{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:10:34Z","timestamp":1792188634324,"version":"4.4.0"},"reference-count":103,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Traumatic brain injury (TBI) is a major public health concern associated with an increased risk of neurodegenerative diseases including Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), and chronic traumatic encephalopathy, yet the underlying molecular mechanisms in repetitive TBI remain poorly defined. This study investigates proteomic and behavioral changes following single and repetitive mild TBI in a mouse model, focusing on molecular alterations in the cortex and hippocampus across acute (48\u2009h) and subacute (1 week) stages. Using shotgun proteomics and bioinformatics approaches, including weighted gene co-expression network analysis (WGCNA) and machine learning, we analyzed the proteomic landscapes of TBI-affected brain regions including the hippocampus and the cortex. We assessed motor and cognitive outcomes at 2-, 7-, and 30-days post-injury to explore functional impairments associated with observed molecular changes. Our findings reveal spatio-temporal injury- and time-specific proteomic changes, with a single TBI promoting neuroprotective and repair mechanisms, while repetitive TBI exacerbating neuronal damage and synaptic deficits in the hippocampus. Key deregulated proteins, including\n                    <jats:italic>Apoa1<\/jats:italic>\n                    ,\n                    <jats:italic>ApoE<\/jats:italic>\n                    ,\n                    <jats:italic>Cox6a1<\/jats:italic>\n                    , and\n                    <jats:italic>Snca<\/jats:italic>\n                    , were linked to neurodegenerative pathways, suggesting molecular connections between TBI and diseases like AD and PD. Behavioral assessments indicated that repetitive TBI significantly impaired motor and cognitive functions, with recovery in motor function by day 30, whereas cognitive deficits persisted. This study provides a detailed analysis of the proteomic and behavioral consequences of TBI, identifying molecular networks as potential biomarkers or therapeutic targets for mitigating long-term cognitive decline associated with repetitive head trauma. These findings underscore the importance of mitochondrial and synaptic integrity in TBI response and suggest that targeting these pathways could reduce neurodegenerative risk following repetitive TBI.\n                  <\/jats:p>","DOI":"10.1038\/s41392-025-02286-9","type":"journal-article","created":{"date-parts":[[2025,6,22]],"date-time":"2025-06-22T19:02:08Z","timestamp":1750618928000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Uncovering injury-specific proteomic signatures and neurodegenerative risks in single and repetitive traumatic brain injury"],"prefix":"10.1038","volume":"10","author":[{"given":"Sarah","family":"Mantash","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soulaimane","family":"Aboulouard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Dakik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanis","family":"Zirem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Ziane-Chaouche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Nehme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7622-8106","authenticated-orcid":false,"given":"Khalil","family":"Mallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marya","family":"El-Kurdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naify","family":"Ramadan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1096-5044","authenticated-orcid":false,"given":"Isabelle","family":"Fournier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9887-072X","authenticated-orcid":false,"given":"Kazem","family":"Zibara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firas","family":"Kobeissy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4318-0817","authenticated-orcid":false,"given":"Michel","family":"Salzet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"2286_CR1","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1177\/0963689717714102","volume":"26","author":"M Galgano","year":"2017","unstructured":"Galgano, M. et al. Traumatic brain injury: current treatment strategies and future Endeavors. Cell Transplant. 26, 1118\u20131130 (2017).","journal-title":"Cell Transplant."},{"key":"2286_CR2","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/B978-0-444-52892-6.00004-0","volume":"127","author":"AC McKee","year":"2015","unstructured":"McKee, A. C. & Daneshvar, D. H. The neuropathology of traumatic brain injury. Handb. Clin. Neurol. 127, 45\u201366 (2015).","journal-title":"Handb. Clin. Neurol."},{"key":"2286_CR3","doi-asserted-by":"publisher","first-page":"855701","DOI":"10.3389\/fimmu.2022.855701","volume":"13","author":"RZ Zheng","year":"2022","unstructured":"Zheng, R. Z. et al. Neuroinflammation following traumatic brain injury: take it seriously or not. Front Immunol. 13, 855701 (2022).","journal-title":"Front Immunol."},{"key":"2286_CR4","first-page":"511","volume":"75","author":"KA Jellinger","year":"2004","unstructured":"Jellinger, K. A. Traumatic brain injury as a risk factor for Alzheimer\u2019s disease. J. Neurol. Neurosurg. Psychiatry 75, 511\u2013512 (2004).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"2286_CR5","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/nrn2808","volume":"11","author":"VE Johnson","year":"2010","unstructured":"Johnson, V. E., Stewart, W. & Smith, D. H. Traumatic brain injury and amyloid-beta pathology: a link to Alzheimer\u2019s disease?. Nat. Rev. Neurosci. 11, 361\u2013370 (2010).","journal-title":"Nat. Rev. Neurosci."},{"key":"2286_CR6","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1089\/neu.2014.3352","volume":"32","author":"HM Bramlett","year":"2015","unstructured":"Bramlett, H. M. & Dietrich, W. D. Long-term consequences of traumatic brain injury: current status of potential mechanisms of injury and neurological outcomes. J. Neurotrauma 32, 1834\u20131848 (2015).","journal-title":"J. Neurotrauma"},{"key":"2286_CR7","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.2174\/0929867321666131217153310","volume":"21","author":"A Rodriguez-Rodriguez","year":"2014","unstructured":"Rodriguez-Rodriguez, A., Egea-Guerrero, J. J., Murillo-Cabezas, F. & Carrillo-Vico, A. Oxidative stress in traumatic brain injury. Curr. Med. Chem. 21, 1201\u20131211 (2014).","journal-title":"Curr. Med. Chem."},{"key":"2286_CR8","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.neulet.2013.03.042","volume":"544","author":"N Tumer","year":"2013","unstructured":"Tumer, N. et al. Overpressure blast-wave induced brain injury elevates oxidative stress in the hypothalamus and catecholamine biosynthesis in the rat adrenal medulla. Neurosci. Lett. 544, 62\u201367 (2013).","journal-title":"Neurosci. Lett."},{"key":"2286_CR9","doi-asserted-by":"publisher","first-page":"943","DOI":"10.3390\/antiox9100943","volume":"9","author":"H Ismail","year":"2020","unstructured":"Ismail, H. et al. Traumatic brain injury: oxidative stress and novel anti-oxidants such as mitoquinone and edaravone. Antioxidants9, 943 (2020).","journal-title":"Antioxidants"},{"key":"2286_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2022.113987","volume":"351","author":"M Tabet","year":"2022","unstructured":"Tabet, M. et al. Mitoquinone supplementation alleviates oxidative stress and pathologic outcomes following repetitive mild traumatic brain injury at a chronic time point. Exp. Neurol. 351, 113987 (2022).","journal-title":"Exp. Neurol."},{"key":"2286_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-10419-1","volume":"12","author":"A Gottlieb","year":"2022","unstructured":"Gottlieb, A. et al. Time dependent analysis of rat microglial surface markers in traumatic brain injury reveals dynamics of distinct cell subpopulations. Sci. Rep. 12, 6289 (2022).","journal-title":"Sci. Rep."},{"key":"2286_CR12","doi-asserted-by":"publisher","first-page":"2264","DOI":"10.1007\/s12640-022-00566-8","volume":"40","author":"C Zhang","year":"2022","unstructured":"Zhang, C. et al. Extracellular mitochondria activate microglia and contribute to neuroinflammation in traumatic brain injury. Neurotox. Res. 40, 2264\u20132277 (2022).","journal-title":"Neurotox. Res."},{"key":"2286_CR13","doi-asserted-by":"publisher","first-page":"10568","DOI":"10.1021\/acs.analchem.8b02682","volume":"90","author":"K Mallah","year":"2018","unstructured":"Mallah, K. et al. Lipid changes associated with traumatic brain injury revealed by 3D MALDI-MSI. Anal. Chem. 90, 10568\u201310576 (2018).","journal-title":"Anal. Chem."},{"key":"2286_CR14","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1074\/mcp.RA119.001604","volume":"18","author":"K Mallah","year":"2019","unstructured":"Mallah, K. et al. Mapping spatiotemporal microproteomics landscape in experimental model of traumatic brain injury unveils a link to Parkinson\u2019s disease. Mol. Cell Proteom. 18, 1669\u20131682 (2019).","journal-title":"Mol. Cell Proteom."},{"key":"2286_CR15","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/0165-0270(84)90007-4","volume":"11","author":"R Morris","year":"1984","unstructured":"Morris, R. Developments of a water-maze procedure for studying spatial learning in the rat. J. Neurosci. Methods 11, 47\u201360 (1984).","journal-title":"J. Neurosci. Methods"},{"key":"2286_CR16","doi-asserted-by":"publisher","first-page":"198","DOI":"10.3389\/fneur.2019.00198","volume":"10","author":"MG de Freitas Cardoso","year":"2019","unstructured":"de Freitas Cardoso, M. G. et al. Cognitive impairment following acute mild traumatic brain injury. Front Neurol. 10, 198 (2019).","journal-title":"Front Neurol."},{"key":"2286_CR17","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-017-0762-x","volume":"17","author":"R Paterno","year":"2017","unstructured":"Paterno, R., Folweiler, K. A. & Cohen, A. S. Pathophysiology and treatment of memory dysfunction after traumatic brain injury. Curr. Neurol. Neurosci. Rep. 17, 52 (2017).","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"2286_CR18","doi-asserted-by":"publisher","first-page":"510","DOI":"10.3390\/traumacare2040042","volume":"2","author":"WS Dodd","year":"2022","unstructured":"Dodd, W. S. et al. Traumatic brain injury and secondary neurodegenerative disease. Trauma Care. 2, 510\u2013522 (2022).","journal-title":"Trauma Care."},{"key":"2286_CR19","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1515\/revneuro-2015-0017","volume":"27","author":"R Gupta","year":"2016","unstructured":"Gupta, R. & Sen, N. Traumatic brain injury: a risk factor for neurodegenerative diseases. Rev. Neurosci. 27, 93\u2013100 (2016).","journal-title":"Rev. Neurosci."},{"key":"2286_CR20","doi-asserted-by":"publisher","first-page":"4540","DOI":"10.1007\/s00415-024-12369-2","volume":"271","author":"MA Khoury","year":"2024","unstructured":"Khoury, M. A. et al. History of traumatic brain injury is associated with increased grey-matter loss in patients with mild cognitive impairment. J. Neurol. 271, 4540\u20134550 (2024).","journal-title":"J. Neurol."},{"key":"2286_CR21","doi-asserted-by":"publisher","first-page":"29","DOI":"10.3389\/fnagi.2013.00029","volume":"5","author":"KR Walker","year":"2013","unstructured":"Walker, K. R. & Tesco, G. Molecular mechanisms of cognitive dysfunction following traumatic brain injury. Front Aging Neurosci. 5, 29 (2013).","journal-title":"Front Aging Neurosci."},{"key":"2286_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neuroscience.2005.01.052","volume":"133","author":"BM Witgen","year":"2005","unstructured":"Witgen, B. M. et al. Regional hippocampal alteration associated with cognitive deficit following experimental brain injury: a systems, network and cellular evaluation. Neuroscience 133, 1\u201315 (2005).","journal-title":"Neuroscience"},{"key":"2286_CR23","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1002\/mas.21719","volume":"42","author":"K Mallah","year":"2023","unstructured":"Mallah, K. et al. Neurotrauma investigation through spatial omics guided by mass spectrometry imaging: target identification and clinical applications. Mass Spectrom. Rev. 42, 189\u2013205 (2023).","journal-title":"Mass Spectrom. Rev."},{"key":"2286_CR24","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12014-024-09485-6","volume":"21","author":"S Maity","year":"2024","unstructured":"Maity, S. et al. Mapping dynamic molecular changes in hippocampal subregions after traumatic brain injury through spatial proteomics. Clin. Proteom. 21, 32 (2024).","journal-title":"Clin. Proteom."},{"key":"2286_CR25","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1093\/brain\/awae305","volume":"148","author":"LM Li","year":"2025","unstructured":"Li, L. M. et al. High-dimensional proteomic analysis for pathophysiological classification of Traumatic Brain Injury. Brain 148, 1015\u20131030 (2025).","journal-title":"Brain"},{"key":"2286_CR26","doi-asserted-by":"publisher","first-page":"1288740","DOI":"10.3389\/fneur.2023.1288740","volume":"14","author":"F Kobeissy","year":"2023","unstructured":"Kobeissy, F. et al. Advances in neuroproteomics for neurotrauma: unraveling insights for personalized medicine and future prospects. Front Neurol. 14, 1288740 (2023).","journal-title":"Front Neurol."},{"key":"2286_CR27","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1074\/mcp.M600157-MCP200","volume":"5","author":"FH Kobeissy","year":"2006","unstructured":"Kobeissy, F. H. et al. Novel differential neuroproteomics analysis of traumatic brain injury in rats. Mol. Cell Proteom. 5, 1887\u20131898 (2006).","journal-title":"Mol. Cell Proteom."},{"key":"2286_CR28","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1016\/j.bbadis.2013.10.015","volume":"1842","author":"X Wang","year":"2014","unstructured":"Wang, X. et al. Oxidative stress and mitochondrial dysfunction in Alzheimer\u2019s disease. Biochim. Biophys. Acta1842, 1240\u20131247 (2014).","journal-title":"Biochim. Biophys. Acta"},{"key":"2286_CR29","doi-asserted-by":"publisher","first-page":"5802","DOI":"10.3390\/ijms21165802","volume":"21","author":"L Pollini","year":"2020","unstructured":"Pollini, L. et al. KCND3-related neurological disorders: from old to emerging clinical phenotypes. Int. J. Mol. Sci. 21, 5802 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"2286_CR30","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1002\/biof.155","volume":"37","author":"CM Quinzii","year":"2011","unstructured":"Quinzii, C. M. & Hirano, M. Primary and secondary CoQ(10) deficiencies in humans. Biofactors 37, 361\u2013365 (2011).","journal-title":"Biofactors"},{"key":"2286_CR31","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1146\/annurev-cellbio-092910-154152","volume":"28","author":"PI Hanson","year":"2012","unstructured":"Hanson, P. I. & Cashikar, A. Multivesicular body morphogenesis. Annu. Rev. Cell Dev. Biol. 28, 337\u2013362 (2012).","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2286_CR32","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/nn.2231","volume":"12","author":"R Klein","year":"2009","unstructured":"Klein, R. Bidirectional modulation of synaptic functions by Eph\/ephrin signaling. Nat. Neurosci. 12, 15\u201320 (2009).","journal-title":"Nat. Neurosci."},{"key":"2286_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4161\/rna.3.1.2495","volume":"3","author":"S Maas","year":"2006","unstructured":"Maas, S., Kawahara, Y., Tamburro, K. M. & Nishikura, K. A-to-I RNA editing and human disease. RNA Biol. 3, 1\u20139 (2006).","journal-title":"RNA Biol."},{"key":"2286_CR34","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1159\/000225957","volume":"55","author":"SK Calderwood","year":"2009","unstructured":"Calderwood, S. K., Murshid, A. & Prince, T. The shock of aging: molecular chaperones and the heat shock response in longevity and aging-a mini-review. Gerontology 55, 550\u2013558 (2009).","journal-title":"Gerontology"},{"key":"2286_CR35","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.neuroscience.2018.09.020","volume":"420","author":"A Kadkova","year":"2019","unstructured":"Kadkova, A., Radecke, J. & Sorensen, J. B. The SNAP-25 protein family. Neuroscience 420, 50\u201371 (2019).","journal-title":"Neuroscience"},{"key":"2286_CR36","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.expneurol.2012.01.013","volume":"246","author":"VE Johnson","year":"2013","unstructured":"Johnson, V. E., Stewart, W. & Smith, D. H. Axonal pathology in traumatic brain injury. Exp. Neurol. 246, 35\u201343 (2013).","journal-title":"Exp. Neurol."},{"key":"2286_CR37","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1177\/107385840000600611","volume":"6","author":"DH Smith","year":"2000","unstructured":"Smith, D. H. & Meaney, D. F. Axonal damage in traumatic brain injury. Neuroscientist 6, 483\u2013495 (2000).","journal-title":"Neuroscientist"},{"key":"2286_CR38","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.tins.2008.02.008","volume":"31","author":"H Fukui","year":"2008","unstructured":"Fukui, H. & Moraes, C. T. The mitochondrial impairment, oxidative stress and neurodegeneration connection: reality or just an attractive hypothesis?. Trends Neurosci. 31, 251\u2013256 (2008).","journal-title":"Trends Neurosci."},{"key":"2286_CR39","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/s00701-005-0674-4","volume":"148","author":"A Buki","year":"2006","unstructured":"Buki, A. & Povlishock, J. T. All roads lead to disconnection?-Traumatic axonal injury revisited. Acta Neurochir. (Wien.). 148, 181\u2013193 (2006).","journal-title":"Acta Neurochir. (Wien.)."},{"key":"2286_CR40","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.bbr.2011.06.012","volume":"224","author":"SR Shultz","year":"2011","unstructured":"Shultz, S. R. et al. A single mild fluid percussion injury induces short-term behavioral and neuropathological changes in the Long-Evans rat: support for an animal model of concussion. Behav. Brain Res. 224, 326\u2013335 (2011).","journal-title":"Behav. Brain Res."},{"key":"2286_CR41","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.jneumeth.2011.09.003","volume":"203","author":"MJ Kane","year":"2012","unstructured":"Kane, M. J. et al. A mouse model of human repetitive mild traumatic brain injury. J. Neurosci. Methods 203, 41\u201349 (2012).","journal-title":"J. Neurosci. Methods"},{"key":"2286_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.84","volume":"2","author":"K Blennow","year":"2016","unstructured":"Blennow, K. et al. Traumatic brain injuries. Nat. Rev. Dis. Prim. 2, 16084 (2016).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"2286_CR43","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.expneurol.2015.05.004","volume":"275","author":"JR Kulbe","year":"2016","unstructured":"Kulbe, J. R. & Geddes, J. W. Current status of fluid biomarkers in mild traumatic brain injury. Exp. Neurol. 275, 334\u2013352 (2016).","journal-title":"Exp. Neurol."},{"key":"2286_CR44","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1523\/JNEUROSCI.1734-20.2020","volume":"41","author":"A Alawieh","year":"2021","unstructured":"Alawieh, A. et al. Complement drives synaptic degeneration and progressive cognitive decline in the chronic phase after traumatic brain injury. J. Neurosci. 41, 1830\u20131843 (2021).","journal-title":"J. Neurosci."},{"key":"2286_CR45","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2020.1727637","volume":"9","author":"AN Murgoci","year":"2020","unstructured":"Murgoci, A. N. et al. Location of neonatal microglia drives small extracellular vesicles content and biological functions in vitro. J. Extracell. Vesicles9, 1727637 (2020).","journal-title":"J. Extracell. Vesicles"},{"key":"2286_CR46","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05737-9","volume":"14","author":"A Capuz","year":"2023","unstructured":"Capuz, A. et al. Astrocytes express aberrant immunoglobulins as putative gatekeeper of astrocytes to neuronal progenitor conversion. Cell Death Dis. 14, 237 (2023).","journal-title":"Cell Death Dis."},{"key":"2286_CR47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.882830","volume":"13","author":"A Capuz","year":"2022","unstructured":"Capuz, A. et al. The antibody dependant neurite outgrowth modulation response involvement in spinal cord injury. Front. Immunol. 13, 882830 (2022).","journal-title":"Front. Immunol."},{"key":"2286_CR48","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.expneurol.2015.01.008","volume":"275","author":"BM Aertker","year":"2016","unstructured":"Aertker, B. M., Bedi, S. & Cox, C. S. Jr Strategies for CNS repair following TBI. Exp. Neurol. 275, 411\u2013426 (2016).","journal-title":"Exp. Neurol."},{"key":"2286_CR49","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.expneurol.2015.08.018","volume":"275","author":"DJ Loane","year":"2016","unstructured":"Loane, D. J. & Kumar, A. Microglia in the TBI brain: the good, the bad, and the dysregulated. Exp. Neurol. 275, 316\u2013327 (2016).","journal-title":"Exp. Neurol."},{"key":"2286_CR50","doi-asserted-by":"publisher","first-page":"fcae223","DOI":"10.1093\/braincomms\/fcae223","volume":"6","author":"RE Woodrow","year":"2024","unstructured":"Woodrow, R. E. et al. Repeat traumatic brain injury exacerbates acute thalamic hyperconnectivity in humans. Brain Commun. 6, fcae223 (2024).","journal-title":"Brain Commun."},{"key":"2286_CR51","doi-asserted-by":"publisher","first-page":"100066","DOI":"10.1016\/j.bionps.2023.100066","volume":"8","author":"J Abi Gerges","year":"2023","unstructured":"Abi Gerges, J., Chalhoub, I., Atallah, C. & Khoury, R. Biomarkers of chronic traumatic encephalopathy: a state-of-the art review. Biomark. Neuropsychiatry 8, 100066 (2023).","journal-title":"Biomark. Neuropsychiatry"},{"key":"2286_CR52","doi-asserted-by":"publisher","first-page":"362","DOI":"10.5607\/en.2019.28.3.362","volume":"28","author":"B Bi","year":"2019","unstructured":"Bi, B. et al. Quantitative proteomic analysis reveals impaired axonal guidance signaling in human postmortem brain tissues of chronic traumatic encephalopathy. Exp. Neurobiol. 28, 362\u2013375 (2019).","journal-title":"Exp. Neurobiol."},{"key":"2286_CR53","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1021\/acs.jproteome.3c00544","volume":"23","author":"J Park","year":"2024","unstructured":"Park, J. et al. Multiplexed quantitative proteomics reveals proteomic alterations in two rodent traumatic brain injury models. J. Proteome Res. 23, 249\u2013263 (2024).","journal-title":"J. Proteome Res."},{"key":"2286_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-45965-9","volume":"13","author":"MY Lee","year":"2023","unstructured":"Lee, M. Y. et al. Proteomic discovery of prognostic protein biomarkers for persisting problems after mild traumatic brain injury. Sci. Rep. 13, 19786 (2023).","journal-title":"Sci. Rep."},{"key":"2286_CR55","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.590669","volume":"11","author":"J Chen","year":"2020","unstructured":"Chen, J. et al. FGF20 protected against BBB disruption after traumatic brain injury by upregulating junction protein expression and inhibiting the inflammatory response. Front. Pharmacol. 11, 590669 (2020).","journal-title":"Front. Pharmacol."},{"key":"2286_CR56","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.brainres.2019.01.022","volume":"1711","author":"S Sagarkar","year":"2019","unstructured":"Sagarkar, S. et al. Repeated mild traumatic brain injury causes persistent changes in histone deacetylase function in hippocampus: implications in learning and memory deficits in rats. Brain Res. 1711, 183\u2013192 (2019).","journal-title":"Brain Res."},{"key":"2286_CR57","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/alzrt241","volume":"6","author":"ML Selenica","year":"2014","unstructured":"Selenica, M. L. et al. Histone deacetylase 6 inhibition improves memory and reduces total tau levels in a mouse model of tau deposition. Alzheimers Res. Ther. 6, 12 (2014).","journal-title":"Alzheimers Res. Ther."},{"key":"2286_CR58","doi-asserted-by":"publisher","first-page":"268","DOI":"10.4062\/biomolther.2024.110","volume":"33","author":"JY Seo","year":"2025","unstructured":"Seo, J. Y. et al. A novel histone deacetylase 6 inhibitor, 4-FHA, improves scopolamine-induced cognitive and memory impairment in mice. Biomol. Ther.33, 268\u2013277 (2025).","journal-title":"Biomol. Ther."},{"key":"2286_CR59","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","volume":"8","author":"W Zhang","year":"2023","unstructured":"Zhang, W., Xiao, D., Mao, Q. & Xia, H. Role of neuroinflammation in neurodegeneration development. Signal Transduct. Target. Ther. 8, 267 (2023).","journal-title":"Signal Transduct. Target. Ther."},{"key":"2286_CR60","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/alzrt42","volume":"2","author":"BE Gavett","year":"2010","unstructured":"Gavett, B. E. et al. Mild traumatic brain injury: a risk factor for neurodegeneration. Alzheimers Res. Ther. 2, 18 (2010).","journal-title":"Alzheimers Res. Ther."},{"key":"2286_CR61","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.biopsych.2021.05.025","volume":"91","author":"BL Brett","year":"2022","unstructured":"Brett, B. L. et al. Traumatic brain injury and risk of neurodegenerative disorder. Biol. Psychiatry 91, 498\u2013507 (2022).","journal-title":"Biol. Psychiatry"},{"key":"2286_CR62","doi-asserted-by":"publisher","first-page":"105991","DOI":"10.1016\/j.nbd.2023.105991","volume":"177","author":"T Saunders","year":"2023","unstructured":"Saunders, T. et al. Neurogranin in Alzheimer\u2019s disease and ageing: a human post-mortem study. Neurobiol. Dis. 177, 105991 (2023).","journal-title":"Neurobiol. Dis."},{"key":"2286_CR63","first-page":"337","volume":"32","author":"NB Chauhan","year":"2014","unstructured":"Chauhan, N. B. Chronic neurodegenerative consequences of traumatic brain injury. Restor. Neurol. Neurosci. 32, 337\u2013365 (2014).","journal-title":"Restor. Neurol. Neurosci."},{"key":"2286_CR64","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s00401-011-0892-1","volume":"123","author":"S Arold","year":"2012","unstructured":"Arold, S. et al. Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer\u2019s disease and apoE TR mouse cortex. Acta Neuropathol. 123, 39\u201352 (2012).","journal-title":"Acta Neuropathol."},{"key":"2286_CR65","doi-asserted-by":"publisher","first-page":"598","DOI":"10.3389\/fphys.2020.00598","volume":"11","author":"H Chew","year":"2020","unstructured":"Chew, H., Solomon, V. A. & Fonteh, A. N. Involvement of lipids in Alzheimer\u2019s disease pathology and potential therapies. Front. Physiol. 11, 598 (2020).","journal-title":"Front. Physiol."},{"key":"2286_CR66","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1007\/s12031-017-0942-9","volume":"62","author":"FN Emamzadeh","year":"2017","unstructured":"Emamzadeh, F. N. Role of apolipoproteins and alpha-synuclein in Parkinson\u2019s disease. J. Mol. Neurosci. 62, 344\u2013355 (2017).","journal-title":"J. Mol. Neurosci."},{"key":"2286_CR67","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.jneuroim.2014.10.010","volume":"277","author":"L Meyers","year":"2014","unstructured":"Meyers, L. et al. A role for Apolipoprotein A-I in the pathogenesis of multiple sclerosis. J. Neuroimmunol. 277, 176\u2013185 (2014).","journal-title":"J. Neuroimmunol."},{"key":"2286_CR68","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1159\/000090676","volume":"21","author":"HC Liu","year":"2006","unstructured":"Liu, H. C. et al. Proteomic identification of lower apolipoprotein A-I in Alzheimer\u2019s disease. Dement. Geriatr. Cogn. Disord. 21, 155\u2013161 (2006).","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"2286_CR69","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-06322-4","volume":"12","author":"M Samangooei","year":"2022","unstructured":"Samangooei, M. et al. Evaluation of S100A12 and Apo-A1 plasma level potency in untreated new relapsing-remitting multiple sclerosis patients and their family members. Sci. Rep. 12, 2160 (2022).","journal-title":"Sci. Rep."},{"key":"2286_CR70","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s11011-023-01330-3","volume":"39","author":"L Feng","year":"2024","unstructured":"Feng, L. et al. Proteomics revealed an association between ribosome-associated proteins and amyloid beta deposition in Alzheimer\u2019s disease. Metab. Brain Dis. 39, 263\u2013282 (2024).","journal-title":"Metab. Brain Dis."},{"key":"2286_CR71","doi-asserted-by":"publisher","first-page":"136","DOI":"10.31083\/j.jin2206136","volume":"22","author":"L Su","year":"2023","unstructured":"Su, L., Zhang, Y., Wang, Y. & Wei, H. Identification of a lncRNA\/circRNA-miRNA-mRNA ceRNA network in Alzheimer\u2019s disease. J. Integr. Neurosci. 22, 136 (2023).","journal-title":"J. Integr. Neurosci."},{"key":"2286_CR72","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1093\/brain\/awx352","volume":"141","author":"E Bereczki","year":"2018","unstructured":"Bereczki, E. et al. Synaptic markers of cognitive decline in neurodegenerative diseases: a proteomic approach. Brain 141, 582\u2013595 (2018).","journal-title":"Brain"},{"key":"2286_CR73","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/s00018-023-04991-6","volume":"80","author":"W XiangWei","year":"2023","unstructured":"XiangWei, W. et al. Clinical and functional consequences of GRIA variants in patients with neurological diseases. Cell Mol. Life Sci. 80, 345 (2023).","journal-title":"Cell Mol. Life Sci."},{"key":"2286_CR74","doi-asserted-by":"publisher","first-page":"111875","DOI":"10.1016\/j.mad.2023.111875","volume":"216","author":"CB Santos-Reboucas","year":"2023","unstructured":"Santos-Reboucas, C. B., Cordovil Cotrin, J. & Dos Santos Junior, G. C. Exploring the interplay between metabolomics and genetics in Parkinson\u2019s disease: insights from ongoing research and future avenues. Mech. Ageing Dev. 216, 111875 (2023).","journal-title":"Mech. Ageing Dev."},{"key":"2286_CR75","doi-asserted-by":"crossref","unstructured":"Asuku, A. O. et al. in Nutrition in Brain Aging and Dementia 109\u2013130 (Springer, 2024).","DOI":"10.1007\/978-981-97-4117-5_5"},{"key":"2286_CR76","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/s10048-016-0478-0","volume":"17","author":"L Tagliafierro","year":"2016","unstructured":"Tagliafierro, L. & Chiba-Falek, O. Up-regulation of SNCA gene expression: implications to synucleinopathies. Neurogenetics 17, 145\u2013157 (2016).","journal-title":"Neurogenetics"},{"key":"2286_CR77","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.3390\/biom14101283","volume":"14","author":"TV Butkova","year":"2024","unstructured":"Butkova, T. V. et al. Candidate molecular biomarkers of traumatic brain injury: a systematic review. Biomolecules 14, 1283 (2024).","journal-title":"Biomolecules"},{"key":"2286_CR78","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.neulet.2016.07.057","volume":"630","author":"K Shee","year":"2016","unstructured":"Shee, K. et al. Alpha-synuclein (SNCA) polymorphisms exert protective effects on memory after mild traumatic brain injury. Neurosci. Lett. 630, 241\u2013246 (2016).","journal-title":"Neurosci. Lett."},{"key":"2286_CR79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1523\/ENEURO.0140-22.2022","volume":"9","author":"S Garbuzova-Davis","year":"2022","unstructured":"Garbuzova-Davis, S., Willing, A. E. & Borlongan, C. V. Apolipoprotein A1 enhances endothelial cell survival in an in vitro model of ALS. Eneuro 9, 1\u201311 (2022).","journal-title":"Eneuro"},{"key":"2286_CR80","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.108932","volume":"27","author":"TZ Tang","year":"2024","unstructured":"Tang, T. Z. et al. Serum amyloid A and mitochondrial DNA in extracellular vesicles are novel markers for detecting traumatic brain injury in a mouse model. iScience 27, 108932 (2024).","journal-title":"iScience"},{"key":"2286_CR81","doi-asserted-by":"publisher","DOI":"10.1177\/1759091420914768","volume":"12","author":"JO Ojo","year":"2020","unstructured":"Ojo, J. O. et al. Unbiased proteomic approach identifies pathobiological profiles in the brains of preclinical models of repetitive mild traumatic brain injury, tauopathy, and amyloidosis. ASN Neuro. 12, 1759091420914768 (2020).","journal-title":"ASN Neuro."},{"key":"2286_CR82","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1097\/CM9.0000000000003061","volume":"138","author":"H Zhang","year":"2025","unstructured":"Zhang, H. et al. Brain injury biomarkers and applications in neurological diseases. Chin. Med. J.138, 5\u201314 (2025).","journal-title":"Chin. Med. J."},{"key":"2286_CR83","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.3892\/etm.2016.3017","volume":"11","author":"J Wang","year":"2016","unstructured":"Wang, J. et al. Serum tau protein as a potential biomarker in the assessment of traumatic brain injury. Exp. Ther. Med. 11, 1147\u20131151 (2016).","journal-title":"Exp. Ther. Med."},{"key":"2286_CR84","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/nrneurol.2013.9","volume":"9","author":"H Zetterberg","year":"2013","unstructured":"Zetterberg, H., Smith, D. H. & Blennow, K. Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood. Nat. Rev. Neurol. 9, 201\u2013210 (2013).","journal-title":"Nat. Rev. Neurol."},{"key":"2286_CR85","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1002\/acn3.510","volume":"5","author":"BC Mouzon","year":"2018","unstructured":"Mouzon, B. C. et al. Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury. Ann. Clin. Transl. Neurol. 5, 64\u201380 (2018).","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"2286_CR86","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2025.149446","volume":"1850","author":"L Ayerra","year":"2025","unstructured":"Ayerra, L. et al. Chronic traumatic brain injury induces neurodegeneration, neuroinflammation, and cognitive deficits in a T cell-dependent manner. Brain Res. 1850, 149446 (2025).","journal-title":"Brain Res."},{"key":"2286_CR87","doi-asserted-by":"publisher","first-page":"e0251315","DOI":"10.1371\/journal.pone.0251315","volume":"16","author":"MI Hiskens","year":"2021","unstructured":"Hiskens, M. I., Schneiders, A. G., Vella, R. K. & Fenning, A. S. Repetitive mild traumatic brain injury affects inflammation and excitotoxic mRNA expression at acute and chronic time-points. PLoS ONE 16, e0251315 (2021).","journal-title":"PLoS ONE"},{"key":"2286_CR88","first-page":"1286","volume":"62","author":"R Vagnozzi","year":"2008","unstructured":"Vagnozzi, R. et al. Temporal window of metabolic brain vulnerability to concussion: a pilot: 1: H-magnetic resonance spectroscopic study in concussed athletes\u2014part III. Neurosurgery 62, 1286\u20131296 (2008).","journal-title":"Neurosurgery"},{"key":"2286_CR89","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1080\/02699052.2017.1312528","volume":"31","author":"ST DeKosky","year":"2017","unstructured":"DeKosky, S. T. & Asken, B. M. Injury cascades in TBI-related neurodegeneration. Brain Inj. 31, 1177\u20131182 (2017).","journal-title":"Brain Inj."},{"key":"2286_CR90","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1136\/jnnp-2012-303938","volume":"84","author":"K Dams-O\u2019Connor","year":"2013","unstructured":"Dams-O\u2019Connor, K. et al. Risk for late-life re-injury, dementia and death among individuals with traumatic brain injury: a population-based study. J. Neurol. Neurosurg. Psychiatry 84, 177\u2013182 (2013).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"2286_CR91","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.nec.2006.10.007","volume":"18","author":"RM Richardson","year":"2007","unstructured":"Richardson, R. M., Sun, D. & Bullock, M. R. Neurogenesis after traumatic brain injury. Neurosurg. Clin. N. Am. 18, 169\u2013181 (2007). xi.","journal-title":"Neurosurg. Clin. N. Am."},{"key":"2286_CR92","doi-asserted-by":"publisher","first-page":"e0287506","DOI":"10.1371\/journal.pone.0287506","volume":"18","author":"MA Graham","year":"2023","unstructured":"Graham, M. A., Juzang, P. T. & White, T. E. Effects of repetitive mild traumatic brain injury on weight gain and chronic behavioral outcomes in male rats. PLoS One 18, e0287506 (2023).","journal-title":"PLoS One"},{"key":"2286_CR93","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/j.clinbiochem.2014.01.028","volume":"47","author":"FG Strathmann","year":"2014","unstructured":"Strathmann, F. G., Schulte, S., Goerl, K. & Petron, D. J. Blood-based biomarkers for traumatic brain injury: evaluation of research approaches, available methods and potential utility from the clinician and clinical laboratory perspectives. Clin. Biochem. 47, 876\u2013888 (2014).","journal-title":"Clin. Biochem."},{"key":"2286_CR94","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559","volume":"9","author":"P Langfelder","year":"2008","unstructured":"Langfelder, P. & Horvath, S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinforma. 9, 559 (2008).","journal-title":"BMC Bioinforma."},{"key":"2286_CR95","doi-asserted-by":"publisher","first-page":"3659","DOI":"10.1002\/elps.201200470","volume":"33","author":"M Raad","year":"2012","unstructured":"Raad, M. et al. Neuroproteomics approach and neurosystems biology analysis: ROCK inhibitors as promising therapeutic targets in neurodegeneration and neurotrauma. Electrophoresis 33, 3659\u20133668 (2012).","journal-title":"Electrophoresis"},{"key":"2286_CR96","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1586\/14789450.2015.1000869","volume":"12","author":"PN Lizhnyak","year":"2015","unstructured":"Lizhnyak, P. N. & Ottens, A. K. Proteomics: in pursuit of effective traumatic brain injury therapeutics. Expert Rev. Proteom. 12, 75\u201382 (2015).","journal-title":"Expert Rev. Proteom."},{"key":"2286_CR97","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/nprot.2017.147","volume":"13","author":"X Zhang","year":"2018","unstructured":"Zhang, X. et al. Proteome-wide identification of ubiquitin interactions using UbIA-MS. Nat. Protoc. 13, 530\u2013550 (2018).","journal-title":"Nat. Protoc."},{"key":"2286_CR98","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","volume":"32","author":"Z Gu","year":"2016","unstructured":"Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32, 2847\u20132849 (2016).","journal-title":"Bioinformatics"},{"key":"2286_CR99","doi-asserted-by":"crossref","unstructured":"Villanueva, R. A. M. & Chen, Z. J. ggplot2: elegant graphics for data analysis, 160\u2013167 (Taylor & Francis, 2019).","DOI":"10.1080\/15366367.2019.1565254"},{"key":"2286_CR100","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498\u20132504 (2003).","journal-title":"Genome Res."},{"key":"2286_CR101","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101482","volume":"5","author":"Y Zirem","year":"2024","unstructured":"Zirem, Y. et al. Real-time glioblastoma tumor microenvironment assessment by SpiderMass for improved patient management. Cell Rep. Med. 5, 101482 (2024).","journal-title":"Cell Rep. Med."},{"key":"2286_CR102","unstructured":"Ribeiro, M. T., Singh, S. & Guestrin, C. In Proc. 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining 1135\u20131144."},{"key":"2286_CR103","first-page":"D1145","volume":"48","author":"EW Deutsch","year":"2020","unstructured":"Deutsch, E. W. et al. The ProteomeXchange consortium in 2020: enabling \u2018big data\u2019 approaches in proteomics. Nucleic Acids Res. 48, D1145\u2013D1152 (2020).","journal-title":"Nucleic Acids Res."}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02286-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02286-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02286-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,22]],"date-time":"2025-06-22T19:02:10Z","timestamp":1750618930000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02286-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,23]]},"references-count":103,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2286"],"URL":"https:\/\/doi.org\/10.1038\/s41392-025-02286-9","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,23]]},"assertion":[{"value":"19 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 June 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"195"}}