Peer Review History

Original SubmissionNovember 22, 2024
Decision Letter - Milad Khorasani, Editor

Dear Dr. Sajo,

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 Apr 14 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.

  • 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'.
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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.

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We look forward to receiving your revised manuscript.

Kind regards,

Milad Khorasani, PhD

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

Reviewer #1: PlosOne Review NR 20/1/25

Clinico-pathological and treatment characteristics of HIV and non-HIV related vulvar cancers: Analysis of a South African cohort

Good study, with comprehensive data. Large HIV positive cohort adds value

Minor

1. Include the core diagnosis in the Abstract, Objective and Materials and Methods ie. vulvar cancer

2. Line 45: “Globally, it accounted for over 45 000 new cases and 17 000 deaths” What is the time period referred to?

3. Correct minor grammatical errors throughout: space between age and year, data was…, p value lower case in Table 1, spelling

4. Table 1: Is the mean or median tumour size documented? Is the p value for co-morbidity as a group or for DM only?

5. In the Discussion on Age, what % of patients in these referenced studies were HIV pos ie. were similar cohorts compared?

Major:

1. Stats in Table 1

Review stats in Table 1eg. HIV neg (69=21.8%) and HIV pos (248=78.2%) for the FIGO stage Early 32 (28.1) vs 82 (71.9) and Advanced 37 (18.3) vs 166 (81.8), with changing the denominator: Early HIV neg 32/69=46.4% vs 82/248=33% in HIV pos and Advanced HIV neg 37/69=53.6% and HIV pos 166/248=66.9%. The change in denominator allows for comparison of HIV pos and HIV neg groups, as the large number of HIV pos cases is a study strength.

2. Remove replication of Results described in words, when already presented in Tables

Reviewer #2: The study investigated the clinical, pathological, and treatment characteristics of patients of HIV and non-HIV-related vulvar cancers. However, my concerns/suggestions are not necessarily a reflection of the quality of the work as the following:

• Although this may seem like a minor issue, the abstract lacks depth and feels somewhat diluted. It merely touches on the topic without offering substantial insights. The manuscript is submitted as a research article, yet its primary objective aligns with a review perspective. Please refine the abstract and introduction to make it more concise, informative, and aligned with the intended research focus.

• Some comments about figures/tables here and there!

o In Figure 1:

� The chart could benefit from data labels for individual points, especially for key inflection years like 2016 or 2019.

� The notation is somewhat ambiguous; clarifying which trend it applies to would improve interpretability.

� Using exponential for cases and linear for mean age may confuse readers unless justified. A brief explanation of why these particular trends were chosen would add clarity.

� The chart lacks contextual information such as the type of cases being studied, geographical scope, or contributing factors that might explain the trends.

� Consider normalizing the scales for easier visual comparison of the trends.

o In Figure 2:

� The chart does not provide information about the population size or geographic scope. Are these proportions relative to the general population, specific cohorts, or testing populations?

� The y-axis labeled “Proportion of HIV status” is vague. Are the proportions normalized to a specific population size or expressed as percentages?

� The chart does not stratify cases by other variables such as age, gender, or risk factors, which could provide deeper insights.

o In figure 3:

� The chart does not specify whether the frequencies are raw counts or adjusted for population growth, age standardization, or other factors.

� There is no indication of geographic or demographic focus.

� The dual y-axes might confuse some viewers, as it is not immediately clear that each cancer is plotted on a different scale.

o Their uploaded file, named as Excel sheet for PLoS ONE manuscript Nov 5, 2024, has some areas of discrepancy such as:

� The Excel sheet includes several derived variables (e.g., tsize_cat5, age_cat9), which may need further clarification to match the previously provided raw data tables, reflecting the information's depth!

� Some columns, like trend and multiple categorizations (e.g., agecat3, age_cat8, age_cat9), may not directly align with the manuscript’s core tables and could require filtering or explanation to ensure relevance reflecting extraneous data.

• While this study marks substantial progress, it would benefit from more rigorous analysis and a deeper interpretation of the findings to strengthen its clinical significance and improve reader comprehension. Additionally, certain sections lack coherence. For instance:

o The introduction presents a limited rationale and requires further expansion to offer a more thorough and well-rounded explanation.

o The results section should go beyond merely presenting data by providing deeper analysis and interpretation, ensuring a logical and seamless flow between findings.

o The clarity and flow, typographical accuracy, and consistency must be part of improvements as essential sections to strengthen the study’s impact and contribution to the field. Consequently, the results demand a more comprehensive analysis and critique to enhance their clarity and relevance.

Reviewer #3: The statastical retrospective review of vulvar cancer patients sheds light to important considerations for women living with HIV for increased monitoring and surveillance to potentially catch vulvar cancers in this population at early disease stages. Minor typographical revisions.

**********

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Reviewer #1: Yes:  Dr Nadine Rapiti

Reviewer #2: No

Reviewer #3: Yes:  Patricia Brothers

**********

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Attachments
Attachment
Submitted filename: PONE-D-24-50571_reviewer edits P.B12FEB2025.pdf
Revision 1

Reviewers’ comments

Reviewer #1: Minor

1. Include the core diagnosis in the Abstract, Objective and Materials i.e. vulvar cancer

Response: The Abstract has been reviewed to include vulvar cancer

2. Line 45: “Globally, it accounted for over 45 000 new cases and 17 000 deaths” What is the time period referred to?

Response: The statement has been corrected as ‘Globally, it accounted for over 45 000 new cases and 17 000 deaths in the 2020 global cancer estimate with age-standardized incidence rate (ASIR) and mortality of 0.9 and 0.3 respectively’

3. Correct minor grammatical errors throughout: space between age and years, data was …p value lower case in Table 1, spelling

Response: Corrections have been made to address the grammatical errors, spellings and spaces included between age and years, and lower case for p values.

4. Table 1: Is the mean or median tumour size documented? Is the p value for co-morbidity as a group or for DM only?

Response: Yes, the average largest diameter of tumour size is compulsory information that is captured in the oncology files of patients with cervical and vulvar cancer in our institution. The p value was for the group of co-morbidity.

5. In the Discussion of Age, what % of patients in these referenced studies were HIV pos i.e. were similar cohorts compared?

Response: Most of the studies from these countries with an average age at diagnosis above 60 years did not report the proportions of HIV in their cohorts which reflects the low prevalence of HIV to allow for comparison in those regions. However, studies from sub-Saharan Africa with high prevalence of HIV, especially the Southern African countries, reported proportions of HIV in the cohorts of vulvar cancers, ranging between 23% and 89%. We did not discuss the proportions of the cohorts with HIV in the discussion on age to avoid repetition as this was mentioned in the paragraphs that reported on HIV.

Major:

1. Review stats in Table 1eg. HIV neg (69=21.8%) and HIV pos (248=78.2%) for the FIGO stage Early 32 (28.1) vs 82 (71.9) and Advanced 37 (18.3) vs 166 (81.8), with changing the denominator: Early HIV neg 32/69=46.4% vs 82/248=33% in HIV pos and Advanced HIV neg 37/69=53.6% and HIV pos 166/248=66.9%. The change in denominator allows for comparison of HIV pos and HIV neg groups, as the large number of HIV pos cases is a study strength.

Response: Thank you for this suggestion. The entire table has been corrected to include the column outputs rather than the row outputs that were initially captured in the table.

2. Remove replication of results described in words, when already presented in the tables.

Response: We have removed duplication of results in words that were already presented in the tables or charts except where to give more clarity.

Reviewer #2:

The study investigated the clinical, pathological, and treatment characteristics of patients of HIV and non-HIV-related vulvar cancers. However, my concerns/suggestions are not necessarily a reflection of the quality of the work as the following:

Although this may seem like a minor issue, the abstract lacks depth and feels somewhat diluted. It merely touches on the topic without offering substantial insights. The manuscript is submitted as a research article, yet its primary objective aligns with a review perspective. Please refine the abstract and introduction to make it more concise, informative, and aligned with the intended research focus.

Response: The study was aimed to describe the clinical, pathological, and treatment characteristics of patients of HIV and non-HIV-related vulvar cancers by retrospectively reviewing this information. It was not a review article but a clinical audit. We have reviewed the abstract and the introduction sections to give better clarity and conciseness to information being passed by the research.

Some comments about figures/tables here and there, study investigated the clinical, pathological and treatment:

Figure 1:

• The chart could benefit from data labels for individual points, especially for key inflection years like 2016 or 2019.

The notation is somewhat ambiguous; clarifying which trend it applies to would improve interpretability.

• Using exponential for cases and linear for mean age may confuse readers unless justified. A brief explanation of why these particular trends were chosen would add clarity.

• The chart lacks contextual information such as the type of cases being studied, geographical scope, or contributing factors that might explain the trends.

• Consider normalizing the scales for easier visual comparison of the trends.

Response: The chart had been modified to answer the raised queries including data labels. Figure 1a showed the raw data while figure 1b showed the normalized scale.

The trendlines were drawn based on the raw data rather than being adjusted for population size or other demographic standardization. The exponential curve was used as it followed the data distribution more. However, to avoid ambiguity, we have changed the trendlines to linear for both variables and this has been corrected in the result. Also, limited individual data labels were included to avoid clumsiness of notation. A chart showing normalized scale was included to enhance clarity. Geographic or demographic population was not considered in creating the chart. It was based on raw count/frequency of vulvar cancers. There was no identifiable factors for the trend except for the possibility of HIV as explained in the discussion section.

Figure 2:

• The chart does not provide information about the population size or geographic scope. Are these proportions relative to the general population, specific cohorts, or testing populations?

• The y-axis labeled “Proportion of HIV status” is vague. Are the proportions normalized to a specific population size or expressed as percentages?

• The chart does not stratify cases by other variables such as age, gender, or risk factors, which could provide deeper insights.

Response: The chart showed the percentage of vulvar cancer patients who were either HIV positive and negative per year. It was not relative to the general population nor did we stratify the chart based on age but by HIV status. We have reviewed the chart to reflect the comments and suggestions. We included figure 2a which showed the distribution (raw frequency) and figure 2b which showed the normalized scale. The axes labelling has been improved to give more clarity.

Figure 3:

• The chart does not specify whether the frequencies are raw counts or adjusted for population growth, age standardization, or other factors.

• There is no indication of geographic or demographic focus.

• The dual y-axes might confuse some viewers, as it is not immediately clear that each cancer is plotted on a different scale.

Response: Raw counts were used to generate the chart based on the frequency of cases seen per year during the study period. It was not adjusted for population growth, age standardization, percentage annual change, or geographic region. It was based on an institutional data of patients with cervical and vulvar cancers seen during the study period.

We have reviewed the chart and the axes have been labelled appropriately for more clarity. Figure 3a showed the frequency of cervical and vulvar cancer seen per year. The y-axis on the left reflects the vulvar cancer frequency while the y-axis on the right reflects the cervical cancer frequency. Figure 3b showed the normalized scale for the two cancers. The comma between the numbers is a dot in the computer systemin our region i.e. 0,6 is 0.6

Other Comments:

• Their uploaded file, named as Excel sheet for PLoS ONE manuscript Nov 5, 2024, has some areas of discrepancy such as:

The Excel sheet includes several derived variables (e.g., tsize_cat5, age_cat9), which may need further clarification to match the previously provided raw data tables, reflecting the information's depth!

• Some columns, like trend and multiple categorizations (e.g., agecat3, age_cat8, age_cat9), may not directly align with the manuscript’s core tables and could require filtering or explanation to ensure relevance reflecting extraneous data.

Response: The variables such as tsize_cat5, age_cat9, agecat3, age_cat8, age_cat9, follow up, in the Excel sheet for PLos ONE were derived variables from the raw data. They were used to stratify or categorize some of the variables such as age, tumour size and also to identify which variables to use for a particular analysis because of several variable names. Excel was used to generate some figures that did not come right on Stata during the analysis. Hence, the reason while the uploaded data showed some derived variables. The variable “trend” contained rearranged patient numbers ‘1-317’that occurred during analysis, it was not a particular variable. Thank you for the kin and diligent observation. To avoid confusion while maintaining transparency, we have filtered/removed some variables from the minimal data set which did not align with the core results of this manuscripts as suggested while leaving some of the derived variables for ease of result replication as required by PLos ONE for the reviewers.

General comments:

While this study marks substantial progress, it would benefit from more rigorous analysis and a deeper interpretation of the findings to strengthen its clinical significance and improve reader comprehension. Additionally, certain sections lack coherence. For instance:

• The introduction presents a limited rationale and requires further expansion to offer a more thorough and well-rounded explanation.

• The results section should go beyond merely presenting data by providing deeper analysis and interpretation, ensuring a logical and seamless flow between findings.

• The clarity and flow, typographical accuracy, and consistency must be part of improvements as essential sections to strengthen the study’s impact and contribution to the field. Consequently, the results demand a more comprehensive analysis and critique to enhance their clarity and relevance.

Response: Thank you for your comments. We have further done review and analysis to add better interpretation and understanding to the work.

The introduction section has been reviewed and made concise to reflect the aim of the study. The results have been reviewed to limit repetition of data presented in words and in tables or charts. And to also give better interpretation. The grammatical errors have been reviewed to improve coherence and clarity of our findings.

Reviewer #3:

The statistical retrospective review of vulvar cancer patients sheds light to important considerations for women living with HIV for increased monitoring and surveillance to potentially catch vulvar cancers in this population at early disease stages. Minor typographical revisions.

Response: Thank you for the diligent review of our work and for your suggestions. We have reviewed the manuscript for grammatical and typographical errors.

Attachments
Attachment
Submitted filename: Rebuttal to PLos ONE March 2025.docx
Decision Letter - Milad Khorasani, Editor

Dear Dr. Sajo,

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 Jul 02 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.

  • 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 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,

Milad Khorasani, PhD

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

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

Reviewer #1: The authors have revised the manuscript well.

There are few minor grammatical corrections:

Discussion:

“Aside the population difference” Insert “from”

“Hence, a need for a prospective ongoing study in our institution to describe this impact”. Correct grammar

“The most common vulvar SCC, basaloid and warty types, are mostly driven by high risk HPV infection and has been found to have better prognosis” Correct to singular

Reviewer #2: The authors have successfully addressed all my comments across the manuscript, achieving full resolution. The revised manuscript reflects significant improvements and demonstrates a strong commitment to scientific rigor, clarity, and transparency. It includes additional methodological details, improved statistical and visual reporting, and a more open discussion of limitations. Based on the thoroughness of the revisions and the full resolution of my concerns, I recommend the revised manuscript for acceptance with no further major revisions.

Reviewer #3: (No Response)

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: Yes:  Nadine Rapiti

Reviewer #2: No

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

Attachments
Attachment
Submitted filename: PlosOne Review.docx
Revision 2

Editor’s comments

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.

Response: We critically reviewed the references again and they are complete and none has been retracted. However, reference 35 and 36 were corrected for proper citation.

Reviewers’ comments: Minor grammatical corrections

1. “Aside the population difference” insert from

Response: “from” has been inserted “Aside from the…”

2. “Hence, a need for a prospective ongoing study in our institution to describe this impact”. Correct grammar

Response: “Hence, there is a need for a prospective study in our institution to describe this impact.

3. “The most common vulvar SCC, basaloid and warty types, are mostly driven by high risk HPV infection and has been found to have better prognosis” correct to singular

Response: The most common vulvar SCC, basaloid or warty type, is mostly driven by high risk HPV infection and has been found to have better prognosis.

**** The minimal dataset did not contain any form of identifier. They contained data used to generate results in the manuscript. I did not insert any other data in this revision.

Attachments
Attachment
Submitted filename: Rebuttal May 2025.docx
Decision Letter - Milad Khorasani, Editor

Clinico-pathological and treatment characteristics of HIV and non-HIV related vulvar cancers: Analysis of a South African cohort

PONE-D-24-50571R2

Dear Dr. Sajo,

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,

Milad Khorasani, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

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

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

**********

Reviewer #1: (No Response)

**********

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:  Dr Nadine Rapiti

**********

Formally Accepted
Acceptance Letter - Milad Khorasani, Editor

PONE-D-24-50571R2

PLOS ONE

Dear Dr. Sajo,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

* All relevant supporting information is included in the manuscript submission,

* There are no issues that prevent the paper from being properly typeset

You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps.

Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

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. Milad Khorasani

Academic Editor

PLOS ONE

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