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: TIO2 NANOPARTICLES AFFECT THE BACTERIAL COMMUNITY STRUCTURE AND EISENIA FETIDA (SAVIGNY, 1826) IN AN ARABLE SOIL
Review round: 1
Reviewer: 2

Output:
Basic reporting: The language is clear and professional. The raw data of the microbial community analyses are provided in an online repository.
A weakness of the manuscript is the quality and labelling of the Figures and Tables which could use improvement. All graphs are quite small and the quality is low which makes it hard to read labels and axis names. The symbols chosen in Figure 1 are 2 could be grouped together for the different treatments e.g. all earthworm treatments are black and different shapes; all earthworm+oats treatments are white and different shapes.
Figure 1: The letter a)-l) are easily overseen, they should be larger and placed at the right of each graph. Differences between treatments in a) and b) are hard to see because of the scale chosen. Maybe a Table would show these more clearly.
Figure 3: This is very crowded and therefore hard to read.
Figure 4 and 8: It is not clear what the three columns depict. In Figure 8 it is not clear what the arrows show. Please add information to clarify this.
Supplementary information
Descriptions and/or legends of the Figures and Tables are needed otherwise it is difficult to understand what is shown.
Table 4: This Table should be moved to the main manuscript.
Experimental design: The authors have studied an important and interesting subject by investigating the effects of the combination of TiO2NP, earthworms and organic matter on a soil microbial community.  The novel aspect of this study is the investigation of effects of combinations of different treatments (TiO2NP, earthworm presence, organic matter addition) on a soil microbial community. The Introduction could emphasize this more by pointing out that most studies focus on effects of changing a single parameter (e.g. addition of nanoparticles or adding earthworms).The objective of the study is clearly stated. Appropriate methods were applied for investigation of the research objective. The description of the experimental design could, however, be improved in parts by giving more details.
l. 83 It would make it easier for the reader if the basic characteristics (e.g. size) of the used NP were given here, rather than only in the Supplementary Information. Also information on the coating or stabilizing agent of TiO2NP is missing. Numerous studies have shown that this can strongly affect behavior and toxicity of NP (e.g. Tan et al. 2017, Environmental Pollution; Li et al. 2013, Environmental Science & Technology; Whitley et al. 2013, Environmental Pollution; Arnaout et al. 2012, Environmental Science & Technology).
l. 91: What kind of kitchen organic waste was fed to the earthworms? Is there the possibility that the earthworms were pre-exposed to e.g. pesticide residues in the organic waste? If this was the case their sensitivity to other chemical stressors might differ from animals that were not pre-exposed.
l. 95: Where pesticides and fertilizers applied to this field?
ll. 101: To increase readability this data could be presented in a Table. Was this data gathered as described in 2.8? If so, please refer to this section.
l. 105: The heading should be more detailed to guide the reader better: “Vessel preparation and experimental design”.
l. 105-109: It is not clear why this procedure was chosen and with which goal.
l. 110-116: It would be easier to understand which treatments were applied by inserting a Table here rather than in the Supplementary Information. How many individuals of E. fetida were used per treatment? What amount of oat seeds was added per treatment? How many replicates were done per treatment? Are these concentrations of TiO2NP environmentally relevant or why were they chosen?
l. 120: It is not clear what the difference between “treatment” and “soil sample” is. How many replicates were measured per time point?
l. 171-175: Would it be possible to create a models with NP, earthworms, oats to explain soil characteristics and earthworm “characteristics”? This way the statistical power would be increased compared to doing multiple t-tests.
l. 174: 2-way t-test
ll. 175: Because of the importance of PCA and CAP analyses for this paper it would be helpful for readers who are less experienced in reading such graphs to briefly explain how to do so.
Validity of the findings: The Results and Discussion section is very long and could benefit from shortening in parts. This way the key findings could be more clearly identified.
The Conclusion is a summary of the findings of the study rather than a Conclusion on how this study has advanced our understanding of interactions in soils.
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: TIO2 NANOPARTICLES AFFECT THE BACTERIAL COMMUNITY STRUCTURE AND EISENIA FETIDA (SAVIGNY, 1826) IN AN ARABLE SOIL
Review round: 3
Reviewer: 1

Output:
Basic reporting: no comment
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: TIO2 NANOPARTICLES AFFECT THE BACTERIAL COMMUNITY STRUCTURE AND EISENIA FETIDA (SAVIGNY, 1826) IN AN ARABLE SOIL
Review round: 3
Reviewer: 2

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: The authors have clearly improved the quality of the manuscript with their revisions.
There are still a few points that should receive more attention.
1) The authors’ response stated that pesticides were only applied to the soil to a very limited extent. This information should appear in the manuscript as well.
2) Possible accumulation of TiO2NP by earthworms is now mentioned in the manuscript, however a reference is missing. References are also missing in ll 474.
3) The Conclusion was changed, however it still mainly is a summary of the data. If this is the goal the heading should be changed to Summary. Otherwise this section needs additional work.


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

Input:
Title: DETECTION OF HUMAN METAPNEUMOVIRUS INFECTION IN CHILDREN UNDER 18 YEARS OLD HOSPITALIZED IN LIMA-PERU
Review round: 1
Reviewer: 1

Output:
Basic reporting: A few style points in regards to the language.
1) Numbers 1-10 should be spelled out, eg one, two, etc. [lines 36, 37, 40, 63, 68, 143, 144, 147, 156, 178, 187, 190, 192, 193, 204, 227]

2) Sentence starting "Therefore..." on line 180 is unclear, I would clarify

3) Sentence starting "As detailed..." on line 157 is unclear as well, please clarify

In regards to literature references, fix citation on line 74.
Experimental design: It is unclear what kind of study is being described. Is it prospective? I would suggest describing the study type in the abstract under methods and line 83 in the main manuscript.
Validity of the findings: Unable to truly assess without knowing what kind of study. I assume that it is prospective given consent was taken. If prospective, it appears to be statistically sound and conclusion is well stated.
Additional comments: I would add a paragraph describing the limitations to your study and how you addressed those limitations if it all possible.

Although there is great content in the discussion, it can be organized to be made clearer and easier to read. I suggest organizing it as such: paragraph 1 describe what you found in your study, paragraph 2 (or more) describe how your findings compare to what is in the literature, next paragraph your strengths and limitations and last the conclusion.


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: DETECTION OF HUMAN METAPNEUMOVIRUS INFECTION IN CHILDREN UNDER 18 YEARS OLD HOSPITALIZED IN LIMA-PERU
Review round: 1
Reviewer: 2

Output:
Basic reporting: The language needs to be improved, for example, line 180-182, it does not make sense. The background is well stated. The article is generally well described, including figures and tables.
Experimental design: 1. Did you look into the co-infection? Does it differ in characteristics / clinical symptoms / signs from those with single hMPV infection? This might affect your findings particularly considering that the study period overlaps with pandemic influenza A H1N1.
2. The methods in abstract is too short.
3. Line 41: "hMPV can cause both upper and lower respiratory tract infections that can develop into potential life threating complications". Where is this sentence concluded from? You did not mention how many patients were AURI or ALRI in the result. You also did not mention any "life threating complications" among hMPV patients.
4. Did you include all ARI patients during the 2-year study period or did you use any sampling approach?
5. Line 86-88: How did you get the ARI definition? Did you use the same case definition for all patients under 18? Is it appropriate to do so? If you did not include fever as one of the criteria to define ARI, will the result be different (any sensitivity analysis)?
6. Line 93: The underlying population is children under 18 years old. It does not make sense to say "or by the parents or respective guardians in the case of underage patients below 18 years of age".
Validity of the findings: 7. I don't see the point of Table 1 (line 138-141). What is your purpose? Also, I don't think it indicates "other etiological agents have a greater association". I guess you wanted to mean "percentage".
8. Line 144: The high percentage of hMPV in infants does not necessarily mean that this is the age group with high risk. The fact that how many ARI patients were tested (denominator) also affects the number of hMPV being positive. This is particularly a problem considering that the tested ARI cases mainly came from infants too. Anyway, can you please clarify the selection bias here?
9. Line 148: "sex of children is not a factor associated with the prevalence of hMPV" conflicts with line 193 "the majority of patients with hMPV infection were male (58.90%)".
10. Line 149-150: It does not make sense "...due to the high frequency of signs and symptoms...". What were you trying to say here? Also, the number of patients who have been hospitalised should be described at the beginning of the result.
11. Line 168: Can you please clarify that there is no selection bias here (the high number of hMPV in March might be due to the large number of ARI samples tested in March)?
12. Line 190: I don't think you have any result indicating this point "early age is associated with greater need for hospitalisation".
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: DETECTION OF HUMAN METAPNEUMOVIRUS INFECTION IN CHILDREN UNDER 18 YEARS OLD HOSPITALIZED IN LIMA-PERU
Review round: 2
Reviewer: 1

Output:
Basic reporting: The language and read of this article has vastly improved. Small typos should be corrected. Line 30, "life threating..." should be corrected to "life threatening...".  Line 61, the I in "Furthermore, It..." should be lowercase. Line 169, "emphazises" should be corrected to "emphasizes". And line 192, "Of the sampled..." should be corrected to "Among the samples..." After those few changes, this article is well written and publishable.
Experimental design: The design is stated much more clearly. I have nothing to add.
Validity of the findings: No comment.
Additional comments: Great job on the revisions.


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: EXPLORING SPATIAL NONSTATIONARY ENVIRONMENTAL EFFECTS ON YELLOW PERCH DISTRIBUTION IN LAKE ERIE
Review round: 1
Reviewer: 1

Output:
Basic reporting: Overall, the article was written in professional English. However, some sentences were not clear and require restructering (line 104; lines 193-194; lines 241-242; lines 285-286; liens 295-296; lines 306-307). Throughout the introduction, methods and discussion ample references are included thereby providing sufficient background/context. A reference for the used package and R statistics is required at line 164 and line 183. The structure of the manuscript conforms to the standard structure. The Figures are relevant and of high enough detail. Readability of figures could be improved by giving the units for the x-axis (Dissolved Oxygen --> mg/l). Based on the description in the text it was impossible to check the raw data for consistency. Headers of raw data did not correspond to the text. Moreover, total number of datapoints mentioned in text (2502) dit not match with the number of datapoints in the raw data (2610). The presented results are sufficient for a publication. The reporting of statistical results is limited, no test values are given. A GAM table with the results for each abiotic factor is missing. At line 222-223 give test values for the statement that a significant difference was found. Can you state that there is a significant difference in AIC at line 235 ?
Experimental design: The manuscript falls within the aims and scope of the journal. The introcution clearly underpins the added value and the research gap of the goal of the manuscript. However, the actual phrasing of the goal can be improved (lines 105-115). It should be formulated more like a goal then as an activity.

Large parts of the methods are described in detail but due to some inconsistenties it does not provide sufficient detail to replicate. The total number of datapoints included mentioned in line 126 does not correspond with the raw data file. Moreover, the headers of the raw data are not self explanatory. Additional information on all headers is required. The two different age groups can not be distinguished in the raw data file. The estimation of fish age mentioned in line 129 requires more explanation. Was this performed by the authors or was this already available in the used dataset. How was this performed? consistent with previous studies? In the methods it is stated that the near bottom living fish were included however the abiotic condtions were mainly measered on the top of the gill net, which differs in space. Potential confounding effects of this depth effect should be mentioned in the discussion. At line 136/137 it is explicetely stating that bottom dwelling fish data was used, does this refer to the previously mentioned 2502 samples or is this a subset?
Validity of the findings: The data could not be checked fully due to unclear headers and discrepancy in the number of datapoints included. Moreover, the methodology was not sufficiently clear regarding fish age. Overall the conclusios based on the performed analyses are clear, linked to the original research question. At line 338-339 a reference is made to the k=4 analyses whereas previously it was indicated that the k=2 analysis provided the best results. Why then discuss the outcomes of the k=4 analysis? The analysis was now limited to presence-absence data, however density data was also collected. The discussion could be improved by discussing not analysing density data.

Figure 3 seems to have an error: the observed datapoints for both the adults and juveniles appear to be identical. This would then inherently results in actually the same relation between presence absence and the environmental factors which is not found. This is especially clear for adult fish in relation to temperature where the density of occurrences does not correspond to the plotted relation.
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: EXPLORING SPATIAL NONSTATIONARY ENVIRONMENTAL EFFECTS ON YELLOW PERCH DISTRIBUTION IN LAKE ERIE
Review round: 1
Reviewer: 2

Output:
Basic reporting: The manuscript provides a useful exercise to explore the spatial non-stationary environmental effects on Yellow perch in Lake Erie. I think this is a worthy study for PeerJ but I do have several critiques that I think need to be addressed before publication. The critiques are summarized in the general comments.

The main context of the manuscript is clear but it needs to be checked for grammar issues. The overall structure of the manuscript follows the logic. The manuscript can be improved with the expansion of discussion and better labels in some figures (e.g. Figure 1 and Figure 6). The details are explained in the general comments section in this review.
Experimental design: The study is original primary research within the scope of the journal. Such studies could be helpful to the Yellow perch fishery in Lake Erie area and can serve as an example of how to apply the GWR model as a complementary tool for species distribution modeling. The manuscript clearly states the goal of the study and well described the methods with sufficient details, but there is little explanation of the research question, the authors need to further explain why biologically these relationships should vary across this relatively small study area.
Validity of the findings: This study is a fine application of the existing package and previously developed model on the distribution of Yellow perch. The data and methods are robust and statistically sound. However, since this is a case study of Yellow perch distribution, I recommend the authors provide more biological speculation/interpretation of the findings instead of statistical interpretation. The conclusion is clearly stated but it is very similar compared with other studies that used the GWR model. The authors need to provide a better ecological/biological conclusion related to the Yellow perch distribution.
Additional comments: The authors need to provide a better ecological/biological meaning of the relationships found between the presence of Yellow perch and environmental variables as well as the motivation of the study in the introduction. There is little explanation for why biologically these relationships between the presence of Yellow perch and environmental variables should vary across the study area. The study area is a relatively small area and the population here could be well mixed if it is a single population. Given this fact, what is the motivation for allowing spatially varied relationships between environmental variables and the presence of Yellow perch? From the results, we could see the GWR fits the data slightly better than a global model of GAM, but given the biology, do the estimated relationships could vary so rapidly over a short distance? What are the biological implications of the estimated relationships?

Lines 91-93: The authors mentioned that the study area has significant environmental variations in the west, central, and east basins. In the absence of any plots of the abiotic variables themselves, it is difficult to assess the impact of the local environmental conditions on the occurrence of Yellow perch across space. Perhaps provide the observed environmental data maps in the manuscript could help the audience.

Generalized additive models (GAM) is also able to allow the spatial variation to be described using a complex spatial field, such as a Gaussian random field. The authors need to mention the reasons why they chose the GWR and the simple GAM in this study, and discuss the possibility to use GAM with a random field to consider spatial variations in the introduction or discussion.

There are 27 years of data (1989-2015), the presence of Yellow perch are likely varying during that time, but the authors only mentioned in the very end of the discussion that no temporal term was included in the models. I suggest the authors plot the residuals by year to look for signatures of temporal effects. The authors also need to discuss how inter-annual changes in the population presence or different regional environmental changes could affect their results.

Line 158: The authors mentioned that they used a fixed number of observations as bandwidth. Do the bandwidth estimates have a biological interpretation? If so, please provide its implication in the results.

Line 201: The authors mentioned that the juveniles were found at 58% of sample sites, but adults were found at 90% sample sites. This is opposite to the information from Figure 2, which shows a very low occurrence of adults in the study area. It also could be the caption was not right.

The GWR is a moving window of GLM at each study site. Are the estimated coefficients of each variable significant at each site? The authors need to describe the significance of the estimated relationships in the results.

Variations in catchability can be confounded with the variation in the distribution in spatial modeling research. The authors did not discuss the issue of catchability in this paper. I suggest the authors expand their discussion on the assumption of constant catchability over space and time and caveats associated with this assumption.

Table 1: Change 'Moran test' to 'Moran test p-value'.

Table 2: If I understand correctly, the data/variables used in some final models were different (e.g. GAM-Adult with three x variables and GWR-Adult with four x variables), so the AIC values cannot be used to compare the models with different input data. I suggest removing the AIC column in the table.

Figure 1: The survey sites need to be clearly shown on the map with the same size of circles. The information provided from figure 1 could be found in figure 2 as well, so I suggest drawing the points with colors that represent values of observed environmental data (e.g. temperature and depth) in figure 1.

Figure 2: The resolution of the figure needs to be improved. Please double check the caption and labels in the figure. I think the circle represents the presence of species.

Figure 4 and Figure 5: Please provide the lines for separating the basins on the map.

Figure 6: The k-mean cluster analysis was conducted using the t-values from the model outputs. Why not using the coefficient estimates? t-values could be used to compute p-values and help determine whether or not the estimated relationships exist. If the authors want to "characterize the spatial zones of species-environmental relationships" (Lines 178-180), I suggest applying the k-mean cluster analysis to the estimated coefficients which represent the magnitude and direction of estimated relationships.


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: EXPLORING SPATIAL NONSTATIONARY ENVIRONMENTAL EFFECTS ON YELLOW PERCH DISTRIBUTION IN LAKE ERIE
Review round: 2
Reviewer: 1

Output:
Basic reporting: The authors have thoroughly adapted their MS based on the comments of both reviewers. Readability has been improved throuhgout. References have been updated. The structure of the MS is professional and corresponds to the journal.
Experimental design: The experimental design, especially the raw data, has improved and it is now more clear why specific decisions were made. Replication is now possible.
Validity of the findings: With the expansion of the discussion the impact of the findings is now more clear.
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: EXPLORING SPATIAL NONSTATIONARY ENVIRONMENTAL EFFECTS ON YELLOW PERCH DISTRIBUTION IN LAKE ERIE
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors have met these criteria.
Experimental design: The authors have met these criteria.
Validity of the findings: The authors have met these criteria.
Additional comments: please see the attachment.


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: COMPREHENSIVE MAP AND FUNCTIONAL ANNOTATION OF THE MOUSE WHITE ADIPOSE TISSUE PROTEOME
Review round: 1
Reviewer: 1

Output:
Basic reporting: The manuscript was written clearly, with a nice summary of contemporary studies in the introduction. It would be even more helpful if the authors could elaborate more on what makes the current study stands out from previous reports. Importantly, unbiased interpretation of MS data and an insightful discussion would be appreciated.

Article structure is clear, and raw data was provided. Figures 1 and 2 are clear. Figure3 needs revision. Secretome section needs to be expanded.

The results provided are relevant to the research theme, but are not strong enough to draw concrete conclusions. Ideally, further experiments (such as western blot) should be performed to validate their results.

Please also see my general comments below.
Experimental design: This manuscript falls within the scope of PeerJ.

It would be helpful if the authors could further explain what’s the deficiency of previous studies. The use of cultured cells instead of real tissue sample? Why could the authors detect more proteins? Better spectrometer and sensitivity so low abundance proteins could be detected? ……

The research question and hypothesis are not clearly defined. It is unclear what’s the goal of this study, to more precisely map the mouse WAT proteome by identifying more proteins? It would be much appreciated if the authors could perform more analysis and further discuss how their new dataset contributes to our current knowledge of the biology of WAT.

Methods section are clearly written.

Please also see my general comments below.
Validity of the findings: Have the authors examined for contaminations in WAT sample? Can the authors validate their WAT samples were indeed WAT by any experimental data?

As mentioned above, the manuscript is lacking meaningful discussion, and it is unclear how this study would benefit the field.

It’s hard to imagine one MS dataset could serve as a baseline reference for future studies, as tissue samples are known to be heterogeneous and require complex preparation procedures. The fact that the most abundant protein observed is serum albumin suggests that WAT samples were contaminated, maybe by blood cells (?). If that is the case, how could the authors confidently analyze data and conclude that the ‘secreted proteins’, particularly for low abundance proteins, are actually synthesized in WAT other than being transported from elsewhere by blood?

Please also see my general comments below.
Additional comments: Obesity and diabetes are important topics in the biological and medical fields. Proteome studies of tissue samples are demanding to reveal the physiological characteristics of specific tissues and the pathological changes. The authors performed proteomic profiling of interscapular WAT collected from female mice, identified >6000 proteins covering about half of the expected human proteins, and predicted 800 secreted proteins of WAT. Aside from the comments above, below are some more detailed comments:
1.	The authors reported 3500 newly identified proteins, are they less abundant than the known WAT proteins from other studies? Maybe add a panel in figure 2 showing the distribution of protein abundance? It would be appreciated if the authors could comment on why their study shared only a fraction (50%-60%) of proteins with previous reports. Please make a similar fig2d but only use the most abundant proteins in this study?
2.	Why did the authors choose to use interscapular WAT? Please include this information in figure1 or at least in figure legends. Could the authors comment on the difference between interscapular WAT and abdominal WAT (Xie et al., 2010)?
3.	The identification criteria in this study are different than others listed in Table2, please explain the reasons.
4.	Line 187, how are these 5270 proteins selected? This number did not appear in any figure or other parts of the text. Why not use the 5057 proteins identified in all 3 runs?
5.	Why didn’t the authors comment on demin and transgelin, two of the 'ten most abundant proteins'? What are they and their relationship to WAT? Are they identified for the first time in WAT?
6.	In figure 3a-c, no legend is provided. Five bars were shown in each panel, what are they? In figure 3d, it would be helpful if the authors could use dash lines to divide the figure and highlight pathways for high, medium, and low-abundance proteins respectively. Please use a larger font in the main figure.
7.	Could the authors expand their discussion on the predicted secreted proteins? What are the top 5 or 10 newly identified (most abundant) secreted proteins? Are they related to the functions of WAT?
8.	Typos and grammar:
-line 84: The mice were fed a standard chow (SC; 10% lipids) diet for 22 weeks.
-line 162: and low-abundance ptoteins were analyzed respectively
-line 217: The major molecular function of WAT proteins were …
-line 252: The function of the high-abundance proteins were mainly related to…


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: COMPREHENSIVE MAP AND FUNCTIONAL ANNOTATION OF THE MOUSE WHITE ADIPOSE TISSUE PROTEOME
Review round: 1
Reviewer: 2

Output:
Basic reporting: Although the manuscript is generally understandable, there are numerous instances where the statements are scientifically inaccurate:
68-69: ‘proteomics technology has garnered many attention recently in biological research’. Many attention is not accurate as attention is not a quantifiable term.
Experimental procedure: use subscripts where necessary, for example: NH4HCO3
Ln 162: typo in ‘ptoteins’
Ln 170-171: In this study, samples of WAT from six C57BL/6J female mice were applied to generate a comprehensive profile of the normal mouse WAT proteome.
‘applied’ is not a proper term here to describe what scientific procedures were performed.
‘The relative protein abundance spans 6 orders of magnitude (Fig. 2C). Additionally, Table 1 showed the ten most abundant proteins in the WAT proteome.’
‘showed’ is not the appropriate verb here – ‘lists’ might be a better term.
Additionally, this sentence can be misleading. The table lists most abundant proteins found in your samples of the WAT proteome and not the WAT proteome in general. Also, this is an observation and not a claim.

The authors have covered some literature in the introduction and results section but have missed several important related studies (see below). Purposeful or unintentional, in either case it is unacceptable.

Figures are hard to read, Figure 3, all panels for example. Please use legible font size. Easy reorganization of panels A to D in figure 3 should easily allow for large font size.

Authors should consider adding pathway maps/figures for results section involving the role of proteins in various cellular pathways.

Complex data is not well represented. Results would be easier to understand if authors provide graphical representation of proteomic distribution.

Since this is not a novel workflow, figure 1 is not informative and necessary.

215-217: ‘nearly 85% of the proteins were present in cells (40.6% proteins present in cell parts, 26.3% in organelles and 17.4% in the macromolecular complex).’ This statement is not clear. What is meant by ‘cell parts’ and which assemblies are referred to in ‘macromolecular complexes’?
218: again clarification is needed: The major molecular function of WAT proteins were catalytic activity (44%) and binding (37.5%).'
Experimental design: There are serious flaws with the study design and result interpretation. In general, this is incomplete study with inconclusive results. The strength of this paper is a combination of technique and data analysis workflow. Label-free 2DLC/MS/MS is a valuable technique for proteomic analysis and when combined with the quantification algorithms such as iBAQ and bioinformatics workflow in a way that authors have used  can lead to insightful results. But authors (1) have not designed a study with clear hypothesis, (2) have not optimized their sample preparation protocol and (3) have not utilized this powerful workflow to gain insightful results. Assuming that the aim was to develop a comprehensive murine WAT proteome reference dataset, the hypothesis is that the workflow that authors have used leads to the most comprehensive murine WAT proteome profile. However, authors have neither analyzed their proteome coverage nor have tried to optimize the coverage. With more than 10% of the most abundant proteins being serum albumin, the sample preparation methods is flawed. There are several studies that have reported difficulties in isolating WAT/BAT proteome stemming from high lipid contents in these samples. In the experimental process, the authors centrifuge samples following homogenization, and harvest supernatant for proteomic analysis. Did authors not observe a later of fat/lipids at the top following the centrifugation step? Generally, several rounds of extractions are needed to clarify fat and get the ideal protein content, which is generally a very small fraction in WAT samples. Several commercially available kits are used particularly to get around the problem of high fat and low protein contents in WAT samples.

Authors bin the proteins in 3 groups based on their abundance, no where in the study do author attempt to optimize the coverage for low abundance protein. If the aim was to comprehensively cover the WAT proteome, authors need to address the flaws in sample preparation and optimize good coverage for low abundance proteins to complete this study. Furthermore, authors suggest that removing albumin would be a good next step in their paper. It is not the next step, it is something absolutely needed to be done as a part of the current study to see some useful data.
195-200: authors mention very briefly the metabolic process/pathway associated with high abundance protein. A lot more efforts are needed to carefully analyze data to see if protein abundance correlates with dominant metabolic processes in WAT and if so, can other associated proteins be identified?
201-206: author compare proteome coverage in the current study with 5 other papers. Authors claim to have identified 3500 proteins that have not been identified before. Assuming that improved proteome coverage reflects improvement over other studies, how do authors explain missing 1061 protein from Forner et al study 1082 proteins from Adachi study and make a claim that current proteome reporting provides comprehensive coverage. Further efforts and the use of multiple sample preparation methods are needed to truly obtain a comprehensive WAT proteome.

The author claim to have identified new protein that were not covered in proteome datasets before, which is not a valid claim as explained below, but in its current state what additional information does this study provide that could not have been predicted from genomic or transcriptomic data sets?
Which anatomical locations were used to collect WAT samples?
Validity of the findings: Considering albumin was the most abundant protein, accounting for the 10% of total proteome – the WAT proteome samples are not representative of the actual physiological condition. Furthermore, the authors have tried to correlate observed protein abundance to cellular function, which, since the samples do not represent normal physiological protein distribution, are useless.

Authors compare the number of proteins identified with those identified in other studies, how was this comparison done?

Discuss protein size distribution

The 5 references the authors have used to compare their proteome with are from several years ago (2001-2009) and in several cases are the studies doe using human samples. Authors have failed to acknowledge and consider data from recent studies done on murine WAT and BAT including:
Feist et. al (2017) Quantitative proteomic analysis of murine white adipose tissue for peritoneal cancer metastasis. Analytical and bioanalytical chemistry, 410(5), 1583-1594.
Hsieh et. al (2013) Altered White Adipose Tissue Protein Profile in C57BL/6J Mice Displaying Delipidative, Inflammatory, and Browning Characteristics after Bitter Melon Seed Oil Treatment. PLoS ONE
Andrade et al. (2014) Proteomic white adipose tissue analysis of obese mice fed with a high-fat diet and treated with oral angiotensin-(1–7). Peptides
Kim et. al. Differential Protein Expression in White Adipose Tissue from Obesity-Prone and Obesity-Resistant Mice in Response to High Fat Diet and Anti-Obesity Herbal Medicines
Peinado et al. Proteomic Profiling of Adipose Tissue from Zmpste24−/− Mice, a Model of Lipodystrophy and Premature Aging, Reveals Major Changes in Mitochondrial Function and Vimentin Processing
Feist et al. 2018 Quantitative proteomic analysis of murine white adipose tissue for peritoneal cancer metastasis.
Ke et al. Differential proteomic analysis of white adipose tissues from T2D KKAy mice by LC‐ESI‐QTOF
Sackmann-Sala et al. Heterogeneity among white adipose tissue depots in male C57BL/6J mice.
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: COMPREHENSIVE MAP AND FUNCTIONAL ANNOTATION OF THE MOUSE WHITE ADIPOSE TISSUE PROTEOME
Review round: 2
Reviewer: 1

Output:
Basic reporting: no comment
Experimental design: no comment
Validity of the findings: no comment
Additional comments: The authors have addressed 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: A SIX-MICRORNA SIGNATURE CAN BETTER PREDICT OVERALL SURVIVAL OF PATIENTS WITH ESOPHAGUS ADENOCARCINOMA
Review round: 1
Reviewer: 1

Output:
Basic reporting: In this study, the authors aim to construct a miRNA-based signature for predicting the prognosis of esophagus adenocarcinoma (EAC) based on the data extracted from The Cancer Genome Atlas (TCGA). The authors downloaded RNA-seq data of 84 EAC cases from the TCGA database. The manuscript might be interesting for the clinicians who are mainly interested in the prognosis of EAC. However, the paper needs some additional works, in particular the statistical methods parts, and some major changes are recommended before considering the paper for publication. The manuscript also needs extensive English editing since there are several typos and grammatical errors.
Experimental design: In addition to this, the similarity index in the Turnitin Originality Report was 38%, and this value exceeded the acceptable level range between 15%-20%. Authors must be careful about citing papers appropriately in their study.
Validity of the findings: My concerns are as follows:

In abstract,

•	In Line 57: Change “The Area under curve (AUC) for ROC” to “The area under the curve (AUC) for ROC” or “The area under the ROC curve”.
•	In Line 58: Use a comma before the word “respectively”.
•	In Line 63-64: It may be good to give a conclusion as the last sentences of the abstract.

In introduction,

•	In Line 57: Change “More often, There …” to “More often, there …”.

In materials and methods,

•	In Line 111: Provide the reference and accession numbers for the datasets.
•	In Line 113: Correct “, Some miRNAs” to “, some miRNAs”.
•	In Line 120: Change “metastasis status, TNM stage” to “metastasis status, and TNM stage”.
•	In Line 121: Although the authors revealed that they used 84 EAC cases, they mentioned in the discussion section (in line 294) there were 87 EACs. They also used totally 84 patients in Table 1. Please check your results and be consistent in the number of total cases.
•	In Line 126: How the authors randomly divided the data into two groups as train and test sets. Which computer program did they use? Why they preferred to split the data 50% rather than 70%-30% or 60%-40%?
•	In Line 131: Correct “algorism” to “algorithm”.
•	In Line 135-137: Did the authors use statistically significant genes to calculate risk score in the formula?
•	In Line 136: Show the formula with a formula number (1) appropriately.
•	In Line 139-153-180-195: The authors mentioned the same approach four times in different parts. Please summarize what you did only one time in the methods section. In addition, why the authors prefer to use the median value as a cut-off? Why did they not try to find any cut-off value with ROC to divide patients into the high and low risk groups?

In Results,

•	In Table 1: Use tab for categories to make the table more readable. In addition to this, recalculate the percentages of each variable, because total percentage exceeds 100% (height 104.8%, tumor size 100.1%, lymph node status 100.1%, metastases 100.1%, stage 100.1%). Correct “femal” and “metastsis”. Delete “(%)” after the words “metastasis” and “stage”.
•	In Table 2: Is risk score categorical variable? If yes, please give the categories in parentheses (high/low) as in other categorical variables. Plus, please use * for p<0.05 and write the phrase “*p<0.05, statistically significant” in the footnote of the table.
•	In Figure 3-4: Use 3 digit for decimals of the p-value in Fig 3(D) (such as p-value<0.001). Which test results were shown with p-values in these figures? Please give the name of the test method in the materials and methods section.
•	In Line 207: As I understood, the authors did not use correlation analysis, however they mentioned: “there was an independent correlation with OS after adjustment for other clinical pathological factors”. If you use correlation analysis, please add correlation analysis to the materials and methods section, else update the sentences.
•	In Line 208-209: In Figure 4, “race” and “TNM stage” was not available in the table. However, there is “caucasion” in Figure 4G. Please update the sentences in these lines or add tables for race and TNM stage.
•	In Line 213: “Moreover, this signature seemed more applicable to male Caucasian patients over 60.” How the authors get this result, please mention in the manuscript which figure shows this result.

In Discussion,

•	In Line 240: Correct “paly” to “play”.
•	In Line 261: Change “about The” to “about the”.
•	In Line 293: Correct “Second, Due” to “Second, due”.
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: A SIX-MICRORNA SIGNATURE CAN BETTER PREDICT OVERALL SURVIVAL OF PATIENTS WITH ESOPHAGUS ADENOCARCINOMA
Review round: 1
Reviewer: 2

Output:
Basic reporting: The language requires considerable improvement. There are numerous places where tense is used incorrectly and syntax errors exist. 2. Many Hsa-miR names are written as Has-miR. Please correct those.
Experimental design: Please describe more clearly how the 6 miRNAs were selected from the 64 miRNAs that had predictive value.

The primary deficiency of the manuscript is the lack of a validation set. While the training and the test sets are fine, the lack of validation makes the study preliminary. It is suggested that the 6 miRNA signature is validated with an independent total RNA or small RNA/circulating miRNA sequencing dataset with clinical parameters for esophageal cancer.
Validity of the findings: The data needs to be validated with a validation set to be meaningful. Please see comments under experimental design.
Additional comments: No additional comments


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

Input:
Title: A SIX-MICRORNA SIGNATURE CAN BETTER PREDICT OVERALL SURVIVAL OF PATIENTS WITH ESOPHAGUS ADENOCARCINOMA
Review round: 2
Reviewer: 1

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


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

Input:
Title: A SIX-MICRORNA SIGNATURE CAN BETTER PREDICT OVERALL SURVIVAL OF PATIENTS WITH ESOPHAGUS ADENOCARCINOMA
Review round: 2
Reviewer: 2

Output:
Basic reporting: No comment
Experimental design: No comment
Validity of the findings: No comment
Additional comments: The authors have appropriately 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: MONENSIN MAY INHIBIT MELANOMA BY REGULATING THE SELECTION BETWEEN DIFFERENTIATION AND STEMNESS OF MELANOMA STEM CELLS
Review round: 1
Reviewer: 1

Output:
Basic reporting: see the overall comments.
Experimental design: see the overall comments.
Validity of the findings: see the overall comments.
Additional comments: Xin H et al investigated the potential therapeutic effect of antibiotic monensin in human melanoma. The authors used three human melanoma cell lines and two normal human control lines and showed monensin was toxic to the melanoma cells but not normal control cells. Monensin was shown to effectively inhibit cell proliferation, migration, invasion and cell cycle progression, while promote apoptosis and differentiation of human melanoma cells. Using the orthotopic xenograft tumor model, the authors demonstrated that monensin effectively inhibited the growth of xenograft tumors in vivo. Mechanistically, the authors showed that monensin affected multiple cancer-related pathways, including TCF/LEF, Smad and STAT3, and induced the terminal differentiation of melanoma cells. Thus, the authors concluded that monensin may be repurposed as an anti-melanoma agent.

The reported findings are interesting and should have significant translational potential. Experimental design was straightforward and reasonably executed. Data analysis and interpretations were appropriate. Overall, the conclusion is supported by the authors’ experimental findings. However, the manuscript can be significantly improved if the following concerns are fully addressed:

1). Figure 6A revealed that monensin up-regulated several proliferation-related pathways. These results are counterintuitive considering monensin’s strong anti-proliferative activity. The authors should provide explanations of such results. Furthermore, the authors should include a constitutive reporter as a positive control to demonstrate the specificity.

2). The authors mentioned that monensin may inhibit melanoma cell growth by inducing terminal differentiation. However, the authors did not include sufficient data on this conclusion. Did the authors observe more production of melanin or upregulation of terminal differentiation markers upon monensin stimulation.

3). The title is somewhat cryptic or ambiguous, and does not reflect the overall conclusion. Thus, the title should be revised.

4). The cited references should be expanded a bit as currently available melanoma therapies should be discussed.

5). The authors should perform extensive spell checks. The manuscript would be greatly benefited from a professional language editing service. Numerous errors are presented throughout the text. For example, “celllines and two nomal human cell lines” in the Abstract. The statement like “Monensin is non-cytotoxic to common human cells at the same dose” is very confusing. For “Common human cells”, do the authors mean “normal control human cells”?


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

Input:
Title: MONENSIN MAY INHIBIT MELANOMA BY REGULATING THE SELECTION BETWEEN DIFFERENTIATION AND STEMNESS OF MELANOMA STEM CELLS
Review round: 1
Reviewer: 2

Output:
Basic reporting: Language needs editing professionally. Other aspects are sufficient.
Experimental design: Solid and sufficient
Validity of the findings: Some statements need to be rephrased. See comments.
Additional comments: Xin and colleagues have investigated the potential of the antibiotic monensin as a chemotherapeutic agent for melanoma. They have shown that monensin inhibits cell proliferation, migration, invasion, induces apoptosis and markers for melanocytic differentiation,  and suppresses melanoma tumor growth in mice. Using reporter assays, the authors demonstrated that monensin affects multiple cancer-related pathways, and speculated that monensin may exert its anti-melanoma effect through a differentiation like mechanism. The strength is the extensive characterization of the effect of monensin on melanoma cells in vitro in multiple readouts at the cellular levels, as well as melanoma growth in vivo. The weakness is the lack of molecular mechanism for the effect of monensin.

Specific comments:

1.	Line 329-340: The statement “Monensin may target cancer cells through differentiation-related signaling pathways” is not supported by data showed. It needs to be rephrased.
2.	It is unclear how the observations from the reporter assay are associated with monensin’s effect on melanoma cells. Unbiased assay such microarray or RNA-seq followed by validation may reveal the transcriptome-wide gene targets of monensin.
3.	Fig. 6. Pathways identified by the candidate approach can be adaptive response, instead of a causative mechanism. This needs to be further discussed.
4.	Line 317-320: Contamination from meat consumption is different from using it as a therapeutic drug, in terms of doses. Therefore, this needs to be considered in the discussion.
5.	What is the rationale for the in vivo dose selection?
6.	The manuscript needs to be edited for language.


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: MONENSIN MAY INHIBIT MELANOMA BY REGULATING THE SELECTION BETWEEN DIFFERENTIATION AND STEMNESS OF MELANOMA STEM CELLS
Review round: 2
Reviewer: 1

Output:
Basic reporting: see general comments
Experimental design: see general comments.
Validity of the findings: see general comments.
Additional comments: The authors were responsive to the reviewers' comments and addressed mot if not all of the comments. The revised manuscript is significantly improved and thus recommended for consideration for acceptance.


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

Input:
Title: MONENSIN MAY INHIBIT MELANOMA BY REGULATING THE SELECTION BETWEEN DIFFERENTIATION AND STEMNESS OF MELANOMA STEM CELLS
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors worked hard to address the reviewer’s comments by revising statements and adding new data. However, the revision is not satisfactory.

Specific comments:

1.Discussion-Paragraph #1, Line 259: “At an early stage, melanoma can be cured by surgery. The treatment of late-stage melanoma is dependent on chemotherapy, however, the effect of chemotherapy is not satisfied.” The statement is inaccurate. The mainstream therapy for advanced melanoma is immunotherapy. Chemotherapy is not effective. Targeted therapy such as BRAF inhibitor show resistance in majority of patience. The authors need to find a melanoma expert to edit the paper.

2. Discussion-Last paragraph: “…and inhibiting pluripotency of melanoma stem cells”. Pluripotency was not defined in the manuscript. Melanoma stem cell theory was still in controversy. The authors need to be careful using melanoma stem cells and/or pluripotency, unless data are provided to proof them. Tumorsphere assay is not sufficient.

3. Conclusion-“ We found that monensin can significantly inhibit human melanoma at a biologically safe dose”: the authors need to justify what it means a biologically safe dose.
Experimental design: OK
Validity of the findings: OK
Additional comments: See above 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: MONENSIN MAY INHIBIT MELANOMA BY REGULATING THE SELECTION BETWEEN DIFFERENTIATION AND STEMNESS OF MELANOMA STEM CELLS
Review round: 3
Reviewer: 1

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


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: OSTEOKINES AND THE VASCULATURE: A REVIEW OF THE IN VITRO EFFECTS OF OSTEOCALCIN, FIBROBLAST GROWTH FACTOR-23 AND LIPOCALIN-2
Review round: 1
Reviewer: 1

Output:
Basic reporting: -	The tables are a good idea and makes it very easy to interpret each study, however, in general the results and conclusion sections are too long, they should be a summary of what occurs in each study, otherwise it is no different to reading about the study in the main text.
-	In the Tables, please ensure a consistent measure of concentration is chosen (for example: ng/ml), to assist the reader in interpreting the differences between the studies.
Experimental design: -	Too much background information is provided on each osteokine in comparison to the discussion on each osteokine and the vasculature effects. A suggestion would be to remove the subheadings ‘circulating concentrations of…., expression of ….. and endocrine functions of…) and only include background information that is needed to discuss and interpret the vasculature effects.
-	Given that this is not a systematic review why have you included a section on the search strategy? If it was review systematically then that will need to be reflected in the title and follow the appropriate guidelines for systematic reviews.
-	At the end of the introduction the aims of the article include a section on the endocrine functions of each osteokine, however, the title for this review is ‘osteokines and the vasculature’ as you pointed out in the text, recent reviews have been completed on the endocrine functions of OCN and FGF-23. It may be beneficial to rethink how much information should be included on the endocrine functions of each osteokine and what is novel about this review, compared to previous ones.
Validity of the findings: -	Please describe what is novel about the section on OCN and the vasculature. A recent review ‘Tacey, A., Qaradakhi, T., Brennan-Speranza, T., Hayes, A., Zulli, A., & Levinger, I. (2018). Potential Role for Osteocalcin in the Development of Atherosclerosis and Blood Vessel Disease. Nutrients, 10(10), 1426’ described the effect of OCN on atherosclerosis development and included all of the studies that were included in your discussion. As there have not been any new studies published since the previous review, what is this section adding to the body of knowledge that was not discussed in the recent review?
-	In the summary and conclusion section, line 492 – 493 you describe that the evidence points towards direct vasoactive properties of the osteokines in human and animal cells. However, in the FGF-23 section you describe in lines 376 - 379 ‘The results presented encourages the hypothesis that the associations and correlations between FGF23 and CVD are most likely due to deleterious effects of altered phosphate and mineral metabolism and indeed that FGF23 levels likely follow, as oppose to direct, cardiovascular disturbances.’
-	Several of the studies that are referred to, especially in the FGF-23 and LCN-2 sections involve microvascular vessels (some examples on lines – 352, 360, 467), yet the focus throughout the text is on atherosclerosis and calcification, which are macrovascular diseases. You may need to clarify whether you are looking at one/both micro- and macro-vascular diseases and adjust the included articles accordingly.
Additional comments: - in the introduction there is too much background on the skeleton and blood vessels as a whole and not enough specificity on what you are discussing. The 3 osteokines you are discussing are only mentioned in ~ 2 sentences of the whole introduction. Further, things that you are not discussing in the main text (osteopontin, osteoprotegerin, sclerostin and DKK1) do not need to be discussed in the introduction. The introduction needs to be shortened and more focused, describing more background and rationale for the review.
-       lines 125 – 128 – There is several mistakes in the reporting of the different forms of OCN, please refer to ‘Li, J.; Zhang, H.; Yang, C.; Li, Y.; Dai, Z. An overview of osteocalcin progress. J. Bone Miner. Metab. 2016, 34,367–379’.


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: OSTEOKINES AND THE VASCULATURE: A REVIEW OF THE IN VITRO EFFECTS OF OSTEOCALCIN, FIBROBLAST GROWTH FACTOR-23 AND LIPOCALIN-2
Review round: 1
Reviewer: 2

Output:
Basic reporting: The review article by Millar et al. summarizes the endocrine functions and in vitro effects of osteokines on vascular cells. This review article is clearly written and well organized with relevant subheadings. Tables are comprehensive and helpful. The review is cross-disciplinary and will be of interest to a wide audience including life science and medical researchers as well as clinicians. Some minor comments are stated below in the “Comments for the author” section.
Experimental design: The search strategy used to retrieve articles related to this literature review is excellent with search encompassing multiple databases. The review article is logically organized into relevant subsections for all the three osteokines described in the text.
Validity of the findings: The conclusions are well supported by the background and existing literature on osteokines. Furthermore, some knowledge gap existing in this field has also been highlighted well towards the end of conclusions.
Additional comments: Some minor comments and suggestions are as follows:
1. Lines 62, 93 & 96: Osteoprotegerin is misspelled (it should be ‘e’ instead of ‘o’ after ‘t’)
2. Line 63:  RANKL should not have a hyphen between K & L.
3. Lines 69 & 95- use a semicolon to separate multiple references and order them chronologically as stated in the “Instructions for authors” submission guidelines on PeerJ website. This needs to be checked throughout the article.
4. Line 76: Abbreviate cardiovascular disease as CVD in addition to writing the full-form (as CVD has been used later in the text in line 377).
5. Line 122: The full-length osteocalcin (OCN) is 95 and 100 amino acid protein in mice and humans respectively. There is a signal peptide of 22 amino acids and a propeptide of 28 amino acids in humans. It’s the mature protein that has 49 amino acids in humans (see Chapter 2- Bone, matrix and mineralization-Pediatric bone-2nd edition-Marc D. McKee, William G. Cole 2012 OR search protein database in NCBI for full length protein sequence). So to say “OCN is 46 and 49 amino acid protein in mice and humans” as stated in this review is not fully correct. Either say “the mature OCN is 46 and 49 ….” OR state “the full-length OCN is 95 and 100… ”
6. Line 145:  “fragment from proteolytic enzymes” sentence needs to be corrected as “fragments released by proteolytic cleavage” (the fragments are not from proteolytic enzymes but are from osteocalcin itself.)
7. Line 151: Hannemann is misspelled (it should be ‘nn’ after ‘Ha’ instead of ‘mm’).
8. Line 163: The suitable word is “identified” instead of “expressed”.
9. Line 241: It should be “suppressed these effects” instead of “suppressed these results”.
10. Lines 260-261: “deserve” instead of “deserves”.
11. Line 266: Change “251 amino acid peptide” to “251 amino acid protein” (its big enough to be called as a protein, in general less than 50 amino acids is designated as a peptide).
12. Line 268: “N-acetylgalactosaminyltransferase” (delete the space between galactosa and minyl)
13. Line 284: It should be “measure” instead of “measures” (as the preceding words say C-terminus FGF23 assays, correct one or the other).
14. Line 335: Write also the full form of ERK as extracellular signal-regulated kinase (as ERK has been used later at multiple places, so would be useful to write its full form here)
15. Lines 338-339: Change “when soluble klotho and phosphate was” to “….were”.
16. Lines 397-398: It should read as “monomer, homodimer, or heterodimer by forming a complex with matrix metalloproteinase-9 (MMP-9)”. Also, LCN-2 stabilizes MMP-9 by preventing MMP-9 from autodegradation rather than increasing its activity. (See Chakraborty et al., Biochim Biophys Acta., 2012.) So to say LCN-2 increases its activity as in line 398 is rather conflicting.
17. Line 424: Change “though” to “through”.
18. Line 430: The full form of MC4R should be written (melanocortin 4 receptor).
19. Line 433: “present” instead of “presents”
20. Lines 455 & 460: H2O2 – It appears there is a 0 (zero) mistakenly typed there instead of O (capital letter O).
21. Line 467: CXCL10 should also be stated in its full form as C-X-C motif chemokine 10.
22. Line 501 & 32: It should read as “have” instead of “having”.
23. Table 2: Legend has “FGF-23”.It should be written as FGF23 just to be consistent with the rest of the text in the review. Another minor correction- enter the units of concentration in the last entry of table 2 - “Richter et al., 2016” which is “10 ng/ml” in the concentration column.


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: OSTEOKINES AND THE VASCULATURE: A REVIEW OF THE IN VITRO EFFECTS OF OSTEOCALCIN, FIBROBLAST GROWTH FACTOR-23 AND LIPOCALIN-2
Review round: 1
Reviewer: 3

Output:
Basic reporting: In this review, the authors introduced and discussed the in vitro effects of OCN, FGF23 and LCN2. They focused on the function of these genes in vasculature including the effects on vascular-related cells. In general, this review was well written with sufficient information and discussion. I have only some suggestions:

1. LCN2 plays an important role in neuroinflammation as well as blood brain barrier. Currently the authors only mentioned these points in a pretty simple way. Could the authors talk more about this since blood brain barrier is related to the topic of vasculature? It should attract more researchers working in these fields.

2. Could the authors make a table and put OCN, FGF23 and LCN2 side by side to summarize the expression pattern of these three genes?
Experimental design: no comments
Validity of the findings: no comments
Additional comments: no comments


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

Input:
Title: OSTEOKINES AND THE VASCULATURE: A REVIEW OF THE IN VITRO EFFECTS OF OSTEOCALCIN, FIBROBLAST GROWTH FACTOR-23 AND LIPOCALIN-2
Review round: 2
Reviewer: 1

Output:
Basic reporting: -	You describe that there is conflicting observational data on these osteokines and vasculature interaction in Lines 74-75. It may be worthwhile including some references here to support this statement and identify the rationale for investigating the osteokine and vasculature interaction.
-	The professionalism of the writing needs to be improved throughout to make it acceptable for publication in this journal, some suggested changes are listed below.
o	Line 40 – ‘our bones’ should be changed to something like bone or the skeleton
o	Line 43 – remove ‘the’
o	Several sentences are too long and confusing, some examples are; lines 100 – 103, lines 109 – 112 and lines 200 – 204. They should be split into several sentences or shortened.
o	Line 109 – what is meant by ‘its abundance’? are you referring to OCN or ucOC?
o	Line 251 – 252 – did not find repeated twice
o	line 323 – 325 – the sentence needs to be made clearer
-	The use of abbreviations is not consistent throughout document, for example osteocalcin is written in full on lines 105 + 109, after the acronym has been used.
-	The abbreviation for undercarboxylated osteocalcin is different in the text (line 102) compared to in Table 1 – this will need to be fixed
Experimental design: - The review is nicely separated into coherent subsections and has a logical flow.
Validity of the findings: no comment
Additional comments: -	In the reporting of uncarboxylated and undercarboxylated osteocalcin the authors should be aware that the form found in circulation is likely undercarboxylated osteocalcin. Whereas fully uncarboxylated osteocalcin likely does not occur endogenously and is only a synthetic compound. You have reported throughout the text that uncarboxylated osteocalcin is the form found in circulation.


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: OSTEOKINES AND THE VASCULATURE: A REVIEW OF THE IN VITRO EFFECTS OF OSTEOCALCIN, FIBROBLAST GROWTH FACTOR-23 AND LIPOCALIN-2
Review round: 2
Reviewer: 2

Output:
Basic reporting: The authors have addressed the concerns highlighted in the previous review. The review reads clear now and is within the scope of the journal.
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: OSTEOKINES AND THE VASCULATURE: A REVIEW OF THE IN VITRO EFFECTS OF OSTEOCALCIN, FIBROBLAST GROWTH FACTOR-23 AND LIPOCALIN-2
Review round: 2
Reviewer: 3

Output:
Basic reporting: I thank the authors for their efforts to make the manuscript look better. I have no more questions.
Experimental design: No comments
Validity of the findings: No comments
Additional comments: No comments


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

Input:
Title: SPAWNING STOCK RECRUITMENT CREATES MISLEADING DYNAMICS UNDER PREDATION RELEASE IN ECOSYSTEM AND MULTI-SPECIES MODELS
Review round: 1
Reviewer: 1

Output:
Basic reporting: The problem is introduced and then a potential solution is assumed in the final paragraph describing the study design. More exploration of the solution (the recruitment cap) prior to that final paragraph in the introduction would help guide the reader, perhaps discussing why they thought this was a good solution and possible pitfalls it may have. The authors make it clear in the discussion that this is only one possible solution, but more discussion of alternatives (a Ricker model?) or possible downsides (this isn’t very mechanistic?), without formally testing anything, would make the paper more complete.

The equations should be presented within the flow of the paper. “For example, Base instantaneous natural mortality (M) was calculated as: [insert equation here].”

Equation 3: While I understand S and R maybe be standard notation for the species diversity index, it is confusing in the context of this paper because a reader might think S and R are spawning biomass and recruitment.

In general, the manuscript needed copy editing, particularly with respect to use of possessive apostrophes. Could copy and paste into a word processor to check for errors? I also found the writing to be unclear at times. For example, the sentences beginning on lines 64, 73, 177, and 244.

Fig. 1: Use consistent y-axis across the 2 panels

Fig. 9: I was rather alarmed by the sharp uptick in the half catch scenario. Of course, this makes sense once I think about it, but it would be good to describe such a stark result in the text, even if it is expected.

Appendix plots: All references to the appendix plots are listed as appendix A rather than the correct appendix plot. These references should be fixed. It would also improve readability if there were a cap/no cap column in the appendix plots (I.e., fill the matrix of panels column-wise instead of row-wise).

All ecosystem indicator plots: The red line and green fill will be difficult for readers with colorblindness. I would recommend a gray fill instead.
Experimental design: The authors equate steepness with resilience. Steepness describes the density-dependence of the stock-recruit relationship. While this is related to resilience, particularly at low spawning biomasses, it is not correct to describe steepness as the resilience of the population across all biomasses. (I would also argue the term “resilience” really only applies at low biomasses anyway, but that is more debatable.) Other parameterizations for the Beverton-Holt model exist that could make more sense in this case—for example the asymptotic recruitment and slope at the origin. So while I agree that some of the dynamics of the uncapped recruitment model are odd, those that rely on the interpretation of steepness as resilience should be examined more closely. As the authors say, if the relationship must go through two fixed points (one being the origin) and has a low initial slope, it must by definition have a high slope later on.

Equation 2: Some rationale for this should be provided.

In order for a reader to replicate the results, the Atlantis model in McGregor et al. 2018 must be publicly available somewhere. Readers should be directed to a github repository or similar for the model.
Validity of the findings: The authors make a several a couple of poignant points in the discussion. First, that their different results for capped and uncapped recruitment do not necessarily imply which is correct (line 304, also paragraph on line 323). Second (and more importantly, I think), that how we parameterize multispecies models has a huge impact on what we infer the effects of predation release to be (line 319). This could even be emphasized!

Paragraph starting on line 248: It looks to me like the ratio exceeds the previously observed values in all recruitment scenarios, which is not how I interpreted what the authors wrote. Also, how do they know this behavior is “falsely” suggesting a change in ecosystem structure? Couldn’t it be correctly suggesting the change?

Fig. 3 and 4: I was curious how the population trajectories appear so smooth when the M time series is not smooth.
Additional comments: In this paper the authors describe a problem that results from ecosystem models borrowing parameterizations for population dynamics from single species models that are generally used on stochastic depleted populations. When these same population models are used in deterministic models on populations near their unfished biomasses, unusual dynamics where populations increase rapidly following predator release (or other declines in mortality) occur. The authors propose to cap recruitment at its unfished level rather than allowing it to increase towards an asymptote, and proceed to explore the impact of doing so on a variety of common indicators used in the analysis of ecosystem models.

Line edits:

44: While size-based models may be simpler, I think they are still aimed for more strategic uses, unlike MICE.

51: Beverton and Holt is not a 2012 paper.

314: Would be good to cite a paper that doesn’t critique balanced harvesting, too


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: SPAWNING STOCK RECRUITMENT CREATES MISLEADING DYNAMICS UNDER PREDATION RELEASE IN ECOSYSTEM AND MULTI-SPECIES MODELS
Review round: 1
Reviewer: 2

Output:
Basic reporting: The manuscript is understandably written and contains sufficient references. It does however contain minor grammatical errors, see for example line 132 and line 161-166.
Also, the reference McGregor et al (2019) should be updated.

Some figures would benefit from more detail. For example in Figure 4, an explanation regarding the relevance of the dashed line would be helpful.

The manuscript would improve by having terms like 'capped recruitment' (line 122) be explained, especially since it will determine model simulations (see line 170).
Experimental design: Overall, the method and data selection should include more details. To be more specific:

Section 2 would benefit from additional information:
The functional form of the Beverton Holt equation should be provided as it determines the value R. Further, more details should be added regarding the functional form for the time-dependent natural mortality, especially because it was mentioned in the section header. The expected value of M was provided but I suggest to add the underlying distribution as well as the choice of Variance etc. This will help the reader to follow the  interpretations of Figure 2 and its implications.

Section 3:
Some data, that is being used in this paper, is not sufficiently introduced. For example, Figure 5 refers to catch data by McGregor et al (2019) but even in that publication the origin of the data is not revealed. This will however have implications. Often data is only available after data documentation commences. That does however not imply that there has not been predation earlier. This possibility should be addressed by the authors as well as the reliability of McGregor's data.
The overall model including fishing of predators should be presented as well as the choice of natural mortality to obtain the results illustrated in Figure 6. Although data from Atlantis was mentioned, it should be pointed out where and how it was incorporated in obtaining the results in Figure 6.

Section 4:
As the diversity measures require data from other species, it should be pointed out which data was used to obtain these values.
Although a simple model was introduced, line 225 mentions an age-structured model that seems to be explained in caption of Figure 8 but should be introduced whenever first needed.
Validity of the findings: The results indicate an interesting behaviour and build the base for further investigations.

Since simulations with 'capping' and 'non-capping' of recruitment seem to yield different results, it would be worth adding a paragraph in the Discussion regarding which choice of more realistic or how to determine which one would be.
Additional comments: No additional comments


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

Input:
Title: DEVELOPMENT OF A SHORT QUESTIONNAIRE BASED ON THE PRACTICE ENVIRONMENT SCALE-NURSING WORK INDEX IN PRIMARY HEALTH CARE
Review round: 1
Reviewer: 1

Output:
Basic reporting: Basic Reporting

The article was written in clear, unambiguous, technically correct British English. There were a few inconsistencies and errors, however.   For example, the use of (,) in decimals rather than (.) and not using z in such words as organisation.  There were a few words misspelled in British English, these can be corrected using search and replace features, notably psichology (psychology), analitical (analytical), dimentsions (dimensions).  See the word docx version for more specific review comments and corrections.

The article included introduction and background demonstrating how the work fits with the field of nursing work environments.  The author(s) especially noted previous work carried out in Spain.  However, the references were somewhat dated (often 10 years old). This paper (DOI: 10.1016/j.ijnurstu.2017.06.003)
would have provided more current work in the field and supplied further support for the work.

The manuscript was organized as suggested in the Instructions for Authors.

Figures were included but in some cases they were not clearly described in the title and legends.  For example, Figure 1. The title states “Selection (%) of each element in the PES-NWI questionnaire (numbers correspond to the item number in the original scale).  There are many numbers in the Figure 1.  The authors were likely referring to the numbering on the Y axis already labeled “ITEM”.  I suggest removing the parenthetical phrase (numbers correspond to the item number in the original scale) and simply label the Y axis “Item Number on Original Scale”.   Also in Figure 1, the column labeled DIFFERENCE 7.3% was confusing.  I believe the difference to which this refers represents the fact that at least 7.3% of participants chose an item to be in the Top Ten over those items remaining.  But in many cases the difference exceeded 7.3%.  Take, for example Item 1.  The difference between Items 1 and 25 (3.42% and 41.1%, respectively) is 37.68%. I suggest removing the column labeled DIFFERENCE from Figure 1.

In Tables 1 the author(s) switch from original numbering (1-31) to new numbering 1-10. Then, in Table 2 they number based on the scheme in Table 1.  I found this confusing.  I feel the better approach would have been to stay with the original number of items so that the reader could compare across Figure and Tables 1 and 2.

Table 3 asks a great deal of the reader who must discern which items from the original subscales are being included in the TOP TEN scale under a new latent variable structure.  Perhaps a good approach, in addition to retaining the original item numbering is to include a column in Figure 1 or Table 1 showing the item’s original number and its original subscale designation. Tables are essential in making the results of a study easily discernable and authors should strive to create tables which can stand alone without requiring readers to peruse the entire text of the article in order to interpret them.

Table 4 needs some attention to detail.  There is a mixture of commas and periods in decimals. Also, it would help the reader to see item number that correspond to the original 31 items.  In this way figures and table can be more easily compared.

I found no reason to conclude the manuscript under review here was published elsewhere or has been subdivided inappropriately.  I did find the 2015 thesis work by the primary author upon which this report was based.

See docx version for further editing comments.
Experimental design: Experimental Design  (Line numbers refer to the pdf version)

The study appears to have followed prevailing ethical standards in the field and country in which the study was conducted.

The manuscript under review describes original primary research apparently drawn from an academic thesis.
It clearly defines the research question which is relevant and meaningful.  The author(s) clearly show how the study builds on past work in the field and fills a gap in the need for a short survey of nurses’ work environments in primary care.  The study has previously been reviewed and found rigorous by the first author’s academic review committee and having read this manuscript, I concur with limitations based on questions regarding the exact methods used.

Before reproducibility can occur the author(s) will need to provide more detailed information on methods used.  Here are two examples (see the docx version for further comments):

Line 94  “…the database was refined on 2 occasions by 2 researchers to minimize error .”   This statement needs further explanation.   Were cases removed due to excessive missing responses or for other reasons?  The author(s) reported a sample size of 268, however, when I opened the data set provided I found 269 cases.  When I conducted factor analysis and chose “Listwise deletion” I had an N of 263.

Lines 154-155   I could not obtain the same alpha on the TOP TEN items as those in the manuscript.  Was this due to the sample chosen and mentioned above? The number of cases I analyzed was 269

I was uncertain of the meaning of lines 168-169  What is meant by “…but lost data for dimensions 3 and 5” ?

Validity of the Findings

I had no trouble downloading and analyzing the data provided.  However, until certain methods are more fully described I cannot comment on the robustness and statistical soundness of the data analyzed or any controls employed in selecting cases to analyze.

Nevertheless, taken at face value, the study appears to have followed acceptable methods of exploratory analysis and survey refinement.
Validity of the findings: Conclusions drawn (line numbers refer to the pdf version)

Lines 184-185   The author(s) state based on their results the shortened TOP TEN version of the NWI survey is “…valid, flexible, rapid and brief…”  They would do well to temper their conclusions a bit more by acknowledging marginal performance of the TOP TEN version in some areas.   For example:

Line  182  “…we obtained stress values < .2 (.184)….”
This reported value (.184) is considered to be fair to poor.  See, for example, the generally accepted scale for Stress Values [Stress Goodness-of-fit 0.200=poor, 0.100=fair, 0.050=good, .025= excellent, 0.000=perfect] found at https://ncss-wpengine.netdna-ssl.com/wp-content/themes/ncss/pdf/Procedures/NCSS/Multidimensional_Scaling.pdf

The test for sampling adequacy (Kaiser-Meyer-Olkin) was reported to be 0.77.  As in the situation mentioned above when attempting to reproduce factor results I could not reproduce the reported KMO value.  Instead, I obtained 0.683 for KMO with a sample of 263.  While the author(s) used a different sample size, their  0.77 is considered marginal for concluding sampling adequacy (0.8 being the usual cutoff).

Certainly, both the “marginal” results for KMO and Stress Values are quite promising.  Still, I suggest that the conclusions drawn from them need a bit of tempering or qualifying.

The author points to 90% predictive power when using the TOP TEN survey to obtain the original values of NWI.  This is not the most robust way to demonstrate the comparability of the two surveys. I suggest that the author(s) explore the strategy suggested by Bland and Altman Plot analysis  ( https://ncss-wpengine.netdna-ssl.com/wp-content/themes/ncss/pdf/Procedures/NCSS/Bland-Altman_Plot_and_Analysis.pdf )
Bland and Altman make the point that a high correlation (or a regression) does not necessarily imply that there is good agreement between the two methods.

Even stronger would be the comparison of both versions’ sensitivity and specificiy for predicting a specified outcome. This is not necessary for this paper but should be considered as a recommendation for further study.
Additional comments: Thank you for the opportunity to review your work.  I found this manuscript interesting, clear (with a few exceptions), and useful for filling gaps in the study of nursing work environments.

Your research approach was straight forward but would have been stronger if you had compared the sensitivity and specificity of the two versions of the PES-NWI (31- and 10-items) for predicting an outcome variable of interest or if you had employed the Bland Altman plot method. That is not to say that you must carry out these additional analyses for acceptance by Peer J.  However, I recommend you consider these more advanced methods of evaluation in your discussion of  limitations and recommendations for future research.
Of greater importance is the need for you to clarify and more fully explain the steps of your research (which I have noted in the review comments above).


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

Input:
Title: DEVELOPMENT OF A SHORT QUESTIONNAIRE BASED ON THE PRACTICE ENVIRONMENT SCALE-NURSING WORK INDEX IN PRIMARY HEALTH CARE
Review round: 1
Reviewer: 2

Output:
Basic reporting: 1.1 Clear and unambiguous, professional English used throughout.
- Weaknesses in English language and writing skills are quite obvious. To improve readability, formulate full sentences (for example methods part of abstract and main manuscript) and rewrite the sentences to make it more understandable and be more precise (e.g. line 78 “Through random sampling we estimated sample size to achieve representatively was 198 participants” or “Statistical analysis (alpha=.05) with SPSS v21” line 102.) Some important statements remain vague: e.g. line 47 “influencing care excellence and clinical outcomes for patients” -> what outcomes, be more specific; line 53 “various elements may be more essential than others to improve care” -> which elements? Moreover, some information seems to fit better in other sections (e.g. line 125 ”Participants were asked to select the 10 items they considered most important to help improve the care provided by nurses in primary health care.” move to method section; Discussion section should be used to discuss the results, not for repeating numbers from the results section (line 177, 179, 182). However, the main unclear aspect refers to the “elements” (what are the elements? Are they the items? Not clear how and why just 10 elements/items are selected for the short version) and the PES-NWI dimensions: instead of reducing the dimensions from 5 to 3, the authors combine two dimensions twice (Participation in management and leadership [original dimensions PES-NWI “Nurse Participation in Hospital Affairs” and “Nurse Manager Ability, Leadership, and Support of Nurses”]; Focus on nursing care and Interdisciplinary relationships [original dimensions PES-NWI “Nursing Foundations for Quality of Care” and “Collegial Nurse–Physician Relations”]. Because of this arbitrary reorganization of the original structure of the PES-NWI, the manuscript and finding remain ambiguous and rather unclear. This needs theoretical support and explanation.
- The reference style is not used consistently (e.g. line 29, 130), references are missing (e.g. line 20), for direct quotes (e.g. p. 1, line 5, 52) page numbers are missing
1.2 Abstract
The abstract is very short lacking information and not providing an adequate overview of the submitted manuscript. Use the word limit and expand the abstract with full sentences and link the parts within the text (especially method part). Moreover, including further essential information such as: Why the assessment of the nurse work environment is important? Why a short version is needed? Study sample contains what/whom? How you define an “element” (result part)?
1.3 Literature references, sufficient field background/context provided
- The first three sentences are not clear how they are related to the topic and they do not introduce very well the topic “nursing work environment”. How “organizational climate” is related to the topic and why it is in questions marks (seems it is an ambiguous concept and needs more explanation).
- Suggestion: start directly with the concept of the work environment; What is it? Why it is important? How the nurses work environment influence outcomes (Why it is important to assess the work environment)? Why PES-NWI is the “best” choice (elaborate and explain “greater methodological strength than the other tools available” (line 30). give examples and evidence underpin you statement).
- Add more latest reference for “greater staff loyalty to the organization and greater professional satisfaction” (line 21; instead of/in combination with McClure et al., 1983).
- Give information to PES-NWI (items, dimension, psychometric evaluation)
- Line 37-39: is the number of items and dimension just for the Spanish version or also for the original version from Lake? Not clear.
- What were the results from content validity analyses (line 39/40).
- “Elements” is defined with a definition (line 50.52) but what is the conclusion of this? What is an “element” in your study? Work environment dimensions? Questionnaire items? Aspects of the work environment?
- Not convincing, why exactly 10 elements are crucial and important? Why not 8 or 15?
- Line 61: Why is it needed to have a short version: “has identified the need for a short version of the PES-NWI” is also not convincing, elaborate the importance of it.
- PHC: would spell it in full because it is not common used and easily to confuse with other terms.
1.4 Professional article structure, figs, tables. Raw data shared
- Structure of the article followed is reasonable. Raw data were shared
1.5. Figures
- Descriptive results of study population would be better structured in a table to improve readability.
- Table 2: nor clear which items matched to the original scale. It seems that the wording changed. This makes it hard to compare with the original PES-NWI scale.
- Figure 1 needs further information because it is not self-explaining (how did you arrive at three groups).
Experimental design: 2.1 Original primary research within Aims and Scope of the journal.
- The article is primary research and fits well in journal scope.
2.2 Research question well defined, relevant & meaningful. It is stated how research fills an identified knowledge gap.
- Research aims and study questions are not clearly formulated. Although the topic is very interesting and important for practice, the rational is not developed very well lacking to explain how the study fills this gap.
2.3 Rigorous investigation performed to a high technical & ethical standard.
- Ethical approval was given. Add a reference indicating which “Spanish and European legislation” you refer (Line 112).
- The funding statement belongs not in the method section but in a separate section at the end of the manuscript.
 2.4 Methods described with sufficient detail & information to replicate.
In this section the following information is missing:
- Line 86: Is there a difference, except of the language between the original PES-NWI version from Lake and the version you used: “We used the 31-item version of the PES-NWI questionnaire (A.p.1) 87 validated and adapted to PHC in Spain”
- Line 88/89: Did the nurses have a choice whether they could complete the survey online or “in person (self administered)”
- Collect and summarize all important information of the scale in one paragraph. At the moment information are spread through the introduction and method section (within the method section in different paragraphs).
- Add information about PES-NWI: how many items in each dimension.
- Add answer options for sociodemographic variables.
- Data analyses is explained but it is not fully clear which data was included. Again, why just 10 elements/items? What if the participants would have reviewed more than ten items as “Yes, it is essential”. Seems they are lead to ten. Arguments line 127-131 are not convincing.
- Although exclusion criteria are stated, they are just formulated as inverse inclusion criteria. An exclusion criteria is an additional characteristic from the sample, that needs to be met.
- The data collection statement (line 82-84) seems to fit better in a separate paragraph “data collection”.
Validity of the findings: 3.1 Data is robust, statistically sound, & controlled.
- Because the study aims and outcomes are not clear, the statistical analyses, results and conclusion seem of limited validity. Information (why a short version would make sense and which items (line 107 “essential elements “top ten”) are chosen) is not sufficiently and convincingly provided.
- Based on the combination of the two dimensions (Participation in management and leadership [original dimensions PES-NWI “Nurse Participation in Hospital Affairs” and “Nurse Manager Ability, Leadership, and Support of Nurses”]; Focus on nursing care and Interdisciplinary relationships [original dimensions PES-NWI “Nursing Foundations for Quality of Care” and “Collegial Nurse–Physician Relations”] the statement line 168/169 is rather unclear.
- Moreover, the allocation of the several items to the dimensions seems not trustworthy, e.g. item “Nurses are offered continuing education programmes” (table 2) is allocated to dimension “Participation in management and leadership” but belongs to the original PES-NWI dimensions “Nursing Foundations for Quality of Care”.
3.2 Conclusion are well stated, linked to original research question & limited to supporting results.
- Because of weaknesses in previous sections—especially introduction, method and analyses section—the discussion and conclusions are in doubt and undermines trust in the results and the connection between research and practice.
Additional comments: Thanks for submitting your manuscript ”Development of a short questionnaire based on the Practice Environment Scale-Nursing Work Index in primary health care”. It seems a very important and needed topic. However, because of several weaknesses, to my mind it does not meet expectations for publication. Please find my comments and suggestions for improvement for each section.


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

Input:
Title: DEVELOPMENT OF A SHORT QUESTIONNAIRE BASED ON THE PRACTICE ENVIRONMENT SCALE-NURSING WORK INDEX IN PRIMARY HEALTH CARE
Review round: 2
Reviewer: 1

Output:
Basic reporting: The author(s) attended to suggestions on reporting and addressed issues pointed out by my original review.  Good job!
Experimental design: Author(s) added analysis as suggested and reported that their results strengthened their conclusions.
Validity of the findings: Author(s) moderated their conclusions in light of further consideration of suggestions.
Additional comments: Your response to reviewers' comments improved your manuscript and enhances its contribution to the field of study.  When you disagreed with a comment you clearly explained your rationale.  Your response was clear, thoughtful, and appropriate.


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

Input:
Title: DEVELOPMENT OF A SHORT QUESTIONNAIRE BASED ON THE PRACTICE ENVIRONMENT SCALE-NURSING WORK INDEX IN PRIMARY HEALTH CARE
Review round: 2
Reviewer: 2

Output:
Basic reporting: Thank you very much for re-submitting your manuscript, for incorporating much of the feedback as well as for providing justification for not making a recommended change.

The manuscript is much improved with the added information (process of establishing the TOP Ten) and the supporting analyses (Bland-Altman statistics).

Upon addressing the few remaining issues listed below, I believe that the manuscript should be considered for publication.
- Consistent use of TOP 10 or TOP Ten
- Typo in Keyword: Design
- Need to add a reference for the statement on lines 103/104 “The five subscales have been shown to have an acceptable internal consistency and reliability (Cronbach Alfa min 0.807, and max 0.916)”
- Lines 151, 158: use the abbreviation PHC
- Line 184 for variable age: add (in years)
- Line 365 D5: add in brackets the name of the subscale, as you did for D3
- Add table titles
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: PEPTIDE-BASED NTA(NI)-NANODISCS FOR STUDYING MEMBRANE ENHANCED FGFR1 KINASE ACTIVITIES
Review round: 1
Reviewer: 1

Output:
Basic reporting: No comment.
Experimental design: No comment.
Validity of the findings: No comment.
Additional comments: The authors have sufficiently responded to my questions.