{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:12:23Z","timestamp":1789539143859,"version":"build-2803163510"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004156","name":"Mahidol University","doi-asserted-by":"publisher","award":["MU-SRF-ST-07A\/66"],"award-info":[{"award-number":["MU-SRF-ST-07A\/66"]}],"id":[{"id":"10.13039\/501100004156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016175","name":"Chulabhorn Royal Academy","doi-asserted-by":"publisher","award":["TNS 2566\/001"],"award-info":[{"award-number":["TNS 2566\/001"]}],"id":[{"id":"10.13039\/100016175","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>To investigate the effects of asiaticoside (AS) and asiatic acid (AA) against radiotherapy on neural stem cells induced from human stem cells from apical papilla (NSCs-hSCAPs) through dose-reduction factor (DRF) evaluation and their radiosensitization on human neuroblastoma SH-SY5Y cells.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>NSCs-hSCAPs were treated with AS or AA (0\u2013500 \u03bcM) and radiation (0\u20138 Gy). Isolated hSCAPs were verified mesenchymal stem cells (MSCs) properties according to standard protocol. Subsequently, NSCs-hSCAPs were characterized by Cresyl violet staining and immunocytochemistry. A culture plate containing the cells was embedded into the solid water and bolus phantom. After CT simulation and treatment planning, dose uniformity to the plate was evaluated. X-ray, AS, and AA toxicity were investigated using cell viability (MTT) assay. Finally, DRF50 was calculated from dose-response curves at 50% cell viability for both cell lines.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>hSCAPs presented MSCs markers. NSCs-hSCAPs were successfully generated due to the Nissl substance, Nestin, and SOX2 positively stained. Dose homogeneity was represented as isodose at 100% covered the cells in the phantom, suggesting that they were received according to prescribed doses. MTT results revealed that AA was more toxic than AS in both cells. X-ray reduced significantly in a number of tested cells and more radiosensitivity was observed in SH-SY5Y. However, the reduction affected by 4 Gy was diminished after AA or AS at 2 \u03bcM applied to NSCs-hSCAPs. Moreover, a significant increase of DRF50 was found at 2 \u03bcM of AA (6.72\u2009\u00b1\u20092.35) and AS (3.84\u2009\u00b1\u20091.41) in NSCs-hSCAPs whereas it did not show in SH-SY5Y. Interestingly, 20 \u03bcM AA could reduce SH-SY5Y cell viability (mean of the cell viability (%) was 25.22\u2009\u00b1\u20091.53 compared to 30.22\u2009\u00b1\u20091.46 in the control group), showing a very large in terms of its effect size (Cohen\u2019s <jats:italic>d<\/jats:italic> value\u2009=\u20091.37).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>AA and AS had a specific radioprotective effect on NSCs-hSCAPs without affecting SH-SY5Y. However, AA might be a better therapeutic agent due to expressing a lethal effect on the irradiated cancer cells.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0325480","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T17:53:43Z","timestamp":1749059623000},"page":"e0325480","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Radioprotective effects of asiaticoside and asiatic acid in neural stem cells derived from human stem cells from apical papilla through increasing dose-reduction factor and their lowering effects on SH-SY5Y cell viability"],"prefix":"10.1371","volume":"20","author":[{"given":"Taweesak","family":"Tangrodchanapong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apisada","family":"Jiso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pimolpun","family":"Changkaew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suphalak","family":"Khachonkham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amarin","family":"Thongsuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6686-5479","authenticated-orcid":true,"given":"Tarinee","family":"Chodchavanchai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phisit","family":"Khemawoot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisarat","family":"Ruangsawasdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Permphan","family":"Dharmasaroja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0827-5207","authenticated-orcid":true,"given":"Anupong Thongklam","family":"Songsaad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"issue":"7","key":"pone.0325480.ref001","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2023.e18222","article-title":"International patterns and trends in the brain cancer incidence and mortality: An observational study based on the global burden of disease","volume":"9","author":"I Ilic","year":"2023","journal-title":"Heliyon"},{"key":"pone.0325480.ref002","article-title":"Radiation-induced brain injury after radiotherapy for brain tumor.","volume-title":"Molecular considerations and evolving surgical management issues in the treatment of patients with a brain tumor","author":"Y Zhihua","year":"2015"},{"issue":"2","key":"pone.0325480.ref003","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1097\/01.coc.0000143016.15783.5b","article-title":"Radiosurgery With or Without Whole-Brain Radiotherapy for Brain Metastases","volume":"28","author":"D Kondziolka","year":"2005","journal-title":"American Journal of Clinical Oncology"},{"issue":"2","key":"pone.0325480.ref004","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/(SICI)1097-4695(199808)36:2<249::AID-NEU11>3.0.CO;2-9","article-title":"Multipotent progenitor cells in the adult dentate gyrus","volume":"36","author":"FH Gage","year":"1998","journal-title":"J Neurobiol"},{"issue":"12","key":"pone.0325480.ref005","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1136\/jnnp.47.12.1338","article-title":"Conservative treatment of delayed cerebral radiation necrosis","volume":"47","author":"PJ Shaw","year":"1984","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0325480.ref006","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3389\/fonc.2012.00073","article-title":"Radiation-induced brain injury: A review","volume":"2","author":"D Greene-Schloesser","year":"2012","journal-title":"Front Oncol"},{"key":"pone.0325480.ref007","doi-asserted-by":"crossref","first-page":"115865","DOI":"10.1016\/j.jep.2022.115865","article-title":"A review of pharmacokinetic and pharmacological properties of asiaticoside, a major active constituent of Centella asiatica (L.) Urb.","volume":"302","author":"Z He","year":"2023","journal-title":"Journal of Ethnopharmacology"},{"issue":"3","key":"pone.0325480.ref008","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3390\/biomedicines9030284","article-title":"Asiatic Acid Prevents Cognitive Deficits by Inhibiting Calpain Activation and Preserving Synaptic and Mitochondrial Function in Rats with Kainic Acid-Induced Seizure","volume":"9","author":"C-W Lu","year":"2021","journal-title":"Biomedicines"},{"issue":"11","key":"pone.0325480.ref009","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1002\/mc.22220","article-title":"Asiatic acid induces endoplasmic reticulum stress and apoptotic death in glioblastoma multiforme cells both in vitro and in vivo","volume":"54","author":"CV Kavitha","year":"2015","journal-title":"Mol Carcinog"},{"issue":"11","key":"pone.0325480.ref010","first-page":"20983","article-title":"The treatment efficacy of asiaticoside in brain glioma","volume":"9","author":"H Zhang","year":"2016","journal-title":"Int J Clin Exp Med"},{"key":"pone.0325480.ref011","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.12659\/MSM.894024","article-title":"Nerve Protective Effect of Asiaticoside against Ischemia-Hypoxia in Cultured Rat Cortex Neurons","volume":"21","author":"T Sun","year":"2015","journal-title":"Med Sci Monit"},{"issue":"2","key":"pone.0325480.ref012","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.xphs.2020.09.015","article-title":"Blood-Brain Barrier Permeability of Asiaticoside, Madecassoside and Asiatic Acid in Porcine Brain Endothelial Cell Model","volume":"110","author":"NA Hanapi","year":"2021","journal-title":"J Pharm Sci"},{"issue":"6859","key":"pone.0325480.ref013","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/35102194","article-title":"Ethical and social considerations of stem cell research","volume":"414","author":"A McLaren","year":"2001","journal-title":"Nature"},{"issue":"4","key":"pone.0325480.ref014","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nm837","article-title":"Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain","volume":"9","author":"MC Nunes","year":"2003","journal-title":"Nat Med"},{"key":"pone.0325480.ref015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/6104738","article-title":"Stem Cells from the Apical Papilla: A Promising Source for Stem Cell-Based Therapy","author":"J Kang","year":"2019","journal-title":"BioMed Research International"},{"issue":"1","key":"pone.0325480.ref016","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1186\/s13287-020-02069-9","article-title":"Potential of resveratrol in enrichment of neural progenitor-like cell induction of human stem cells from apical papilla","volume":"11","author":"A Songsaad","year":"2020","journal-title":"Stem Cell Res Ther"},{"key":"pone.0325480.ref017","doi-asserted-by":"crossref","DOI":"10.1590\/1678-7757-2023-0209","article-title":"Characterization of neural stem cells derived from human stem cells from the apical papilla undergoing three-dimensional neurosphere induction","volume":"31","author":"AT Songsaad","year":"2023","journal-title":"J Appl Oral Sci"},{"issue":"1","key":"pone.0325480.ref018","doi-asserted-by":"crossref","first-page":"34","DOI":"10.5617\/jeb.781","article-title":"Electrical characterization of bolus material as phantom for use in electrical impedance and computed tomography fusion imaging","volume":"5","author":"PK Grewal","year":"2014","journal-title":"Journal of Electrical Bioimpedance"},{"issue":"9","key":"pone.0325480.ref019","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1111\/j.1755-5949.2012.00365.x","article-title":"Basic fibroblast growth factor protects C17.2 cells from radiation-induced injury through ERK1\/2","volume":"18","author":"P Luan","year":"2012","journal-title":"CNS Neurosci Ther"},{"key":"pone.0325480.ref020","doi-asserted-by":"crossref","DOI":"10.1080\/21691401.2018.1536062","article-title":"Estimation of radiation dose-reduction factor for cerium oxide nanoparticles in MRC-5 human lung fibroblastic cells and MCF-7 breast-cancer cells","volume":"46","author":"N Abdi Goushbolagh","year":"2018","journal-title":"Artif Cells Nanomed Biotechnol"},{"issue":"6","key":"pone.0325480.ref021","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1118\/1.597396","article-title":"ICRU Report 50\u2014Prescribing, Recording and Reporting Photon Beam Therapy","volume":"21","author":"D Jones","year":"1994","journal-title":"Medical Physics"},{"issue":"3","key":"pone.0325480.ref022","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4300\/JGME-D-12-00156.1","article-title":"Using Effect Size\u2014or Why the P Value Is Not Enough","volume":"4","author":"GM Sullivan","year":"2012","journal-title":"Journal of Graduate Medical Education"},{"issue":"2","key":"pone.0325480.ref023","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1007\/s12015-021-10218-7","article-title":"Mouse Neural Stem Cell Differentiation and Human Adipose Mesenchymal Stem Cell Transdifferentiation Into Neuron- and Oligodendrocyte-like Cells With Myelination Potential","volume":"18","author":"AK Santos","year":"2022","journal-title":"Stem Cell Rev Rep"},{"issue":"9","key":"pone.0325480.ref024","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/nm747","article-title":"Neuronal replacement from endogenous precursors in the adult brain after stroke","volume":"8","author":"A Arvidsson","year":"2002","journal-title":"Nat Med"},{"issue":"2","key":"pone.0325480.ref025","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/scrt450","article-title":"Mesenchymal stem cells of dental origin as promising tools for neuroregeneration","volume":"5","author":"G Varga","year":"2014","journal-title":"Stem Cell Res Ther"},{"issue":"4","key":"pone.0325480.ref026","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"M Dominici","year":"2006","journal-title":"Cytotherapy"},{"issue":"6","key":"pone.0325480.ref027","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.joen.2008.03.001","article-title":"The hidden treasure in apical papilla: the potential role in pulp\/dentin regeneration and bioroot engineering","volume":"34","author":"GT-J Huang","year":"2008","journal-title":"J Endod"},{"issue":"1","key":"pone.0325480.ref028","doi-asserted-by":"crossref","first-page":"34","DOI":"10.4062\/biomolther.2019.065","article-title":"Differentiation of Human Mesenchymal Stem Cells towards Neuronal Lineage: Clinical Trials in Nervous System Disorders","volume":"28","author":"R Hern\u00e1ndez","year":"2020","journal-title":"Biomol Ther (Seoul)"},{"issue":"4","key":"pone.0325480.ref029","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1007\/s11033-021-06301-4","article-title":"Neurospheres: a potential in vitro model for the study of central nervous system disorders","volume":"48","author":"L da Silva Siqueira","year":"2021","journal-title":"Mol Biol Rep"},{"issue":"3","key":"pone.0325480.ref030","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1385\/MN:34:3:153","article-title":"Strengths and limitations of the neurosphere culture system","volume":"34","author":"JB Jensen","year":"2006","journal-title":"Mol Neurobiol"},{"issue":"2","key":"pone.0325480.ref031","first-page":"83","article-title":"Cresyl violet stain for Nissl bodies","volume":"30","author":"KH Worthy","year":"2017","journal-title":"Stain Technol"},{"key":"pone.0325480.ref032","first-page":"727542","article-title":"Molecular Biomarkers for Embryonic and Adult Neural Stem Cell and Neurogenesis","author":"J Zhang","year":"2015","journal-title":"Biomed Res Int"},{"key":"pone.0325480.ref033","doi-asserted-by":"crossref","first-page":"101305","DOI":"10.1016\/j.inat.2021.101305","article-title":"Cognitive sequelae of radiotherapy in primary brain tumors","volume":"26","author":"S Ram\u00edrez-Guerrero","year":"2021","journal-title":"Interdisciplinary Neurosurgery"},{"issue":"11","key":"pone.0325480.ref034","doi-asserted-by":"crossref","first-page":"6041","DOI":"10.21873\/anticanres.12954","article-title":"Technical Advances in Radiation Therapy for Brain Tumors","volume":"38","author":"C Scaringi","year":"2018","journal-title":"Anticancer Res"},{"issue":"6","key":"pone.0325480.ref035","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1212\/WNL.39.6.789","article-title":"Radiation-induced dementia in patients cured of brain metastases","volume":"39","author":"LM DeAngelis","year":"1989","journal-title":"Neurology"},{"issue":"6","key":"pone.0325480.ref036","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1097\/WCO.0b013e32833f8cb5","article-title":"Novel insights into the management of brain metastases","volume":"23","author":"V Gondi","year":"2010","journal-title":"Curr Opin Neurol"},{"issue":"4","key":"pone.0325480.ref037","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.ijrobp.2019.08.003","article-title":"Quantitative Imaging Biomarkers of Damage to Critical Memory Regions Are Associated With Post-Radiation Therapy Memory Performance in Brain Tumor Patients","volume":"105","author":"KR Tringale","year":"2019","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"1","key":"pone.0325480.ref038","doi-asserted-by":"crossref","first-page":"10149","DOI":"10.1038\/s41598-024-59694-0","article-title":"Investigation of high-dose radiotherapy\u2019s effect on brain structure aggravated cognitive impairment and deteriorated patient psychological status in brain tumor treatment","volume":"14","author":"J Ma","year":"2024","journal-title":"Sci Rep"},{"issue":"39","key":"pone.0325480.ref039","doi-asserted-by":"crossref","first-page":"13005","DOI":"10.1523\/JNEUROSCI.1784-10.2010","article-title":"Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors","volume":"30","author":"AS Ivy","year":"2010","journal-title":"J Neurosci"},{"issue":"2","key":"pone.0325480.ref040","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/pro6.1149","article-title":"A Review of Proton Therapy - Current Status and Future Directions","volume":"6","author":"R Mohan","year":"2022","journal-title":"Precis Radiat Oncol"},{"issue":"34","key":"pone.0325480.ref041","doi-asserted-by":"crossref","first-page":"3810","DOI":"10.1200\/JCO.2014.57.2909","article-title":"Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial","volume":"32","author":"V Gondi","year":"2014","journal-title":"J Clin Oncol"},{"key":"pone.0325480.ref042","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/bs.podrm.2020.07.005","article-title":"Validation of in-vitro bioassay methods: Application in herbal drug research","volume":"46","author":"G Indrayanto","year":"2021","journal-title":"Profiles Drug Subst Excip Relat Methodol"},{"issue":"1","key":"pone.0325480.ref043","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1749-8546-7-15","article-title":"Evaluation of the anticancer potential of six herbs against a hepatoma cell line","volume":"7","author":"N Weerapreeyakul","year":"2012","journal-title":"Chin Med"},{"issue":"9343","key":"pone.0325480.ref044","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/S0140-6736(02)11398-5","article-title":"Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: a comparative study","volume":"360","author":"M Klein","year":"2002","journal-title":"The Lancet"},{"issue":"6","key":"pone.0325480.ref045","doi-asserted-by":"crossref","DOI":"10.1016\/S1470-2045(17)30194-8","article-title":"European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas","volume":"18","author":"M Weller","year":"2017","journal-title":"The Lancet Oncology"},{"issue":"13","key":"pone.0325480.ref046","doi-asserted-by":"crossref","first-page":"10669","DOI":"10.3390\/ijms241310669","article-title":"Neurotoxicity from Old and New Radiation Treatments for Brain Tumors","volume":"24","author":"R Soffietti","year":"2023","journal-title":"Int J Mol Sci"},{"key":"pone.0325480.ref047","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1515\/biol-2020-0015","article-title":"Protective Effect of Asiaticoside on Radiation-induced Proliferation Inhibition and DNA Damage of Fibroblasts and Mice Death","volume":"15","author":"H Shen","year":"2020","journal-title":"Open Life Sci"},{"issue":"1","key":"pone.0325480.ref048","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s11011-017-0143-9","article-title":"Asiatic acid prevents the quinolinic acid-induced oxidative stress and cognitive impairment","volume":"33","author":"C Loganathan","year":"2018","journal-title":"Metab Brain Dis"},{"issue":"1","key":"pone.0325480.ref049","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1038\/s41598-018-19930-w","article-title":"Mitochondrial biogenesis and metabolic hyperactivation limits the application of MTT assay in the estimation of radiation induced growth inhibition","volume":"8","author":"Y Rai","year":"2018","journal-title":"Sci Rep"},{"issue":"5","key":"pone.0325480.ref050","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/aps.2012.3","article-title":"Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells","volume":"33","author":"M Xu","year":"2012","journal-title":"Acta Pharmacol Sin"},{"key":"pone.0325480.ref051","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"46","author":"CA Lipinski","year":"2001","journal-title":"Adv Drug Deliv Rev"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0325480","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T17:53:54Z","timestamp":1749059634000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0325480"}},"subtitle":[],"editor":[{"given":"Fabio","family":"Sallustio,","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,6,4]]},"references-count":51,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0325480","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,4]]}}}