In vitro cytotoxicity (irritant potency) of toothpaste ingredients

Shaira R. Kasi; Sanne Roffel; Mutlu Özcan; Susan Gibbs; Albert J. Feilzer

doi:10.1371/journal.pone.0318565

Peer Review History

Original SubmissionJuly 31, 2024
11 Sep 2024 Decision Letter - Tanay Chaubal, Editor PONE-D-24-31912In vitro cytotoxicity (irritant potency) of toothpaste ingredientsPLOS ONE Dear Dr. Feilzer, 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 Oct 26 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. 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If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Additional Editor Comments: I thank you for submitting an interesting manuscript. However, there are comments made by reviewers which potentially could make your manuscript more robust. [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: N/A Reviewer #2: N/A ****** 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: No 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: The study highlights the potential for certain toothpaste ingredients to harm the cells. The strength of the paper is the use of a bilayered RHG model, which enhances the relevance of the findings to human oral health. However, the study's limitation lies in the inability to directly compare in vitro concentrations with those in commercial toothpaste, which could affect the interpretation of the results. These are stated as limitation in the manuscript. Authors are requested to make certain clarifications in the paper. 1. Were the experiments conducted in triplicates/duplicates? Were the data from MTT values normalized? before comparing? If not, it is advised to show the data (MTT observations) properly in a table form. 2. What statistcal analyses was performed? please state and show statistical values legibly. 3. The changes in the histology is not mentioned in detail anywhere in the manuscript. It is required to state and show observde changes clearly. what are the changes observed. 4. Photographs depicting the RHG model and preparation will benefit readers. it is recommended to add them. 5. The discussion part can be improved in terms of comparing the obsrvations to exisiting evidences in the literature rather than just reporting the obervations. Reviewer #2: The aim and purpose of the work is very well exposed. This study reminds so interesting and have got and excellent clinical transpolation. Please describe in more detail the statistical analysis used. ****** 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: Spoorthi Ravi Banavar Reviewer #2: Yes: Evelin Bachmeier ******** [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.0318565.r001
Revision 1
29 Oct 2024 Author Response 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: N/A Reviewer #2: N/A ________________________________________ 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: No Original raw data are uploaded as supplementary file 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: The study highlights the potential for certain toothpaste ingredients to harm the cells. The strength of the paper is the use of a bilayered RHG model, which enhances the relevance of the findings to human oral health. However, the study's limitation lies in the inability to directly compare in vitro concentrations with those in commercial toothpaste, which could affect the interpretation of the results. These are stated as limitation in the manuscript. Authors are requested to make certain clarifications in the paper. 1. Were the experiments conducted in triplicates/duplicates? Were the data from MTT values normalized? before comparing? If not, it is advised to show the data (MTT observations) properly in a table form. The experiments are conducted in duplicate. The data from the MTT are per culture and test material compared to that of unexposed RHG of the same culture as well as to the values of exposure to the test vehicle only. The data are ‘normalized’ to the results of the exposure to the test vehicle per culture. Clarification is added to the text: “All experiments were conducted in two independent experiments, each using a different batch of RHG which had been grown separately at different times.” “The data from the MTT assay are per RHG exposed to a test material compared to that of unexposed RHG of the same RHG batch as well as to the values obtained from exposure to the test vehicle only. The data are shown normalized to the results of the exposure to the test vehicle per culture.” 2. What statistical analyses was performed? please state and show statistical values legibly. Data in duplicate are reported as average and standard deviation. The calculation of the EC10 and EC 50 values was done by 4-point logistic regression. The text is changed: “Values were obtained by linear regression 4 point logistic analysis based on changes in metabolic activity (MTT). The web-based EC50 Calculator of AAT Bioquest [28] was used.” 3. The changes in the histology is not mentioned in detail anywhere in the manuscript. It is required to state and show observed changes clearly. What are the changes observed. The observed changes are added to the figure legend (Fig. 3) 4. Photographs depicting the RHG model and preparation will benefit readers. it is recommended to add them. A figure (Fig. 1) depicting the RHG model in a MTT is added to the manuscript. 5. The discussion part can be improved in terms of comparing the observations to existing evidences in the literature rather than just reporting the observations. The plan involved initially assessing the toxicity of all potentially harmful ingredients in toothpaste using the MTT assay based on the RHG model. After this study, we will begin testing toothpastes containing these ingredients. The current results reflect a single exposure to the test materials. For instance, when testing a toothpaste, these substances may either attenuate or potentiate each other’s effects. Additionally, we emphasized that our MTT assay was conducted in an RHG model rather than with single cell types. Therefore, we decided not to compare our observations with the existing scientific literature at this stage. Furthermore, we have already demonstrated that the RHG model produces similar tissue responses when exposed to materials, as shown in Buskermolen’s study. Reviewer #2: The aim and purpose of the work is very well exposed. This study reminds so interesting and have got and excellent clinical transpolation. Please describe in more detail the statistical analysis used. After the thorough review of the PLOS reviewers and during answering their questions, we realized that the linear regression used on the MTT data was outdated. Consequently, we reanalyzed the data using a 4-point logistic analysis. We replaced the bar graphs ( Fig. 2) with logistic regression plots, which offer better insights into the slope differences between the test materials. We have clarified in the text that the 4-point logistic analysis was performed using ATT’s web-based calculator. All necessary data to reproduce the analysis have been included in a supplementary file. 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: Spoorthi Ravi Banavar Reviewer #2: Yes: Evelin Bachmeier ________________________________________ [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. ________________________________________ In compliance with data protection regulations, you may request that we remove your personal registration details at any time. (Remove my information/details). Please contact the publication office if you have any questions. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0318565.r002
27 Dec 2024 Decision Letter - Tanay Chaubal, Editor PONE-D-24-31912R1In vitro cytotoxicity (irritant potency) of toothpaste ingredientsPLOS ONE Dear Dr. Feilzer, 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: I thank you for responding to the reviewers' comments. However, there still minor revisions which are required as per reviewers' comments. ============================== Please submit your revised manuscript by Feb 10 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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, Tanay Chaubal 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 #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Thank you for addressing our comments. The manuscript describes the methods and results as required. However, it is recommended to always perform experiments in triplicates and not duplicates. Additionally, I would like to point that the standard deviations noted in the experiments are very wide and this is a point of concern especially when done in duplicates. If this cannot be addressed now, please mention in the limitation. Additionally, it is recommended to depict the pictures of the RHG model before and during histology. this will benefit readers. Reviewer #2: All request have been answered. Recommendatons have been attended. The article is very interesting. Ethical aspects have been taken into account. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Spoorthi Ravi Banavar Reviewer #2: Yes: Evelin Bachmeier ******** [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.0318565.r003
Revision 2
9 Jan 2025 Author Response Reviewer #1: Thank you for addressing our comments. The manuscript describes the methods and results as required. However, it is recommended to always perform experiments in triplicates and not duplicates. Additionally, I would like to point that the standard deviations noted in the experiments are very wide and this is a point of concern especially when done in duplicates. If this cannot be addressed now, please mention in the limitation. Additionally, it is recommended to depict the pictures of the RHG model before and during histology. this will benefit readers. We add the following text to the discussion section: The MTT values exhibited for certain chemicals a significant variability at specific concentrations, particularly in the steep sections of the graphs, leading to high standard deviations. However, since the X-axis is on a logarithmic scale and is used to determine EC10 and EC50 values, this variability does not impact the final potency scoring. This study followed a previously established standard operating procedure for the Epidermal Equivalent potency assay.[29] This procedure outlines how to perform dose-finding for any unknown coded chemical (with unknown molecular mass) to obtain an EC50 value by conducting two independent experiments. We previously demonstrated that this methodology is transferable to various commercially available and in-house reconstructed skin models, even in international ring studies. [6] Now, we show that it is not only suitable for assessing skin irritant potency in reconstructed human skin models but can also be applied to reconstructed human gingival models. N.B. also we add one reference M. A. T. Teunis et al., “International ring trial of the epidermal equivalent sensitizer potency assay: Reproducibility and predictive capacity,” ALTEX, vol. 31, no. 3, pp. 251–268, 2014, doi: 10.14573/altex.1308021. Additionally we changed figure 3 in accordance with the suggestion of the reviewer. Attachments Attachment Submitted filename: Response to the reviewers 9-1-25.docx https://doi.org/10.1371/journal.pone.0318565.r004
19 Jan 2025 Decision Letter - Tanay Chaubal, Editor In vitro cytotoxicity (irritant potency) of toothpaste ingredients PONE-D-24-31912R2 Dear Dr. Albert Joseph Feilzer, 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, Tanay Chaubal 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 #1: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Thank you for addressing my review comments. If possible, it would be good (recommend) including detailed image of RHG model and its preparation, before and after histology. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Spoorthi Ravi Banavar ******** https://doi.org/10.1371/journal.pone.0318565.r005
Formally Accepted
22 Jan 2025 Acceptance Letter - Tanay Chaubal, Editor PONE-D-24-31912R2 PLOS ONE Dear Dr. Feilzer, 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. Tanay Chaubal Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0318565.r006

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