The SII-PNI score: A novel composite biomarker for personalized mortality risk prediction in peritoneal dialysis patients

Min Zhou; Guoyi Wang; Ping Yue; Hua Lin; Min Chen; Xuan Chen; Jinwen Zhao; Yong Xu

doi:10.1371/journal.pone.0338086

Peer Review History

Original SubmissionJuly 2, 2025
18 Sep 2025 Decision Letter - Zubing Mei, Editor Dear Dr. Zhou, Strengths: The combination of SII (reflecting inflammation and immune balance) and PNI (reflecting nutritional status) into a single prognostic tool is novel for the PD population. This approach holistically captures the intertwined pathophysiology of inflammation and malnutrition, a key driver of outcomes in ESKD. The primary strength of this research is its direct translational potential. The SII-PNI score is derived from inexpensive, universally available blood tests (CBC with differential, serum albumin), making it highly feasible for implementation in diverse clinical settings, including resource-limited ones, without additional cost. The study employs a robust methodological framework. The use of a long-term retrospective cohort (≈18 years), multivariate Cox regression models with progressive adjustment for key confounders, Kaplan-Meier analysis, and ROC curves provides a solid foundation for the conclusions. The application of Random Survival Forests adds a modern, robust validation of the importance of the underlying components. The stratification into four distinct risk groups (G1-G4) is clinically intuitive and effectively discriminates populations with vastly different survival outcomes. The identification of the G4 (high SII + low PNI) group as having a dramatically increased risk (adjusted HRs ~3.4-4.3) is a compelling and clinically actionable finding. Areas for Clarification and Improvement: The use of cohort median values (SII=791, PNI=46) for stratification is statistically valid for this study but limits immediate generalizability. The manuscript would be significantly strengthened by: Providing a justification for using medians over established clinical cut-offs or optimally selected thresholds (e.g., via Youden's index from ROC analysis). Acknowledging that these cut-offs may be population-specific and require external validation in independent, multi-center cohorts to establish universal thresholds. Model Adjustment and Variable Selection: The rationale for adjusting for lymphocyte count (Model 2) and triglyceride (Model 3) specifically should be explained in more depth, as these are components of or closely related to the indices being studied. While the persistence of significance after their adjustment strengthens the result, the reasoning behind including them needs clarity to avoid potential overadjustment. It is crucial to confirm that the proportional hazards assumption was tested and upheld for all Cox models presented. Data Presentation: The Confidence Intervals (CIs) in Table 2 for some estimates, particularly for CVD and Infection mortality, are extremely wide (e.g., 2.41-19.60). This is likely due to the low number of events (n=13 and n=9). This should be explicitly acknowledged as a limitation, indicating that these point estimates, while suggestive of a strong effect, are imprecise and require validation in larger studies. Clinical Implementation Pathway: While the clinical utility is clear, a brief discussion on the proposed concrete next steps for implementing this score would be valuable. For example: Should it be calculated at baseline? At regular intervals? How should a patient's change in risk group over time be interpreted and acted upon? Overall Comments This is a well-conducted and highly relevant study that makes a significant contribution to the field of nephrology and precision medicine for PD patients. The SII-PNI score is a simple, inexpensive, and powerful tool that effectively identifies high-risk individuals who could benefit from intensified multifactorial management strategies. The authors have provided strong initial evidence for its validity. I recommend major revisions , addressing the points above regarding cut-offs, model justification, data presentation, and clarification of limitations, as well as the following Reviewers' comments. 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. 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, Zubing Mei, MD,PH.D 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 in your Funding Statement: “This research was supported by Huai'an Municipal Health Commission Research Project (Grant number HAWJ2024006), Huai'an, China.” Please provide an amended statement that declares all the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now. Please also include the statement “There was no additional external funding received for this study.” in your updated Funding Statement. Please include your amended Funding Statement within your cover letter. We will change the online submission form on your behalf. 3. Thank you for stating the following financial disclosure: “This research was supported by Huai'an Municipal Health Commission Research Project (Grant number HAWJ2024006), Huai'an, China.” 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. 4. We note that your Data Availability Statement is currently as follows: All relevant data are within the manuscript and its Supporting Information files. Please confirm at this time whether or not your submission contains all raw data required to replicate the results of your study. Authors must share the “minimal data set” for their submission. PLOS defines the minimal data set to consist of the data required to replicate all study findings reported in the article, as well as related metadata and methods (https://journals.plos.org/plosone/s/data-availability#loc-minimal-data-set-definition). For example, authors should submit the following data: - The values behind the means, standard deviations and other measures reported; - The values used to build graphs; - The points extracted from images for analysis. Authors do not need to submit their entire data set if only a portion of the data was used in the reported study. If your submission does not contain these data, please either upload them as Supporting Information files or deposit them to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories. If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If data are owned by a third party, please indicate how others may request data access. 5. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Reviewer #1: Explicar melhor a lógica biológica da combinação SII + PNI. Diferenciar explicitamente por que o índice composto supera os componentes isolados. Adicionar um fluxograma do estudo (pacientes avaliados, incluídos, excluídos). O trabalho é de tema relevante e aborda estratificação de risco em pacientes de diálise peritoneal (DP), área de grande importância clínica. O uso de um índice composto (SII-PNI) é uma abordagem original, combinando marcadores inflamatórios e nutricionais de fácil obtenção. 330 pacientes com longo período de acompanhamento (2005–2023) oferecem base robusta para análise. Better explain the biological logic of the SII + PNI combination.Clearly differentiate why the composite index outperforms the isolated components.Add a flowchart of the study (evaluated patients, included, excluded).The work is on a relevant topic and addresses risk stratification in peritoneal dialysis (PD) patients, an area of great clinical importance. The use of a composite index (SII-PNI) is an original approach, combining easy-to-obtain inflammatory and nutritional markers. 330 patients with a long follow-up period (2005–2023) provide a robust basis for analysis. Reviewer #2: I have read through the manuscript thoroughly, and I commend the authors for providing a research paper on such a topic. I find the manuscript interesting, as it provides valuable prognostic information on peritoneal dialysis patients. I recommend that this paper has a significant feature that qualifies it for publication. ****** 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: MARCELA LARA MENDES 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. 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.0338086.r001
Revision 1
23 Oct 2025 Author Response Dear editor and reviewers, Thank you for the opportunity to revise our manuscript (PONE-D-25-34712). We appreciate the constructive feedback from the academic editor and reviewers. We have carefully addressed all comments and made substantial revisions to the manuscript. Below is a point-by-point response to the comments. Response to Academic Editor: 1.Comment: The use of cohort median values (SII=791, PNI=46) for stratification is statistically valid for this study but limits immediate generalizability. The manuscript would be significantly strengthened by: 1.1 Providing a justification for using medians over established clinical cut-offs or optimally selected thresholds (e.g., via Youden's index from ROC analysis). Response: We thank the editor for this insightful comment regarding the use of cut-offs. We have carefully considered the suggestion to determine optimal cut-offs for SII and PNI individually using ROC analysis (e.g., via Youden's index). In our study, we deliberately chose not to pursue population-specific optimal cut-offs for the individual SII and PNI components for the following reasons: 1.Focus on the Novel Composite Score: The primary innovation of our work is the introduction of the SII-PNI score as a composite biomarker. Our ROC analysis (Fig 4, Table 3) demonstrates that this composite score itself has an excellent and superior predictive ability (AUC: 0.80) compared to SII or PNI alone (AUC: 0.58 for both) for all-cause mortality. This validates that the synergy between the two markers, rather than refining their individual thresholds, is the key to its prognostic power. 2. Clinical Practicality and Reproducibility: The use of cohort medians is an objective, transparent, and easily reproducible method for initial risk stratification. It avoids the risk of generating overfitted, population-specific cut-offs that may not generalize well to other cohorts, especially given that our study is a pioneering investigation of this composite score in the peritoneal dialysis (PD) patients. 3. Literature Support and Common Practice: Our approach is consistent with the current literature and common practice in this field. There is no universally established clinical cut-off value for SII or PNI in PD populations. Previous studies have employed a variety of data-driven distribution-based methods, strongly supporting the use of medians in our exploratory study. For instance: Peng et al[1] stratified PD patients by PNI quartiles, the cut-off value was 36.6. Li et al [2] used 38.6 to define low and high PNI group in PD population. Li et al [3] used ROC-derived SII cut-offs of 1168.13 (all-cause) and 625.19 (CVD), which differ substantially from each other and from values in other studies. Tang et al [4] divided PD patients based on SII tertile (e.g., <456.76 and >819.03). Crucially, Alves et al [5] directly used the median value (SII=722.80) to stratify their PD cohort, demonstrating the acceptance of this method. This lack of a gold standard and the heterogeneity in published cut-offs further justify our use of a simple, transparent, and distribution-based median split for this initial investigation of the novel SII-PNI score. Therefore, we believe that for this initial validation of a novel composite score, the use of transparent, distribution-based median cut-offs is not only statistically valid but also strategically preferable to avoid over-optimism and to facilitate initial, straightforward risk categorization before universal thresholds are established in the future. We also added a justification for using median values in the “Methods section” (Line 142-145). We agree that establishing universal thresholds is an important future goal and have explicitly highlighted the need for external validation of our approach (including the median cut-offs) in larger, multi-center cohorts in the “Discussion section” (Lines 388-394). 1.2 Acknowledging that these cut-offs may be population-specific and require external validation in independent, multi-center cohorts to establish universal thresholds. Response: We completely agree with this astute observation. We acknowledge that the cut-off values identified in our single-center study are indeed population-specific and require validation in larger, independent, and multi-center cohorts to establish universal clinical thresholds. We have now explicitly stated this important limitation and the need for future external validation in the revised “Discussion section” (Lines 388-394). We believe that our study serves as a crucial first step, providing the foundational evidence and a practical methodology for future multi-center studies to build upon. 2.Comment: Model Adjustment and Variable Selection: 2.1 The rationale for adjusting for lymphocyte count (Model 2) and triglyceride (Model 3) specifically should be explained in more depth, as these are components of or closely related to the indices being studied. While the persistence of significance after their adjustment strengthens the result, the reasoning behind including them needs clarity to avoid potential overadjustment. Response: We thank the editor for this insightful comment regarding our model adjustments. We agree that lymphocyte count and triglyceride levels are biologically related to the components of SII and PNI, and their adjustment warrants a clear rationale to avoid overadjustment. Our intention was not to treat them as conventional confounders but to perform a stringent sensitivity analysis. Adjustment for Lymphocyte Count: The SII-PNI score is a composite marker representing the interplay between inflammation and nutrition/immunity. Its prognostic value is hypothesized to lie in this integrative nature. By adjusting for lymphocyte count alone in Model 2, we aimed to test the robustness of the SII-PNI group association. If the strong association between the high-risk group (G4) and mortality persisted even after accounting for one of its key components, it would provide powerful evidence that the risk is not merely driven by lymphopenia alone, but by the combined effect captured by the SII-PNI score. The fact that the hazard ratios for G4 remained highly significant and even increased after this adjustment strongly supports the notion that the SII-PNI score provides unique prognostic information beyond its individual parts. Adjustment for Triglyceride: Dyslipidemia is a common feature in PD patients and is closely linked to both systemic inflammation and nutritional status. It can be considered a downstream consequence or a parallel manifestation of the metabolic derangement in the inflammation-malnutrition axis. Including triglyceride in Model 3 allowed us to test whether the association of the SII-PNI score with mortality was independent of this key metabolic correlate. The persistence of a strong, significant association further strengthens the conclusion that the SII-PNI score captures a risk that is not simply a proxy for dyslipidemia. We also expanded the explanation for adjusting for lymphocyte count and triglycerides in the “Statistical Analysis” (Line 156-160): “We adjusted for lymphocyte count to determine if the SII-PNI score provides prognostic value beyond its cellular components, further adjusted for triglycerides, a metabolic parameter closely linked to both inflammation and nutrition in ESKD, to test the independence of the SII-PNI score from related metabolic disturbances.” 2.2. It is crucial to confirm that the proportional hazards assumption was tested and upheld for all Cox models presented. Response: We thank the editor for highlighting this crucial methodological point. We confirm that the proportional hazards (PH) assumption was tested for all Cox proportional hazards models presented in the manuscript. The assumption was assessed using Schoenfeld residuals and for each variable, and no significant deviations from the PH assumption were found (all test p-values > 0.05). We have now explicitly stated this in the “Statistical Analysis” (Line 160-162) section of the revised manuscript to ensure clarity and methodological rigor. 3.Comment: Data Presentation: The Confidence Intervals (CIs) in Table 2 for some estimates, particularly for CVD and Infection mortality, are extremely wide (e.g., 2.41-19.60). This is likely due to the low number of events (n=13 and n=9). This should be explicitly acknowledged as a limitation, indicating that these point estimates, while suggestive of a strong effect, are imprecise and require validation in larger studies. Response: We sincerely thank the editor for this accurate and important observation. We completely agree that the wide CIs for the hazard ratios of cardiovascular and infection-related mortality in our fully adjusted models are a direct consequence of the low number of events (13 and 9, respectively). This inevitably leads to imprecision in the point estimates. We have now explicitly acknowledged this as a key limitation in the “Discussion section” (Line 338-342) of the revised manuscript. We have taken care to clarify that while the large magnitude of the hazard ratios strongly suggests a substantial and clinically important effect of the high-risk SII-PNI group on these cause-specific mortalities, the exact estimates are unstable due to the small sample size for these endpoints. Therefore, these findings should be interpreted as hypothesis-generating and require confirmation in larger prospective studies with a sufficient number of events to provide more precise estimates. 4.Comment: Clinical Implementation Pathway: While the clinical utility is clear, a brief discussion on the proposed concrete next steps for implementing this score would be valuable. For example: Should it be calculated at baseline? At regular intervals? How should a patient's change in risk group over time be interpreted and acted upon? Response: We thank the editor for this excellent suggestion, which helps bridge the gap between our research findings and clinical practice. We agree that a discussion on the potential implementation steps is valuable and have now added a new paragraph to the “Discussion section” (Line 401-405) to address this. We state: “We suggest calculating the SII-PNI score at PD initiation and every 6 months to dynamically assess risk. A transition to a higher risk group should prompt comprehensive evaluation of inflammatory and nutritional status, followed by tailored interventions (e.g., dietary support, anti-inflammatory strategies).” Responses to reviewers comments Reviewer 1’s Comments 1. Better explain the biological logic of the SII + PNI combination Response: We thank the reviewer for this crucial comment. We have now enhanced the biological rationale throughout the manuscript to better explain the synergy between SII and PNI. In the Introduction section (Line 74-78): “The combination of SII and PNI offers a unique opportunity to simultaneously capture two inextricably linked pathophysiological axes: systemic inflammation and nutritional status. In ESKD, inflammation and malnutrition are intertwined in a vicious cycle that synergistically drives adverse outcomes, and the SII-PNI score holistically captures this interplay.” In Discussion scetion (Line 343-348): “While inflammation and malnutrition are recognized intertwined culprits in PD morbidity and mortality, most prior studies focused on single or limited markers. The SII-PNI score captures this interplay and offers a more holistic view of the inflammation-immunity-nutrition axis, focusing on synergistic effects that individual markers miss.” 2. Clearly differentiate why the composite index outperforms the isolated components Response: We have now made direct comparisons in the results and discussion section to explicitly highlight the superior performance of the composite index. In the Results 3.3 (Line 269-273): “ROC analysis demonstrated that SII-PNI score showed superior discriminative power for all-cause mortality compared to SII or PNI alone (AUC: 0.80 vs. 0.58 and 0.58, respectively), confirming the composite index provides synergistic prognostic value (Figure 4a). The same applied to CVD and infection-associated mortality (Figure 4b-c).” In the Discussion section (Line 348-350): “This is evidenced by its significantly higher AUC compared to SII, PNI, or CRP alone, demonstrating that the composite score provides excellent prognostic value.” 3. Add a flowchart of the study Response: We thank the reviewer for this suggestion. We have now included a patient selection flowchart as Fig 1 in the manuscript, detailing the number of patients assessed, included, and excluded, along with the reasons for exclusion. This enhances the transparency of our study population selection. Reviewer 2’s Comments Response: We sincerely thank Reviewer 2 for their positive and encouraging comments on our work. We are glad that the reviewer found our manuscript interesting and valuable. References 1. Peng F, Chen W, Zhou W, Li P, Niu H, Chen Y, et al. Low prognostic nutritional index associated with cardiovascular disease mortality in incident peritoneal dialysis patients. Int Urol Nephrol. 2017; 49(6): 1095-1101. https://doi.org/ 10.1007/s11255-017-1531-0 PMID: 28185108 2. Li X, Zhou X, Li K, Pu L, He X, Liu X, et al. Enhanced prognostic value of a composite nutritional-inflammatory index (P-CONUT) for predicting mortality risk in patients initiating peritoneal dialysis. PLoS One. 2025; 20(5): e0323318. https://doi.org/ 10.1371/journal.pone.0323318 PMID: 40403009 3. Li G, Yu J, Jiang S, Wu K, Xu Y, Lu X, et al. Systemic Immune-Inflammation Index Was Significantly Associated with All-Cause and Cardiovascular-Specific Mortalities in Patients Receiving Peritoneal Dialysis. J Inflamm Res. 2023; 16: 3871-3878. https://doi.org/ 10.2147/JIR.S426961 PMID: 37671129 4. Tang R, Chen J, Zhou Q, Deng J, Zhan X, Wang X, et al. Association between systemic immune inflammation Index and all-cause mortality in incident peritoneal dialysis-treated CKD patients: a multi-center retrospective cohort study. BMC Nephrol. 2024; 25(1): 8. https://doi.org/ 10.1186/s12882-023-03451-4 PMID: 38172773 5. Alves TVG, Giarola LTP, Oliveira Junior WV,Rios DRA Hematological indices derived from complete blood count and unfavorable outcomes in patients under-going peritoneal dialysis. J Bras Nefrol. 2025; 47(4): e20250017. https://doi.org/ 10.1590/2175-8239-JBN-2025-0017en PMID: 40939199 Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0338086.r002
18 Nov 2025 Decision Letter - Zubing Mei, Editor The SII-PNI Score: A Novel Composite Biomarker for Personalized Mortality Risk Prediction in Peritoneal Dialysis Patients PONE-D-25-34712R1 Dear Dr. 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. 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. For questions related to billing, please contact billing support . 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, Zubing Mei, MD,PH.D Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0338086.r003
Formally Accepted
Acceptance Letter - Zubing Mei, Editor PONE-D-25-34712R1 PLOS ONE Dear Dr. Zhou, 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. 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. Zubing Mei Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0338086.r004

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 .