{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:51:41Z","timestamp":1787014301914,"version":"build-2736575974"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"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":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Huntington disease (HD) is a neurodegenerative disease caused by the abnormal expansion of a polyglutamine tract resulting from a mutation in the\n                    <jats:italic>HTT<\/jats:italic>\n                    gene. Oxidative stress has been identified as a significant contributing factor to the development of HD and other neurodegenerative diseases, and targeting anti-oxidative stress has emerged as a potential therapeutic approach. CHCHD2 is a mitochondria-related protein involved in regulating cell migration, anti-oxidative stress, and anti-apoptosis. Although CHCHD2 is highly expressed in HD cells, its specific role in the pathogenesis of HD remains uncertain. We postulate that the up-regulation of CHCHD2 in HD models represents a compensatory protective response against mitochondrial dysfunction and oxidative stress associated with HD. To investigate this hypothesis, we employed HD mouse striatal cells and human induced pluripotent stem cells (hiPSCs) as models to examine the effects of CHCHD2 overexpression (CHCHD2-OE) or knockdown (CHCHD2-KD) on the HD phenotype. Our findings demonstrate that CHCHD2 is crucial for maintaining cell survival in both HD mouse striatal cells and hiPSCs-derived neurons. Our study demonstrates that CHCHD2 up-regulation in HD serves as a compensatory protective response against oxidative stress, suggesting a potential anti-oxidative strategy for the treatment of HD.\n                  <\/jats:p>","DOI":"10.1038\/s41419-024-06523-x","type":"journal-article","created":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T04:02:27Z","timestamp":1707537747000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["CHCHD2 up-regulation in Huntington disease mediates a compensatory protective response against oxidative stress"],"prefix":"10.1038","volume":"15","author":[{"given":"Xuanzhuo","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinman","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huili","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3154-0985","authenticated-orcid":false,"given":"Anding","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9030-0976","authenticated-orcid":false,"given":"Mahmoud A.","family":"Pouladi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2576-3441","authenticated-orcid":false,"given":"Xiaohong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,10]]},"reference":[{"key":"6523_CR1","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/S0140-6736(07)60111-1","volume":"369","author":"FO Walker","year":"2007","unstructured":"Walker FO. Huntington\u2019s disease. Lancet. 2007;369:218\u201328.","journal-title":"Lancet"},{"key":"6523_CR2","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1007\/s12041-018-0963-3","volume":"97","author":"D Arneson","year":"2018","unstructured":"Arneson D, Zhang Y, Yang X, Narayanan M. Shared mechanisms among neurodegenerative diseases: from genetic factors to gene networks. J Genet. 2018;97:795\u2013806.","journal-title":"J Genet"},{"key":"6523_CR3","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.bbrc.2007.05.093","volume":"359","author":"CM Chen","year":"2007","unstructured":"Chen CM, Wu YR, Cheng ML, Liu JL, Lee YM, Lee PW, et al. Increased oxidative damage and mitochondrial abnormalities in the peripheral blood of Huntington\u2019s disease patients. Biochem Biophys Res Commun. 2007;359:335\u201340.","journal-title":"Biochem Biophys Res Commun"},{"key":"6523_CR4","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1046\/j.1471-4159.2001.00689.x","volume":"79","author":"MB Bogdanov","year":"2001","unstructured":"Bogdanov MB, Andreassen OA, Dedeoglu A, Ferrante RJ, Beal MF. Increased oxidative damage to DNA in a transgenic mouse model of Huntington\u2019s disease. J Neurochem. 2001;79:1246\u20139.","journal-title":"J Neurochem"},{"key":"6523_CR5","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1002\/1873-3468.12964","volume":"592","author":"PR Angelova","year":"2018","unstructured":"Angelova PR, Abramov AY. Role of mitochondrial ROS in the brain: from physiology to neurodegeneration. FEBS Lett. 2018;592:692\u2013702.","journal-title":"FEBS Lett"},{"key":"6523_CR6","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1196\/annals.1427.036","volume":"1147","author":"JA Johnson","year":"2008","unstructured":"Johnson JA, Johnson DA, Kraft AD, Calkins MJ, Jakel RJ, Vargas MR, et al. The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann N. Y Acad Sci. 2008;1147:61\u201369.","journal-title":"Ann N. Y Acad Sci"},{"key":"6523_CR7","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.pharmthera.2015.11.003","volume":"157","author":"I Buendia","year":"2016","unstructured":"Buendia I, Michalska P, Navarro E, Gameiro I, Egea J, Le\u00f3n R. Nrf2-ARE pathway: an emerging target against oxidative stress and neuroinflammation in neurodegenerative diseases. Pharm Ther. 2016;157:84\u2013104.","journal-title":"Pharm Ther"},{"key":"6523_CR8","doi-asserted-by":"publisher","first-page":"660843","DOI":"10.3389\/fnagi.2021.660843","volume":"13","author":"TR Kee","year":"2021","unstructured":"Kee TR, Espinoza Gonzalez P, Wehinger JL, Bukhari MZ, Ermekbaeva A, Sista A, et al. Mitochondrial CHCHD2: disease-associated mutations, physiological functions, and current animal models. Front Aging Neurosci. 2021;13:660843.","journal-title":"Front Aging Neurosci"},{"key":"6523_CR9","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1093\/nar\/gks1454","volume":"41","author":"S Aras","year":"2013","unstructured":"Aras S, Pak O, Sommer N, Finley R Jr, H\u00fcttemann M, Weissmann N, et al. Oxygen-dependent expression of cytochrome c oxidase subunit 4-2 gene expression is mediated by transcription factors RBPJ, CXXC5 and CHCHD2. Nucleic Acids Res. 2013;41:2255\u201366.","journal-title":"Nucleic Acids Res"},{"key":"6523_CR10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.mito.2014.10.003","volume":"20","author":"S Aras","year":"2015","unstructured":"Aras S, Bai M, Lee I, Springett R, H\u00fcttemann M, Grossman LI. MNRR1 (formerly CHCHD2) is a bi-organellar regulator of mitochondrial metabolism. Mitochondrion. 2015;20:43\u201351.","journal-title":"Mitochondrion"},{"key":"6523_CR11","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.jns.2017.08.647","volume":"381","author":"M Funayama","year":"2017","unstructured":"Funayama M, Park JS, Amo T, Funayama T, Akamatsu W, Sue CM, et al. CHCHD2 deficiency leads to mitochondrial dysfunction and increasing oxidative stress in human neuroblastoma SH-SY5Y cells. J Neurol Sci. 2017;381:226.","journal-title":"J Neurol Sci"},{"key":"6523_CR12","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1038\/cdd.2014.194","volume":"22","author":"Y Liu","year":"2015","unstructured":"Liu Y, Clegg HV, Leslie PL, Di J, Tollini LA, He Y, et al. CHCHD2 inhibits apoptosis by interacting with Bcl-x L to regulate Bax activation. Cell Death Differ. 2015;22:1035\u201346.","journal-title":"Cell Death Differ"},{"key":"6523_CR13","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1177\/1073858419871214","volume":"26","author":"W Zhou","year":"2020","unstructured":"Zhou W, Ma D, Tan EK. Mitochondrial CHCHD2 and CHCHD10: roles in neurological diseases and therapeutic implications. Neuroscientist. 2020;26:170\u201384.","journal-title":"Neuroscientist"},{"key":"6523_CR14","doi-asserted-by":"publisher","first-page":"217.e219","DOI":"10.1016\/j.neurobiolaging.2015.10.040","volume":"38","author":"CH Shi","year":"2016","unstructured":"Shi CH, Mao CY, Zhang SY, Yang J, Song B, Wu P, et al. CHCHD2 gene mutations in familial and sporadic Parkinson\u2019s disease. Neurobiol Aging. 2016;38:217.e219\u2013217.e213.","journal-title":"Neurobiol Aging"},{"key":"6523_CR15","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1212\/WNL.0000000000002170","volume":"85","author":"K Ogaki","year":"2015","unstructured":"Ogaki K, Koga S, Heckman MG, Fiesel FC, Ando M, Labb\u00e9 C, et al. Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders. Neurology. 2015;85:2016\u201325.","journal-title":"Neurology"},{"key":"6523_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15500","volume":"8","author":"H Meng","year":"2017","unstructured":"Meng H, Yamashita C, Shiba-Fukushima K, Inoshita T, Funayama M, Sato S, et al. Loss of Parkinson\u2019s disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c. Nat Commun. 2017;8:15500.","journal-title":"Nat Commun"},{"key":"6523_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/08039488.2018.1478991","volume":"73","author":"L Zhou","year":"2019","unstructured":"Zhou L, Wang G, Nan C, Wang H, Liu Z, Bai H. Abnormalities in P300 components in depression: an ERP-sLORETA study. Nord J Psychiatry. 2019;73:1\u20138.","journal-title":"Nord J Psychiatry"},{"key":"6523_CR18","doi-asserted-by":"publisher","first-page":"11023","DOI":"10.1073\/pnas.0504921102","volume":"102","author":"F Borovecki","year":"2005","unstructured":"Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas HD, et al. Genome-wide expression profiling of human blood reveals biomarkers for Huntington\u2019s disease. Proc Natl Acad Sci USA. 2005;102:11023\u20138.","journal-title":"Proc Natl Acad Sci USA"},{"key":"6523_CR19","doi-asserted-by":"publisher","first-page":"3883","DOI":"10.1093\/hmg\/dds216","volume":"21","author":"M Feyeux","year":"2012","unstructured":"Feyeux M, Bourgois-Rocha F, Redfern A, Giles P, Lefort N, Aubert S, et al. Early transcriptional changes linked to naturally occurring Huntington\u2019s disease mutations in neural derivatives of human embryonic stem cells. Hum Mol Genet. 2012;21:3883\u201395.","journal-title":"Hum Mol Genet"},{"key":"6523_CR20","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.stemcr.2017.01.022","volume":"8","author":"X Xu","year":"2017","unstructured":"Xu X, Tay Y, Sim B, Yoon SI, Huang Y, Ooi J, et al. Reversal of phenotypic abnormalities by CRISPR\/Cas9-mediated gene correction in Huntington disease patient-derived induced pluripotent stem cells. Stem Cell Rep. 2017;8:619\u201333.","journal-title":"Stem Cell Rep"},{"key":"6523_CR21","doi-asserted-by":"publisher","first-page":"2788","DOI":"10.1093\/hmg\/ddaa184","volume":"29","author":"GEB Wright","year":"2020","unstructured":"Wright GEB, Caron NS, Ng B, Casal L, Casazza W, Xu X, et al. Gene expression profiles complement the analysis of genomic modifiers of the clinical onset of Huntington disease. Hum Mol Genet. 2020;29:2788\u2013802.","journal-title":"Hum Mol Genet"},{"key":"6523_CR22","doi-asserted-by":"publisher","first-page":"2494","DOI":"10.1016\/j.celrep.2019.02.008","volume":"26","author":"J Ooi","year":"2019","unstructured":"Ooi J, Langley SR, Xu X, Utami KH, Sim B, Huang Y, et al. Unbiased profiling of isogenic Huntington disease hPSC-derived CNS and peripheral cells reveals strong cell-type specificity of CAG length effects. Cell Rep. 2019;26:2494\u20132508.e2497.","journal-title":"Cell Rep"},{"key":"6523_CR23","doi-asserted-by":"publisher","first-page":"2799","DOI":"10.1093\/hmg\/9.19.2799","volume":"9","author":"F Trettel","year":"2000","unstructured":"Trettel F, Rigamonti D, Hilditch-Maguire P, Wheeler VC, Sharp AH, Persichetti F, et al. Dominant phenotypes produced by the HD mutation in STHdh(Q111) striatal cells. Hum Mol Genet. 2000;9:2799\u2013809.","journal-title":"Hum Mol Genet"},{"key":"6523_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02983-z","volume":"11","author":"X Xu","year":"2020","unstructured":"Xu X, Ng B, Sim B, Radulescu CI, Yusof N, Goh WI, et al. pS421 huntingtin modulates mitochondrial phenotypes and confers neuroprotection in an HD hiPSC model. Cell Death Dis. 2020;11:809.","journal-title":"Cell Death Dis"},{"key":"6523_CR25","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1093\/hmg\/ddq026","volume":"19","author":"MA Pouladi","year":"2010","unstructured":"Pouladi MA, Xie Y, Skotte NH, Ehrnhoefer DE, Graham RK, Kim JE, et al. Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression. Hum Mol Genet. 2010;19:1528\u201338.","journal-title":"Hum Mol Genet"},{"key":"6523_CR26","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.3390\/molecules24081583","volume":"24","author":"A Singh","year":"2019","unstructured":"Singh A, Kukreti R, Saso L, Kukreti S. Oxidative stress: a key modulator in neurodegenerative diseases. Molecules. 2019;24:1583.","journal-title":"Molecules"},{"key":"6523_CR27","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1196\/annals.1427.008","volume":"1147","author":"EC Stack","year":"2008","unstructured":"Stack EC, Matson WR, Ferrante RJ. Evidence of oxidant damage in Huntington\u2019s disease: translational strategies using antioxidants. Ann N. Y Acad Sci. 2008;1147:79\u201392.","journal-title":"Ann N. Y Acad Sci"},{"key":"6523_CR28","unstructured":"Saravanan J, Praveen Thaggikuppe K, Meghana J, Vishnu K. Nrf2 as a potential therapeutic target for treatment of Huntington\u2019s disease. In: Natalia S, editor. From pathophysiology to treatment of huntington\u2019s disease. Rijeka: IntechOpen; 2022."},{"key":"6523_CR29","doi-asserted-by":"publisher","first-page":"e4676","DOI":"10.1073\/pnas.1614943114","volume":"114","author":"L Quinti","year":"2017","unstructured":"Quinti L, Dayalan Naidu S, Tr\u00e4ger U, Chen X, Kegel-Gleason K, Ll\u00e8res D, et al. KEAP1-modifying small molecule reveals muted NRF2 signaling responses in neural stem cells from Huntington\u2019s disease patients. Proc Natl Acad Sci USA. 2017;114:e4676\u2013e4685.","journal-title":"Proc Natl Acad Sci USA"},{"key":"6523_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-9-84","volume":"9","author":"WM van Roon-Mom","year":"2008","unstructured":"van Roon-Mom WM, Pepers BA, t Hoen PA, Verwijmeren CA, den Dunnen JT, Dorsman JC, et al. Mutant huntingtin activates Nrf2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington\u2019s disease. BMC Mol Biol. 2008;9:84.","journal-title":"BMC Mol Biol"},{"key":"6523_CR31","doi-asserted-by":"publisher","first-page":"e1000590","DOI":"10.1371\/journal.pgen.1000590","volume":"5","author":"JM Baughman","year":"2009","unstructured":"Baughman JM, Nilsson R, Gohil VM, Arlow DH, Gauhar Z, Mootha VK. A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis. PLoS Genet. 2009;5:e1000590.","journal-title":"PLoS Genet"},{"key":"6523_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04602-5","volume":"13","author":"Y Ruan","year":"2022","unstructured":"Ruan Y, Hu J, Che Y, Liu Y, Luo Z, Cheng J, et al. CHCHD2 and CHCHD10 regulate mitochondrial dynamics and integrated stress response. Cell Death Dis. 2022;13:156.","journal-title":"Cell Death Dis"},{"key":"6523_CR33","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1042\/BJ20101431","volume":"433","author":"AM McGee","year":"2011","unstructured":"McGee AM, Baines CP. Complement 1q-binding protein inhibits the mitochondrial permeability transition pore and protects against oxidative stress-induced death. Biochem J. 2011;433:119\u201325.","journal-title":"Biochem J"},{"key":"6523_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67457-w","volume":"10","author":"S Noh","year":"2020","unstructured":"Noh S, Phorl S, Naskar R, Oeum K, Seo Y, Kim E, et al. p32\/C1QBP regulates OMA1-dependent proteolytic processing of OPA1 to maintain mitochondrial connectivity related to mitochondrial dysfunction and apoptosis. Sci Rep. 2020;10:10618.","journal-title":"Sci Rep"},{"key":"6523_CR35","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1158\/1541-7786.MCR-14-0165-T","volume":"13","author":"Y Wei","year":"2015","unstructured":"Wei Y, Vellanki RN, Coyaud \u00c9, Ignatchenko V, Li L, Krieger JR, et al. CHCHD2 is coamplified with EGFR in NSCLC and regulates mitochondrial function and cell migration. Mol Cancer Res. 2015;13:1119\u201329.","journal-title":"Mol Cancer Res"},{"key":"6523_CR36","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.1038\/s41418-019-0482-7","volume":"27","author":"W Liu","year":"2020","unstructured":"Liu W, Duan X, Xu L, Shang W, Zhao J, Wang L, et al. CHCHD2 regulates mitochondrial morphology by modulating the levels of Opa1. Cell Death Differ. 2020;27:2014\u201329.","journal-title":"Cell Death Differ"},{"key":"6523_CR37","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/nrn3570","volume":"14","author":"MA Pouladi","year":"2013","unstructured":"Pouladi MA, Morton AJ, Hayden MR. Choosing an animal model for the study of Huntington\u2019s disease. Nat Rev Neurosci. 2013;14:708\u201321.","journal-title":"Nat Rev Neurosci"},{"key":"6523_CR38","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","volume":"131","author":"K Takahashi","year":"2007","unstructured":"Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861\u201372.","journal-title":"Cell"},{"key":"6523_CR39","doi-asserted-by":"publisher","first-page":"16","DOI":"10.12703\/r\/11-16","volume":"11","author":"J Kaye","year":"2022","unstructured":"Kaye J, Reisine T, Finkbeiner S. Huntington\u2019s disease iPSC models-using human patient cells to understand the pathology caused by expanded CAG repeats. Fac Rev. 2022;11:16.","journal-title":"Fac Rev"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-024-06523-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-024-06523-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-024-06523-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T04:02:41Z","timestamp":1707537761000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-024-06523-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,10]]},"references-count":39,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["6523"],"URL":"https:\/\/doi.org\/10.1038\/s41419-024-06523-x","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,10]]},"assertion":[{"value":"3 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 January 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 February 2024","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":"126"}}