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: IDENTIFICATION OF KIF4A AS A PAN-CANCER DIAGNOSTIC AND PROGNOSTIC BIOMARKER VIA BIOINFORMATICS ANALYSIS AND VALIDATION IN OSTEOSARCOMA CELL LINES
Review round: 1
Reviewer: 2

Output:
Basic reporting: Overall, the manuscript is concise and clear. The authors should carefully describe the results in the Results section with sufficient details such as p-value.
Experimental design: The authors addressed the research questions by appropriate experimental design.  Methods had been described with details. It can be improved by providing more specific information of some materials used in the experiment. Please find the details in the comments.
Validity of the findings: The scientific findings are sound.
Additional comments: KIF4A has been implicated in multiple types of cancer, such as prostate cancer, lung cancer, colorectal carcinoma, etc. To investigate how KIF4A affects cancer cell progression, Pan and colleagues compared gene expression from 12 cancer types. The authors identified KIF4A significantly increased in 11 different types of cancer. The authors confirmed the upregulation of KIF4A in different types of osteosarcoma cells. Silencing KIF4A via siRNA significantly decreased cell proliferation and increased cell apoptosis. Overall, the manuscript is concise. The study can be improved with the following specific points being appropriately addressed.
1.	What is the efficiency of siRNA transfection? Besides the qPCR, did the authors confirm the downregulation of KIF4A by Western blot?
2.	Did the siRNA of the KIF4A downregulate the expression of KIF4A to the same level as the normal osteoblast hFOB1.19 cells?
3.	Did you compare the cell proliferation and apoptosis of KIF4A knockdown with the normal osteoblast cells?
4.	Please specify the Wnt antibody. Is it Wnt3a?
5.	Did you test the abundance of phosphorylated Beta-catenin?
6.	In the figure 5, the bar graph did not math with the FACS figures.


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: IDENTIFICATION OF KIF4A AS A PAN-CANCER DIAGNOSTIC AND PROGNOSTIC BIOMARKER VIA BIOINFORMATICS ANALYSIS AND VALIDATION IN OSTEOSARCOMA CELL LINES
Review round: 1
Reviewer: 3

Output:
Basic reporting: The authors used bioinformatics to find the KIF4A as a pan-cancer diagnostic and prognostic biomarker. The osteosarcoma cell lines have been retrieved to validate the performance results. The idea is of interest, but there are major points that need to be addressed to meet the quality requirement of the journal.

- English should be improved.

- There lacks of literature review on bioinformatics-based OS analysis.

- Abstract is written unclearly. It did not emphasize the hypotheses and objective of this study.

- From lines 53-57, I suggest not to include them in the "Introduction" since it mentioned the results.

- Abbreviation should be defined at the first appearance.
Experimental design: - Source codes should be provided for replicating the methods.

- Did the authors concern about the batch effect removal in their datasets?

- TCGA has been used in previous bioinformatics studies such as PMID: 32942564 and PMID: 33086550. Thus, it is suggested to refer to more works in this description.
Validity of the findings: - The authors should compare the predictive performance with the previous works on the same problem/data.

- Survival analysis has been conducted. Why did the authors not use Hazard Cox analysis?

- The authors should have additional validation data related to RNA-seq or gene expression level.
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: IDENTIFICATION OF KIF4A AS A PAN-CANCER DIAGNOSTIC AND PROGNOSTIC BIOMARKER VIA BIOINFORMATICS ANALYSIS AND VALIDATION IN OSTEOSARCOMA CELL LINES
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: Thanks for addressing all the comments or concerns. The manuscript looks fine.


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: IDENTIFICATION OF KIF4A AS A PAN-CANCER DIAGNOSTIC AND PROGNOSTIC BIOMARKER VIA BIOINFORMATICS ANALYSIS AND VALIDATION IN OSTEOSARCOMA CELL LINES
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors have addressed my concerns.
Experimental design: The authors have addressed my concerns.
Validity of the findings: The authors have addressed my concerns.
Additional comments: The authors have addressed my concerns.


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: IDENTIFICATION OF KIF4A AS A PAN-CANCER DIAGNOSTIC AND PROGNOSTIC BIOMARKER VIA BIOINFORMATICS ANALYSIS AND VALIDATION IN OSTEOSARCOMA CELL LINES
Review round: 2
Reviewer: 3

Output:
Basic reporting: No comment.
Experimental design: No comment.
Validity of the findings: No comment.
Additional comments: My previous comments have been addressed well.


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: DESTABILIZATION OF EPCAM DIMER IS ASSOCIATED WITH INCREASED SUSCEPTIBILITY TOWARDS CLEAVAGE BY TACE
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript presented by Zagar T et al (ID 58778) is an interesting report on the effect of the destabilization of the EpCAM dimer by the TACE protease.

The topic i interesting and the results and conclusions are well argumented. The literature is sufficiently appropriate, exhaustive and centered.

The structure of the article is well planned, as well as figures. However, some colors are not well suitable, especially in figure 2. Then, page numbers are lacking.

The most important issue to be raised is about English language and the sloppiness of some terms.
Experimental design: Research is within the aims and scope of the Journal

Research question are well defined and meaningful

Rigorous investigation performed

Methods described sufficiently well, but some changes and improvements are required.
Validity of the findings: NO comment
Additional comments: The manuscript (ID 58778) is well designed and interesing, contributing valuable novelties in the field.
However, a revision of the style and of the English language are required.
Considering that no further experiments are needed in my opinion, my choice is a minor revision, but only if the English style and sloppiness are improved.

In particular, in the Methods:
1-The title of the firs paragraph should be amended to: "In silico construction and Molecular dynamic simulations of EpEX". Otherwise, is not easy to comprehend why is the first paragraph.
2- "Molecular weight analysis" should precede the "CD", that should in turn become "CD analysis".
3- RALLS and LALLS should be better explained in the methods, better than in the Results.

Then, please define better than at present the abbreviations: for example Molecular weight (Mw) should be defined the first time, then use always Mw! Also the acronym "TACE", should be better explained in line 39, as well as in the Abstract.
Again, the article "the" or "a" should be added before singular names. See line 23, before 'oligomeric state' and check throughout the whole manuscript.
Careful with the commas and full stops: line 146, pH 7.4, not 7,4. Check hroughout the whole manuscript.
Then, finally, the page numbers are lacking and some color figures are not well suitable (light green and yellow, Figure 2).
In general, if you could improve the resolution of all the figures should be better.

Other points:
Line 17, amend 'fully explained' with "fully understood".
Line 20, change 'mutant forms' with "mutants"
Line 41, before "secretase" the greek term is lacking.
Line 53, shift "only" after "take place".
Line 83-84, the sentence "After inizial minimization with protein fixed" is not very clear.
Line 147, ZnCl2: 2 must be underscored.
Line 242, change 'has' with "had".
Line 258, change to: "The peaks relative to... are symmetric, while the EpEX peak..."
Line 299, add "to be" after "appear"
Line 308, amend to: "challenging to be dected and accurately quantified"
Line 326, change to "a prolonged"
Line 331, change '9' with "nine"
Line 365, shift "for the first time" at the end of the sentence (line 366)
Line 373, delete "be" before "needed".
Lines 374 and 376: what is "CANDIS"?
Line 401, amend the sentence to "...oligomeric state either in solution or on the cell surface".


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: DESTABILIZATION OF EPCAM DIMER IS ASSOCIATED WITH INCREASED SUSCEPTIBILITY TOWARDS CLEAVAGE BY TACE
Review round: 1
Reviewer: 2

Output:
Basic reporting: In this manuscript, the Authors designed, expressed, purified, and characterized two different mutants with distinct oligomeric states of EpCAM ectodomain (EpEX) protein. The purified recombinant proteins ( EpEX wt, dimeric and monomeric mutants, and TACE-EX) were used to study the role of the oligomeric state's effect on the proteolytic processing by TACE ectodomain.  By comparing the proteolytic processing of EpEX wt, EpEX monomeric, and dimeric mutants, they concluded that EpCAM could only be efficiently cleaved as a monomer, indicating that these mutants are valuable tools to elucidate the role of the oligomeric state of EpCAM in the regulation of RIP.
The manuscript, in general, complies with the basic requirements of the journal; It is well written, clearly stated the aim of the study, the hypothesis and experimental evidence are consistent and interesting to the audience, figures and raw data are appropriate.
However, before publication, some minor observations might improve the manuscript.
1)	Please correct  the spelling error in lines 47 and 84
2)	Line 69-7 …… confirming the role of EpCAM's oligomerization...

To confirm the role of oligomerization of EpCAM in the RIP,  experiment with cells using these valuable mutants are needed. To be consistent with experimental evidence, discussion, and conclusions, please change "confirming" by something like "strongly indicating."

3)	It is indeed surprising that Anti His Ab did not recognize the TACE-EX (Fig 3A). Since TACE-EX was also purified using the His6-tag, it will be desirable to provide some experimental evidence that this observation was because of the absence of His-tag in the purified protein.
4)	To improve Fig1B, 2A, 2B, 2D, 3A,3B,3C, and 3D, is it possible to change the yellow-orange color?
All Alfanumeric in the figure labels should be in “black.”
Experimental design: The research question is clearly defined, experimental approach, and the methods are well described.
Validity of the findings: Their results, discusión, and conclusion are consistent with the aim of the study.
Additional comments: The data shown here with the recombinant proteins  EpEX wt, dimeric and monomeric mutants contribute to advance the role of oligomerization of EpCAM in the RIP.
These monomeric and dimeric mutants will be valuable tools to confirm in cell experiments the EpCAM oligomeric state's role in this interesting molecule's biological function.


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: BLUE MUSSEL (MYTILUS SPP.) CULTIVATION IN MESOHALINE EUTROPHIED INNER COASTAL WATERS: MITIGATION POTENTIAL, THREATS AND COST EFFECTIVENESS
Review round: 1
Reviewer: 1

Output:
Basic reporting: line 56-58. “The mitigation potenial...” I believe that it can be hard for many readers to understand this sentence. Since it is a quite important finding I suggest that you rephrase and develop the reasoning.

line 93. Did Stadmark and Conley, 2011 say that mussel cultivation is one of the most promising measures?

line 99-102. It is not clear to me what you are meaning with these sentences?

line 106-107. I do not believe that this is relevant to state what is possible. There are many places where you don´t find Dreissena and Mytilus is very small.

Line 132 It seems strange to begin this very long sentence with therefore.

Line 196 It also seems strange to begin this sentence with therefore.

Line 206 Same goes for this sentence
Experimental design: There are many different types of data, investigations and experiments that are presented in this paper. It makes it a bit hard to read and grasp. I really do not see the point with spending so much effort and space in the status environmental status of the inner coast waters. It seem rather like background information and could perhaps be moved to an Appendix?
I am also a bit skeptical a bout the economic section which has been much more thoroughly examined many times before.

However, the data from the pilot farms is important. I suggest to focus on presenting and discussing the results from these farms.

As I interpret it, the main knowledge gap you fill is that you can describe the mitigation potential for mussel farms in mesohaline inner coastal waters. Your result points that out that the overall potential is quite small. Even if scaling up our farms many magnitudes the effect will be very small. On top of that you describe risks with aggregation of Vibero, that harvest fails and weak economic potential. This can be clearer in the conclusion and abstract.
Validity of the findings: line 442-450. Subsequently, if 50% of the GWB was covered with mussel farms. , they would take up 257 t N and reduce TN concentration to 34.6 μmol l-1 within September (Tab. 3). According to the linear regression model (Tab. 3, C), reduced nitrogen would increase the Secchi depth by 7.83 cm...
and line 457-460
I consider this a main finding of the study. This should be highlighted in abstract and conclusion

line 470. Farms loosing their stocks has been very common in Baltic mussel farming trials, I believe that this result also should be highlighted and discussed more since it has huge potential impact on the mitigation function.

line 517-553 Seems to fit better as introduction rather then discussion

line 575-579 These findings should be discussed in relation to models and projection using lab values e.g. FARM
Additional comments: I believe that this is an important study. However it can be clearer and more focused.


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: BLUE MUSSEL (MYTILUS SPP.) CULTIVATION IN MESOHALINE EUTROPHIED INNER COASTAL WATERS: MITIGATION POTENTIAL, THREATS AND COST EFFECTIVENESS
Review round: 1
Reviewer: 2

Output:
Basic reporting: The paper by Ritzenhofen et al. „Blue mussel (Mytilus spp.) cultivation in mesohaline eutrophied inner coastal waters: mitigation potential, threats and cost effectiveness“ is a very timely contribution to improve the knowledge base of the novel aquaculture activities in the Baltic Sea and beyond.

The paper is very well and clearly written. I only have the following minor recommendations:

In the abstract section, please add the density of Vibrio spp. in the reference areas (sediments/mussels). If their density was zero, just spell this clearly out. From the abstract section it is not clear if you measured Vibrio in the biodeposits (e.g. using sediment trap to collect biodeposits) or you sampled bottom sediments (including reworked biodeposits and other material) or both. Importantly, in the discussion section you actually say that “Even though high concentrations were observed in the bio deposits in the water column, the sediment concentrations did not increase compared to the reference site.” This suggests that the Vibrio statement above is a bit of oversell (i.e. not ecologically relevent at larger spatial scales) and instead you should use the latter statement in the abstract.
Perhaps, you need to spell out the scenario of mitigation compensation (how the scenario was priced) as this background information very much defines whether the activity is economically feasible or not.
Add to the introduction or method section information about the prevalence/rarity of natural mussel beds in your studied ecosystems.
Line 93: Please cite also to a recent publication that dealt with the mitigation potential of Mytilus in the whole Baltic Sea region: Kotta, J.; Futter, M.; Kaasik, A.; Liversage, K.; Rätsep, M.; Barboza, F.R.; Bergström, L.; Bergström, P.; Bobsien, I.; Díaz, E.; Herkül, K.; Jonsson, P.R.; Korpinen, S.; Kraufvelin, P.; Krost, P.; Lindahl, O.; Lindegarth, M.; Lyngsgaard, M.M.; Mühl, M.; Sandman, A.N.; Orav-Kotta, H.; Orlova, M.; Skov, H.; Rissanen, J.; Šiaulys, A.; Vidakovic, A.; Virtanen, E. 2020. Cleaning up seas using blue growth initiatives: mussel farming for eutrophication control in the Baltic Sea. STOTEN, 709, 136144.
In addition, you miss another important publication in the field, which very much relates to the current paper: Andreas Michael Holbach et al. 2020 A spatial model for nutrient mitigation potential of blue mussel farms in the western Baltic Sea. https://doi.org/10.1016/j.scitotenv.2020.139624
Line 108: Do you mean a relative small negative environmental impact?
Line 164: Sediment types consist mostly of ....
Add to the discussion section a statement that says how often you expect in your study areas conditions with chl > 20. Now it is not clear if this is a short term phenomenon or some estuaries can experience such conditions troughout the summer.
In the conclusion section, a statement about the effects of Vibrio at the ecosystem level is too far reached as the elevated densities were measured in biodeposits only and not in the sediment.
Experimental design: No comments
Validity of the findings: No additional comments, see my minor comments under the section of basic reporting.
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: BLUE MUSSEL (MYTILUS SPP.) CULTIVATION IN MESOHALINE EUTROPHIED INNER COASTAL WATERS: MITIGATION POTENTIAL, THREATS AND COST EFFECTIVENESS
Review round: 2
Reviewer: 1

Output:
Basic reporting: I believe that the paper has improved a lot. I still believe it would have been easier to read and comprehend if less focus had been on the economics and the background environmental status of the coast. However, I am happy with the changes

I do not really understand what you mean with threats in the title? Mitigation threats or farming threats or environmental threats?
Line 66. This is Vibrio sink hypothesis is interesting I hope you investigate it!
Line 97. I guess that the reference Wikström et al 2020 would rather support the previous sentence in line 91-94. I found a similar citation error in the previous version too, please check that the references are correct.
Experimental design: no comment
Validity of the findings: no comment
Additional comments: no comment


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

Input:
Title: OSTEOLOGY, RELATIONSHIPS AND FUNCTIONAL MORPHOLOGY OF WEIGELTISAURUS JAEKELI (DIAPSIDA, WEIGELTISAURIDAE) BASED ON A COMPLETE SKELETON FROM THE UPPER PERMIAN KUPFERSCHIEFER OF GERMANY
Review round: 1
Reviewer: 1

Output:
Basic reporting: Correct
Experimental design: This is a descriptive palaeontological paper
Validity of the findings: The newwly described fossil is of a great scientific value
Additional comments: This is a very well executed piece of palaeontological work and it is hard to find any substantial deficiency in the descriptive part of the paper. However, illustrations require some modification before they are published. For instance, it is hardly useful for the reader to have political maps presented on  Fig. 1. One may easily find the district of Mansfeld-Südharz in the state of Saxony-Anhalt in smartphone without consulting this scientific paper. I suggest that rather the extend of the Kupferschiefer and the Zechstein Basin is shown with location of the finding.
One may ask for what purpose contours of bones on photographs on Figs 2, 3, 5, 6 and 17 are retouched, the same outlines being repeated on Fig. 3A and B, 17A and !7 B and 19. This obliterates the actual information provided by the fossil and unnecessarily mixes facts with interpretations. I suggest that these outlines are removed.
The reconstruction shows an animal in an unrealistic pose. In result, the patagial spars are so close to each other in their presumably resting folded orientation that there is little space for the patagium, whereas the appendages protrude straight to sides, in a gliding(?) orientation.
Probably the most interesting aspect of the paper from functional point of view, is the convincing evidence that the patagia were located ventro-laterally, which required their upward elevation during flight. Such a non-optimal arrangement requires historical explanation and the authors convincingly propose that they are homologous to the external rows of gastralia.
The long thin tail in flying reptiles (line 1636) is designed rather for stabilizing flight (like a rod in rocket) than for steering, which requires flattening of the tail.
The methodology of phylogenetic analysis used by the authors allows to receive any expected results by assembling appropriate matrix of data. The resulting cladogram is thus hardly a surprise.
No doubt that the paper deserves publication after some modification of pictures.

Jerzy Dzik


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: OSTEOLOGY, RELATIONSHIPS AND FUNCTIONAL MORPHOLOGY OF WEIGELTISAURUS JAEKELI (DIAPSIDA, WEIGELTISAURIDAE) BASED ON A COMPLETE SKELETON FROM THE UPPER PERMIAN KUPFERSCHIEFER OF GERMANY
Review round: 1
Reviewer: 2

Output:
Basic reporting: Adding a figure is suggested.
Experimental design: no comment
Validity of the findings: no comment
Additional comments: The article is well organized, informative and scientifically relevant, thus I have only very few remarks:
At line 253-256 the Authors wrote that an anterodorsal (internarial) process of the premaxilla much longer than the alveolar proces is known in Weigeltisaurids, while in nearly all other reptiles the alveolar process is longer, however the same condition occurs in the Drepanosauromorpha in which this element is known, i. e. Megalancosaurus (Renesto and Dalla Vecchia 2005) and Vallesaurus (Renesto and Binelli 2005),  and in Pterosaurs (e.g.  Eudimorphodon, Rhamphorhynchus...), maybe this could be reported.

I definitely agree with the new reconstruction of the pattern of the patagials proposed by the Authors, but would  suggest to briefly discuss (and dismiss) Frey et al. (1997) reconstruction with most of the patagials inserted anteriorly, that could possibly  have been folded.

Also, at line 1629-1632, when the authors state that Weigeltisaurids had a low wing configuration, suggesting they had a peculiar gliding mechanism, a reference colud be made to the fact that low-wing structure  may decrease stability but increase manoeuvrability, as hypothesized by Frey et al. (2003) for active fliers.

In summarizing previous phylogenies the authors should include also Renesto and Binelli 2005 just for sake of completeness.

Adding a drawing of the skull reconstructed in lateral view could be very informative.

Frey E., Buchy M. C. and Martill D. M  (2003) Middle- and bottom- decker Cretaceous pterosaurs: unique designs in active flying vertebrates. In Buffetaut E. and Mazin J.M.  (eds) 2003 Evolution and Paleobiology of Pterosaurs Geological Society Special Oublications 217:267-274. The Geological Society of  London


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: OSTEOLOGY, RELATIONSHIPS AND FUNCTIONAL MORPHOLOGY OF WEIGELTISAURUS JAEKELI (DIAPSIDA, WEIGELTISAURIDAE) BASED ON A COMPLETE SKELETON FROM THE UPPER PERMIAN KUPFERSCHIEFER OF GERMANY
Review round: 1
Reviewer: 3

Output:
Basic reporting: I thank the editors (and possibly the authors who proposed my name) for their invitation to review this work. As I am currently working on weigeltisaurid anatomy in the context of my PhD, I aim here to provide a constructive and objective review, and not to prevent the publication of this paper.

As stated by the authors, the main goal of the study is to provide an accurate description of the weigeltisaurid specimen SMNK-PAL 2882, explore the systematic position of the weigeltisauridae, and discuss the homology of the enigmatic patagial spars. This work was long overdue and I commend the authors on their precise anatomical study of this specimen. Nevertheless, I think that some minor issues need to be addressed in a revised manuscript:

1. How was SMNK-PAL 2882 identified as Weigeltisaurus jaekeli? Bulanov and Sennikov (Pal. Jour., 2015:1110) explicitly refer this specimen to the genus Weigeltisaurus but not to the species W. jaekeli. Please address this in the manuscript.

2. I suggest adding a ‘Systematic Paleontology’ section to (a). reassess the attribution of the specimen; (b). provide an emended diagnosis for W. jaekeli based on your phylogeny; (c). summarize the previous studies of this specimen.

3. Thank you for providing your matrix. However, Scheyer et al. (Roy. Soc. Open. Sci., 2020) have provided a revision of its 2018 version, but this study is not mentioned here. Please reference this article and explain why their modifications were not included in your work.

4. There is no mention of recent hypotheses on early amniote evolution (e.g. Laurin and Piñeiro, Front. Earth. Sci., 2017; Ford and Benson, Nat. Ecol. Evol., 2020). This may impact your discussion on early diapsid relationships, considering you refer to Orovenator (a varanopid according to Ford and Benson, 2019, 2020). If you prefer to maintain a more consensual view pertaining replication of such results, please say so.

5. I see some problems with the figures: (a). I suggest modifying Fig. 1 to illustrate the geological setting (please indicate Kupferschiefer strata, Ellrich city and precise locality if known); (b). Some bone colors are too similar on Fig. 3B and a portion of the right hemimandible is not figured; (c). Additional captions are welcome on Fig. 4 (e.g. tooth regions; tooth numbers; resorption pits; replacement teeth); (d). The photographs on Figs. 7A and 14A are not very sharp and the individual bones are therefore hard to follow.
Experimental design: See Remarks 1 and 3 in ‘Basic reporting’ section.
Validity of the findings: No comment.
Additional comments: Some minor general comments on the manuscript:

1. Incorrect specimen numbers: SMNK-PAL 2882, not SMNK 2882. Updated numbers for the MNHN collections are available online (https://science.mnhn.fr/). Note that R.L. Carroll and P.J. Currie erroneously refer to ‘1908-11-13a’ instead of ‘1908-11-18a’ for Thadeosaurus. The updated number for this specimen is MNHN.F.MAP360a. I provided the updated numbers below. Please correct occurrences in the manuscript and check other specimen numbers for similar mistakes.

2. Your ‘History of Research’ section is very similar to the summaries provided by Schaumberg et al. (Pal. Z., 2007:160-161) and Bulanov and Sennikov (Pal. Jour., 2015:1101-1104). I suggest shortening the first section to focus on the history of the studied specimen.

3. The Dentition section is hard to follow, for the most part due to Fig. 4, which I highly suggest revising (see ‘Basic Reporting’, point 5).

4. As noted, the clade Avicephala was described relative to Neodiapsida. However, the definition of neodiapsida was changed by Reisz et al. (Proc. Roy. Soc., 2011:3733), and includes weigeltisaurids in your analysis. Thus, I believe you should not refer to “Avicephala (sensu Senter, 2004)” but ‘Avicephala (sensu nuovo)’. I suggest you provide a new definition for this clade.

5. Your conclusion should be improved to include all results in the manuscript such as your interesting hypothesis of the patagial spars as lateral gastralia, or the grouping weigeltisaurids and drepanosauromorphs under Avicaphala in your analysis.

6. Please include the age and provenance of SMNK-PAL 2882 in all relevant figure captions. e.g. ‘Figure 2: The skeleton of SMNK-PAL 2882 (Weigeltisaurus jaekeli, Lopingian, Germany)’. Use the age and locality you deem adequate.

Some minor comments to improve the manuscript:

line 69: “The most highly specialized” -> “One of the most…”
line 79: add ‘in’/’near’ between “Ellrich” and “the Mansfeld mining district”
line 190: “All elements of the palate and braincase are absent”. Some unidentified bones on Fig. 3A could be unidentifiable elements from the palate or braincase. Please be less affirmative.
lines 204-207: hard to follow, please reformulate. Line 205 should refer to the tarsus instead of the carpus?
line 363: “blunted point” -> this appears quite sharp to me on Fig. 3A
line 364 (nasal section): Bulanov and Sennikov (2015:1107) describe an anterolateral crest on the Weigeltisaurus holotype. Is it visible on this specimen?
line 377: ‘contribution to’ instead of “contribution for”
line 378: “This contact is sigmoid […] dorsal process of the maxilla” -> This is not clearly visible on Fig. 3.
line 386 (maxilla section): There is no mention of the preorbital fenestra described on Coelurosauravus and Weigeltisaurus by Bulanov and Sennikov. This may be a diagnostic character of weigeltisaurids. If it is unpreserved on the specimen, please say so.
line 386 (maxilla section): Please, indicate the tooth number and compare it to other weigletisaurids (this may be placed in the dentition section)
line 404: MNHN.F.MAP327a-b instead of MNHN 1908-5-2, correct all occurrences.
line 416 (prefrontal section): can you see the foramen for the nasolacrimal duct described in Coelurosauravus? If not please say so.
line 416: reference Fig. 3 here
line 419: “prefrontal boss” -> I cannot see it on Fig. 3.
lines 426-428: “transverse breadth” -> as preserved or once reconstructed? This is not the same, I believe you mean ‘dorsoventral height’ (once reconstructed).
line 441 (frontal section): can you see traces of the median ventral lamina described in Coelurosauravus? If not please say so.
lines 464-469: “U-shaped frontoparietal contact”. Possibly, but the ‘zigzaged’ suture described in Coelurosauravus (Bulanov and Sennikov, 2015:417) seems plausible based on Fig. 3. If not, please say so.
line 534: replace the first “and” by a ‘,’
line 540: This is incorrect for Coelurosauravus (Bulanov and Sennikov, 2015:419)
line 567 (postorbital & prefrontal section): you say both bones are hard to distinguish and possibly fused, yet you describe and figure them as distinct elements. Please rephrase.
line 568: “fused into a single element” -> you should reference extant squamates here.
line 593: I suggest you also number the parietal horns.
line 682: “surangular” -> please indicate on Fig. 3.
line 689 “splenial” -> please indicate on Fig. 3.
line 729: remove ‘.’
line 810: “distinct diapophysis” -> please indicate on Fig. 5 or 6.
line 813 “dichocephalous cervical rib” -> refer to a Figure here.
line 816: Please provide value for cervical centrum height-length ratio.
line 817: MNHN.F.MAP317b instead of MNHN 1908-11-22a. Correct all occurrences.
line 899: see minor general comment 1.
line 903 “anterior and posterior cavities” -> add ‘in lateral view’
line 942 (chevrons section): Please compare your observations to that of Evans (Zool. Journ. Lin. Soc., 1982).
line 1005 (cleithrum): a cleithrum is also reported in Acerosodontosaurus.
line 1012 (clavicle): please indicate the clavicle on Fig. 7B
line 1042: “It does not bear any prominent crests or ridges” -> Could they have been obliterated due to postmortem compression?
line 1047: MNHN.F.MAP325a instead of MNHN 1908-11-21a
line 1058: MNHN.F.MAP360b instead of MNHN 1908-11-19a
line 1250: “median tibial condyle” -> please indicate on Fig. 15
line 1273: “There is no clear, proximally projecting cnemial crest” -> Yet you figure and describe it. If you consider it to be present bur reduced compared to other taxa, please say so.
line 1333 (metatarsus): please describe metatarsal V in more detail, including key characters coded in your matrix (e.g. outer process, hooking, etc.)
line 1441: this should refer to the 7th patagial instead of the 6th?
line 1472: see minor general comment 4.
line 1492: please provide translation for German terms.
line 1671: add ‘of weigeltisaurids’ after “As the patagials”.
line 1707 ‘Smith and Evans (1996)’ instead of “Smith and Evans (1992)”
line 1709: are the differences between both ‘Youngina’ forms based on personal observations? If so, please add “pers. obs.”
line 1921: ‘S2’ instead of “S@”

Matrix: ‘Petrolacosaurus kansensis’ instead of “Petrolacosaurus kansasensis”


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: OSTEOLOGY, RELATIONSHIPS AND FUNCTIONAL MORPHOLOGY OF WEIGELTISAURUS JAEKELI (DIAPSIDA, WEIGELTISAURIDAE) BASED ON A COMPLETE SKELETON FROM THE UPPER PERMIAN KUPFERSCHIEFER OF GERMANY
Review round: 2
Reviewer: 1

Output:
Basic reporting: The revisions are adequately addressed, minor items to take into account are indicated below.
Experimental design: No comment.
Validity of the findings: No comment.
Additional comments: The authors have adequately addressed all of the requested revisions, including my own. They have argued strongly in favor of keeping a detailed ‘History of Research’ section. This is fine and, as correctly stated, is relevant for readers not familiar with weigeltisaurids.
There are, however, a few very minor items that need to be addressed before acceptance. Otherwise the revisions are adequate and the modified figures are very helpful:

1. Please address the following items in the Systematic Paleontology section:
- Line 188: The taxonomic authority should be in brackets: “(Weigelt, 1930)”.
- Lines 190-205: A chresonymy of W. jaekeli would be more pertinent in a revision of all of the specimens previously referred to this taxon, which is not the case here. Thus, I suggest providing only a synonymy sensu stricto for W. jaekeli in this work.
Furthermore, I strongly suggest following Matthews (Paleontology, 1973) and others, summarized in Sachs et al. (PeerJ, 2016) for the format of chresonymies. This is necessary to avoid confusion between taxonomic authorities and bibliographic references. If the authors find it pertinent, such a chresonymy could be provided for SMNK-PAL 2882 only, in the “referred material” paragraph.
- A “Holotype” paragraph should be included in this section even if it is not the specimen described here.

2. Please address the following items on the figures and figure captions:
- Fig. 3A: the interpretive lines have been removed, please correct the caption.
- Fig. 4: 21 should refer to a “maxillary” tooth position instead? 18 and 32 refer to “mandibular” and “dentary” tooth positions respectively, please keep only one.
- Fig. 6: “A.” and “B.” are bolded in the caption, but not in other figs. Please keep the same format for all captions.
- Figs. 12-13: Please indicate individual metacarpals as done in the tarsus (Figs. 17-18).

3. Please address the following items in the text:
- Line 130: the correct reference is De Stefano (1903) and this item is missing from the reference list.
- Line 254: Weigeltisaurus jaekeli should be in italics.
- Lines 303-304: I believe the bracketed references in the quote should be removed.
- Line 557: outer margins “are” discernable (not “is”).
- Line 861: remove one “of”.
- Line 1362: this should refer to MNHN.F.MAP325 instead.
- Lines 315, 646, 1123-1124, 1209, 1497, 2074: remove additional space. Check for others I might have missed.


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: OSTEOLOGY, RELATIONSHIPS AND FUNCTIONAL MORPHOLOGY OF WEIGELTISAURUS JAEKELI (DIAPSIDA, WEIGELTISAURIDAE) BASED ON A COMPLETE SKELETON FROM THE UPPER PERMIAN KUPFERSCHIEFER OF GERMANY
Review round: 3
Reviewer: 1

Output:
Basic reporting: Almost all revisions have been adequately addressed. I only have a few minor comments.
Experimental design: No comment.
Validity of the findings: No comment.
Additional comments: I am really sorry for nitpicking in an otherwise excellent manuscript, but there remain a few very minor items to correct in the synonymy.

Synonymies are subject to a highly standardized format, and must include taxonomic authorities, if nothing else. References of works simply using previously established names should thus be removed.
A “simple” example could thus be: [Weigeltisaurus jaekeli (Weigelt, 1930a) removed as it is the valid name]

Palaeochamaeleo jaekeli Weigelt, 1930a
Gracilisaurus ottoi Weigelt, 1930b
Coelurosauravus jaekeli (Weigelt, 1930a)

Additional information could be included if the authors or the editors find it pertinent. Most journals require references to the first page where a name is established and all figures in that work. Authorities of new combinations may also be included, in which case the valid name should be re-included as it is a new combination.
If the authors wish to add such information, I suggest following the guidelines of specialized paleontological journals for all entries (e.g. JVP).

Other minor items:
Line 195: ‘Schaumberg et al., 2007’ instead of ‘Schaumberg, 2007’ but I suggest removing this, see above
Line 199: ‘patagials’ not ‘patagial’


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: MOLECULAR EPIDEMIOLOGY OF VANCOMYCIN-RESISTANT ENTEROCOCCUS FAECIUM CLINICAL ISOLATES IN A TERTIARY CARE HOSPITAL IN SOUTHERN THAILAND: A RETROSPECTIVE STUDY
Review round: 1
Reviewer: 1

Output:
Basic reporting: The grammar needs to be corrected
Experimental design: The results are supported by the analysis
Validity of the findings: Conclusions and discussion should be expanded. More specifically, practical guidance (even though speculation) should be provided for monitoring VRE infection.
Additional comments: This is an interesting manuscript by Saengsuwan et al that studies the molecular epidemiology of vancomycin-resistant Enterococcus (VRE) faecium in southern Thailand hospitals. The authors show that molecular techniques can  detect antibiotic resistant genes and inform monitoring techniques for VRE. This manuscript is a step forward in the framing of policies for VRE monitoring.  It is written in a very simple and easy to follow manner. The conclusions are supported by the analysis. There are some minor concerns that need to be addressed before publication at PeerJ

1)	Medical history of the patients- past drugs etc should be mentioned if any
2)	The authors should aim to run the analysis on some other populations apart from Thailand. In its current form, there is a huge population bias and the results may not be generalizable. Further more, the results should be contrasted with (Bhatt et al. 2015b) and (Said & Abdelmegeed 2019)
3)	Please expand this discussion more “Meropenem and gentamicin are β-lactam and
aminoglycoside antibiotics, respectively, and combinations of meropenem and aminoglycosides might be alternative therapies for multi- and VRE infections.”
4)	Is there a correlation between age and VRE infection?
5)	The figure legends should be expanded
6)	Please check for grammar


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: MOLECULAR EPIDEMIOLOGY OF VANCOMYCIN-RESISTANT ENTEROCOCCUS FAECIUM CLINICAL ISOLATES IN A TERTIARY CARE HOSPITAL IN SOUTHERN THAILAND: A RETROSPECTIVE STUDY
Review round: 1
Reviewer: 2

Output:
Basic reporting: - The authors have screened a decent number of nosocomial enterococci (~9000), of which 90 isolates were VRE and therefore selected for the study. However, these are important numbers that should be mentioned in the abstract and main text.

- Table 4 heading needs to be corrected. In addition to the List of antibiotics used, the table also contains other details that should be mentioned in the heading.

- All the tables are numbered as table 1 (Line 1 of pages 26,28,30,32,36,38)

-Figure 1: The figure legend mentions lane 6 = ddl genes and vanB positive from a clinical strain, but in the figure the bands are labeled as 16SrRNA and E.faceium. The authors need to correct this.
Experimental design: Method section: Detection of van genes and virulence genes is mentioned twice (Line 134-157)
Validity of the findings: The authors mentioned that year 2014 had the highest number of VRE isolates which is correct but the reason for its selection is wrong. The authors compared the number of VRE isolates in 2014 (28) to the total number of VRE isolates i.e. 90. The authors need to actually compare the VRE(%)  in table 1. The fact that the year 2014 had the highest percentage (4.3%) of VRE positive strains makes this year with the highest prevalence of VRE.

The same thing also applies while comparing other characteristics. For eg., when comparing the gender ratio, the number of VRE isolates is higher in females than in males, and this may be because of more sampling from females compared to males.
Additional comments: The current study monitors the prevalence of drug-resistant Enterococcus faecium in a tertiary care hospital in Southern Thailand. This is an important study that is well performed and written and the results are discussed in detail.

Comments:
- Antimicrobial resistance profiles: The  authors need to explain why all the 90 VRE isolates were not tested against different antibiotics
- As mentioned in the above section, the authors need to also consider the total number of isolates when comparing different characteristics such as year, gender, age, source, and hospital unit


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: MOLECULAR EPIDEMIOLOGY OF VANCOMYCIN-RESISTANT ENTEROCOCCUS FAECIUM CLINICAL ISOLATES IN A TERTIARY CARE HOSPITAL IN SOUTHERN THAILAND: A RETROSPECTIVE STUDY
Review round: 1
Reviewer: 3

Output:
Basic reporting: The paper is well written, straightforward, and easy to read.
Experimental design: 'no comment'
Validity of the findings: Conclusions are consistent with the results presented.
Additional comments: The current manuscript reports the surveillance of vancomycin-resistant enterococci (E. faecium and E. faecalis) from a hospital in southern Thailand collected for eight-years. Authors find >50% VRE strains were isolated from >65 yr old. They found VRE samples were detected highest in urine specimens (28.9%) among all the specimens collected. Multiple-PCR and Genotyping study with ERIC-PCR finds that these strains contain a high frequency of esp gene, necessary for colonization and biofilm formation and vanA gene, reported in the MDR and vancomycin-resistant E. faecium.

The authors present the surveillance study of VRE in a hospital setting in Thailand, which offers essential health concerns for a developing country. The paper is well written, straightforward, and easy to read. Conclusions are consistent with the results presented. I will recommend the report to be accepted in its current form.
- Some comments:
- Authors can submit MDR strains reported in the manuscript to NCBI.
-Thank you for providing the raw data. However, your supplemental files need more descriptive metadata, and it will be useful for readers and your NCBI submission. For. e.g., Strain name, isolated from which specimen and genotyped, raw sequence.


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: MOLECULAR EPIDEMIOLOGY OF VANCOMYCIN-RESISTANT ENTEROCOCCUS FAECIUM CLINICAL ISOLATES IN A TERTIARY CARE HOSPITAL IN SOUTHERN THAILAND: A RETROSPECTIVE STUDY
Review round: 2
Reviewer: 1

Output:
Basic reporting: Good
Experimental design: solid
Validity of the findings: Good
Additional comments: Congratulations on a good 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: MOLECULAR EPIDEMIOLOGY OF VANCOMYCIN-RESISTANT ENTEROCOCCUS FAECIUM CLINICAL ISOLATES IN A TERTIARY CARE HOSPITAL IN SOUTHERN THAILAND: A RETROSPECTIVE STUDY
Review round: 2
Reviewer: 2

Output:
Basic reporting: The manuscript meets the criteria of reporting.
Experimental design: The manuscript meets the criteria of PeerJ.
Validity of the findings: Please see the General comments sections below.
Additional comments: This study by Phanvasri Saengsuwan et al investigates the prevalence of virulence and antibiotic resistance genes from a tertiary care teaching hospital in Thailand. The authors have utilized molecular biology techniques (including Multiplex PCR and ERIC-PCR) and Antimicrobial susceptibility assays to analyze the prevalence of resistance genes in patient samples. Overall, it is an interesting study and certainly useful to monitor VRE infection in hospitals. The manuscript can be accepted in the current format for publication in PeerJ. However, the authors should be more careful before drawing the comparison between male and female participants (line number 185), since these numbers are not normalized against the total number of male and female participants (out of 9273 participants mentioned in Table 1). It is also recommended to test all the VRE isolates against all different antibiotics, this would enable more meaningful conclusions to be drawn.


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: SEMINAR-CASE LEARNING MODEL IMPROVES CLINICAL TEACHING: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL
Review round: 1
Reviewer: 1

Output:
Basic reporting: The intention of the authors is to evaluate the use of seminar-based teaching as compared to the more traditional lecture-based teaching. To no surprise, they find that the seminar-based method provides may advantages. This is a common finding and, sadly enough, this study does not contribute new knowledge on the topic.
Overall, the study lacks in rigour in methods (lack of validated measures) and in the reporting. See comments below.

The introduction is poor and the literature review is shallow.
Statements meant to provide a rationale for the study is poorly described and backed up only with editorials and “perspective” articles (Formenti et al. & Armstrong et al.,)
The first sentence states challenges of “the network information era” and diversification of educational models as a problem with reference to a editorial journal comment. Why are these problems?
“Nowadays, clinical medical students have poor clinical application ability of medical knowledge (Armstrong et al. 2018).”

The author claims that the origin of “seminar” is German and refers to Skeff et al., 1986. I disagree, I would say it orginates from the latin “Seminarium” and I cannot find that the origin is mentioned in the Skeff et al. paper.

The authors mix “seminar” as a method with the method “Case-based learning” and their own "Seminar-case learning model". This makes it confusing and not convincing. Overall, the study lacks anchoring in clearly defined concepts and conceptual framework. Thus, the results of the comparison cannot contribute to new knowledge.

Table 3 has wrong labels on experimental and control groups which is detrimental to the discussion and conclusions. (based on the presented numbers and the text “42 people in the control group and 50 people in the experimental group completed the anonymous questionnaire”)
Experimental design: Methods
The outcome measures (theoretical examination and the case analysis examination) are poorly described and not validated in other research.
Validity of the findings: Results
The authors state that “Both the average scores of the theoretical test and the case analysis test of the experimental group are higher than the average scores of the control group”
This is not true since the p value for the comparison of the theoretical test is not below the selected critical value of 0.05.

Discussion
Also in the discussion the authors refer to improvements in the theoretical test without a significant p-value: “The results showed that not only the students' theoretical performance was improved by the seminar-case learning model,”.

Conclusions
Solid conclusions cannot be drawn because outcome measures are poorly described and not anchored in a thorough conceptual framework.
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: SEMINAR-CASE LEARNING MODEL IMPROVES CLINICAL TEACHING: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL
Review round: 1
Reviewer: 2

Output:
Basic reporting: Basic reporting
•	English is clear and easy to understand.
        Please give space before the bracket of a reference in the in-text citation.

•	In the introduction, the justification to test the seminar-case learning model in an RCT
is not adequately presented. Authors should revisit the article from Thistlethwaite et  al. 2012 (The systematic review of the effectiveness of case-based learning in health
professional education. A BEME systematic review: BEME Guide No. 23) and use this article to provide evidence on literature gaps on Case-Based Learning. The authors should be able to show in the introduction how this study differed from others and how the result will add to the body of knowledge.

.     Authors should have a clear research question and hypothesis at the end of the introduction section.

•	Some sentences were not in the correct sections of the article. For example, in the last paragraph of the introduction, the authors reported methods and findings. In the section of participation and groups, the authors mentioned information about participants and statistical analysis of participants’ characteristics, that should be moved to the result section. Please check throughout the manuscript to ensure that information are written in correct sections of the article.
Experimental design: •      Authors requested oral consent from the students. I wonder if this approach has been approved by the ethical committee. It is also not clear if students have obtained information that their decision for participation or nonparticipation will influence their grades. The authors should also explain how they will ensure that students in the control group does not get less benefit in learning compared to the experimental group.
•	This experiment was conducted in a few weeks. Students in both groups may interact with each other. The authors should discuss the possibility of contamination between groups.
•	Courses in both groups are introduced by one lead author. Blinding is not possible. The authors should discuss this issue and how it can influence the result of the experiment.
Validity of the findings: •	Authors should report how the instruments to measure the outcome were developed and validated. I understand that there are two measurements: the theoretical examination and a questionnaire. The validity and reliability of the instruments should be discussed.
•	The authors found no statistical difference in the theoretical test between two groups. This is not in-line with the references that authors use as a basis for the choice of seminar-case learning model. Authors should be able to explain this phenomenon. It is not enough to state that as the average score of of the experiment group is higher means that this model can promote understanding of the theoretical knowledge.
Additional comments: •	There are a lot of studies on innovation in medical education to nurture clinical reasoning (or authors mention in as clinical thinking). Active learning has also been advocated for years as a preference over lecture. I cannot see why it is important to compare both methods.
•	Nevertheless, this is a nice report of innovation in medical education. The authors introduced a case-based learning approach, that they named ‘seminar-case learning model’ for graduate students. Please consider reporting this innovation as a case study in education, rather than as original research. Or, authors can enrich the data using some qualitative research approaches such as interviews or focus group discussion, to explore more understanding about how students learned using this approach and how the practice implication was in the work-based 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: SEMINAR-CASE LEARNING MODEL IMPROVES CLINICAL TEACHING: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL
Review round: 1
Reviewer: 3

Output:
Basic reporting: Although the language is mostly appropriate, there are quite a few errors in the English used, both errors in grammar as in style. I would recommend the authors to ask a native(ish) speaker to review the text to improve its style.

The number and depth of the references provided appears to be adequate and sufficient.

The raw data is shared, including relevant figures and tables. The structure of the article is concise and professional.

The article is self contained with a relevant result, but strictly speaking, there was no central hypothesis formulated. Instead, the conclusion is stated in the introduction ("The seminar-case learning model showed significantly superior to the
65 traditional teaching method.") I would recommend leaving this out, and replacing it by a hypothesis. This hypothesis is suggested in both the abstract and the introduction, but never officially stated.
Experimental design: The research is within the Aims and Scope of the journal.

The research question is not very well defined, although it is relevant and meaningful. The purpose is stated, but a clear cut central hypothesis is not formulated. Therefore, the endpoints are not clear and the interpretation a bit questionable. Is higher test scores the proof of superiority, or the students' satisfaction? Moreover, the end results are presented as being (statistically) significant, which is only true for the 'Case analysis test score'. But is a <5 point difference on a 100 point scale indeed 'clinically' or scholarly significant? A more precise formulation beforehand would improve this interpretation. Would this be a clinical trial, this would probably proof a 'non inferiority' at best.

The investigation itself throws up some questions:
1. The ethical approval is in Chinese. I trust the authors to be writing the thruth, but I can't check that.
2. The approval of the test subjects was oral, not written, and thus can't be checked. In this specific context it is perhaps acceptable, but stil, something to frown upon.
3. Patient data is shared through WeChat. As I do not live in China, I can't check this, but in Western Europe, sharing of these data through a non-encrypted AND medical-grade App, is a breach of law. Specific medical Apps should have been used for this in Western Europe (and I suspect, the US). This is not negative to the research itself, but if this is accepted and/or standard practice, I would recommend stating this specifically in the text.
4. The specific test used on the students is unclear. Apparently, both groups received the same test? Is this a standard test used? Was is a test specifically designed and/or made for this research? If so, the risk for bias exists, if the test is more focused on clinical reasoning or details shared during the seminars. Especially if the test is written AFTER the seminars. Elaboration on this point is advised.
5. I cannot infer from the text whether the group size in which the seminars and lectures are given is the same. If not, this could induce bias. Elaboration on this part, or dicussion of this in the Discussion would be helpful.
6. I have the suspicion that the results of the Questionnaire is wrong, as the results showed suggest less 'Better understanding diseases and knowledge'. If it is correct as presented, please discuss this in the article.
Validity of the findings: I have not replicated the statistical analysis, but as such, looking at the data, it looks plausible, so I have no reason to doubt the conclusion.
My interpretation is that the data is robust, and sound.

My main point of criticism is, as stated before, lack of formal cut-off and/or end-points formulated beforehand.

The conclusion, that seminar style teaching is superior is therefore a bit strong, althoug a suggestion of possible superiority is present. The wording used, 'more efficient', can only be concluded if the total amount of hours invested (both from students and faculty) is accounted for. This, however, is unknown, or at least not mentioned in the article.
Additional comments: It is an interesting read, and could be an important read as well. Although there is need for some major revisions (mostly due to the formulation of the Original hypothesis), I think it is worth the effort to make these revisions.
Also, I repeat my recommendation for a thorough English language review. I can understand that it must be (very) hard for a Chinese native speaker to write in English, for which I extend my praise. But some improvement is required for definitive 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: SEMINAR-CASE LEARNING MODEL IMPROVES CLINICAL TEACHING: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL
Review round: 2
Reviewer: 1

Output:
Basic reporting: Authors need to check some references as attached in the comments in the pdf file.
Experimental design: The research question is now also much more clear than the previous one. More supports are needed to show how research fills an identified knowledge gap.
Some issues in the method section need elaboration. Please refer to the comment in the pdf files.
Validity of the findings: This part is very much improved.
Additional comments: Overall, the manuscript is very much improved. Please kindly refer to some comments in the pdf file.


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

Input:
Title: SEMINAR-CASE LEARNING MODEL IMPROVES CLINICAL TEACHING: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL
Review round: 2
Reviewer: 2

Output:
Basic reporting: The English used has markedly improved.
The structure, literature references are up to standard.
In my view, the study still lacks a well-defined hypothesis, and therefore makes the central conclusion a lot less sturdy
Experimental design: The lack of a central hypothesis makes the design of the experiment a bit shoddy.
After all, what is the reason for this experiment? A higher score on the test (the main outcome), a happier student? Something else? Is efficacy something to consider?
I still think that a well defined central hypothesis would greatly increase the study's value.
Validity of the findings: Within the scope of a preliminary study, the validity is good. The statistics seem solid.
But a 'hard' conclusion is lacking. Due to the lack of a central hypothesis, even a non-conclusive can't be stated. That is too bad in my view. I'm convinced that with a different starting point, a better conclusion could be reached.
Additional comments: The reason that I state 'major revisions', is due to the fact that the central hypothesis is a fundamental part of the paper. Therefore, the term 'minor revisions' seems inappropriate.


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: SEMINAR-CASE LEARNING MODEL IMPROVES CLINICAL TEACHING: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL
Review round: 3
Reviewer: 1

Output:
Basic reporting: No comments. The English is high standard, as was the previous version (as compared to the first).
Good structure and context provided.

In the PDF, the word efficacy is damaged somehow. I'm not sure if that was caused by the PDF generation, as the Word document is OK.
Experimental design: The presence of a clear description of a central hypothesis makes the article a lot more impactful in my view. Especially compared to the previous version.

The only advice in this context is, perhaps, to provide a bit more insight in efficacy:
As the students in the study group state, they experience (a bit) more stress. So, apparently, they put in more hours. This could be seen as less efficacious.
On the other hand, from a university (of even patient's) view, the effect from an equal amount of hours invested by the teachers, seems to be a bit higher in the study group. The costs are (usually) on the side of room-space and teacher's hours, so this is a higher efficacy on that part. Some remarks on this part would elucidate perhaps a bit more.

Perhaps this comment is confusing. I hope you understand my points.
Validity of the findings: The conclusion seems reasonable and correct.
Additional comments: None, besides compliments for the improvements in the article.


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

Input:
Title: SEMINAR-CASE LEARNING MODEL IMPROVES CLINICAL TEACHING: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL
Review round: 4
Reviewer: 1

Output:
Basic reporting: Up to standard, same as before
Experimental design: Up to standards, and withing aims and scope of PeerJ.
Validity of the findings: No further comments.
Additional comments: None


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

Input:
Title: EFFICACY OF AN IMPROVED METHOD TO SCREEN SEMIOCHEMICALS OF INSECT
Review round: 1
Reviewer: 1

Output:
Basic reporting: The authors do not seem to realize that this technique was reported almost 20 years ago, for example, see:
Weissbecker B, Holighaus G, Schütz S. Gas chromatography with mass spectrometric and electroantennographic detection: analysis of wood odorants by direct coupling of insect olfaction and mass spectrometry. J Chromatogr A. 2004 Nov 12;1056(1-2):209-16. PMID: 15595552.

Cai L, Koziel JA, O'Neal ME. Determination of characteristic odorants from Harmonia axyridis beetles using in vivo solid-phase microextraction and multidimensional gas chromatography-mass spectrometry-olfactometry. J Chromatogr A. 2007 Apr 13;1147(1):66-78. doi: 10.1016/j.chroma.2007.02.044. Epub 2007 Feb 20. PMID: 17359983.

Sebastian Paczkowski, Marta Paczkowska, Stefan Dippel, Norman Schulze, Stefan Schütz, Tilman Sauerwald, Alexander Weiß, Marco Bauer, Jörg Gottschald, Claus-Dieter Kohl,
The olfaction of a fire beetle leads to new concepts for early fire warning systems,
Sensors and Actuators B: Chemical,
Volume 183,
2013,
Pages 273-282,
ISSN 0925-4005,
https://doi.org/10.1016/j.snb.2013.03.123.
Experimental design: See comments under 1
Validity of the findings: See comments under 1
Additional comments: The coupling of GC/MS and EAD was reported almost 20 years ago, see references above. Thus, this work is not novel, and at the least, the authors must cite the previous work, and then explain how their method is different, or better, or what advantages it has over the previously published methods of coupling GC/MS and EAD


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: EFFICACY OF AN IMPROVED METHOD TO SCREEN SEMIOCHEMICALS OF INSECT
Review round: 1
Reviewer: 2

Output:
Basic reporting: This MS may be is the first work that assembling gas chromatography (GC) to electroantennography (EAD), and mass spectrometry (MS) to identify semiochemicals. I think that is necessary that the authors explain the objective of the work, because there is no new information in the MS. Weissbecker et al. (2004) reported the first GC-MS/EAD with antennae of the old house borer Hylotrupes bajulus, a widespread insect pest of coniferous timbers. I think that is not correct that the authors do not include in the references of his work the paper of Weissbecker et al. (2004).The MS requires major changes, before acceptance in PeerJ. For instances, results of many of the figures do not contribute with quality of the paper, I think that they can be selected a new insects pest to demonstrate the use of GC-EAD/MS, or with the information of the fig. 2 or 3, demonstrate what is the lower amount injected of the sample to stimulate the insect antenna.
Experimental design: No comment
Validity of the findings: No comment
Additional comments: The MS requires major changes, before acceptance in PeerJ. For instances, results of many of the figures do not contribute with quality of the paper, I think that they can be selected a new insects pest to demonstrate the use of GC-EAD/MS, or with the information of the fig. 2 or 3, demonstrate what is the lower amount injected of the sample to stimulate the insect antenna.


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: HIGH FRUCTOSE EXPOSURE MODIFIES THE AMOUNT OF ADIPOCYTE-SECRETED MICRORNAS INTO EXTRACELLULAR VESICLES IN SUPERNATANTS AND PLASMA
Review round: 1
Reviewer: 1

Output:
Basic reporting: Minor points:

-	Table 1 and Table 3 should be presented the same way, since it is quite hard to follow accordingly with the text. Format is acceptable, but both tables should be presented the same way. For instance, presenting first miRNAs data in tissue and then in plasma (as in Table 3). I really appreciate the Ct values appearing alongside with Delta Ct calculations.

-	It would be appreciated that Figure 1c would come together with a quantification plot.

-	Careful! Throughout the text, the are words that appear together. Please revise spelling.

In 3T3-L1 cell culture:
-	“Cells cultures” should be replaced for “cell culture”
-	“SFB” should be replaced for “FBS”
Experimental design: -	I am very interested in the methodology used to differentiate 3T3-L1. Based on my experience, these cells should be differentiating at least 8 days to reach enough amount of lipid droplets within the adipocytes. Nevertheless, you maintain the cells for 6 days, and at day 2 the differentiation cocktail is replaced for fructose. Do you have any image of the cells at day 6, or RedOil staining that confirms the differentiation success?

-	Another point about methodology refers to the miRNA isolation from EVs of supernatants and rat plasma. Did you perform preamplification after retrotranscription?

-	The dose of fructose was chosen based on previous studies. A time-course using different doses would be interesting to check whether miRNAs fluctuate their expression. Is the dose used resembling physiology? And are in vitro and in vivo approaches comparable in terms of fructose amounts?
Validity of the findings: No comments.
Additional comments: This manuscript is an interesting study about the modulation of miRNA expression patterns upon fructose exposure. Considering the huge impact that miRNAs can trigger at tissue level, this is an attractive study relating epigenetics and fructose intake. The research involves both in vitro and in vivo studies, enhancing the strength of the data presented. However, to strengthen these findings, I suggest several comments to take into account.

Major points:

-	Considering that miRNAs are able to target mRNA at tissue level, it would be interesting to analyse the expression of plausible targets of your candidate miRNAs in 3T3-L1 cells and rats’ adipose tissue. In case you could validate a specific mRNA as a target of your candidate miRNAs, functional test such as luciferase assays would be highly enlightening.

-	Why have you focused in these specific 8 miRNAs? Considering previous literature, there are more miRNAs which have been previously reported to be implicated in adipose tissue physiology. Have you considered to perform arrays to obtain a wider view of miRNA expression profiles? Is this a future line of research?

-	How would you explain different patterns in cells and rats? Have you checked the homology between your candidate miRNAs between humans and rats? Could in vivo data be translated into humans to use plasma miRNAs as biomarkers or tissue miRNAs as therapeutic tools?

-	Please revise Figure 2. Data presented do not match with the text and the tables. For instance, in the discussion you point that miR-223-3p expression in 3T3-L1 cells was augmented upon fructose, agreeing with data presented in Table 1. Nevertheless, Figure 2 shows a global decrease both in vitro and in vivo. The same with miR-342-3p.

-	In discussion section, you point at discrepancies between studies referring to miRNA expression. Have you elucidated which could be the reason attending to the differences? You claim that fructose is inducing a decrease in miR-223-3p levels in EVs in rat plasma, while previous studies showed the opposite. Considering that the feeding was longer, it would make sense to decipher the miRNA fluctuation according to fructose exposure.


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: HIGH FRUCTOSE EXPOSURE MODIFIES THE AMOUNT OF ADIPOCYTE-SECRETED MICRORNAS INTO EXTRACELLULAR VESICLES IN SUPERNATANTS AND PLASMA
Review round: 1
Reviewer: 2

Output:
Basic reporting: This is an interesting article and it is structured logically.
Background knowledge is introduced thoroughly.
Figures and results are shown clearly and raw data is supplied.
Experimental design: This research is highly relevant to the journal.
The research question is well defined and the rigorous investigation is performed to a high technical and ethical standard.
Sufficient details are given in the methods to replicate.
Validity of the findings: The results are validated and the conclusion is well stated accordingly.
Additional comments: Overall this is article is well presented.
The research question is novel and it is properly investigated.

In line 301-303, you mentioned the hypertrophy of adipocytes because there is an increase in total adipocyte area. However, the area of individual adipocyte was not mentioned. It would be better if you could discuss on the total area vs size of individual adipiocyte  (% of large adipocyte or average of adipocyte area) based on your results.


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: HIGH FRUCTOSE EXPOSURE MODIFIES THE AMOUNT OF ADIPOCYTE-SECRETED MICRORNAS INTO EXTRACELLULAR VESICLES IN SUPERNATANTS AND PLASMA
Review round: 2
Reviewer: 1

Output:
Basic reporting: After revising this second version of the manuscript, I agree with all the comments and consequently, the manuscript is accepted in the present form, with no more comments.
Experimental design: After revising this second version of the manuscript, I agree with all the comments and consequently, the manuscript is accepted in the present form, with no more comments.
Validity of the findings: After revising this second version of the manuscript, I agree with all the comments and consequently, the manuscript is accepted in the present form, with no more comments.
Additional comments: After revising this second version of the manuscript, I agree with all the comments and consequently, the manuscript is accepted in the present form, with no more 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 ANTI-NUTRIENT, PHYTOCHEMICAL, AND MICRONUTRIENT CONTENTS OF DIFFERENT PROCESSED RUBBER (HEVEA BRASILIENSIS) SEED MEALS
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript presents valuable findings of composition changes in processed rubber seed meals. The general structure can be easy to follow, but upon careful reading, there are some issues that I would like to comment.

Line 28-29 (Abstract): "...rubber seeds are largely underutilized given its perception as inedible/toxic, therefore the quest for product diversification of rubber seed."
I don’t understand the logic of this sentence. Maybe “product diversification” is not the right term.

The Abstract is generally self-contained (except L.28-29), however, I am wary about conclusion relating hydrogen cyanide (see my comment on Validity of the Findings).

The Introduction provides an overview of the chemical composition of rubber seed. However, the discussion of rubber seed processing is lacking. The writing also needs improvement:
- Several literatures cited in the Introduction (e.g. Akinmutimi, 2004; Nwokolo, 1996; Lukman et al, 2018; Siti et al, 2013) are not included in the References
- Line 56-58: "Importantly, that excess of 25% (...) protein-rich foods." Citation needed.
- For information that may constantly change, (Nwokolo, 1996) seems like an outdated reference for rubber plantation area and rubber seed production. Maybe it provides rubber seed yield (tonnes seed/ha), but since it is not on the reference list, I cannot evaluate for myself. In any case, the data for the plantation area should be referenced with recent literature.
- Line 71-77: This part lacks coherence. In the beginning, the statement is vague ("high essential nutritive value", "considerable amounts"), but the next sentence contains very precise numbers (two decimal digits). The author also mentions rubber seed meal, rubber seed protein isolates, and rubber seed oil. It must be clear what the authors mean by these, and how they are connected to the previous sentence. I would suggest the author to re-write this part, substantiate the vague statements with numbers and/or compare with "conventional seed meals".
- Line 91-93: "...the processing of rubber seed can involve a range of activities, such as, boiling, fermentation, roasting, as well as other forms of heat treatment." This should be more elaborate. As I mentioned before, there should be more critical overview in the Introduction that leads to the reason for selecting processing methods.

Results and Discussion should be presented in reasonable order (following order in tables, or otherwise any reasonable groupings). If the authors choose a certain grouping in the discussion (e.g., components that increase, components that decrease), it will help the reader if the paragraph starts by explaining what will be discussed, e.g "The contents of component X, Y, Z increased after processing"

In the discussion, whether a value is a requirement (minimum) or limit (maximum) should be clear to evaluate quality. Specific comments:
- Line 332-334: from the sentence, I think it should be tannin maximum limit instead of minimum
- Line 333, 349: I don't think it is necessary to state the unit twice: 120 mg/kg (equivalent to 12 mg/100g). Just use mg/100 g so it is consistent throughout Discussion.
- Serving portion should be indicated for evaluation of RDI/RDA.

I would suggest that the discussion on anti-nutrient and phytochemicals is divided into separate sections. This is related to my previous comment, because the evaluation of anti-nutrient should refer to the maximum limit. On the other hand, discussion on phytochemicals is not as strict because there are potential benefits in some compounds.

Line 472: Please clarify, is RDA for B vitamins for the sum of B1, B2, B3 or for each?

RDI and RDA should be added in the Abbreviation list.

Figure 1 is too general. The explanation in Line 110-114 and Figure 2 is adequate. I would suggest removing Figure 1.

Figure 2 needs revision:
- Raw rubber seed (meal is missing)
- Fermentation (3--days in other line)
- I think there should be dry milling step after oven drying and fermentation

Tables can be more informative (self-contained): I would suggest adding one column in each table as reference values (maximum/safe limit for anti-nutrient, RDI/RDA for phytochemical and micronutrients).

Table 1: Phenols in BRSM has no superscript

Table 2: Why is selenium not discussed? What is the meaning of dash (-) for nickel? If not detected, please state.
Experimental design: No comment
Validity of the findings: The result is promising as a basis for practical application. However, I have some comments as follows:

The Methods mention that the results are from triplicate determination, however, the submitted data only show duplicate results. Perhaps the author can correct this discrepancy.

I think there should be a comparison with other processing methods of rubber seed. The authors already cite at least two references (Aguihe et al, 2017; Udo et al, 2018) that discuss similar RSM components. However, there is only one mention of Udo et al in the discussion about TI. There might be other relevant literature that has not been referred to. The comparison would also help explain how the process influences the composition.

I find the authors' conclusion on hydrogen cyanide is problematic. First of all the authors already mentioned that the safety limit of HCN is 1 mg/100 g, which could not be met by any of the processes although FRSM came close. (note: I also think L348 should be maximum limit, not minimum). Second of all, the authors conclude that the processed RSM are safe based on lethal dose. I believe the unpleasantness caused by HCN would occur way below the lethal dose. I would suggest the authors presenting a more convincing argument for the safety of processed RSM. Otherwise, I happily accept that the current process has not yet succeeded in removing HCN, but already heading toward the right direction.

Line 520: "Given that the rubber seed is a poor source of micronutrients." I find this statement comes out of nowhere. The way the authors discussing the result, it is difficult to reach this conclusion.
Additional comments: Just a suggestion, I think it would help if there is a graph (e.g radar charts) that compare the three processed RSM together without overly repeating the results.


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 ANTI-NUTRIENT, PHYTOCHEMICAL, AND MICRONUTRIENT CONTENTS OF DIFFERENT PROCESSED RUBBER (HEVEA BRASILIENSIS) SEED MEALS
Review round: 1
Reviewer: 2

Output:
Basic reporting: In general, the authors had done a good job in writing the article.
Experimental design: Good experimental design
Validity of the findings: No comments; good findings
Additional comments: The manuscript is written well except for minor grammatical errors in the text. Overall, this paper can be accepted.


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 ANTI-NUTRIENT, PHYTOCHEMICAL, AND MICRONUTRIENT CONTENTS OF DIFFERENT PROCESSED RUBBER (HEVEA BRASILIENSIS) SEED MEALS
Review round: 2
Reviewer: 1

Output:
Basic reporting: The authors have made an excellent revision and addressed almost all of major issues in the previous version. The English writing still needs some work to improve clarity.

Aside of the English, I only have some minor comments:

- L25-27 (Abstract): Maybe add "...to produce edible oil and protein" since the next sentence mention "protein source"

- L321: This sentence still mention "triplicate measurement"

- L445-446: I think it should be "...equal to 1776 g of FRSM and 743 g of BRSM"

- Table 2: safety limit units need to be clarified (whether mg/100 mg on the heading or mg and µg)

- There seems to be differences of alkaloid values for FRSM between Table 1 and supplementary file. This might be due to glitch in Excel, but please check.
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: LOCAL-SCALE IMPACT OF WIND ENERGY FARMS ON RARE, ENDEMIC, AND THREATENED PLANT SPECIES
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript “Habitat disturbance by wind energy farms effects on protected plant diversity at local scale. A case study of Dealurile Agighiolului Natura 2000 site” by Urziceanu et al surveyed plant species around the disturbed and undisturbed plots near wind farm turbines to examine the impact of wind farm on plant biodiversity. The topic of this study is worth investigating and the findings that disturbance decreased species richness provide valuable evidence for the wind farm impacts. The manuscript is well-written. Below I have some questions about the methodology and findings.
Experimental design: I suggest to include basic geographical information about the study region, in particular climate conditions and vegetation types. This information provides important background to understand the wind farm impact on plants because climate also affects the resilience of plants to disturbance.

Regarding the methodology, the authors took samples from within 50 m distance from the wind farm. What is the justification for this distance choice? How does the wind farm disturbance impact vary with distance? Besides, the authors need to give more information about how to define undisturbed and disturbed plots in their field survey. This is very important for this study but for now, there is just a vague description that is not clear to me. It would also be great to include photos of the disturbed plots.

It seems the authors focused on the impact of protected species and found decreased diversity, which is fair. I am wondering what would be the impact on unprotected species? Because the protected species might be more vulnerable to disturbance and the unprotected species might be more resilient to disturbance (which is why they are not on the red list). A related question is about the general impact of wind farm on vegetation, in addition to plant diversity. There are also properties like vegetation coverage, biomass, etc. It would be great if the authors can put their findings of plant diversity under the context of general impacts of wind farms on vegetation, which makes the paper more attractive to a broader audience. Perhaps adding relevant discussion in the introduction or discussion section would be good enough. For example, there are also relevant studies reporting positive effects of wind farm on plants at either local and large scales, e.g., Xu 2018 and Li 2018.
Validity of the findings: Minor comments:
It would be helpful to include some photos of the landscape of the sampled wind farm region.

Where are the sampled locations? Is it possible to please add them to the map?

Figure 1. Please include latitude/longitude and the location of the study region from a global or regional perspective, e.g., a zoomed map view to indicate the location from the world/regional map.

L165-169: I feel the authors need to provide more information about the disturbed area. Is it an area previously occupied by wind farm facility and later recovered, or is it still currently occupied by the operation of wind farm facility? They are two different cases. The former denotes a legacy disturbance effect while the latter denotes a persistent disturbance effect.

L250-251: “The annuals are more frequent in disturbed plots, comparing with the perennial, more frequent in undisturbed plots”. The wind farm disturbance indeed changed plant diversity, but how to explain the differences between perennials and annuals?

References
Xu, K., He, L., Hu, H., Liu, S., Du, Y., Zhiwei, W., … Li, L. (2019). Positive ecological effects of wind farms on vegetation in China ’ s Gobi desert. Scientific Reports, (October 2018), 1–11. https://doi.org/10.1038/s41598-019-42569-0
Li, Y., Kalnay, E., Motesharrei, S., Rivas, J., Kucharski, F., Kirk-Davidoff, D., … Zeng, N. (2018). Climate model shows large-scale wind and solar farms in the Sahara increase rain and vegetation. Science, 361(6406), 1019–1022. https://doi.org/10.1126/science.aar5629
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: LOCAL-SCALE IMPACT OF WIND ENERGY FARMS ON RARE, ENDEMIC, AND THREATENED PLANT SPECIES
Review round: 1
Reviewer: 2

Output:
Basic reporting: The authors of this manuscript, entitled ” Habitat disturbance by wind energy farms effects on protected plant diversity at local scale. A case study of Dealurile Agighiolului Natura 2000 site (Dobrogea, Romania)” present a study on the impact of wind farm developments on natural habitats, with an example from Dobrogea region (Romania). Their major goal is to evaluate the pressures on protected plant species after 10 years of operational history of the Agighiol wind energy farm (Dealurile Agighiolului Natura 2000 site, Dobrogea, Romania) by comparing across the 17 selected wind turbines the plots covering disturbed habitats with their corresponding proximal pair-plot covering undisturbed habitats, but also by partitioning beta-diversity components within each plot type and among the two types.

The language is quite complicated and wording is entangled. I suggest acquiring the help of a native speaker for simplifying and improving the language and wording/phrasing, which in the current state suffers greatly and affects reading, being in many cases unnecessarily complicated. Such simplification of the language would serve well the entire study by enhancing reading and proper delivery of information, subsequently increasing the value of the paper.

The manuscript has sufficient references to develop the background and support the findings. The figures are well-designed, however, the figure captions should be removed from the figure and be presented as text.

The structure of the manuscript is not ideal. Some paragraphs have to be moved between sections, some sections (especially the Discussion part) have to be better developed and clearly presented in relation to the obtained results.
Experimental design: The paper presents original data and the study falls within the scope of the journal.

It seems, however, that the authors have missed in presenting the working hypothesis/hypotheses, aspect that I've highlighted in my review, presented in the attached pdf. The imact of the results is well defined and meaningful, bringing more insight over the proposed research topic.

The statistical analyses are correct and fit the data used in this study. The given details are sufficient and offer the possibility to replicate them. Some additional anayses are suggested for a more thorough approach of the subject, including functional diversity, species eveness and providing additional information on plant communities.

Some methods should be better explained to highlight their importance and meaning and why where they chosen for this study.
Validity of the findings: The study is valuable by approaching an important topic in the context of increased infrastructure developments nowadays for the production of green energy, however it is poorly presented and lacks a good flow in both language and argumentation.

It seems that the disturbance level is rather difficult to evaluate in the case of undisturbed plots due to a lack of information on the community structure prior to wind farm development, which in my opinion affects the value of the results and overall conclusions. There is a way to overcome this caveat that I present in the pdf containing Major and Minor observations to the msc.

Raw data are provided and should provide enough support for any replication of the study.

Conclusions should be better developed in relation to the hypothesys that will be formulated by the authors.

These aspects can be corrected by reconsidering all sections of the manuscript, including additional analyses.
Additional comments: The suggested changes would be required before the manuscript can be considered for publication in PEERJ. I thus recommend a Major Revision and would be happy to re-visit the next version of the manuscript, when submitted, and receive the author’s reply to my comments.

I wish the authors good luck and present my Major Observations and Minor comments in the attached pdf.


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

Input:
Title: LOCAL-SCALE IMPACT OF WIND ENERGY FARMS ON RARE, ENDEMIC, AND THREATENED PLANT SPECIES
Review round: 2
Reviewer: 1

Output:
Basic reporting: The revised manuscript addressed most of my comments. But I am not satisfied with some responses.
For example, the authors replied my original comment "Where are the sampled locations? Is it possible to please add them to the map?" by "We redraw the map and included more details." However, I could not find the sampled locations on the redrawn map.

There are still occasional unclear sentences or with grammatic errors, for example,
L19-21; L350-353
Experimental design: NA
Validity of the findings: NA
Additional comments: NA


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: SPMLMI: PREDICTING LNCRNA–MIRNA INTERACTIONS IN HUMANS USING A STRUCTURAL PERTURBATION METHOD
Review round: 1
Reviewer: 1

Output:
Basic reporting: In this study, Xu et al. developed a computational method, called SPMLMI, to predict IncRNA–miRNA interactions in humans. This study is well designed and the manuscript is well organized.
Experimental design: Why do the authors take two lncRNAs SNHG14 and MALAT1 as case studies?
Validity of the findings: The authors should describe in more detail how the predicted interactions are judged as true values in cross-validation.
Additional comments: 1. The authors should discuss the limitations of their method and describe the scope of application and considerations for using the method accordingly, so that the reader can use or evaluate the method.
2. The data collection section needs to be described in more detail.
3. Why do the authors take two lncRNAs SNHG14 and MALAT1 as case studies?
4. Could you give some discussions how to use predicted lncRNA-miRNA interactions to predict miRNA-disease associations and lncRNA-disease associations as the future direction of this work (PMIDs: 24002109 and 29045685)?
5. The authors should describe in more detail how the predicted interactions are judged as true values in cross-validation.
6. You should revise your English writing carefully and eliminate small errors in the paper to make the paper easier to understand.
7. The sentence of " However, the roles of most lncRNAs in cellular processes have yet to be determined, and we can safely predict that many new functions will be discovered. “should have references of paper with PMIDs of 27345524 and 30247501.


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: SPMLMI: PREDICTING LNCRNA–MIRNA INTERACTIONS IN HUMANS USING A STRUCTURAL PERTURBATION METHOD
Review round: 1
Reviewer: 2

Output:
Basic reporting: In this work, the authors develop a miRNA-lncRNA interaction predictive method based on network analysis, which considering the expression similarity between miRNAs and the similarity between lncRNAs respectively.  Compared with previous ceRNA binary network, the added links between same node type improve the correlation of genes’ expression. Additionally, the higher AUC of SPMLMI comparing other 2 method indicates the higher accuracy of this approach. However, there are still several problems need to be explained.
Experimental design: no comment
Validity of the findings: no comment
Additional comments: Major Points:
1. The description of method is brief. Authors would better describe the interaction score and structural perturbation method in detail.
2. There is no consistent threshold in SPMLMI, such as significance or the top 10% with the highest score, for the prediction method. In the two application cases, the authors focused on the top 20 and 120 prediction results respectively.
3. It is mentioned in this paper that lncRNA has high tissue specificity, but it’s not reflected in the process of network construction.
4. Two case studies identified important lncRNA targeted miRNA, there was no further verification and biological explanation for their predicted interactions.


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: SPMLMI: PREDICTING LNCRNA–MIRNA INTERACTIONS IN HUMANS USING A STRUCTURAL PERTURBATION METHOD
Review round: 2
Reviewer: 1

Output:
Basic reporting: It could be accepted for publication.
Experimental design: Good design
Validity of the findings: reliable findings
Additional comments: could be accepted


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: SPMLMI: PREDICTING LNCRNA–MIRNA INTERACTIONS IN HUMANS USING A STRUCTURAL PERTURBATION METHOD
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors have addressed the majority of my questions. The following papers (PMID: 32193291; PMID: 27365046; PMID: 26304537) should be cited which are closely associated with this work.
Experimental design: no other comments
Validity of the findings: no other comments
Additional comments: The authors have addressed the majority of my questions. The following papers (PMID: 32193291; PMID: 27365046; PMID: 26304537) should be cited which are closely associated with this work.