Voltammetric analysis for distinguishing portal hypertension-related from malignancy-related ascites: A proof of concept study

Moises Muley; Umberto Vespasiani-Gentilucci; Antonio De Vincentis; Marco Santonico; Giorgio Pennazza; Simona Sanguedolce; Cristiana De Luca; Francesco Plotti; Antonio Picardi; Raffaele Antonelli-Incalzi

doi:10.1371/journal.pone.0233350

Peer Review History

Original SubmissionApril 6, 2020
14 Apr 2020 Decision Letter - Matias A Avila, Editor PONE-D-20-09873 Voltammetric analysis for distinguishing portal hypertension-related from malignancy-related ascites: a proof of concept study. PLOS ONE Dear M.D. De Vincentis, 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 by the reviewers. In addition to that, it is important that you make sure that your report meets the criteria of utility validation and availability described in: http://journals.plos.org/plosone/s/submission-guidelines#loc-methods-software-databases-and-tools, and the STROBE gudelines/checklist: http://www.strobe-statement.org. We would appreciate receiving your revised manuscript by May 29 2020 11:59PM. 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The PLOS ONE style templates can be found at http://www.plosone.org/attachments/PLOSOne_formatting_sample_main_body.pdf and http://www.plosone.org/attachments/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. [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: I read with interest this manuscript. The study by Antonio De Vincentis described Voltammetric analysis for distinguishing portal hypertension-related from malignancy- related ascites. The manuscript is well written and presented, conclusions are sound. The topic is of interest to the scientific community. I have only one minor revision: -The authors should discussion in the conclusion how they intend to further improve the accuracy of this technique in future studies. This is a proof of concept study and I think that is important to give future prospects for studies. Reviewer #2: The paper its related to a study, through Voltammetric analysis, for distinguishing portal hypertension-related from malignancy related ascites. The paper is interesting, but authors should convince the reviewer that the proposed method is valid, by comparing it with the literature. Moreover, better information on experimental set-up (BioNote), in particular, technical data and some figures related to measurements, must be given for a broader audit of the paper (sensor researchers). ****** 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: Andrea Casadei Gardini 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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0233350.r001
Revision 1
2 May 2020 Author Response Answer to the comments Reviewer #1: I read with interest this manuscript. The study by Antonio De Vincentis described Voltammetric analysis for distinguishing portal hypertension-related from malignancy-related ascites. The manuscript is well written and presented, conclusions are sound. The topic is of interest to the scientific community. I have only one minor revision: -The authors should discussion in the conclusion how they intend to further improve the accuracy of this technique in future studies. This is a proof of concept study and I think that is important to give future prospects for studies. Answer to the comment: We are glad the reviewer appreciated our work and we thank him/her for the comment. The analysis of electrochemical properties of a given fluid may account upon a huge variety of experimental conditions, i.e., broadly speaking, of experimental electrical fields. [26] Thus, comparing different experimental conditions to identify that or those yielding the best discriminatory capacity is expected to further simplify the experimental procedure as well as to increase its diagnostic accuracy. Furthermore, a more detailed characterization of ascites will allow verify whether a given e-tongue finding, i.e., a well-defined electrochemical pattern, recognizes selected determinants and, thus, points at a distinctive chemical composition. Finally, portal hypertension is a heterogeneous condition as for etiology and severity, and neoplastic ascites also has many determinants and variable physicochemical properties. Thus, expanding the library to compare different and well-sized categories of either hemodynamic or neoplastic ascites is expected to provide potential insight into the diagnostic properties of the e-tongue. Indeed, we cannot exclude that selected clinical and pathophysiological conditions will benefit the most from the classificatory and prognostic properties of the e-tongue. In this perspective, the follow up of patients might be of interest to test the prognostic properties of the voltammetric findings versus outcomes such as responsivity of ascites to diuretic therapy or survival. These considerations are now available in the “Discussion” section on pages 13 to 14, lines 290 to 300, and in the “Conclusion” section on page 14, lines 319 to 321. Reviewer #2: The paper its related to a study, through Voltammetric analysis, for distinguishing portal hypertension-related from malignancy related ascites. The paper is interesting, but authors should convince the reviewer that the proposed method is valid, by comparing it with the literature. Moreover, better information on experimental set-up (BioNote), in particular, technical data and some figures related to measurements, must be given for a broader audit of the paper (sensor researchers). Answer to the comment: We thank the reviewer for his/her comment. Concerning the comparison of BIONOTE with scientific literature on the field, it is worth remarking that no experiment using this sensor in ascitic fluid has been reported so far. However, we had previously tested BIONOTE for classification of other biological fluid. [18-20] In the revised manuscript, the measurement process using BIONOTE has been illustrated in a figure, i.e., Figure 1) to make it clearer to any kind of reader. Generally, chemical sensors are based on specific or non-specific sensing materials. The kind of sensing material could contribute to obtain selective or non-selective sensors. Accordingly, Biosensors are specific sensors and their sensing mechanisms is so called “key-lock”. Using a sensing material on the transducer requires particular processes of manufacturing in order to obtain reproducible and repeatable sensors. In our case we used a non-functionalized sensor, in particular no sensing materials are used on the electrode surface. The sensing material has an advantage for bio-medical applications (in general), but two disadvantages for the specific application here presented. The advantage consists in the possibility of selecting a well defined sensing element interacting with a specific biomarker or a specific compound of interest for the sample under test, increasing sensor performance in terms of sensitivity, resolution and, obviously, selectivity. However, the approach of this paper is the fingerprinting and not the identification and/or quantification of specific biomarkers. Moreover, the process of covering the surface of the sensor with a chemical interactive material requests another technological step which affects the overall reproducibility of the sensor. The commercial electrode (Au, Pt, Ag) with a dedicated electronic interface developed by the Unit of Electronics for Sensor Systems of Campus Bio-Medico di Roma guarantees the reproducibility and repeatability of measurement as shown in other papers [25,26,35]. In the future this kind of approach could reduce the operational costs of the device. We did not include these comments in the text because they seems more suited for a pure technological journal. However, the bases of the voltammetric analyses are reported in detail in the above cited references and in the following three. Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0233350.r002
5 May 2020 Decision Letter - Matias A Avila, Editor Voltammetric analysis for distinguishing portal hypertension-related from malignancy-related ascites: a proof of concept study PONE-D-20-09873R1 Dear Dr. De Vincentis, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. 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 enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and 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. With kind regards, Matias A Avila, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0233350.r003
Formally Accepted
13 May 2020 Acceptance Letter - Matias A Avila, Editor PONE-D-20-09873R1 Voltammetric analysis for distinguishing portal hypertension-related from malignancy-related ascites: a proof of concept study Dear Dr. De Vincentis: I am 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 notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, 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. For any other questions or concerns, please email plosone@plos.org. Thank you for submitting your work to PLOS ONE. With kind regards, PLOS ONE Editorial Office Staff on behalf of Dr Matias A Avila Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0233350.r004

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