Mediterranean diet effects on vascular health and serum levels of adipokines and ceramides

Mario Daidone; Alessandra Casuccio; Maria Grazia Puleo; Alessandro Del Cuore; Gaetano Pacinella; Tiziana Di Chiara; Domenico Di Raimondo; Palmira Immordino; Antonino Tuttolomondo

doi:10.1371/journal.pone.0300844

Peer Review History

Original SubmissionNovember 28, 2023
24 Jan 2024 Decision Letter - Aleksandra Klisic, Editor PONE-D-23-37552Mediterranean diet effects on vascular health and serum levels of adipokines and ceramides.PLOS ONE Dear Dr. Tuttolomondo, 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. Please submit your revised manuscript by Mar 09 2024 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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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. When completing the data availability statement of the submission form, you indicated that you will make your data available on acceptance. We strongly recommend all authors decide on a data sharing plan before acceptance, as the process can be lengthy and hold up publication timelines. Please note that, though access restrictions are acceptable now, your entire data will need to be made freely accessible if your manuscript is accepted for publication. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. 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Please include a separate caption for each figure in your manuscript. 5. Please include a copy of Table 2 which you refer to in your text on page 16. 6. 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. 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: No Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: Yes 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: No ****** 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: No 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: The manuscript addresses an interesting topic. The collected data are unique, the employed statistical methods rather basic and there is room left for improvements. My main comments are indeed on the performed statistical analysis. 1. It is nice to see that data are attached. Please, provide the code use to obtain the results in the tables as well. Nevertheless, I feel unacceptable that the data are not anonymized. All patients information, also phone numbers, are available to anyone with access to the link in the paper. This is a clear violation of the privacy and it is rather sloppy and annoying. 2. The use of parametric tests is in general sound, but all tests are based on quite strong assumptions. In the main text, the authors state that they check for these assumptions, please provide evidence that they are met. 3. The employed statistical methods are too basic. I strongly suggest to consider random effects regression models to better account for the longitudinal structure of the data. As before, a residual analysis should be performed and discussed to ensure the reliability of the results. Instead of looking at one variable at the time, a full model should be considered and variable selection procedure implemented and discussed. I further suggest to discuss the potential impact of missing values, which are likely to arise in studies of this type (and it is not clear if any missing values is present in the current study too). Reviewer #2: The study titled "Mediterranean diet effects on vascular health and serum levels of adipokines and ceramides" conducted by Daidone and colleagues evaluated the effect of Mediterranean diet on serum levels of adipokines and ceramides. The study is not well-designed. The topic is not novel and the way of presentation of results are not accurate. The English language needs extensive revisions by a native. Reviewer #3: Daidone et al. have performed a study on the association of the Mediterranean diet with vascular health and serum adipokines. The study is well-conducted and well-written. I have some comments to consider: - The introduction section is unnecessarily lengthy. The authors should try to focus on the main ideas and the rationale for performing the study. - Figure 1 is not completed as the numbers are not added to the flowchart. - The first paragraph of the discussion should focus on the main findings of the manuscript. It should be revised. ****** 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. https://doi.org/10.1371/journal.pone.0300844.r001
Revision 1
22 Feb 2024 Author Response Dear Dr. Tuttolomondo, When submitting your revision, we need you to address these additional requirements. Dear Editor thank you for the evaluation of our manuscript and for the chance to submit a revised version of our manuscript 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 We ensured it 2. When completing the data availability statement of the submission form, you indicated that you will make your data available on acceptance. We strongly recommend all authors decide on a data sharing plan before acceptance, as the process can be lengthy and hold up publication timelines. Please note that, though access restrictions are acceptable now, your entire data will need to be made freely accessible if your manuscript is accepted for publication. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If you are unable to adhere to our open data policy, please kindly revise your statement to explain your reasoning and we will seek the editor's input on an exemption. Please be assured that, once you have provided your new statement, the assessment of your exemption will not hold up the peer review process. We upadated and corrected our data sharing 3. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ 4. Please include a separate caption for each figure in your manuscript. We included a caption for each figure in our manuscript 5. Please include a copy of Table 2 which you refer to in your text on page 16. Table 2 is present on the text now 6. 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. We included the captions Reviewers' comments: Dear Editor, Thank you very much for the useful revision comments and for the chance to submit a revised version of our manuscript. You will find above our answers to the reviewer comments. 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: The manuscript addresses an interesting topic. The collected data are unique, the employed statistical methods rather basic and there is room left for improvements. My main comments are indeed on the performed statistical analysis. 1. It is nice to see that data are attached. Please, provide the code use to obtain the results in the tables as well. Nevertheless, I feel unacceptable that the data are not anonymized. All patients information, also phone numbers, are available to anyone with access to the link in the paper. This is a clear violation of the privacy and it is rather sloppy and annoying. As indicated by the reviewer we removed the information available in the previous version of the attached data that have been enclosed only for a mistake. 2. The use of parametric tests is in general sound, but all tests are based on quite strong assumptions. In the main text, the authors state that they check for these assumptions, please provide evidence that they are met. Dear reviewer thanks for your interesting comments that could be important for the verification of the assumption of the observed significance. We have performed for all variables, in particular with regard of the quantitative variables, the test of normality of the data by kolmogorov-Smirnov test with Lilliefors correction. We found non-significant comforting results about the normality of the data and not relying only on the kolmogorov-Smirnov test. Thus, we repeated the data analysis also with nonparametric statistical procedures that provided identical results with the same significance emerged. Moreover, further sustainment concerning the results that have emerged can also be attributed to the fact that we compared patients at different study times through the paired data methodology, and this seemed to us to be further evidence of the goodness of fit of the data. Therefore, we have chosen to present the data only as means by reporting the parametric results according to ANOVA analysis.This choice is linked to our willness to not furtherly burden the text by reporting all the normality significances for the different variables. 3. The employed statistical methods are too basic. I strongly suggest to consider random effects regression models to better account for the longitudinal structure of the data. As before, a residual analysis should be performed and discussed to ensure the reliability of the results. Instead of looking at one variable at the time, a full model should be considered and variable selection procedure implemented and discussed. I further suggest to discuss the potential impact of missing values, which are likely to arise in studies of this type (and it is not clear if any missing values is present in the current study too). We thank the reviewer again for this additional comment. Indeed in a previous draft of the manuscript we have had wondered of including some regression analyses that , also on the light of your suggestions, we have now decided to resubmit. It seemed to us that the results obtained and presented in the two tables were already sufficient to demonstrate the objectives of the study, but indeed the multivariable regression model for the variables seem to result adequate to be furtherly analyzed since lipid profile, markers of vascular damage such as RHI and AIX, and serum levels of visfatin, adiponectin, and resistin, could furtherly emphasizes the role of these clinical variables as markers of efficacy of the Mediterranean diet in the studied subjects. On the other hand, regarding the request for missing data, since this is a one-year study (6- and 12-month follow-ups) and not a large number of participants, we did not have a drop out of patients and the completeness of the collected data exceeds 98% for all variables. Consequently, we do not believe that this issue could have affected the results of our study. Reviewer #2: The study titled "Mediterranean diet effects on vascular health and serum levels of adipokines and ceramides" conducted by Daidone and colleagues evaluated the effect of Mediterranean diet on serum levels of adipokines and ceramides. The study is not well-designed. The topic is not novel and the way of presentation of results are not accurate. The English language needs extensive revisions by a native Dear reviewer Thank you for your comments In our answers to reviewer 1 we added some further information on the statistical analysis and on the design of the study With regard of the issue of novelty as expressed on the text the findings of this prospective study concerning the observed positive effects of adherence to a Mediterranean-style diet on adipokine serum levels, ceramide serum levels and an index of vascular health, such as RHI, may help to explain the cardiovascular and cerebrovascular protective relationship reported in previous studies from our own group with regard to ischaemic stroke, in particular, the atherosclerotic subtype (65), hamorrhagic cerebrovascular disorders (66) and congestive heart failure (67-69). This integrated evaluation is new, whereas the effects of a Mediterranean Diet on ceramide and adipokine serum levels it is novel finding. We furtherly revised the English style of the manuscript by a mother tongue revisor (see the Editing certification) Reviewer #3: Daidone et al. have performed a study on the association of the Mediterranean diet with vascular health and serum adipokines. The study is well-conducted and well-written. I have some comments to consider: - The introduction section is unnecessarily lengthy. The authors should try to focus on the main ideas and the rationale for performing the study. Dear reviewer thanks for your interesting comment. As suggested, we completely revised the introduction with the aim of making the paragraph more focused on the background that led us to design this study. - Figure 1 is not completed as the numbers are not added to the flowchart. Dear reviewer, “see figure 1” has been written by mistake. We provided to delete it from the definitive manuscript - The first paragraph of the discussion should focus on the main findings of the manuscript. It should be revised. Thanks again for your suggestion. We added a little paragraph in which are synthetizes the main findings of our study. 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 Attachments Attachment Submitted filename: response to reviewers.docx https://doi.org/10.1371/journal.pone.0300844.r002
6 Mar 2024 Decision Letter - Aleksandra Klisic, Editor Mediterranean diet effects on vascular health and serum levels of adipokines and ceramides. PONE-D-23-37552R1 Dear Dr. Tuttolomondo, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at http://www.editorialmanager.com/pone/ and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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, Aleksandra Klisic Academic Editor PLOS ONE 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 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 #1: (No Response) Reviewer #2: (No Response) Reviewer #3: (No Response) ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: (No Response) Reviewer #2: (No Response) Reviewer #3: (No Response) ****** 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: (No Response) Reviewer #2: (No Response) Reviewer #3: (No Response) ****** 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: (No Response) Reviewer #2: (No Response) Reviewer #3: (No Response) ****** 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: (No Response) Reviewer #2: (No Response) Reviewer #3: (No Response) ****** 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 Reviewer #3: No ******** https://doi.org/10.1371/journal.pone.0300844.r003

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