{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:44:01Z","timestamp":1787028241291,"version":"build-2736575974"},"reference-count":59,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Pontocerebellar hypoplasia is a rare neurodegenerative syndrome characterized by severe hypoplasia or atrophy of pons and cerebellum that may be associated with other brain malformations, microcephaly, optic nerve atrophy, dystonia, ataxia and neuromuscular disorders. At this time, there are 17 variants of PCH distinguished by clinical presentation and distinctive radiological and biochemical features in addition to pontine and cerebellar hypoplasia. PCH1 is defined as PCH variant associated with anterior horn degeneration in the spinal cord with muscle weakness and hypotonia, and is associated with recessive variants in genes VRK1, EXOSC3, EXOSC8, EXOSC9 and SLC25A46. Neuromuscular manifestations may clinically present as amyotrophic lateral sclerosis (ALS), motor neuropathy (HMN) or neuronopathy (non-5q spinal muscular atrophy; SMA) or sensorimotor polyneuropathy (HMSN). Physiologic functions of PCH1-associated genes include regulation of RNA metabolism, mitochondrial fission and neuronal migration. Overall, complex phenotypes associated with PCH1 gene variants ranging from PCH and related neurodevelopmental disorders combined with neuromuscular disorders to isolated neuromuscular disorders have variable outcomes with isolated neuromuscular disorders typically having later onset with better outcomes. Improved understanding of pathogenesis of pontocerebellar hypoplasia and its association with motor neuronopathies and peripheral neuropathies may provide us with valuable insights and lead to potential new therapeutic targets for neurodegenerative disorders.<\/jats:p>","DOI":"10.3390\/genes16050585","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T11:02:27Z","timestamp":1747306947000},"page":"585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pontocerebellar Hypoplasia Type 1 and Associated Neuronopathies"],"prefix":"10.3390","volume":"16","author":[{"given":"Mario","family":"\u0160karica","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyula","family":"Acsadi","sequence":"additional","affiliation":[{"name":"Division of Neurology, Connecticut Children\u2019s Medical Center, St. Hartford, CT 06106, USA"},{"name":"Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT 06030, USA"},{"name":"Department of Neurology, University of Connecticut School of Medicine, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasha A.","family":"\u017divkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Neurology and CMT Program at Yale, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"van Dijk, T., Baas, F., Barth, P.G., and Poll-The, B.T. (2018). What\u2019s new in pontocerebellar hypoplasia? An update on genes and subtypes. Orphanet J. Rare Dis., 13.","DOI":"10.1186\/s13023-018-0826-2"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s12311-020-01135-5","article-title":"Pontocerebellar hypoplasia: A pattern recognition approach","volume":"19","author":"Rusch","year":"2020","journal-title":"Cerebellum"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sanchez-Albisua, I., Frolich, S., Barth, P.G., Steinlin, M., and Krageloh-Mann, I. (2014). Natural course of pontocerebellar hypoplasia type 2A. Orphanet J. Rare Dis., 9.","DOI":"10.1186\/1750-1172-9-70"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/0387-7604(93)90080-R","article-title":"Pontocerebellar hypoplasias. An overview of a group of inherited neurodegenerative disorders with fetal onset","volume":"15","author":"Barth","year":"1993","journal-title":"Brain Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.ejpn.2018.03.011","article-title":"Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype correlations and diagnostic guidelines based on new cases and overview of the literature","volume":"22","author":"Ivanov","year":"2018","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1136\/jnnp.40.4.370","article-title":"Anterior horn cell disease associated with pontocerebellar hypoplasia in infants","volume":"40","author":"Goutieres","year":"1977","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1136\/adc.36.185.96","article-title":"Cerebellar hypoplasia in Werdnig-Hoffmann disease","volume":"36","author":"Norman","year":"1961","journal-title":"Arch. Dis. Child."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/cge.13084","article-title":"Extension of the phenotype of biallelic loss-of-function mutations in SLC25A46 to the severe form of pontocerebellar hypoplasia type I","volume":"93","author":"Braunisch","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.nmd.2022.04.007","article-title":"Distal spinal muscular atrophy featured by predominant calf muscle involvement in VRK1 associated disease\u2014Case series and review","volume":"32","author":"Demaegd","year":"2022","journal-title":"Neuromuscul. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/mus.26779","article-title":"Identification of a homozygous VRK1 mutation in two patients with adult-onset distal hereditary motor neuropathy","volume":"61","author":"Greenbaum","year":"2020","journal-title":"Muscle Nerve"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1097\/CND.0000000000000096","article-title":"Expanding phenotype of VRK1 mutations in motor neuron disease","volume":"17","author":"Nguyen","year":"2015","journal-title":"J. Clin. Neuromuscul. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1136\/jnnp-2019-320717","article-title":"Expanding the spectrum of genes responsible for hereditary motor neuropathies","volume":"90","author":"Previtali","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.nmd.2021.05.008","article-title":"New subtype of PCH1C caused by novel EXOSC8 variants in a 16-year-old Spanish patient","volume":"31","author":"Bellusci","year":"2021","journal-title":"Neuromuscul. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/s10038-020-00853-2","article-title":"Novel EXOSC9 variants cause pontocerebellar hypoplasia type 1D with spinal motor neuronopathy and cerebellar atrophy","volume":"66","author":"Sakamoto","year":"2021","journal-title":"J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sung, A., Moretti, P., and Shaibani, A. (2021). Adult-onset spinal muscular atrophy due to mutations in the VRK1 gene. Neurol. Genet., 7.","DOI":"10.1212\/NXG.0000000000000599"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zivkovic, S.A., Nowak, R.J., and DiCapua, D. (2024). CMT2 and distal hereditary motor neuropathy associated with VRK1 variants: Case series. Neuromuscul. Disord., 47.","DOI":"10.1016\/j.nmd.2024.105254"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Eggens, V.R., Barth, P.G., Niermeijer, J.M., Berg, J.N., Darin, N., Dixit, A., Fluss, J., Foulds, N., Fowler, D., and Hortobagyi, T. (2014). EXOSC3 mutations in pontocerebellar hypoplasia type 1: Novel mutations and genotype-phenotype correlations. Orphanet J. Rare Dis., 9.","DOI":"10.1186\/1750-1172-9-23"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1093\/hmg\/ddz060","article-title":"Loss of Cajal bodies in motor neurons from patients with novel mutations in VRK1","volume":"28","author":"Rihan","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Martin-Doncel, E., Rojas, A.M., Cantarero, L., and Lazo, P.A. (2019). VRK1 functional insufficiency due to alterations in protein stability or kinase activity of human VRK1 pathogenic variants implicated in neuromotor syndromes. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-49821-7"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lazo, P.A., and Morejon-Garcia, P. (2023). VRK1 variants at the cross road of Cajal body neuropathogenic mechanisms in distal neuropathies and motor neuron diseases. Neurobiol. Dis., 183.","DOI":"10.1016\/j.nbd.2023.106172"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrm.2015.15","article-title":"The regulation and functions of the nuclear RNA exosome complex","volume":"17","author":"Kilchert","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/ng.3354","article-title":"Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder","volume":"47","author":"Abrams","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/s41580-024-00785-1","article-title":"Molecular mechanisms of mitochondrial dynamics","volume":"26","author":"Tabara","year":"2025","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Adebayo, M., Singh, S., Singh, A.P., and Dasgupta, S. (2021). Mitochondrial fusion and fission: The fine-tune balance for cellular homeostasis. FASEB J., 35.","DOI":"10.1096\/fj.202100067R"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Boopathy, S., Luce, B.E., Lugo, C.M., Hakim, P., McDonald, J., Kim, H.L., Ponce, J., Ueberheide, B.M., and Chao, L.H. (2024). Identification of SLC25A46 interaction interfaces with mitochondrial membrane fusogens Opa1 and Mfn2. J. Biol. Chem., 300.","DOI":"10.1101\/2023.12.29.573615"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.15252\/emmm.201506159","article-title":"SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome","volume":"8","author":"Janer","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Dong, J., Chen, L., Ye, F., Tang, J., Liu, B., Lin, J., Zhou, P.H., Lu, B., Wu, M., and Lu, J.H. (2024). Mic19 depletion impairs endoplasmic reticulum-mitochondrial contacts and mitochondrial lipid metabolism and triggers liver disease. Nat. Commun., 15.","DOI":"10.1038\/s41467-023-44057-6"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1093\/brain\/aww212","article-title":"Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia","volume":"139","author":"Wan","year":"2016","journal-title":"Brain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/ajmg.a.10863","article-title":"Extended phenotype of pontocerebellar hypoplasia with infantile spinal muscular atrophy","volume":"117A","author":"Sztriha","year":"2003","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.ajhg.2009.07.006","article-title":"Spinal muscular atrophy with pontocerebellar hypoplasia is caused by a mutation in the VRK1 gene","volume":"85","author":"Renbaum","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1093\/brain\/awac452","article-title":"Early onset hereditary neuronopathies: An update on non-5q motor neuron diseases","volume":"146","author":"Zambon","year":"2023","journal-title":"Brain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1080\/21678421.2020.1746343","article-title":"VRK1 variants in two Portuguese unrelated patients with childhood-onset motor neuron disease","volume":"21","author":"Silva","year":"2020","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.2169\/internalmedicine.2126-18","article-title":"Novel VRK1 mutations in a patient with childhood-onset motor neuron disease","volume":"58","author":"Yamaura","year":"2019","journal-title":"Intern. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1212\/WNL.0000000000002813","article-title":"Novel motor phenotypes in patients with VRK1 mutations without pontocerebellar hypoplasia","volume":"87","author":"Stoll","year":"2016","journal-title":"Neurology"},{"key":"ref_35","first-page":"1491","article-title":"Mutations in VRK1 associated with complex motor and sensory axonal neuropathy plus microcephaly","volume":"70","author":"Lotze","year":"2013","journal-title":"JAMA Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1097\/WCO.0000000000001307","article-title":"The evolving spectrum of complex inherited neuropathies","volume":"37","author":"Rossor","year":"2024","journal-title":"Curr. Opin. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1002\/humu.23639","article-title":"Insights into the genotype-phenotype correlation and molecular function of SLC25A46","volume":"39","author":"Abrams","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/ng.2254","article-title":"Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration","volume":"44","author":"Wan","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41573-022-00612-2","article-title":"Amyotrophic lateral sclerosis: A neurodegenerative disorder poised for successful therapeutic translation","volume":"22","author":"Mead","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/s41582-024-01049-4","article-title":"Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis","volume":"21","author":"Faller","year":"2025","journal-title":"Nat. Rev. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Oliveira, D., Assoni, A.F., Alves, L.M., Sakugawa, A., Melo, U.S., Teles, E.S.A.L., Sertie, A.L., Caires, L.C., Goulart, E., and Ghirotto, B. (2024). ALS-associated VRK1 R321C mutation causes proteostatic imbalance and mitochondrial defects in iPSC-derived motor neurons. Neurobiol. Dis., 198.","DOI":"10.1016\/j.nbd.2024.106540"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.mito.2017.06.007","article-title":"Recessive mutation in EXOSC3 associates with mitochondrial dysfunction and pontocerebellar hypoplasia","volume":"37","author":"Schottmann","year":"2017","journal-title":"Mitochondrion"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.mito.2005.01.002","article-title":"Mitochondrial dysfunction and its role in motor neuron degeneration in ALS","volume":"5","author":"Manfredi","year":"2005","journal-title":"Mitochondrion"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.nmd.2007.08.001","article-title":"Rhabdomyolysis in pontocerebellar hypoplasia type 2 (PCH-2)","volume":"18","author":"Barth","year":"2008","journal-title":"Neuromuscul. Disord."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ghasemi, M.R., Tehrani Fateh, S., Moeinafshar, A., Sadeghi, H., Karimzadeh, P., Mirfakhraie, R., Rezaei, M., Hashemi-Gorji, F., Rezvani Kashani, M., and Fazeli Bavandpour, F. (2024). Broadening the phenotype and genotype spectrum of novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review. BMC Med. Genom., 17.","DOI":"10.1186\/s12920-024-01810-0"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wang, C., Ge, Y., Li, R., He, G., and Lin, Y. (2023). Novel compound heterozygous missense variants in TOE1 gene associated with pontocerebellar hypoplasia type 7. Gene, 862.","DOI":"10.1016\/j.gene.2023.147250"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1136\/jnnp-2017-315607","article-title":"Cerebellar atrophy in neurodegeneration-a meta-analysis","volume":"88","author":"Gellersen","year":"2017","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1002\/acn3.51050","article-title":"VRK1 (Y213H) homozygous mutant impairs Cajal bodies in a hereditary case of distal motor neuropathy","volume":"7","author":"Marcos","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Morejon-Garcia, P., Keren, B., Marcos-Alcalde, I., Gomez-Puertas, P., Mochel, F., and Lazo, P.A. (2021). Dysfunctional Homozygous VRK1-D263G Variant Impairs the Assembly of Cajal Bodies and DNA Damage Response in Hereditary Spastic Paraplegia. Neurol. Genet., 7.","DOI":"10.1212\/NXG.0000000000000624"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/acn3.701","article-title":"A novel VRK1 mutation associated with recessive distal hereditary motor neuropathy","volume":"6","author":"Feng","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s10038-018-0553-5","article-title":"A novel mutation in VRK1 associated with distal spinal muscular atrophy","volume":"64","author":"Li","year":"2019","journal-title":"J. Hum. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1002\/acn3.50912","article-title":"Motor neuron diseases caused by a novel VRK1 variant\u2014A genotype\/phenotype study","volume":"6","author":"Sedghi","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1007\/s00415-013-6896-0","article-title":"EXOSC3 mutations in isolated cerebellar hypoplasia and spinal anterior horn involvement","volume":"260","author":"Biancheri","year":"2013","journal-title":"J. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/s10038-023-01207-4","article-title":"A missense variant in EXOSC8 causes exon skipping and expands the phenotypic spectrum of pontocerebellar hypoplasia type 1C","volume":"69","author":"Zaki","year":"2024","journal-title":"J. Hum. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Boczonadi, V., Muller, J.S., Pyle, A., Munkley, J., Dor, T., Quartararo, J., Ferrero, I., Karcagi, V., Giunta, M., and Polvikoski, T. (2014). EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. Nat. Commun., 5.","DOI":"10.1038\/ncomms5287"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.ajhg.2018.03.011","article-title":"Variants in EXOSC9 disrupt the RNA exosome and result in cerebellar atrophy with spinal motor neuronopathy","volume":"102","author":"Burns","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Bizzari, S., Hamzeh, A.R., Mohamed, M., Al-Ali, M.T., and Bastaki, F. (2020). Expanded PCH1D phenotype linked to EXOSC9 mutation. Eur. J. Med. Genet., 63.","DOI":"10.1016\/j.ejmg.2019.01.012"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1002\/mds.26716","article-title":"SLC25A46 mutations underlie progressive myoclonic ataxia with optic atrophy and neuropathy","volume":"31","author":"Charlesworth","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1159\/000464445","article-title":"SLC25A46 mutations associated with autosomal recessive cerebellar ataxia in north african families","volume":"17","author":"Hammer","year":"2017","journal-title":"Neurodegener. Dis."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/5\/585\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:33:31Z","timestamp":1760031211000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/5\/585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,15]]},"references-count":59,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["genes16050585"],"URL":"https:\/\/doi.org\/10.3390\/genes16050585","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,15]]}}}