Peer Review History

Original SubmissionMarch 10, 2020
Decision Letter - Stephen L Atkin, Editor

PONE-D-20-06167

Variation of Percent of Body fat, Waist, and Cross Sectional Areas of Abdominal Adipose Tissue after Single Unilateral Cryolipolysis-Using the sequential split-body trials-

PLOS ONE

Dear Dr. 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.

The reviewers have  raised several area that need to be addressed including both methodological and statistical issues. The manuscript needs to be clearly written and particularly with a more focused discussion, and be proof read by a native English speaker.

Please submit your revised manuscript by Sep 14 2020 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Stephen L Atkin, MD

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please include in your Methods section the date ranges over which you recruited participants to this study.

3. Thank you for submitting your clinical trial to PLOS ONE and for providing the name of the registry and the registration number. The information in the registry entry suggests that your trial was registered after patient recruitment began. PLOS ONE strongly encourages authors to register all trials before recruiting the first participant in a study.

As per the journal’s editorial policy, please include in the Methods section of your paper:

1) your reasons for your delay in registering this study (after enrolment of participants started);

2) confirmation that all related trials are registered by stating: “The authors confirm that all ongoing and related trials for this drug/intervention are registered”.

Please also ensure you report the date at which the ethics committee approved the study as well as the complete date range for patient recruitment and follow-up in the Methods section of your manuscript.

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

"This study was supported by the Gachon University research fund of 2018. (GCU-2018-5258)"

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:

"Yes, the funder's specification was described in the main text file."

5. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

6. Please amend your manuscript to include your abstract after the title page.

7. Please include a separate caption for each figure in your manuscript.

8. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files.

9. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

[Note: HTML markup is below. Please do not edit.]

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: Yes

Reviewer #2: Partly

Reviewer #3: Partly

**********

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

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

**********

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

Reviewer #3: Yes

**********

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: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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: 1. There are grammatical errors throughout. Please have native English speaker review and edit, and correct syntax, diction, tense, and punctuation. For example, in intro you say that VATS and SATS are "various." This is not correct english. There are more errors throughout the paper. Not a "weakness" but a risk, or disadvantage, etc.

2. The title needs to be improved. It's not the variation you are presenting, but the effect of cryolipolysis on adipose tissue. There's a difference in the meaning of the word "variation."

3. BMI should be spelled out in its first appearance in the manuscript.

4. Your paper has many strengths, but in its current form with sentence structure and english writing errors it makes it difficult to read.

5. Why would visceral fat change if the cryolipolysis is only on the subcutaneous fat?

6. How do you determine metabolism of the fat?

7. Does the patients medical condition, such as Diabetes or heart condition improve as a result of decreased VATS?

8. How do you control for anatomic variability with visceral fat, since the internal anatomy of a patient may change between CT scan sessions?

Overall, the paper has merit and several strengths, but needs more work to present the information in a more coherent fashion.

Reviewer #2: The manuscript entitled ‘Variation of Percent of Body fat, Waist, and Cross Sectional Areas of Abdominal Adipose Tissue after Single Unilateral Cryolipolysis-Using the sequential split-body trials’ with the aim to explore if single session unilateral cryolipolysis on left abdomen could change visceral and subcutaneous adipose tissue (VAT/SAT) in 12 weeks.

The manuscript can be further improved based on the comments below.

Abstract

Mean, sd to be stated for the figures. Figures for men to be included. P value for 1.2 cm2 (3.6%) to be stated. cm2 to be written as cm^2 (2 in superscript form).

Materials and Methods

Page 4, title 'Material and Method' to be stated as Materials and Methods.

Page 4, the statement ‘All participants were provided with written informed consents.’ requires revision.

Page 4, sample size calculation write up requires revision. More input parameters to be provided i.e 1 or 2 tailed, alpha (0.05), power of study etc. Non-centrality parameter δ 4, critical t 2.314495, degree of freedom 15, total sample size 16 are output parameters.

Page 5, statistical analysis section to be placed at the end of the materials and methods section. Paired t test for what comparison to be clearly stated e.g. Initial week and 12-week.

Results

Page 6, the word mean, sd to be stated where applicable.

Page 7, p value to be stated for all results/findings.

Table 1, the name of the statistical test to be denoted in the table footnote as well as in the statistical analysis section. For the Waist to Hip Ratio, was the value for the SD (initial visit and 8 weeks) zero or there was a value at 2nd decimal point onward? .9 to be stated as 0.9 Decimal point for the p values to be standardized. The dark background to be discarded and replaced with words.

Presentation format of .0 or 0. for figures to be standardized throughout the manuscript [text, table, figure(s)].

Active sentences to be written in passive form.

List of references and citation of references in the text did not meet the journal format.

Reviewer #3: The study presents an orderly and very clear methodology, with interesting results. But unfortunately, the discussion does not clearly present the effect of cryolipolysis on visceral fat, nor does it justify this effect, making the necessary correlation with the literature.

**********

6. 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

Reviewer #3: No

[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.

Revision 1

1. There are grammatical errors throughout. Please have native English speaker review and edit, and correct syntax, diction, tense, and punctuation. For example, in intro you say that VATS and SATS are "various." This is not correct english. There are more errors throughout the paper. Not a "weakness" but a risk, or disadvantage, etc.

I have had the manuscript checked by a native English speaker.

2. The title needs to be improved. It's not the variation you are presenting, but the effect of cryolipolysis on adipose tissue. There's a difference in the meaning of the word "variation."

I have modified the title according to your recommendation.

3. BMI should be spelled out in its first appearance in the manuscript.

I have spelled out body mass index (BMI) on its first appearance following your advice.

4. Your paper has many strengths, but in its current form with sentence structure and english writing errors it makes it difficult to read.

I have had the manuscript checked by a native English speaker.

5. Why would visceral fat change if the cryolipolysis is only on the subcutaneous fat?

Visceral adiposity is known for being a metabolic risk depot related to T2DM and dyslipidemia, according to recent animal studies.

Our hypothesis is that cold induced browning of visceral fat is possible, similar to that of subcutaneous fat.

6. How do you determine metabolism of the fat?

In general, most published studies have measured adipocytokines, such as interleukin and caspase from the fat. However, we did not check the chemical profile, but determined the expressed visceral to subcutaneous ratio and used this as a metabolic parameter. This has been described in the last part of the Discussion section.

7. Does the patients medical condition, such as Diabetes or heart condition improve as a result of decreased VATS?

All the subjects were recruited without any metabolic abnormalities, such as DM or thyroid diseases. This has been mentioned in the Methods and Materials section.

8. How do you control for anatomic variability with visceral fat, since the internal anatomy of a patient may change between CT scan sessions?

We measured the cross-sectional areas of adipose tissues at the umbilicus level (first lumbar vertebra) after fasting for 8 hours, before beginning the study and at 12 weeks.

Overall, the paper has merit and several strengths, but needs more work to present the information in a more coherent fashion.

Reviewer #2: The manuscript entitled ‘Variation of Percent of Body fat, Waist, and Cross Sectional Areas of Abdominal Adipose Tissue after Single Unilateral Cryolipolysis-Using the sequential split-body trials’ with the aim to explore if single session unilateral cryolipolysis on left abdomen could change visceral and subcutaneous adipose tissue (VAT/SAT) in 12 weeks.

The manuscript can be further improved based on the comments below.

Abstract

Mean, sd to be stated for the figures. Figures for men to be included. P value for 1.2 cm2 (3.6%) to be stated. cm2 to be written as cm^2 (2 in superscript form).

Materials and Methods

Page 4, title 'Material and Method' to be stated as Materials and Methods.

Page 4, the statement ‘All participants were provided with written informed consents.’ requires revision.

Page 4, sample size calculation write up requires revision. More input parameters to be provided i.e 1 or 2 tailed, alpha (0.05), power of study etc. Non-centrality parameter δ 4, critical t 2.314495, degree of freedom 15, total sample size 16 are output parameters.

Page 5, statistical analysis section to be placed at the end of the materials and methods section. Paired t test for what comparison to be clearly stated e.g. Initial week and 12-week.

Results

Page 6, the word mean, sd to be stated where applicable.

Page 7, p value to be stated for all results/findings.

Table 1, the name of the statistical test to be denoted in the table footnote as well as in the statistical analysis section. For the Waist to Hip Ratio, was the value for the SD (initial visit and 8 weeks) zero or there was a value at 2nd decimal point onward? .9 to be stated as 0.9 Decimal point for the p values to be standardized. The dark background to be discarded and replaced with words.

Presentation format of .0 or 0. for figures to be standardized throughout the manuscript [text, table, figure(s)].

Active sentences to be written in passive form.

List of references and citation of references in the text did not meet the journal format.

Thank you for your review and the detailed comments. All the corrections have been made per your recommendations.

Reviewer #3: The study presents an orderly and very clear methodology, with interesting results. But unfortunately, the discussion does not clearly present the effect of cryolipolysis on visceral fat, nor does it justify this effect, making the necessary correlation with the literature.

Thank you for your comments.

I will revise the manuscript and highlight the effects of cryolipolysis on visceral fat. I also aim to support my hypothesis with the required references.

Decision Letter - Stephen L Atkin, Editor

Cryolipolysis induced abdominal fat change -split-body trials-

PONE-D-20-06167R1

Dear Dr. 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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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,

Stephen L Atkin, MD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

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 #2: Partly

Reviewer #3: Yes

**********

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

Reviewer #2: Yes

Reviewer #3: N/A

**********

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 #2: Yes

Reviewer #3: 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 #2: Yes

Reviewer #3: 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 #2: Table 1 & Table 1 Rev

Visceral-to-Subcutaneous Fat Ratio - add 0 in front of dot

Visceral-to-Total Fat Ratio - add 0 in front of dot

Reviewer #3: All the doubts from the reviwers were response by the authors. I believe that the article is prepared for publication.

**********

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 #2: No

Reviewer #3: No

Formally Accepted
Acceptance Letter - Stephen L Atkin, Editor

PONE-D-20-06167R1

Cryolipolysis-induced abdominal fat change -split-body trials-

Dear Dr. Lee:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Stephen L Atkin

Academic Editor

PLOS ONE

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .