{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T20:22:39Z","timestamp":1757622159781,"version":"3.44.0"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG072587"],"award-info":[{"award-number":["AG072587"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Anti-A\u03b2 antibodies are important tools for identifying structural features of aggregates of the A\u03b2 peptide and are used in many aspects of Alzheimer\u2019s disease (AD) research. Our laboratory recently reported the generation of a polyclonal antibody, pAb<jats:sub>2AT-L<\/jats:sub>, that is moderately selective for oligomeric A\u03b2 over monomeric and fibrillar A\u03b2 and recognizes the diffuse peripheries of A\u03b2 plaques in AD brain tissue but does not recognize the dense fibrillar plaque cores. This antibody was generated against 2AT-L, a structurally defined A\u03b2 oligomer mimic composed of three A\u03b2-derived \u03b2-hairpins arranged in a triangular fashion and covalently stabilized with three disulfide bonds. In the current study, we set out to determine if pAb<jats:sub>2AT-L<\/jats:sub> is neuroprotective against toxic aggregates of A\u03b2 and found that pAb<jats:sub>2AT-L<\/jats:sub> protects human iPSC-derived neurons from A\u03b2<jats:sub>42<\/jats:sub>-mediated toxicity at molar ratios as low as 1:100 antibody to A\u03b2<jats:sub>42<\/jats:sub>, with a ratio of 1:25 almost completely rescuing cell viability. Few other antibodies have been reported to exhibit neuroprotective effects at such low ratios of antibody to A\u03b2. ThT and TEM studies indicate that pAb<jats:sub>2AT-L<\/jats:sub> delays but does not completely inhibit A\u03b2<jats:sub>42<\/jats:sub> fibrillization at sub-stoichiometric ratios. The ability of pAb<jats:sub>2AT-L<\/jats:sub> to inhibit A\u03b2<jats:sub>42<\/jats:sub> toxicity and aggregation at sub-stoichiometric ratios suggests that pAb<jats:sub>2AT-L<\/jats:sub> binds toxic A\u03b2<jats:sub>42<\/jats:sub> oligomers and does not simply sequester monomeric A\u03b2<jats:sub>42<\/jats:sub>. These results further suggest that toxic oligomers of A\u03b2<jats:sub>42<\/jats:sub> share significant structural similarities with 2AT-L.<\/jats:p>","DOI":"10.1371\/journal.pone.0331024","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T17:42:29Z","timestamp":1757353349000},"page":"e0331024","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antibodies raised against a structurally defined A\u03b2 oligomer mimic protect human iPSC neurons from A\u03b2 toxicity at sub-stoichiometric concentrations"],"prefix":"10.1371","volume":"20","author":[{"given":"Sarah M.","family":"Ruttenberg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakia","family":"Dhaoui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9724-6298","authenticated-orcid":true,"given":"Adam G.","family":"Kreutzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2273-1029","authenticated-orcid":true,"given":"James S.","family":"Nowick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"pone.0331024.ref001","article-title":"The amyloid-\u03b2 oligomer hypothesis: beginning of the third decade","volume":"64","author":"EN Cline","year":"2018","journal-title":"JAD"},{"issue":"2","key":"pone.0331024.ref002","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3390\/biophysica2020010","article-title":"Amyloid-\u03b2 oligomers: multiple moving targets","volume":"2","author":"D Shea","year":"2022","journal-title":"Biophysica"},{"issue":"19","key":"pone.0331024.ref003","doi-asserted-by":"crossref","first-page":"6751","DOI":"10.3390\/molecules27196751","article-title":"Conformational essentials responsible for neurotoxicity of A\u03b242 aggregates revealed by antibodies against oligomeric A\u03b242","volume":"27","author":"C Song","year":"2022","journal-title":"Molecules"},{"key":"pone.0331024.ref004","doi-asserted-by":"crossref","first-page":"117715","DOI":"10.1016\/j.bmc.2024.117715","article-title":"A turn for the worse: A\u03b2 \u03b2-hairpins in Alzheimer\u2019s disease","volume":"105","author":"SM Ruttenberg","year":"2024","journal-title":"Bioorg Med Chem"},{"issue":"22","key":"pone.0331024.ref005","doi-asserted-by":"crossref","first-page":"4540","DOI":"10.1039\/D3OB00509G","article-title":"Recent developments in the chemical biology of amyloid-\u03b2 oligomer targeting","volume":"21","author":"Y Wang","year":"2023","journal-title":"Org Biomol Chem"},{"issue":"1","key":"pone.0331024.ref006","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41392-023-01484-7","article-title":"Amyloid \u03b2-based therapy for Alzheimer\u2019s disease: challenges, successes and future","volume":"8","author":"Y Zhang","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"pone.0331024.ref007","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.biochi.2017.07.011","article-title":"Structural studies of amyloid-\u03b2 peptides: Unlocking the mechanism of aggregation and the associated toxicity","volume":"140","author":"R Aleksis","year":"2017","journal-title":"Biochimie"},{"issue":"1","key":"pone.0331024.ref008","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00401-018-1846-7","article-title":"Diffusible, highly bioactive oligomers represent a critical minority of soluble A\u03b2 in Alzheimer\u2019s disease brain","volume":"136","author":"W Hong","year":"2018","journal-title":"Acta Neuropathol"},{"issue":"1","key":"pone.0331024.ref009","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1038\/s41467-023-38494-6","article-title":"Early events in amyloid-\u03b2 self-assembly probed by time-resolved solid state NMR and light scattering","volume":"14","author":"J Jeon","year":"2023","journal-title":"Nat Commun"},{"key":"pone.0331024.ref010","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.cbpa.2021.05.004","article-title":"Exploring amyloid oligomers with peptide model systems","volume":"64","author":"TD Samdin","year":"2021","journal-title":"Curr Opin Chem Biol"},{"issue":"23","key":"pone.0331024.ref011","doi-asserted-by":"crossref","first-page":"8920","DOI":"10.3390\/ijms21238920","article-title":"Antibody fragments as tools for elucidating structure-toxicity relationships and for diagnostic\/therapeutic targeting of neurotoxic amyloid oligomers","volume":"21","author":"ALB Bitencourt","year":"2020","journal-title":"Int J Mol Sci"},{"key":"pone.0331024.ref012","unstructured":"Although some A\u03b2 antibodies have been approved to treat Alzheimer\u2019s disease, their use as a therapeutic remains controversial due to their low efficacy and high incidence of life-threatening side effects."},{"issue":"2","key":"pone.0331024.ref013","doi-asserted-by":"crossref","DOI":"10.1002\/pep2.24333","article-title":"Generation and study of antibodies against two triangular trimers derived from A\u03b2","volume":"116","author":"AG Kreutzer","year":"2023","journal-title":"Peptide Sci"},{"issue":"1","key":"pone.0331024.ref014","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1021\/acscentsci.3c00592","article-title":"Antibodies raised against an A\u03b2 oligomer mimic recognize pathological features in Alzheimer\u2019s disease and associated amyloid-disease brain tissue","volume":"10","author":"AG Kreutzer","year":"2023","journal-title":"ACS Cent Sci"},{"issue":"6","key":"pone.0331024.ref015","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.cell.2011.05.034","article-title":"The human brain in a dish: the promise of iPSC-derived neurons","volume":"145","author":"R Dolmetsch","year":"2011","journal-title":"Cell"},{"key":"pone.0331024.ref016","doi-asserted-by":"crossref","first-page":"112924","DOI":"10.1016\/j.biopha.2022.112924","article-title":"Cell models for Alzheimer\u2019s and Parkinson\u2019s disease: at the interface of biology and drug discovery","volume":"149","author":"S Cetin","year":"2022","journal-title":"Biomed Pharmacother"},{"issue":"1","key":"pone.0331024.ref017","doi-asserted-by":"crossref","DOI":"10.1002\/cpcb.51","article-title":"Transcription factor-mediated differentiation of human iPSCs into neurons","volume":"79","author":"MS Fernandopulle","year":"2018","journal-title":"Curr Protoc Cell Biol"},{"issue":"4","key":"pone.0331024.ref018","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.stemcr.2017.08.019","article-title":"Scalable production of iPSC-derived human neurons to identify Tau-lowering compounds by high-content screening","volume":"9","author":"C Wang","year":"2017","journal-title":"Stem Cell Reports"},{"issue":"13","key":"pone.0331024.ref019","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1002\/cbic.201900097","article-title":"What is the \u201cRelevant\u201d Amyloid \u03b242 concentration?","volume":"20","author":"JA Raskatov","year":"2019","journal-title":"Chembiochem"},{"issue":"38","key":"pone.0331024.ref020","doi-asserted-by":"crossref","first-page":"11506","DOI":"10.1002\/anie.201706279","article-title":"Suppression of oligomer formation and formation of non-toxic fibrils upon addition of mirror-image A\u03b242 to the natural l-enantiomer","volume":"56","author":"S Dutta","year":"2017","journal-title":"Angew Chem Int Ed Engl"},{"issue":"1","key":"pone.0331024.ref021","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jmb.2009.12.016","article-title":"The recombinant amyloid-beta peptide Abeta1-42 aggregates faster and is more neurotoxic than synthetic Abeta1-42","volume":"396","author":"VH Finder","year":"2010","journal-title":"J Mol Biol"},{"issue":"1","key":"pone.0331024.ref022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12952-017-0066-3","article-title":"Do anti-amyloid beta protein antibody cross reactivities confound Alzheimer disease research?","volume":"16","author":"S Hunter","year":"2017","journal-title":"J Negat Results Biomed"},{"issue":"46","key":"pone.0331024.ref023","doi-asserted-by":"crossref","first-page":"32131","DOI":"10.1074\/jbc.M114.594846","article-title":"Monoclonal antibodies against A\u03b242 fibrils distinguish multiple aggregation state polymorphisms in vitro and in Alzheimer disease brain","volume":"289","author":"A Hatami","year":"2014","journal-title":"J Biol Chem"},{"issue":"1","key":"pone.0331024.ref024","article-title":"An N-terminal antibody promotes the transformation of amyloid fibrils into oligomers and enhances the neurotoxicity of amyloid-beta: the dust-raising effect","volume":"12","author":"Y-H Liu","year":"2015","journal-title":"J Neuroinflammation"},{"key":"pone.0331024.ref025","unstructured":"pAb2AT-L, 6E10, and 4G8 all exhibited significant binding to recombinant A\u03b242 by ELISA. 6E10 and 4G8 exhibited stronger binding than pAb2AT-L (S5 Fig). Before treating the cells, the concentrations of all three antibodies were compared by absorbance at 280\u2009nm using a nanodrop and confirmed to be in the same range, with pAb2AT-L exhibiting a lower absorbance than 6E10 and 4G8. 2023."},{"issue":"9","key":"pone.0331024.ref026","doi-asserted-by":"crossref","first-page":"5284","DOI":"10.1007\/s12035-022-02909-0","article-title":"p38 MAPK is a major regulator of amyloid beta-induced IL-6 expression in human microglia","volume":"59","author":"H Lin","year":"2022","journal-title":"Mol Neurobiol"},{"issue":"14","key":"pone.0331024.ref027","doi-asserted-by":"crossref","first-page":"11569","DOI":"10.3390\/ijms241411569","article-title":"T1AM\/TAAR1 system reduces inflammatory response and \u03b2-amyloid toxicity in human microglial HMC3 cell line","volume":"24","author":"B Polini","year":"2023","journal-title":"IJMS"},{"key":"pone.0331024.ref028","doi-asserted-by":"crossref","first-page":"3652402","DOI":"10.1155\/2022\/3652402","article-title":"Isorhamnetin attenuated the release of interleukin-6 from \u03b2-amyloid-activated microglia and mitigated interleukin-6-mediated neurotoxicity","volume":"2022","author":"P-C Wei","year":"2022","journal-title":"Oxid Med Cell Longev"},{"issue":"10","key":"pone.0331024.ref029","first-page":"136","article-title":"Role of pro-inflammatory cytokines released from microglia in Alzheimer\u2019s disease","volume":"3","author":"W-Y Wang","year":"2015","journal-title":"Ann Transl Med"},{"issue":"5618","key":"pone.0331024.ref030","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1126\/science.1079469","article-title":"Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis","volume":"300","author":"R Kayed","year":"2003","journal-title":"Science"},{"key":"pone.0331024.ref031","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1750-1326-2-18","article-title":"Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers","volume":"2","author":"R Kayed","year":"2007","journal-title":"Mol Neurodegener"},{"issue":"8","key":"pone.0331024.ref032","doi-asserted-by":"crossref","first-page":"722","DOI":"10.2174\/1567205017666201109093848","article-title":"Targeting pathological amyloid aggregates with conformation-sensitive antibodies","volume":"17","author":"A Bigi","year":"2020","journal-title":"Curr Alzheimer Res"},{"issue":"1","key":"pone.0331024.ref033","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13195-023-01361-z","article-title":"A single-domain antibody detects and neutralises toxic A\u03b242 oligomers in the Alzheimer\u2019s disease CSF","volume":"16","author":"A Bigi","year":"2024","journal-title":"Alzheimers Res Ther"},{"issue":"7","key":"pone.0331024.ref034","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1016\/j.neurobiolaging.2010.09.020","article-title":"Nanobody specific for oligomeric \u03b2-amyloid stabilizes nontoxic form","volume":"33","author":"S Kasturirangan","year":"2012","journal-title":"Neurobiol Aging"},{"issue":"3","key":"pone.0331024.ref035","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.jmb.2009.01.061","article-title":"Direct in vivo intracellular selection of conformation-sensitive antibody domains targeting Alzheimer\u2019s amyloid-beta oligomers","volume":"387","author":"G Meli","year":"2009","journal-title":"J Mol Biol"},{"issue":"10","key":"pone.0331024.ref036","doi-asserted-by":"crossref","first-page":"5515","DOI":"10.1007\/s12035-023-03406-8","article-title":"Dual efficacy of a catalytic anti-oligomeric A\u03b242 scFv antibody in clearing A\u03b242 aggregates and reducing A\u03b2 burden in the brains of Alzheimer\u2019s disease mice","volume":"60","author":"C Song","year":"2023","journal-title":"Mol Neurobiol"},{"issue":"4","key":"pone.0331024.ref037","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.jmb.2008.09.068","article-title":"Anti-oligomeric Abeta single-chain variable domain antibody blocks Abeta-induced toxicity against human neuroblastoma cells","volume":"384","author":"A Zameer","year":"2008","journal-title":"J Mol Biol"},{"key":"pone.0331024.ref038","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.neuropharm.2015.07.038","article-title":"The protective effects and underlying mechanism of an anti-oligomeric A\u03b242 single-chain variable fragment antibody","volume":"99","author":"Y Zhang","year":"2015","journal-title":"Neuropharmacology"},{"key":"pone.0331024.ref039","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.intimp.2018.12.014","article-title":"Novel antibody against oligomeric amyloid-\u03b2: Insight into factors for effectively reducing the aggregation and cytotoxicity of amyloid-\u03b2 aggregates","volume":"67","author":"X Zhang","year":"2019","journal-title":"Int Immunopharmacol"},{"issue":"3","key":"pone.0331024.ref040","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.nbd.2009.08.007","article-title":"An amyloid-beta protofibril-selective antibody prevents amyloid formation in a mouse model of Alzheimer\u2019s disease","volume":"36","author":"A Lord","year":"2009","journal-title":"Neurobiol Dis"},{"issue":"31","key":"pone.0331024.ref041","doi-asserted-by":"crossref","first-page":"10369","DOI":"10.1523\/JNEUROSCI.5721-09.2010","article-title":"Generation and therapeutic efficacy of highly oligomer-specific beta-amyloid antibodies","volume":"30","author":"H Hillen","year":"2010","journal-title":"J Neurosci"},{"key":"pone.0331024.ref042","unstructured":"Several anti-Abeta antibodies or antibody fragments do exhibit protective effects at 1:1 or greater antibody-to-Abeta molar ratios. 2023."},{"issue":"12","key":"pone.0331024.ref043","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1021\/acschemneuro.5b00231","article-title":"Antibody against small aggregated peptide specifically recognizes toxic A\u03b2-42 oligomers in Alzheimer\u2019s Disease","volume":"6","author":"RU Bodani","year":"2015","journal-title":"ACS Chem Neurosci"},{"issue":"1","key":"pone.0331024.ref044","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-46306-5","article-title":"A rationally designed humanized antibody selective for amyloid beta oligomers in Alzheimer\u2019s disease","volume":"9","author":"E Gibbs","year":"2019","journal-title":"Sci Rep"},{"issue":"7","key":"pone.0331024.ref045","doi-asserted-by":"crossref","first-page":"4292","DOI":"10.1074\/jbc.M511018200","article-title":"Targeting Amyloid-\u03b2 Peptide (A\u03b2) oligomers by passive immunization with a conformation-selective monoclonal antibody improves learning and memory in A\u03b2 precursor protein (APP) transgenic mice","volume":"281","author":"EB Lee","year":"2006","journal-title":"J Biol Chem"},{"issue":"12","key":"pone.0331024.ref046","doi-asserted-by":"crossref","first-page":"4542","DOI":"10.3390\/ijms21124542","article-title":"Rationally designed antibodies as research tools to study the structure-toxicity relationship of amyloid-\u03b2 oligomers","volume":"21","author":"R Limbocker","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"6","key":"pone.0331024.ref047","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1111\/jnc.14118","article-title":"A human ScFv antibody that targets and neutralizes high molecular weight pathogenic amyloid-\u03b2 oligomers","volume":"142","author":"A Sebollela","year":"2017","journal-title":"J Neurochem"},{"issue":"7","key":"pone.0331024.ref048","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1093\/brain\/awac023","article-title":"A calcium-sensitive antibody isolates soluble amyloid-\u03b2 aggregates and fibrils from Alzheimer\u2019s disease brain","volume":"145","author":"AM Stern","year":"2022","journal-title":"Brain"},{"key":"pone.0331024.ref049","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/2051-5960-2-43","article-title":"Oligomer-targeting with a conformational antibody fragment promotes toxicity in A\u03b2-expressing flies","volume":"2","author":"J Wacker","year":"2014","journal-title":"Acta Neuropathol Commun"},{"key":"pone.0331024.ref050","unstructured":"It should be noted that pAb2AT-L and other anti-Abeta antibodies have two antigen binding sites which may allow each antibody to bind two Abeta aggregates at once."},{"key":"pone.0331024.ref051","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s00775-014-1131-8","article-title":"The hairpin conformation of the amyloid \u03b2 peptide is an important structural motif along the aggregation pathway","volume":"19","author":"A Abelein","year":"2014","journal-title":"J Biol Inorg Chem"},{"issue":"1","key":"pone.0331024.ref052","doi-asserted-by":"crossref","first-page":"3014","DOI":"10.1038\/s41467-020-16566-1","article-title":"A\u03b2(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage","volume":"11","author":"S Ciudad","year":"2020","journal-title":"Nat Commun"},{"issue":"33","key":"pone.0331024.ref053","doi-asserted-by":"crossref","first-page":"18340","DOI":"10.1021\/jacs.3c03980","article-title":"A hairpin motif in the Amyloid-\u03b2 peptide is important for formation of disease-related oligomers","volume":"145","author":"M Khaled","year":"2023","journal-title":"J Am Chem Soc"},{"issue":"22","key":"pone.0331024.ref054","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2219216120","article-title":"Probing differences among A\u03b2 oligomers with two triangular trimers derived from A\u03b2","volume":"120","author":"AG Kreutzer","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"35","key":"pone.0331024.ref055","doi-asserted-by":"crossref","first-page":"15595","DOI":"10.1073\/pnas.1001740107","article-title":"Stabilization of neurotoxic Alzheimer amyloid-beta oligomers by protein engineering","volume":"107","author":"A Sandberg","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0331024.ref056","doi-asserted-by":"crossref","first-page":"101125","DOI":"10.1016\/j.nantod.2021.101125","article-title":"Spontaneous formation of \u03b2-sheet nano-barrels during the early aggregation of Alzheimer\u2019s amyloid beta","volume":"38","author":"Y Sun","year":"2021","journal-title":"Nano Today"},{"issue":"9","key":"pone.0331024.ref057","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1021\/bi802046n","article-title":"Structural characterization of a soluble amyloid beta-peptide oligomer","volume":"48","author":"L Yu","year":"2009","journal-title":"Biochemistry"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0331024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T17:42:51Z","timestamp":1757353371000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0331024"}},"subtitle":[],"editor":[{"given":"J\u00e9r\u00f4me","family":"Robert","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,8]]},"references-count":57,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0331024","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2025,9,8]]}}}