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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: Yes

Reviewer #3: Partly

Reviewer #4: No

Reviewer #5: Yes

Reviewer #6: Yes

Reviewer #7: Partly

Reviewer #8: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: N/A

Reviewer #4: Yes

Reviewer #5: Yes

Reviewer #6: Yes

Reviewer #7: Yes

Reviewer #8: I Don't Know

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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: No

Reviewer #4: No

Reviewer #5: Yes

Reviewer #6: Yes

Reviewer #7: Yes

Reviewer #8: Yes

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

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: No

Reviewer #4: Yes

Reviewer #5: Yes

Reviewer #6: Yes

Reviewer #7: No

Reviewer #8: No

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Reviewer #1: The idea is fair new. Please check the document with track changes.-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Reviewer #2: The manuscript titled "A Goat Experimental Epistaxis Model: Hemostatic Effect of Stop Nosebleeds Device" addresses a clinically relevant issue by testing a novel hemostatic device. The study design and results are promising; however, there are areas where the manuscript could be improved.

Abstract:

The abstract effectively summarizes the study but would benefit from specifying areas requiring further research, such as long-term outcomes or human clinical trials. Additionally, it should explicitly acknowledge the inherent limitation of translating findings from a goat model to human clinical applications to provide a more balanced perspective.

Introduction:

1.While the introduction highlights the importance of managing epistaxis and introduces the device, it lacks a robust justification for selecting goats as the model organism. Including a comparison to other animal models in the literature would strengthen this section.

2.The novelty of the "Stop Nosebleeds" device is mentioned, but it would be helpful to include a brief comparison with existing hemostatic devices or agents.

Material and methods:

1.Device Mechanism: The cooling mechanism's contribution to hemostasis is not directly validated. Adding data on nasal tissue temperature or citing similar studies could substantiate this claim.

2.Bleeding Time Measurement: The criteria for determining complete hemostasis (absence of visible blood pooling) should be supported with additional references or validation.

Results:

1.The variability in bleeding times (e.g., control group SD = 75.7 seconds) raises questions about potential inconsistencies in wound creation or animal responses. Addressing this variability in the discussion would be useful.

2.The results rely solely on text and tables, which, while clear, lack complementary visual aids like graphs or charts.

Discussion:

1.Indirect comparisons: The discussion summarizes the findings of other hemostatic agents but does not directly compare their outcomes (e.g., bleeding times, efficacy rates) to the Stop Nosebleeds device. It lacks quantitative comparisons, such as how the bleeding times achieved with ABS or MPH differ from those achieved with the Stop Nosebleeds device.

2.No focus on device uniqueness: While it mentions similarities to other devices, the unique advantages or disadvantages of the Stop Nosebleeds device (e.g., simplicity, cooling mechanism) compared to ABS, MPH, or oxidized cellulose are not highlighted.

3.Contextualize for clinical use: Address why the Stop Nosebleeds device could be advantageous in real-world scenarios (e.g., first-aid use, portability, or safety in anticoagulated patients).

Reviewer #3: Dear authors,

Thank you for this interesting manuscript about a new device to stop nasal bleeding. Although I think this manuscript may be interesting as initial research to keep developing the device, I found there are major thing that need to be addressed before publication.

General

English revision necessary

No preoperative blood sampling? How do you know coagulation was normal? And platelet count or other variables that may affect bleeding? Although each animal was its own control, it may have affected results, please, state this in the text.

Major changes

Pg 7, lines 7-8. How did you ensure all punch defects were same depth and affecting same structures? It can massively change bleeding. Please, state this in the text.

Pg 7, line 15. How did you control time to haemostasis? Relieving the pressure periodically? How was this performed (both with manual compression and the device)? Please, state this in the text.

Pg7, line 7. After induction, how was anaesthetia monitored?? How do you know arterial blood pressure and the other variables were normal and they did not affect bleeding? How did you control anaesthetic depth? Any preoperative analgesia administered? Please, state this in the text.

Pg 9. Isoflurane or sevoflurane were used? Change it in the text or figure as necessary.

Pg 7, line 13. Manual compression was always performed first? How was controlled that local haemostasia was not affecting second bleeding?? Why not randomizing? Please, state this in the text.

Pg 10, line 2. Your primary outcome was the number of wounds which stop bleeding. There is no information about this in the results section. If that was your primary outcome, why the sample size calculation was performed with time (following ARRIVE guidelines)? Please, state this in the text.

Pg 10, line 10. In the sample size calculation, you obtained 10 animals, but then, you performed 2 different experiments with only 5 animals per group, explain that (can we trust results of the two separate groups? Enough number of animals per group?). Where did you obtain your mean difference between groups to perform the sample size calculation? Previous studies? Preliminary study? Please, state this in the text.

Pg 12, results. Redundant information, no need for text and table telling the same.

Pg 13, line 11. Antibiotic and anti-inflammatory administration should be moved to Materials & Methods.

Pg 14, lines 4 - 6. How is your device compared to other methods? Advantages and disadvantages?

Pg 14, lines 7 - 9. Paragraph about antibiotics / anti-inflammatory not necessary.

Pg 14, lines 9 - 11. Haemostasis was achieved with both methods, please, state this in the text to make it clear.

Pg 14, lines 12 - 13. You cannot state that it may be highly effective in clinical settings, because, as you stated in the introduction, epistaxis can be caused by multiple situations and pathologies and you just performed a punch (lesion) please, rephrase and change this in the text to make it clear.

Pg 14, discussion. How do we know that the pressure and cold from the device did not affect nasal mucosal integrity long-term? Any studies on that? Please, state this in the text.

Thank you very much for this interesting manuscript.

Your faithfully.

Reviewer #4: El tema es bastante interesante pero debe mejorar lo siguiente, el documento no se encuentra en el formato de la revista ni tampoco cumple con los parámetros mínimos de ella. Ojo con el número de línea. El resumen se excede las 300 palabras. No hay homogeneidad en todo el documento. Se encuentra muy desordenado. No se encuentra el título de materiales y métodos, como a la vez la guía para el protocolo. Las figuras se deben poner “Fig.1”, “Fig.2” etc. Las tablas no están en el formato que corresponde. Falta coherencia en el escrito. Solo el 20.6% son citas del 2019 al 2024 significa que el 79.3% son fuentes menores de los 5 años. No se encuentran las citas número 26, 27 y 28 nombradas en la bibliografía. Todas las citas no se encuentran con las normas Vancouver que es lo que indica la revista si no una mezcla de esta con normas apa. Tener cuidado, y también tengan en cuenta la homogeneidad en estas mismas.

Reviewer #5: Abstract: Appropriate and crysp

Introduction: Appropriate and satisfactoryReview

Materials & Methods: Research techniques and methodology used are appropriate with standard statistical design application. Planning and conduct of experiments are appropriate as per the topic chosen.

Results & Appendices: The result have been appropriately presented in an elaborate and systemic manner, precisely interpreted and properly discussed with appropriate discussion.

Discussion: Discussion is critical with valid justification addressing all the objectives mentioned

Summary: Appropriate and satisfactory

Reviewer #6: - Heparin used in control group and other with stop bleeding device and regular

- ways of conducting bleeding in experimental animal not clear

- Statistical analysis can be modified with positive and control group with standard deviation

- IACUC year agreement of protocol approval should be stated for experimental design

- References need more up date from 2019 until now

Reviewer #7: In the abstract section, the method and results should have been given piece by piece, and should have been written without specifying them separately. The photographs used in the material method section should be referenced if they are the photographs taken by the authors themselves. There are font differences in the article. If the right and left nasal mucosa of the same animal were to be used, the number of animals should have been higher, it is quite insufficient. Clinical parameters indicating the health status of the animals should have been clearly presented. The specified device is available for use in humans, Animal and human nasal mucosa and epithelium are histologically different. This difference may cause problems in comparing the results with other articles. Human structure and tissue are closer to laboratory animals, so why was a goat chosen, it would have been more appropriate to do it on a laboratory animal.The reference articles used are old, the number of articles in the last 5 years is low.

Reviewer #8: In the abstract and a large part of the manuscript it's not clear if the tested device is expected ultimately to be used in human or goat nasal bleeding. In the abstract, it might be wise to briefly outline the mechanism of action of this device, the descrition of the method and the chronology of the acts are not clear, the conclusion of this study on goats seems to have been extrapolated to human without sufficient caution in the terms used.

In the first part of the introduction it's not clear if the authors talk about goats or humans.

In the material and method section, the description of the device is not clear. An expansion of the device is mentionned but this is not described precisely enough. Even though it seems obvious, there is one or two references missing on the effect on temperature ans compression on the speed of clot formation and stopping of bleeding. A reference would also be useful to support the fact stated here that goat's nasal blood flow most closely resembles that of human beings. On the other part the anatomy of goat's muzzle seems a little bit different from these of the human's nose, so the good coaptation of the device in either species might be questionable. What is normal diet of the experimental animals during the study.

Some informations about the experimental animals mentioned in the result part like age and weight would have a better place in the material and method section. Description of anesthesy doesn't mention the use of premedication (which could influence the vasomotor status of the mucosa and so the bleeding). Is this the case ? The description and chronology of experimental acts as the road map of the protocol is not clear. The lab profil mentioned as part of a data collection sheet should be described with more detail as the protocol of assessment of "re-bleeding" (timing of examination and criteria)

In table 1 goats which were heparinized should be identified.

In the context of One Health and good practices about antibiotic use is it really necessary to administer antibiotics for two 5mm diameter wounds surgicaly performed in the cranial part of the nasal mucosa. At any rate, this precision should be taken up in the material and methods rather then in the results section. Again in the discussion there is confusion between the condition, the results ant the conclusions in goats and humans. The other studies in animal models mentioned used mainly topical or general chemical agents to stop bleeding and seem to me difficult to compare with or to support the findings in the reviewed study about a mechanical device. In the other hand, if we come back to the idea of carrying out this experiment on goats, we can see that most of the other animals models mainly concern rabbits.

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Reviewer #1: Yes:  Prof. Dr. Qaes Talb Al-Obaidi

Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

Reviewer #5: No

Reviewer #6: Yes:  Amira Saad Helal Hassenin

Reviewer #7: No

Reviewer #8: Yes:  Caudron Isabelle

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Submitted filename: Review of the document.docx

A Goat Experimental Epistaxis Model: Hemostatic Effect of Stop Nosebleeds Device

PONE-D-24-52201R1

Dear Dr. Abu-Shaheen,

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,

Mehmet Baysal

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

Reviewer #2: All comments have been addressed

Reviewer #4: (No Response)

Reviewer #5: 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 #4: Partly

Reviewer #5: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #4: No

Reviewer #5: 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 #4: Yes

Reviewer #5: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #4: No

Reviewer #5: Yes

**********

Reviewer #1: (No Response)

Reviewer #2: The author has addressed my concerns, particularly regarding quantitative comparisons, including bleeding times with ABS, MPH, and the Stop Nosebleeds device, as well as the device's uniqueness. These clarifications enhance the manuscript’s rigor and clarity.

I appreciate the revisions and have no further major concerns. The manuscript is now more robust and will contribute valuable insights to the field.

Reviewer #4: Al documento no se le realizó ningún cambio anteriormente sugerido, no está en el formato de la revista, no tiene línea de seguimiento continua, no está bien escrito en inglés, no hay coherencia en algunos párrafos. Introducción: "active bleeding from inside the nose or nasal cavity" - "active bleeding from the nasal cavity" (más conciso; "inside" y "nasal cavity" es redundante). Además, la gramática: “Children (2-10 years) and adults (50-80 years) are most commonly affected.” - es mejor y más natural decir: “...are the most commonly affected age groups.” También, “Treatment strategies for epistaxis include pressing the nostrils...” - Suena más informal para un artículo científico; sería mejor reemplazarlo por: “Initial management includes digital compression of the nostrils…"

Resultados: Mejorar la redacción, coherencia y conectores; también pueden usar términos como “recorded” o “summarizes”, “achieve hemostasis” y “substantially more time”, que son más apropiados científicamente. Además de reorganizar algunas frases largas para que fueran más fáciles de leer.

Discusión: Igualmente ocurre en la discusión, no hay coherencia ni claridad entre ideas, falta mejorar la precision del lenguaje escrito como “friendly use device”, que suena poco científica y académica, que se puede cambiar por “a user-friendly first-aid device”. Recomendaría la consistencia terminológica en algunas palabras como “Stop Nosebleeds” y “stop-nosebleed device” (idealmente en cursiva si es nombre comercial: Stop Nosebleeds), mejorar conectores ("likewise", "collectively", "for example"), mejorar la estructura del párrafo final ya que, el párrafo de cierre es largo, además de que se puede dividir en dos, mostrando las limitaciones del estudio y recomendaciones para futuras investigaciones. Conclusiones: Se repite dos veces seguidas "results"; ojo con la coherencia y redacción en los párrafos, mejorar los conectores igualmente, cerrar el escrito o el párrafo final enfatizando la relevancia del estudio y sus aportes. Bibliografía: Tiene más del 70% de fuentes científicas pasados los 5 años, están escritas en forma de Vancouver y normas APA, no hay coherencia en el escrito de cada una (si se escribe el Doi son a todas las fuentes no a medias).

Reviewer #5: Abstract: Appropriate and crysp

Introduction: Appropriate and satisfactoryReview

Materials & Methods: Research techniques and methodology used are appropriate

with standard statistical design application. Planning and conduct of experiments are

appropriate as per the topic chosen.

Results & Appendices: The result have been appropriately presented in an elaborate

and systemic manner, precisely interpreted and properly discussed with appropriate

discussion.

Discussion: Discussion is critical with valid justification addressing all the objectives

mentioned

Summary: Appropriate and satisfactory

**********

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:  Qaes T. Al-Obaidi

Reviewer #2: No

Reviewer #4: No

Reviewer #5: Yes:  Dr R H Bhatt

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