PONE-D-25-38257

Maternal and Demographic Factors Influencing Oral Candida albicans in Infants: A Stratified Analysis Using a Novel Partial Linear Semiparametric Mixed-effects Model

PLOS ONE

Dear Dr. Wu,

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Geelsu Hwang, Ph.D.

Academic Editor

PLOS ONE

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“NIH/NIDCR R01DE031025 and NSF SCC 2238208”

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b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories. You also have the option of uploading the data as Supporting Information files, but we would recommend depositing data directly to a data repository if possible.

Please update your Data Availability statement in the submission form accordingly.

5. In the online submission form you indicate that your data is not available for proprietary reasons and have provided a contact point for accessing this data. Please note that your current contact point is a co-author on this manuscript. According to our Data Policy, the contact point must not be an author on the manuscript and must be an institutional contact, ideally not an individual. Please revise your data statement to a non-author institutional point of contact, such as a data access or ethics committee, and send this to us via return email. Please also include contact information for the third party organization, and please include the full citation of where the data can be found.

6. Thank you for stating the following in the Acknowledgments Section of your manuscript:

“Leon, Alomeir, Xiao and Wu were partly supported by NIH/NIDCR R01DE031025 and NSF SCC 2238208.”

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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:

“NIH/NIDCR R01DE031025 and NSF SCC 2238208”

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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: No

Reviewer #2: Yes

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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: No

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: Leon et al have written a study that used a biostatistical model to analyze infants’ genetic susceptibility to increased risk of dental caries due to C.albicans & Str. mutans collaboration.

The clinical problem is sound and their approach interesting. However, there are severe problems in the article. The involvement and presentation of the biostatistical model is given in a mathematical format. First look, it seemed convincing, with the formulas used. At the closer look, it was very difficult to read, and finally, it was so complicated and specified that I was not able to interpret the method. As a MD, PhD and clinical researcher, I have no such background education or qualification to be able to comment on the method. After considering, I am quite sure that this regards most of the colleague readers as well. Subsequently, perhaps the best forum for this mathematical model is not a clinical medicine publication but a biostatical journal? Therefore, I would recommend that the present paper, or at least the method, should be published in a journal of the correct discipline with mathematically qualified referees. Maybe the clinical part could be rewritten afterwards, by referring that study?

If the article is however meant to be read as a clinical research, there are further concerns:

Abstract:

- The results are not given at all; the authors move straight from the methods to the interpretation.

- The whole description of a clinical study should be written in past tense, i.e., in imperfect, not in the present tense.

Introduction:

- The clinical problem and the previous works were well described.

- Line 49: there is a missing word, or the use of the reference is not correct.

- Tables should be numbered by their appearance in the text; however, here, Table 3 comes first in the text (line 54).

- The authors have set their objective as to explore the potential protective or risk factors; however, I did not find any hypothesis formulated.

- Instead, there is a lengthy explanation (lines 65-81) of how their method should work - I think this kind of promotion should be placed in the discussion part.

Methods:

- Please see above. The mathematical modeling is not adequately placed, requiring specialists on the field, not MDs, to judge it. The replication of the study is not possible.

- Supposing that this research is a clinical, observative study, there are some serious flaws in the methods: the descriptions of the study setting and background population, the selection criteria of the patients, definitions of the primary and secondary outcomes and the conditions studied, ethical permissions, and other statistical methods used, are lacking. No sample size is given, let alone sample size or effect size calculations.

Results:

- It seems that the authors have mixed here some background information and results as well. The paragraph 3.1 should be rewritten, separating them to their adequate places.

- Paragraph 3.2. includes a Fig 1 legend. However, there were no figures within the submission files.

- I understood that the authors have calculated correlation coefficients for some background information. However, the presentation in the tables is not sufficient, e.g., all tables lack patient numbers completely - mere percents are not enough. Confidence intervals are told to be expressed in the tables 2+3, but they are not. Deduction of the most important finding is impossible from the Tables.

Discussion:

- Includes a lot of previous data but not a result summary, deep discussion of the present results, their impact on the clinical work, or the patients. How did this work benefit the studied children?

Reviewer #2: 1. In the Results section, several predictors (e.g., maternal education, plaque index, antifungal use) were selected by the lasso procedure but did not reach statistical significance (Table 2). The manuscript should clearly distinguish between predictors that are statistically significant, those that improve predictive performance, and those with potential clinical implications, to avoid overstating conclusions.

2. The Discussion section alternates between biological, behavioral, and socioeconomic explanations for higher Candida prevalence in Black infants. This should be revised to provide a consistent, evidence-based rationale that integrates vertical and horizontal transmission pathways with social determinants of health.

3. The estimation procedure of the PLSMM model (Section 2.1–2.4) is highly technical and may not be easily reproducible. The authors should supplement the description with intuitive explanations, pseudocode or flowcharts, and additional details about tuning parameter selection, convergence criteria, and software implementation.

4. Table 2 (stratified analysis) shows non-significant race effects, while Table 3 (non-stratified analysis) reports race as a strong predictor (p = 0.0002). The manuscript should explicitly address this discrepancy, clarifying why stratification attenuates the race effect and what this implies about confounding or mediation.

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Reviewer #1: No

Reviewer #2: No

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Maternal and Demographic Factors Influencing Oral Candida albicans in Infants: A Stratified Analysis Using a Novel Partial Linear Semiparametric Mixed-effects Model

PONE-D-25-38257R1

Dear Dr. Wu,

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.

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Kind regards,

Geelsu Hwang, Ph.D.

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 #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 #2: Yes

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

Reviewer #2: Yes

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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 #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 #2: Yes

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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 #2: The authors have modified the manuscript according to the reviewer's comments completely. All the points have been addressed as well as implemented in the manuscript appropriately. The manuscript is now acceptable.

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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 #2: No

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