{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:21:11Z","timestamp":1787026871783,"version":"build-2736575974"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:00:00Z","timestamp":1718928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background and objective<\/jats:title>\n                    <jats:p>Neuroinflammatory processes have been identified as playing a crucial role in the pathophysiology of various neurodegenerative diseases, including idiopathic normal-pressure hydrocephalus (iNPH). iNPH, defined as a common disease of cognitive impairment in older adults, poses major challenges for therapeutic interventions owing to the stringent methodological requirements of relevant studies, clinical heterogeneity, unclear etiology, and uncertain diagnostic criteria. This study aims to assess the relationship between circulating inflammatory biomarkers and iNPH risk using bidirectional two-sample Mendelian randomization (MR) combined with meta-analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In our bidirectional MR study, genetic data from a genome-wide association study (GWAS) involving 1,456 iNPH cases and 409,726 controls of European ancestry were employed. Single-nucleotide polymorphisms (SNPs) associated with exposures served as instrumental variables for estimating the causal relationships between iNPH and 132 types of circulating inflammatory biomarkers from corresponding GWAS data. Causal associations were primarily examined using the inverse variance-weighted method, supplemented by MR-Egger, weighted median, simple mode, and weighted mode analyses. In the results, heterogeneity was assessed using the Cochran\n                      <jats:italic>Q<\/jats:italic>\n                      test. Horizontal pleiotropy was evaluated through the MR-Egger intercept test and the MR pleiotropy residual sum and outliers test. Sensitivity analysis was conducted through leave-one-out analysis. Reverse MR analyses were performed to mitigate bias from reverse causality. Meta-analyses of identical inflammatory biomarkers from both data sources strengthened the findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Results indicated a genetically predicted association between Interleukin-16 (IL-16) [OR: 1.228, 95% CI: 1.049\u20131.439,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011], TNF-related apoptosis ligand (TRAIL) [OR: 1.111, 95% CI: 1.019\u20131.210,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.017] and Urokinase-type plasminogen activator (uPA) [OR: 1.303, 95% CI: 1.025\u20131.658,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.031] and the risk of iNPH. Additionally, changes in human Glial cell line-derived neurotrophic factor (hGDNF) [OR: 1.044, 95% CI: 1.006\u20131.084,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.023], Matrix metalloproteinase-1 (MMP-1) [OR: 1.058, 95% CI: 1.020, 1.098,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003] and Interleukin-12p70 (IL-12p70) [OR: 0.897, 95% CI: 0.946\u20130.997,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.037] levels were identified as possible consequences of iNPH.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our MR study of inflammatory biomarkers and iNPH, indicated that IL-16, TRAIL, and uPA contribute to iNPH pathogenesis. Furthermore, iNPH may influence the expression of hGDNF, MMP-1, and IL-12p70. Therefore, targeting specific inflammatory biomarkers could be promising strategy for future iNPH treatment and prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2024.1412434","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T01:06:29Z","timestamp":1718931989000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring causal correlations of inflammatory biomarkers in idiopathic normal-pressure hydrocephalus: insights from bidirectional Mendelian randomization analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Jianglong","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianpeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanjie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjun","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1056\/NEJM196507152730301","article-title":"Symptomatic occult hydrocephalus with \u201cnormal\u201d cerebrospinal-fluid pressure. A treatable syndrome","volume":"273","author":"Adams","year":"1965","journal-title":"N. Engl. J. Med."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ajhg.2016.11.007","article-title":"Genome-wide association study identifies 27 loci influencing concentrations of circulating cytokines and growth factors","volume":"100","author":"Ahola-Olli","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"866313","DOI":"10.3389\/fnagi.2022.866313","article-title":"Pathophysiological mechanisms underlying idiopathic normal pressure hydrocephalus: a review of recent insights","volume":"14","author":"Bonney","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1002\/jrsm.1346","article-title":"Meta-analysis and Mendelian randomization: a review","volume":"10","author":"Bowden","year":"2019","journal-title":"Res. Synth. Methods"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s12987-023-00472-x","article-title":"Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases","volume":"20","author":"Braun","year":"2023","journal-title":"Fluids Barriers CNS"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1007\/s10654-018-0424-6","article-title":"Mendelian randomization with a binary exposure variable: interpretation and presentation of causal estimates","volume":"33","author":"Burgess","year":"2018","journal-title":"Eur. J. Epidemiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1093\/ije\/dyr036","article-title":"Avoiding bias from weak instruments in Mendelian randomization studies","volume":"40","author":"Burgess","year":"2011","journal-title":"Int. J. Epidemiol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"6.23.1","DOI":"10.1002\/0471142735.im0623s22","article-title":"Measurement of interleukin 16","author":"Center","year":"2001","journal-title":"Curr. Protoc. Immunol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1007\/s00394-022-02994-w","article-title":"Tea consumption and risk of lower respiratory tract infections: a two-sample Mendelian randomization study","volume":"62","author":"Chen","year":"2023","journal-title":"Eur. J. Nutr."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"301","DOI":"10.5114\/fn.2017.72389","article-title":"Levels of selected pro- and anti-inflammatory cytokines in cerebrospinal fluid in patients with hydrocephalus","volume":"55","author":"Czubowicz","year":"2017","journal-title":"Folia Neuropathol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2724","DOI":"10.1007\/s00415-023-11604-6","article-title":"Association between vascular risk factors and idiopathic normal pressure hydrocephalus: a Mendelian randomization study","volume":"270","author":"Deng","year":"2023","journal-title":"J. Neurol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"jcs255919","DOI":"10.1242\/jcs.255919","article-title":"Urokinase-type plasminogen activator-mediated crosstalk between N-cadherin and \u03b2-catenin promotes wound healing","volume":"134","author":"Diaz","year":"2021","journal-title":"J. Cell Sci."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"RC209","DOI":"10.1523\/JNEUROSCI.22-04-j0001.2002","article-title":"Lack of tumor necrosis factor-related apoptosis-inducing ligand but presence of its receptors in the human brain","volume":"22","author":"D\u00f6rr","year":"2002","journal-title":"J. Neurosci."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s40001-023-01609-2","article-title":"Circulating inflammatory biomarkers and risk of intracranial aneurysm: a Mendelian randomization study","volume":"29","author":"Fang","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1285106","DOI":"10.3389\/fimmu.2023.1285106","article-title":"Exploring causal correlations between inflammatory cytokines and ankylosing spondylitis: a bidirectional Mendelian-randomization study","volume":"14","author":"Fang","year":"2023","journal-title":"Front. Immunol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e1812","DOI":"10.1212\/WNL.0000000000207113","article-title":"Associations between CSF markers of inflammation, White matter lesions, and cognitive decline in individuals without dementia","volume":"100","author":"Gertje","year":"2023","journal-title":"Neurology"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1007\/s00109-009-0484-x","article-title":"Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in central nervous system inflammation","volume":"87","author":"Hoffmann","year":"2009","journal-title":"J. Mol. Med."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.neurobiolaging.2016.11.017","article-title":"Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype","volume":"51","author":"Janelidze","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/S0006-8993(00)03042-0","article-title":"Roles of urokinase type plasminogen activator in a brain stab wound","volume":"887","author":"Kataoka","year":"2000","journal-title":"Brain Res."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/nri3499","article-title":"Metalloproteinases and their natural inhibitors in inflammation and immunity","volume":"13","author":"Khokha","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"27","DOI":"10.18502\/ijaai.v21i1.8610","article-title":"Correlation of serum levels of interleukine-16, CCL27, tumor necrosis factor-related apoptosis-inducing ligand, and B-cell activating factor with multiple sclerosis severity","volume":"21","author":"Kouchaki","year":"2022","journal-title":"Iran J. Allergy Asthma Immunol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/s41586-022-05473-8","article-title":"FinnGen provides genetic insights from a well-phenotyped isolated population","volume":"613","author":"Kurki","year":"2023","journal-title":"Nature"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"312526","DOI":"10.4061\/2011\/312526","article-title":"Cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus","volume":"2011","author":"Leinonen","year":"2011","journal-title":"Int. J. Alzheimers Dis."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1269494","DOI":"10.3389\/fgene.2023.1269494","article-title":"Positive association between omega-3\/6 polyunsaturated fatty acids and idiopathic normal pressure hydrocephalus: a Mendelian randomization study","volume":"14","author":"Li","year":"2023","journal-title":"Front. Genet."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1241237","DOI":"10.3389\/fnagi.2023.1241237","article-title":"Comparison of cerebrospinal fluid space between probable normal pressure hydrocephalus and Alzheimer\u2019s disease","volume":"15","author":"Li","year":"2023","journal-title":"Front. Aging Neurosci."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"779899","DOI":"10.3389\/fphar.2021.779899","article-title":"Inflammatory cytokines and risk of ischemic stroke: a Mendelian randomization study","volume":"12","author":"Li","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1126\/science.8493557","article-title":"GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons","volume":"260","author":"Lin","year":"1993","journal-title":"Science"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/8834822","article-title":"Inflammatory markers in cerebrospinal fluid from patients with hydrocephalus: a systematic literature review","volume":"2021","author":"Lolansen","year":"2021","journal-title":"Dis. Markers"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.neuron.2009.08.039","article-title":"Immune activation in brain aging and neurodegeneration: too much or too little?","volume":"64","author":"Lucin","year":"2009","journal-title":"Neuron"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12987-022-00309-z","article-title":"Cerebrospinal fluid biomarkers that reflect clinical symptoms in idiopathic normal pressure hydrocephalus patients","volume":"19","author":"Lukkarinen","year":"2022","journal-title":"Fluids Barriers CNS"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.1016\/j.wneu.2015.07.005","article-title":"Epidemiology of idiopathic normal pressure hydrocephalus: a systematic review of the literature","volume":"84","author":"Mart\u00edn-L\u00e1ez","year":"2015","journal-title":"World Neurosurg."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1046\/j.1365-2567.2000.00997.x","article-title":"Interleukin-16 stimulates the expression and production of pro-inflammatory cytokines by human monocytes","volume":"100","author":"Mathy","year":"2000","journal-title":"Immunology"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s12987-021-00256-1","article-title":"Lumbar and ventricular CSF concentrations of extracellular matrix proteins before and after shunt surgery in idiopathic normal pressure hydrocephalus","volume":"18","author":"Minta","year":"2021","journal-title":"Fluids Barriers CNS"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3390\/brainsci6010006","article-title":"The effects of hypoxia and inflammation on synaptic signaling in the CNS","volume":"6","author":"Mukandala","year":"2016","journal-title":"Brain Sci."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"2333721416643702","DOI":"10.1177\/2333721416643702","article-title":"Idiopathic normal pressure hydrocephalus: a review for general practitioners","volume":"2","author":"Nassar","year":"2016","journal-title":"Gerontol. Geriatr. Med."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/s41467-020-14389-8","article-title":"Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis","volume":"11","author":"Papadimitriou","year":"2020","journal-title":"Nat. Commun."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.neulet.2008.08.020","article-title":"Blood brain barrier (BBB) dysfunction associated with increased expression of tissue and urokinase plasminogen activators following peripheral thermal injury","volume":"444","author":"Patel","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1186\/1742-2094-9-188","article-title":"Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson\u2019s disease","volume":"9","author":"Pisani","year":"2012","journal-title":"J. Neuroinflammation"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.molmed.2019.11.008","article-title":"Glymphatic system impairment in Alzheimer\u2019s disease and idiopathic normal pressure hydrocephalus","volume":"26","author":"Reeves","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"S2-4","DOI":"10.1227\/01.NEU.0000168185.29659.C5","article-title":"Diagnosing idiopathic normal-pressure hydrocephalus","volume":"57","author":"Relkin","year":"2005","journal-title":"Neurosurgery"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1159\/000334862","article-title":"Serum levels of matrix metalloproteinases: implications in clinical neurology","volume":"67","author":"Romi","year":"2012","journal-title":"Eur. Neurol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"467","DOI":"10.2147\/CIA.S360736","article-title":"A comparison of cerebrospinal fluid Beta-amyloid and tau in idiopathic normal pressure hydrocephalus and neurodegenerative dementias","volume":"17","author":"Said","year":"2022","journal-title":"Clin. Interv. Aging"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s43586-021-00092-5","article-title":"Mendelian randomization","volume":"2","author":"Sanderson","year":"2022","journal-title":"Nat. Rev. Methods Primers"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ije\/dyg070","article-title":"\u201cMendelian randomization\u201d: can genetic epidemiology contribute to understanding environmental determinants of disease?","volume":"32","author":"Smith","year":"2003","journal-title":"Int. J. Epidemiol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/S0197-4580(02)00187-2","article-title":"Normal pressure hydrocephalus triggers intrathecal production of TNF-alpha","volume":"24","author":"Tarkowski","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"837","DOI":"10.3171\/2007.9.17572","article-title":"Noninvasive biomarkers in normal pressure hydrocephalus: evidence for the role of neuroimaging","volume":"110","author":"Tarnaris","year":"2009","journal-title":"J. Neurosurg."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"787","DOI":"10.2217\/bmm.09.37","article-title":"Ongoing search for diagnostic biomarkers in idiopathic normal pressure hydrocephalus","volume":"3","author":"Tarnaris","year":"2009","journal-title":"Biomark Med."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1743-8454-3-11","article-title":"Biomarkers in chronic adult hydrocephalus","volume":"3","author":"Tarnaris","year":"2006","journal-title":"Cerebrospinal Fluid Res."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1111\/cns.13526","article-title":"Pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus","volume":"26","author":"Wang","year":"2020","journal-title":"CNS Neurosci. Ther."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/nature20411","article-title":"Ageing, neurodegeneration and brain rejuvenation","volume":"539","author":"Wyss-Coray","year":"2016","journal-title":"Nature"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"985729","DOI":"10.3389\/fimmu.2022.985729","article-title":"Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: a Mendelian randomization","volume":"13","author":"Xiang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1186\/s12967-023-04612-7","article-title":"Bidirectional Mendelian randomization analysis of the genetic association between primary lung cancer and colorectal cancer","volume":"21","author":"Xiao","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1002\/alz.12399","article-title":"Plasma IL-12\/IFN-\u03b3 axis predicts cognitive trajectories in cognitively unimpaired older adults","volume":"18","author":"Yang","year":"2022","journal-title":"Alzheimers Dement."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1093\/ije\/dyaa241","article-title":"Systemic inflammatory regulators and risk of Alzheimer\u2019s disease: a bidirectional Mendelian-randomization study","volume":"50","author":"Yeung","year":"2021","journal-title":"Int. J. Epidemiol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1038\/s41590-023-01588-w","article-title":"Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets","volume":"24","author":"Zhao","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref56","article-title":"Association between viral infections and glioma risk: a two-sample bidirectional Mendelian randomization analysis. BMC Med. 21:487. doi: 10.1186\/s12916-023-03142-9","author":"Zhong","year":"2023"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2024.1412434\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T01:06:32Z","timestamp":1718931992000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2024.1412434\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,21]]},"references-count":56,"alternative-id":["10.3389\/fnagi.2024.1412434"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2024.1412434","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,21]]},"article-number":"1412434"}}