{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:29:42Z","timestamp":1789576182595,"version":"build-2803163510"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":32,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Yunnan Fundamental Research Projects","award":["CB23059C065A"],"award-info":[{"award-number":["CB23059C065A"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Spinal infections (SI) are on the rise due to an aging population and the prevalence of more invasive procedures. This study aims to systematically review the microbiological spectrum of SI to enhance diagnostic accuracy and inform effective antibiotic treatment strategies. The last search was conducted on May 9th, 2024, from databases including EMBASE, PubMed, and Web of Science. The outcome variable is infection rate, and the detection method used should be blood culture, tissue culture, or molecular biology method. Two researchers independently extracted research data and evaluated its quality using the JBI Critical Appraisal Tools. Out of 14,639 identified records, 156 studies (encompassing 13,539 patients) were included. Staphylococcus aureus was identified as the most prevalent pathogen, with pooled infection rates of 17.6% (95%CI: 12.8\u201322.9%;\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>2<\/jats:italic>\n                    <\/jats:sup>\n                    =93%) in blood culture, 16.8% (95%CI: 14.0\u201319.8%;\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>2<\/jats:italic>\n                    <\/jats:sup>\n                    =96%) in tissue culture, and 12.0% (95%CI: 9.3\u201315.0%;\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>2<\/jats:italic>\n                    <\/jats:sup>\n                    =35%) in molecular methods. The bacterial spectrum also featured\n                    <jats:italic>Staphylococcus epidermidis<\/jats:italic>\n                    ,\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    , and\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (MTB). Molecular methods, particularly metagenomic next-generation sequencing (mNGS), demonstrated markedly superior sensitivity for MTB detection, with a pooled rate of 9.7% (95%CI: 4.6\u201316.3%;\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>2<\/jats:italic>\n                    <\/jats:sup>\n                    =90%) compared to 1.3% (95%CI: 0.6\u20132.1%;\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>2<\/jats:italic>\n                    <\/jats:sup>\n                    =86%) by tissue culture. The odds ratio for MTB detection with mNGS versus conventional culture was 4.24 (95%CI: 1.68\u201310.73). This review confirms that a core group of pathogens, including\n                    <jats:italic>Staphylococcus aureus, Staphylococcus epidermidis<\/jats:italic>\n                    , MTB, and\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    . Our findings underscore that tissue culture is fundamental for common pyogenic bacteria, while metagenomic next-generation sequencing is indispensable for detecting fastidious organisms like MTB.\n                    <jats:italic>Trial registration<\/jats:italic>\n                    : The protocol was registered with PROSPERO (No. CRD42023427429). Registered on May 28, 2023\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-28576-4","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T04:15:42Z","timestamp":1764303342000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The bacterial spectrum of spinal infections based on blood culture, tissue culture, and molecular methods: a systematic review and meta-analysis"],"prefix":"10.1038","volume":"15","author":[{"given":"Rui","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liye","family":"Zi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbing","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guozhong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"issue":"12","key":"28576_CR1","doi-asserted-by":"publisher","first-page":"2464","DOI":"10.1007\/s00259-019-04393-6","volume":"46","author":"E Lazzeri","year":"2019","unstructured":"Lazzeri, E. et al. Joint EANM\/ESNR and ESCMID-endorsed consensus document for the diagnosis of spine infection (spondylodiscitis) in adults. Eur. J. Nucl. Med. Mol. Imaging 46(12), 2464\u20132487 (2019).","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"issue":"1","key":"28576_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0030-5898(20)32044-7","volume":"27","author":"RR Calderone","year":"1996","unstructured":"Calderone, R. R. & Larsen, J. M. Overview and classification of spinal infections. Orthop. Clin. North Am. 27(1), 1\u20138 (1996).","journal-title":"Orthop. Clin. North Am."},{"key":"28576_CR3","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1093\/jac\/dkq303","volume":"65","author":"T Gouliouris","year":"2010","unstructured":"Gouliouris, T., Aliyu, S. H. & Brown, N. M. Spondylodiscitis: Update on diagnosis and management. J. Antimicrob. Chemother. 65, 311\u2013324 (2010).","journal-title":"J. Antimicrob. Chemother."},{"issue":"1","key":"28576_CR4","first-page":"53","volume":"9","author":"AL Gasbarrini","year":"2005","unstructured":"Gasbarrini, A. L. et al. Clinical features, diagnostic and therapeutic approaches to haematogenous vertebral osteomyelitis. Eur. Rev. Med. Pharmacol. Sci. 9(1), 53\u201366 (2005).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"issue":"2","key":"28576_CR5","doi-asserted-by":"publisher","first-page":"27","DOI":"10.14245\/kjs.2017.14.2.27","volume":"14","author":"JW Kwon","year":"2017","unstructured":"Kwon, J. W., Hyun, S. J., Han, S. H., Kim, K. J. & Jahng, T. A. Pyogenic vertebral osteomyelitis: Clinical features, diagnosis, and treatment. Korean J. Spine. 14(2), 27\u201334 (2017).","journal-title":"Korean J. Spine."},{"issue":"1","key":"28576_CR6","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.jiph.2010.01.001","volume":"3","author":"GS Skaf","year":"2010","unstructured":"Skaf, G. S. et al. Pyogenic spondylodiscitis: an overview. J. Infect. Public Health 3(1), 5\u201316 (2010).","journal-title":"J. Infect. Public Health"},{"issue":"6","key":"28576_CR7","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1016\/j.jiph.2023.04.010","volume":"16","author":"J Kim","year":"2023","unstructured":"Kim, J., Oh, S. H., Kim, S. W. & Kim, T. H. The epidemiology of concurrent infection in patients with pyogenic spine infection and its association with early mortality: A nationwide cohort study based on 10,695 patients. J. Infect. Public Health. 16(6), 981\u2013988 (2023).","journal-title":"J. Infect. Public Health."},{"issue":"11","key":"28576_CR8","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2019-232540","volume":"12","author":"E Papachristodoulou","year":"2019","unstructured":"Papachristodoulou, E., Kakoullis, L., Louppides, S. & Panos, G. Granulomatous infective spondylitis in a patient presenting with progressive difficulty in walking: The differential between tuberculosis and brucellosis. BMJ Case Rep. 12(11), e232540 (2019).","journal-title":"BMJ Case Rep."},{"key":"28576_CR9","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.827528","volume":"12","author":"X Chen","year":"2022","unstructured":"Chen, X., Ye, J., Lei, H. & Wang, C. Novel potential diagnostic serum biomarkers of metabolomics in osteoarticular tuberculosis patients: A preliminary study. Front. Cell Infect. Microbiol. 12, 827528 (2022).","journal-title":"Front. Cell Infect. Microbiol."},{"issue":"2","key":"28576_CR10","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.nic.2015.01.003","volume":"25","author":"ET Tali","year":"2015","unstructured":"Tali, E. T., Oner, A. Y. & Koc, A. M. Pyogenic spinal infections. Neuroimaging Clin. N. Am. 25(2), 193\u2013208 (2015).","journal-title":"Neuroimaging Clin. N. Am."},{"issue":"3","key":"28576_CR11","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1055\/s-2000-9342","volume":"4","author":"SF Hetem","year":"2000","unstructured":"Hetem, S. F. & Schils, J. P. Imaging of infections and inflammatory conditions of the spine. Semin. Musculoskelet. Radiol. 4(3), 329\u2013347. https:\/\/doi.org\/10.1055\/s-2000-9342 (2000).","journal-title":"Semin. Musculoskelet. Radiol."},{"issue":"4","key":"28576_CR12","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1007\/s00586-015-4318-y","volume":"25","author":"JP Rutges","year":"2016","unstructured":"Rutges, J. P., Kempen, D. H., van Dijk, M. & Oner, F. C. Outcome of conservative and surgical treatment of pyogenic spondylodiscitis: A systematic literature review. Eur. Spine J. 25(4), 983\u2013999 (2016).","journal-title":"Eur. Spine J."},{"issue":"2","key":"28576_CR13","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/s00264-011-1384-6","volume":"36","author":"WY Cheung","year":"2012","unstructured":"Cheung, W. Y. & Luk, K. D. Pyogenic spondylitis. Int. Orthop. 36(2), 397\u2013404 (2012).","journal-title":"Int. Orthop."},{"issue":"2","key":"28576_CR14","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1053\/j.semnuclmed.2017.11.001","volume":"48","author":"M Raghavan","year":"2018","unstructured":"Raghavan, M., Lazzeri, E. & Palestro, C. J. Imaging of Spondylodiscitis. Semin. Nucl. Med. 48(2), 131\u2013147 (2018).","journal-title":"Semin. Nucl. Med."},{"issue":"Suppl 2","key":"28576_CR15","first-page":"8","volume":"16","author":"A Leone","year":"2012","unstructured":"Leone, A. et al. Imaging of spondylodiscitis. Eur. Rev. Med. Pharmacol. Sci. 16(Suppl 2), 8\u201319 (2012).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"issue":"1","key":"28576_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2023.115926","volume":"106","author":"A Both","year":"2023","unstructured":"Both, A. et al. The added value of a commercial 16S\/18S-PCR assay (UMD-SelectNA, Molzym) for microbiological diagnosis of spondylodiscitis: An observational study. Diagn. Microbiol. Infect. Dis. 106(1), 115926 (2023).","journal-title":"Diagn. Microbiol. Infect. Dis."},{"issue":"10","key":"28576_CR17","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1080\/00365540802119994","volume":"40","author":"K Fuursted","year":"2008","unstructured":"Fuursted, K., Arpi, M., Lindblad, B. E. & Pedersen, L. N. Broad-range PCR as a supplement to culture for detection of bacterial pathogens in patients with a clinically diagnosed spinal infection. Scand. J. Infect. Dis. 40(10), 772\u2013777 (2008).","journal-title":"Scand. J. Infect. Dis."},{"key":"28576_CR18","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3389\/fcimb.2017.00060","volume":"7","author":"AF Sheikh","year":"2017","unstructured":"Sheikh, A. F. et al. Pathogen identification in suspected cases of pyogenic spondylodiscitis. Front. Cell Infect. Microbiol. 7, 60 (2017).","journal-title":"Front. Cell Infect. Microbiol."},{"issue":"12","key":"28576_CR19","doi-asserted-by":"publisher","first-page":"4220","DOI":"10.1007\/s00586-023-07707-3","volume":"32","author":"H Huang","year":"2023","unstructured":"Huang, H. et al. Pathogen detection in suspected spinal infection: metagenomic next-generation sequencing versus culture. Eur. Spine J. 32(12), 4220\u20134228 (2023).","journal-title":"Eur. Spine J."},{"issue":"2","key":"28576_CR20","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1007\/s00586-021-07026-5","volume":"31","author":"C Ma","year":"2022","unstructured":"Ma, C. et al. The potential of metagenomic next-generation sequencing in diagnosis of spinal infection: A retrospective study. Eur. Spine J. 31(2), 442\u2013447 (2022).","journal-title":"Eur. Spine J."},{"issue":"6","key":"28576_CR21","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1016\/j.spinee.2023.02.001","volume":"23","author":"G Wang","year":"2023","unstructured":"Wang, G. et al. Application of metagenomic next-generation sequencing in the detection of pathogens in spinal infections. Spine J. 23(6), 859\u2013867 (2023).","journal-title":"Spine J."},{"key":"28576_CR22","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.jare.2021.09.012","volume":"38","author":"Z Diao","year":"2022","unstructured":"Diao, Z., Han, D., Zhang, R. & Li, J. Metagenomics next-generation sequencing tests take the stage in the diagnosis of lower respiratory tract infections. J. Adv. Res. 38, 201\u2013212 (2022).","journal-title":"J. Adv. Res."},{"issue":"7","key":"28576_CR23","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1111\/odi.13968","volume":"28","author":"Y Zhu","year":"2022","unstructured":"Zhu, Y. et al. Bacterial spectrum analysis and antimicrobial susceptibility study of osteoradionecrosis of the jaw in Southern China. Oral Dis. 28(7), 2015\u20132025 (2022).","journal-title":"Oral Dis."},{"key":"28576_CR24","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71","volume":"372","author":"MJ Page","year":"2021","unstructured":"Page, M. J. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372, n71 (2021).","journal-title":"BMJ"},{"issue":"1","key":"28576_CR25","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.1080\/21505594.2020.1855923","volume":"11","author":"AM Ramirez","year":"2020","unstructured":"Ramirez, A. M. et al. SarA plays a predominant role in controlling the production of extracellular proteases in the diverse clinical isolates of Staphylococcus aureus LAC and UAMS-1. Virulence 11(1), 1738\u20131762 (2020).","journal-title":"Virulence"},{"issue":"4","key":"28576_CR26","doi-asserted-by":"publisher","first-page":"e00372","DOI":"10.1128\/mSphere.00372-19","volume":"4","author":"E Sherman","year":"2019","unstructured":"Sherman, E., Bayles, K., Moormeier, D., Endres, J. & Wei, T. Observations of shear stress effects on staphylococcus aureus biofilm formation. mSphere 4(4), e00372-e419 (2019).","journal-title":"mSphere"},{"issue":"4","key":"28576_CR27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008443","volume":"16","author":"L Visvabharathy","year":"2020","unstructured":"Visvabharathy, L. et al. Group 1 CD1-restricted T cells contribute to control of systemic Staphylococcus aureus infection. PLoS Pathog. 16(4), e1008443 (2020).","journal-title":"PLoS Pathog."},{"issue":"1","key":"28576_CR28","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1080\/21505594.2021.1878688","volume":"12","author":"G Cheung","year":"2021","unstructured":"Cheung, G., Bae, J. S. & Otto, M. Pathogenicity and virulence of Staphylococcus aureus. Virulence 12(1), 547\u2013569 (2021).","journal-title":"Virulence"},{"key":"28576_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2025.07.020","author":"IJE Kouijzer","year":"2025","unstructured":"Kouijzer, I. J. E. et al. Treatment and follow-up of vascular graft and endograft infection: Delphi consensus document. Clin. Microbiol. Infect. https:\/\/doi.org\/10.1016\/j.cmi.2025.07.020 (2025).","journal-title":"Clin. Microbiol. Infect."},{"issue":"622","key":"28576_CR30","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.bbrc.2022.06.068","volume":"24","author":"TY Huang","year":"2022","unstructured":"Huang, T. Y., Jiang, Y. E. & Scott, D. A. Culturable bacteria in the entire acne lesion and short-chain fatty acid metabolites of Cutibacterium acnes and Staphylococcus epidermidis isolates. Biochem. Biophys. Res. Commun. 24(622), 45\u201349 (2022).","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"1","key":"28576_CR31","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s00402-025-06032-2","volume":"145","author":"A Werner","year":"2025","unstructured":"Werner, A. et al. Diagnostic value of preoperative joint aspiration for periprosthetic shoulder infection: Analysis of microbiological aspects and preoperative ICM minor criteria. Arch. Orthop. Trauma Surg. 145(1), 413 (2025).","journal-title":"Arch. Orthop. Trauma Surg."},{"issue":"35","key":"28576_CR32","doi-asserted-by":"publisher","first-page":"13099","DOI":"10.12998\/wjcc.v10.i35.13099","volume":"10","author":"YF Mo","year":"2022","unstructured":"Mo, Y. F. et al. Surgery combined with antibiotics for thoracic vertebral Escherichia coli infection after acupuncture: A case report. World J. Clin. Cases 10(35), 13099\u201313107 (2022).","journal-title":"World J. Clin. Cases"},{"issue":"9","key":"28576_CR33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107186","volume":"9","author":"A Culotti","year":"2014","unstructured":"Culotti, A. & Packman, A. I. Pseudomonas aeruginosa promotes Escherichia coli biofilm formation in nutrient-limited medium. PLoS ONE 9(9), e107186 (2014).","journal-title":"PLoS ONE"},{"issue":"1","key":"28576_CR34","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s12275-021-0478-0","volume":"59","author":"Y Yuan","year":"2021","unstructured":"Yuan, Y. et al. Extracellular products-mediated interspecific interaction between Pseudomonas aeruginosa and Escherichia coli. J. Microbiol. 59(1), 29\u201340 (2021).","journal-title":"J. Microbiol."},{"issue":"4","key":"28576_CR35","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3390\/diseases10040082","volume":"10","author":"C Lama","year":"2022","unstructured":"Lama, C. et al. Evaluation of Xpert MTB\/RIF Assay, MTB culture and line probe assay for the detection of MDR Tuberculosis in AFB Smear negative specimens. Diseases 10(4), 82 (2022).","journal-title":"Diseases"},{"issue":"2","key":"28576_CR36","doi-asserted-by":"publisher","first-page":"151","DOI":"10.4103\/ijmy.ijmy_86_23","volume":"12","author":"S Kanade","year":"2023","unstructured":"Kanade, S., Mohammed, Z., Kulkarni, A. & Nataraj, G. Comparison of xpert MTB\/RIF assay, line probe assay, and culture in diagnosis of pulmonary tuberculosis on bronchoscopic specimen. Int. J. Mycobacteriol. 12(2), 151\u2013156 (2023).","journal-title":"Int. J. Mycobacteriol."},{"key":"28576_CR37","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.00537-25","volume":"19","author":"Y Chen","year":"2025","unstructured":"Chen, Y., Tang, H., Zheng, J., Yang, Q. & Han, D. Transforming tuberculosis diagnosis with clinical metagenomics: Progress and roadblocks. J. Clin. Microbiol. 19, e0053725 (2025).","journal-title":"J. Clin. Microbiol."},{"issue":"15","key":"28576_CR38","doi-asserted-by":"publisher","first-page":"1646194","DOI":"10.3389\/fcimb.2025.1646194","volume":"11","author":"Y Li","year":"2025","unstructured":"Li, Y. et al. Optimization of decision thresholds for Mycobacterium tuberculosis can effectively improve the performance of mNGS in tuberculosis diagnosis. Front. Cell Infect. Microbiol. 11(15), 1646194 (2025).","journal-title":"Front. Cell Infect. Microbiol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-28576-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-28576-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-28576-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T15:23:53Z","timestamp":1777130633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-28576-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,28]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["28576"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-28576-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,28]]},"assertion":[{"value":"22 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2025","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":"45566"}}