Peer Review History

Original SubmissionApril 30, 2025
Decision Letter - Hiroyoshi Iwata, Editor

Dear Dr. Han,

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.

Both reviewer reports recommended minor revision , and their comments were consistent in suggesting relatively small but important changes. Therefore, we invite you to submit a revised version

Please submit your revised manuscript by Nov 21 2025 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.

When submitting your revision, please include the following:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s), uploaded as a separate file labeled Response to Reviewers.
  • A marked-up copy of your manuscript with changes highlighted, labeled Revised Manuscript with Track Changes.
  • A clean version of your revised manuscript without tracked changes, labeled Manuscript.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

We look forward to receiving your revised manuscript.

Hiroyoshi Iwata, MD, MSc, PhD

Academic Editor

PLOS ONE

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Additional Editor Comments:

Decision on Manuscript: Heavy Metal Exposure and Its Impact on Inflammatory Ratios in Minors: The Mediating Role of BMI

Thank you for submitting your manuscript to PLOS ONE.

Both reviewer reports recommended minor revision, and their comments were consistent in suggesting relatively small but important changes.

In light of this, the editorial decision is to invite you to submit a revised version of your manuscript.

Please carefully address each of the reviewers’ comments in your revision and provide a point-by-point response.

We look forward to receiving your revised manuscript.

Best regards,

Hiroyoshi Iwata, MD, PhD

Academic Editor

PLOS ONE

[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?

Reviewer #1: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

Reviewer #1: The manuscript “Heavy Metal Exposure and Its Impact on Inflammatory Ratios in Minors: The Mediating Role of BMI” offers insight into the effect of heavy metals on the health of the minors which has been exclusively studied in adults till now, imparting novelty to the present work. But the manuscript needs certain modifications to enhance its suitability for publication in this journal, which are listed below:

1. Manuscript needs to be checked by native English speaker to negate any language related errors, in result section, prefer to keep the same verb tense which is fluctuating from past to simple present tense.

2. The abbreviations for neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, platelet-to-neutrophil ratio, and neutrophil-to-monocyte ratio have been mentioned in introduction section. Do not specify the same in section 2.3 (line no 102).

3.Include the significance of the inflammatory markers for better understanding of the relationship between heavy metals and inflammatory markers.

Reviewer #2: This study explores the relationship between heavy metal exposure and inflammatory ratios in minors, with BMI as a potential mediator, using NHANES 2007–2018 data. The large sample size and age-group stratification strengthen the findings. The use of linear regression and mediation analysis is appropriate and reveals consistent patterns: blood Pb, Cd, and Hg are significantly associated with inflammatory ratios, and BMI mediates 20–40% of these effects. The results are clearly presented and the conclusions are supported by the data. I recommend that the authors expand the methodology and figure legends.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

**********

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Attachments
Attachment
Submitted filename: Comments.docx
Revision 1

Response to Reviewer 1:

Reviewer #1: The manuscript “Heavy Metal Exposure and Its Impact on Inflammatory Ratios in Minors: The Mediating Role of BMI” offers insight into the effect of heavy metals on the health of the minors which has been exclusively studied in adults till now, imparting novelty to the present work. But the manuscript needs certain modifications to enhance its suitability for publication in this journal, which are listed below:

1.Manuscript needs to be checked by native English speaker to negate any language related errors, in result section, prefer to keep the same verb tense which is fluctuating from past to simple present tense.

Response 1: We sincerely appreciate the reviewer’s valuable suggestion. In response, we have carefully refined the language throughout the manuscript to improve clarity and precision without altering the original meaning. Furthermore, the verbs in the Methods and Results sections have been consistently revised to the past tense where appropriate. All these revisions are clearly highlighted in the tracked changes of the revised manuscript.

2.The abbreviations for neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, platelet-to-neutrophil ratio, and neutrophil-to-monocyte ratio have been mentioned in introduction section. Do not specify the same in section 2.3 (line no 102).

Response 2: We sincerely thank the reviewer for the insightful comment. The abbreviations PC, NC, LC, and MC in Section 2.3 (line 102) refer to platelet count, neutrophil count, lymphocyte count, and monocyte count, respectively. These abbreviations differ from those defined earlier in the Introduction (i.e., NLR, LMR, PLR, PNR, and NMR), which represent ratio-based indicators. As PC, NC, LC, and MC appear for the first time in this section, we have retained their definitions here for clarity.

3.Include the significance of the inflammatory markers for better understanding of the relationship between heavy metals and inflammatory markers.

Response 3: We have added a description in lines 72–78 of the Introduction section, emphasizing the close association between heavy metal exposure, disruption of immune homeostasis, and the promotion of systemic inflammation. This revision helps readers better understand the relationship between heavy metals and inflammatory responses.

Response to Reviewer 2:

Reviewer #2: This study explores the relationship between heavy metal exposure and inflammatory ratios in minors, with BMI as a potential mediator, using NHANES 2007–2018 data. The large sample size and age-group stratification strengthen the findings. The use of linear regression and mediation analysis is appropriate and reveals consistent patterns: blood Pb, Cd, and Hg are significantly associated with inflammatory ratios, and BMI mediates 20–40% of these effects. The results are clearly presented and the conclusions are supported by the data. I recommend that the authors expand the methodology and figure legends.

Response: We have added a detailed description of the mediation effect in Section 2.6 “Mediation analysis” of the Methods, lines 135-147. In addition, we have revised and enriched the contents to provide clearer explanations of variables, models, and significance indicators in Figure 4 (Section 3.5, lines 246–256). The legend for Figure 4 has also been made more detailed to improve clarity, lines 257-260.

Attachments
Attachment
Submitted filename: Response to Reviewers.docx
Decision Letter - Hiroyoshi Iwata, Editor

Heavy Metal Exposure and Its Impact on Inflammatory Ratios in Minors: The Mediating Role of BMI

PONE-D-25-21195R1

Dear Dr. Han,

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

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

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

Kind regards,

Hiroyoshi Iwata, MD, MSc, PhD, FACP

Academic Editor

PLOS One

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

Reviewer #1: The manuscript has been revised with all comments being addressed; therefore, it is now suitable for publication.

Reviewer #2: Using adult BMI cutoffs for children can lead to misclassification and may substantially affect the accuracy of the study’s interpretations, as pediatric BMI must be assessed using age- and sex-specific percentiles rather than adult thresholds.

**********

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

**********

Attachments
Attachment
Submitted filename: PlosOne comments.pdf
Formally Accepted
Acceptance Letter - Hiroyoshi Iwata, Editor

PONE-D-25-21195R1

PLOS One

Dear Dr. Han,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS One. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

* All relevant supporting information is included in the manuscript submission,

* There are no issues that prevent the paper from being properly typeset

You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps.

Lastly, 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.

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If we can help with anything else, please email us at customercare@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. Hiroyoshi Iwata

Academic Editor

PLOS One

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