Simultaneous evaluation of metabolomic and inflammatory biomarkers in children with different body mass index (BMI) and waist-to-height ratio (WHtR)

Erika Chavira-Suárez; Cecilia Rosel-Pech; Ernestina Polo-Oteyza; Mónica Ancira-Moreno; Isabel Ibarra-González; Marcela Vela-Amieva; Noemi Meraz-Cruz; Carlos Aguilar-Salinas; Felipe Vadillo-Ortega

doi:10.1371/journal.pone.0237917

Peer Review History

Original SubmissionJanuary 15, 2020
16 Apr 2020 Decision Letter - Nayanatara Arun Kumar, Editor PONE-D-20-01403 Simultaneous evaluation of metabolomic and inflammatory biomarkers in children with different body mass index (BMI) and waist-to-height ratio (WHtR) PLOS ONE Dear Aithors 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 proco and Interprate the statistical analysis as suggested by the Reviewer. Likewise please do the changes in the ============================== We would appreciate receiving your revised manuscript When you are ready to submit your revision, Kindly resubmit with al the quereiess recified log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols 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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Nayanatara Arun Kumar Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 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 1. Thank you for including your competing interests statement; " I have read the journal's policy and the authors of this manuscript have the following competing interests: EPO is the Director of Fondo Nestlé para la Nutrición in the Fundación Mexicana para la Salud. The other authors have indicated they have no financial relationships relevant to this article to disclose." We note that one or more of the authors are employed by a commercial company: Fondo Nestlé para la Nutrición in the Fundación Mexicana para la Salud. Please provide an amended Funding Statement declaring this commercial affiliation, as well as a statement regarding the Role of Funders in your study. If the funding organization did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries and/or research materials, please review your statements relating to the author contributions, and ensure you have specifically and accurately indicated the role(s) that these authors had in your study. You can update author roles in the Author Contributions section of the online submission form. Please also include the following statement within your amended Funding Statement. “The funder provided support in the form of salaries for authors [insert relevant initials], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.” If your commercial affiliation did play a role in your study, please state and explain this role within your updated Funding Statement. 2. Please also provide an updated Competing Interests Statement declaring this commercial affiliation along with any other relevant declarations relating to employment, consultancy, patents, products in development, or marketed products, etc. Within your Competing Interests Statement, please confirm that this commercial affiliation does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests) . If this adherence statement is not accurate and there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. Please include both an updated Funding Statement and Competing Interests Statement in your cover letter. We will change the online submission form on your behalf. Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests 2. 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 [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: Partly Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: 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 ****** 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 ****** 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: Vadillo-Ortega and collaborators have studied changes in metabolic and inflammatory markers in obese children. Since these children show altered some of the metabolic markers but not those of inflammation, they conclude that the metabolic changes must precede the inflammatory ones. It is difficult to follow the changes that occur, since the p values obtained in the ANOVAS or in the tests used are not indicated. These p-values must be included in order to be able to properly assess the changes that have occurred. In addition, although the differences obtained in the post-hoc tests are indicated, it is not clear what they refer to specifically. Perhaps it would be better to indicate the differences in the post-hoc tests, and between which groups, at the bottom of the tables. Differences with reference 40 should be commented on more extensively, since the parameters evaluated were different. It would be interesting to evaluate leukocyte, lymphocyte, erythrocyte, platelet, CRP, and transaminase levels to see if the differences obtained in Marginean's and collaborators' study are also replicated in the children of the present study. I find it difficult, although this is a personal opinion, to think that only metabolic changes are the inducers of obesity in these children. Minor points: All numbers in all tables should always include a maximum of three significant digits. For example, in Table 1, the systolic pressure values include a figure of 104±10.5 and a figure of 108.2±12. The data should be more uniform, e.g. 104±11 and 108±12. In table 1 the % is expressed and then the amount in parentheses; the amount should be indicated first and the percentage in parentheses (and the heading should be N (%)). In Table 4, since the insulin values have been measured, they should be included. Why were only 12 amino acids measured? There is no difference between groups when comparing the different acyl-carnitines. It might be better to include this table as a supplementary table. Reviewer #2: Manuscript describes an interesting cross sectional study that measured metabolic and inflammatory biomarkers in Mexican children with different levels of adiposity. Targeted metabolomics and appropriate statistical tools have been used for data analysis. Even with acknowledged limitations of relatively small sample size, lack of life-style and dietary data, study provides good information which would be very useful for future studies. ****** 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 [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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0237917.r001
Revision 1
30 May 2020 Author Response Responses to Reviewer #1: Corrections were made and highlighted in green, as they appear in the file named “Revised manuscript with track changes”. 1. p-values with statistical significance were included in tables. We modified all Tables to clarify their content. Old table 4 is now Supplementary Table 1 (S1). New Table 4 describes multivariate analysis. 2. Two paragraphs were added in Discussion addressing Marginean's study (Lines 299-304). 3. All numbers in tables were converted to include a maximum of three significant digits. 4. Insulin values were added in New Table 4. 5. Number of measured amino acids was limited by the pre-designed commercial kit. However, we selected this kit because all groups of amino acids were represented according to their metabolic fate. 6. Bivariate analysis that included acylcarnitines concentrations (old Figure 4) was included in Supplementary Table 1 Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0237917.r002
16 Jun 2020 Decision Letter - Nayanatara Arun Kumar, Editor PONE-D-20-01403R1 Simultaneous evaluation of metabolomic and inflammatory biomarkers in children with different body mass index (BMI) and waist-to-height ratio (WHtR) PLOS ONE Dear Dr. Felipe Vadillo-Ortega 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. ============================== Dear authors Based on the reviewers comment on this manuscript. considerin. Kindly submit the revised at the earlies Please submit your revised manuscript by 30th June 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 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, Nayanatara Arun Kumar Academic Editor PLOS ONE [Note: HTML markup is below. Please do not edit.] [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.0237917.r003
Revision 2
17 Jul 2020 Author Response Mexico City, May 14,2020 Rebuttal letter Responses to Reviewer #1: Corrections were made and highlighted in green, as they appear in the file named “Revised manuscript with track changes”. 1. p-values with statistical significance were included in tables. We modified all Tables to clarify their content. Old table 4 is now Supplementary Table 1 (S1). New Table 4 describes multivariate analysis. 2. Two paragraphs were added in Discussion addressing Marginean's study (Lines 299-304). 3. All numbers in tables were converted to include a maximum of three significant digits. 4. Insulin values were added in New Table 4. 5. Number of measured amino acids was limited by the pre-designed commercial kit. However, we selected this kit because all groups of amino acids were represented according to their metabolic fate. 6. Bivariate analysis that included acylcarnitines concentrations (old Figure 4) was included in Supplementary Table 1 Additional changes: Other corrections were made, they appear turquoise highlighted in the file named “Revised manuscript with track changes”. 1. Line 4: biomarkers instead of markers. 2. Line 8: corresponding author affiliation number. 3. Line 139: Gluc and TAG initials instead of Glucose and TG. 4. Line 149: initials of Insulin (Ins) was added. 5. Lines 151 and 152: initials of Gluc and Ins instead of the complete name. 6. Line 181, 192, 214, and 246: schoolchildren instead of school children. 7. Line 185, 196: initial definitions were included in the figure legend. 8. Line 189 -190, 250: NG initials instead of N. 9. Line 219- 227: all paragraph was modified. 10. Line 289 and 294: tyrosine and Val words were changed for phenylalanine, and ornithine such as valine (complete word). Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0237917.r004
6 Aug 2020 Decision Letter - Nayanatara Arun Kumar, Editor Simultaneous evaluation of metabolomic and inflammatory biomarkers in children with different body mass index (BMI) and waist-to-height ratio (WHtR) PONE-D-20-01403R2 Dear Dr. Vadillo-Ortega, 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, Nayanatara Arun Kumar Academic Editor PLOS ONE Additional Editor Comments (optional): Dear authors Very sorry for the delay in the decision from my side. The reviewers comments have been addressed and i congragulate all the auhtors . this paper can be accepted for the publication . with best wishes Dr. Nayana tara Arun KUmar Associate Professor in Physiology Kasturba Medical College, Mangalore Reviewers' comments: https://doi.org/10.1371/journal.pone.0237917.r005
Formally Accepted
12 Aug 2020 Acceptance Letter - Nayanatara Arun Kumar, Editor PONE-D-20-01403R2 Simultaneous evaluation of metabolomic and inflammatory biomarkers in children with different body mass index (BMI) and waist-to-height ratio (WHtR) Dear Dr. Vadillo-Ortega: 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. Nayanatara Arun Kumar Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0237917.r006

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 .