{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T09:50:34Z","timestamp":1774950634781,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:00:00Z","timestamp":1671753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UID\/Multi\/00709\/2019"],"award-info":[{"award-number":["UID\/Multi\/00709\/2019"]}]},{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["2021.07854.BD"],"award-info":[{"award-number":["2021.07854.BD"]}]},{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["POCI-01\u20130145-FEDER-029311"],"award-info":[{"award-number":["POCI-01\u20130145-FEDER-029311"]}]},{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["POCI-01-0247-FEDER-045311"],"award-info":[{"award-number":["POCI-01-0247-FEDER-045311"]}]},{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["POCI-01-0145-FEDER-022122"],"award-info":[{"award-number":["POCI-01-0145-FEDER-022122"]}]},{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["BID\/FCS\/2020"],"award-info":[{"award-number":["BID\/FCS\/2020"]}]},{"name":"European Regional Development Fund","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"European Regional Development Fund","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"European Regional Development Fund","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"European Regional Development Fund","award":["UID\/Multi\/00709\/2019"],"award-info":[{"award-number":["UID\/Multi\/00709\/2019"]}]},{"name":"European Regional Development Fund","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"European Regional Development Fund","award":["2021.07854.BD"],"award-info":[{"award-number":["2021.07854.BD"]}]},{"name":"European Regional Development Fund","award":["POCI-01\u20130145-FEDER-029311"],"award-info":[{"award-number":["POCI-01\u20130145-FEDER-029311"]}]},{"name":"European Regional Development Fund","award":["POCI-01-0247-FEDER-045311"],"award-info":[{"award-number":["POCI-01-0247-FEDER-045311"]}]},{"name":"European Regional Development Fund","award":["POCI-01-0145-FEDER-022122"],"award-info":[{"award-number":["POCI-01-0145-FEDER-022122"]}]},{"name":"European Regional Development Fund","award":["BID\/FCS\/2020"],"award-info":[{"award-number":["BID\/FCS\/2020"]}]},{"name":"Santander Totta","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"Santander Totta","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"Santander Totta","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"Santander Totta","award":["UID\/Multi\/00709\/2019"],"award-info":[{"award-number":["UID\/Multi\/00709\/2019"]}]},{"name":"Santander Totta","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"Santander Totta","award":["2021.07854.BD"],"award-info":[{"award-number":["2021.07854.BD"]}]},{"name":"Santander Totta","award":["POCI-01\u20130145-FEDER-029311"],"award-info":[{"award-number":["POCI-01\u20130145-FEDER-029311"]}]},{"name":"Santander Totta","award":["POCI-01-0247-FEDER-045311"],"award-info":[{"award-number":["POCI-01-0247-FEDER-045311"]}]},{"name":"Santander Totta","award":["POCI-01-0145-FEDER-022122"],"award-info":[{"award-number":["POCI-01-0145-FEDER-022122"]}]},{"name":"Santander Totta","award":["BID\/FCS\/2020"],"award-info":[{"award-number":["BID\/FCS\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of death and long-term disability in the perinatal period. Currently, therapeutic hypothermia is the standard of care for this condition with modest efficacy and strict enrollment criteria. Therapy with umbilical cord blood cells (UCBC) has come forward as a strong candidate for the treatment of neonatal HIE, but no preclinical studies have yet compared the action of UCBC combined with hypothermia (HT) with the action of each therapy by itself. Thus, to evaluate the potential of each therapeutic approach, a hypoxic-ischemic brain lesion was induced in postnatal day ten rat pups; two hours later, HT was applied for 4 h; and 24, 48, and 72 h post-injury, UCBC were administered intravenously. The neonatal hypoxic-ischemic injury led to a brain lesion involving about 48% of the left hemisphere that was not improved by HT (36%) or UCBC alone (28%), but only with the combined therapies (25%; p = 0.0294). Moreover, a decrease in glial reactivity and improved functional outcomes were observed in both groups treated with UCBC. Overall, these results support UCBC as a successful therapeutic approach for HIE, even when treatment with therapeutic hypothermia is not possible.<\/jats:p>","DOI":"10.3390\/ijms24010257","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T03:05:56Z","timestamp":1672110356000},"page":"257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hypothermia Does Not Boost the Neuroprotection Promoted by Umbilical Cord Blood Cells in a Neonatal Hypoxia-Ischemia Rat Model"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3951-1599","authenticated-orcid":false,"given":"In\u00eas","family":"Serrenho","sequence":"first","affiliation":[{"name":"Health Sciences Research Center (CICS-UBI), University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0985-7487","authenticated-orcid":false,"given":"Carla M.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Crioestaminal (Stemlab S.A.), 3060-197 Cantanhede, Portugal"}]},{"given":"M\u00e1rio","family":"Gr\u00e3os","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Biocant, Technology Transfer Association, 3060-197 Cantanhede, Portugal"},{"name":"Institute for Interdisciplinary Research, University of Coimbra (IIIUC), 3030-789 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2291-9988","authenticated-orcid":false,"given":"Alexandra","family":"Dinis","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Care Unit, Hospital Pedi\u00e1trico, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3004-561 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2087-4042","authenticated-orcid":false,"given":"Bruno","family":"Manadas","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Institute for Interdisciplinary Research, University of Coimbra (IIIUC), 3030-789 Coimbra, Portugal"}]},{"given":"Gra\u00e7a","family":"Baltazar","sequence":"additional","affiliation":[{"name":"Health Sciences Research Center (CICS-UBI), University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,23]]},"reference":[{"key":"ref_1","first-page":"CD003311","article-title":"Cooling for newborns with hypoxic ischaemic encephalopathy","volume":"1","author":"Jacobs","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/pr.2013.206","article-title":"Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990","volume":"74","author":"Lee","year":"2013","journal-title":"Pediatr. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/B978-0-444-64029-1.00010-2","article-title":"Neonatal encephalopathy and hypoxic-ischemic encephalopathy","volume":"162","author":"Gunn","year":"2019","journal-title":"Handb. Clin. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s10561-011-9262-4","article-title":"Isolation of three important types of stem cells from the same samples of banked umbilical cord blood","volume":"13","author":"Phuc","year":"2012","journal-title":"Cell Tissue Bank."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.jpeds.2013.11.036","article-title":"Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy","volume":"164","author":"Cotten","year":"2014","journal-title":"J. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4603","DOI":"10.1038\/s41598-020-61311-9","article-title":"Autologous cord blood cell therapy for neonatal hypoxic-ischaemic encephalopathy: A pilot study for feasibility and safety","volume":"10","author":"Tsuji","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1089\/scd.2009.0049","article-title":"Human cord blood transplantation in a neonatal rat model of hypoxic-ischemic brain damage: Functional outcome related to neuroprotection in the striatum","volume":"19","author":"Magalhaes","year":"2010","journal-title":"Stem Cells Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.neuroscience.2012.03.009","article-title":"The dose-response effect of acute intravenous transplantation of human umbilical cord blood cells on brain damage and spatial memory deficits in neonatal hypoxia-ischemia","volume":"210","author":"Greggio","year":"2012","journal-title":"Neuroscience"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"147001","DOI":"10.1016\/j.brainres.2020.147001","article-title":"Multiple doses of umbilical cord blood cells improve long-term brain injury in the neonatal rat","volume":"1746","author":"Penny","year":"2020","journal-title":"Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.brainres.2012.05.066","article-title":"Neuroglial activation and Cx43 expression are reduced upon transplantation of human umbilical cord blood cells after perinatal hypoxic-ischemic injury","volume":"1487","author":"Wasielewski","year":"2012","journal-title":"Brain Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.lfs.2013.10.017","article-title":"Intra-arterial transplantation of human umbilical cord blood mononuclear cells in neonatal hypoxic-ischemic rats","volume":"96","author":"Greggio","year":"2014","journal-title":"Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1002\/sctm.17-0074","article-title":"Long-Term Recovery After Endothelial Colony-Forming Cells or Human Umbilical Cord Blood Cells Administration in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy","volume":"6","author":"Grandvuillemin","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12974-018-1089-5","article-title":"Effects of umbilical cord blood cells, and subtypes, to reduce neuroinflammation following perinatal hypoxic-ischemic brain injury","volume":"15","author":"McDonald","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.braindev.2018.08.007","article-title":"Effects of human umbilical cord blood CD34(+) cell transplantation in neonatal hypoxic-ischemia rat model","volume":"41","author":"Yu","year":"2019","journal-title":"Brain Dev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Serrenho, I., Rosado, M., Dinis, A., Cardoso, M.C., Graos, M., Manadas, B., and Baltazar, G. (2021). Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Systematic Review of Preclinical Studies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063142"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7665","DOI":"10.1038\/s41598-018-25902-x","article-title":"Hypothermia broadens the therapeutic time window of mesenchymal stem cell transplantation for severe neonatal hypoxic ischemic encephalopathy","volume":"8","author":"Ahn","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Park, W.S., Sung, S.I., Ahn, S.Y., Yoo, H.S., Sung, D.K., Im, G.H., Choi, S.J., and Chang, Y.S. (2015). Hypothermia augments neuroprotective activity of mesenchymal stem cells for neonatal hypoxic-ischemic encephalopathy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120893"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.bbi.2018.02.006","article-title":"Interaction between hypothermia and delayed mesenchymal stem cell therapy in neonatal hypoxic-ischemic brain injury","volume":"70","author":"Herz","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_19","first-page":"144","article-title":"Neuroinflammation and neuroimmune dysregulation after acute hypoxic-ischemic injury of developing brain","volume":"2","author":"Bhalala","year":"2014","journal-title":"Front. Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"105541","DOI":"10.1016\/j.earlhumdev.2022.105541","article-title":"Long-term neuropsychological and behavioral outcome of mild and moderate hypoxic ischemic encephalopathy","volume":"165","author":"Halpin","year":"2022","journal-title":"Early Hum. Dev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"F220","DOI":"10.1136\/adc.2008.148205","article-title":"Long-term outcome after neonatal hypoxic-ischaemic encephalopathy","volume":"95","author":"Jongmans","year":"2010","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1093\/jpepsy\/jsp049","article-title":"Behavioral outcome in children with a history of neonatal encephalopathy following perinatal asphyxia","volume":"35","author":"Swaab","year":"2010","journal-title":"J. Pediatr. Psychol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/apa.14821","article-title":"Systematic review: Long-term cognitive and behavioural outcomes of neonatal hypoxic-ischaemic encephalopathy in children without cerebral palsy","volume":"109","author":"Schreglmann","year":"2020","journal-title":"Acta Paediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1080\/14653240601139846","article-title":"UC blood hematopoietic stem cells and therapeutic angiogenesis","volume":"9","author":"Goldberg","year":"2007","journal-title":"Cytotherapy"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1515\/revneuro-2016-0022","article-title":"Animal models of hypoxic-ischemic encephalopathy: Optimal choices for the best outcomes","volume":"28","author":"Huang","year":"2017","journal-title":"Rev. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1161\/STROKEAHA.112.674481","article-title":"Immediate hypothermia is not neuroprotective after severe hypoxia-ischemia and is deleterious when delayed by 12 hours in neonatal rats","volume":"43","author":"Sabir","year":"2012","journal-title":"Stroke"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nrneurol.2015.13","article-title":"The role of inflammation in perinatal brain injury","volume":"11","author":"Hagberg","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.pneurobio.2017.10.006","article-title":"Brain-immune interactions in perinatal hypoxic-ischemic brain injury","volume":"159","author":"Li","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"ref_29","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":"Bregere","year":"2022","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"113457","DOI":"10.1016\/j.expneurol.2020.113457","article-title":"Animal models for neonatal brain injury induced by hypoxic ischemic conditions in rodents","volume":"334","author":"Hamdy","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1159\/000454830","article-title":"Evaluations of Intravenous Administration of CD34+ Human Umbilical Cord Blood Cells in a Mouse Model of Neonatal Hypoxic-Ischemic Encephalopathy","volume":"38","author":"Ohshima","year":"2016","journal-title":"Dev. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.lfs.2016.06.004","article-title":"The therapeutic effect of CD133(+) cells derived from human umbilical cord blood on neonatal mouse hypoxic-ischemic encephalopathy model","volume":"157","author":"Kidani","year":"2016","journal-title":"Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2013.04.001","article-title":"Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species","volume":"106\u2013107","author":"Semple","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_34","first-page":"173","article-title":"Human Umbilical Cord Blood Cells Have Trophic Effects on Young and Aging Hippocampal Neurons in Vitro","volume":"1","author":"Chen","year":"2010","journal-title":"Aging Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.neulet.2005.01.070","article-title":"Human umbilical cord blood cells express neurotrophic factors","volume":"380","author":"Fan","year":"2005","journal-title":"Neurosci. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Burnsed, J.C., Chavez-Valdez, R., Hossain, M.S., Kesavan, K., Martin, L.J., Zhang, J., and Northington, F.J. (2015). Hypoxia-ischemia and therapeutic hypothermia in the neonatal mouse brain--a longitudinal study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118889"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/pr.2015.100","article-title":"Therapeutic hypothermia and hypoxia-ischemia in the term-equivalent neonatal rat: Characterization of a translational preclinical model","volume":"78","author":"Patel","year":"2015","journal-title":"Pediatr. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10833","DOI":"10.1038\/s41598-020-67532-2","article-title":"Variability and sex-dependence of hypothermic neuroprotection in a rat model of neonatal hypoxic-ischaemic brain injury: A single laboratory meta-analysis","volume":"10","author":"Wood","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Pignataro, G., Baba, N., Wang, F., Iizuka, M., Shen, Y., Yamashita, T., Takaishi, K., Tsuru, E., Matsushima, S., and Miyamura, M. (2019). Induction of regional chemokine expression in response to human umbilical cord blood cell infusion in the neonatal mouse ischemia-reperfusion brain injury model. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221111"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/ana.410090206","article-title":"The influence of immaturity on hypoxic-ischemic brain damage in the rat","volume":"9","author":"Rice","year":"1981","journal-title":"Ann. Neurol."},{"key":"ref_41","first-page":"e59878","article-title":"Low-Cost Gait Analysis for Behavioral Phenotyping of Mouse Models of Neuromuscular Disease","volume":"149","author":"Wertman","year":"2019","journal-title":"J. Vis. Exp."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"160018","DOI":"10.1038\/sdata.2016.18","article-title":"The FAIR Guiding Principles for scientific data management and stewardship","volume":"3","author":"Wilkinson","year":"2016","journal-title":"Sci. Data"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/257\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:49:11Z","timestamp":1760147351000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,23]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24010257"],"URL":"https:\/\/doi.org\/10.3390\/ijms24010257","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,23]]}}}