{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T15:33:19Z","timestamp":1786807999174,"version":"build-2736575974"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["COOPER23G0"],"award-info":[{"award-number":["COOPER23G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["RO1GM127374"],"award-info":[{"award-number":["RO1GM127374"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["RO1HL160726"],"award-info":[{"award-number":["RO1HL160726"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R35GM118139"],"award-info":[{"award-number":["R35GM118139"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["RO1HL153988"],"award-info":[{"award-number":["RO1HL153988"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Premature termination codon (PTC) diseases account for \u223c12% of all human disease mutations. Although there are no FDA approved treatments for increasing PTC readthrough, one readthrough inducing drug, ataluren, has conditional approval for treatment of Duchenne muscular dystrophy elsewhere. Ataluren displays low toxicity in clinical trials for treatment of PTC diseases, but its therapeutic effects are inconsistent. The messenger RNA (mRNA) sequence context of a PTC is a major determinant of PTC readthrough efficiency. We have shown that ataluren stimulates readthrough exclusively by competitively inhibiting release factor complex (RFC) catalysis of translation termination. Here, using an in vitro reconstituted system, we demonstrate that PTC identity and the immediately adjacent mRNA sequence contexts modulate RFC activity in terminating peptide elongation. Such modulation largely determines the effectiveness of ataluren in stimulating readthrough, whether added alone or in combination with either the aminoglycoside G418 or an anticodon edited aa-tRNA, which stimulate readthrough by mechanisms orthogonal to that of ataluren. Our results suggest a potential rationale for the variability of ataluren effectiveness in stimulating readthrough. We hypothesize that patients harboring a PTC mutation within a sequence context promoting strong interaction with RFC will be resistant to ataluren, but that ataluren treatment will be more effective for patient sequences conferring weaker interaction with RFC.<\/jats:p>","DOI":"10.1093\/nar\/gkaf216","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T15:21:42Z","timestamp":1741360902000},"source":"Crossref","is-referenced-by-count":4,"title":["Mechanism-based approach in designing patient-specific combination therapies for nonsense mutation diseases"],"prefix":"10.1093","volume":"53","author":[{"given":"Saleem\u00a0Y","family":"Bhat","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Pennsylvania , Philadelphia , PA\u00a0 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpan","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Pennsylvania , Philadelphia , PA\u00a0 19104 ,","place":["United States"]},{"name":"Department of Physiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia , PA\u00a0 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Pennsylvania , Philadelphia , PA\u00a0 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Physiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia , PA\u00a0 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1820-711X","authenticated-orcid":false,"given":"John\u00a0D","family":"Lueck","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry , Rochester , NY\u00a0 14642 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yale\u00a0E","family":"Goldman","sequence":"additional","affiliation":[{"name":"Department of Physiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia , PA\u00a0 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6989-9788","authenticated-orcid":false,"given":"Barry\u00a0S","family":"Cooperman","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Pennsylvania , Philadelphia , PA\u00a0 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,29]]},"reference":[{"key":"2025041601021926300_B1","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1002\/humu.20763","article-title":"A meta-analysis of nonsense mutations causing human genetic disease","volume":"29","author":"Mort","year":"2008","journal-title":"Hum Mutat"},{"key":"2025041601021926300_B2","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1007\/s00439-017-1779-6","article-title":"The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies","volume":"136","author":"Stenson","year":"2017","journal-title":"Hum Genet"},{"key":"2025041601021926300_B3","doi-asserted-by":"publisher","first-page":"483","DOI":"10.3171\/jns.2002.96.3.0483","article-title":"Spontaneous spinal cerebrospinal fluid leaks and minor skeletal features of Marfan syndrome: a microfibrillopathy","volume":"96","author":"Schrijver","year":"2002","journal-title":"J Neurosurg"},{"key":"2025041601021926300_B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.apcsb.2022.06.001","article-title":"Translation termination codons in protein synthesis and disease","volume":"132","author":"Lombardi","year":"2022","journal-title":"Adv Protein Chem Struct Biol"},{"key":"2025041601021926300_B5","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nature05756","article-title":"PTC124 targets genetic disorders caused by nonsense mutations","volume":"447","author":"Welch","year":"2007","journal-title":"Nature"},{"key":"2025041601021926300_B6","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1146\/annurev-med-120611-144851","article-title":"Ataluren as an agent for therapeutic nonsense suppression","volume":"64","author":"Peltz","year":"2013","journal-title":"Annu Rev Med"},{"key":"2025041601021926300_B7","doi-asserted-by":"publisher","first-page":"12508","DOI":"10.1073\/pnas.1605336113","article-title":"Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression","volume":"113","author":"Roy","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"2025041601021926300_B8","doi-asserted-by":"publisher","first-page":"785","DOI":"10.3390\/ph14080785","article-title":"Ataluren\u2014promising therapeutic premature termination codon readthrough frontrunner","volume":"14","author":"Michorowska","year":"2021","journal-title":"Pharmaceuticals"},{"key":"2025041601021926300_B9","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s10020-018-0024-7","article-title":"Advances in therapeutic use of a drug-stimulated translational readthrough of premature termination codons","volume":"24","author":"Dabrowski","year":"2018","journal-title":"Mol Med"},{"key":"2025041601021926300_B10","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1146\/annurev-genom-091212-153527","article-title":"Therapeutics based on stop codon readthrough","volume":"15","author":"Keeling","year":"2014","journal-title":"Annu Rev Genom Hum Genet"},{"key":"2025041601021926300_B11","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1039\/C4MD00081A","article-title":"When proteins start to make sense: fine-tuning of aminoglycosides for PTC suppression therapy","volume":"5","author":"Shalev","year":"2014","journal-title":"Med Chem Commun"},{"key":"2025041601021926300_B12","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.molmed.2023.01.004","article-title":"Readthrough compounds for nonsense mutations: bridging the translational gap","volume":"29","author":"Spelier","year":"2023","journal-title":"Trends Mol Med"},{"key":"2025041601021926300_B13","doi-asserted-by":"publisher","first-page":"659","DOI":"10.3390\/biomedicines11030659","article-title":"Recoding of nonsense mutation as a pharmacological strategy","volume":"11","author":"Temaj","year":"2023","journal-title":"Biomedicines"},{"key":"2025041601021926300_B14","doi-asserted-by":"publisher","first-page":"6101","DOI":"10.3390\/ijms24076101","article-title":"Emerging personalized opportunities for enhancing translational readthrough in rare genetic diseases and beyond","volume":"24","author":"Wagner","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2025041601021926300_B15","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1038\/s41467-019-08329-4","article-title":"Engineered transfer RNAs for suppression of premature termination codons","volume":"10","author":"Lueck","year":"2019","journal-title":"Nat Commun"},{"key":"2025041601021926300_B16","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.omtn.2022.04.033","article-title":"Efficient suppression of endogenous CFTR nonsense mutations using anticodon-engineered transfer RNAs","volume":"28","author":"Ko","year":"2022","journal-title":"Mol Ther Nucleic Acids"},{"key":"2025041601021926300_B17","doi-asserted-by":"publisher","first-page":"e1641","DOI":"10.1002\/wrna.1641","article-title":"Therapeutic promise of engineered nonsense suppressor tRNAs","volume":"12","author":"Porter","year":"2021","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"2025041601021926300_B18","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1038\/s41586-023-06133-1","article-title":"Engineered tRNAs suppress nonsense mutations in cells and in vivo","volume":"618","author":"Albers","year":"2023","journal-title":"Nature"},{"key":"2025041601021926300_B19","doi-asserted-by":"publisher","first-page":"102032","DOI":"10.1016\/j.omtn.2023.102032","article-title":"Transfer RNA-mediated restoration of potassium current and electrical correction in premature termination long-QT syndrome hERG mutants","volume":"34","author":"Blomquist","year":"2023","journal-title":"Mol Ther Nucleic Acids"},{"key":"2025041601021926300_B20","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/s41586-022-04533-3","article-title":"AAV-delivered suppressor tRNA overcomes a nonsense mutation in mice","volume":"604","author":"Wang","year":"2022","journal-title":"Nature"},{"key":"2025041601021926300_B21","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.3390\/biomedicines12061284","article-title":"Therapeutic nonsense suppression modalities: from small molecules to nucleic acid-based approaches","volume":"12","author":"Morais","year":"2024","journal-title":"Biomedicines"},{"key":"2025041601021926300_B22","doi-asserted-by":"publisher","first-page":"314","DOI":"10.3390\/ph17030314","article-title":"Readthrough activators and nonsense-mediated mRNA decay inhibitor molecules: real potential in many genetic diseases harboring premature termination codons","volume":"17","author":"Benslimane","year":"2024","journal-title":"Pharmaceuticals"},{"key":"2025041601021926300_B23","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1038\/s41588-024-01878-5","article-title":"Genome-scale quantification and prediction of pathogenic stop codon readthrough by small molecules","volume":"56","author":"Toledano","year":"2024","journal-title":"Nat Genet"},{"key":"2025041601021926300_B24","doi-asserted-by":"publisher","first-page":"e1009538","DOI":"10.1371\/journal.pgen.1009538","article-title":"Transcriptome-wide investigation of stop codon readthrough in Saccharomyces cerevisiae","volume":"17","author":"Mangkalaphiban","year":"2021","journal-title":"PLoS Genet"},{"key":"2025041601021926300_B25","doi-asserted-by":"publisher","first-page":"2486","DOI":"10.1038\/s41467-024-46703-z","article-title":"Extended stop codon context predicts nonsense codon readthrough efficiency in human cells","volume":"15","author":"Mangkalaphiban","year":"2024","journal-title":"Nat Commun"},{"key":"2025041601021926300_B26","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1093\/nar\/gkx1315","article-title":"Eukaryotic translational termination efficiency is influenced by the 3\u2032 nucleotides within the ribosomal mRNA channel","volume":"46","author":"Cridge","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2025041601021926300_B27","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1021\/acs.biochem.8b01280","article-title":"Interrogation of eukaryotic stop codon readthrough signals by in vitro RNA selection","volume":"58","author":"Anzalone","year":"2019","journal-title":"Biochemistry"},{"key":"2025041601021926300_B28","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1080\/15476286.2015.1068497","article-title":"Translational readthrough potential of natural termination codons in eucaryotes\u2013the impact of RNA sequence","volume":"12","author":"Dabrowski","year":"2015","journal-title":"RNA Biol"},{"key":"2025041601021926300_B29","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1016\/j.cell.2016.10.046","article-title":"Decoding mammalian ribosome-mRNA states by translational GTPase complexes","volume":"167","author":"Shao","year":"2016","journal-title":"Cell"},{"key":"2025041601021926300_B30","doi-asserted-by":"publisher","first-page":"e13429","DOI":"10.7554\/eLife.13429","article-title":"Kinetics of initiating polypeptide elongation in an IRES-dependent system","volume":"5","author":"Zhang","year":"2016","journal-title":"eLife"},{"key":"2025041601021926300_B31","doi-asserted-by":"publisher","first-page":"e2020599118","DOI":"10.1073\/pnas.2020599118","article-title":"Ataluren and aminoglycosides stimulate read-through of nonsense codons by orthogonal mechanisms","volume":"118","author":"Ng","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"2025041601021926300_B32","doi-asserted-by":"publisher","first-page":"2413","DOI":"10.1038\/s41467-022-30080-6","article-title":"Ataluren binds to multiple protein synthesis apparatus sites and competitively inhibits release factor-dependent termination","volume":"13","author":"Huang","year":"2022","journal-title":"Nat Commun"},{"key":"2025041601021926300_B33","doi-asserted-by":"publisher","first-page":"15410","DOI":"10.1073\/pnas.2535183100","article-title":"Divergent tRNA-like element supports initiation, elongation, and termination of protein biosynthesis","volume":"100","author":"Jan","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"2025041601021926300_B34","doi-asserted-by":"publisher","first-page":"3084","DOI":"10.1016\/S0021-9258(18)89476-5","article-title":"Elongation factor 1 alpha from Saccharomyces cerevisiae. Rapid large-scale purification and molecular characterization","volume":"260","author":"Thiele","year":"1985","journal-title":"J Biol Chem"},{"key":"2025041601021926300_B35","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1107\/S0907444902003001","article-title":"Purification and crystallization of the yeast elongation factor eEF2","volume":"58","author":"J\u00f8rgensen","year":"2002","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"2025041601021926300_B36","article-title":"mRNA decay pathways use translation fidelity and competing decapping complexes for substrate selection","author":"Celik","year":"2017"},{"key":"2025041601021926300_B37","doi-asserted-by":"publisher","first-page":"242","DOI":"10.3390\/biom13020242","article-title":"A high-throughput assay for in vitro determination of release factor-dependent peptide release from a pretermination complex by fluorescence anisotropy\u2014application to nonsense suppressor screening and mechanistic studies","volume":"13","author":"Ghelfi","year":"2023","journal-title":"Biomolecules"},{"key":"2025041601021926300_B38","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1021\/acsmedchemlett.8b00472","article-title":"New in vitro assay measuring direct interaction of nonsense suppressors with the eukaryotic protein synthesis machinery","volume":"9","author":"Ng","year":"2018","journal-title":"ACS Med Chem Lett"},{"key":"2025041601021926300_B39","doi-asserted-by":"publisher","first-page":"e177","DOI":"10.1093\/nar\/gkt686","article-title":"Dicodon monitoring of protein synthesis (DiCoMPS) reveals levels of synthesis of a viral protein in single cells","volume":"41","author":"Barhoom","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2025041601021926300_B40","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1002\/jcp.24630","article-title":"Monitoring collagen synthesis in fibroblasts using fluorescently labeled tRNA pairs","volume":"229","author":"Liu","year":"2014","journal-title":"J Cell Physiol"},{"key":"2025041601021926300_B41","doi-asserted-by":"publisher","first-page":"596\u20138","DOI":"10.1016\/S0076-6879(67)12089-2","article-title":"Isolation of sRNA from intact yeast cells","volume":"12","author":"Holley","year":"1967","journal-title":"Methods Enzymol"},{"key":"2025041601021926300_B42","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/nsmb1074","article-title":"Rapid ribosomal translocation depends on the conserved 18\u201355 base pair in P-site transfer RNA","volume":"13","author":"Pan","year":"2006","journal-title":"Nat Struct Mol Biol"},{"key":"2025041601021926300_B43","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1261\/rna.1257509","article-title":"Synthesis and functional activity of tRNAs labeled with fluorescent hydrazides in the D-loop","volume":"15","author":"Pan","year":"2009","journal-title":"RNA"},{"key":"2025041601021926300_B44","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1385\/1592591949","volume-title":"In Vitro Mutagenesis Protocols","author":"Braman","year":"2002"},{"key":"2025041601021926300_B45","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1126\/science.abi7801","article-title":"Mechanisms that ensure speed and fidelity in eukaryotic translation termination","volume":"373","author":"Lawson","year":"2021","journal-title":"Science"},{"key":"2025041601021926300_B46","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1006\/jmbi.1995.0438","article-title":"The efficiency of translation termination is determined by a synergistic interplay between upstream and downstream sequences in Saccharomyces cerevisiae","volume":"251","author":"Bonetti","year":"1995","journal-title":"J Mol Biol"},{"key":"2025041601021926300_B47","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.celrep.2014.04.058","article-title":"Cryoelectron microscopic structures of eukaryotic translation termination complexes containing eRF1\u2013eRF3 or eRF1\u2013ABCE1","volume":"8","author":"Preis","year":"2014","journal-title":"Cell Rep"},{"key":"2025041601021926300_B48","doi-asserted-by":"publisher","first-page":"e12","DOI":"10.1017\/S0033583518000100","article-title":"The enigmatic ribosomal stalk","volume":"51","author":"Liljas","year":"2018","journal-title":"Q Rev Biophys"},{"key":"2025041601021926300_B49","doi-asserted-by":"publisher","first-page":"12005","DOI":"10.1093\/nar\/gkae748","article-title":"The ABCF ATPase New1 resolves translation termination defects associated with specific tRNAArg and tRNALys&gt;isoacceptors in the P site","volume":"52","author":"Turnbull","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"2025041601021926300_B50","doi-asserted-by":"publisher","article-title":"Systematic analysis of nonsense variants uncovers peptide release rate as a novel modifier of nonsense-mediated mRNA decay efficiency","author":"Kolakada","DOI":"10.1101\/2024.01.10.575080"},{"key":"2025041601021926300_B51","doi-asserted-by":"publisher","article-title":"Single-molecule studies of cognate and near-cognate elongation in an in vitro eukaryotic translation system","author":"Fritsch","DOI":"10.1101\/2024.08.29.609187"},{"key":"2025041601021926300_B52","doi-asserted-by":"publisher","first-page":"e103365","DOI":"10.15252\/embj.2019103365","article-title":"Molecular mechanism of translational stalling by inhibitory codon combinations and poly (A) tracts","volume":"39","author":"Tesina","year":"2020","journal-title":"EMBO J"},{"key":"2025041601021926300_B53","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1002\/cpdd.647","article-title":"Safety, tolerability, and pharmacokinetics of single ascending doses of ELX-02, a potential treatment for genetic disorders caused by nonsense mutations, in healthy volunteers","volume":"8","author":"Leubitz","year":"2019","journal-title":"Clin Pharmacol Drug Dev"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/53\/6\/gkaf216\/62807747\/gkaf216.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/53\/6\/gkaf216\/62807747\/gkaf216.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T01:03:00Z","timestamp":1744765380000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/doi\/10.1093\/nar\/gkaf216\/8099985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,20]]},"references-count":53,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,3,20]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkaf216","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.11.13.623453","asserted-by":"object"}]},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,4,11]]},"published":{"date-parts":[[2025,3,20]]},"article-number":"gkaf216"}}