Quality of life in adults with Down syndrome: A mixed methods systematic review

Ogochukwu Ann Ijezie; Jane Healy; Philip Davies; Emili Balaguer-Ballester; Vanessa Heaslip

doi:10.1371/journal.pone.0280014

Peer Review History

Original SubmissionSeptember 7, 2022
10 Oct 2022 Decision Letter - Muhammad Shahzad Aslam, Editor PONE-D-22-24936Quality of life in adults with Down syndrome: A mixed methods systematic reviewPLOS ONE Dear, 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 24 November 2022 If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” c) If any authors received a salary from any of your funders, please state which authors and which funders. d) If you did not receive any funding for this study, please state: “The authors received no specific funding for this work.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf 3. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The abstract of the study presents numerous abbreviations, when the publisher's specifications suggest that acronyms should not appear in the abstract. I only find this detail. The rest seems impeccable to me. Reviewer #2: The authors present a good research paper. • The relevance of the topic: Good. • Introduction: Good. • Methodology: Can be improved. • Results: Good. • Discussion: Good. However, ACCEPT AFTER MINOR REVISION. In general, the paper follows an adequate structure and correct scientific support and can be published considering some limitations. The study is interesting in the field of people with Down syndrome. However, there are a series of limitations that should be considered. In the first place, carry out a review of the existing literature related to the subject, being essential to inquire into the Plos One journal itself, since there are papers related to its manuscript that can help to improve it. Therefore, include those references, if any, especially from the last five years. In addition, recommend reading some papers related to the topic of adults with down syndrome: Gámez-Calvo, L., Gamonales, J. M., León, K., & Muñoz-Jiménez, J. (2022). Influence of Balance on the Quality of Life of People with Down Syndrome in School and Adult Ages: A Literature Review. MHSalud, 19(1), 1-15. https://doi.org/10.15359/mhs.19-1.6 Gámez-Calvo, L., Gamonales, J.M., Silva-Ortíz, A.M., & Muñoz-Jiménez, J. (2022). Benefits of hippotherapy in elderly people: Scoping review. Journal of Human Sport and Exercise, 17(2), 302-313. https://doi.org/10.14198/jhse.2022.172.06 Hamadelseed, O., Elkhidir, I. H., & Skutella, T. (2022). Psychosocial Risk Factors for Alzheimer’s Disease in Patients with Down Syndrome and Their Association with Brain Changes: A Narrative Review. Neurology and Therapy, 1-23. Rodríguez-Grande, E. I., Buitrago-López, A., Torres-Narváez, M. R., Serrano-Villar, Y., Verdugo-Paiva, F., & Ávila, C. (2022). Therapeutic exercise to improve motor function among children with Down Syndrome aged 0 to 3 years: a systematic literature review and meta analysis. Scientific reports, 12(1), 1-11. Silva-Ortiz, A., Gamonales, J., Gámez-Calvo, L., & Muñoz-Jiménez, J. (2020). Beneficios de la actividad física inclusiva para personas con síndrome de Down: revisión sistemática. SPORT TK: Revista EuroAmericana de Ciencias del Deporte, 9(2), 81–94. https://doi.org/10.6018/sportk.454201 Specific comments. Title: It is correct. Abstract. Incorporate in the summary, a more precise sentence of the results. Introduction. This section presents the problem in a coherent and clear manner with the correct support of the scientific literature. However, it is convenient to update the references, since there are different works related to the subject and no mention is made, and it would even be interesting to mention the different existing works related to technological advances in people with down syndrome. Also, it could be a future study of review. Methods. Modify the method section and incorporate the sections: Design. - Study design. To write the design section, we recommend that you take some of the following methodologists as references. Ato, M., López-García, J. J., & Benavente, A. (2013). A classification system for research designs in psychology. Anales de Psicología/Annals of Psychology, 29(3), 1038-1059. Montero, I., & León, O.G. (2007). A guide for naming research studies in psychology. International Journal of Clinical and Health Psychology, 7(3), 847-862. Results. Summary of study data and table are correct. Conclusion. Differentiate the discussion of the main conclusions of the work. To do this, you must create this section. And modify the limitations of the study and locate them in said section at the end. Also, they must be direct, and highlight the main contributions of the study. References. They should be reviewed and updated according to the publication standards. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0280014.r001
Revision 1
9 Dec 2022 Author Response Dear Academic Editor, Thank you for the email dated 10 October 2022. We are delighted that both you and the reviewers highlighted that the paper follows an appropriate structure, is properly scientifically grounded, and is of interest in the field of people with Down syndrome. We would like to thank you and the reviewers for your suggestions to further strengthen the paper and for discovering relevant ideas for future research. We would like to express our sincere gratitude for taking your precious time to provide in-depth comments that have significantly improved the quality of our paper. We have reviewed the comments and generally agree with them. Where possible, we have made changes to the manuscript based on your observations and those of the reviewers. We have discovered 2 recently published articles and added them to our review. Instead of 37 studies initially included, we have 39 studies. For the sake of transparency, we have marked the following in green: i) The new included papers in the S2 Table and S3 Table. ii) Updated page numbers in S1 Checklist PRISMA 2020 Checklist. We have updated Fig 1 and Fig 2. We also marked your comments (journal requirements) and those of the reviewers in black and our answers are marked as the “Authors’ Response” in green. As requested, we have also included the following in our submission: 1. A marked-up copy of our manuscript that highlights changes made to the original version labelled ‘Revised Manuscript with Track Changes.’ 2. An unmarked version of our revised paper without tracked changes as a separate file labelled ‘Manuscript.’ We hope that these revisions will give you and the reviewers’ comments sufficient consideration and that the paper will be accepted for publication in the PLOS ONE Journal. We take this opportunity to thank everyone involved in the process. Yours sincerely, Ogochukwu Ann Ijezie PhD student Department of Computing and Informatics P256, Poole House, Talbot Campus, BH12 5BB Bournemouth University, United Kingdom oijezie@bournemouth.ac.uk Corresponding Author (On the behalf of all authors) Journal requirements: • Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 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 Authors’ Response: Thank you for your comment. This has been completed. • Thank you for stating the following financial disclosure: “The authors received no specific funding for this work and was conducted as part of a PhD project.” At this time, please address the following queries: a) Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution. b) State what role the funders took in the study. If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” c) If any authors received a salary from any of your funders, please state which authors and which funders. d) If you did not receive any funding for this study, please state: “The authors received no specific funding for this work.” Authors’ Response: We are grateful for your feedback. We chose the fourth option from your comments relevant to our work as it is not funded and also updated the statement in our cover letter. Hence, we have amended our manuscript as follows: “The authors received no specific funding for this work.” • 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. Authors’ Response: Thank you for your comment. This has been completed. Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #1 and Reviewer #2 1. Is the manuscript technically sound, and do the data support the conclusions? Yes Authors’ Response: We are grateful for your feedback. 2. Has the statistical analysis been performed appropriately and rigorously? Yes Authors’ Response: We are grateful for your feedback. 3. Have the authors made all data underlying the findings in their manuscript fully available? Yes Authors’ Response: We are grateful for your feedback. 4. Is the manuscript presented in an intelligible fashion and written in standard English? Yes Authors’ Response: We are grateful for your feedback. 5. Review Comments to the Author Reviewer #1: The abstract of the study presents numerous abbreviations, when the publisher's specifications suggest that acronyms should not appear in the abstract. I only find this detail. The rest seems impeccable to me. Authors’ Response: Many thanks for raising this point. In response to this comment, we have addressed this by eliminating abbreviations where possible in the abstract (see page 2 of the revised manuscript). Reviewer #2: The authors present a good research paper. • The relevance of the topic: Good. • Introduction: Good. • Methodology: Can be improved. • Results: Good. • Discussion: Good. However, ACCEPT AFTER MINOR REVISION. In general, the paper follows an adequate structure and correct scientific support and can be published considering some limitations. The study is interesting in the field of people with Down syndrome. However, there are a series of limitations that should be considered. In the first place, carry out a review of the existing literature related to the subject, being essential to inquire into the Plos One journal itself, since there are papers related to its manuscript that can help to improve it. Therefore, include those references, if any, especially from the last five years. In addition, recommend reading some papers related to the topic of adults with down syndrome: Gámez-Calvo, L., Gamonales, J. M., León, K., & Muñoz-Jiménez, J. (2022). Influence of Balance on the Quality of Life of People with Down Syndrome in School and Adult Ages: A Literature Review. MHSalud, 19(1), 1-15. https://doi.org/10.15359/mhs.19-1.6. Gámez-Calvo, L., Gamonales, J.M., Silva-Ortíz, A.M., & Muñoz-Jiménez, J. (2022). Benefits of hippotherapy in elderly people: Scoping review. Journal of Human Sport and Exercise, 17(2), 302-313. https://doi.org/10.14198/jhse.2022.172.06. Hamadelseed, O., Elkhidir, I. H., & Skutella, T. (2022). Psychosocial Risk Factors for Alzheimer’s Disease in Patients with Down Syndrome and Their Association with Brain Changes: A Narrative Review. Neurology and Therapy, 1-23. Rodríguez-Grande, E. I., Buitrago-López, A., Torres-Narváez, M. R., Serrano-Villar, Y., Verdugo-Paiva, F., & Ávila, C. (2022). Therapeutic exercise to improve motor function among children with Down Syndrome aged 0 to 3 years: a systematic literature review and meta analysis. Scientific reports, 12(1), 1-11. Silva-Ortiz, A., Gamonales, J., Gámez-Calvo, L., & Muñoz-Jiménez, J. (2020). Beneficios de la actividad física inclusiva para personas con síndrome de Down: revisión sistemática. SPORT TK: Revista EuroAmericana de Ciencias del Deporte, 9(2), 81–94. https://doi.org/10.6018/sportk.454201. Authors’ Response: We are thankful for these comments and for raising interesting points. We have revised the methodology section (see pages 5 to 7 of the revised manuscript). We really appreciate the recommended papers. We read them and realised that only paper III was appropriate for our study. For papers I and V, only the abstract was written in English, paper II (it was not suitable for our study as it talked about hippotherapy) and paper IV (it focused on children with Down syndrome aged 0 to 3 years. As requested, we conducted a search from the last five years (2017 – 2022) for existing literature in the PLOS ONE journal. We found four articles published within the timeline related to our manuscript and added them to the introduction on page 3: I. Lancioni GE, Singh NN, O’Reilly MF, Sigafoos J, Alberti G, Del Gaudio V, et al. (2022) People with intellectual and sensory disabilities can independently start and perform functional daily activities with the support of simple technology. PLoS ONE 17(6): e0269793. https://doi.org/10.1371/journal.pone.0269793. II. De-Rosende-Celeiro I, Torres G, Seoane-Bouzas M, Ávila A (2019) Exploring the use of assistive products to promote functional independence in self-care activities in the bathroom. PLoS ONE 14(4): e0215002. https://doi.org/10.1371/journal.pone.0215002. III. Haddad F, Bourke J, Wong K, Leonard H (2018) An investigation of the determinants of quality of life in adolescents and young adults with Down syndrome. PLoS ONE 13(6): e0197394. https://doi.org/10.1371/journal.pone.0197394. The aim of paper III was to investigate determinants of health-related quality of life of young people with Down syndrome, with a focus on the identification of risk and protective factors pertaining not only to the individuals themselves but also to their family environment. We did not include it as part of the included studies because our manuscript only focused on the quality of life in adults with Down syndrome. We extracted only relevant information and included it in the introduction (see page 3) and discussion (see page 23) sections. IV. Gandy KC, Castillo HA, Ouellette L, Castillo J, Lupo PJ, Jacola LM, et al. (2020) The relationship between chronic health conditions and cognitive deficits in children, adolescents, and young adults with down syndrome: A systematic review. PLoS ONE 15(9): e0239040. https://doi.org/10.1371/journal.pone.0239040. Additionally, we found an article published in 2014 and included it in the discussion section: V. Foley K-R, Girdler S, Bourke J, Jacoby P, Llewellyn G, Einfeld S, et al. (2014) Influence of the Environment on Participation in Social Roles for Young Adults with Down Syndrome. PLoS ONE 9(9): e108413.https://doi.org/10.1371/journal.pone.0108413. For paper V, the age group of young adults were: 16 – 18 years (first age group), 19 – 22 years and 23 – 31 years. During analysis, they merged all the age groups together. We did not include it as part of the included studies because our manuscript only focused on aged 18 years and above. We have extracted only relevant information and included it in the discussion section (see page 23 of the revised manuscript). We hope we addressed this section in line with your request. Specific comments. 6. Title: It is correct. Authors’ Response: We appreciate your comment. 7. Abstract. Incorporate in the summary, a more precise sentence of the results. Authors’ Response: Many thanks for raising this point. In response to this comment, we have addressed this by writing the abstract in a more precise format (see page 2 of the revised manuscript). 8. Introduction. This section presents the problem in a coherent and clear manner with the correct support of the scientific literature. However, it is convenient to update the references, since there are different works related to the subject and no mention is made, and it would even be interesting to mention the different existing works related to technological advances in people with down syndrome. Also, it could be a future study of review. Authors’ Response: Many thanks for the kind words and for providing excellent suggestions as they helped strengthened the quality of our work, unearthed good ideas and gave a different perspective on proffering solutions for adults with Down syndrome via information and communication technology. We have addressed this by updating the references based on existing works related to the technological advances in people with Down syndrome (see page 3 of the revised manuscript). 9. Methods. Modify the method section and incorporate the sections: Design. - Study design. To write the design section, we recommend that you take some of the following methodologists as references. Ato, M., López-García, J. J., & Benavente, A. (2013). A classification system for research designs in psychology. Anales de Psicología/Annals of Psychology, 29(3), 1038-1059. Montero, I., & León, O.G. (2007). A guide for naming research studies in psychology. International Journal of Clinical and Health Psychology, 7(3), 847-862. Authors’ Response: Many thanks for the recommended papers. We read the papers and realised that they were not really suitable for our methods section as they did not specify methodologies used in systematic reviews. Since our study is on mixed methods systematic review, we found two recently published articles to address your comment which are: I. Stern, C., Lizarondo, L., Carrier, J., Godfrey, C., Rieger, K., Salmond, S., Apostolo, J., Kirkpatrick, P. and Loveday, H., 2020. Methodological guidance for the conduct of mixed methods systematic reviews. JBI evidence synthesis, 18(10), pp.2108-2118. https://doi.org/10.11124/jbisrir-d-19-00169. II. Lizarondo, L., Stern, C., Apostolo, J., Carrier, J., de Borges, K., Godfrey, C., Kirkpatrick, P., Pollock, D., Rieger, K., Salmond, S. and Vandyk, A., 2022. Five common pitfalls in mixed methods systematic reviews: lessons learned. Journal of Clinical Epidemiology, 148, pp. 178-183. https://doi.org/10.1016/j.jclinepi.2022.03.014 The articles are located on page 5 of the revised manuscript. 10. Results. Summary of study data and table are correct. Authors’ Response: We are grateful for your feedback in this section. We discovered 2 recently published articles. We extracted the data, appraised the studies and synthesised and added them to our review: I. Landuran, Audrey, Hélène Sauzéon, Charles Consel, and Bernard N’Kaoua (2022). Evaluation of a smart home platform for adults with Down syndrome. Assistive Technology, pp.1-11. https://doi.org/10.1080/10400435.2022.2075487 II. María Auxiliadora Robles-Bello, David Sánchez-Teruel, Nieves Valencia Naranjo & Rafael Delgado Rodríguez (2022). Preliminary Study on Emotional Competence in Adults with Down Syndrome, International Journal of Disability, Development and Education, 69:6, 2136-2154. https://doi.org/10.1080/1034912X.2020.1840532 There was a numerical error in the manuscript with track changes (see page 15), which has been corrected in the revised manuscript and does not affect the overall result. 11. Conclusion. Differentiate the discussion of the main conclusions of the work. To do this, you must create this section. And modify the limitations of the study and locate them in said section at the end. Also, they must be direct, and highlight the main contributions of the study. Authors’ Response: Thank you so much for your recommendation. We have differentiated the main findings of the study, moved the limitations at the end and made the conclusions more explicit. We are unsure if we have adequately addressed this as you requested. If not, we are happy to revise it again. 12. References. They should be reviewed and updated according to the publication standards. Authors’ Response: We have amended and updated our reference list to meet PLOS ONE guidelines. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0280014.r002
5 Apr 2023 Decision Letter - Muhammad Shahzad Aslam, Editor Quality of life in adults with Down syndrome: A mixed methods systematic review PONE-D-22-24936R1 Dear Dr. Ijezie, 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, Muhammad Shahzad Aslam, Ph.D.,M.Phil., Pharm-D 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 ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? 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 #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 #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 #2: (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: Yes: José M. Gamonales ******** https://doi.org/10.1371/journal.pone.0280014.r003
Formally Accepted
14 Apr 2023 Acceptance Letter - Muhammad Shahzad Aslam, Editor PONE-D-22-24936R1 Quality of life in adults with Down syndrome: A mixed methods systematic review Dear Dr. Ijezie: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Muhammad Shahzad Aslam Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0280014.r004

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