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: SHORT-TERM INTERVAL AEROBIC EXERCISE TRAINING DOES NOT IMPROVE MEMORY FUNCTIONING IN RELAPSING-REMITTING MULTIPLE SCLEROSIS—A RANDOMIZED CONTROLLED TRIAL
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: I am satisfied with all the revisions to the manuscript and have no further comment. The authors should be credited by their inputs to 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: SHORT-TERM INTERVAL AEROBIC EXERCISE TRAINING DOES NOT IMPROVE MEMORY FUNCTIONING IN RELAPSING-REMITTING MULTIPLE SCLEROSIS—A RANDOMIZED CONTROLLED TRIAL
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors have adequately addressed my questions.
Experimental design: Design and study elements are now clear.
Validity of the findings: Valid and important 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: FOUNDER EFFECTS DRIVE THE GENETIC STRUCTURE OF PASSIVELY DISPERSED AQUATIC INVERTEBRATES
Review round: 1
Reviewer: 1

Output:
Basic reporting: Line 56: "Predicting the outcome of these factors…" What are 'these factors'? Are you refering to the two listed in the previous sentence, or the whole set listed in the first paragraph?

LIne 59: "dispersing" The verb tense seems wrong to me. But, this could be a matter of style.

In general, there is an excessive use of ambiguous pronouns to start sentences. Using words like 'it', 'these', 'they', and so on decreases comprehension by the reader. Ambiguous pronouns are used abundantly throughout the MS and I strongly suggest that the authors edit their MS to specifically remove these words, especially when they are used in the begining of a sentence.

Lines 103-108: In this final paragraph of the introduction, the authors outline what they did. It would be nice to follow those enumerated sentences with a few sentences about what they found. What are the main take-aways?

Line 117: "which are major taxonomic groups in the zooplankton". This phrase would imply that zooplankton are themselves a proper taxanomic group which (emphasis on the word 'the'), of course, they are not.
Experimental design: No comment.
Validity of the findings: No comment.
Additional comments: Overall, I found this paper to be interesting and well thought out. I do not have any substantial comments on it and I look forward to seeing it published. I believe that it will be useful for the field.


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: FOUNDER EFFECTS DRIVE THE GENETIC STRUCTURE OF PASSIVELY DISPERSED AQUATIC INVERTEBRATES
Review round: 1
Reviewer: 2

Output:
Basic reporting: The MS is clear and well documented. Figures are easily understandable and of good quality.
The MS could nonetheless be checked further by an English native as some sentences read awkward to me (I'm not an English native, I can hence be wrong).
Experimental design: The question is extremely well posed and is relevant. The authors used a simulation-approach to tackle the question and the simulation design is very good to me.
Notably, the set of parameters is well defined and well argumented. My only worry concern the use of a single founding individual (although other scenarios are simulated); to me authors should justify it better, and/or include further results for other scenarios. For instance, authors could easily confront results from 1 vs. 20 founder for some figures to clearly show what the impact of increasing the number of founders is. They argue that 1 founder is a likely scenario for instance for glacial lakes, but there are many other scenarios where I guess 20 founders is also likely.
Validity of the findings: No Comment
Additional comments: That's a good and interesting paper. I have easily read it, it is easy to follow and it tackle a fascinating question. Although I'm not a specialist, the methodology and overall simulation design seem robust to me (but see my comment about the scenario of a single founder).
I have provided some comments and some corrections in an attached file. Two of these comments should be seriously considered by the authors: one concern some results that sounds illogical to me (but authors may have an explanation, and/or I may have missed something) and the other concerns the choice of presenting only the results with a single founder.
I'm sure you'll be able to easily deal with these comments.
Good luck


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: FOUR TYROSINE RESIDUES OF THE RICE IMMUNE RECEPTOR XA21 ARE NOT REQUIRED FOR INTERACTION WITH THE CO-RECEPTOR OSSERK2 OR RESISTANCE TO XANTHOMONAS ORYZAE PV. ORYZAE
Review round: 1
Reviewer: 1

Output:
Basic reporting: Caddell et al describes four tyrosine residues in XA21 that are not required for interaction with OsSERK2 and are not required for resistance to Xoo.  Of the residues they investigated, they found four of nine were unable to autophosphorylate in vitro, and none of these were required for resistance.  When transgenically expressed in rice, mutation of these four residues still allowed detection of the RaxX21-sY peptide.  They found that Y786F maintained interaction in yeast, showing that catalytic activity is not the sole determinant of XA21-OsSERK2 interaction.
While this paper is overall scientifically sound and well written, I do have some concerns that would improve the paper:

Basic Reporting

The language is generally clear, intro and background show context, and most references are included.  Some figures need some work to improve clarity and/or description of experiment.  Raw data is supplied.

Major Concerns
1.	Figure 4:  This figure is overexposed and/or has too much protein loaded so that you can’t see the expression.  It’s a big smear without a particular band.  The authors say no signal was detected in Kitaake, but with the exposure there definitely appears to be a band ~150 kDa.  Without knowing what the size should be (since it’s never listed), it’s hard to say if this is a valid conclusion.  The Coomassie stain also shows that the protein is not equally loaded.  The right panel is also very dark

Minor concerns
2.	Line 285: specify that the immunoblotting was done in in vitro purified recombinant protein (E. coli).
3.	Line 325: what is the molecular weight of XA21-GFP?  This isn’t said anywhere in the paper.
4.	.
5.	Figure 5:  It is difficult to see the orange line and could be a problem especially for color blind people.  Make the orange a thicker line or make the graphs bigger so it’s easier to see.
6.	Line 367: what do XB3 and XB15 do?  This is not in the introduction (other XB’s are in the introduction).
7.	Figure 7: HA-XB3 should be 52kDa, but the gel is run too far to see this size (lowest ladder marker is 55 kDa).  The protein looks like the wrong size (~70kDa or faint band at ~55 kDa).  If it’s the faint band put an arrow to denote correct protein.
8.	Figure 1: combine B and C into one panel
9.	Line 428-429: FLAGELLIN SENSING 2
10.	The amino acid annotation is not consistent throughout the paper, e.g. Leu vs leucine switches throughout the Discussion
11.	Line 480: reference missing
12.	Line 481: transphosphorylate
Experimental design: Original primary research is in the scope of the journal, the research question is fairly well defined, and it is stated how the research fills a knowledge gap.  The methods are fairly well described but some details need clarified.

Major Concerns
1.	Figure 6: the background levels for all panels are high and increase over time (compare to background/mock for Fig 5).  Why is this?  This may indicate contamination of the peptide.

Minor concerns
2.	Figure 3: Lesion length was calculated on plants with four to eleven leaves.  Did you mean “using” four to eleven leaves, or four to eleven leaves as the age/stage?  If age, this is a big difference in age and disease response can vary greatly based on age.  If not age, this is unclear.  This wording is the same in supplemental Figure 4.
3.	Figure 5 and 6: “ROS production in rice leaves (n=3)…” Is this three leaves?  And are these from the same plant or three individual plants?  In the methods they say they did four biological replicates.  Is this the average of the four biological reps?
Validity of the findings: Data is fairly robust and statistically sound, but could use some additional experiments and/or clarification.  Conclusions are fairly well stated but a few things should be addressed.

Major concerns
1.	There are no experiments that look at the phosphorylation of the tyrosine residues in plants.
2.	Lines 357-360: The comparison to wildtype can not be made unless all of these ROS assays were done in the same experiment/same graph.  This does not look like the case since they all look like separate experiments.  If this comparison is to be made, wildtype and the mutants should all be compared in a single experiment.

Minor concerns
3.	Line 293-294.  How do you conclude that “interaction among potential phosphosites, e.g., the phorphorylation of Ser697, may regulate tyrosine autophosphorylation.”?  There is no evidence that shows this.
4.	The authors never look at transphosphorylation in the paper.
Additional comments: no comment


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

Input:
Title: FOUR TYROSINE RESIDUES OF THE RICE IMMUNE RECEPTOR XA21 ARE NOT REQUIRED FOR INTERACTION WITH THE CO-RECEPTOR OSSERK2 OR RESISTANCE TO XANTHOMONAS ORYZAE PV. ORYZAE
Review round: 1
Reviewer: 2

Output:
Basic reporting: The writing and structure of the manuscript are clear and orthodox, and the manuscript includes all the relevant references.
Experimental design: The experimental design is appropriate, and the results constitute original primary research. The questions are well-defined, relevant and meaningful. The methods are appropriate and well described.
Validity of the findings: The data seems robust.

I have doubts regarding whether the western blots provided as loading control in specific figures really correspond to the experimental blots shown, since the shape of several bands is considerably different (e.g. Fig 1C). This should be clarified or substituted.
Additional comments: My main concern about this article relies on whether or not the phenotypes observed in several experiments are really associated to phosphorylation or catalytic activity. In several instances, the phenotypic results do not seem to correlate with the observations regarding phosphorylation, which would at least justify significant modifications to the manuscript to explain these observations. Examples are below:

- Based on the figure 2, the authors suggest that several tyrosine residues play important role in XA21 kinase activity, since their YD variants have abolished phosphorylation. However, their respective YF variants (except Y786F) keep autophosphorylation, suggesting that phosphorylation in these residues does not really play a role in XA21 kinase activity. Considering the important steric alterations caused by YD mutations, it seems likely that the XA21 YD mutations have an impact in the correct folding of the protein, rather than their phosphorylation being required for kinase activity.

- A similar scenario is suggested by the results shown in figure 7. The D842N kinase-inactive version maintains the interaction with the tested XA21 interactors; sames as the YF variants. However, these interactions are abolished by several YD mutations, suggesting a problem in protein folding rather than specific effects of phosphorylation in these residues.

- Other examples come from the use of the Y786F mutant. This mutation abolishes autophosphorylation. However, transgenic lines expressing this XA21 mutant are resistant to Xoo (as other YF mutations). However, in the same instance, all the YD variants fail to provide resistance. Similarly, in the Figure 6, the authors associate the higher ROS value in the Y698F mutant to its hyperactive autophosphorylation shown in the figure 2. However, again, the Y786F, which loses completely the autophosphorylation activity, shows a ROS value similar to WT XA21.

In addition to this, the authors mention in the discussion that they observed that the mutation XA21Y829F does not abolish tyrosine autophosphorylation, and was not selected for further characterization. They mention the interest of doing mutagenesis analysis of this residue (mutant that they already have). Considering the relevance of the equivalent tyrosine residue in other RLKs, the correlation of the results presented in this manuscript with a similar analysis of the Y829F seems essential to uncouple potential effects of mutation of Y residues in phosphorylation and in the general folding of the protein, as I mentioned 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: FOUR TYROSINE RESIDUES OF THE RICE IMMUNE RECEPTOR XA21 ARE NOT REQUIRED FOR INTERACTION WITH THE CO-RECEPTOR OSSERK2 OR RESISTANCE TO XANTHOMONAS ORYZAE PV. ORYZAE
Review round: 1
Reviewer: 3

Output:
Basic reporting: Cadell et al investigates the role of tyrosine phosphorylation in regulating the function of XA21, a rice immune receptor that recognizes a sulfated peptide from Xanthomonas oryzae and provides resistance against this bacterial pathogen. In this work the authors report that recombinant XA21 autophosphorylates on tyrosine residues in vitro. Using site-directed mutagenesis, nine Tyr to Phe substitutions were made within the juxtamembrane and kinase domains of XA21. Four of these substitutions completely abolished in vitro autophosphorylation of XA21 on Tyr. The role of these four Tyr residues on overall XA21 function was further investigated by testing Tyr to Phe mutants for in vitro 32P-ATP autophosphorylation, XA21-mediated response to Rax21-sY peptide, XA21-mediated resistance to Xanthomonas, and XA21 interaction with known interacting proteins including SERK2. None of the four Tyr to Phe substitutions tested had any detrimental effect on  these phenotypes, with the exception of Y786F disrupting XA21 autophosphorylation. In contrast, individual Tyr-Asp substitutions at the same four Tyr residues disrupted XA21 autophosphorylation, XA21-mediated response to Rax2-sY peptide and resistance to Xoo. The main conclusion of the study is that phosphorylation of the four Tyr residues identified is not required for XA21-mediated resistance or XA21 binding to interacting signaling proteins.

The manuscript is clearly written with background material that is relevant to the research topic.

There are several issues with the quality of figures that should be addressed:

Fig. 1C. The bands shown in the anti-pY blot seem to be upside down relative to the bands shown on the blot within the corresponding raw data file. Also, the contrast of this image has been adjusted to the point where it is difficult to assess if there are quantitative differences between bands, an important consideration for interpreting these results (see concerns regarding interpretation of this blot below).

The quality of the blot shown in Fig 4 left panel is poor (particularly when looking at the raw data file for this blot), to the point that it is difficult to assess levels of XA21-GFP expression.

Several legends do not provide details regarding sample size and replication: Fig. 1, no information about replication of results; Fig 5, no sample size for (A) or (B); Fig 6, no sample size; Fig. 7, no information about replication for (A) or (B).
Experimental design: Methods are well-described and technically sound. The research question is clearly defined.
Validity of the findings: Major concerns:

1. Figure 1C shows that altering any of four Tyr residues to Phe completely eliminates detectable Tyr phosphorylation in vitro. Based on these results, the authors conclude on line 259 that these four Tyr residues are potential phosphorylation sites. However, if there is a single site of Tyr phosphorylation on XA21, I would expect that only one of the four substitutions would be necessary to completely eliminate signal on the blot. If there are multiple sites of Tyr phosphorylation, then quantitative decreases in signal should occur. Therefore, it is difficult to see how four distinct Tyr to Phe substitutions would each completely abolish Tyr phosphorylation. The simplest explanation I can think of is that the Tyr to Phe substitutions are causing structural changes in XA21 that prevent Tyr autophosphorylation from occurring. This possibility needs to be more clearly stated throughout the manuscript including the discussion.
      Also, there is no direct evidence in this work that any of the four Tyr residues selected for functional analysis are actually phosphorylated (confirmation by mass spec would be necessary for this, and would greatly strengthen conclusions of this work).  While the authors are careful in the final conclusion section not to refer to the four Tyr residues as bona fide phosphorylation sites, there are multiple places within the manuscript that seem to suggest that these residues are indeed phosphorylated. For example, line 42 of abstract states that “in vivo phosphorylation of the identified tyrosine residues is not required for XA21-mediated immunity…”. Although technically correct (Tyr to Phe substitutions would prevent phosphorylation IF they are in fact phosphorylation sites), readers could be misled by this statement into thinking that these residues are indeed phosphorylated in vivo. The title of the manuscript is also misleading for similar reasons, and should be changed to more accurately reflect conclusions that can be drawn from data– rather than “Phosphorylation of the rice immune receptor XA21 on four tyrosine residues” perhaps simply state that “Four tyrosine residues of XA21 are not required for…”.

 Other misleading statements that should be corrected: line 116  “… in vivo phosphorylation of the identified tyrosine residues is not required…”; line 373 “…indicating that phosphorylation of these four residues is not required for their interactions.”; line 484 “…interaction is not dependent on XA21 phosphorylation of these specific tyrosine residues.” Also, remove or alter sentence “These results suggest…” starting on line 378.

2. Another issue with Fig 1C is the poor contrast adjustment of the blot. By my eye the bands for both Y889F and Y894F appear to be weaker than WT, suggesting that they could be sites of Tyr phosphorylation.  The bands on this blot and on blots from replicate experiments should be quantified to help readers assess this possibility.

3. In previous work (Liu et al 2002) the authors performed phosphoamino acid analysis of autophosphorylated XA21 and did not find any evidence of phosphorylated tyrosine. The authors should comment on this discrepancy in results- is ability to detect phos-Tyr in current work due to greater sensitivity of antibody? Different in vitro conditions?

4. Aspartic acid is not structurally similar to phos-Tyr and is more likely to disrupt protein structure  than act as a phosphomimic. Because of this, Tyr to Asp substitutions are not commonly made, and Tyr to Asp substitutions are not predicted to be phosphomimetic as stated in line 318. There is a strong possibility that phenotypes observed with Tyr to Asp variants in this work are due to structural perturbations of XA21 rather than effects due to phosphomimic, and this should be more clearly stated in results and discussion.

Minor concerns:

1. The authors report that Y698F in Fig. 2 is hyper-phosphorylated, but Y907F phosphorylation also seems increased relative to WT. Quantitation of bands in blot would be helpful.

2. Line 476-477: “rice expressing XA21Y786F-GFP are resistant to Xoo, suggesting that XA21 catalytic activity is not required for resistance” should be revised. Y786F does not autophosphorylate in vitro, but that does not mean it lacks catalytic activity. The only conclusion that can be made from this result is that the ability of XA21 to autophosphorylate in vitro does not correlate with XA21 function in resistance in planta.
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: FOUR TYROSINE RESIDUES OF THE RICE IMMUNE RECEPTOR XA21 ARE NOT REQUIRED FOR INTERACTION WITH THE CO-RECEPTOR OSSERK2 OR RESISTANCE TO XANTHOMONAS ORYZAE PV. ORYZAE
Review round: 2
Reviewer: 1

Output:
Basic reporting: Caddell et al has made significant improvements to the quality of the paper.  Although no additional experiments were performed to address some of my concerns about the phosphorylation status of the variants in vivo or whether the variants can transphosphorylate, the authors have satisfactorily addressed these concerns in the text.  The title of the manuscript has changed to more accurately reflect the scope of the study.  Significant improvements have also been made to increase the clarity of the figures.  While the brightness/contrast has been adjusted in Fig. 4 to improve the visibility of the Xa21-GFP bands, and the size of the expected protein is listed in the main text (~170 kDa), it would still be preferred to include this expected size in the figure legend since there is a second band visible ~130 kDa.
Experimental design: No additional experiments were performed since the last review, and clarifications have been made about the experimental design.
Validity of the findings: Appropriate clarifications have been made about the validity of the findings and the scope of the project.
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: FOUR TYROSINE RESIDUES OF THE RICE IMMUNE RECEPTOR XA21 ARE NOT REQUIRED FOR INTERACTION WITH THE CO-RECEPTOR OSSERK2 OR RESISTANCE TO XANTHOMONAS ORYZAE PV. ORYZAE
Review round: 2
Reviewer: 2

Output:
Basic reporting: no additional comments
Experimental design: no additional comments
Validity of the findings: no additional comments
Additional comments: The revised manuscript addresses all of my previous concerns.

A few minor edits:
Densitometry measurements in Fig 1B show Y936F phosphorylation is reduced, similar to Y889F and Y894F. Was this consistently observed across multiple experiments? If so, Y936F should be added to this statement on Line 265: “Tyrosine phosphorylation also appeared slightly reduced in XA21JKY889F and XA21JKY894F, whereas the other tyrosine directed mutants maintained a signal similar to wild-type XA21JK (Fig. 1B)”.

Please correct misplaced modifier on line 295: “we carried out immunoblotting of in vitro recombinant proteins purified from E. coli with anti-pY antibodies” to clarify that purification of E coli proteins was not done with anti-pY.


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: CHANGES IN INTENTIONAL BINDING EFFECT DURING A NOVEL PERCEPTUAL-MOTOR TASK
Review round: 1
Reviewer: 1

Output:
Basic reporting: The authors investigated how the intentional binding is modulated through progress of perceptual-motor learning. Instead of using self-paced action task in the original studies by Haggard, authors created a task which needs practice to do successfully. Participants were grouped depending on how they improved their performance. The question is interesting.

There are two major concerns. First, the control task was not well-designed. The authors aimed at investigating ‘sense of time not associated with IB’ in the control task. If this was true, the only difference between the main and control tasks should be the occurrence of IB. However, the control task of this study is different from the main task in visual and auditory stimuli and tactile feedback. In addition, the number of trials of the control task was only 18 though. It is hard to say what the results of the subtraction (line 192) express.

Second, in this study, the timing of the presentation of the sound was randomly delayed. I am wondering if longer delay reduces the sense of agency and vice versa.
As far as I know, previous studies have shown that the timing of a sound resulted by one’s action is perceptually bound to the action. In short, motor actions cause the intentional binding (motor actions -> IB). This does not mean that sense of agency causes the intentional binding (motor action -> SoA -> IB). Instead, shortened perceived time could also cause the sense of agency (motor action -> IB -> SoA).
I hope the authors explain that there is no need to worry the possibility that the manipulated delay of sensory feedback contaminates the sense of agency and justify the methodology of this manuscript.

Minor comments

Title page
Do the third and fifth authors have same names?

Abstract (line 33)
What change is thought to be an improvement is not clear.

Introduction line 57 and Discussion line 234
In my understanding, the underlying mechanism of temporal binding is still to be investigated. Please refer the papers based on which the authors have understood that the perceptual-motor learning and SoA generation have similar mechanisms.

Devices and software
Please write the refresh rate of the display.

Experimental task
Please write the size of the stimuli in visual angle (deg).

Figure 1
I was not able to understand the figure. Please clarify what the arrows indicate.
Experimental design: Please see 1.
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: CHANGES IN INTENTIONAL BINDING EFFECT DURING A NOVEL PERCEPTUAL-MOTOR TASK
Review round: 1
Reviewer: 2

Output:
Basic reporting: The authors reviewed literature well and reported interesting findings supported by their data. I hope my comments below will be helpful.

Was the manuscript proofread by native, professional English speaker? I do not think English in the manuscript is intelligible and professional. Example follows:
Line 25: After what? Though I know it means 200-700 ms after the keypress, it should be revised.
L28: What do “sets” mean?
L33: should be revised: “improvement” not “changes (improvement)”.

L57: I did not understand how learning and agency share similar mechanisms. Do you mean reward and motivation? If so, you may need to mention here the internal-prediction and/or comparator account for the generation of agency.

L76: This sentence is misleading because IB is an implicit measure of agency but does not directly reflect explicit awareness of agency, in nature (though IB and explicit measure “can be” related each other in some situations).

L83: Please describe and cite precisely as much as possible. See below:
Outcome binding–Postdictive process: Moore, J. W., Lagnado, D., Deal, D. C., & Haggard, P. (2009). Feelings of control: contingency determines experience of action. Cognition, 110(2), 279-283. doi:10.1016/j.cognition.2008.11.006
Action binding–Predictive process: Moore, J. W., & Haggard, P. (2008). Awareness of action: Inference and prediction. Consciousness and Cognition, 17(1), 136-144. doi:10.1016/j.concog.2006.12.004
Combination of the two: Moore, J. W., Wegner, D. M., & Haggard, P. (2009). Modulating the sense of agency with external cues. Consciousness and Cognition, 18(4), 1056-1064. doi:10.1016/j.concog.2009.05.004

L86: I guess the emotional aspect (ie. Yoshie, Takahata) should be discussed in the following paragraphs.

L139: As detailed information is missing, I think the description in Fig 1 caption should be moved to the main text. Viewing distance should be reported.

L146: Readers may misunderstand as a “computational” model.

L147: Moore & Obhi 2012 is just a review paper. I guess interval estimation method for the first time was employed in the following study: Engbert, K., Wohlschlager, A., Thomas, R., & Haggard, P. (2007). Agency, subjective time, and other minds. Journal of Experimental Psychology: Human Perception and Performance, 33(6), 1261-1268. doi:10.1037/0096-1523.33.6.1261

L147: What does “detect causal relationship” mean? Simply, your task includes keypress action and its auditory consequences, and assesses motor performance and IB.

L163: Number of trials for each delay condition should be reported (although we can easily assume 6 trials each).

L184: How did you analyzed the 3 delays (200/500/700 ms)? As a within-factor? Or collapsed them?

L187: A plausible reason for dividing 10 sets into 5 blocks should be mentioned, as the clusters were determined based on the 1st and 10th sets. Perhaps, you divided to avoid underpower (type 2 error) due to multiple comparison between 10 sets?

L204: Suppl tables were cited several times, and I think these data are important for understanding the results well. So, if available, the authors should include these tables in the main text.

L289: This sentence seems to be too conclusive: which “may have” acted as?

L308: Demanet 2013 and Barlas 2013 showed effects of physical effort and action options on agency but not effect of attention. Please correct them and/or add appropriate citation if needed.

L316: It should be temporal judgment task, not agency judgment task.

L331: did not “show” major?

L350: What do the “predicted time” and “simulation time” mean? Please specify.

Overall: the authors use the term “post-error” as if it is adverb (e.g. occurs post-error; effect post-error for). But is it grammatically correct?

Suppl Data: Non-English words were found in the “cluster” sheet. Use English only.

Suppl Video: English subtitles may be required as she said something in non-English.
Experimental design: The authors stated that the present task is novel. But, as discussed in lines 244-258, the task is indeed partially based on the previous ones. Although novelty itself does not matter, I would recommend describing how novel the task is and how it is (un)related to the previous ones in the Introduction or Method section rather than Discussion.

This task is designed to induce perceptual-motor learning. However, it is unclear what was learned. The authors have assumed that similar sensorimotor mechanisms (i.e., internal prediction, post-hoc matching, and error correction) underlie the perceptual-motor learning and generation of agency. Thus, ideally, the present task should induce sensorimotor-like learning. In traditional perceptual-motor learning paradigms, sensorimotor coordination and motor control are learned. For example, correspondence between arm movement and its “biased” visual feedback is learned due to updates of internal model, and consequently individuals can smoothly control their arm and the feedback (e.g. rotated mouse paradigm: Imamizu et al. 2000). On the other hand, in the present task, participants viewed a moving object, expected when it comes to the center of screen, and executed one keypress movement at the desired timing. I am concerned that this task indeed induces a learning of computation and estimation of the temporal information, like a time-to-contact estimation (Tresilian, 1995). To enhance your findings, I would recommend clarifying the underlying nature of your task.

Clusters 1 and 2 were defined by the differentials between first and last sets, not by overall amount of error. Am I correct? Based on the Results section and Fig 5, both interpretation may be possible. Please clarify.
Validity of the findings: The discussion on reward is interesting but speculative. Whether amount of error is rewarding depends on whether participants know the amount of their own error. Although I understand there were no feedback about the performance, how and to what extent did the participants know the amount of error and its variation? And, to what extent did the participants feel their (varying) error as rewarding. These should be potential future directions.

L262: In my understanding, Di Costa et al. (2017) did not use a between-design (there were no groups). Please check. If so, the following discussion at L263-68 would be subject to amendment.

L284: Post-error boost is found mainly for the action binding (Di Costa et al. 2017). Action binding relies more on predictive mechanism, according to Moore & Haggard (2008). Thus, your assumption “post-error boost as a postdictive mechanism” might not be valid.
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: CHANGES IN INTENTIONAL BINDING EFFECT DURING A NOVEL PERCEPTUAL-MOTOR TASK
Review round: 1
Reviewer: 3

Output:
Basic reporting: The study investigates how intentional binding (compression of perceived duration between voluntary action and its outcome) is influenced by learning of a perceptual-motor task prior to the intentional binding task. This has been achieved by using a novel paradigm that integrates the tasks of perceptual-motor learning and intentional binding along with each other. Results show that intentional binding tends to increase over time as participant’s performance improves in perceptual-motor task. The task is novel and interesting and the results have a implication for understanding intentional binding in context to other tasks (something that majority of the IB studies ignore by studying IB in isolation), and is something that I take great interest in. Authors have not a great job in designing, conducting the study and explaining the results.
However, there are some portions with respect to methodology that need more explanation. It is my strong belief that answering these points will greatly help in improving the shape of the manuscript. I have given my comments in chronological order followed by general comments for each section.
1.	Basic Reporting
a.	Line 18-19: “Thus far,….investigated”. The line is not clear and doesn’t correctly reflect the experiment that the authors conducted.
b.	Line 33-34: ”….IB is elevated when strong perceptual-motor learning occurs”, the word strong is not needed. In my opinion, it would be sufficient to say that IB is elevated when perceptual-motor learning occurs.
c.	Line 78-81: “However, …..unclear” the sentence is unnecessarily long and complicated, I would suggest that the sentence should be rephrased to make it clearer.
d.	Line 100-103: The authors talk about Di Costa et al. (2017) and rightly point that although the study shows post error boost in sense of agency they do not show how binding changes across time. However, the statement “it was also unproven whether the occurrence  of errors asa postdictive mechanism enhances the IB effect” might not be the right conclusion based on the study. Results from the study clearly show that the same trial outcome does not influence the IB value. The authors should revisit the results and clearly state the original results. Authors have also missed a very important result from the study, the fact that the Di Costa et al. (2017) looked at the relationship between learning rate and IB,  showing that the post error boost in IB is not a result of error in previous trial but rather a result of learning from previous trial. In my opinion authors should include the result in their manuscript as it is very closely linked to what the authors aim at investigating.
e.	Line 104- Line 112: The section on dopaminergic neurons and the idea that task difficulty is linked to reinforcemnt learning looks a bit out of place and the role that the section is playing in the introduction is not clear. I would suggest either moving the section to the discussion, or making it short and integrating it with the earlier paragraph. The lines do not provide a strong enough rational to form the basis of hypothesis introduced in the next paragraph.
f.	Research question needs to be specified clearly and strong rational should be provided for the research question
g.	There are few grammatical errors in the manuscripts as well as few typographical erros ( line 268: from instead of form). Also, some sentences are unncessarily complex. Proof reading the document will help remove such errors in the mansucript.
Experimental design: 2.	Experimental Design
a.	The experimental design is really interesting and definitely provides a novel approach to look the relationship between perceptual motor-task and intentional binding.
b.	Line 116-117: Authors hypothesize that post-error increase in binding effects will not be present for group with low level of difficulty. However, based on the rationale authors provide for the hypothesize, same hypothesis should also be given for high levels of difficulty  (or have authors decided to include only participants below a certain error thereshold)
c.	Line 120: Chronoligcally, aim should preced the hypothesis. Authors may need to rewrite the introduction section in order to make these changes.
d.	Line 125: “We then aimed….” The line reads as if the aim was decided in a post-hoc fashion after the initial clusters were identified. I would suggest that instead of calling it an aim of the study it can be rephrased to ….” We  then  investigate whether…..”. Also, it might help to keep  a distinction between thing that were planned prior to study (the aim, hypothesis) and the things that were obtained post-hoc, the clusters, results. However, this is not a comment against the manuscript, how the authors choose to present the results depend on the style they are following.
e.	Line 153: In the preliminary task the SOA between key press and presentation of tone is randomly selected between 1-1000 ms. However, because true randomization is being done there is a chance that participants get familiarized only with very short or very long SOA’s. This might influence how well they are able to perform the interval estimation task at later point of time.
f.	Line 162: “The mean value obtained from 18 values was used as baseline”. Does the mean value here refer to the estimate given by participants or to the mean of the error between actual and reported SOA.
g.	Line 165: The control task that the authros have used might not be a able to provide a pro[per baseline. It would have been great if a second control condition could be included that might measure how participants are estimating duration between keypress and outcome when they don’t perform any percpetual motor task. Only then one can talk about the effect that performing a perceptual motor task might have on estimates of intentional binding. (For example, perofrming a perceptual motor task prior to IB task might result in depletion of attentional rsources required to estimate interval in proper fashion, this would mean that results on IB do nto reflect SoA, they are rather reflecting some other cognitive process).
h.	Line 185: More details should be given about the clustering procedures in the data analysis section. From text it seems that the difference in error value between first and last set was used for clustering, but I am not sure.
i.	Line 188: What is the rationale of clubbing two sets together to have 5 blocks. How does decreasing the number of blocks helpful in the data analysis. Will results be different if we take 10 sets for analysis instead of 5 blocks. Why 5 blocks can we just have 2 or 3 blocks.
j.	Line 192-193: Mean of time estimates from control block were taken separately for the three SOAs or results for the three SOAs was combined together.
k.	Line 208-211: Authors say that  difference between first and last block was significantly greater for cluster 2 compared to cluster 1 and go on to conclude that cluster 2 showed motor improvement as task progressed. However the conclusion doesn’t follow from the analysis.  The t-test in line 209 suggests that learning is more in cluster 2 compared to cluster 1. In fact, supplementary table 2 shows that difference between 1st and 5th block is significant in both cluster1 and cluster 2.
l.	Line 218-219. No statistical test has been conducted to support the conclusion that differnce between 1st and last block is greater in cluster 2 than cluster 1. Such a statement can only be made after analysing the interaction between cluster and block, which authors don’t look at.
m.	Instead of performing cluster analysis and logistic regression would have provided more insight into the exact nature of the relationship between error and intentional binding in that trial.
n.	The way data has been analyzed, it is averageing IB values as well as error values across trials within a block. Thereby not taking advantage of the time-series data available to the authors. A trial by trial analysis would have been more interesting.  Also, based on current analysis it is impossible to say whether the increase in intentionalbinding is postdictive effect of error or post error boost in intentional binding (some thing that authors suggest Di Costa et al., 2017) dosent.
Validity of the findings: 3.	Validity of the design
a.	Line 250-254: Authors talk about why libets clock cannot be used by taking a counterfactual situation stating problems with the liebts clock task. The paragraph needs to rephrased and made less complex.
b.	Line 269: Authrs introudce a new classification Unsuitable and sutiable, I would suggest that authors should stick to a single convention through out the paper.
c.	Line 271, 283: You have not investigated post-error boost, please modify the line.
d.	Line 285-289: As post error boost is not explicitly investigated, the lines are speculations and should be menitoned as such.
e.	Line 290-299: Dopaminergic explanaiton of what is happening is important but  should be preceeded by discussion of behavioural studies investigating percpetual-motor learning. A complete explanation at Dopaminergic level dosen’t help as authros are not looking at that level of cognitive processes.
f.	Authors should also discuss the implication of these results for mechanisms of SoA / Intentional binding.
g.	A greater discussion linking other studies with control, associations, eprcpetual-motor learning and inentional bindnig with current manuscript is needed.
Additional comments: 4.	General Comments
a.	57-58: The authors suggest that the mechanism underlying both SoA and perceptual learning is similar. The argument in the paragraph suggests that both sense of agency and perceptual-motor learning involve actions, outcomes and are modulated by motivation. It would be wrong to say that both have similar mechanisms.
b.	63-64: it is not clear how temporal compression of interval can help individual determiner their sense of agency. In my understanding there is a correlation between IB and explicit SoA (that too not always!).  There is no implication of causality in the original paper by Haggard.
c.	Line 86: Authors attribute the results in Yoshie & Haggard, 2013 to rewards and penalties, the original paper attributes the effect to emotional valence and explicitly say that their results cannot be due to any kind of gain that subjects attach the outcome.


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: CHANGES IN INTENTIONAL BINDING EFFECT DURING A NOVEL PERCEPTUAL-MOTOR TASK
Review round: 2
Reviewer: 1

Output:
Basic reporting: 1-1
Grammar of this manuscript became good now. However, I still felt difficulty in understanding what authors wanted to say very often. Some sentences did not even make sense.

For example, Line 18 'How IB may change over the course of a perceptual-motor task, however, has not been explicitly investigated' could be read as if the authors measured how the degrees of IB changes in the time course of each trial. This sentence is grammatically correct but it would be appropriate to say 'perceptual-motor learning' (instead of 'perceptual-motor task') in this context.

1-2 [Line 51-52]
The sentence is not precise.

First, we feel SoA even when we make an action spontaneously without any explicit goals or purposes. IB has been found in the experiments where participants were required to make actions spontaneously without any goals.

Second, motor control is the process to reduce the differences among them. SoA would come up when the differences among them were small.

1-3 [Line 71-73]
What Vinding and Pedersen showed was that when the intention to act is formed in advance, it entails a stronger SoA than when the intention is immediately followed by the action. Vinding and Pedersen did not mention that there was difference in the goal between two types of intention in their paradigm.

1-4 [Line 76-78]
The people who have read Haggard & Clark (2002) will guess what the authors wanted to say by these two sentences. But many readers would not understand them.

1-5 [Line 241-242]
This sentence does not make sense.
Do you mean that the conventional tasks do not consider the possibility that perceptual-motor learning would change the degree of binding?

1-6
Please check the submission guideline. You usually do not use 'et al.' to refer two-author studies.

1-7 [Line 263-268]
It was hardly possible for me to guess what the authors wanted to say.

1-8
The discussion about the reward system was a little bit speculative.

Reduction of error (i.e., increase of reward) increased SoA in the cluster 2 participants. How is the result of this study consistent with the previous study by Di Costa et al.?

1-9 [Line 340]
To conclude that the postdictive mechanism worked in the IB task, the authors need to test if the IB decreases when the feedback of the perceptual-motor task was given after the estimation of the delay of the tone.
Experimental design: 2-1
The refresh rate of this study (60Hz) was very low to ask participants to make a quick motion watching a stimulus moving at high speed.
Researchers studying time perception have tried to increase the refresh rate of monitors as high as possible (>100Hz).

2-2
Time perception measured by traditional action tasks is supposed to contain the effects of
1. intention to act,
2. action-related proprioceptive feedback and
3. individual difference in the perceived timing of a tone.

Haggard measured the effect #2 by applying TMS to the motor area of participants.
Haggard and other researchers have controlled the effect #3 by passive listening conditions where participants reported timing of a tone without action execution.

In the present study, the experimental task would include the effects of
1. intention to act,
2. action-related proprioceptive feedback,
3. individual difference in the perceived duration between a visuo-motor event and a tone,
4. motor performance of each trial,
 and
5. improvement in motor performance.

It is unclear which factors were  controlled by the control task where the perceived duration between two tones was measured.

I suppose the aim of the study is to measure the effect #5. The effect #1-4 could be controlled by taking the performance in the first block as a baseline.
Validity of the findings: Please plot the error of the perceptual-motor task as a function of the perceived duration (perceived duration - actual duration).
Additional comments: The authors could discuss the possibility that the sense of agency plays a role in motor learning.


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: CHANGES IN INTENTIONAL BINDING EFFECT DURING A NOVEL PERCEPTUAL-MOTOR TASK
Review round: 2
Reviewer: 2

Output:
Basic reporting: I appreciate the efforts that the authors made. The quality of the manuscript has been improved. I would like to provide some more minor comments.

L221-236:
Please specify what ES (effect size?) indicates. Cohen's d or r?

Table 1:
For cluster 1, p-value seems too high. Is this typo?

Tables 2 and 4:
For 95%CIs, zero in the ones place should not be omitted (just for consistency).

All Tables:
I recommend making the numbers of decimal places consistent.  For example in Table 1, -0.6601593 -> -0.660.
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: CHANGES IN INTENTIONAL BINDING EFFECT DURING A NOVEL PERCEPTUAL-MOTOR TASK
Review round: 3
Reviewer: 1

Output:
Basic reporting: Each paragraph of the introduction part became clear and precise now.

Comment 1-1
Line 80 'Therefore, ...'
The idea described here was initially followed a sentence that Vinding et al showed that the size of IB is dependent on the purpose of the action. Now the sentence was revised. The authors need to correct the sentence following the revised sentence.

Comment 1-2
Line 82
This paragraph could be moved to line 69 (after the first sentence of the paragraph). This change will make it easier for readers to follow the flow of the logic.

Comment 1-3
Line 93
I should have commented about this point earlier but are the contributions of predictive process and of volition/planning same?

Comment 1-4
Line 130
Does authors hypothesize that the IB disappears after the participant completes motor learning process though many IB studies have shown the presence of IB in simple tasks which do not require motor learning?
Experimental design: I should have suggested this point earlier but the error values (absolute distance values without sign) do not have the information how the participants tended to press the button earlier or later than the correct timing. The tendency would reflect time perception of the participants. It would be great if the authors could plot relative error values of a few participants from the two clusters.
Validity of the findings: Comment 3-1
The authors plotted the IB values as a function of the actual interval of the stimulus to respond to my suggestion. What I wanted to suggest the authors was to plot the error values of the hand action task as a function of IB (a scatter plot with x (or y): perceived duration - actual duration [ms] and y (or x): error value [px]). If the error in the action was critical to the size of IB, the error values (y) and the IB values (x) should correlate to each other.

I would also suggest the authors to plot the IB values as a function of the change in error values of each trial compared to the former trial. Correlation between them will support the discussion that reduction in error facilitated the IB.

Comment 3-2
Line 325
This sentence could be read as if Hon et al. (2013) showed that the sense of agency is reduced when the participants were required to focus on the task very well.

Hon et al. (2013) reported that the sense of agency was low in the high cognitive load condition. Their results suggest that the sense of agency is reduced when the attention was taken away from the action and the result of the action.
Additional comments: The authors often use the word 'optimal'. I guess the authors supposed that the sense of agency could be drawn as a U shape model where too easy or too demanding second task (i.e., too low or too high requirement of attention to the second task) reduces the sense of agency. Is this understanding correct?

Line 282
This sentence sounds as if the authors did not design the task optimally to each participant.

Line 333
It was not clear what the authors thought to be 'optimal'.


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: SCREENING OF PROGNOSTIC BIOMARKERS FOR ENDOMETRIAL CARCINOMA BASED ON A CERNA NETWORK
Review round: 1
Reviewer: 1

Output:
Basic reporting: This work , although not pointing a novel idea , is basically well designed observational study.

the Introduction is basic but written plain and straight forward
 The methods are well sectioned and summarised
Experimental design: The design is within scope . A basic observational study . The current knowledge regarding non coding RNA is vast and many studies relates to early diagnosis or prognosis

no technical or ethical issues are present

The methods are well described
Validity of the findings: Again ,  I do not find the result to be ground breaking .
The results are well described and discussed nd contributes to the body of knowledge in this field
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: SCREENING OF PROGNOSTIC BIOMARKERS FOR ENDOMETRIAL CARCINOMA BASED ON A CERNA NETWORK
Review round: 1
Reviewer: 2

Output:
Basic reporting: No comment.
Experimental design: Functional and enrichment analysis of ceRNAs should be described in a more detailed manner in method section.
In general, methods should be described with sufficient information to be reproducible by another investigator.
Validity of the findings: Findings are awesome and discussion includes all the critical assessments of the findings with similar studies.
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: SCREENING OF PROGNOSTIC BIOMARKERS FOR ENDOMETRIAL CARCINOMA BASED ON A CERNA NETWORK
Review round: 1
Reviewer: 3

Output:
Basic reporting: Needs work. I believe that the article uses clear English to describe the study design and setup but could use some work on the following aspects
1) There are a lot of spelling and grammatical errors that can be resolved with a spell check and some minor proofreading.
2) Additionally, the authors use confusing terminology which reduces the readability of the manuscript. For example, in lines 67-69 they say” We recruited 461 EC patients …” and follow it up by saying no ethics approval was required since they downloaded the data. This reduces clarity and occurs a few more times in the manuscript.
3) The results section is very hard to follow because the authors frequently describe the sub parts out of order (see explanations for figure 9, and 10) for example. This is compounded by the fact that most of the figure captions do not contain enough details. I encourage the authors to separately add a legend to each subpart of the figure in addition to the caption to improve the readability of the figures.
Additionally, text in the results section itself is often just 1-2 lines for the entire figure(See fig 5 and 6).  I request the authors to invest some time in detailing the analysis, the findings and its significance to the biological question at hand for each figure. This will greatly help the reader understand the authors reasoning for performing the analysis
I believe that the background/context of the study has been laid out sufficiently and relevant literature has been cited. Although some more work is required on a few lines in the introduction (see lines 33-36 specifically), it is clear what the authors have set out to accomplish.
With respect to the figures, it’s my opinion that the authors have created some extraneous figures. For example, in figure 3, parts C and D while interesting, are redundant and do not really convey any biological relevance by themselves. The authors do not spend any of the discussion explaining their rationale behind the analysis strategy either and the reader could use some help following the scientific rationale for this analysis (this is especially true in case of figure 4 where they have applied network analysis and stated the results without any analyses of the results, why it was done in the first place or explaining why its significance).
 Please try to focus the data in service of the question at hand, which in itself needs some clarification ( moving some figures to supplementary data will also help)
The submission seems self-contained
Experimental design: I believe that the current work is original primary research that is within the aims and scope of the journal.
I commend the authors for clearly defining the research question at hand and explaining its relevance to the understanding of RNA networks in EC
I believe that the authors have attempted to clearly explain the methodology. In order to encourage reproducibility of their analysis, the authors may consider hosting the code on a repository such as github so that all readers can access and recreate their findings.
I believe that the authors have thoroughly investigated the mRNA, lncRNA and miRNA profiles of endometrial carcinoma that was accessible from TCGA. I believe that the study meets the prevailing ethical standards in the field
Validity of the findings: I believe that the findings in this study are valid. However, especially for the part of the paper that deals with generating the prognostic markers, I believe that the authors need to separate the data into a training and validation data set. They have data from 463 patients and I believe that they can easily accomplish this. This will greatly enhance the credibility of the generated biomarkers instead of solely relying on the AUROC number and the Kaplan Meier curves.
I find the manuscript somewhat hard to follow since the authors identify 8 prognostic markers, calculate their predictive power and build a network around them only to identify two more mRNA( PSAT1and KIF23)? If these are the two genes they are proposing as biomarkers, can they rerun the AUROC with them( for a total of 10 mRNA or use just these 2) ? If not, why was this part of the analysis performed? It seems removed from the original intent of the paper and seems to take it in an unclear direction. I am also confused by them running GSEA on these 2 genes and analyzing it instead of analyzing the GSEA profiles of the 8 mRNA that they propose. I think that this part of the paper merits more explanation of scientific rationale.
Additional comments: I believe that the authors have made a strong attempt to understand the interactions between mRNA-miRNA and lnRNA expression in endometrial cancer. Their analysis while often excessive cannot be faulted for not being thorough.
Overall, I think that the readability and applicability of the paper will be greatly improved by focusing
1)	The questions that the authors are trying to address: are you identifying prognostic markers or performing a RNA network analysis?
2)	The data you are providing to answer this question: some figures are redundant and others have not been explained thoroughly. Then sub-network analysis section of the paper in particular needs to be evaluated with this lens


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: SCREENING OF PROGNOSTIC BIOMARKERS FOR ENDOMETRIAL CARCINOMA BASED ON A CERNA NETWORK
Review round: 2
Reviewer: 1

Output:
Basic reporting: I believe that the article uses clear English to describe the study design and setup
I believe that the background/context of the study has been laid out sufficiently and relevant literature has been cited.
The submission is self contained and the figures make sens
Experimental design: I believe that the current work is within the aims and scope of the journal.
I believe that the authors have attempted to clearly explain the methodology. In order to encourage reproducibility of their analysis, the authors may consider hosting the code on a repository such as github so that all readers can access and recreate their findings.
I believe that the authors have thoroughly investigated the mRNA, lncRNA and miRNA profiles of endometrial carcinoma that was accessible from TCGA. I believe that the study meets the prevailing ethical standards in the field
Validity of the findings: I believe that the findings in this study are valid.
Additional comments: I believe that the authors have addressed most of my concerns and re-worked the paper sufficiently. I commend the authors on reworking the figures to present a coherent paper.
There are some minor edits
1) Some figures are not described in the text still (eg 5K and 5L).
2) In order to encourage reproducibility of their analysis, the authors may consider hosting the code on a repository such as github so that all readers can access and recreate their findings.
3) i don't follow how the authors validated their top 4 miRNA and mRNA's since they mention they didnt do a training and validation data set? How was figure 7 generated? please clarify: Is this qPCR data?
4) the discussion is lengthy and gives too may examples of RNA's and their roles in cancer. Some editing will help contextualize this study better
5) it gets a little confusing with all the lincRNA, mRNA and miRNA names being used int he manuscript. is it possible to make a simplified schematic summarizing the findings at the very end?


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

Input:
Title: THE RECENT EXPANSION OF FOX SPARROW (PASSERELLA ILIACA ILIACA) BREEDING RANGE INTO THE NORTHEASTERN UNITED STATES
Review round: 1
Reviewer: 1

Output:
Basic reporting: This manuscript is well written and well analyzed.  The figure works.
Experimental design: The author has done an adequate job of gathering data to demonstrate the expansion of the distribution of Fox Sparrow to the south in the eastern portion of its range.
Validity of the findings: These findings are quite valid and interesting to ornithologists
Additional comments: With respect to the discussion, no mention is made of the fact that expansions southward are somewhat counter-intuitive.  This can be seen in elevational studies to (e.g., Mortiiz et al. 2008, see Montane Shrew).  There is also nothing about historical range change in this species which over the last 10,000 years probably included many of the areas of the recent expansion.  I think the author could also bring up the issues of climate change and what was predicted for Fox Sparrow (and possibly examining Blackpoll Warbler and Bicknell's Thrush) by recent broad analyses of North American birds that have suggested climate will drive most species northward.

Here are couple of other recent studies on avian range expansion in North America.  I think putting what Fox Sparrows are doing in the broader ornithological perspective is too good an opportunity to miss.

Ingenloff, K., Hensz, C.M., Anamza, T., Barve, V., Campbell, L.P., Cooper, J.C., Komp, E., Jimenez, L., Olson, K.V., Osorio-Olvera, L. and Owens, H.L., 2017. Predictable invasion dynamics in North American populations of the Eurasian collared dove Streptopelia decaocto. Proc. R. Soc. B, 284(1862), p.20171157.

Butcher, J.A., Collier, B.A., Silvy, N.J., Roberson, J.A., Mason, C.D. and Peterson, M.J., 2014. Spatial and temporal patterns of range expansion of white‐winged doves in the USA from 1979 to 2007. Journal of biogeography, 41(10), pp.1947-1956.

Specific comments:

Line 160.  This is a little bit of an overstatement.  While there is documentation that the species occurs on the high mountains of the Adirondacks.  This is based on a single record (so far).

Line 198.  yet they are now widely reported in New Hampshire and Maine during June and July.  This isn't really true.  It is just a wording issue, but Fox sparrows are now reported from the high elevations in coniferous forest of northern and western Maine and northern New Hampshire.

Line 232.  Change to: "Exapansion of breeding  Fox sparrows"

Line 236.  "Banks (1970) suggested a similar explanation for the spread of Fox Sparrows onto the western slopes of the Cascade Mountains of Oregon (but see Marshall et al. (2003))."

This should be expanded on, clearly Marshall disagreed with this hypothesis, why?

Figure 3.  I think this could be made better by adding in data that addresses the availability of suitable habitat across elevations in polygons related to the area of expansion.  I assume the high frequency of lower elevation records in Maine could be related to latitude and/or habitat management.


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

Input:
Title: THE RECENT EXPANSION OF FOX SPARROW (PASSERELLA ILIACA ILIACA) BREEDING RANGE INTO THE NORTHEASTERN UNITED STATES
Review round: 1
Reviewer: 2

Output:
Basic reporting: The author has submitted a well written manuscript that adheres to the expected structure of a scientific contribution. The author has consulted a broad array of appropriate literature and citizen science data. I was particularly pleased to see that the North American Birds series had been consulted, though I was surprised that no citations came from the review of the regional summaries; surely those authors have also pointed out the increase in this species? The figures are clear, and the first two figures very clearly support the Discussion. I am on the fence about whether Figure 3 is needed, as I suspect that text including the mean and standard deviation of these sightings might be sufficient (there is not much text otherwise spent describing or interpreting this pattern in the Discussion).

I believe that this manuscript is missing the required dataset submission. The author indicates that all data are publicly available through eBird. However, additional records may come to light as existing, older field notes are added to the database, or as other records are re-reviewed when regional reviewers adjust filters, and this could potentially change the results of a repeated analysis. As it stands now, the reader cannot completely duplicate the analysis that the author undertook. I would suggest following the PRISM workflow that PeerJ requests for systematic reviews, and then upload the Excel files from the resulting eBird datasets.

Did the author check The Kingbird journal for additional New York records?
Experimental design: The author has focused on a regional expansion of a summering species into the northeastern United States. While this paper presents no new data, it is a thorough review of published records that have not been assembled into a single narrative before. Birders and ornithologists in the region are already aware of the expanding range of this species as a breeder, but the expansion has not been thoroughly reviewed before. The extra effort made to compare frequency, standardized against two more common species, is appreciated.

My concern, however, relates to the PeerJ expectations for this kind of manuscript. PeerJ states, "Manuscripts that report range extensions, life history information, or the description of new species or other taxa should address a biological question or hypothesis as the focus of the submission." While this submission does place the story of range expansion into the context of a hypothesized influence from increased habitat modification in the region, the manuscript does not explicitly test this. To do this, the author would need to quantify which areas have increased pressure and compare this to observed increases in breeding season records. I am not sure that this level of forestry data is available, so I wonder if there could be a rougher scale approach comparing areas with no logging pressure versus those with pressure (e.g. compare wilderness to non-wilderness mountains within State and National Forests)?

The author cites a few instances of documented nesting, but most of these records do not have documentation of nesting. How many of these observations were of two individuals, and are there any data on females being present? Or are they all unpaired, singing males? There is a difference between unpaired males summering south of their range versus breeding there. Both are part of a single phenomenon, I would think; as a species expands, the vanguard would be unpaired males. But if almost all of these observations are of unpaired males, then this manuscript is documenting a changing behavior of unpaired (and presumably second calendar year individuals) rather than a difference in breeding distribution. We see this in lots of other species, where younger birds don't make it to the core breeding range for their first summer as an adult (particularly in shorebirds, but there are many, many reports of passerines doing this in the pages of North American Birds and in eBird).
Validity of the findings: This manuscript demonstrates sufficient scientific rigor to accomplish its goal of documenting the increasing presence of Fox Sparrow in New England in summer.

The comparison of the expanding range to the spruce fir regional harvest rates needs more investigation and quantification. This is related to the hypothesis testing issue I listed in Experimental Design, is critical for the context of this expansion. No references are cited to back up any statements about increased or changing forestry regimes. This is particularly needed in lines 233-234.

Line 97 indicates that the choice of resolution for the grid was arbitrary. I agree that there is no true guideline for size to use, but I would like to see investigation of the effect of grid size on the results. 10 km^2 strikes me as being quite large for this study; does revisiting with 5 and 1 km^2 grids change your results? Your overall study covers very few grid cells at the 10 km^2 resolution.
Additional comments: I have a minor note about scientific/common names here. The Red Fox Sparrow is an informally recognized common name (common names in North America are only assigned at the species level by the American Ornithological Society's Check-list Committee). In general usage, Red Fox Sparrow refers to a subspecies group, not a particular subspecies. That is, Red Fox Sparrow is P. i. iliaca and P. i. zaboria. This contribution focuses on P. i. iliaca, and the common name of Eastern Fox Sparrow is typically assigned to this one (see Rising 1996, for example). The manuscript's title is correct, but there are some additional uses within the text that should be corrected, particularly line 30.

eBird is cited incorrectly; they prefer that you use this: Sullivan, B.L., C.L. Wood, M.J. Iliff, R.E. Bonney, D. Fink, and S. Kelling. 2009. eBird: a citizen-based bird observation network in the biological sciences. Biological Conservation 142: 2282-2292. I would also suggest adding some text to explain that these are vetted observations by peers, not just acceptance of all observations from observers at all experience levels.

Need a broader citation for North American Birds as a journal (list publisher, at minimum) and explain that the other titles are previous titles for the same journal. Maybe a phrase to explain that this is a vetted review of regional bird records for each season?

Line 57: delete hyphen in "breeding-bird"

Line 90-92: awkward sentence, could be rephrased or broken into two to explain why this decision was made.

Lines 154, 165, and elsewhere: can remove the minus in front of the longitude, as indicating that the degrees are West makes the minus unnecessary.

Line 167: extra parenthesis can be deleted.

Line 200: delete hyphen in "breeding-range"

Lines 204, 208, 217: delete hyphen in "breeding-season"

Lines 206-207: need to include some citations to back this up, I'm not sure which of these efforts would have been focused widely enough to describe rarities as opposed to the budworm-focused species.

Line 212: need a citation for the Quebec trend.

Figure 2: delete hyphen in "breeding-season". Figure legend should indicated what the solid and hyphenated lines mean.


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

Input:
Title: THE RECENT EXPANSION OF FOX SPARROW (PASSERELLA ILIACA ILIACA) BREEDING RANGE INTO THE NORTHEASTERN UNITED STATES
Review round: 1
Reviewer: 3

Output:
Basic reporting: This manuscript is well put together, well written and I see no issues with the general outline of the manuscript.
Experimental design: This is not an experiment as such, but an analysis of a set of observations in the wild, so this feature not completely relevant.  However, it does in general meet the criteria for ths section.  The issue it analyzes is interesting.  The methods used for analysis make sense and are described in good and clear detail.
Validity of the findings: The finding seem to be valid and the comparisons made to other species make sense and strengthen the argument that this change in Fox Sparrow distribution is real and not a reflection of increased observer activity in the region or habitat.  I personally would like to see more speculation or consideration of what this distributional change indicates by considering other bird species found in the same habitat in this range and other species that are expanding their range southward in this part of North America.
Additional comments: My main concern with this paper is that there is not a real attempt to place the changes in distribution of Fox Sparrow into context with other species in the region.  The two groups of species, I’d like to see some consideration of would be species that are extending their breeding range south in the NE US, and those species that occupy the same sort of habitat as Fox Sparrow.  In terms of species extending their range, I don’t know the specifics of the part of North America, but I know for example has Merlin has extended its breeding range south across much of its range in eastern North America. Are there others, perhaps species more focused in NE US, that might give insights into the changes happening in Fox Sparrow.  Similarly, Fox Sparrow shares its habitat with some other species.  I’m thinking particularly of species that occupy early successional clearings in coniferous forests.  While Bicknell’s Thrush and Blackpoll Warbler are, I think, good species in terms of range and association with coniferous forest, neither are really tied to the specific habitat that Fox Sparrow uses.  Gain, I don’t know the details of bird distributions in the northeast well enough to suggest a suite of species.  The only one that occurs to me is Mourning Warbler.  It has a much broader range and I wouldn’t expect them to be expanding their range, but you might see evidence of greater abundance or habitat occupancy if the Fox Sparrow response is not unique to that species.  I don’t really expect a detailed analysis of other species, but at least some consideration of other species with analogous range changes or occupying habitat that might be responding to changes in forestry management in similar ways.

It would be really helpful to have a map that shows the range (or at least southern limit) of breeding Fox Sparrows in eastern Canada at some reference time period when the expansion begin.  This would put the expansion into the NE US more in context

Line 100	People entering traveling counts into e-bird are supposed to place their point at the midpoint of the route they traveled, not the starting point as stated here.  Doesn’t really change this issue, but might reduce the number of times that an observation came from the “wrong” grid cell, since the farthest the observer birded from the mapped point would be half the distance it would be if the starting point was mapped.

Line 129	States that Keith and Fox 2013 describe Fox Sparrow as common migrant in New Hampshire, but line 154 gives Keith and Fox as source for breeding record from New Hampshire.  I think the seasonal status of Fox Sparrow in New Hampshire given by Keith and Fox needs to be better described.

Line 151-152	This sentence provides information on occurrences in Maine in 1999 and 2000, but reference supporting this is a 1999 paper, which couldn’t possibly have information on a 2000 year.

Line 167-169 	This is a run on sentence that should probably be broken up.  I would put a period after “significance” and delete “but.”  Also I think the ) following July 2016 should be a comma.

Lines 167-174	Can any sources be cited for the information in this paragraph?

Lines 186-188	The difference in elevational distribution between Maine and New Hampshire is interesting and a figure (Figure 3) is used to support this difference.  In the discussion, this difference is not talked about at all.  The paragraph of lines 220-228 suggests to me that the lower elevation distribution in Maine and the fact that the summering records in Vermont and New York are in high elevation sites reflects habitat availability and not some other factor.  However, the paragraph at 220-228 does not mention the elevational distribution of the summer records at all.  One alternate possibility I have considered is that it is a reflection of time that the population has been established.  The idea here is that Fox Sparrows expands range into high elevation krummholz habitat, and as the population expands is able to move into the structurally similar lowland early successional areas in logged spruce forest.  I wonder if there would be any temporal pattern in the elevational distribution of birds in Maine and New Hampshire with earlier records being concentrated at high elevations.

Lines 204-207	Can any sources be provided for “ornithological investigations” in the 1980s in this geography mentioned in this sentence.

Line 236 – 238  I think it would be worth an additional line or 2 about the Oregon situation because the suggestion of Marshall et al is that the extension of the known range to the western Cascades might be a reflection of accessability rather than an actual range change.  Given that they don’t provide any data, this is purely speculation, and given that this paper goes to some trouble to deal with this possibility in the NE US, I think it is worth being more explicit here about the parallels between the two cases.


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: POSTURE SIMILARITY INDEX: A METHOD TO COMPARE HAND POSTURES IN SYNERGY SPACE
Review round: 1
Reviewer: 1

Output:
Basic reporting: In all the manuscript, the English language must be improved. The current phrasing makes comprehension difficult. Some examples: lines 28-29, 60-64, 83-86, 135-136.

Abstract

Line 27: “Wonderful” may not be the most descriptive term while “several” may be a bit limited.
In “background” (Lines 26 to 33), the link between the idea of “effort” to adopt/change hand posture, and the goal of the study to quantify the similarity between hand postures is unclear.

Line 41, PCA is a widely used dimensionality reduction technique, already successfully applied on hand postures characterization (e.g. Gentner & Classen, 2006; Koul, Cavallo, Ansuini, & Becchio, 2016). What is the novelty of the present study? Authors should stress the added value of their study.

Introduction

Line 61: This paragraph is very difficult to understand. It starts with “however” but to me the presence of redundancy is equivalent to the sentences above, explaining the necessity to coordinate many muscles and articulatory joints.

Line 68-69: “…execution, sometimes even managing every single variable for executing a task successfully”, the authors should reference this hypothesis.

Line 70-71: “…the CNS forms a synergy (a group of relatively independent variables) (Latash, 2008b), that combines multiple elements which result in the successful performance of the task”. This is a very unusual and obscure definition of synergies. What are “relatively independent variables”? What are the “multiple elements” combined? And what is the link between these synergies, these variables and these elements?

Knowing that SNC control muscles or group of muscles (that results into kinematic trajectories), how invariances at the kinematic level are reliably representing the control command?
The authors should also define the term “eigenpostures” (e.g. lines 83-86).

At the end of the introduction, the link between effort, synergies and posture similarity index is still unclear.

In the rest, they justify this study by mentioning the necessity to increase the degrees of freedom and define from that, a similarity index. It not really clear to me the innovation here and in the authors should clearly argue better for their technique in the introduction.
Experimental design: Method & Results
Lines 180: “Cut-off frequency for the filter was set to 4.5Hz for removing any possible effect of physiological tremors in static postures”. This cut-off value is surprising and low, the authors should reference studies using a similar value.

Lines 182: “Trials were concatenated”. Is the concatenation of different trials creating artifact (e.g jump)? Did the authors control this?

Lines 214: “By projecting hand postures in synergy subspace, we can take the dimensionality reduction approach (Santello, 1998) or take the stance that the control signal that helps controlling multiple degrees of freedom simultaneously (Todorov, 2002; Todorov et al., 2004).”
Among many others, this formulation is very difficult to understand. In all cases, Todorov’s model is not against the idea of a dimensionality reduction approach, it’s rather a complementary account.

Lines 222-224: “Assuming there is no relation between trials we selected a random trial from five trials for every posture separately, resulting in 100 selected trials per subject (one trial per posture).” Why did they proceed in this way?

Some of the figures may need some additional work to improve quality (i.e. F2), some of them are redundant or not necessary (i.e. F2; F8 panel B) or can be merged in one figure (i.e. F1 and F3; F4 and F5). Authors may want to move some of the figures or tables in the supp. materials (i.e. Table)
Validity of the findings: Discussion
Line 428: “This article showcases a novel approach for comparing hand postures using synergies (PCA).” Unfortunately, it is not clearly visible why this method should be new, see my comments in introduction.

Line 435: The link between “kinematic effort” and similarities between postures is still unjustified.

At the end of the discussion, when the authors go through the goal of the study, I mainly see the description of a method to extract kinematic synergies and compare between them. If this is the goal, they should better justify how such a commonly used technique (PCA) is here used in a “different” way.
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: POSTURE SIMILARITY INDEX: A METHOD TO COMPARE HAND POSTURES IN SYNERGY SPACE
Review round: 1
Reviewer: 2

Output:
Basic reporting: -The work targeting building similarity index between for hand postures. From a total of 100 different postures, individual finger Kinematics were captured by wearable tracking sensor system. PCA was used to extract kinematic synergies. Experimentally, the developed PSI was validated to identify various postures.
-The work from technical point of view is interesting, however, the usability of the work and the future implementation is still weak and not very much connected with the result. I believe this part (the connection) should be much enhanced.
-The introduction is kind of long and discusses various issues that are not in the essential point of the work direction. I believe the introduction could be enhanced/shortened.
- References are old
Experimental design: well covered
Validity of the findings: Not as I expected. Some figures of the finding are hard to understand. What was the original postures represented on the screen? All individuals were requested to follow the same postures?
Additional comments: - The idea of the work is interesting and the reported resulting are promising. The above issues are needed to make the story worth to read.


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

Input:
Title: POSTURE SIMILARITY INDEX: A METHOD TO COMPARE HAND POSTURES IN SYNERGY SPACE
Review round: 2
Reviewer: 1

Output:
Basic reporting: The writing’s quality improved but a lot of sentences are still a bit confused, I will suggest asking a native English speaker to correct the manuscript before publication.

Introduction:
Page 3, Line 69: “low” instead of “lower”, there is no comparison here so ne need for “-er”
Page 3, Line 71: “small” instead of “smaller”
Page 3, Line 76: “This has been attempted probably because of the notion that designing better grasping robots must essentially involve learning from human grasping.” This sentence is complicated and should be reformulated
Page, Line 91: “field” instead of “fields”

Materials and Mehods
Figure 1: increase the size of the font in A’s labels
Figure 2: explain in the caption, why three pictures on the screen? Why one is colored? And why is there a F letter on the right?
Page 7, Line 214: “The experiment consisted of two different tasks, the first task was performing internally constrained postures which include 70 postures, and the rest 30 are constrained postures which involve object manipulation.” This sentence should be reformulated.
Page 8, Line 228: “All the trials were carefully observed by the experimenter and any trial in which the posture was not faithfully performed was repeated.” How many trials on average were repeated?
Page 8, Line 230: “All joint angles” instead of “All the joint angles”
Page 9, Line 253: Suppress “there is”
Page 10, Line 283: “slight” and “slightly” are a bit redundant, please find a synonym
Page 14, Line 395: “Individual PC ratio (F) is multiplied by respective weights (λ) and summed for generating PSI index as in following are present in Supplemental Table S4.” This sentence should be reformulated.
Page 14, Line 408: ”So, in this case, since we chose the same posture (but different trials), so that the data has a relatively large overlap.. changing from one trial’s posture to another requires minimal effort.” This sentence should be reformulated.
Page 14, Line 412: “An advantage of this method is it compares and quantify similarity in synergy space rather than joint angle space.” This sentence should be reformulated.

Results:
Page 15, Line 442: “with previous studies” instead of “with the previous study”
Page 16, Line 456: “one of the possible reasons is task involved in the experiment” incorrect wording
Page 17, Line 489: “only those postures found in 7 subjects are more are presented here for illustration purpose and brevity” incorrect wording
Page 17, Line 492: “include” instead of “includes”
Page 17, Line 493: “the number […] was” instead of “were”
Page 17, Line 503: Specify associated statistical results
Page 17, Line 504: “in in”

Discussion:
Page 18, Line 509: “exploits use” incorrect wording
Page 18, Line 523: “we used idea further” incorrect wording
Page 19, Line 559: “take into account of” suppress the “of”
Page 19, Line 562: “Sometime PSI does not result in intuitive numbers while comparing two postures, possible major reason behind this because of degrees of freedom and the large number of tasks involved.” Incorrect wording
Experimental design: satisfactory
Validity of the findings: satisfactory
Additional comments: Authors have well clarified the manuscript and made clear the goal of the study: creating an index to compare posture. As explicitly stated now, this manuscript describes a new method.

However, theoretical insights for neuroscience or robotic are for the moment absent.


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: POSTURE SIMILARITY INDEX: A METHOD TO COMPARE HAND POSTURES IN SYNERGY SPACE
Review round: 2
Reviewer: 2

Output:
Basic reporting: The revised manuscript is well enhanced based on the previous comments. Figures are well designed now and the story is clear.
Experimental design: Well defined
Validity of the findings: Enough and represent the target of the work
Additional comments: No additional comments