{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T16:46:50Z","timestamp":1793724410321,"version":"4.6.1"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-45839-w","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T13:34:58Z","timestamp":1774445698000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["N2-(1-carboxyethyl)-2\u2032-deoxyguanosine as a genotoxic glycation marker associated with chromatin architectural alterations in oral squamous cell carcinoma"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7858-1737","authenticated-orcid":false,"given":"Gulnaz","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizwana Sanaullah","family":"Waraich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hurtamina","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5530-1383","authenticated-orcid":false,"given":"Rifat Zubair","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"issue":"5","key":"45839_CR1","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1308\/rcsbull.2025","volume":"107","author":"K Dhingra","year":"2025","unstructured":"Dhingra, K. Oral cancer: a global threat. J. Indian Med. Assoc. 107, (5), 257\u2013259. https:\/\/doi.org\/10.1308\/rcsbull.2025 (2025).","journal-title":"J. Indian Med. Assoc."},{"key":"45839_CR2","doi-asserted-by":"publisher","first-page":"155489","DOI":"10.1016\/j.prp.2024.155489","volume":"261","author":"D Jagadeesan","year":"2024","unstructured":"Jagadeesan, D. et al. Comprehensive insights into oral squamous cell carcinoma: diagnosis, pathogenesis, and therapeutic advances. Pathol. \u2013 Res. Pract. 261, 155489. https:\/\/doi.org\/10.1016\/j.prp.2024.155489 (2024).","journal-title":"Pathol. \u2013 Res. Pract."},{"key":"45839_CR3","unstructured":"Pepper, T. S.S. Cancer of the oral mucosa. Treasure Island (FL): StatPearls; (2024). https:\/\/pubmed.ncbi.nlm.nih.gov\/33351426\/."},{"key":"45839_CR4","unstructured":"Service, N. H. Lip and oral cavity (ICD-10 C00, C02\u2013C06) London, UK: NHS England Digital; (2023). https:\/\/digital.nhs.uk\/ndrs\/data\/cancer-data-training-materials\/staging-sheets\/lip-and-oral-cavity."},{"issue":"7","key":"45839_CR5","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/S1470-2045(17)30438-2","volume":"18","author":"B O\u2019Sullivan","year":"2017","unstructured":"O\u2019Sullivan, B. et al. The TNM classification of malignant tumours-towards common understanding and reasonable expectations. Lancet Oncol. 18, (7), 849\u2013851. https:\/\/doi.org\/10.1016\/S1470-2045(17)30438-2 (2017).","journal-title":"Lancet Oncol."},{"key":"45839_CR6","unstructured":"Wang, X. Z.Z. Oral cancer (IntechOpen, 2021). https:\/\/www.intechopen.com\/chapters\/75405."},{"key":"45839_CR7","unstructured":"Ferlay, J. E. et al. F. Global cancer observatory: Cancer Today Lyon (International Agency for Research on Cancer, 2022). https:\/\/gco.iarc.who.int\/today."},{"issue":"8","key":"45839_CR8","doi-asserted-by":"publisher","first-page":"e0236359","DOI":"10.1371\/journal.pone.0236359","volume":"15","author":"N Anwar","year":"2020","unstructured":"Anwar, N. et al. Oral cancer: Clinicopathological features and associated risk factors in a high risk population presenting to a major tertiary care center in Pakistan. PLoS One. 15, (8), e0236359. https:\/\/doi.org\/10.1371\/journal.pone.0236359 (2020).","journal-title":"PLoS One"},{"issue":"2","key":"45839_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/dj12020025","volume":"12","author":"MF Khan","year":"2024","unstructured":"Khan, M. F., Hayhoe, R. P. & Kabir, R. Exploring the risk factors for oral cancer in Pakistan: a systematic literature review. J. Oral Maxillofacial Pathol. 12, (2), 1\u201319. https:\/\/doi.org\/10.3390\/dj12020025 (2024).","journal-title":"J. Oral Maxillofacial Pathol."},{"issue":"19","key":"45839_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cancers14194967","volume":"14","author":"M Gonz\u00e1lez-Moles","year":"2022","unstructured":"Gonz\u00e1lez-Moles, M., Aguilar-Ruiz, M. & Ramos-Garc\u00eda, P. Challenges in the early diagnosis of oral cancer, evidence gaps and strategies for improvement: A scoping review of systematic reviews. Cancers 14, (19), 1\u201324. https:\/\/doi.org\/10.3390\/cancers14194967 (2022).","journal-title":"Cancers"},{"issue":"11","key":"45839_CR11","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1038\/s41415-024-8118-9","volume":"237","author":"W Jerjes","year":"2024","unstructured":"Jerjes, W. Addressing oral cancer inequalities: a multifaceted approach to equitable healthcare. Br. Dent. J. 237, (11), 837\u2013841. https:\/\/doi.org\/10.1038\/s41415-024-8118-9 (2024).","journal-title":"Br. Dent. J."},{"issue":"6","key":"45839_CR12","first-page":"265","volume":"13","author":"PGS Dhungana","year":"2025","unstructured":"Dhungana, P. G. S. Oral cancer: A public health challenges- a narrative review. Int. J. Creative Res. Thoughts. 13, (6), 265\u2013268 (2025). https:\/\/ijcrt.org\/papers\/IJCRT2012xxxx.pdf","journal-title":"Int. J. Creative Res. Thoughts"},{"issue":"1","key":"45839_CR13","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s40538-025-00784-0","volume":"12","author":"K Gu","year":"2025","unstructured":"Gu, K. et al. Molecular mechanism study on the contribution of open-fire flue-curing technology to tobacco leaf aroma. Sci. Rep. 12, (1), 63. https:\/\/doi.org\/10.1186\/s40538-025-00784-0 (2025).","journal-title":"Sci. Rep."},{"issue":"7","key":"45839_CR14","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.3390\/molecules25071734","volume":"25","author":"M Bano\u017ei\u0107","year":"2020","unstructured":"Bano\u017ei\u0107, M., Joki\u0107, S., A\u010dkar, \u0110., Bla\u017ei\u0107, M. & \u0160ubari\u0107, D. J. M. Carbohydrates\u2014key players in tobacco aroma formation and quality determination. Molecules 25, (7), 1734. https:\/\/doi.org\/10.3390\/molecules25071734 (2020).","journal-title":"Molecules"},{"issue":"11","key":"45839_CR15","doi-asserted-by":"publisher","first-page":"4140","DOI":"10.1039\/C2CS35025D","volume":"41","author":"WC Yiliang","year":"2012","unstructured":"Yiliang, W. C. Flavour chemistry of methylglyoxal and glyoxal. Chem. Soc. Rev. 41, (11), 4140\u20134149. https:\/\/doi.org\/10.1039\/C2CS35025D (2012).","journal-title":"Chem. Soc. Rev."},{"issue":"2","key":"45839_CR16","doi-asserted-by":"publisher","first-page":"405","DOI":"10.3390\/nu15020405","volume":"15","author":"K Phuong-Nguyen","year":"2023","unstructured":"Phuong-Nguyen, K., McNeill, B. A., Aston-Mourney, K. & Rivera, L. R. Advanced glycation end-products and their effects on gut health. Nutrients 15, (2), 405. https:\/\/doi.org\/10.3390\/nu15020405 (2023).","journal-title":"Nutrients"},{"issue":"1","key":"45839_CR17","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.bone.2022.116526","volume":"100","author":"C Schalkwijk","year":"2020","unstructured":"Schalkwijk, C. & Stehouwer, C. Methylglyoxal, a highly reactive dicarbonyl compound, in diabetes, its vascular complications, and other age-related diseases. Physiol. Rev. 100, (1), 407\u2013461. https:\/\/doi.org\/10.1016\/j.bone.2022.116526 (2020).","journal-title":"Physiol. Rev."},{"issue":"10","key":"45839_CR18","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.1021\/acs.chemrestox.2c00160","volume":"35","author":"SWT Lai","year":"2022","unstructured":"Lai, S. W. T., Lopez Gonzalez, E. D. J., Zoukari, T., Ki, P. & Shuck, S. C. Methylglyoxal and its adducts: Induction, repair, and association with disease. Crit. Rev. Biochem. Mol. Biol. 35, (10), 1720\u20131746. https:\/\/doi.org\/10.1021\/acs.chemrestox.2c00160 (2022).","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"issue":"12","key":"45839_CR19","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.1021\/bi101933p","volume":"50","author":"D Tamae","year":"2011","unstructured":"Tamae, D., Lim, P., Wuenschell, G. E. & Termini, J. Mutagenesis and repair induced by the DNA advanced glycation end product N2-(1-carboxyethyl)-2\u2032-deoxyguanosine in human cells. Biochemistry 50, (12), 2321\u20132329. https:\/\/doi.org\/10.1021\/bi101933p (2011).","journal-title":"Biochemistry"},{"issue":"2","key":"45839_CR20","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1006\/bbrc.1999.1528","volume":"264","author":"M Pischetsrieder","year":"1999","unstructured":"Pischetsrieder, M., Seidel, W., M\u00fcnch, G. & Schinzel, R. N2-carboxyethyl-2\u2019-deoxyguanosine, a nonenzymatic glycation adduct of DNA, induces single-strand breaks and increases mutation frequencies. Biochem. Biophys. Res. Commun. 264, (2), 544\u2013549. https:\/\/doi.org\/10.1006\/bbrc.1999.1528 (1999).","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"10","key":"45839_CR21","doi-asserted-by":"publisher","first-page":"e202101159","DOI":"10.26508\/lsa.202101159","volume":"4","author":"AK Ciminera","year":"2021","unstructured":"Ciminera, A. K., Shuck, S. C. & Termini, J. Elevated glucose increases genomic instability by inhibiting nucleotide excision repair. Life Sci. Alliance. 4, (10), e202101159. https:\/\/doi.org\/10.26508\/lsa.202101159 (2021).","journal-title":"Life Sci. Alliance"},{"issue":"9","key":"45839_CR22","doi-asserted-by":"publisher","first-page":"1814","DOI":"10.1021\/bi901924b","volume":"49","author":"GE Wuenschell","year":"2010","unstructured":"Wuenschell, G. E. et al. Mutagenic potential of DNA glycation: Miscoding by (R)- and (S)-N2-carboxyethyl-2\u2019-deoxyguanosine. Biochemistry 49, (9), 1814\u20131821. https:\/\/doi.org\/10.1021\/bi901924b (2010).","journal-title":"Biochemistry"},{"key":"45839_CR23","unstructured":"Hope, C. N2-(1-carboxyethyl)-2\u2032-deoxyguanosine (CEdG) a potential biomarker for diabetes: ClinicalTrials.gov; 2019 [updated November 1, 2019]. https:\/\/ichgcp.net\/clinical-trials-registry\/NCT02065310?utm."},{"issue":"3","key":"45839_CR24","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.cmet.2018.08.014","volume":"28","author":"J Chaudhuri","year":"2018","unstructured":"Chaudhuri, J. et al. The role of advanced glycation end products in aging and metabolic diseases: bridging association and causality. Cell Metabol. 28, (3), 337\u2013352. https:\/\/doi.org\/10.1016\/j.cmet.2018.08.014 (2018).","journal-title":"Cell Metabol."},{"key":"45839_CR25","unstructured":"Rossi, Y. S. J. inventor; City of Hope, assignee. Methods of quantifying N2-(1-carboxyethyl)-2\u2032-deoxyguanosine (CEDG) and synthesis of oligonucleotides containing CEdG. (2010). United States patent US20100102218A1."},{"issue":"2","key":"45839_CR26","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1021\/acs.chemrestox.6b00414","volume":"30","author":"R Jaramillo","year":"2017","unstructured":"Jaramillo, R. et al. DNA advanced glycation end products (DNA-AGES) are elevated in urine and tissue in an animal model of type 2 diabetes. Chem. Res. Toxicol. 30, (2), 689\u2013698. https:\/\/doi.org\/10.1021\/acs.chemrestox.6b00414 (2017).","journal-title":"Chem. Res. Toxicol."},{"issue":"2","key":"45839_CR27","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1038\/sj.ki.5000064","volume":"69","author":"H Li","year":"2006","unstructured":"Li, H. et al. N2-carboxyethyl-2\u2032-deoxyguanosine, a DNA glycation marker, in kidneys and aortas of diabetic and uremic patients. Kidney Int. 69, (2), 388\u2013392. https:\/\/doi.org\/10.1038\/sj.ki.5000064 (2006).","journal-title":"Kidney Int."},{"key":"45839_CR28","doi-asserted-by":"publisher","first-page":"102186","DOI":"10.1016\/j.molmet.2025.102186","volume":"98","author":"EJ Lopez Gonzalez","year":"2025","unstructured":"Lopez Gonzalez, E. J. et al. Methylglyoxal-induced RNA modifications decrease RNA stability and translation and are associated with type 2 diabetes. Mol. Metabolism. 98, 102186. https:\/\/doi.org\/10.1016\/j.molmet.2025.102186 (2025).","journal-title":"Mol. Metabolism"},{"key":"45839_CR29","doi-asserted-by":"publisher","unstructured":"Synold, T. W., Termini, J. & Shuck, S. inventor; City of Hope., assignee. Methods of quantifying methylglyoxal\u2013induced nucleic acid adducts. United States patent. 11 https:\/\/doi.org\/10.1021\/tx8002217 (2023).\u00a0","DOI":"10.1021\/tx8002217"},{"issue":"11","key":"45839_CR30","doi-asserted-by":"publisher","first-page":"2148","DOI":"10.1021\/tx800224y","volume":"21","author":"T Synold","year":"2008","unstructured":"Synold, T. et al. Advanced glycation end products of DNA: Quantification of N2-(1-carboxyethyl)-2\u2032-deoxyguanosine in biological samples by liquid chromatography electrospray ionization tandem mass spectrometry. Chem. Res. Toxicol. 21, (11), 2148\u20132155. https:\/\/doi.org\/10.1021\/tx800224y (2008).","journal-title":"Chem. Res. Toxicol."},{"issue":"1","key":"45839_CR31","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1186\/1471-2407-10-260","volume":"10","author":"V Bedin","year":"2010","unstructured":"Bedin, V., Adam, R. L., de S\u00e1, B. C. S., Landman, G. & Metze, K. Fractal dimension of chromatin is an independent prognostic factor for survival in melanoma. BMC Cancer. 10, (1), 260. https:\/\/doi.org\/10.1186\/1471-2407-10-260 (2010).","journal-title":"BMC Cancer"},{"issue":"12","key":"45839_CR32","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1093\/jnci\/djy063","volume":"110","author":"B Nielsen","year":"2018","unstructured":"Nielsen, B. et al. Association between proportion of nuclei with high chromatin entropy and prognosis in gynecological cancers. J. Natl Cancer Inst. 110, (12), 1400\u20131408. https:\/\/doi.org\/10.1093\/jnci\/djy063 (2018).","journal-title":"J. Natl Cancer Inst."},{"issue":"8","key":"45839_CR33","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3390\/tomography11080087","volume":"11","author":"D Andrade","year":"2025","unstructured":"Andrade, D., Gifford, H. C. & Das, M. Assessment of influencing factors and robustness of computable image texture features in digital images. Tomography 11, (8), 87. https:\/\/doi.org\/10.3390\/tomography11080087 (2025).","journal-title":"Tomography"},{"issue":"6","key":"45839_CR34","doi-asserted-by":"publisher","first-page":"e1293","DOI":"10.1002\/cnr2.1293","volume":"3","author":"TY Rahman","year":"2020","unstructured":"Rahman, T. Y., Mahanta, L. B., Choudhury, H., Das, A. K. & Sarma, J. D. Study of morphological and textural features for classification of oral squamous cell carcinoma by traditional machine learning techniques. Cancer Rep. 3, (6), e1293. https:\/\/doi.org\/10.1002\/cnr2.1293 (2020).","journal-title":"Cancer Rep."},{"issue":"1","key":"45839_CR35","doi-asserted-by":"publisher","first-page":"107","DOI":"10.3390\/atmos16010107","volume":"16","author":"X Gao","year":"2025","unstructured":"Gao, X. et al. Analytical methods for atmospheric carbonyl compounds: a review. J. Environ. Sci. 16, (1), 107. https:\/\/doi.org\/10.3390\/atmos16010107 (2025).","journal-title":"J. Environ. Sci."},{"issue":"1","key":"45839_CR36","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1111\/prd.12542","volume":"96","author":"A Radaic","year":"2024","unstructured":"Radaic, A. et al. Biological biomarkers of oral cancer. Periodontol 2000. 96, (1), 250\u2013270. https:\/\/doi.org\/10.1111\/prd.12542 (2024).","journal-title":"Periodontol 2000"},{"key":"45839_CR37","doi-asserted-by":"crossref","unstructured":"Cohen, J. Statistical power analysis for the behavioral sciences 2nd edn (Routledge, 2013).","DOI":"10.4324\/9780203771587"},{"issue":"4","key":"45839_CR38","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1002\/pst.185","volume":"4","author":"SA Julious","year":"2005","unstructured":"Julious, S. A. Sample size of 12 per group rule of thumb for a pilot study. Pharm. Stat. 4, (4), 287\u2013291. https:\/\/doi.org\/10.1002\/pst.185 (2005).","journal-title":"Pharm. Stat."},{"key":"45839_CR39","unstructured":"Addenbrooke\u2019s, N. H. S. & Trust, C. Histopathology department manual: Cambridge University Hospitals NHS Foundation Trust."},{"key":"45839_CR40","unstructured":"IHC-WORLD. H&E staining method and protocol \u2013 Harris 2024. Available from: https:\/\/ihcworld.com\/2024\/01\/25\/he-staining-method-and-protocol-harris\/."},{"key":"45839_CR41","unstructured":"Nova Scotia Community College (NSCC) \/ & Hartlen, M. Routine hematoxylin and eosin (H&E): Regressive method \u2014 histotechnology lab manual Nova Scotia (Canada): NSCC; 2022 [updated September 5, 2022]. Available from: https:\/\/pressbooks.nscc.ca\/histotechnology\/chapter\/88\/."},{"key":"45839_CR42","unstructured":"IHC\u2013World. Antigen retrieval method for free floating sections \u2014 IHC\u2013world 2024 [updated January 21, 2024]. Available from: https:\/\/ihcworld.com\/2024\/01\/21\/antigen-retrieval-method-for-free-floating-sections\/."},{"issue":"8","key":"45839_CR43","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1177\/002215540305100803","volume":"51","author":"H Ino","year":"2003","unstructured":"Ino, H. Antigen retrieval by heating en bloc for pre-fixed frozen material. Acta Histochem. Cytochem. 51, (8), 995\u20131003. https:\/\/doi.org\/10.1177\/002215540305100803 (2003).","journal-title":"Acta Histochem. Cytochem."},{"key":"45839_CR44","doi-asserted-by":"publisher","unstructured":"Suzuki, T., Matsuzaki, T. & Takata, K. J. Fluorescence counter-staining of cell nuclear DNA for multi-color laser confocal microscopy. 31(4), 297\u2013301. https:\/\/doi.org\/10.1267\/ahc.31.297 (1998).","DOI":"10.1267\/ahc.31.297"},{"issue":"10","key":"45839_CR45","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1021\/tx0501278","volume":"18","author":"M Frischmann","year":"2005","unstructured":"Frischmann, M., Bidmon, C., Angerer, J. & Pischetsrieder, M. Identification of DNA adducts of methylglyoxal. Chem. Res. Toxicol. 18, (10), 1586\u20131592. https:\/\/doi.org\/10.1021\/tx0501278 (2005).","journal-title":"Chem. Res. Toxicol."},{"issue":"10","key":"45839_CR46","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1021\/tx049929d","volume":"17","author":"M Schneider","year":"2004","unstructured":"Schneider, M. et al. Determination of glycated nucleobases in human urine by a new monoclonal antibody specific for N2-carboxyethyl-2\u2019-deoxyguanosine. Chem. Res. Toxicol. 17, (10), 1385\u20131390. https:\/\/doi.org\/10.1021\/tx049929d (2004).","journal-title":"Chem. Res. Toxicol."},{"issue":"7","key":"45839_CR47","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3390\/biom9070253","volume":"9","author":"NK Roy","year":"2019","unstructured":"Roy, N. K. et al. Isoform-specific role of Akt in oral squamous cell carcinoma. Biomolecules 9, (7), 253. https:\/\/doi.org\/10.3390\/biom9070253 (2019).","journal-title":"Biomolecules"},{"issue":"7","key":"45839_CR48","doi-asserted-by":"publisher","first-page":"e68224","DOI":"10.1371\/journal.pone.0068224","volume":"8","author":"A Das","year":"2013","unstructured":"Das, A., Bhattacharya, A., Chakrabarty, S., Ganguli, A. & Chakrabarti, G. Smokeless tobacco extract (STE)-induced toxicity in mammalian cells is mediated by the disruption of cellular microtubule network: a key mechanism of cytotoxicity. PLoS One. 8, (7), e68224. https:\/\/doi.org\/10.1371\/journal.pone.0068224 (2013).","journal-title":"PLoS One"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45839-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45839-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45839-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T12:53:24Z","timestamp":1776430404000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45839-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["45839"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-45839-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]},"assertion":[{"value":"6 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2026","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"}},{"value":"The study was approved by the Institutional Review Board (IRB), Jinnah Postgraduate Medical Center (JPMC), Jinnah Hospital, Karachi (Ref No. NO.F.2\u201381\/2020-GENL\/48723\/JPMC), and was conducted in accordance with the ethical principles of the Declaration of Helsinki. Written informed consent was obtained from all participants prior to inclusion in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent"}}],"article-number":"12715"}}