTAS
Review round: 2
Reviewer: 1

Output:
Basic reporting: The profile of RNA m6A modification in PE placenta could be a breakthrough to reveal the mechanism of PE. However, there is a lack of verifications.
Experimental design: The sample size is small.
Validity of the findings: There are no additional experiments to verify their results or hypothesis.
Additional comments: The knowledge about RNA m6A modification is now widely accumulated in various samples. Therefore, subsequent verification is a necessity to accept this manuscript. I regret that the authors did not perform additional experiments.


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: INTEGRATED ANALYSIS OF THE TRANSCRIPTOME-WIDE M6A METHYLOME IN PREECLAMPSIA AND HEALTHY CONTROL PLACENTAS
Review round: 3
Reviewer: 1

Output:
Basic reporting: In abstract, authors described "However, the profiling of m6A modification and its potential
role in preeclampsia (PE) has not yet been studied." But there is a report regarding to profiling of m6A in PE placentas. It should be described like "The number of reports regarding to the profiling of m6A modification and its potential role in the placenta of preeclampsia (PE) is a little.

The authors should show the "particular site" of HSPA1A by genomic locus, and also should indicate it by an arrow in Fig 3G.

The annotations for Fig 3 is not matched in the manuscript.

There is no plot in Fig 4C.
Experimental design: As pointed out in the above section, this is not a first report that profiling of PE placentas were performed. The authors should make clear their original research aims.

line 201 to 207.
First, the authors should show the quality of their extracted RNA. Next, why have the authors show the results of only qRT-PCR even though they have done RNA-Seq?
The authors should show the expression levels by RNA-Seq results, too, regarding to the genes in Figure 1. When describing about gene expression, the gene names should be in italic.

Regarding to conjoint analysis, which category did the HSPA1A belong? There is no HSPA1A in table S3 although the authors show the upregulation o HSPA1A mRNA levels in Figure 6B. And what do the authors think about the final effects of each category to translation?
Validity of the findings: The authors should show the results of m6A peaks in gene level, too. How many genes have both up- and down- regulated m6A peaks? How many modified peaks are there in one gene?  When performing conjoint analysis, how did the authors divide the transcripts that both up- and down- regulated m6A peaks exist?

Why are the authors interested in the distribution of altered m6A peaks by chromosomes?What does it mean concerning m6A modifications? There is no consideration regarding to this result. The result of Fig 3E is not needed in this manuscript.

Regarding to Fig 3G and 3H, the authors should show the map of HSPA1A transcript so that the readers can know where are UTRs and where is the stop codon. In addition, the authors should show the peaks of HSPA1A in every 8 sample (4 PE and 4 Control). Furthermore, it seems there are two different blue colors in Fig 3G and H.

Regarding to Fig 5C, what relationship exist between m6A modification and the novel transcripts possessed coding capabilities? There is no additional experiments regarding these transcripts. The result of Fig 5C is not needed in this manuscript.

How does it work to final output when the m6A modification of "particular" HSPA1A changed from 1% to 2.5% of total in Fig 6A?  There is a dissociation between transcript levels and m6A % at "particular" site and protein levels.
Additional comments: line 275 to 276, the authors have not investigated "the role of placental m6A in PE" in this manuscript. The effects of alteration of m6A appear to be nothing more than speculation except HSPA1A. Therefore, it is overestimation. As well as the same reason, the results of GO or KEGG is just annotation. We do not know whether these pathways are activated or repressed eventually in PE placentas. Therefore the volume of discussion regarding to the results of GO or KEGG is too much.


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: DEVELOPMENT OF A NOVEL NANOFLOW LIQUID CHROMATOGRAPHY-PARALLEL REACTION MONITORING MASS SPECTROMETRY-BASED METHOD FOR QUANTIFICATION OF ANGIOTENSIN PEPTIDES IN HUVEC CULTURES
Review round: 1
Reviewer: 1

Output:
Basic reporting: This article is written in correct English. It is conform to professional standards os courtesy and expression.
This article should be develop some literature approaches notably in MRM approaches which are the most used actually.
The structure of the article should conform to an acceptable format but some figures must be changed.
Experimental design: This article aimed to develop an analytical method using liquid chromatography tandem mass spectrometry (LC-MS/MS) for the determination of angiotensin peptides (Ang I, Ang (1-9), Ang II, Ang (1-7), Ang (1-5), Ang III, Ang IV) in human umbilical vein endothelial cell (HUVEC) culture supernatant. However some studies have been already developped this type of approaches. The originality lies in the use of PRM mode and nano-HPLC. Nevertheless the authors do not speak of the MRM approaches developed previously which are also sensitive.
Why not use a nano-LC-MS/MS
Validity of the findings: Some problems in this study :

- Only one peptide is used to identify and quantify
- We don't see any extraction percentage ?  matrix effect ? (which is very important)
- The authors don't use radiolabelled standards (only one why ?). Indeed, ACE silencing is partial and it's was better to add for example a radiolabelled AngI.

- In Figure 1 : optimization of LC-MS/MS parameters seams not good. We do not see well on the figure but it's seams FWHM was too large (>30s). With this kind of nano-HPLC system it's not good.
- We don't understand how RSD is calculated (how much injections, how much days, etc ..). It's very important to have these informations
- We don't understand Figure 3 (SD ???), why peak areas ?
Figure 5 : why use areas and not % recovery
Additional comments: This article an interesting alternative analytical method using liquid chromatography tandem mass spectrometry (LC-MS/MS) for the determination of angiotensin peptides using nano-HPLC and PRM approaches.
Nevertheless, some important points would be changed like the use of raiodrlabelled peptides (eg AngI). and some figures would be changed. Complete absence of information from one of the main parameters when working with LC-MS(MS): matrix effect. This would be of great importance in this work, since LLE is used for sample preparation and the matrices are complex. The method seams to be validated but does not follow the criteria of an international validation guide.


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: DEVELOPMENT OF A NOVEL NANOFLOW LIQUID CHROMATOGRAPHY-PARALLEL REACTION MONITORING MASS SPECTROMETRY-BASED METHOD FOR QUANTIFICATION OF ANGIOTENSIN PEPTIDES IN HUVEC CULTURES
Review round: 1
Reviewer: 2

Output:
Basic reporting: 1.	Title is unclear. The authors reported the development of a novel nanoflow liquid chromatography parallel reaction monitoring mass spectrometry-based (method? platform?) for quantification of angiotensin peptides in HUVEC cultures.

2.	The authors introduced the liquid chromatography-mass spectrometry methods in lines 75-86, which could contain more introduction on how this method works. The authors should also highlight the novelty of current method they are using - what are the developments the authors have done based on this existing technique as indicated in the title?

3.	Abbreviations should still be defined upon first use, such as EDTA in line 142, TFA in line 147, etc.

4.	Many figures do not have units for the retention time. The figures should be replotted more professionally with higher resolution and larger text. The tick labels on all the axis should also be carefully chosen. Supplementary figures are also too small to see.
Experimental design: 1.	Experimental methods part, line 143, 2-mercaptoethanol manufacturer and final concentration should be specified.

2.	The authors detected the 7 Ang peptides using only one labeled isotope based on pre-built library. Is there any calibration steps or control experiments conducted before the experiments to verify the detection? In figure 2, the authors also mentioned the signal-to-noise ratio as “high”, could this be quantified?

3.	The authors showed the sample stability for 6 hours as well as intra-day stability. The authors envision how many hours of stability this method could achieve at maximum?
Validity of the findings: 1.	The authors should elaborate more on the detection limit results from the built standard curves by providing an exact range in the experimental results session starting line 242.

2.	The recovery rate of Ang I using SPE is significantly higher than the other Ang peptides. Could the authors elaborate more on this point?
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: DEVELOPMENT OF A NOVEL NANOFLOW LIQUID CHROMATOGRAPHY-PARALLEL REACTION MONITORING MASS SPECTROMETRY-BASED METHOD FOR QUANTIFICATION OF ANGIOTENSIN PEPTIDES IN HUVEC CULTURES
Review round: 1
Reviewer: 3

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: The manuscript presents development of Liquid Chromatography- Paralel Reaction Monitoring Mass Spectrometry  method to evaluate few angiotensin peptides in HUVEC culture supernatant. Recently various modifications of LC-MS method for angiotensins peptides analysis in cell cultures and tissues were described and successfully used in numerous studies (some examples: Hybrid Tandem Mass Spectrometry and Linear Ion Trap High-Resolution Mass Spectrometry, Matrix-Assisted Laser Desorption/Ionization Quadrupole Ion Trap Time-Of-Flight Five Tandem Mass Spectrometry, Electrospray Ionization Triple Quadrupole Mass Spectrometry etc.).
The Authors described in details their reliable work and proved high sensitivity, efficiency and precision of established method. However, there is one weakness of this work- it is limited to a few peptides only and one type of cell culture. Did the Authors try to apply described analytical technique in other type of cell culture or human/ animal tissue?


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: DEVELOPMENT OF A NOVEL NANOFLOW LIQUID CHROMATOGRAPHY-PARALLEL REACTION MONITORING MASS SPECTROMETRY-BASED METHOD FOR QUANTIFICATION OF ANGIOTENSIN PEPTIDES IN HUVEC CULTURES
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: My comments are addressed in the revised manuscript.


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

Input:
Title: DEVELOPMENT OF A NOVEL NANOFLOW LIQUID CHROMATOGRAPHY-PARALLEL REACTION MONITORING MASS SPECTROMETRY-BASED METHOD FOR QUANTIFICATION OF ANGIOTENSIN PEPTIDES IN HUVEC CULTURES
Review round: 2
Reviewer: 2

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


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

Input:
Title: NUMERICAL INVESTIGATION OF MICROBIAL QUORUM SENSING UNDER VARIOUS FLOW CONDITIONS
Review round: 1
Reviewer: 1

Output:
Basic reporting: -	In general, English is clear and professional and the paper is well written. I have few comments regarding the use of single words /missing definitions, in light of the readership of the Journal:
o	In the abstract (lines 20-21), the microbial aggregates are defined “heterogeneously distributed”. The author should specify if the heterogeneity regards the spatial location, the dimension or the bacterial density.
o	In the abstract (line 30), the definition “zero-order production kinetic” is used. I wonder if such a specific term is needed in the abstract.
o	In the Material and Methods (line 101), the acronym “ADRE” is used. Given the readership, it should be explained.
o	In the Material and Methods (line 149), it is not clear what the expression “shown below” is referring to.
o	In the Material and Methods (line 159), Mach number is not defined.
-	The introduction is in general well structured. However, I would recommend the addition of a paragraph (probably after line 84) about the experimental findings on the influence of flow on QS. The papers Kim at al. (2016) and Kirisits et al. (2007) (already cited by the authors) could be a good starting point. In addition, the role of EPS production should be mentioned and the knowledge gap being filled by this paper should be better highlighted.
-	In the structure of the paper, the section Conclusion have been replaced by the section Implications. In my opinion, this does not damage the readability of the paper, however such a structure does not conform to PeerJ Standards.
-	Figures are in general relevant and the quality is adequate.  However, I have some comments:
o	In Fig. 1, the “transport distances” reported in lines 199-201 should be marked on the x-axis or using vertical lines. In addition, having colored areas instead of colored lines would ease the interpretation of the figure.
o	Fig. 3, the legends in panel (b), (c) and (d) are not easily readable. They should be bigger.
o	Fig. 4, I found the different scale between the up- and downstream distances quite confusing. I would suggest to find a more straightforward representation.
-	Raw data are not supplied, however the numerical model is adequately described.
Experimental design: -	Given the fact that the journal is primarily intended for Biological Sciences, the authors should:
o	Improve the clarity and readability of the Material and Methods for the journal readership by making sure all the quantities and methodologies are clearly defined (see some of my comments in point 1). The same principle should be applied to the whole paper.
o	Along the same line, in the first paragraph of the Results section (lines 164-167), an explanation of the choice of the Pe range and Da should be introduced.
o	Introduce some more quantitative examples of the implications of their findings in experimental scenarios (like the one introduced in lines 183-189).
o	Give examples of “zero-order production reactions” (line 226).
-	What is the assumption which is made on the geometry (and dimension) of the aggregate (line 165)? Is it a point source? This point should be clearly mentioned, since the assumption could be difficult to reconcile with the reality.
Validity of the findings: -	In order to increase the impact of the work, some examples of the implications in "real-life" experimental scenarios should be introduced (see point 2).
-	In the paragraph Implications, which replaced the Conclusions, the conclusions should be clearly stated before moving to the implications
Additional comments: In the paper from Jung and Meile, a numerical model, implemented using LB method, is developed to study QS in microbial aggregates exposed to varying fluid flow. The effect of advective transport, bacterial density, signal production rate and induction are explored. In addition, approximate analytical solutions describing the concentration profiles under different flow and reaction rates are given.

The suggested work is interesting and I recommend it for publication once the issues reported in the following will be addressed. The issues/ comments are presented above according to the Editorial Criteria.


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: NUMERICAL INVESTIGATION OF MICROBIAL QUORUM SENSING UNDER VARIOUS FLOW CONDITIONS
Review round: 1
Reviewer: 2

Output:
Basic reporting: The authors present a numerical modeling approach for the quorum sensing (QS) process under different flow conditions in a heterogeneously distributed microbial environment and they claim that the advection and the increasing signal production in the system effects the spatial extent of QS induction. Discussing the role of the diffusive and advective transport on QS induction by using numerical methods could not be assumed as a novel approach. However, every single numerical experiment is valuable for understanding such complex biological systems better. In that sense, the authors show the importance of enhanced signal production on the spatial propagation of QS induction and they emphasis how QS induction can be decoupled via the effect of the transport of signaling molecules through numerical examples and simulations.

The language of the paper is fluent, clear and understandable for the readers of a scientific journal. The manuscript is well structured. The context of their research is explained in the Introduction part, numerical methods they have used are declared in Material&Methods part and their numerical results are interpreted and supported by simulations in Results&Discussions part.

I suggest the authors to examine and cite the following manuscripts:
A comprehensive review on QS:
Mathematical Modelling of Bacterial Quorum Sensing: A Review https://doi.org/10.1007/s11538-016-0160-6

A ‘shrinking’ approach for spatially heterogeneous distributed cells, like colonies and biofilms:
An Approximative Approach for single cell spatial modeling quorum sensing https://doi.org/10.1089/cmb.2014.0198

A very important manuscript for QS researches:
Mathematical Modelling of Quorum Sensing in Bacteria
https://doi.org/10.1093/imammb/18.3.263
Experimental design: This manuscript consist of novel numerical experimental results. In mathematical biology, every single numerical example enable us to understand a complex system. Their results are supporting the biological hypothesis about the effect of increasing signal production on the spatial propagation of QS induction. The methods of numerical experiments are described in details and supported by simulations.
Validity of the findings: No comment
Additional comments: The numerical outputs in the manuscript are interesting and they are supporting the experimental biological researches. I recommend to publish this research in the scientific journal PeerJ with above suggestions.


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

Input:
Title: NUMERICAL INVESTIGATION OF MICROBIAL QUORUM SENSING UNDER VARIOUS FLOW CONDITIONS
Review round: 1
Reviewer: 3

Output:
Basic reporting: The paper is well-written and in main parts easy to follow and understand. I especially appreciate the effort the authors have undertaken to give a very good literature review and general introduction to the topic. The figures are helpful and of good quality; the labelling together with the text captions is sufficient.
Experimental design: As no experimental data have been used, nothing to supply as raw data.
Parts of this section may be relevant also for the design of the simulations, few points will be addressed in the next section.
Validity of the findings: 1. Concerning the simulation experiments, I would have expected more explanation about the choice of the Lattice-Boltzmann method, especially the advantages of this method compared to others which were already used in this context (e.g. Frederick, M.R. et al.  A mathematical model of quorum sensing in patchy biofilm communities with slow background flow, Canad. Appl. Math. Quarterly 18 (267-298), which considers a more refined, more realistic model with a thin-film approximation.
Side question to this: is it correct that the simulations have been run in two space dimensions?

2. Some clarification about the simulation set-up would be appreciated (e.g. abound lines 155-160):
Maybe I have overseen, is it stated somewhere explicitly, where the bacteria are located? From the resulting figures I guess, it should be at (x=0, y=1), but why only at one certain point, is it really chosen as a peak ? It would help a lot to define somewhere explicitly the B-hat. Is it correct, that the bacterial distribution was chosen as time-constant? This is not very realistic, assuming that the QS tends to its steady state means a time frame where also bacterial growth would be relevant.
In this context: I didn‘t fully understand how (18) would define multiple microbial aggregates, shouldn‘t this been done via B, not via the signal A itself?
An additional question concerning „the steady state“: such a system may easily show up bistability, i.e. it would be important to check that out, also to define, which one is chosen as „the“ steady state. For the simulations, it means that chosing the initial conditions differently, the simulations may tend to another steady state. This problem hasn‘t been addressed at all, but may play a big role for the calling distance and other phenomena.

3. Concerning aspects like the calling distance: The simulations have been run in two space dimensions (as far as I got it), but a realistic situation would be 3D. Of course, produced signal molecules would „spread“ much more in 3D than in 2D, and by that reach only lower levels, and reducing potential calling distances.

4. Concerning notation,  I found the term Da (e.g. in eqation (7) ff.) difficult to read, as it contains a hidden A (for the signalling molecule concentration), thus not being just a constant inhomogeneity or so. Better to have the A clearly visible, also to check about linearity. And it concerns e.g. formula (17), as here, A may be included in Da (or I‘m missing a clear argumentation, why it‘s not the case here).

5. Some more critical discussion, also about potential weaknesses or aspects to improve, would help.
Additional comments: Minor comments:

* line 27: I wouldn‘t call these empirical / regression functions „approximate analytical solutions“,
for me that would mean there was done maybe some model simplification or expansion and then to take an approximation. Here, it‘s mainly simulation-based.
* a bit similar for the title: reading „Mathematical investigation“ I had expected some model analysis, qualitative behaviour study or something similar, not just simulations. Simulations are fine, of course, but then maybe call the paper „Simulation study of ...“?
* line 143: it reads a bit misleading that the concentrations of signling molecule are doubled – to be precise, the production is doubled, right?

I commend the authors for their thorough simulation study and the interesting ideas behind. Before acceptance, some terms and details for the assumptions behind should be clarified and made better visible, as stated above, before Acceptance.


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

Input:
Title: NUMERICAL INVESTIGATION OF MICROBIAL QUORUM SENSING UNDER VARIOUS FLOW CONDITIONS
Review round: 2
Reviewer: 1

Output:
Basic reporting: Authors have done a nice job addressing prior concerns. No further comments for the paper.
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: NUMERICAL INVESTIGATION OF MICROBIAL QUORUM SENSING UNDER VARIOUS FLOW CONDITIONS
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors present a numerical modeling approach for the quorum sensing (QS) process under different flow conditions in a heterogeneously distributed microbial environment and they claim that the advection and the increasing signal production in the system effects the spatial extent of QS induction.
Experimental design: No comment
Validity of the findings: The numerical outputs in the manuscript are interesting and they are supporting the experimental biological researches in the literature.
Additional comments: In this second review, the authors made some valuable changes based on the reviewers' comments. The title of the manuscript has been revised from 'mathematical investigation to 'numerical investigation' in accordance with its content. Some key references of QS research have been added to the reference list. I recommend to publish this research in the scientific journal 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: NUMERICAL INVESTIGATION OF MICROBIAL QUORUM SENSING UNDER VARIOUS FLOW CONDITIONS
Review round: 2
Reviewer: 3

Output:
Basic reporting: The paper is well-written and in main parts easy to follow and understand. I especially appreciate the effort the authors have undertaken to clarify all points which have been raised in the first review process, the paper has been improved a lot in many details.

I focus here in my report only on the changed points, where necessary; all other points were fine already in the first submitted version or have been fully clarified from my point of view.
Experimental design: No (wet) experiments are contained in the article, thus no data to share, but
the programming code has been supplied.
Validity of the findings: All points have been fully clarified.
I do not fully agree with the authors‘ answer concerning the bistability, as this is also possible with the jump function, but as this point is really a side-question, it can be ignored for the present paper.
Additional comments: I recommend the publication of this paper in its present form.


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: TET1 MAY CONTRIBUTE TO HYPOXIA-INDUCED EPITHELIAL TO MESENCHYMAL TRANSITION OF ENDOMETRIAL EPITHELIAL CELLS IN ENDOMETRIOSIS
Review round: 1
Reviewer: 1

Output:
Basic reporting: 1.	Basic reporting. Authors explore the role of TET1 with in the frame of hypoxia and endometriosis pathogenesis. The body of this work aims to show hypoxia induces increased TET1 expression through HIF2a which increases 5-mhc driving increase EMT.

In general the language was satisfactory, a strong proofreading will be helpful for the final round of edits.
	Examples include – consistent spacing between end of text and citations
-	Line 45: debris – not debrises
-	Line 244: N-cadherin – not N-cadherine
Introduction was written in a way that minimized previously published research by using language such as: could and may. These works have been published and are the ideas of those authors.
Transitions within the introduction between topics will significantly aid in the flow and readability.
TET1, TET2, and TET3 were previously characterized in human samples of endometriosis this work should be acknowledged within the introduction or the strong language of “the function of TET1 has not yet been well characterized” should be altered.
Figure 1 - ectopic images are very hard to see higher quality photomicrographs are necessary for readers to come to the same conclusions as authors. Within Figure 1D there is a floating scale bar in the middle of the image. And the labelling in 1D is not explained or referenced anywhere the 1Da,b,c,d,-i.
Figure 2 – symbols used within the figure need to be defined in the figure legend *, #, &.
N’s should be included in each figure legend
Table 1 – it needs to be indicated somewhere within the table that eutopic and ectopic endometria are matched samples
Table 3 – does not provide a significant amount of information and the data can be easily written into the text of the results.
Experimental design: 2.	Experimental design. Authors used protein analysis through IHC and Western blots to visualize TET1 and EMT in endometriosis. They then used a cell line to look at hypoxia and EMT markers in endometrial tissue. Finally, authors linked TET1 to Hif2a with a pull down assay.
Research question – Authors are attempting to explain the pathogenesis of endometriosis. EMT has long been recognized as a player in endometriosis and may publications have discussed the role of hypoxia in the initiation of EMT. There have additionally been a number of players that have been linked to the hypoxia induced EMT: Hif1a, TAF1, Perostin. Thus the knowledge gap is unclear.
Within the methods antibodies were cited but concentrations were not, please add.
It is unclear why only Ishikawa cells were used. Ishikawa cells are an endometrial cancer cell line which most likely carries a very different profile than the non-malignant endometriosis cells. There are a few endometriosis epithelial cell lines available that may have been better suited for these experiments. It is understandable that one is trying to show cells from the uterus become endometriotic cells but using only one cell line is not sufficient to represent this data.
Validity of the findings: 3.	Validity of the findings. Authors showed an increase in TET1 expression in ectopic lesions compared to control and eutopic endometrium. TET1 increase was correlated with changes in cadherins. Hypoxia was shown to be related to TET1 changes.

The use of human biopsies made the exploration of TET1 expression highly translatable.

It is unclear what the role of cell type localization of TET1 plays in this phenotype. Both the normal and the eutopic endometrium express TET1 within the stroma while the ectopic endometrium shows epithelial expression. This divergence is seemingly imperative to the story and needs significant expounding. Additionally, what is the expression of TET1 in normal ovaries specifically the epithelium. An additional panel of normal ovary would be beneficial.

The antibody used is suggested to be nuclear therefore an explanation as to why the staining appears cytoplasmic or images which clarify this is necessary.

Figure 1Ac you are unable to discern the endometriotic lesion being highlighted. In fact, all of these lesions are difficult to discern as endometriosis as no underlying stroma appears to be present.

Figure 1D. Again the lesion is very difficult to depict. The TET1 expression appears to be in the stroma and not epithelial which contradicts what was seen in 1A.

A clear discussion on why these results significantly differ from that found in Roca 2016 are necessary.

What controls were in place to assure the siRNA knockdown worked? The siTET does not appear to rescue hypoxia induced TET1 expression.

Figure 4. needs to have normaxia controls. Readers are unable to determine if the reduction is biologically relevant without seeing if the alterations cause a return to normal. Additionally, while there was a reduction in TET1 after siHIF-1a it was not eliminated, thus a discussion on other players is necessary.

A clear discussion on why these results differ from previously published with respect to TET1 and HIF1a are necessary. Both Tsai 2014 and Cheng 2018 show direct interact of TET1 and HIF1a. With Tsai showing it’s role in hypoxia induced EMT.

The in vitro experiments do not represent endometriosis and if they authors were able to link the mechanism from endometrial epithelial cells back to the endometriosis tissue it would strengthen the work. Do the ectopic lesions express HIF1a, HIF2a or Vim?
Additional comments: An infographic explaining the relationship between all presented parties and how they interact to promote disease would be highly beneficial.


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: TET1 MAY CONTRIBUTE TO HYPOXIA-INDUCED EPITHELIAL TO MESENCHYMAL TRANSITION OF ENDOMETRIAL EPITHELIAL CELLS IN ENDOMETRIOSIS
Review round: 1
Reviewer: 2

Output:
Basic reporting: The manuscript by Wu et al study the role of TET1, a DNA methylase in regulating hypoxia induced EMT in endometriosis. The current conclusions are of sufficient novelty and breadth of interest to merit publication in PeerJ. However, English should be checked and refined as needed throughout the manuscript. Here are few of the examples:

Line 57. Please correct transcript factor to transcription factor
Line 124. Please correct table number 2. Global 5-hmC levels are shown in table 3.
Line 244. Please correct N-cadherine to N-cadherin
Line 250. Please correct down-expressed to down-regulation
Line 282. Please correct transcript factor to transcription factor
Line 297, 288, 305, 306. Please correct the sentences.
Line 299. Please correct Hyper-methylation to Hypermethylation
Experimental design: No comment.
Validity of the findings: For Figure 2 A and B.

1) Authors reported N-cadherin expression peaks at 8 hour during hypoxia conditions. However, surprisingly the levels go down drastically at 24 hours (See Figure 2A and B). This is contradictory and authors need to clarify or comment on the expression pattern.

2) Please explain the meaning of symbols * and # in figure legends
Additional comments: Please be consistent with symbols throughout the manuscript. For example, hours in manuscript are sometime refered as h or sometime as hr.


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: TET1 MAY CONTRIBUTE TO HYPOXIA-INDUCED EPITHELIAL TO MESENCHYMAL TRANSITION OF ENDOMETRIAL EPITHELIAL CELLS IN ENDOMETRIOSIS
Review round: 1
Reviewer: 3

Output:
Basic reporting: 1.	The authors should check that all the labels of figures and tables in this article are correctly ordered. For example, in line 124, table 2 is not correct.
2.	The description of Figure legends should be concise and pointed. For instance, The description of Figure 3 is too lengthy and to some extent similar to methods. What’s more, the markers of significance like # and * are not described in figure 2 which may confuse the readers. Further, please don’t show conclusions in figure legends. Please check all the figure legends to make sure they are suitable.
3.	Please optimize the figure setting. For example, the text in Fig3A is deviated. Fig 2B lose some information.
4.	Pay attention to the front, tense and grammar, I wish you can polish this article in English writing. Line 155, “in vitro” should be in italic; line 189, “ul” should be 1.	The authors should check that all the labels of figures and tables in this article are correctly ordered. For example, in line 124, table 2 is not correct.
2.	The description of Figure legends should be concise and pointed. For instance, The description of Figure 3 is too lengthy and to some extent similar to methods. What’s more, the markers of significance like # and * are not described in figure 2 which may confuse the readers. Further, please don’t show conclusions in figure legends. Please check all the figure legends to make sure they are suitable.
3.	Please optimize the figure setting. For example, the text in Fig3A is deviated. Fig 2B lose some information.
4.	Pay attention to the front, tense and grammar, I wish you can polish this article in English writing. Line 155, “in vitro” should be in italic; line 189, “ul” should be “μl”, line 244, “N-cadherine” is wrongly spelled. The tense is in chaos in this article.
5.	It will be better to show the fluorescent images of fig1D in higher power field to see the colocalization of TET1 and N-cadherin more clear.
l”, line 244, “N-cadherine” is wrongly spelled. The tense is in chaos in this article.
5.	It will be better to show the fluorescent images of fig1D in higher power field to see the colocalization of TET1 and N-cadherin more clear.
Experimental design: 1. I was confused about the Fig1E, what do the numbers in X-axis and Y-axis mean? And the method for Fig1E should be clarified.
2. Are there any literatures reporting about the oxygen concentration of endometriosis? Why do you choose 5% O2 as condition.
3. The change from N-cadherin to Vimentin seems a bit unconvincing. Though N-cadherin and Vimentin are both markers for mesenchymal transition, from figure2B it seems the change tendency of vimentin is more similar to TET1. Maybe you can add more evidence of vimentin expression in endometriosis to make the story more reasonable.
4. You use the all endometrium and endometriosis tissue to extract the genomic DNA for 5-hmC analysis. I wondered how can it represent the glandular epithelial cells which are mainly studied in this article.
5.Why do you choose TET1 to study rather than TET2, TET3; which are also demethylation enzymes.
Validity of the findings: 1.	Why do you not choose student T test in your article?
2.	From Fig4C, the TET1 regulated by HIF1a seems not so robust?
3.     Please show raw data for histograms in figures.
Additional comments: Please extrude the highlight of this article in discussion and make the discussion more  concise.


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: TET1 MAY CONTRIBUTE TO HYPOXIA-INDUCED EPITHELIAL TO MESENCHYMAL TRANSITION OF ENDOMETRIAL EPITHELIAL CELLS IN ENDOMETRIOSIS
Review round: 2
Reviewer: 1

Output:
Basic reporting: There is still a scale bar in the middle of the image of Figure 2. JJ.
Experimental design: No comment
Validity of the findings: No comment
Additional comments: This reviewer found that the authors made significant changes and answered all of my concerns to satisfaction.


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: TET1 MAY CONTRIBUTE TO HYPOXIA-INDUCED EPITHELIAL TO MESENCHYMAL TRANSITION OF ENDOMETRIAL EPITHELIAL CELLS IN ENDOMETRIOSIS
Review round: 2
Reviewer: 2

Output:
Basic reporting: No comments.
Experimental design: No comments.
Validity of the findings: No comments.
Additional comments: The revised version of the manuscript and the rebuttal provided by the authors adequately address most comments and suggestions in the current version of the manuscript. Overall, it id appropriate for publication in PeerJ.