{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:06:34Z","timestamp":1767834394182,"version":"3.49.0"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS099461"],"award-info":[{"award-number":["R01NS099461"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS125653"],"award-info":[{"award-number":["R01NS125653"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS110808"],"award-info":[{"award-number":["R01NS110808"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS111230"],"award-info":[{"award-number":["R01NS111230"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL139543"],"award-info":[{"award-number":["R01HL139543"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R25NS065729"],"award-info":[{"award-number":["R25NS065729"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Neonatal hypoxic-ischemic encephalopathy (HIE) remains a leading cause of long-term neurologic morbidity. Fifty percent of HIE cases are mild and do not have clearly defined therapeutic interventions. Emergent evidence now demonstrates that up to 25% of children with mild HIE suffer motor and developmental delay by 18 months and 35% have cognitive impairments by age 5 years. Interestingly, the hippocampus, which is responsible for learning and memory, does not show overt injury but does demonstrate volume changes on imaging that correlate with cognitive and behavioral outcomes. Although there is extensive data regarding pathophysiological changes following moderate and severe HIE, there is a paucity of understanding regarding the extent, duration, and compensatory adaptations in the mild neonatal HIE brain. We performed hippocampal proteomic analysis using a swine model of mild neonatal hypoxia-asphyxia. Hippocampi were collected at 24 or 72 hours after injury, and proteomics was performed by liquid chromatography tandem mass spectrometry (LC-MS\/MS). Pathway analysis demonstrated that several metabolic pathways are temporally regulated after mild HIE. Specifically, amino acid, carbohydrate, and one-carbon metabolism increased at 24 hours while fat metabolism and oxidative phosphorylation decreased at 24 hours. Downregulation of oxidative phosphorylation was more pronounced at 72 hours. Our data demonstrate that metabolic reprogramming occurs after mild HIE, and these changes persist up to 72 hours after injury. These results provide new evidence that mild HIE disrupts brain metabolism, emphasizing the need for a better understanding of the underlying pathophysiology of mild HIE and development of targeted therapeutic interventions for this population.<\/jats:p>","DOI":"10.1371\/journal.pone.0320869","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T17:26:57Z","timestamp":1745515617000},"page":"e0320869","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Proteomic analysis of hippocampus reveals metabolic reprogramming in a piglet model of mild hypoxic ischemic encephalopathy"],"prefix":"10.1371","volume":"20","author":[{"given":"Dawn B.","family":"Lammert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1140-8768","authenticated-orcid":true,"given":"Regina F.","family":"Fernandez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuyun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond C.","family":"Koehler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Scafidi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2379-1370","authenticated-orcid":true,"given":"Joseph","family":"Scafidi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"issue":"3","key":"pone.0320869.ref001","doi-asserted-by":"crossref","first-page":"e148","DOI":"10.1542\/neo.22-3-e148","article-title":"Neonatal encephalopathy: beyond hypoxic-ischemic encephalopathy","volume":"22","author":"JB Russ","year":"2021","journal-title":"Neoreviews"},{"issue":"4","key":"pone.0320869.ref002","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1001\/jamapediatrics.2014.3269","article-title":"Hypoxic-ischemic encephalopathy: a review for the clinician","volume":"169","author":"M Douglas-Escobar","year":"2015","journal-title":"JAMA Pediatr"},{"issue":"10","key":"pone.0320869.ref003","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1001\/archneur.1976.00500100030012","article-title":"Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study","volume":"33","author":"HB Sarnat","year":"1976","journal-title":"Arch Neurol"},{"issue":"15","key":"pone.0320869.ref004","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1056\/NEJMcps050929","article-title":"Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy","volume":"353","author":"S Shankaran","year":"2005","journal-title":"N Engl J Med"},{"issue":"4","key":"pone.0320869.ref005","doi-asserted-by":"crossref","first-page":"e20160659","DOI":"10.1542\/peds.2016-0659","article-title":"Early EEG grade and outcome at 5 years after mild neonatal hypoxic ischemic encephalopathy","volume":"138","author":"DM Murray","year":"2016","journal-title":"Pediatrics"},{"key":"pone.0320869.ref006","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.earlhumdev.2018.02.007","article-title":"Mild hypoxic ischaemic encephalopathy and long term neurodevelopmental outcome - A systematic review","volume":"120","author":"JM Conway","year":"2018","journal-title":"Early Hum Dev"},{"issue":"1","key":"pone.0320869.ref007","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/jon.13052","article-title":"Brain injury patterns in hypoxic ischemic encephalopathy of term neonates","volume":"33","author":"PS Bobba","year":"2023","journal-title":"J Neuroimaging"},{"key":"pone.0320869.ref008","doi-asserted-by":"crossref","first-page":"55","DOI":"10.2174\/1874440001812010055","article-title":"Magnetic resonance imaging findings of term and preterm hypoxic-ischemic encephalopathy: a review of relevant animal models and correlation to human imaging","volume":"12","author":"KA Jisa","year":"2018","journal-title":"Open Neuroimag J"},{"issue":"5","key":"pone.0320869.ref009","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1038\/s41390-023-02695-y","article-title":"Subcortical brain volumes in neonatal hypoxic-ischemic encephalopathy","volume":"94","author":"LMN Kebaya","year":"2023","journal-title":"Pediatr Res"},{"issue":"3","key":"pone.0320869.ref010","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/dmcn.15369","article-title":"Brain volumes and functional outcomes in children without cerebral palsy after therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy","volume":"65","author":"APC Spencer","year":"2023","journal-title":"Dev Med Child Neurol"},{"issue":"1","key":"pone.0320869.ref011","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1093\/ilar.47.1.32","article-title":"Brief update on animal models of hypoxic-ischemic encephalopathy and neonatal stroke","volume":"47","author":"FJ Northington","year":"2006","journal-title":"ILAR J"},{"key":"pone.0320869.ref012","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000523990","article-title":"The vannucci model of hypoxic-ischemic injury in the neonatal rodent: 40 years later","volume":"44","author":"SJ Vannucci","year":"2022","journal-title":"Dev Neurosci"},{"issue":"12","key":"pone.0320869.ref013","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1177\/0271678X18797328","article-title":"Perinatal hypoxic-ischemic brain injury in large animal models: relevance to human neonatal encephalopathy","volume":"38","author":"RC Koehler","year":"2018","journal-title":"J Cereb Blood Flow Metab"},{"issue":"1","key":"pone.0320869.ref014","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0378-3782(79)90022-7","article-title":"Comparative aspects of the brain growth spurt","volume":"3","author":"J Dobbing","year":"1979","journal-title":"Early Hum Dev"},{"issue":"1","key":"pone.0320869.ref015","doi-asserted-by":"crossref","first-page":"92","DOI":"10.3945\/an.116.013243","article-title":"early-life nutrition and neurodevelopment: use of the piglet as a translational model","volume":"8","author":"AT Mudd","year":"2017","journal-title":"Adv Nutr"},{"issue":"10","key":"pone.0320869.ref016","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1002\/pmic.201000722","article-title":"Reversed-phase chromatography with multiple fraction concatenation strategy for proteome profiling of human MCF10A cells","volume":"11","author":"Y Wang","year":"2011","journal-title":"Proteomics"},{"issue":"2","key":"pone.0320869.ref017","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1021\/pr300624g","article-title":"Statistical inference from multiple iTRAQ experiments without using common reference standards","volume":"12","author":"SM Herbrich","year":"2013","journal-title":"J Proteome Res"},{"issue":"3","key":"pone.0320869.ref018","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/jnc.14072","article-title":"Developmental regulation and localization of carnitine palmitoyltransferases (CPTs) in rat brain","volume":"142","author":"JN Jernberg","year":"2017","journal-title":"J Neurochem"},{"issue":"W1","key":"pone.0320869.ref019","doi-asserted-by":"crossref","first-page":"W566-70","DOI":"10.1093\/nar\/gkv468","article-title":"ClustVis: a web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap","volume":"43","author":"T Metsalu","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"6441","key":"pone.0320869.ref020","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1126\/science.aav8130","article-title":"Single-cell genomics identifies cell type-specific molecular changes in autism","volume":"364","author":"D Velmeshev","year":"2019","journal-title":"Science"},{"issue":"4","key":"pone.0320869.ref021","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41590-019-0323-3","article-title":"A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape","volume":"20","author":"P Hubel","year":"2019","journal-title":"Nat Immunol"},{"issue":"11","key":"pone.0320869.ref022","doi-asserted-by":"crossref","first-page":"e27544","DOI":"10.1371\/journal.pone.0027544","article-title":"PLD$ is involved in phagocytosis of microglia: expression and localization changes of PLD4 are correlated with activation state of microglia","volume":"6","author":"Y Otani","year":"2011","journal-title":"PLoS One"},{"issue":"1","key":"pone.0320869.ref023","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/neup.12235","article-title":"TMEM119 marks a subset of microglia in the human brain","volume":"36","author":"J Satoh","year":"2016","journal-title":"Neuropathology"},{"key":"pone.0320869.ref024","doi-asserted-by":"crossref","first-page":"112951","DOI":"10.1016\/j.fct.2022.112951","article-title":"Immunoproteasome subunit PSMB8 regulates microglia-mediated neuroinflammation upon manganese exposure by PERK signaling","volume":"163","author":"T Guo","year":"2022","journal-title":"Food Chem Toxicol"},{"issue":"1","key":"pone.0320869.ref025","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s11689-019-9292-y","article-title":"Mitochondrial aminoacyl-tRNA synthetase disorders: an emerging group of developmental disorders of myelination","volume":"11","author":"AS Fine","year":"2019","journal-title":"J Neurodev Disord"},{"issue":"8","key":"pone.0320869.ref026","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1261\/rna.071720.119","article-title":"Aminoacyl-tRNA synthetases","volume":"26","author":"MA Rubio Gomez","year":"2020","journal-title":"RNA"},{"issue":"3","key":"pone.0320869.ref027","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1021\/acs.chemrev.7b00181","article-title":"Lysine acetylation goes global: from epigenetics to metabolism and therapeutics","volume":"118","author":"I Ali","year":"2018","journal-title":"Chemical Reviews"},{"issue":"12","key":"pone.0320869.ref028","doi-asserted-by":"crossref","first-page":"e50520","DOI":"10.1371\/journal.pone.0050520","article-title":"The metabolomic profile of umbilical cord blood in neonatal hypoxic ischaemic encephalopathy","volume":"7","author":"BH Walsh","year":"2012","journal-title":"PLoS One"},{"issue":"5","key":"pone.0320869.ref029","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3390\/metabo12050467","article-title":"Neonatal hypoxic-ischemic brain injury alters brain acylcarnitine levels in a mouse model","volume":"12","author":"AM Dave","year":"2022","journal-title":"Metabolites"},{"issue":"15","key":"pone.0320869.ref030","doi-asserted-by":"crossref","first-page":"e15221","DOI":"10.1097\/MD.0000000000015221","article-title":"Acylcarnitine profile in neonatal hypoxic-ischemic encephalopathy: The value of butyrylcarnitine as a prognostic marker","volume":"98","author":"O L\u00f3pez-Su\u00e1rez","year":"2019","journal-title":"Medicine (Baltimore)"},{"issue":"3","key":"pone.0320869.ref031","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1124\/pharmrev.121.000408","article-title":"Acylcarnitines: nomenclature, biomarkers, therapeutic potential, drug targets, and clinical trials","volume":"74","author":"M Dambrova","year":"2022","journal-title":"Pharmacol Rev"},{"issue":"2","key":"pone.0320869.ref032","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/(SICI)1096-9861(19970113)377:2<262::AID-CNE8>3.0.CO;2-1","article-title":"Primary sensory and forebrain motor systems in the newborn brain are preferentially damaged by hypoxia-ischemia","volume":"377","author":"LJ Martin","year":"1997","journal-title":"J Comp Neurol"},{"issue":"5","key":"pone.0320869.ref033","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1203\/00006450-199611000-00014","article-title":"A piglet survival model of posthypoxic encephalopathy","volume":"40","author":"M Thoresen","year":"1996","journal-title":"Pediatric Research"},{"issue":"16","key":"pone.0320869.ref034","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1001\/jama.2017.14972","article-title":"Effect of therapeutic hypothermia initiated after 6 hours of age on death or disability among newborns with hypoxic-ischemic encephalopathy: a randomized clinical trial","volume":"318","author":"AR Laptook","year":"2017","journal-title":"JAMA"},{"key":"pone.0320869.ref035","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1159\/000369007","article-title":"Additive neuroprotection of a 20-HETE inhibitor with delayed therapeutic hypothermia after hypoxia-ischemia in neonatal piglets","volume":"37","author":"J Zhu","year":"2015","journal-title":"Developmental Neuroscience"},{"key":"pone.0320869.ref036","doi-asserted-by":"crossref","first-page":"111921","DOI":"10.1016\/j.bbr.2019.111921","article-title":"Spatial T-maze identifies cognitive deficits in piglets 1 month after hypoxia-ischemia in a model of hippocampal pyramidal neuron loss and interneuron attrition","volume":"369","author":"R Singh","year":"2019","journal-title":"Behav Brain Res"},{"issue":"2","key":"pone.0320869.ref037","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1007\/s12015-021-10213-y","article-title":"Microglia and stem-cell mediated neuroprotection after neonatal hypoxia-ischemia","volume":"18","author":"C Br\u00e9g\u00e8re","year":"2022","journal-title":"Stem Cell Rev Rep"},{"issue":"1","key":"pone.0320869.ref038","doi-asserted-by":"crossref","first-page":"e13674","DOI":"10.1111\/apha.13674","article-title":"Microglia-leucocyte axis in cerebral ischaemia and inflammation in the developing brain","volume":"233","author":"A Rayasam","year":"2021","journal-title":"Acta Physiol (Oxf)"},{"key":"pone.0320869.ref039","doi-asserted-by":"crossref","first-page":"1074287","DOI":"10.3389\/fped.2022.1074287","article-title":"The effect of erythropoietin on neonatal hypoxic-ischemic encephalopathy: An updated meta-analysis of randomized control trials","volume":"10","author":"J-J Pan","year":"2022","journal-title":"Front Pediatr"},{"issue":"1","key":"pone.0320869.ref040","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13052-020-00822-7","article-title":"Identification of novel biomarkers for neonatal hypoxic-ischemic encephalopathy using iTRAQ","volume":"46","author":"Y Zhu","year":"2020","journal-title":"Ital J Pediatr"},{"key":"pone.0320869.ref041","first-page":"e2200054","article-title":"A comparative proteomic analysis for non-invasive early prediction of hypoxic-ischemic injury in asphyxiated neonates","author":"S Gurtoo","year":"2023","journal-title":"Proteomics Clinical Applications"},{"issue":"2","key":"pone.0320869.ref042","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/jnc.14574","article-title":"The S100B story: from biomarker to active factor in neural injury","volume":"148","author":"F Michetti","year":"2019","journal-title":"J Neurochem"},{"issue":"1","key":"pone.0320869.ref043","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s00431-008-0711-4","article-title":"Umbilical artery blood S100beta protein: a tool for the early identification of neonatal hypoxic-ischemic encephalopathy","volume":"168","author":"J Qian","year":"2009","journal-title":"Eur J Pediatr"},{"issue":"3","key":"pone.0320869.ref044","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1159\/000252972","article-title":"Cerebral amino acid profiles after hypoxia-reoxygenation and N-acetylcysteine treatment in the newborn piglet","volume":"97","author":"LL Jantzie","year":"2010","journal-title":"Neonatology"},{"issue":"4","key":"pone.0320869.ref045","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25042035","article-title":"Metabolite biomarkers for early ischemic-hypoxic encephalopathy: an experimental study using the NeoBase 2 MSMS Kit in a rat model","volume":"25","author":"Y Shevtsova","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"11","key":"pone.0320869.ref046","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1111\/j.1651-2227.1993.tb12601.x","article-title":"Excitatory amino acids in the cerebrospinal fluid of asphyxiated infants: relationship to hypoxic-ischemic encephalopathy","volume":"82","author":"H Hagberg","year":"1993","journal-title":"Acta Paediatr"},{"issue":"1","key":"pone.0320869.ref047","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/s00134-007-0880-z","article-title":"Postresuscitation N-acetylcysteine treatment reduces cerebral hydrogen peroxide in the hypoxic piglet brain","volume":"34","author":"T-F Lee","year":"2008","journal-title":"Intensive Care Med"},{"key":"pone.0320869.ref048","doi-asserted-by":"crossref","first-page":"26-33.e1","DOI":"10.1016\/j.jpeds.2017.03.065","article-title":"The frequency and severity of magnetic resonance imaging abnormalities in infants with mild neonatal encephalopathy","volume":"187","author":"BH Walsh","year":"2017","journal-title":"J Pediatr"},{"issue":"7","key":"pone.0320869.ref049","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1177\/0883073819828625","article-title":"Current practice of therapeutic hypothermia for mild hypoxic ischemic encephalopathy","volume":"34","author":"CL Saw","year":"2019","journal-title":"J Child Neurol"},{"issue":"1","key":"pone.0320869.ref050","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1001\/jamapediatrics.2017.3044","article-title":"Mild neonatal encephalopathy-how, when, and how much to treat?","volume":"172","author":"GA Lodygensky","year":"2018","journal-title":"JAMA Pediatrics"},{"key":"pone.0320869.ref051","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.pediatrneurol.2022.06.006","article-title":"Association between early EEG background and outcomes in infants with mild HIE undergoing therapeutic hypothermia","volume":"134","author":"N Natarajan","year":"2022","journal-title":"Pediatr Neurol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0320869","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T17:27:15Z","timestamp":1745515635000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0320869"}},"subtitle":[],"editor":[{"given":"Samiullah","family":"Khan","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,24]]},"references-count":51,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0320869","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,24]]}}}