Association between lifestyle-related factors and low back pain: Evidence from a Japanese population–based study

Soya Kawabata; Noriaki Kurita; Takuya Nikaido; Ryoji Tominaga; Yuji Endo; Nobuyuki Fujita; Shin-ichi Konno; Seiji Ohtori

doi:10.1371/journal.pone.0328684

Peer Review History

Original SubmissionApril 8, 2025
Decision Letter - Hiroshi Hashizume, Editor PONE-D-25-17481Association between lifestyle-related factors and low back pain: Evidence from a Japanese population–based studyPLOS ONE Dear Dr. Fujita, 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 Jun 23 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. 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The participants did not provide consent for public data sharing, and the data include potentially identifying information. Access to the data can be requested from the corresponding author, pending approval from the Ethics Committee of Fukushima Medical University.” All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. 5. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. 6. One of the noted authors is a group or consortium “Clinical Research Committee of the Japanese Society of Lumbar Spine Disorders” In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript. Please also indicate clearly a lead author for this group along with a contact email address. 7. 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. Additional Editor Comments: Two reviewers have evaluated your manuscript. The editor believes that Reviewer 2's comments will be useful in improving the quality of your paper. I look forward to your response. [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 ******** 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 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 ****** 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 ****** 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: Thank you for submitting great article that this cross-sectional study investigated the relationship between lifestyle-related factors (LRFs) and low back pain (LBP) in a Japanese population. Using data from a nationwide survey of 2,188 randomly selected Japanese adults, the researchers examined how various LRFs relate to the presence, severity, and chronicity of LBP. The study found that several LRFs were significantly associated with current LBP: higher body mass index (BMI), alcohol consumption, smoking, and dyslipidemia. When analyzing pain severity, smoking, lack of exercise, and dyslipidemia were associated with moderate/severe pain. For chronic LBP (lasting more than 3 months), smoking was the only significant LRF identified. The researchers concluded that LRFs play a crucial role in LBP, with smoking and dyslipidemia being particularly notable risk factors. Smoking was the only factor associated with all three aspects: presence, severity, and chronicity of LBP. I have some comments for publishment. Q1. Please provide more specific details about how participants were recruited. Was the invitation sent by mail using the residential registry, or was the study advertised through email or telephone? The recruitment method should be clearly stated as it could potentially introduce selection bias in your study population. Q2. Regarding the comorbidities mentioned (dyslipidemia, diabetes, and hypertension), please clarify whether participants who were receiving treatment, such as medication, were included in these groups. This information is important for understanding the composition of your study population and could impact the interpretation of your results. Q3. The rationale for investigating self-image regarding body shape (such as "Obese") is not explained in the Introduction section. Please provide justification for including this variable in your study. The reader needs to understand why self-perception of body image was considered relevant to low back pain, and how this connects to your theoretical framework or previous research findings. Q4. Please provide a more in-depth discussion about why dyslipidemia was associated with pain severity but not with chronic LBP. The authors suggest that this relationship might be due to the association between dyslipidemia and disc degeneration. However, it is well established that disc degeneration increases with age, and this aspect was not specifically examined in your study. I recommend developing a more nuanced interpretation of these findings. For instance, could there be different pathophysiological mechanisms at play in acute versus chronic pain? Might dyslipidemia affect nociceptive processing or inflammatory pathways that influence pain severity without necessarily contributing to pain chronicity? Alternatively, could there be confounding factors or mediating variables that explain this seemingly paradoxical relationship? A more comprehensive discussion of these possibilities would strengthen the paper. Q5. I notice that despite finding a significant association between alcohol consumption and current LBP (OR=1.37, 95% CI: 1.04-1.80, P=0.025), there is no discussion of this relationship in your paper. Please add commentary on this finding in the Discussion section. Consider addressing potential mechanisms through which alcohol consumption might influence LBP, whether there are dose-dependent effects, how your findings compare with previous literature on this topic, and any clinical implications. This would provide a more complete interpretation of all significant results identified in your study. Reviewer #2: The authors reported that multiple lifestyle-related factors (LRFs) are associated with the prevalence of low back pain (LBP) in a cross-sectional study of 2,188 subjects. Among the LRFs, dyslipidemia was associated with the presence and severity of LBP, whereas smoking was associated with both its severity and chronicity. Both dyslipidemia and smoking are well-known risk factors for low back pain (LBP), as supported by accumulating evidence from previous reports. Dyslipidemia has been reported as a contributing factor to disc degeneration; however, its association with lumbar spinal epidural lipomatosis and canal stenosis may also correlate with the presence and severity of LBP (Fujita. Spine Surg Relat Res 2021; 5(2): 61-67). I hope this manuscript encourages all spine surgeons to focus not only on surgical treatment but also on improving lifestyle-related factors. I am pleased to inform the authors that this manuscript is worthy of publication in PLOS ONE. ****** 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: Yes: Masatoshi Teraguchi 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. 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Revision 1
29 May 2025 Author Response Response to Reviewers We sincerely thank the Academic Editor and the reviewers for their thoughtful evaluation of our manuscript. Please find enclosed the revised version of our manuscript along with a detailed response to the reviewers’ comments. The feedback provided was highly valuable in guiding our revisions. Changes made in the manuscript are highlighted in yellow. We believe that these revisions have substantially improved the quality of the manuscript. Academic editor 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. Response) We have revised the manuscript to ensure that it adheres to PLOS ONE’s style requirements, including formatting and file naming conventions. 2. Thank you for stating the following financial disclosure: “This study was supported by a scholarship donation from Eli Lilly Japan K.K., and a research grant from the Japanese Society of Lumbar Spine Disorders. “ 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. Response) We have added the following statement to clarify the role of the funders, as requested: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." This sentence has been included in the cover letter accordingly. 3. Thank you for stating the following in the Competing Interests section: “This study was supported by a scholarship donation from Eli Lilly Japan K.K.” Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf. Response) We appreciate the helpful guidance. We have added the following statement to both the cover letter and the manuscript, as requested: "This does not alter our adherence to PLOS ONE policies on sharing data and materials." 4. In the online submission form, you indicated that “The data underlying this study cannot be shared publicly due to participant confidentiality and ethical restrictions. The participants did not provide consent for public data sharing, and the data include potentially identifying information. Access to the data can be requested from the corresponding author, pending approval from the Ethics Committee of Fukushima Medical University.” All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. Response) We apologize for the oversight. The full dataset cannot be made publicly available due to ethical restrictions and participant confidentiality, as informed consent for open data sharing was not obtained and the data contain potentially identifying information. Interested researchers may request access to the data by contacting the Clinical Research Committee of the Japanese Society of Lumbar Spine Disorders via Dr. Takuya Nikaido (Associate Professor, Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine; Email: nikataku@gmail.com), pending approval from the Ethics Committee of Fukushima Medical University. We hope this approach complies with the journal’s data sharing policy, and we appreciate your understanding regarding the ethical considerations involved. 5. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Response) The corresponding author already has an ORCID iD. We will complete the validation process in Editorial Manager as requested. 6. One of the noted authors is a group or consortium “Clinical Research Committee of the Japanese Society of Lumbar Spine Disorders” In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript. Please also indicate clearly a lead author for this group along with a contact email address. Response) We appreciate the helpful guidance. We have decided to list the "Clinical Research Committee of the Japanese Society of Lumbar Spine Disorders" as the affiliated organization rather than listing the individual authors. 7. 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. Response) We have added several relevant references and corrected previously inappropriate or inaccurate citations in the reference list. All changes have been made to ensure accuracy and consistency with PLOS ONE’s formatting and citation guidelines. Reviewer #1: Q1. Please provide more specific details about how participants were recruited. Was the invitation sent by mail using the residential registry, or was the study advertised through email or telephone? The recruitment method should be clearly stated as it could potentially introduce selection bias in your study population. Response) We appreciate the reviewer’s valuable feedback. In response to the reviewer’s comment, we deleted the sentence “Surveyors visited the participants’ residences to distribute and collect the survey forms” due to insufficient explanation, and created a new sentence to clarify the procedure in more detail. Page 6, lines 94 to 98: Before the survey, a letter requesting participation was sent in advance to the selected individuals. Subsequently, trained surveyors visited their homes and hand-delivered the self-administered survey forms enclosed in detention envelopes. Upon retrieval, the surveyors confirmed directly with the participants or their household members that the forms had been completed by the participants themselves. Page 6, lines 101: Participants were rewarded with a gift card for completing the survey. Q2. Regarding the comorbidities mentioned (dyslipidemia, diabetes, and hypertension), please clarify whether participants who were receiving treatment, such as medication, were included in these groups. This information is important for understanding the composition of your study population and could impact the interpretation of your results. Response) We appreciate the reviewer’s insightful comment. As the information regarding comorbidities was obtained through a self-administered questionnaire, we were only able to assess the presence or absence of conditions such as dyslipidemia, diabetes, and hypertension. Unfortunately, we did not collect data on whether participants were receiving treatment (e.g., medication) for these conditions. We acknowledge that the treatment status may influence the interpretation of our results, and we have clarified this limitation in the manuscript accordingly. Page 7, lines 122: ; however, treatment status for these comorbidities was not assessed Q3. The rationale for investigating self-image regarding body shape (such as "Obese") is not explained in the Introduction section. Please provide justification for including this variable in your study. The reader needs to understand why self-perception of body image was considered relevant to low back pain, and how this connects to your theoretical framework or previous research findings. Response) We appreciate the reviewer’s thoughtful comment. In response, we have added the following sentence and a relevant reference to the manuscript to clarify the rationale for including self-image regarding body shape. This addition reflects previous findings that self-perceived body shape may impact health behaviors and comorbidities, and supports its relevance in the context of LBP. Page 4, lines 65 to 68: “Beyond these physical and clinical indicators, self-image regarding body shape—a form of subjective health perception—has also gained attention as a psychosocial factor influencing lifestyle-related diseases and overall health status [11].” Page 21, lines 367 to Page 22, lines 370: Ramos-Vera C, Quispe-Callo G, Basauri-Delgado M, Calizaya-Milla YE, Casas-Gálvez C, Gálvez-Díaz NDC, et al.The mediating role of healthy behaviors and self-perceived health in the relationship between eating behaviors and comorbidity in adults. Arch Public Health. 2024;82(1):203. doi: 10.1186/s13690-024-01435-w Q4. Please provide a more in-depth discussion about why dyslipidemia was associated with pain severity but not with chronic LBP. The authors suggest that this relationship might be due to the association between dyslipidemia and disc degeneration. However, it is well established that disc degeneration increases with age, and this aspect was not specifically examined in your study. I recommend developing a more nuanced interpretation of these findings. For instance, could there be different pathophysiological mechanisms at play in acute versus chronic pain? Might dyslipidemia affect nociceptive processing or inflammatory pathways that influence pain severity without necessarily contributing to pain chronicity? Alternatively, could there be confounding factors or mediating variables that explain this seemingly paradoxical relationship? A more comprehensive discussion of these possibilities would strengthen the paper. Response) We appreciate the reviewer’s insightful comment regarding the differential association of dyslipidemia with pain severity and chronicity. In response, we have expanded the Discussion section to include a possible explanation based on existing literature. Specifically, we now note that this discrepancy may be due to confounding factors such as obesity and physical inactivity, which are closely related to both dyslipidemia and chronic LBP. For example, a large cohort study involving more than 18,000 adults found that low HDL-C and high triglyceride levels initially predicted an increased risk of chronic LBP, but these associations disappeared after adjusting for BMI and lifestyle variables. We have cited this study and suggested that the lack of a significant association between dyslipidemia and chronic LBP in our analysis may reflect the influence of such unmeasured confounders or mediators. We believe this addition provides a more nuanced interpretation of our findings. Page 16, lines 254 to 259: These discrepancies may be explained by confounding factors such as obesity and physical inactivity, which are often associated with both dyslipidemia and chronic LBP. For example, in a large cohort study involving over 18,000 adults, low HDL-C and high triglyceride levels were initially associated with an increased risk of chronic LBP. However, these associations disappeared after adjusting for body mass index and lifestyle variables [8]. This suggests that the link between dyslipidemia and chronic pain may be mediated by adiposity rather than a direct causal effect. In our study, the absence of a significant association between dyslipidemia and chronic LBP may similarly reflect the influence of unmeasured confounders or mediating variables [8]. Q5. I notice that despite finding a significant association between alcohol consumption and current LBP (OR=1.37, 95% CI: 1.04-1.80, P=0.025), there is no discussion of this relationship in your paper. Please add commentary on this finding in the Discussion section. Consider addressing potential mechanisms through which alcohol consumption might influence LBP, whether there are dose-dependent effects, how your findings compare with previous literature on this topic, and any clinical implications. This would provide a more complete interpretation of all significant results identified in your study. Response) We appreciate the reviewer’s thoughtful comment regarding the lack of discussion on the association between alcohol consumption and current LBP. In response, we have added the following paragraph to the Discussion section. We believe this addition addresses the comment by providing context from the literature and acknowledging the clinical implications of our findings. Page 17, lines 277 to 284: Furthermore, this study identified alcohol consumption as an independent risk factor for current LBP. According to a systematic review by Ferreira et al., alcohol consumption is slightly associated with LBP; however, no dose-response relationship was identified [19]. Additionally, Vaajala et al. reported that excessive alcohol intake during adolescence increases the risk of developing LBP in adulthood [18]. Based on these findings, it is advisable to avoid excessive alcohol consumption from the perspective of LBP prevention. Page 23, lines 394 to 396: Ferreira PH, Pinheiro MB, Machado GC, Ferreira ML. Is alcohol intake associated with low back pain? A systematic review of observational studies. Man Ther. 2013;18(3):183–190. doi:10.1016/j.math.2012.11.008 Reviewer #2: The authors reported that multiple lifestyle-related factors (LRFs) are associated with the prevalence of low back pain (LBP) in a cross-sectional study of 2,188 subjects. Among the LRFs, dyslipidemia was associated with the presence and severity of LBP, whereas smoking was associated with both its severity and chronicity. Both dyslipidemia and smoking are well-known risk factors for low back pain (LBP), as supported by accumulating evidence from previous reports. Dyslipidemia has been reported as a contributing factor to disc degeneration; however, its association with lumbar spinal epidural lipomatosis and canal stenosis may also correlate with the presence and severity of LBP (Fujita. Spine Surg Relat Res 2021; 5(2): 61-67). I hope this manuscript encourages all spine surgeons to focus not only on surgical treatment but also on improving lifestyle-related factors. I am pleased to inform the authors that this manuscript is worthy of publication in PLOS ONE. Response) We appreciate the reviewer’s positive evaluation and insightful comments. In response to the suggestion, we have added a sentence to the Discussion to elaborate on the potential involvement of dyslipidemia in lumbar spinal epidural lipomatosis and canal stenosis, as described by Fujita et al. (Spine Surg Relat Res 2021). This addition supports the broader pathophysiological link between dyslipidemia and LBP severity and presence, beyond disc degeneration alone. We also appreciate the r Attachments Attachment Submitted filename: Responses to Reviewers.docx https://doi.org/10.1371/journal.pone.0328684.r002
Decision Letter - Hiroshi Hashizume, Editor Association between lifestyle-related factors and low back pain: Evidence from a Japanese population–based study PONE-D-25-17481R1 Dear Dr. Fujita, 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. 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. 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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: 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? 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: 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: Yes 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: 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: After careful review of the revised manuscript, I am pleased to confirm that the authors have successfully addressed all previously identified concerns. The modifications made to the paper have significantly strengthened its scholarly contribution, and I believe the revised work is now methodologically sound, well-structured, and presents findings that will be of considerable value to the academic community. Therefore, I consider this revised paper to be entirely appropriate and highly worthy of publication in your esteemed journal. Reviewer #2: The authors have appropriately revised their manuscript to a level suitable for publication in PLOS ONE. I am pleased to recommend acceptance of this manuscript for publication in the journal. ****** 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 ******** https://doi.org/10.1371/journal.pone.0328684.r003
Formally Accepted
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