A novel approach for measuring allostatic load highlights differences in stress burdens due to race, sex and smoking status

Aleah Bailey; Alexis Payton; Jonathon Fleming; Julia E. Rager; Ilona Jaspers

doi:10.1371/journal.pone.0323788

Peer Review History

Original SubmissionDecember 4, 2024
4 Dec 2024 Author Response https://doi.org/10.1371/journal.pone.0323788.r001
11 Mar 2025 Decision Letter - katsuya oi, Editor PONE-D-24-53214A Novel Approach for Measuring Allostatic Load Highlights Differences in Stress Burdens due to Race, Sex and Smoking StatusPLOS ONE Dear Dr. Jaspers, 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. Please submit your revised manuscript by Apr 19 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. 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, katsuya oi, PhD Academic Editor PLOS ONE Journal requirements: When submitting your revision, we need you to address these additional requirements. 1. 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 2. Thank you for stating the following financial disclosure: “AB, AP, and IJ were supported by the Environmental Protection Agency Cooperative Agreement with the University of North Carolina at Chapel Hill (UNC) CR 84033801, AB was supported by a pre-doctoral traineeship [National Research Service Award T32 ES007126] from the National Institute of Environmental Health Sciences, National Institutes of Health. This work was supported in part by a grant to UNC Chapel Hill from the Howard Hughes Medical Institute (HHMI) through the Gilliam Fellows Program.” Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. 3. Thank you for stating the following in the Acknowledgments Section of your manuscript: “AB, AP, and IJ were supported by the Environmental Protection Agency Cooperative Agreement with the University of North Carolina at Chapel Hill (UNC) CR 84033801, AB was supported by a pre-doctoral traineeship [National Research Service Award T32 ES007126] from the National Institute of Environmental Health Sciences, National Institutes of Health. This work was supported in part by a grant to UNC Chapel Hill from the Howard Hughes Medical Institute (HHMI) through the Gilliam Fellows Program.” We note that you have provided funding information that is currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. 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: “AB, AP, and IJ were supported by the Environmental Protection Agency Cooperative Agreement with the University of North Carolina at Chapel Hill (UNC) CR 84033801, AB was supported by a pre-doctoral traineeship [National Research Service Award T32 ES007126] from the National Institute of Environmental Health Sciences, National Institutes of Health. This work was supported in part by a grant to UNC Chapel Hill from the Howard Hughes Medical Institute (HHMI) through the Gilliam Fellows Program.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 4. When completing the data availability statement of the submission form, you indicated that you will make your data available on acceptance. We strongly recommend all authors decide on a data sharing plan before acceptance, as the process can be lengthy and hold up publication timelines. Please note that, though access restrictions are acceptable now, your entire data will need to be made freely accessible if your manuscript is accepted for publication. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If you are unable to adhere to our open data policy, please kindly revise your statement to explain your reasoning and we will seek the editor's input on an exemption. Please be assured that, once you have provided your new statement, the assessment of your exemption will not hold up the peer review process. 5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. 6. 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. [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: Yes Reviewer #2: Yes Reviewer #3: No ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: I Don't Know ****** 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 Reviewer #3: 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 Reviewer #3: 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: Page 4; Lines 84-86: “Systolic and diastolic blood pressure data was available for 34 participants and used to develop the acute stress score.” Where do you explain why only 34 of 63 participants had blood pressure data? Perhaps I missed that, seems here would be a good spot. Page 4; Lines 93-97: “Blood containing tubes were then centrifuged and serum was stored at -80°C. The blood was then centrifuged at 1200 x g for 10 minutes, and the serum layer was transferred to a fresh tube and stored at -80°C until samples were collected from all participants.” Repetitious? Why a semi-repeated sentence? Page 7; line 162: “…demographic groups, race, sex and smoking status.” Never have read of smoking status being categorized as a demographic group before. Interesting categorization. Page 17; Lines 396-397: Why is a Table inserted into References List? Overall, an interesting method for assessing allostatic load. Reviewer #2: Dear Author, Thank you so much for the opportunity to review this article. I think with a few revisions, it will be ready to go! Here are some recommendations: -Introduction: -Line 49: - I understand your need to state this, but it is very abrupt here. I recommend moving it down to line 57 and combining it here to highlight its importance in relation to measurable biomarkers as the indicators. -Methods: -2.5.2- Line 130: Can you please identify in the first ordinal regression model what systolic/diastolic blood pressures you are utilizing to categorize the three-class model (normal, elevated, and hypertensive stage 1 and 2) vs two class model (normal, elevated)? I understand this is just being used to describe why you weighted your data the way you did. But, it’s useful to readers who may have notions on what is elevated vs HTN 1 or 2. -2.6-2.7-Line 156-162: Can you please describe why you used a p-value of <.1 for your t-tests and ANOVAs, when regular statistical significance is usually <.05? -Results: -3.1-Line 175: Please identify “The mean age of participants was 28 years old, ranging from XX years to XX years.” -3.1- Line 175-176: Were these self-reported genders and/or race/ethnicities or did they come from a medical record? Please identify either here or in section 2.1 when identifying who your participants are and how you collected their demographic data; this is especially important to explain when working with marginalized groups and you have a pretty substantial non-Hispanic Black subgroup (49%). Especially because you talk about this in the Discussion. -Discussion: -No significant differences in acute stress due to race or sex- this is interesting and should be addressed in the Limitations, as it is kind of an outlier compared to prior literature. -References: Please double check your last reference as it is running below your Table 1. Thank you very much for this opportunity. Jenny Reviewer #3: Thank you for the opportunity to review your manuscript! Exploring allostatic load measurement using the Toxicological Prioritization Index (ToxPi) framework is a novel and exciting approach. However, this manuscript fails to exhibit a nuanced understanding of allostatic load as a preclinical indicator, its evolving history in measurement, and the existing knowledge regarding racial disparities of allostatic load that have been studied for decades. The manuscript lacks a declared purpose/objective, and that lack of clear focus diminishes it. If invited by the editor for a revise and resubmit, I highly recommend narrowing the scope of the paper to address exclusively the novel method you propose, proving the concept, and use your background section to exhibit deep understanding of how allostatic load measurement has evolved and the gap in current measurement that you are addressing. I strongly recommend dropping any inferences from your novel proof of concept intended to be generalized for an entire population, especially with a small sample size. Group differences tests cannot illustrate causation. Some of the causal inferences you ground in your review of extant literature are not justified. Prominent examples include: “Adverse psychosocial experiences and SDOH can lead to chronic activation of the hypothalamic pituitary adrenal (HPA) axis, resulting in allostatic load, or stress-related physiological dysregulation” (line 51-52; McEwen, 2022). I believe this statement is more accurate than not; however, allostatic load has likely had temporal variations over one’s lifecourse, and this statement is more true for childhood and adolescence. There are better sources to cite than a brother’s commentary on his sibling’s life work in a memorial article about another scientific field. Why not cite the source article where possible causation was explored in scientific specificity? McEwen C.A., McEwen B.S. Social structure, adversity, toxic stress, and intergenerational poverty: an early childhood model. Annu. Rev. Sociol. 2017;43:445–472. doi: 10.1146/annurev-soc-060116-053252. “However, the disproportionate risk of allostatic load for Black women is likely due to the added burden of navigating gender inequalities in addition to race- and class- based discrimination, and adopting maladaptive behaviors to cope such as suppressing emotions, working harder to prove worthiness, excessive self reliance, overcommitting to help others, and postponing self-care” (line 248-251; Allen et al, 2019). The cited study explicitly states that it was intended to be a hypothesis-generating study and that it should not be interpreted in any way as inferring causation. ****** 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: Yes: Jenny Clift Reviewer #3: 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. https://doi.org/10.1371/journal.pone.0323788.r002
Revision 1
11 Apr 2025 Author Response A novel approach for measuring allostatic load highlights differences in stress burdens due to race, sex and smoking status Manuscript ID: PONE-D-24-53214 Response to the Reviewers Editorial revisions: 1. The Financial Disclosure statement was modified as following and moved from the Acknowledgements section to the Funding Statement section of the online submission form as stated in the cover letter: “AB, AP, and IJ were supported by the Environmental Protection Agency Cooperative Agreement with the University of North Carolina at Chapel Hill (UNC) CR 84033801, AB was supported by a pre-doctoral traineeship [National Research Service Award T32 ES007126] from the National Institute of Environmental Health Sciences, National Institutes of Health. This work was supported in part by a grant to UNC Chapel Hill from the Howard Hughes Medical Institute (HHMI) through the Gilliam Fellows Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” 2. We have modified the data availability statement to indicate that all data are included within the main manuscript or Supporting Information files. Specifically, Table S7 provides raw data for allostatic load biomarker concentrations, and Table S8 contains the raw stress score data 3. Captions for our Supporting Information files have now been included at the end of the manuscript. Additionally, in-text citations have been modified to align with the Supporting Information guidelines. 4. We have modified out acknowledgements statement as stated in the cover letter: “The authors acknowledge and thank the study coordinators for their dedication an effort in recruiting participants, facilitating sample collection and processing, and managing study operations. The authors also thank the study participants for their time and commitment.” 5. We have revised the manuscript to comply with PLOS ONE’s style requirements and updated the file names to align with the journal’s naming guidelines. Reviewer #1 Comment: Page 4; Lines 84-86: “Systolic and diastolic blood pressure data was available for 34 participants and used to develop the acute stress score.” Where do you explain why only 34 of 63 participants had blood pressure data? Perhaps I missed that, seems here would be a good spot. Response: We apologize for the confusion. This is a retrospective study of data collected from four different studies. However, one of the studies (IRB # 05-2547) did not collect blood pressure data during study visits. To ensure this is explicitly stated in the methods section, an additional sentence was included stating “Since this is a retrospective analysis integrating data from four studies, blood pressure measurements were not collected in one study (IRB #05-2547), resulting in systolic and diastolic blood pressure data available for 34 of the 63 participants, which was used to develop the acute stress score.” (Lines 95-97). Comment: Page 4; Lines 93-97: “Blood containing tubes were then centrifuged and serum was stored at -80°C. The blood was then centrifuged at 1200 x g for 10 minutes, and the serum layer was transferred to a fresh tube and stored at -80°C until samples were collected from all participants.” Repetitious? Why a semi-repeated sentence? Response: We apologize for this oversight and thank the reviewer for pointing this out. We acknowledge the redundancy in the original text and have revised it for clarity and conciseness. The updated sentence now reads: “Blood samples were centrifuged at 1200 x g for 10 minutes, and the serum layer was transferred to a fresh tube and stored at -80°C until samples analyses.” (Lines 103-105). Comment: Page 7; line 162: “…demographic groups, race, sex and smoking status.” Never have read of smoking status being categorized as a demographic group before. Interesting categorization. Response: We recognize that smoking status is typically considered a dynamic, behavioral, or health-related variable rather than a static demographic characteristic. To improve clarity and ensure appropriate categorization, we have revised the sentence to distinguish smoking status from demographic factors. The updated sentence now reads, “Additionally, Two-way ANOVA tests were used to evaluate mean differences in acute stress, secondary mediators, and allostatic load in groups stratified by sex, race, or smoking status.” (Lines 173 – 174). Additionally, to ensure this change is consistent throughout the manuscript, we have removed “demographic” from sentences in lines 171 and 210. Finally, Figure legends were updated to “Fig 2. Stress outcomes by race, sex and smoking status” (Line 205) and “Fig 3. Stratified stress outcomes by race, sex and smoking status” in (Line 210). Comment: Page 17; Lines 396-397: Why is a Table inserted into References List? Overall, an interesting method for assessing allostatic load. Response: Thank you for your careful review of the manuscript and feedback. The table was accidentally placed within the references list due to a formatting error. We have now corrected this issue by repositioning the table appropriately and included it directly after the first paragraph in which it is cited page 9 (Lines 182 – 184). Reviewer #2 Comment: Line 49: - I understand your need to state this, but it is very abrupt here. I recommend moving it down to line 57 and combining it here to highlight its importance in relation to measurable biomarkers as the indicators. Response: We thank the reviewer for their suggestion. We have restructured that paragraph to read: “Allostatic load reflects long-term physiological strain resulting from prolonged activation of the sympathetic-adrenal-medullary (SAM) and hypothalamic pituitary adrenal (HPA) axes due to chronic stress exposure [5]. Allostatic load biomarkers include primary mediators, such as cortisol, epinephrine, and noradrenaline, which directly reflect adrenal function, and secondary mediators, which capture the downstream effects of chronic stress on cardiovascular (HDL and total cholesterol), metabolic (Hba1c) and inflammatory (C-reactive protein and fibrinogen) pathways [6]. These biomarkers can then be combined into a score to provide an objective measure of cumulative stress load and its physiological consequences [7].” (Lines 61 – 68). This revision improves the flow and better connects allostatic load to how it is measured with biomarkers. Comment: Methods:-2.5.2- Line 130: Can you please identify in the first ordinal regression model what systolic/diastolic blood pressures you are utilizing to categorize the three-class model (normal, elevated, and hypertensive stage 1 and 2) vs two class model (normal, elevated)? I understand this is just being used to describe why you weighted your data the way you did. But, it’s useful to readers who may have notions on what is elevated vs HTN 1 or 2. Response: To clarify, we used the standard American Heart Association (AHA) guidelines for blood pressure classification to categorize participants into the three-class and two-class models. To explicitly state this in the manuscript, we have revised the sentence to read: “For the three-blood pressure class model, participants were grouped into normal (systolic BP < 120 mm Hg and diastolic BP < 80 mm Hg, n=15), elevated (systolic BP 120 – 129 mm Hg and diastolic BP < 80 mm Hg, n=4), and hypertensive stage 1 (systolic BP 130 – 139 mm Hg or diastolic BP 80 - 89 mm Hg, n=11) and stage 2 (systolic BP � 140 mm Hg or diastolic BP � 90 mm Hg, n=4), with a total of 15 hypertensive participants” (Lines 137 – 141). Comment: Methods: -2.6-2.7-Line 156-162: Can you please describe why you used a p-value of <.1 for your t-tests and ANOVAs, when regular statistical significance is usually <.05? Response: We apologize for this confusion and have revised the phrasing in the manuscript to clarify that the significance threshold is set to p<0.05 for all analyses. The p< 0.1 values are presented to highlight trends, while p<0.05 remains the threshold for statistical significance. Additionally, we have updated the results to ensure that this distinction is clear: • Line 200-202 has been modified to “Non-smokers had greater acute stress (p=0.035) and higher allostatic load, albeit not statistically significant (p=0.089), compared to smokers (Fig 2C and 2I).” • Line 220-221 has been modified to “Black participants also had greater AL than white participants, albeit not statistically significant (p=0.068) (Fig 2G).” • Lines 221-223 has been modified to “Black females had higher AL scores than White females (p=0.006) and higher scores than Black males, albeit not statistically significant (p=0.081). Similarly, White males had higher AL than White females, albeit not statistically significant (p=0.081), suggesting that the relationship between sex and stress burdens may vary by race (Fig 3G)”. Comment: Results:-3.1-Line 175: Please identify “The mean age of participants was 28 years old, ranging from XX years to XX years.” Response: The sentence has been updated to “Study participants consisted of healthy adults aged 18-43 years who were 1) non-smokers not routinely exposed to secondhand tobacco smoke or 2) active cigarette smokers.” (Line 87-88) Comment: Results-3.1- Line 175-176: Were these self-reported genders and/or race/ethnicities or did they come from a medical record? Please identify either here or in section 2.1 when identifying who your participants are and how you collected their demographic data; this is especially important to explain when working with marginalized groups and you have a pretty substantial non-Hispanic Black subgroup (49%). Especially because you talk about this in the Discussion. Response: We thank the reviewer for this suggestion. To clarify, sex and race/ethnicity were self-reported by the participants. To explicitly state this in the methods section, we have added the following sentence to Section 2.1, “Participants provided self-reported demographic information, including sex, race and ethnicity, as well as information on medical history.” (Line 88-89) Comment: Discussion- No significant differences in acute stress due to race or sex- this is interesting and should be addressed in the Limitations, as it is kind of an outlier compared to prior literature. Response: We thank the reviewer for their feedback. The limitations section has been expanded to include a discussion on the limitations of not detecting differences in acute stress due to sex and race. (Lines 282 – 304) Comment: References: Please double check your last reference as it is running below your Table 1. Response: We apologize for this mistake – the Table has been moved within the manuscript file (Lines 182-184). Reviewer #3: Comment: The manuscript lacks a declared purpose/objective, and that lack of clear focus diminishes it. If invited by the editor for a revise and resubmit, I highly recommend narrowing the scope of the paper to address exclusively the novel method you propose, proving the concept, and use your background section to exhibit deep understanding of how allostatic load measurement has evolved and the gap in current measurement that you are addressing. I strongly recommend dropping any inferences from your novel proof of concept intended to be generalized for an entire population, especially with a small sample size. Group differences tests cannot illustrate causation. Some of the causal inferences you ground in your review of extant literature are not justified. Response: We appreciate the reviewer’s feedback and acknowledge the need for a clearer statement of purpose. The study aims to introduce and validate a novel allostatic load measure, emphasizing its contribution to the field rather than using it to make broad inferences about population-level differences. We have significantly revised the introduction (Lines 50-84) to clarify the overall objective and the discussion to better contextualize our results and avoid causal language and overgeneralizations. Specifically, our revised Introduction focuses on a) the need for unbiased biomarker assessment of allostatic load and b) the limitations of current allostatic load approaches. Additionally, we have expanded the limitations section to mention the moderate sample size of our study. Comment: Prominent examples include: “Adverse psychosocial experiences and SDOH can lead to chronic activation of the hypothalamic pituitary adrenal (HPA) axis, resulting in allostatic load, or stress-related physiological dysregulation” (line 51-52; McEwen, 2022). I believe this statement is more accurate than not; however, allostatic load has likely had temporal variations over one’s life course, and this statement is more true for childhood and adolescence. There are better sources to cite than a brother’s commentary on his sibling’s life work in a memorial article about another scientific field. Why not cite the source article where possible causation was explored in scientific specificity? (McEwen C.A., McEwen B.S. Social structure, adversity, toxic stress, and intergenerational poverty: an early childhood model. Annu. Rev. Sociol. 2017;43:445–472. doi: 10.1146/annurev-soc-060116-053252.) Response: We agree that allostatic load varies over the life course. To address the reviewer’s concern, we revised the statement to “Biomarker-based measures provide a more objective method for assessing cumulative stress burden. Allostatic load reflects long-term physiological strain resulting from prolonged activation of the sympathetic-adrenal-medullary (SAM) and hypothalamic pituitary adrenal (HPA) axes due to chronic stress exposure” (Lines 60-63). Additionally, we appreciate the reviewer’s note regarding the citation and have corrected this mistake by referencing the source article discussing mechanisms underlying the relationship between stress and allostatic load (McEwen & Stellar, 1993), Line 50. Comment: “However, the disproportionate risk of allostatic load for Black women is likely due to the added burden of navigating gender inequalities in addition to race- and class- based discrimination and adopting maladaptive behaviors to cope such as suppressing emotions, working harder to prove worthiness, excessive self-reliance, overcommitting to help others, and postponing self-care” (line 248-251; Allen et al, 2019). The cited study explicitly states that it was intended to be a hypothesis-generating study and that it should not be interpreted in any way as inferring causation. Response: We apologize for this oversight and acknowledge that Allen et al., 2019 is a hypothesis-generating study, and have revised the sentence to ensure it does not imply causation. The sentence now reads, “However, the disproportionate risk of allostatic load for Black women has been hypothesized to result, in part, from the compounded burden of navigating both gender inequalities and race- and class- based discrimination. In response to stress, Black women are believed to adopt maladaptive coping strategies including suppressing emotions, working harder to prove worthiness, excessive self-reliance, overcommitting to help others, and postponing self-care, which could further contribute to physiological stress burdens (39)” (Lines 272-275). We believe it is important to include some discussion of potential contributing factors to the observed higher allostatic load scores in Black women and believe this article provides valuable insights; however, acknowledge that it was not proven but hypothesized in the cited article. The revised wording maintains the mention of this article while making it clear that these findings are exploratory. Attachments Attachment Submitted filename: Response to Reviewers (5).docx https://doi.org/10.1371/journal.pone.0323788.r003
15 Apr 2025 Decision Letter - katsuya oi, Editor <p>A novel approach for measuring allostatic load highlights differences in stress burdens due to race, sex and smoking Status PONE-D-24-53214R1 Dear Dr. Jaspers, 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. Per my independent reading of the revised manuscript, I applaud the authors' detailed attention to the feedback they received, including valuable insights from Reviewer #3. I believe the revisions are appropriate and well executed. 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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, katsuya oi, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0323788.r004
Formally Accepted
Acceptance Letter - katsuya oi, Editor PONE-D-24-53214R1 PLOS ONE Dear Dr. Jaspers, 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. 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. katsuya oi Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0323788.r005

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 .