PONE-D-22-22264Changes in cortisol awakening responses (CAR) in menopausal women through short-term marine healing retreat program with specific factors affecting each CAR parameterPLOS ONE

Dear Dr. Seoeun Lee,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

It is undoubtedly potentially a good work and one that addresses a multifactorial and therefore difficult topic. However, there are a number of considerations that need to be addressed in depth. Among these, in addition to what has been stated by the reviewers, I would like to highlight: (1) The wording as well as the level of English should be thoroughly revised (2) Clarifying the research objective (and hypothesis) in terms of the research question (3) The section on instruments, which should be briefly described and which involve their scores, should be deepened (4) The presentation of the results should be improved. (3) The presentation of results should be ordered, prioritised and logically summarised, as should the tables, which contain too much information and are therefore difficult to understand (and there are too many of them). (4) The discussion should be rephrased according to the objective and research question, as well as according to the description of the results.

Please submit your revised manuscript by Jan 18 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Juan-Luis Castillo-Navarrete, Ph.D.

Academic Editor

PLOS ONE

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4. Thank you for stating the following in the Acknowledgments Section of your manuscript:

“This work was supported by the Wando Marine Healing Blue Zone Creation Project funded by the Presidential Committee for Balanced National Development in South Korea.

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

“This work was supported by the Wando Marine Healing Blue Zone Creation Project funded by the Presidential Committee for Balanced National Development in South Korea.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: With all due respect for the work of the authors, it is however my opinion that the MS, who deals with an important topic in the field of improving the quality of life, needs a profound reorganization. The introduction is unnecessarily verbose. It does not stimulate or justify interest in the topic right from the first sentences. The purpose of the research is not clear, nor the choice of the population is justified (the experimental group is not at all described in its clinical characteristics in the relative missing paragraph "study population", for example for the possible intake of drugs that could modify HPA axis activities; spontaneous/surgical menopause?)

The results paragraph should be rewritten by providing the reader with a clear and detailed explanation of what has resulted, and taking away the feeling of simply being sent back to reading what is reported in the table!

Discussion may be improved including possible mechanisms and including a comment/comparison with similar studies in the area.

Reviewer #2: Congratulations to the authors for make a detailed analysis of multiple variables that may affect changes in cortisol awakening responses (CAR) in menopausal women through short-term marine healing retreat program.

Statistical analysis is adequate for the study of the data available. It is necessary to review the paragraph that describes Table 3 in the results. The multivariate analysis of WHR on AUCi parameter is not found in supplementary table S9.

In the same paragraph, the description of table S2 that indicates the existence of significant differences between BMI values for the high, middle, and low AUCi groups is confusing, because the values 25±2.6; 24±2.5 and 25±2.7 for high, middle and low AUCi respectively, are very similar.

The authors present a comprehensive discussion of their results associated with the main findings of the study. Based on the changes in AVE and AUCg evidenced according to the BMI, it would be interesting for subsequent studies with larger populations to include the analysis of changes in oxidative stress markers.

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Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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PONE-D-22-22264R1Changes in cortisol awakening responses (CAR) in menopausal women through short-term marine healing retreat program with specific factors affecting each CAR parameterPLOS ONE

Dear Dr. Seoeun Lee,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

ACADEMIC EDITOR: Thanking you for the effort involved in revising your paper which deals with a very interesting subject. The new version of your paper has improved substantially, however there are certain aspects that need to be improved and/or clarified. In addition to what has been expressed by the reviewers, I would like to point out some key aspects.

In the paragraph starting on line 249, TG and BDNF are addressed, in this regard:

(1) No mention is made in the methodology about the measurement of TG and BDNF, even more so considering the difficulties involved in measuring the latter, therefore:

(1.1) How was peripheral BDNF measured? Serum? Plasma? Platelets?

(1.2) What were the conditions of peripheral blood sampling (a simple forced aspiration at the time of peripheral blood sampling is sufficient to degranulate platelets and thus increase "plasma" BDNF levels) (https://doi.org/10.1016/j.neurobiolaging.2004.03.002).

(1.3) Was anticoagulant used to receive the peripheral blood sample? Which one?

(1.4) How long were the collection tubes left for before centrifugation, how long were they centrifuged, at what speed?

(1.5) What technique was used to measure BDNF? ELISA? If so, does it adequately discriminate mature BDNF from proBDNF (http://dx.doi.org/10.1038/srep17989)?

(1.6) How were TGs determined? methodology? sampling conditions?

(2) It is hypothesised that the exercise programme would reduce BDNF levels, how is this explained? Even more so, when there is ample literature reporting increased BDNF levels as a result of physical exercise and cognitive training (https://doi.org/10.1038/s41380-019-0639-2 ; https://doi.org/10.3390/ijms22168814).

(3) In the supplementary tables the units of TG and BDNF are not indicated.

The above points are relevant to clarify, even more so when peripheral BDNF levels have been proposed as a way to assess the integrity of the HPA axis, given its inverse relationship with cortisol levels (http://dx.doi.org/10.1038/s41386-019-0391-y ; https://doi.org/10.3109/07853890.2015.1131327). Please ensure that your decision is justified on PLOS ONE’s publication criteria and not, for example, on novelty or perceived impact.

For Lab, Study and Registered Report Protocols: These article types are not expected to include results but may include pilot data. 

==============================

Please submit your revised manuscript by Mar 25 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Juan-Luis Castillo-Navarrete, Ph.D.

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I got to read the first version of the MS. I must admit that this second version of the manuscript has been greatly improved.

However, it still needs more care in the introduction/discussion/as well as in the abstract

There are many inaccuracies, with sentences left there in inappropriate places: results are still presented in the introduction or extensions of the research on absolutely different topics are hypothesized. I am referring to the possible involvement of the mechanisms underlying oxidative stress in the effects induced by marine living on CAR. Why not bring up the stimulating effect of the marine environment on the thyroid?

I want to clarify that, in my opinion, you have not studied three different types of CAR but rather have used different ways of mathematically expressing the physiological increase in cortisol, which is evident in the first hour after waking up. It is up to the authors to decide which method is best adapted to the proposed protocol and thus make it easier to read the work.

In addition, even before talking about further studies, the authors should still apply themselves to make this work intelligible and acceptable according to the standards set by PlosOne

Reviewer #2: I appreciate the effort in restructuring the manuscript to respond to the reviewers' comments. The structure of the new manuscript satisfies the requirements sent by the reviewers, however I suggest two minor revision:

- In p9 L181 include "normal" to compare with high:...more in the group with a "normal" waist-to-hip ratio (WHR) than...

- Considering the adjustments made in the manuscript , it seems appropriate to include in the results a brief description about the supplementary tables S10 y S11, in order to guide the reader in the subsequent discussion of the scopes of the study.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Changes in cortisol awakening responses (CAR) in menopausal women through short-term marine healing retreat program with specific factors affecting each CAR index

PONE-D-22-22264R2

Dear Dr. Seoeun Lee,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Juan-Luis Castillo-Navarrete, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments:

It is really gratifying to see how the writing has evolved and how it has improved substantially. Undoubtedly it is, in my opinion, a contingent issue, so I have no doubt that this paper will be a contribution to the scientific community.

Reviewers' comments: