PONE-D-21-18590

Influence of adiposity and physical activity on the cardiometabolic association pattern of lipoprotein subclasses to aerobic fitness in prepubertal children

PLOS ONE

Dear Dr. Kvalheim,

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.

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Martin Senechal, PhD

Academic Editor

PLOS ONE

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“The study was funded by the Research Council of Norway (grant number 221047/F40) and the Gjensidige Foundation (grant number 1042294). None of the funding agencies had any role in the study design, data collection, analysis or interpretation of the data, or in writing the manuscripts.”

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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:

“SAA, grant number 221047/F40, The Research Council of Norway, https://www.forskningsradet.no/, and GKR, grant number 1042294, The Gjensidige Foundation, https://www.gjensidigestiftelsen.no/, none of the funders played any role in the 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: Partly

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

Reviewer #1: I Don't Know

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: Yes

Reviewer #2: No

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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: Important note: This review pertains only to ‘statistical aspects’ of the study and so ‘clinical aspects’ [like medical importance, relevance of the study, ‘clinical significance and implication(s)’ of the whole study, etc.] are to be evaluated [should be assessed] separately/independently. Further please note that any ‘statistical review’ is generally done under the assumption that (such) study specific methodological [as well as execution] issues are perfectly taken care of by the investigator(s). This review is not an exception to that and so does not cover clinical aspects {however, seldom comments are made only if those issues are intimately / scientifically related & intermingle with ‘statistical aspects’ of the study}. Agreed that ‘statistical methods’ are used as just tools here, however, they are vital part of methodology [and so should be given due importance].

COMMENTS: Your ABSTRACT is well drafted but assay type. Please note that it is preferable to divide the ABSTRACT with small sections like ‘Objective(s)’, ‘Methods’, ‘Results’, ‘Conclusions’, etc. which is an accepted practice of most of the good/standard journals [including this one]. It will definitely be more informative then, I guess, whatever the article type may be.

“Why [refer to ‘Availability of data’ section on page 14] the data analyzed in this article are added as Suppl. Mat.”? Moreover, note that most of the ‘Correlations of AF, lipoproteins, physical activity and adiposity’ as reported/displayed in Suppl. Mat. 2 are generally ‘low’. In this context, please read the following [which is pasted from one standard textbook on ‘Research Methodology’]. I am sure that the authors already know these things, however, it is very essential to keep the limitations in mind while interpreting results {which unfortunately are not interpretated adequately}.

Statistical test usually used to assess significance of Pearson’s ‘Correlation coefficient (r)’ is ‘t’ [where t = { r � [(n-2) / (1-r2)] }for df=n-2, n is sample size] and here Ho is that the population/standard value of ‘r’ is zero. You need r=0.878 to be significant at 5% when n=5 but you need r=0.273 only, if n=50 & you need r=0.088 only, if n=500. Because ‘P-value’ heavily depends on sample size, it is customary to use the (available in most text books on ‘Biostatistics’ or on ‘www/net’) guidelines [very strongly suggesting] to consider an absolute value of ‘Correlation coefficient’ for interpreting positive or negative correlations (and do not rely only on corresponding ‘P’-value but also consider an absolute value of ‘Correlation coefficient’). [This argument is equally applicable to non-parametric Spearman’s ‘Correlation coefficient (ρ)’ as well.]

I request the authors to confirm the level of measurement of “Aerobic fitness test” scores [as said in concerned section that the test measured the total distance covered during a 10-minutes run. {and that Children ran from one end-line to another (20 m apart) in a to-and-fro movement intermittently, with 15-second work periods and 15-second breaks}. Moreover, you stated that “We used a PA descriptor of 23 intervals defined by counts per minute (cpm) covering the entire intensity spectrum”. In this context (just reminder), please read the following [which is again pasted from the same textbook on ‘Research Methodology’].

Though the measures/tools used are appropriate, most of them yield data that are in [at the most] ‘ordinal’ level of measurement [and not in ratio level of measurement for sure {as the score two times higher does not indicate presence of that parameter/phenomenon as double (for example, a Visual Analogue Scales VAS score or say ‘depression’ score)}]. Then application of suitable non-parametric test(s) is/are indicated/advisable [even if distribution may be ‘Gaussian’ (i.e. normal)]. Agreed that there is/are no non-parametric test(s)/technique(s) available to be used as alternative in all situation(s) [suitable / most desired/applicable], but should be used whenever/wherever they are available.

It is true that variable ‘time’ is ‘ratio’ but the procedure to record it could change level of measurement. One should just watch-out though it is definitely appreciable that “All variables were thus log-transformed, mean-centered and standardized to unit variance prior to the statistical analysis. After log transformation, normal probability plots showed that only CM, VLDL and a few of their subclasses in addition to TG still deviated from normal distribution”.

Further I request the authors to read the article {just for information, authors are likely to have done this already} titled ‘Relative Importance of Borderline and Elevated Levels of Coronary Heart Disease Risk Factors’ (Ann Intern Med. 2005;142:393-402) & kindly note that I am not asking you to change the study design, but frankly speaking, ‘clinical aspects’ [like medical importance, relevance of the study, ‘clinical significance and implication(s) of the whole study, etc.] are not very clear and so in my considered opinion, should be assessed separately/independently.

Reviewer #2: The subject is of interest as these molecules may aid in pinpointing the molecular pathways linking health and disease in children and how they are influenced by lifestyle behaviours, such as physical activity, fitness and levels of adiposity. However, there are several issues described below that limit the interpretation of the findings generated

* I would consider renaming the title: Independent associations of aerobic fitness, physical activity and adiposity with lipoprotein subclasses in pre-pubertal children and also report the separate associations for PA and adiposity to the lipoprotein subclasses. This could be included as supplementary material. In my opinion, this is a more thorough approach with greater transparency.

* In the abstract, please include some basic information regarding your population. For example, the number of participants included, average age, BMI, waist circumference etc. It would also be helpful for the reader for this to be included in a Table in the main manuscript.

* The opening paragraph of the introduction contains one very long sentence. Consider revising.

* Please make it clear in the second paragraph of the introduction that you are referring to your previous work. The way it is worded presently implies that you are referring to the current study

* The last two sentences of the introduction would be better placed in the discussion

* More information is required regarding the accelerometers. For example, how did you define non-wear time? How many valid days were required as a minimum? It is also important to adjust for wear-time in the analysis. You also state that time spent in PA intensities obtained from the vertical axis was calculated for the subjects. Please include this information

* As a minimum, you need to state that your analysis is observational, meaning that you cannot prove biological mechanisms or demonstrate causality; reverse causality is also a possibility whereby those with a greater burden of obesity may be less likely to engage in greater volumes or intensities of physical activity

* Assuming this data is not available, the lack of adjustment for important confounders (i.e. diet quality, birthweight and socioeconomic status) needs to be addressed.

* The resolution for Figure 1 is too low to review

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: renamed_7e70c.docx

PONE-D-21-18590R1

Influence of adiposity and physical activity on the cardiometabolic association pattern of lipoprotein subclasses to aerobic fitness in prepubertal children

PLOS ONE

Dear Dr. Kvalheim,

Thank you for submitting your manuscript to PLOS ONE and thank you for addressing most of the comments from previous reviewers. We believe you should consider one comment raised by reviewer two, who feels that it could be better addressed. Also, as part of PLOS ONE publication criteria, make sure the manuscript meets the requirements from reporting guidelines. We feel that this study is reported in a way that does not fully meet those requirements. 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 Dec 03 2021 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,

Martin Senechal, PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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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: (No Response)

Reviewer #2: (No Response)

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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: (No Response)

Reviewer #2: Yes

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

Reviewer #1: (No Response)

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: (No Response)

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: (No Response)

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: COMMENTS: Most of the comments made on earlier draft by me (and hopefully by other respected reviewers also) were/are attended [though I am not convinced about few arguments & the way they are made]. I recommend the acceptance as the manuscript now (even earlier I accepted/appreciated the potential of this article) has achieved acceptable level, in my opinion.

Reviewer #2: The authors have done a good job of addressing previous comments. However, I still think the tables including PA descriptors and cardiometaboilc info should be included in this manuscript. It seems a little unrealistic to expect the reader to look elsewhere for this rudimentary information.

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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

[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.

Influence of adiposity and physical activity on the cardiometabolic association pattern of lipoprotein subclasses to aerobic fitness in prepubertal children

PONE-D-21-18590R2

Dear Dr. Kvalheim,

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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Kind regards,

Martin Senechal, PhD

Academic Editor

PLOS ONE