PONE-D-24-50752BMI-Mediated Association between Glyphosate Exposure and Increased Risk of Atherosclerotic Heart Disease: A Large-Scale Cross-Sectional StudyPLOS ONE

Dear Dr. Meirong Zhou,

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PLOS ONE

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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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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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: Yes

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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: 1) The study highlights a significant association between glyphosate exposure and ASCVD but does not differentiate between the effects of acute and chronic exposure. Could the authors clarify whether the findings suggest a more prominent role for long-term, chronic exposure versus short-term, acute exposure in the development of ASCVD?

2) While BMI is presented as a mediator in this association, have the authors considered other potential mediators, such as inflammatory markers or oxidative stress pathways? Exploring these could provide a more comprehensive understanding of the mechanisms underlying the association between glyphosate exposure and ASCVD

3) Consider providing a more extensive comparison with global studies, particularly those investigating glyphosate exposure in high-use agricultural regions (e.g., Latin America, Southeast Asia) and among populations with varying baseline risks for ASCVD. This would enhance the contextualization of the study findings and highlight the broader relevance of the research.

Reviewer #2: Line 130-134 alcohol consumption classification, it would be good to use standardized NIAAA classification https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking so that it is easier for comparison with other studies.

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Reviewer #1: Yes: Sze Loon CHOW

Reviewer #2: No

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BMI-Mediated Association between Glyphosate Exposure and Increased Risk of Atherosclerotic Heart Disease: A Large-Scale Cross-Sectional Study

PONE-D-24-50752R1

Dear Dr. Meirong Zhou,

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,

Hean Teik Ong

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 #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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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: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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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: Yes

Reviewer #2: Yes

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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: Yes

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: Authors have addressed and answered the reviewer's comments. The research paper highlighted the importance of BMI as a mediator in developing Atherosclerotic Heart Disease

Reviewer #2: Your research paper on BMI-Mediated Association between Glyphosate Exposure and Increased Risk of

Atherosclerotic Heart Disease is a relevant since CVD is the top cause of mortality in the world, and obesity is increasingly pervasive in all society.

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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: Yes: CHOW Sze Loon

Reviewer #2: No

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