{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:31:55Z","timestamp":1793295115434,"version":"4.5.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100017160","name":"Beni Suef University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017160","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>A new accurate, precise thin layer chromatographic (TLC densitometric) approach was developed for the simultaneous analysis of ergotamine tartrate (ERG), phenobarbital sodium (PHEN), caffeine anhydrous (CAF), dipyrone sodium (DIP) and meprobamate (MEP) in their pure form and in their combined formulation; (MIGRANIL tablets). TLC separation depended on using a stationary phase of TLC plates F<jats:sub>254<\/jats:sub> (20\u2009\u00d7\u200910\u00a0cm) and using a developing system of ethyl acetate: methanol: n- hexane (8:2:3, by volume) with UV scanning at 254\u00a0nm for ERG, PHEN, CAF and DIP. For MEP, detection was done at 560\u00a0nm after spraying with 0.3% ethanolic solution of para -dimethylaminobenzaldehyde (PDAB) and heating at 110 \u00baC for 30\u00a0min. Analysis was performed in the concentration intervals of 0.06-2, 0.15\u20135\u00a0\u00b5g\/band for ERG and PHEN, respectively; while for CAF, DIP and MEP it was done in the ranges of 0.3-9, 0.5\u201310, 1\u2013100\u00a0\u00b5g\/band, respectively. Moreover, the method was used for the quantitation of the five studied drugs in their unique formulation and the recovery% was calculated and found to be 102.04, 100.73, 100.65, 99.91, 1nd 101.77% for ERG, PHEN, CAF, DIP, and MEP, in order and all these outcomes proved excellent selectivity of the method. Other validation parameters were tested following ICH guidelines. Accuracy ranged from 98.02 to 100.53% while the obtained %RSD of interday day precision ranged from 1.215 to 1.940%. The environmental impact and performance of the method was tested with several tools; Analytical eco-scale, green analytical procedure index (GAPI), Analytical GREEnness Metric Approach (AGREE), Blue applicability grade index (BAGI), and RGB additive color model. Results ensured minimum hazardous effect on health and environment. This is the first analytical approach developed for simultaneous analysis of the quinary mixture which can be easily applied in any analytical laboratory.<\/jats:p>","DOI":"10.1038\/s41598-024-79518-5","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T12:54:49Z","timestamp":1734353689000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["TLC densitometric approach for concurrent determination of quinary mixture for treatment of migraine with appraisal to method greenness and whiteness"],"prefix":"10.1038","volume":"14","author":[{"given":"Marco M. Z.","family":"Sharkawi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa A.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nehal F.","family":"Farid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada S.","family":"Abdelwahab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"79518_CR1","unstructured":"https:\/\/www.webmd.com\/migraines-headaches\/migraines-headaches-migraines"},{"key":"79518_CR2","unstructured":"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2740949"},{"key":"79518_CR3","unstructured":"The British Pharmacopeia Vols. I and II (Her Majesty\u2019s Stationary Office, 2007)."},{"key":"79518_CR4","unstructured":"Martindale The Complete drug Reference 33rd Edn (Pharmaceutical, 2002)."},{"key":"79518_CR5","doi-asserted-by":"publisher","unstructured":"Sawynok, J. Caffeine and pain. Pain 152, 726\u2013729 at (2011). https:\/\/doi.org\/10.1016\/j.pain.2010.10.011","DOI":"10.1016\/j.pain.2010.10.011"},{"key":"79518_CR6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1365-2044.1973.tb00283.x","volume":"28","author":"A Lal","year":"1973","unstructured":"Lal, A., Pandey, K., Chandra, P. & Pande, S. B. Dipyrone for treatment of post-operative pain. Anaesthesia. 28, 43\u201347 (1973).","journal-title":"Anaesthesia"},{"key":"79518_CR7","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jpba.2010.07.018","volume":"54","author":"K Karthikeyan","year":"2011","unstructured":"Karthikeyan, K., Arularasu, G. T., Murali, V. & Chandrasekara Pillai, K. Identification, isolation, characterization and response factor determination of process-related impurity in meprobamate drug substance. J. Pharm. Biomed. Anal. 54, 208\u2013212 (2011).","journal-title":"J. Pharm. Biomed. Anal."},{"key":"79518_CR8","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/chromsci\/45.5.251","volume":"45","author":"M Aranda","year":"2007","unstructured":"Aranda, M. & Morlock, G. Simultaneous determination of caffeine, ergotamine, and metamizol in solid pharmaceutical formulation by HPTLC-UV-FLD with mass confirmation by online HPTLC-ESI-MS. J. Chromatogr. Sci. 45, 251\u2013255 (2007).","journal-title":"J. Chromatogr. Sci."},{"key":"79518_CR9","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.pharma.2022.01.003","volume":"80","author":"A Ayman","year":"2022","unstructured":"Ayman, A., Zeid, A. M., Wahba, M. E. K. & EL-Shabrawy, Y. Simultaneous determination of ergotamine, caffeine and dipyrone in their ternary mixture by applying double divisor and first derivative ratio spectra methods. Ann. Pharm. Fr. 80, 718\u2013729 (2022).","journal-title":"Ann. Pharm. Fr."},{"key":"79518_CR10","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1590\/S0103-50532007000700020","volume":"18","author":"MS Di Nezio","year":"2007","unstructured":"Di Nezio, M. S. et al. A home-made hybrid system for the simultaneous determination of ergotamine, dipyrone and caffeine in pharmaceutical preparations. J. Braz. Chem. Soc. 18, 1439\u20131442 (2007).","journal-title":"J. Braz. Chem. Soc."},{"key":"79518_CR11","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1007\/s10809-005-0217-4","volume":"60","author":"GB Golubitskii","year":"2005","unstructured":"Golubitskii, G. B., Budko, E. & Ivanov, V. M. Quantitative analysis of pentalgin ICN tablets by gradient and isocratic high-performance liquid chromatography. J. Anal. Chem. 60, 961\u2013966 (2005).","journal-title":"J. Anal. Chem."},{"key":"79518_CR12","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1002\/jssc.202000256","volume":"43","author":"NF Farid","year":"2020","unstructured":"Farid, N. F., Naguib, I. A., Abdelhamid, N. S., Anwar, B. H. & Magdy, M. A. Validated ecofriendly chromatographic method for quantitative determination of anti-migraine quaternary mixture. J. Sep. Sci. 43, 2330\u20132337 (2020).","journal-title":"J. Sep. Sci."},{"key":"79518_CR13","doi-asserted-by":"crossref","unstructured":"Ragab, M. T., Ramadan, N. K., El-Ragehy, N. A. & El-Zeany, B. A. Thin layer chromatography\u2013spectrodensitometric determination of a three-component mixture of propyphenazone, caffeine, ergotamine tartrate, and two of their impurities with application to tablets, spiked human plasma, and green profile assessment. J. Planar. Chromatogr. Mod. TLC 36, 295\u2013305\u00a0(2023).","DOI":"10.1007\/s00764-023-00248-x"},{"key":"79518_CR14","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1080\/10826076.2011.629387","volume":"35","author":"YM Issa","year":"2012","unstructured":"Issa, Y. M., Hassoun, M. E. M. & Zayed, A. G. Simultaneous determination of Paracetamol, caffeine, domperidone, ergotamine tartrate, propyphenazone, and drotaverine HCL by high performance liquid chromatography. J. Liquid Chromatogr. Relat. Technol. 35, 2148\u20132161 (2012).","journal-title":"J. Liquid Chromatogr. Relat. Technol."},{"key":"79518_CR15","first-page":"344","volume":"7","author":"D Bhosale","year":"2012","unstructured":"Bhosale, D. & Nikalje, A. P. G. Development and validation of RP-Chromatography for simultaneous determination of Paracetamol, caffeine, ergotamine and prochlorperazine in tablets. Asian J. Pharm. Sci. 7, 344\u2013351 (2012).","journal-title":"Asian J. Pharm. Sci."},{"key":"79518_CR16","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1080\/01496395.2014.914953","volume":"49","author":"F Ibrahim","year":"2014","unstructured":"Ibrahim, F. & Wahba, M. E. K. Liquid chromatographic determination of ergotamine tartrate in its combined tablets using fluorimetric and UV detection: Application to content uniformity testing. Sep. Sci. Technol. (Philadelphia) 49, 2228\u20132240 (2014).","journal-title":"Sep. Sci. Technol. (Philadelphia)"},{"key":"79518_CR17","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1093\/chromsci\/bmab093","volume":"60","author":"NF Farid","year":"2022","unstructured":"Farid, N. F., Abdelhamid, N. S., Naguib, I. A., Anwar, B. H. & Magdy, M. A. Quantitative determination of anti-migraine quaternary mixture in presence of p-Aminophenol and 4-Chloroacetanilide. J. Chromatogr. Sci. 60, 538\u2013544 (2022).","journal-title":"J. Chromatogr. Sci."},{"key":"79518_CR18","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1093\/chromsci\/bms175","volume":"51","author":"MA Sultan","year":"2013","unstructured":"Sultan, M. A. et al. Capillary electrophoretic determination of antimigraine formulations containing caffeine, ergotamine, Paracetamol and domperidone or metoclopramide. J. Chromatogr. Sci. 51, 502\u2013510 (2013).","journal-title":"J. Chromatogr. Sci."},{"key":"79518_CR19","first-page":"033","volume":"3","author":"TS Belal","year":"2014","unstructured":"Belal, T. S., Khamis, E. F., el Yazbi, F. A. & Hamdy, M. M. A. High performance liquid chromatographic determination of the ternary mixture of caffeine, dipyrone and drotaverine hydrochloride in tablets dosage form. J. Appl. Pharm. Sci. 3, 033\u2013039 (2014).","journal-title":"J. Appl. Pharm. Sci."},{"key":"79518_CR20","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1080\/01496395.2014.957317","volume":"50","author":"FF Belal","year":"2015","unstructured":"Belal, F. F., El-Din, S., Tolba, M. K., Elmansi, H. & M. M. & Determination of two ternary mixtures for migraine treatment using HPLC method with ultra violet detection. Sep. Sci. Technol. (Philadelphia). 50, 592\u2013603 (2015).","journal-title":"Sep. Sci. Technol. (Philadelphia)"},{"key":"79518_CR21","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s10337-017-3263-9","volume":"80","author":"JC Vieira","year":"2017","unstructured":"Vieira, J. C. et al. HPLC\u2013DAD method for simultaneous determination of dipyrone (Metamizole) and caffeine in tablets and identification of major degradation product by direct infusion ESI\u2013MS. Chromatographia 80, 489\u2013495 (2017).","journal-title":"Chromatographia"},{"key":"79518_CR22","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.chroma.2013.12.048","volume":"1327","author":"MC Marra","year":"2014","unstructured":"Marra, M. C. et al. Ultra-fast determination of caffeine, dipyrone, and acetylsalicylic acid by capillary electrophoresis with capacitively coupled contactless conductivity detection and identification of degradation products. J. Chromatogr. A. 1327, 149\u2013154 (2014).","journal-title":"J. Chromatogr. A"},{"key":"79518_CR23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.microc.2016.01.009","volume":"127","author":"F Belal","year":"2016","unstructured":"Belal, F., El-Din, M. S., Tolba, M., El-Awady, M. & Elmansi, H. Analysis of four antimigraine drugs in two ternary mixtures by sweeping-micellar electrokinetic chromatography with retention factor gradient effect and dynamic pH junction. Microchem. J. 127, 11\u201321 (2016).","journal-title":"Microchem. J."},{"key":"79518_CR24","first-page":"465","volume":"45","author":"MA Abounassif","year":"1990","unstructured":"Abounassif, M. A., Gad-Kariem, E. A. & Wahbi, A. M. High performance liquid chromatographic determinations of Khellin, phenobarbitone and dipyrone combination in tablets. Farmaco. 45, 465\u2013472 (1990).","journal-title":"Farmaco"},{"key":"79518_CR25","unstructured":"Wen, L. & Fang, H. H. Simultaneous determination of four components in the compound child phenobarbital tablet using ultraviolet spectrophotometry. Bull. Hunan Med. Univ. 27, 83\u201384\u00a0(2002)."},{"key":"79518_CR26","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0014-827X(02)01265-X","volume":"57","author":"JT Franeta","year":"2002","unstructured":"Franeta, J. T. et al. HPLC assay of acetylsalicylic acid, Paracetamol, caffeine and phenobarbital in tablets. Farmaco. 57, 709\u2013713 (2002).","journal-title":"Farmaco"},{"key":"79518_CR27","unstructured":"Aziz, A. A. & Ahmed, K. Simultaneous determination of paracetamol with different active pharmaceutical ingredient (Api) and excipient in. Sci. Int. (Lahore) 27, 6173\u20136176\u00a0(2015)."},{"key":"79518_CR28","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1039\/c0ay00696c","volume":"3","author":"U Hass","year":"2011","unstructured":"Hass, U., D\u00fcnnbier, U., Massmann, G. & Pekdeger, A. Simultaneous determination of psychoactive substances and their metabolites in aqueous matrices by ultrahigh-performance liquid chromatography-tandem mass spectrometry. Anal. Methods 3, 902\u2013910 (2011).","journal-title":"Anal. Methods"},{"key":"79518_CR29","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1093\/jat\/bku029","volume":"38","author":"F B\u00e9valot","year":"2014","unstructured":"B\u00e9valot, F., Bottinelli, C., Cartiser, N., Fanton, L. & Guitton, J. Quantification of five compounds with heterogeneous physicochemical properties (morphine, 6-monoacetylmorphine, cyamemazine, meprobamate and caffeine) in 11 fluids and tissues, using automated solid-phase extraction and gas chromatography-tandem mass spectrometry. J. Anal. Toxicol. 38, 256\u2013264 (2014).","journal-title":"J. Anal. Toxicol."},{"key":"79518_CR30","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.trac.2012.03.013","volume":"37","author":"A Ga\u0142uszka","year":"2012","unstructured":"Ga\u0142uszka, A., Migaszewski, Z. M., Konieczka, P. & Namie\u015bnik, J. Analytical Eco-scale for assessing the greenness of analytical procedures. TrAC - Trends Anal. Chem. vol. 37, 61\u201372 (2012).","journal-title":"TrAC - Trends Anal. Chem. vol"},{"key":"79518_CR31","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.talanta.2018.01.013","volume":"181","author":"J P\u0142otka-Wasylka","year":"2018","unstructured":"P\u0142otka-Wasylka, J. A new tool for the evaluation of the analytical procedure: Green analytical procedure index. Talanta 181, 204\u2013209 (2018).","journal-title":"Talanta"},{"key":"79518_CR32","doi-asserted-by":"crossref","first-page":"10076","DOI":"10.1021\/acs.analchem.0c01887","volume":"92","author":"F Pena-Pereira","year":"2020","unstructured":"Pena-Pereira, F., Wojnowski, W. & Tobiszewski, M. AGREE - Analytical GREEnness Metric Approach and Software. Anal. Chem. 92, 10076\u201310082 (2020).","journal-title":"Anal. Chem."},{"key":"79518_CR33","doi-asserted-by":"crossref","first-page":"7598","DOI":"10.1039\/D3GC02347H","volume":"25","author":"N Manousi","year":"2023","unstructured":"Manousi, N., Wojnowski, W., P\u0142otka-Wasylka, J. & Samanidou, V. Blue applicability grade index (BAGI) and software: A new tool for the evaluation of method practicality. Green Chem. 25, 7598\u20137604 (2023).","journal-title":"Green Chem."},{"key":"79518_CR34","doi-asserted-by":"crossref","unstructured":"Pawe\u0142, M. N.& Pawe\u0142 K. What color is your method? Adaptation of the RGB additive color model to analytical method evaluation. Anal. Chem. 91(6), 10342\u201310352 (2019).","DOI":"10.1021\/acs.analchem.9b01872"},{"key":"79518_CR35","unstructured":"ICH guideline Q14 on analytical procedure development. In International Conference on Harmonisation 31\u00a0(2022)."},{"key":"79518_CR36","unstructured":"The United States Pharmacopeia, National Formulary 35, United States Pharmacopeia 30th Ed. (Convention Inc., 2012)."},{"key":"79518_CR37","volume-title":"Clarke\u2019s Analysis of Drugs and Poisons","author":"AC Moffat","year":"2011","unstructured":"Moffat, A. C., Osselton, M. D., Widdop, B. & Watts, J. Clarke\u2019s Analysis of Drugs and Poisons 4th edn. (Pharmaceutical Press, Berlin, 2011).","edition":"4"},{"key":"79518_CR38","doi-asserted-by":"crossref","first-page":"62","DOI":"10.30526\/32.3.2283","volume":"32","author":"NA Sabir","year":"2019","unstructured":"Sabir, N. A. & Al-Janabi, K. W. S. Colorimetric determination of meprobamate after a simple derivatization. Ibn AL-Haitham J. Pure Appl. Sci. 32, 62\u201369 (2019).","journal-title":"Ibn AL-Haitham J. Pure Appl. Sci."},{"key":"79518_CR39","doi-asserted-by":"crossref","unstructured":"AboulMagd, A. M., Abdelwahab, N. S., Abdelrahmam, M. M., Abdel-Rahman, H. H. & Farid, N. F. Lipophilicity study of diffirent cephalosporins: Computational prediction of minimum inhibitory concentration using salting-out chromatography. J. Pharm. Biomed. Anal.\u00a0206, 114358\u00a0(2021).","DOI":"10.1016\/j.jpba.2021.114358"},{"key":"79518_CR40","doi-asserted-by":"crossref","unstructured":"Farid, N. F. & Abdelwahab, N. S. Development and validation of different chromatographic methods for analysis of cabergoline in the presence of its degradation products: Studying degradation profile. Chromatographia 82 (2019).","DOI":"10.1007\/s10337-019-03763-4"},{"key":"79518_CR41","doi-asserted-by":"crossref","first-page":"111197","DOI":"10.1016\/j.microc.2024.111197","volume":"205","author":"HM Marzouk","year":"2024","unstructured":"Marzouk, H. M., Gouda, A. S., Rezk, M. R. & Abdel-Megied, A. M. Innovative eco-friendly stability-indicating HPLC-PDA method for simultaneous determination of the emerging antiviral drugs against COVID-19 infection molnupiravir and favipiravir; degradation kinetic studies along with LC-MS based structure elucidation. Microchem. J. 205, 111197 (2024).","journal-title":"Microchem. J."},{"key":"79518_CR42","doi-asserted-by":"crossref","first-page":"108048","DOI":"10.1016\/j.microc.2022.108048","volume":"183","author":"NF Farid","year":"2022","unstructured":"Farid, N. F. & Abdelwahab, N. S. A new HPLC methodology for the analysis of metronidazole and dexibuprofen: Application to pharmacokinetic study and comparative greenness assessment. Microchem. J. 183, 108048 (2022).","journal-title":"Microchem. J."},{"key":"79518_CR43","doi-asserted-by":"crossref","first-page":"107582","DOI":"10.1016\/j.microc.2022.107582","volume":"179","author":"NF Farid","year":"2022","unstructured":"Farid, N. F., Elgendy, M. O. & Abdelwahab, N. S. Sustainable TLC-densitometric method for pharmacokinetic study of the concurrently used ibuprofen and metronidazole: Green metric assessment. Microchem. J. 179, 107582 (2022).","journal-title":"Microchem. J."},{"key":"79518_CR44","doi-asserted-by":"crossref","first-page":"117211","DOI":"10.1016\/j.trac.2023.117211","volume":"166","author":"M Shi","year":"2023","unstructured":"Shi, M. et al. Overview of sixteen green analytical chemistry metrics for evaluation of the greenness of analytical methods. TrAC - Trends Anal. Chem. 166, 117211 (2023).","journal-title":"TrAC - Trends Anal. Chem."},{"key":"79518_CR45","doi-asserted-by":"crossref","first-page":"111060","DOI":"10.1016\/j.microc.2024.111060","volume":"204","author":"MMZ Sharkawi","year":"2024","unstructured":"Sharkawi, M. M. Z., Safwat, M. T. & Abdelwahab, N. S. Ecofriendly UPLC-MS\/MS method for simultaneous assay of veterinary drugs residues; erythromycin, sulfadiazine and trimethoprim in edible chicken tissues, evaluation of method greenness and whiteness. Microchem. J. 204, 111060 (2024).","journal-title":"Microchem. J."},{"key":"79518_CR46","volume-title":"High-Performance Thin-Layer Chromatography (HPTLC)","author":"MM Srivastava","year":"2010","unstructured":"Srivastava, M. M. High-Performance Thin-Layer Chromatography (HPTLC) (Springer, Heidelberg, 2010)."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-79518-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-79518-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-79518-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T16:59:52Z","timestamp":1744217992000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-79518-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,16]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["79518"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-79518-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,16]]},"assertion":[{"value":"21 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"30477"}}