Meta-analysis of the effectiveness and safety of robotic-assisted versus laparoscopic transabdominal preperitoneal repair for inguinal hernia

Xi Li; Yue-Juan Li; Hui Dong; Deng-Chao Wang; Jian Wei

doi:10.1371/journal.pone.0298989

Peer Review History

Original SubmissionOctober 5, 2023
14 Dec 2023 Decision Letter - Lovenish Bains, Editor PONE-D-23-32269Meta-analysis of the effectiveness and safety of robotic-assisted versus laparoscopic transabdominal preperitoneal repair for inguinal herniaPLOS ONE Dear Dr. Wei, 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. ============================== ACADEMIC EDITOR: The analysis is well-written and manuscript has good flow. It would benefit from a clearer distinction from existing studies on robotic vs. laparoscopic inguinal hernia repair. Most articles on this subject have mentioned longer operative times and increased costs with robotic repair. Do address how this work differentiates itself from previous research on the topic and adds to the literature. With experienced surgeons at the helm, robotic surgery has transcended the realm of mere feasibility and proven its versatility. While longer operative times can occur during the initial learning curve, the choice between robotic and non-robotic approaches should be individualized based on surgeon expertise, patient factors, and resource availability. ============================== Please submit your revised manuscript by Jan 28 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). 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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, Lovenish Bains, MS, FNB, FACS, FRCS (Glas), FICS, FIAGES 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. 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. Additional Editor Comments: The analysis is well-written and manuscript has good flow. It would benefit from a clearer distinction from existing studies on robotic vs. laparoscopic inguinal hernia repair. Most articles on this subject have mentioned longer operative times and increased costs with robotic repair. Do address how this work differentiates itself from previous research on the topic and adds to the literature. With experienced surgeons at the helm, robotic surgery has transcended the realm of mere feasibility and proven its versatility. While longer operative times can occur during the initial learning curve, the choice between robotic and non-robotic approaches should be individualized based on surgeon expertise, patient factors, and resource availability. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: Yes Reviewer #5: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: I Don't Know Reviewer #5: I Don't Know ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: Yes Reviewer #5: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: Yes Reviewer #5: 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: I enjoyed reading and reviewing this paper, because: the research question is well defined, the methodology is appropriate; the statistical analyses in result section are appropriate and figures and tables highlight the trends well. In discussion authors have done well to bring out important points. This paper brings forth new information worthy of dissemination. Reviewer #2: I appreciate your manuscript for taking up a meta analysis of Robotically assisted inguinal hernia repair in comparison to the laparoscopical mesh repair. the manuscript is well written. However, I have few suggestions/ observations: 1. You have mentioned Da Vinci Robot in your introduction. It is not clear whether you have focused on this brand only or included cases operated with other systems, too. and if so, was there any difference in the outcomes? 2. in the Discussion, you have mentioned 2D imaging a limitation of laparoscopic surgery as compared to 3D view available with Robotic surgery. It is now well established that the newer laparoscopic systems provide 3D imaging too. This comparison may not be appropriate now a days. 3. You have already mentioned limitations of the study due to less number of published articles especially RCTs. This statement may be further stressed in the manuscript i.e., limited data of these preliminary studies Thanks and regards. Reviewer #3: This is a very well written article on a very pertinent topic. There are a few minor grammar issues: line 115 has a clause that is not a sentence ("For a detailed overview of the selection process as shown in Figure 1); the titles of the Meta analysis results subsections have inconsistent capitalizations (line 142, 158). In the discussion (line 211), the authors state that the robotic platform "significantly reduces the risk of intraoperative damage..." but this is not supported by the results, as noted in the next sentence. Excellent job noting the limitations to the study, including ambiguous follow-up. There are two other considerations for robotics not mentioned (worth consideration): perceived improved ergonomics and less steep learning curve for robotic inguinal hernia repair. In the Figures, there are no units labeled (Figure 2 = minutes?). There is wide variability of operative time in the included studies (30 to 109 minutes), which can give a reader pause regarding the strength of the data input with such variable times. For Figure 3, presumably the unit is Days; this suggests that Choi et al's study had a mean operative time of 30 minutes and a mean stay of 3.4 days, which is either an error or quite an outlier that again makes the data suspect. Figure 4 presumably has the unit of US dollar (100?) and again, there is a very wide variance (3-52). An important question often neglected is whether the authors calculated the cost of acquiring the robot into the cost (where that acquisition cost for laparoscopy towers and tools if often not included, offering an unfair cost comparison). Clarification of the above would greatly strengthen this article and its discussion points. Overall, this study has an excellent design and is very well written. Reviewer #4: I complement the authors for a comprehensive meta-analysis on this topic. A few minor suggestions/observations are as appended in the attached reviewer file. The authors are requested to go through the same and submit satisfactory rebuttals. Reviewer #5: The authors have reported a meta-analysis of the effectiveness and safety of robotic-assisted versus laparoscopic transabdominal preperitoneal repair for inguinal hernia. The Meta-analysis though well written does not convey any new information that is not already available in literature. ****** 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: Professor Dhananjaya Sharma Reviewer #2: Yes: Mohammed Amir Reviewer #3: No Reviewer #4: Yes: Shrirang Vasant Kulkarni Reviewer #5: 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. Attachments Attachment Submitted filename: PLOS rTAPP Vs lTAPP.pdf https://doi.org/10.1371/journal.pone.0298989.r001
Revision 1
17 Dec 2023 Author Response We would like to thank you for your help with this manuscript. We would also like to thank the reviewer for their professional comments. We have revised the manuscript substantially after reading the comments provided by the reviewer. The revisions are shown in coloured text. The following are our point-by-point responses to the reviewer(s)’ comments. Response to Reviewer Reviewer #1 1. I enjoyed reading and reviewing this paper, because: the research question is well defined, the methodology is appropriate; the statistical analyses in result section are appropriate and figures and tables highlight the trends well. In discussion authors have done well to bring out important points. Response: Thank you very much for your positive feedback and thorough review of our manuscript. We appreciate your acknowledgment of the well-defined research question, appropriate methodology, and the sound statistical analyses in the results section. Your constructive feedback is valuable to us, and we are committed to addressing any suggested improvements to enhance the overall quality of the manuscript. Reviewer #2 I appreciate your manuscript for taking up a meta analysis of Robotically assisted inguinal hernia repair in comparison to the laparoscopical mesh repair. the manuscript is well written. However, I have few suggestions/ observations: 1. You have mentioned Da Vinci Robot in your introduction. It is not clear whether you have focused on this brand only or included cases operated with other systems, too. and if so, was there any difference in the outcomes? Response: In the introduction, we mentioned the Da Vinci Robot to emphasize the technological background of robot-assisted inguinal hernia repair. In our study, we did not exclusively focus on a specific robotic system but included cases operated with various systems. These systems include, but are not limited to, the Da Vinci Robot. We believe that this broad coverage contributes to a more comprehensive understanding of the application of robot-assisted surgery in inguinal hernia repair. 2. in the Discussion, you have mentioned 2D imaging a limitation of laparoscopic surgery as compared to 3D view available with Robotic surgery. It is now well established that the newer laparoscopic systems provide 3D imaging too. This comparison may not be appropriate now a days. Response: Thank you for your thoughtful review and valuable comments. We appreciate your observation regarding the mention of 2D imaging as a limitation of laparoscopic surgery in the Discussion section. We acknowledge the advancements in laparoscopic technology, including the availability of newer systems that provide 3D imaging. This represents a significant development that enhances the capabilities of laparoscopic surgery. In light of this, we have revised the Discussion section to accurately reflect the current state of laparoscopic imaging technology and to avoid any inappropriate comparisons with robotic surgery. Inappropriate comparisons have already been removed from the Discussion section of the revised manuscript. 3. You have already mentioned limitations of the study due to less number of published articles especially RCTs. This statement may be further stressed in the manuscript i.e., limited data of these preliminary studies Response: Thank you for your insightful comments. We appreciate your suggestion to further stress the limitations of our study related to the scarcity of published articles, particularly randomized controlled trials (RCTs). In response to your feedback, we have enhanced the emphasis on this limitation in the manuscript. Specifically, we have highlighted the challenge posed by the limited number of available studies, especially RCTs, and the potential impact on the robustness of our findings. This has been addressed in the revised version to provide a more comprehensive discussion on the limitations of our research. Reviewer #3 1.This is a very well written article on a very pertinent topic. There are a few minor grammar issues: line 115 has a clause that is not a sentence ("For a detailed overview of the selection process as shown in Figure 1); the titles of the Meta analysis results subsections have inconsistent capitalizations (line 142, 158). Response: (1) Thank you for your careful review and constructive feedback. We appreciate your keen observation regarding the grammar issue on line 115. Following your suggestion, we have revised the sentence to enhance clarity. The modified sentence now reads: "A detailed overview of the selection process is shown in Figure 1." (2) We have carefully addressed the inconsistency in capitalizations for the titles of the Meta-analysis results subsections, as pointed out in your comments. 2.In the discussion (line 211), the authors state that the robotic platform "significantly reduces the risk of intraoperative damage..." but this is not supported by the results, as noted in the next sentence. Response: Thank you for your careful review and valuable feedback. We appreciate your attention to detail and have duly noted your concern regarding the statement in the discussion (line 211) about the robotic platform "significantly reducing the risk of intraoperative damage." In response to your observation, we have revised the manuscript to accurately reflect the intended meaning. The modified sentence now reads: "The repair of inguinal hernia using RTAPP is deemed safe. This meta-analysis suggests that there is no statistically significant difference between robotic and laparoscopic approaches in terms of overall complication rate, incidence of seroma, and readmission rate." We believe this modification aligns with your comments and better represents the study's findings. If you have any further suggestions, please feel free to let us know. 3. Excellent job noting the limitations to the study, including ambiguous follow-up. There are two other considerations for robotics not mentioned (worth consideration): perceived improved ergonomics and less steep learning curve for robotic inguinal hernia repair. Response: Thank you for your positive feedback and insightful suggestions. In response to your valuable comments, we have made relevant modifications to the limitations section. Specifically, we have included considerations for perceived improved ergonomics and a less steep learning curve for robotic inguinal hernia repair. The revised section now contains the statement: "Perceived improved ergonomics and less steep learning curve for robotic inguinal hernia repair may have an impact on the study results and conclusions." 4. In the Figures, there are no units labeled (Figure 2 = minutes?). There is wide variability of operative time in the included studies (30 to 109 minutes), which can give a reader pause regarding the strength of the data input with such variable times. For Figure 3, presumably the unit is Days; this suggests that Choi et al's study had a mean operative time of 30 minutes and a mean stay of 3.4 days, which is either an error or quite an outlier that again makes the data suspect. Figure 4 presumably has the unit of US dollar (100?) and again, there is a very wide variance (3-52). An important question often neglected is whether the authors calculated the cost of acquiring the robot into the cost (where that acquisition cost for laparoscopy towers and tools if often not included, offering an unfair cost comparison). Response: (1) We have reconfirmed the data related to operative time outcome measures in the studies, and the information is accurate. The unit for operative time is minutes. The meta-analysis reveals significant variation in the operative time required for RTAPP across different studies, potentially influenced by factors such as surgeon experience, surgical complexity, and limited sample sizes. We have addressed this concern in the revised discussion section, specifically in the segment discussing operative times. If you have any further suggestions or need additional clarification, please feel free to let us know. (2) Thank you for your careful review of our manuscript and for raising questions regarding Figure 3. We appreciate your concerns and are willing to provide some explanations to address any potential misunderstandings. The unit in Figure 3 is indeed "Days," which is the time unit we have applied in the manuscript. Regarding the data from Choi et al.'s study, we have re-examined our data, and we can confirm the accuracy of the reported values. Choi et al.'s study indicates an average operative time of 30 minutes and an average length of stay of 3.4 days. While these data may appear to differ from some other studies, we would like to emphasize that variations in study design and patient populations can lead to different outcomes. In our research, we adhered to rigorous methodology and conducted thorough data analysis to ensure the reliability and accuracy of our results. We understand that these data may deviate from average values reported in some literature, but we believe this reflects the diversity of our study population and the specific context of our research. Thank you for your valuable feedback, and we look forward to hearing any further suggestions you may have. (3) Thank you for your thorough review and valuable comments. Regarding Figure 4, the unit of cost is in thousand US dollars ($1000), and we have reconfirmed the accuracy of the data from the original texts of the three studies. The reported values are accurate and precise. In terms of cost calculation, we appreciate your astute observation. Among the three studies, only Prabhu et al.'s 2020 study provided a detailed breakdown of the cost components. Costs per case were collected and reported, including total cost, operating room cost (calculated based on the cost per minute of operating room time required for the case), and disposable/reusable cost. The latter was calculated to cover both disposable and reusable materials, including robotic instruments. Reviewer #4 1. Inguinal hernia, being a clinical diagnosis, ultrasound may not be required as an inclusion criteria. Response: Thank you for your feedback. Considering that inguinal hernia is primarily diagnosed clinically, we acknowledge that ultrasound may not be an essential inclusion criterion. Therefore, we have modified the study criteria accordingly in the revised manuscript. 2. This has, to a certain extent, limited the application of this technology to patients in underdeveloped regions and those without health insurance coverage. '..to patients in underdeveloped..' may be replaced with '..for patients in underdeveloped..'. Response: Thank you for your valuable feedback. We appreciate your insightful suggestions. Following your recommendation, we have made the necessary modifications in the revised manuscript. The sentence now reads as follows: "This has, to a certain extent, limited the application of this technology for patients in underdeveloped regions and those without health insurance coverage." 3. Laparoscopic systems also may offer three-dimensional images. Response: Thank you for your thoughtful review and valuable comments. We appreciate your observation regarding the laparoscopic systems also may offer three-dimensional images. We acknowledge the advancements in laparoscopic technology, including the availability of newer systems that provide 3D imaging. This represents a significant development that enhances the capabilities of laparoscopic surgery. In light of this, we have revised the Discussion section to accurately reflect the current state of laparoscopic imaging technology and to avoid any inappropriate comparisons with robotic surgery. Inappropriate comparisons have already been removed from the Discussion section of the revised manuscript. Reviewer #5 1. The authors have reported a meta-analysis of the effectiveness and safety of robotic-assisted versus laparoscopic transabdominal preperitoneal repair for inguinal hernia. The Meta-analysis though well written does not convey any new information that is not already available in literature. Response: Thank you for your thorough review of our manuscript and your valuable suggestions. We have taken note of your observation that our meta-analysis may not have provided novel information not already present in the existing literature. However, we would like to elaborate on some specific aspects of our study to provide a clearer understanding. Firstly, in this research, we included 10 studies, of which 5 were recently published in 2023. This is a distinctive feature of our study, as we made a concerted effort to ensure that the latest data and research findings were incorporated into our analysis, aiming to offer readers the most up-to-date insights into current practices. Secondly, we intentionally focused solely on the TAPP (transabdominal preperitoneal) surgical approach to avoid the influence of other surgical methods on our results. This decision was made to make our study more focused and targeted, providing detailed information about a specific surgical approach. We believe this approach contributes to a deeper understanding of the effectiveness and safety of TAPP surgery while minimizing interference from other surgical methods, thus enhancing the reliability of our conclusions. While our study may not have introduced entirely new perspectives, we hope that by including the latest research and concentrating on the TAPP surgical approach, we have offered readers a more comprehensive and updated insight. We are open to further suggestions from you to enhance the quality and contribution of our research. Thank you once again for your review and feedback. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0298989.r002
2 Feb 2024 Decision Letter - Lovenish Bains, Editor Meta-analysis of the effectiveness and safety of robotic-assisted versus laparoscopic transabdominal preperitoneal repair for inguinal hernia PONE-D-23-32269R1 Dear Dr. Wei, 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. 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 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, Lovenish Bains, MS, FNB, FACS, FRCS (Glas), FICS, FIAGES Academic Editor PLOS ONE Additional Editor Comments (optional): 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 #2: All comments have been addressed Reviewer #4: 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 #2: Yes Reviewer #4: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes Reviewer #4: 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 #2: Yes Reviewer #4: 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 #2: Yes Reviewer #4: 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 #2: Thank you very much for addressing reviewers' comments including mine. It appears appropriate and well balanced now. 7 Reviewer #4: (No Response) ****** 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 #2: No Reviewer #4: Yes: SHRIRANG VASANT KULKARNI ******** https://doi.org/10.1371/journal.pone.0298989.r003
Formally Accepted
15 Feb 2024 Acceptance Letter - Lovenish Bains, Editor PONE-D-23-32269R1 PLOS ONE Dear Dr. Wei, 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. Lovenish Bains Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0298989.r004

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