Peer Review History
| Original SubmissionJanuary 4, 2020 |
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PONE-D-20-00301 Foreskin surface area is not associated with sub-preputial microbiome composition or penile cytokines. PLOS ONE Dear Dr. Prodger, 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. Specifically, Reviewer 1 has detailed a weak correlation and the suggestion of submission as a short report. Alternately, additional information in a fuller manuscript would be appropriate. We would appreciate receiving your revised manuscript by Apr 16 2020 11:59PM. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols Please include the following items when submitting your revised manuscript:
Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Noreen J. Hickok, Ph.D. Academic Editor PLOS ONE Journal Requirements: 1. When submitting your revision, we need you to address these additional requirements.
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 http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. 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. [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: Partly Reviewer #2: Yes ********** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No 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: In this manuscript, Kigozi et al. analyzed the association between the foreskin surface area and HIV-1 risk by measuring the correlation between foreskin size and anaerobes or pro-inflammatory cytokines. While I found this work of interests, the following concerns should be raised. 1. Manuscript type. This study reports a very specific result of weak correlations between the foreskin surface area and anaerobes or pro-inflammatory cytokines. Considering the significance and the manuscript length, in this case, I would suggest the authors to format it as a “Brief report”, “Communications” or “Letter to the editor” rather than a “Research article”. 2. Technical issues. The analysis on abundance of bacteria was based-on 16S rRNA profiling, mainly on Genus-level. I strongly recommend the authors to (a) go deeper on 97% or 99% OTU level for higher precision, and (b) also from the functional aspect using 16S-based function annotation method (e.g. PICRUSt). 3. In the current results, since there is no individual genus was associated with the foreskin surface area that may influence the risk of HIV-1, is there any probability that the risk is correlated with the combination of multiple organisms? A machine-based approach / regression analysis of multiple-taxon / PCA may inspire new findings, or further confirm the current results. 4. Line #126, for specific anaerobic genera previously found to be associated with HIV-1 risk, each of them should be cited, or linked to the previous studies (e.g. listed in a table to summarize each of the genera and its citation(s)). 5. The resolution of Figure 1 should be improved. Reviewer #2: Thank you for the opportunity to review this brief, but well-written manuscript. The study appears well-conducted and contributes novel information to the study of MMC and HIV risk. I have only minor comments: Methods: • It seems unusual to have ethics information at the end of the methods. If this is a journal style requirement, fine, but otherwise it is more common to lead with ethics information. • Which R version was used? Any specific packages? Results: • Graphical results of numeric IL-8 analysis are mentioned in the methods but not presented. • It’s possible that the genera previously associated with HIV risk are incorrect. Was a larger analysis conducted? I don’t necessarily advocate a fishing expedition, but given the negative results, perhaps other genera might be important here. Discussion: • I am not sure about the strength of the conclusions given the fact that this is a single, relatively small study. Changing “indicating” to “suggesting” on line 155 may adequately temper the language. Supplement: • Total bacterial load and quantitative IL8 data are not present in the spreadsheet ********** 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: Ryan Cook [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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. |
| Revision 1 |
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PONE-D-20-00301R1 Foreskin surface area is not associated with sub-preputial microbiome composition or penile cytokines. PLOS ONE Dear Dr. Prodger, 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. Specifically, I have asked you to expand your discussion to place it more securely in the context of the field, especially your previous work. We would appreciate receiving your revised manuscript by Jun 08 2020 11:59PM. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols Please include the following items when submitting your revised manuscript:
Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Noreen J. Hickok, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (if provided): These findings are of significance because they (1) show no correlation between foreskin size and anaerobic bacterial load and (2) because they are on update on your previous findings that DID suggest a correlation. Could you please address your previous studies and succinctly point out the assumptions/analyses/small sample sizes that led you to draw your previous conclusions...and how they differ from your current study. Also, please address the issue that these are all adults who are being circumcised to lower their chances of contracting AIDS yet they don't have AIDS and they presumably have been sexually active. Is it possible that these subjects are also skewed? Thus, please bring the paper into context on the level of subject selection and previous studies. [Note: HTML markup is below. Please do not edit.] [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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. |
| Revision 2 |
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PONE-D-20-00301R2 Foreskin surface area is not associated with sub-preputial microbiome composition or penile cytokines. PLOS ONE Dear Dr. Prodger, 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. I am afraid that I am asking you to look at your discussion again and to expand this section as detailed below. We would appreciate receiving your revised manuscript by Jun 13 2020 11:59PM. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols Please include the following items when submitting your revised manuscript:
Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Noreen J. Hickok, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (if provided): I am sorry, but I still ask you to expand your Conclusions/Discussion section. In your introduction, you state, "We previously reported that on the penis both the density of specific anaerobic bacterial genera 67 and local levels of pro-inflammatory cytokines are associated with increased risk of HIV-1 68 seroconversion in uncircumcised men [5, 6]. Additionally, the abundance of anaerobic genera 69 on the penis correlates positively with local concentrations of these cytokines [5]. One possible 70 interpretation for these findings is that anaerobic bacteria increase HIV-1 risk by driving penile 71 inflammation. Mucosal inflammation is a demonstrated risk factor for cervico-vaginal HIV-1 72 acquisition, and is associated with an increased number and relative susceptibility of HIV-1 73 target cells in the mucosa [7, 8], altered dendritic cell sampling [9], and decreased epithelial 74 barrier function [10, 11]. 75 An epidemiologic study showed that a larger foreskin surface area is also associated with an 76 increased risk of HIV-1 seroconversion [12]. Since coverage of the glans on the non-erect penis 77 is variable and dependent on foreskin size, a deeper foreskin fold from a larger foreskin could 78 result in a less aerobic environment that might preferentially promote anaerobic bacterial growth 79 and induce inflammation. However, it has not yet been explored if foreskin size is associated 80 with penile microbiome composition and local inflammation." I ask that you indicate any weaknesses in your study as well as putting these studies into the context of the other studies that you have cited. Some explanation of what they found and what you found, other than it is not what you found, is needed. Please expand this section so as to increase its relation to the publications in the field. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: [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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. |
| Revision 3 |
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Foreskin surface area is not associated with sub-preputial microbiome composition or penile cytokines. PONE-D-20-00301R3 Dear Dr. Prodger, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, 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 enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and 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. With kind regards, Noreen J. Hickok, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: |
| Formally Accepted |
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PONE-D-20-00301R3 Foreskin surface area is not associated with sub-preputial microbiome composition or penile cytokines. Dear Dr. Prodger: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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. Noreen J. Hickok Academic Editor PLOS ONE |
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