Peer Review History

Original SubmissionJuly 25, 2020
Decision Letter - Xianwu Cheng, Editor

PONE-D-20-23161

Plasminogen Activator Inhibitor-1 in poorly controlled vs well controlled Type-2 Diabetes Mellitus patients; a cross-sectional study in a district hospital in Ghana

PLOS ONE

Dear Dr Serwaa

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 Jan 15 2021 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Xianwu Cheng, M.D., Ph.D., FAHA

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information.

3. We noted that you refer to this study as a cross-sectional study through out the manuscript, but according to your description we would not consider this a cross-sectional study but rather a case control study. In order to avoid confusion we would suggest that you change the wording in your manuscript and avoid referring to this study as a cross-sectional study.

4.Please provide a sample size and power calculation in the Methods, or discuss the reasons for not performing one before study initiation.

5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

Additional Editor Comments (if provided):

None.

[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: No

**********

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: I found the research to be rigorous, thorough, reasonable, and well-written. I found the investigation as needed for the patients studied and invites’ other researchers to do the same for their patrons. The research agrees with and builds upon prior research.

The wording and spelling conform with U.S. English minus the few words below. These words are listed for the researchers to confirm the spelling is correct for their intended audience.

U.S. English Your Document

etiology aetiology

Analyzed Analysed

Dyslipidemia Dyslipidaemia

Glycemic Glycaemic

Glycosylated Glycosylatedcated

Hematological Haematological

Hemoglobin Haemoglobin

hemostasis haemostasis

Hyperinsulinemia Hyperinsulinaemia

ischemic ischaemic

neighboring neighbouring

Reviewer #2: The authors provide an interesting and potential important manuscript describing "Plasminogen activator inhibitor-1 in poorly controlled vs well controlled Type-2 diabetes melitus patients; a cross-sectional study in a district hospital in Ghana", The main issues concerning this paper are those concerning the potential associations between PAI-1 and glycaemic.

There are some weak points that need to be addressed by the authors

Major

1. The ratio of male to female in the subgroup is unbalanced, and additional data are needed to explain the gender difference of PAI-1.( see Table1 below)

2. In the table below, abnormal distribution of blood lipids and blood glucose occurred simultaneously between groups. How to determine the relationship between PAI-1 and blood glucose?( see Table2 below)

**********

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: Gerald D. Redwine

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.

Attachments
Attachment
Submitted filename: PONE-20-23161_reviewer.docx
Revision 1

Dear Editor,

Thank you for your email. I am pleased to resubmit manuscript number: PONE-D-20-23161 titled “Plasminogen Activator Inhibitor-1 in poorly controlled vs well controlled Type-2 Diabetes Mellitus patients; a case-control study in a district hospital in Ghana" for your consideration.

The concerns raised by the editorial team have been addressed and highlighted below and in the respective sections in the manuscript. I look forward to your favourable response.

Thank you.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

The manuscript meets PLOS ONE’s style requirements.

2. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information.

The Questionnaire for the study has been uploaded as a supporting document

3. We noted that you refer to this study as a cross-sectional study throughout the manuscript, but according to your description we would not consider this a cross-sectional study but rather a case control study. In order to avoid confusion we would suggest that you change the wording in your manuscript and avoid referring to this study as a cross-sectional study.

The ‘cross-sectional study’ wording in the entire document has been replaced with ‘case-control study’

4. Please provide a sample size and power calculation in the Methods, or discuss the reasons for not performing one before study initiation.

The sample size and power calculation has been included in the Methods

5. 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.

Captions have been included in the Supporting Information files

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I found the research to be rigorous, thorough, reasonable, and well-written. I found the investigation as needed for the patients studied and invites’ other researchers to do the same for their patrons. The research agrees with and builds upon prior research.

The wording and spelling conform with U.S. English minus the few words below. These words are listed for the researchers to confirm the spelling is correct for their intended audience.

U.S. English Your Document

etiology aetiology

Analyzed Analysed

Dyslipidemia Dyslipidaemia

Glycemic Glycaemic

Glycosylated Glycosylatedcated

Hematological Haematological

Hemoglobin Haemoglobin

hemostasis haemostasis

Hyperinsulinemia Hyperinsulinaemia

ischemic ischaemic

neighboring neighbouring

Changes have been made and all of the above words now conform to U.S. English in the manuscript

Reviewer #2: The authors provide an interesting and potential important manuscript describing "Plasminogen activator inhibitor-1 in poorly controlled vs well controlled Type-2 diabetes melitus patients; a cross-sectional study in a district hospital in Ghana", The main issues concerning this paper are those concerning the potential associations between PAI-1 and glycaemic.

There are some weak points that need to be addressed by the authors

Major

1. The ratio of male to female in the subgroup is unbalanced, and additional data are needed to explain the gender difference of PAI-1 (see Table1 below).

This has been rectified and the gender ratio is balanced now

2. In the table below, abnormal distribution of blood lipids and blood glucose occurred simultaneously between groups. How to determine the relationship between PAI-1 and blood glucose? (see Table2 below).

The relationship between PAI-1 and fasting blood glucose has been established and data embedded in the manuscript.

Attachments
Attachment
Submitted filename: PAI-1 RESPONSE TO EDITOR.docx
Decision Letter - Xianwu Cheng, Editor

PONE-D-20-23161R1

Plasminogen Activator Inhibitor-1 in poorly controlled vs well controlled Type-2 Diabetes Mellitus patients; a case-control study in a district hospital in Ghana

PLOS ONE

Dear Dr Serwaa,

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 March 31. 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Xianwu Cheng, M.D., Ph.D., FAHA

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

Although the authors put effort to somewhat address origial concerns, this editors and the second reviewer that the number of men and women remains the same as before, and other data in table1 have not changed. It is hard to accept the explanation for the previous problem. The author should review the data, re-count and re-statistical analysis it. It'll be final revision time to cosider for publish this paper.

[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 #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: No

**********

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

Reviewer #2: No

**********

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: Dear author

Thank you very much for adjusting the gender ratio. However, the number of men and women remains the same as before, and other data in table1 have not changed. I'm sorry that I cannot accept the explanation for the previous problem. The author should review the data, re-count and collate it.

Best Whishes

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachments
Attachment
Submitted filename: Response to PONE-D-20-23161_R1.doc
Revision 2

Dear Editor,

Thank you for your email. I am pleased to resubmit manuscript number: PONE-D-20-23161 titled “Plasminogen Activator Inhibitor-1 in poorly controlled vs well controlled Type-2 Diabetes Mellitus patients; a case-control study in a district hospital in Ghana" for your consideration.

The concern raised by the editorial team have been addressed and highlighted below and in the respective sections in the manuscript. I look forward to your favourable response.

Thank you.

Reviewer’s comment

Thank you very much for adjusting the gender ratio. However, the number of men and women remains the same as before, and other data in table 1 have not changed. I'm sorry that I cannot accept the explanation for the previous problem. The author should review the data, re-count and collate it.

Authors’ response

First, the data has been reviewed, recounted and re collated to address the appropriate percentage distribution of the participants’ gender. However, the ratio of male to female in the subgroup still remains unbalanced. It is not possible to balance the gender now, this could have been done at the data collection stage; it cannot be undertaken after data collection. In the methodology we did not indicate anyway where that we controlled for gender (i.e. Collecting equal number of males and females in each arm/sub-group). We therefore have acknowledged this as a limitation of the study.

Second, additional data for comparison of mean PAI-1 activity and PAI-1 Ag level across Gender was analysed and reported as below.

Comparison of PAI-1 activity and PAI-1 Ag level across Gender

The mean PAI-1 activity between males and females were not significantly different (5.25±3.27 vs 5.25±3.90, p=0.998). Similarly, no significant differences were observed between PAI-1 Ag level in males and females (25.83±16.85 vs 26.42±21.92, p=0.888). With respect to the Type II diabetic group, no significant difference was observed for both PAI-1 activity (5.80±3.90 vs 5.80±4.65, p=0.996) and PAI-1 Ag level (28.52±20.13 vs 29.91± 26.15, p=0. 822) between males and females. Also, in the control group, PAI-1 activity (4.17±0.63 vs 4.15±0.97, p=0.951) and PAI-1 Ag level (20.44±3.38 vs 19.45 ± 3.36, p=0.459) were not significantly different across the different groups of gender.

Table 3: Comparison of PAI-1 activity and PAI-1 Ag across Gender

Gender

p-value

Both groups Male Female

PAI-1 Activity level (U/mL) 5.25 ± 3.27 5.25 ± 3.90 0.998

PAI-1 Ag level (ng/mL) 25.83 ± 16.85 26.42 ± 21.92 0.888

T2DM Participants

PAI-1 Activity level (U/mL) 5.80 ± 3.90 5.80 ± 4.65 0.996

PAI-1 Ag level (ng/mL) 28.52 ± 20.13 29.91 ± 26.15 0.822

Healthy Controls

PAI-1 Activity level (U/mL) 4.17 ± 0.63 4.15 ± 0.97 0.951

PAI-1 Ag level (ng/mL) 20.44 ± 3.38 19.45 ± 3.36 0.459

Data are presented as Mean ± standard deviation (SD); PAI-1= Plasminogen activator inhibitor-1; Ag= Antigen

Acknowledged limitations of the study.

The study was limited by our inability to determine the specific polymorphisms of the PAI-1 gene in the T2DM subjects. Also, the ratio of male to female in both subgroups were unbalanced, the non-significant difference may have been masked by the unbalanced gender. To help address this limitation we, recommend that participants be matched for age and gender in future studies.

Attachments
Attachment
Submitted filename: PAI-1 RESPONSE TO EDITOR.docx
Decision Letter - Xianwu Cheng, Editor

Plasminogen Activator Inhibitor-1 in poorly controlled vs well controlled Type-2 Diabetes Mellitus patients; a case-control study in a district hospital in Ghana

PONE-D-20-23161R2

Dear Dr Serwaa

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,

Xianwu Cheng, M.D., Ph.D., FAHA

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Both of original reviewers have indicated acceptance.

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: (No Response)

**********

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: Thank you for your explanation. Although there is gender imbalance in the data, there is no significant difference in PAI-1 level among each group, which excludes the influence caused by gender deviation, and the credibility of the results is enhanced to a certain extent.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Formally Accepted
Acceptance Letter - Xianwu Cheng, Editor

PONE-D-20-23161R2

Plasminogen Activator Inhibitor-1 in poorly controlled vs well controlled Type-2 Diabetes Mellitus patients; a case-control study in a district hospital in Ghana

Dear Dr. Serwaa:

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

Associate Prof. Xianwu Cheng

Academic Editor

PLOS ONE

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