PONE-D-21-24785Circulating sLR11 levels predict severity of pulmonary hypertension due to left heart diseasePLOS ONE

Dear Dr. Konishi,

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One of the reviewer pointed out some statistical problems, so please respond them.

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Yoshiaki Taniyama, MD, PhD

Academic Editor

PLOS ONE

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2. Thank you for providing the following Funding Statement:  

Tsukuba Research Institute, Sekisui Medical Co. Ltd. provided support in the form of salaries for Hiroyuki Ebinuma. The specific roles of these authors are articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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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?

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

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

Reviewer #1: Yes

Reviewer #2: Yes

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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

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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

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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: This version has been satisfactorily responded to my original comments. The conclusion is supported by the results presented in this manuscript. The methods and discussion are well written. This reviewer has no further comments.

Reviewer #2: The authors conduct the analysis of 34 patients to examine whether sLR11 is associated with PH in PH-LHD with 5 years follow-up. The results showed the association between sLR11 and the severity of PH.

1. Statistical analysis: “baseline characteristics….using two-sided two-sample T-tests for normally distributed continuous variables”. Are all baseline characteristics normally distributed? If not, how about non-normally distributed variables?

2. Statistical Analysis: “Raw counts and percentages are described as mean and standard deviation”. Please clarify what this statement!

3. Results: 28 out of 66 MR patients were excluded from the original enrolled sample. Are there any characteristics difference between these 28 and the remaining patients?

4. Results: “Median age was 64.8±13.1”. So 64.8 is median age but what 13.1 is? IQR? Please clarify this. Similar question applies to other reported information.

5. Results: There are many typos or errors here and there!! This is quite a surprising to see for a revised manuscript. Also, it might be benefit to use English editing as well. To name some examples,

a. “there was not a variable that had 0.95 multiple correlation coefficient > 0.95.” Please clarify what this statement means?

b. “We defined to the objective variable was mPAP and selected an explanation variable which is high in degree of influence on an objective variable that cardiovascular risk factor.” Please clarify what this statement means.

6. Results. “Based on our previous normal human sLR11 level of…, we established an upper limit of normal for sLR11 of 9.4..” Please provide more detail how this was establish? If this criteria is from previous work, please cite appropriate reference.

7. Tables 1 and 3. “data are presented as n,…mean,…or median.” Please make clear notes which variables were presented in mean and which in median.

8. Table 2. Please add degree of freedom information for the F-statistic. Otherwise, it doesn’t have any meaning with only F-stat.

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Reviewer #1: No

Reviewer #2: No

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Circulating sLR11 levels predict severity of pulmonary hypertension due to left heart disease

PONE-D-21-24785R1

Dear Dr. Konishi,

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.

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Kind regards,

Yoshiaki Taniyama, MD, PhD

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

Reviewer #2: All comments have been addressed

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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: (No Response)

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

Reviewer #1: Yes

Reviewer #2: (No Response)

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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: (No Response)

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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: (No Response)

**********

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: This reviewer have no further comments on the revised manuscript. The manuscript was well revised and should be published as soon as possible.

Reviewer #2: (No Response)

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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: No

Reviewer #2: No