Predictive value of CD86 for the occurrence of sepsis (Sepsis-3) in patients with infection

Dan lv; Keji Zhang; Changqing Zhu; Xinhui Xu; Hao Gong; Li Liu

doi:10.1371/journal.pone.0302063

Peer Review History

Original SubmissionMay 14, 2023
16 Aug 2023 Decision Letter - Mian Pan, Editor PONE-D-23-11681Predictive value of CD86 for the occurrence of sepsis (Sepsis-3) in patients with infectionPLOS ONE Dear Dr. Zhang, 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 Sep 30 2023 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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Additional Editor Comments: We have received the reports from our advisors on your manuscript, "Predictive value of CD86 for the occurrence of sepsis (Sepsis-3) in patients with infection", which you submitted to PLOS ONE. Based on the advice received, the Editors feel that your manuscript could be reconsidered for publication should you be prepared to incorporate major revisions. When preparing your revised manuscript, you are asked to carefully consider the reviewer comments which are attached, and submit a list of responses to the comments. COMMENTS FOR THE AUTHOR: Reviewer #1: This study wants to explore the value of the costimulatory molecule CD86 in the early diagnosis of sepsis in the emergency department and explore the value of HLA in the prognosis of patients with sepsis. The authors pointed out that CD86 is an independent predictor of the occurrence of sepsis in patients with infection in the emergency department and has a certain value in the early clinical diagnosis of sepsis in such patients. The Manuscript needs some minor revisions: -Improve the English form. -It is unclear how control patients were enrolled. Do they always come from the emergency room? are they patients with fever? The authors should clarify the description of this group. - the tables and figures are clear except for figure 2, the symbols are not clear and are small, also the figure should be divided into A and B. Reviewer #2: The authors have written a nice manuscript which is a prospective study. 1. Variables with P<0.15 in the univariable regression analysis were selected for multivariable logistic regression analysis (MVA). Why not only variables with significant value p<0.05 were taken for MVA 2. Why were blood samples collected after 1st dose of antibiotics, and not at baseline? 3. How can variables with such low odds ratios [PLT (OR=0.99, 95%CI: 0.986-0.997, P=0.001), IL-10 (OR=1.01)] be statistically significant? What is the outcome of odds ratio for these variables? 4. In Methods - Please write clearly what was the primary end-point of the study. Writing to explore the value of CD86 and HLA-DR in sepsis, is very vague 5.How many patients who were initially classified as "non-sepsis" later turned into "sepsis" during the course of hospital stay? How were these patients accounted for? This letter contains confidential information, is for your own use, and should not be forwarded to third parties. [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: No ****** 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: No ****** 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: This study wants to explore the value of the costimulatory molecule CD86 in the early diagnosis of sepsis in the emergency department and explore the value of HLA in the prognosis of patients with sepsis. The authors pointed out that CD86 is an independent predictor of the occurrence of sepsis in patients with infection in the emergency department and has a certain value in the early clinical diagnosis of sepsis in such patients. The Manuscript needs some minor revisions: -Improve the English form. -It is unclear how control patients were enrolled. Do they always come from the emergency room? are they patients with fever? The authors should clarify the description of this group. - the tables and figures are clear except for figure 2, the symbols are not clear and are small, also the figure should be divided into A and B. Reviewer #2: The authors have written a nice manuscript which is a prospective study. 1. Variables with P<0.15 in the univariable regression analysis were selected for multivariable logistic regression analysis (MVA). Why not only variables with significant value p<0.05 were taken for MVA 2. Why were blood samples collected after 1st dose of antibiotics, and not at baseline? 3. How can variables with such low odds ratios [PLT (OR=0.99, 95%CI: 0.986-0.997, P=0.001), IL-10 (OR=1.01)] be statistically significant? What is the outcome of odds ratio for these variables? 4. In Methods - Please write clearly what was the primary end-point of the study. Writing to explore the value of CD86 and HLA-DR in sepsis, is very vague 5. How many patients who were initially classified as "non-sepsis" later turned into "sepsis" during the course of hospital stay? How were these patients accounted for? ****** 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: Sumeet Mirgh ******** [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/. 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Revision 1
16 Oct 2023 Author Response Title: Predictive value of CD86 for the occurrence of sepsis (Sepsis-3) in patients with infection Journal: PLoS ONE Response to Reviewers’ comments Dear Editor, We thank you for your careful consideration of our manuscript. We appreciate your response and overall positive initial feedback and made modifications to improve the manuscript. After carefully reviewing the comments made by the Reviewers, we have reorganized the literature data, modified the manuscript to improve the presentation of our results and their discussion, therefore providing a complete context for the research that may be of interest to your readers. We hope that you will find the revised paper suitable for publication, and we look forward to contributing to your journal. Please do not hesitate to contact us with other questions or concerns regarding the manuscript. Best regards, Keji Zhang Reviewer #1 The Manuscript needs some minor revisions: -Improve the English form. Response: We thank the Reviewer. The manuscript was proofread. -It is unclear how control patients were enrolled. Do they always come from the emergency room? are they patients with fever? The authors should clarify the description of this group. Response: We thank the Reviewer for the comment. In this study, the patients who visited the emergency room were enrolled if they were >18 years of age and had a confirmed infection or were with a high suspicion of infection with clear clinical symptoms. The patients who were highly suspected of having an infection with clear clinical symptoms were also required to meet at least two of the following four diagnostic criteria for systemic inflammatory response syndrome [1]: 1) body temperature of >38℃ or <36℃, 2) heart rate of >90 beats/min, 3) respiratory rate of >20 breaths/min, or partial pressure of carbon dioxide of <32 mmHg, and 4) peripheral white blood cell count of >12,000/mm3 or <4000/mm3. Then, all patients with confirmed infection or highly suspected of infection were divided into the sepsis and the non-sepsis groups according to the Sepsis-3 standard [2]. Finally, the patients with sepsis were divided into the sepsis-survival and sepsis-death groups according to whether the patient died or not. Therefore, there were no healthy controls, and all patients had infection (or were highly suspected of). It was clarified in the manuscript. - the tables and figures are clear except for figure 2, the symbols are not clear and are small, also the figure should be divided into A and B. Response: We thank the Reviewer for the comment. We agree that the group symbols were small and kind of lost in the line. Figure 2A represents the CD86%, HLA, and CD86 mRNA, while Figure 2B presents the flow cytometry outputs of CD86 among the three groups. It was revised accordingly. Reviewer #2 The authors have written a nice manuscript which is a prospective study. Response: We thank the Reviewer for his/her appreciation of our work. 1. Variables with P<0.15 in the univariable regression analysis were selected for multivariable logistic regression analysis (MVA). Why not only variables with significant value p<0.05 were taken for MVA Response: We thank the Reviewer for the comment. Due to the effect of other covariates, some characteristics not significant in the univariable regression analyses may be significant in the multivariable regression. Therefore, we selected variables with P<0.15 in the univariable regression analysis. In addition, the sample size was relatively small, particularly the sepsis-death groups, and using a higher P-value decreases the risk of missing a variable that would be significant in the multivariable analysis. P-values thresholds as high as 0.25 have been reported [3-5]. Still, we agree that using a more stringent threshold could change the variables included in the multivariable models. The results will have to be confirmed in larger multicenter studies. It was added in the Discussion. 2. Why were blood samples collected after 1st dose of antibiotics, and not at baseline? Response: We are deeply sorry for the error that occurred during manuscript preparation and translation. The blood samples were taken after admission and before the first dose of antibiotics. It was corrected. 3. How can variables with such low odds ratios [PLT (OR=0.99, 95%CI: 0.986-0.997, P=0.001), IL-10 (OR=1.01)] be statistically significant? What is the outcome of odds ratio for these variables? Response: We thank the Reviewer for the comment. It is because the determination of the odds ratio is based on the change of one unit of PLT, for example. Therefore, for each change of 1×109/L, the odds of sepsis decrease by 1%. Since the PLT levels are in the range of 91-316 ×109/L, a change of 1×109/L (which is small relative to the platelet levels) will lead to a small change in odds. It is a common observation with continuous variables in logistic regression models. For IL-10, the range was large, which could explain the results. In addition, in a multivariable analysis, each variable is adjusted for all the others [6-8]. 4. In Methods - Please write clearly what was the primary endpoint of the study. Writing to explore the value of CD86 and HLA-DR in sepsis, is very vague Response: We agree with the Reviewer. The primary study endpoint was the factors associated with a diagnosis of sepsis. The secondary study endpoint was the factors associated with mortality among patients with sepsis. It was clarified in the manuscript. 5. How many patients who were initially classified as “non-sepsis” later turned into “sepsis” during the course of hospital stay? How were these patients accounted for? Response: The Reviewer raises a good point. Twenty-three patients changed from non-sepsis to sepsis during hospitalization. They were grouped in the sepsis group after meeting the diagnostic criteria for sepsis. It was clarified in the Methods and Results. 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 Response: We revised the manuscript accordingly. 2. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. Response: It was verified. 3. Thank you for stating the following in the Acknowledgments Section of your manuscript: This work was supported by the Science and Technology Support Project for Medical Guidance (Chinese and Western Medicine) of Shanghai Municipal and the Science and Technology Commission in 2018 [No.18411967000]. The sponser had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Response: We are a little confused. The Journal asks here to add the funding information in the manuscript, but in the request just below, the Journal asks to remove all funding information from the manuscript. For now, we followed the instructions provided in point #1 and removed all funding statements from the manuscript. We note that you have provided funding information that is not 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: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Response: We follow the instructions provided in point #1 and removed all funding statements from the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 4. 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. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ Response: We are now providing the ORCID iD for the corresponding author. 5. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. Response: It was revised. 6. 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. Response: We do not provide any supporting information. References 1. Chakraborty RK, Burns B. Systemic Inflammatory Response Syndrome. StatPearls. Treasure Island (FL)2022. 2. Sansom DM, Manzotti CN, Zheng Y. What’s the difference between CD80 and CD86? Trends Immunol. 2003;24(6):314-9. Epub 2003/06/18. doi: 10.1016/s1471-4906(03)00111-x. PubMed PMID: 12810107. 3. Bursac Z, Gauss CH, Williams DK, Hosmer DW. Purposeful selection of variables in logistic regression. Source Code Biol Med. 2008;3:17. Epub 2008/12/18. doi: 10.1186/1751-0473-3-17. PubMed PMID: 19087314; PubMed Central PMCID: PMCPMC2633005. 4. Sauerbrei W, Perperoglou A, Schmid M, Abrahamowicz M, Becher H, Binder H, et al. State of the art in selection of variables and functional forms in multivariable analysis-outstanding issues. Diagn Progn Res. 2020;4:3. Epub 2020/04/09. doi: 10.1186/s41512-020-00074-3. PubMed PMID: 32266321; PubMed Central PMCID: PMCPMC7114804. 5. Chowdhury MZI, Turin TC. Variable selection strategies and its importance in clinical prediction modelling. Fam Med Community Health. 2020;8(1):e000262. Epub 2020/03/10. doi: 10.1136/fmch-2019-000262. PubMed PMID: 32148735; PubMed Central PMCID: PMCPMC7032893. 6. Ranganathan P, Pramesh CS, Aggarwal R. Common pitfalls in statistical analysis: Logistic regression. Perspect Clin Res. 2017;8(3):148-51. Epub 2017/08/23. doi: 10.4103/picr.PICR_87_17. PubMed PMID: 28828311; PubMed Central PMCID: PMCPMC5543767. 7. Roalfe AK, Holder RL, Wilson S. Standardisation of rates using logistic regression: a comparison with the direct method. BMC Health Serv Res. 2008;8:275. Epub 2008/12/31. doi: 10.1186/1472-6963-8-275. PubMed PMID: 19113996; PubMed Central PMCID: PMCPMC2661894. 8. Stoltzfus JC. Logistic regression: a brief primer. Acad Emerg Med. 2011;18(10):1099-104. Epub 2011/10/15. doi: 10.1111/j.1553-2712.2011.01185.x. PubMed PMID: 21996075. Attachments Attachment Submitted filename: Responed-letter.docx https://doi.org/10.1371/journal.pone.0302063.r002
6 Feb 2024 Decision Letter - Chiara Lazzeri, Editor PONE-D-23-11681R1Predictive value of CD86 for the occurrence of sepsis (Sepsis-3) in patients with infectionPLOS ONE Dear Dr. Zhang, 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 Mar 22 2024 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, Chiara Lazzeri Academic Editor PLOS ONE Journal Requirements: 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. 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 #3: (No Response) ******** 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 #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #3: 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 #3: No ****** 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 #3: 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 #3: The authors present a well performed observational study and the manuscript is well organized and written. The control group with infection and signs of systemic inflammation is well chosen and reflects the clinical question sepsis biomarkers are needed for. To my understanding the data availability does not fulfill PLOS requirements. The data should either be available from a repository or you should explain why not. Apart from that the manuscript is suitable or publication. Apart from that I have only minor remarks that might be considered by the author but are not relevant for the deission to publish. The discussion is a little bit lengthy reviewing a lot of molecular biology mainly of interest to a small section of the potentiall readership. Maybe citing a good review cold shorten it, but as mentioned this might just be my personell preference. In table one I am not sure if you relly should test for significant differences in septic shock, ventialition or SOFA scores. All these variables ae hallmarks of organ failure and therefore the fulfillment of sepsis-3 criteria and the differences between the sepsis and non-sepsis group are therefore not random by design. ****** 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 #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.0302063.r003
Revision 2
19 Mar 2024 Author Response Title: Predictive value of CD86 for the occurrence of sepsis (Sepsis-3) in patients with infection Journal: PLOS ONE Response to Reviewers' comments Dear Editor, We thank you for your careful consideration of our manuscript. We appreciate your response and overall positive initial feedback and made modifications to improve the manuscript. After carefully reviewing the comments made by the Reviewers, we have reorganized the literature data, modified the manuscript to improve the presentation of our results and their discussion, therefore providing a complete context for the research that may be of interest to your readers. We hope that you will find the revised paper suitable for publication, and we look forward to contributing to your journal. Please do not hesitate to contact us with other questions or concerns regarding the manuscript. Best regards, Keji Zhang Academic Editor Journal Requirements: 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 thank the Academic Editor. We verified our references. We did not cite any references flagged as retracted on PubMed. Reviewer #3 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 #3: (No Response) 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 #3: Yes 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #3: 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 #3: No Response: We thank the Reviewer for the comment. As per local regulations in our hospital, we are not allowed to upload our data on public registries for now, but the data can be made available to researchers upon reasonable request. As a result, we are unable to provide the requested deposition at this time. We understand the importance of these processes and will continue to explore possibilities for compliance with such requirements in the future. 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 #3: 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 #3: The authors present a well performed observational study and the manuscript is well organized and written. The control group with infection and signs of systemic inflammation is well chosen and reflects the clinical question sepsis biomarkers are needed for. To my understanding the data availability does not fulfill PLOS requirements. The data should either be available from a repository or you should explain why not. Apart from that the manuscript is suitable or publication. Response: We thank the Reviewer for the comment. As per local regulations in our hospital, we are not allowed to upload our data on public registries, but the data can be made available to researchers upon reasonable request. As a result, we are unable to provide the requested deposition at this time. We understand the importance of these processes and will continue to explore possibilities for compliance with such requirements in the future. Apart from that I have only minor remarks that might be considered by the author but are not relevant for the deission to publish. The discussion is a little bit lengthy reviewing a lot of molecular biology mainly of interest to a small section of the potentiall readership. Maybe citing a good review cold shorten it, but as mentioned this might just be my personell preference. Response: We thank the Reviewer for the comment. We agree with the Reviewer that this study did not examine the exact molecular biology and that the discussion, even if explanatory, might be superfluous to many of the readership. Therefore, as suggested, we cited good reviews, but kept the discussion considering that it explains our results. Hence, the interested readership will be able to seek more information. In table one I am not sure if you relly should test for significant differences in septic shock, ventialition or SOFA scores. All these variables ae hallmarks of organ failure and therefore the fulfillment of sepsis-3 criteria and the differences between the sepsis and non-sepsis group are therefore not random by design. Response: We understand the Reviewer’s comment. We simply wanted to show the characteristics of the patients. Attachments Attachment Submitted filename: Response letter.docx https://doi.org/10.1371/journal.pone.0302063.r004
27 Mar 2024 Decision Letter - Chiara Lazzeri, Editor Predictive value of CD86 for the occurrence of sepsis (Sepsis-3) in patients with infection PONE-D-23-11681R2 Dear Dr. Zhang, 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. 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, Chiara Lazzeri Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0302063.r005
Formally Accepted
1 Apr 2024 Acceptance Letter - Chiara Lazzeri, Editor PONE-D-23-11681R2 PLOS ONE Dear Dr. Zhang, 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 If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks 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. Chiara Lazzeri Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0302063.r006

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