{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:08:22Z","timestamp":1791925702925,"version":"4.3.4"},"reference-count":112,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007057","name":"Norfolk Southern","doi-asserted-by":"publisher","award":["104022"],"award-info":[{"award-number":["104022"]}],"id":[{"id":"10.13039\/100007057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007057","name":"Norfolk Southern","doi-asserted-by":"publisher","award":["GM\u2010131839"],"award-info":[{"award-number":["GM\u2010131839"]}],"id":[{"id":"10.13039\/100007057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007057","name":"Norfolk Southern","doi-asserted-by":"publisher","award":["S10 OD020012"],"award-info":[{"award-number":["S10 OD020012"]}],"id":[{"id":"10.13039\/100007057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007057","name":"Norfolk Southern","doi-asserted-by":"publisher","award":["ADDF 20170101"],"award-info":[{"award-number":["ADDF 20170101"]}],"id":[{"id":"10.13039\/100007057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>The most significant genetic risk factor for late\u2010onset Alzheimer's disease (AD) is <jats:italic>APOE4<\/jats:italic>, with evidence for gain\u2010 and loss\u2010of\u2010function mechanisms. A clinical need remains for therapeutically relevant tools that potently modulate <jats:italic>APOE<\/jats:italic> expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We optimized small interfering RNAs (di\u2010siRNA, GalNAc) to potently silence brain or liver <jats:italic>Apoe<\/jats:italic> and evaluated the impact of each pool of <jats:italic>Apoe<\/jats:italic> on pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In adult 5xFAD mice, siRNAs targeting CNS <jats:italic>Apoe<\/jats:italic> efficiently silenced <jats:italic>Apoe<\/jats:italic> expression and reduced amyloid burden without affecting systemic cholesterol, confirming that potent silencing of brain <jats:italic>Apoe<\/jats:italic> is sufficient to slow disease progression. Mechanistically, silencing <jats:italic>Apoe<\/jats:italic> reduced APOE\u2010rich amyloid cores and activated immune system responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>These results establish siRNA\u2010based modulation of <jats:italic>Apoe<\/jats:italic> as a viable therapeutic approach, highlight immune activation as a key pathway affected by <jats:italic>Apoe<\/jats:italic> modulation, and provide the technology to further evaluate the impact of <jats:italic>APOE<\/jats:italic> silencing on neurodegeneration.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13703","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T06:26:14Z","timestamp":1708410374000},"page":"2632-2652","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Silencing <i>Apoe<\/i> with divalent\u2010siRNAs improves amyloid burden and activates immune response pathways in Alzheimer's disease"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9442-1249","authenticated-orcid":false,"given":"Chantal M.","family":"Ferguson","sequence":"first","affiliation":[{"name":"RNA Therapeutics Institute, University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Hildebrand","sequence":"additional","affiliation":[{"name":"RNA Therapeutics Institute, University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno M. D. C.","family":"Godinho","sequence":"additional","affiliation":[{"name":"RNA Therapeutics Institute, University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julianna","family":"Buchwald","sequence":"additional","affiliation":[{"name":"RNA Therapeutics Institute, University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimas","family":"Echeverria","sequence":"additional","affiliation":[{"name":"RNA Therapeutics Institute, University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Coles","sequence":"additional","affiliation":[{"name":"RNA Therapeutics Institute, University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Grigorenko","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenc","family":"Vangjeli","sequence":"additional","affiliation":[{"name":"RNA Therapeutics Institute, University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyn","family":"Sousa","sequence":"additional","affiliation":[{"name":"RNA Therapeutics Institute, University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"McHugh","sequence":"additional","affiliation":[{"name":"RNA Therapeutics Institute, University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Hassler","sequence":"additional","affiliation":[{"name":"RNA Therapeutics Institute, University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Santarelli","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB)  Esch\u2010sur\u2010Alzette Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Heneka","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB)  Esch\u2010sur\u2010Alzette Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny","family":"Rogaev","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Khvorova","sequence":"additional","affiliation":[{"name":"RNA Therapeutics Institute, University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-148-5-200803040-00008"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.2.210"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410370509"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.05.006"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47945-8"},{"key":"e_1_2_11_8_1","first-page":"4985","article-title":"Profile and regulation of apolipoprotein E (ApoE) expression in the CNS in mice with targeting of green flourescent protein gene to teh ApoE locus","volume":"26","author":"Xu Q","year":"2006","journal-title":"Neurobiol Dis"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3513311"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4157(83)90001-1"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.050004797"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6179"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3773-11.2011"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-263"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1411543"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1054-16.2016"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0337-1"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.11.014"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26043"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3765"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.85"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja505986a"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx818"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615758"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0205-0"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.8b00365"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx507"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-1661-0_11"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25158"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050767"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty895"},{"key":"e_1_2_11_35_1","article-title":"Fast gene set enrichment analysis","author":"Gennady K","year":"2021","journal-title":"bioRxiv"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13040-019-0204-1"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqaa078"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12918-017-0420-6"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.24956.2"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.09.039"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00905-6"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23762-0"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23111-1"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1007800"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.03.099"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2020.06.006"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.08.017"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1389-0344(01)00067-3"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh019"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(06)12009-1"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160572"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12202"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep38187"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep43577"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1202-06.2006"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-7-8"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt258"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3182345e46"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00787-6"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006270"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep13489"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1542-12.2012"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1871-19.2019"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0296-9"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171265"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-019-0729-z"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-020-00394-4"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2012.04.016"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1604"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0351-3"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24016"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.018"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0051-1"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1609896113"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.127829"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.127738"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107777"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12335"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-071013-014300"},{"key":"e_1_2_11_82_1","first-page":"R235","article-title":"Genes, pathways and risk prediction in Alzheimer's disease","volume":"28","author":"Hardy J","year":"2019","journal-title":"Hum Mol Genet"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-020-0358-9"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0228-7"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa670"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01548-0"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.08.008"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107908"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00577-1"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90606"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.02.025"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01456-w"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2102191118"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508693102"},{"key":"e_1_2_11_95_1","article-title":"ApoE isoforms differentially regulate neuronal membrane proteasomes to shift the threshold for pathological aggregation of endogenous Tau","author":"Paradise V","year":"2022","journal-title":"Biorxiv"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-015-0250-y"},{"key":"e_1_2_11_97_1","first-page":"rs.3.rs","article-title":"ApoE Alzheimer's Disease A\u03b2\u2010amyloid plaque morphology varies according to APOE isotype","author":"Caesar I","year":"2023","journal-title":"Research Square Platform LLC"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03550160069041"},{"key":"e_1_2_11_99_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410380319"},{"key":"e_1_2_11_100_1","first-page":"574","article-title":"Relative risk of Alzheimer disease and age\u2010at\u2010onset distributions, based on APOE genotypes among elderly African Americans, Caucasians, and Hispanics in New York City","volume":"58","author":"Tang MX","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_11_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.06.003"},{"key":"e_1_2_11_102_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14279-8"},{"key":"e_1_2_11_103_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0611-3"},{"key":"e_1_2_11_104_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.294.5545.1354"},{"key":"e_1_2_11_105_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.06.026"},{"key":"e_1_2_11_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)41380-X"},{"key":"e_1_2_11_107_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.2011"},{"key":"e_1_2_11_108_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2994-18.2019"},{"key":"e_1_2_11_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)34954-8"},{"key":"e_1_2_11_110_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00556-6"},{"key":"e_1_2_11_111_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.05.010"},{"key":"e_1_2_11_112_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.10.022"},{"key":"e_1_2_11_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.09.001"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.13703","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T14:53:02Z","timestamp":1759935182000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.13703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,20]]},"references-count":112,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/alz.13703"],"URL":"https:\/\/doi.org\/10.1002\/alz.13703","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,20]]},"assertion":[{"value":"2023-05-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}