{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:27:18Z","timestamp":1788323238118,"version":"build-2803163510"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"wellcome trust","doi-asserted-by":"publisher","award":["098051"],"award-info":[{"award-number":["098051"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"wellcome trust","doi-asserted-by":"publisher","award":["100699"],"award-info":[{"award-number":["100699"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"wellcome trust","doi-asserted-by":"publisher","award":["WT089622MA"],"award-info":[{"award-number":["WT089622MA"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"medical research council","doi-asserted-by":"publisher","award":["G0300212"],"award-info":[{"award-number":["G0300212"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ec","award":["MSCA-ITN-2016-LISTEN-722098"],"award-info":[{"award-number":["MSCA-ITN-2016-LISTEN-722098"]}]},{"DOI":"10.13039\/501100020172","name":"rnid","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100020172","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100020172","name":"rnid","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100020172","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Age-related hearing loss in humans (presbycusis) typically involves impairment of high frequency sensitivity before becoming progressively more severe at lower frequencies. Pathologies initially affecting lower frequency regions of hearing are less common. Here we describe a progressive, predominantly low-frequency recessive hearing impairment in two mutant mouse lines carrying different mutant alleles of the\n                    <jats:italic>Klhl18<\/jats:italic>\n                    gene: a spontaneous missense mutation (\n                    <jats:italic>Klhl18<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>lowf<\/jats:italic>\n                    <\/jats:sup>\n                    ) and a targeted mutation (\n                    <jats:italic>Klhl18<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>tm1a(KOMP)Wtsi<\/jats:italic>\n                    <\/jats:sup>\n                    ). Both males and females were studied, and the two mutant lines showed similar phenotypes. Threshold for auditory brainstem responses (ABR; a measure of auditory nerve and brainstem neural activity) were normal at 3 weeks old but showed progressive increases from 4 weeks onwards. In contrast, distortion product otoacoustic emission (DPOAE) sensitivity and amplitudes (a reflection of cochlear outer hair cell function) remained normal in mutants. Electrophysiological recordings from the round window of\n                    <jats:italic>Klhl18<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>lowf<\/jats:italic>\n                    <\/jats:sup>\n                    mutants at 6 weeks old revealed 1) raised compound action potential thresholds that were similar to ABR thresholds, 2) cochlear microphonic potentials that were normal compared with wildtype and heterozygous control mice and 3) summating potentials that were reduced in amplitude compared to control mice. Scanning electron microscopy showed that\n                    <jats:italic>Klhl18<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>lowf<\/jats:italic>\n                    <\/jats:sup>\n                    mutant mice had abnormally tapering of the tips of inner hair cell stereocilia in the apical half of the cochlea while their synapses appeared normal. These results suggest that Klhl18 is necessary to maintain inner hair cell stereocilia and normal inner hair cell function at low frequencies.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0258158","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T15:29:14Z","timestamp":1633102154000},"page":"e0258158","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0916-7347","authenticated-orcid":true,"given":"Neil J.","family":"Ingham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navid","family":"Banafshe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Panganiban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4566-3858","authenticated-orcid":true,"given":"Julia L.","family":"Crunden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morag A.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen P.","family":"Steel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"pone.0258158.ref001","doi-asserted-by":"crossref","first-page":"e3000194","DOI":"10.1371\/journal.pbio.3000194","article-title":"Mouse screen reveals multiple new genes underlying mouse and human hearing loss","volume":"17","author":"NJ Ingham","year":"2019","journal-title":"PLOS Biol"},{"key":"pone.0258158.ref002","author":"MA Lewis","year":"2021","journal-title":"Collateral damage: Identification and characterisation of off-target mutations causing deafness from a targeted knockout programme"},{"key":"pone.0258158.ref003","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/s41467-017-00595-4","article-title":"A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction","volume":"8","author":"MR Bowl","year":"2017","journal-title":"Nat. Comm"},{"key":"pone.0258158.ref004","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.cell.2013.06.022","article-title":"Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes","volume":"154","author":"JK White","year":"2013","journal-title":"Cell"},{"key":"pone.0258158.ref005","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1479-7364-7-13","article-title":"Update on the kelch-like (KLHL) gene family","volume":"7","author":"BS Dhanoa","year":"2013","journal-title":"Human Genomics"},{"key":"pone.0258158.ref006","first-page":"1193","article-title":"The BTB\/POZ Domain: A new protein-protein interaction motif common to DNA- and actin-binding proteins","volume":"6","author":"O Albagli","year":"1995","journal-title":"Cell Growth and Differentiation"},{"key":"pone.0258158.ref007","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1002\/bies.20500","article-title":"Born to bind: the BTB protein-protein interaction domain","volume":"28","author":"R Perez-Torrado","year":"2006","journal-title":"BioEssays"},{"key":"pone.0258158.ref008","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1073\/pnas.0308347100","article-title":"Scaffolding of Keap1 to the actin cytoskeleton controls the function of Nrf2 as key regulator of cytoprotective phase 2 genes","volume":"101","author":"MI Kang","year":"2004","journal-title":"PNAS"},{"key":"pone.0258158.ref009","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/S0092-8674(00)00088-X","article-title":"The Polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel","volume":"102","author":"DL Minor","year":"2000","journal-title":"Cell"},{"key":"pone.0258158.ref010","doi-asserted-by":"crossref","first-page":"6550","DOI":"10.1128\/MCB.20.17.6550-6567.2000","article-title":"In-depth mutational analysis of the promyelocytic leukemia zinc finger BTB\/POZ domain reveals motifs and residues required for biological and transcriptional functions","volume":"20","author":"A Melnick","year":"2000","journal-title":"Mol. Cell. Biology"},{"key":"pone.0258158.ref011","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/ncb1056","article-title":"Targeting of protein ubiquitination by BTB\u2013Cullin3 \u2013Roc1 ubiquitin ligases","volume":"5","author":"M Furukawa","year":"2003","journal-title":"Nature Cell Biol"},{"key":"pone.0258158.ref012","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nature01985","article-title":"BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3","volume":"425","author":"L Xu","year":"2003","journal-title":"Nature"},{"key":"pone.0258158.ref013","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1242\/bio.2011018","article-title":"The CUL3-KLHL18 ligase regulates mitotic entry and ubiquitylates Aurora-A","volume":"1","author":"S Moghe","year":"2012","journal-title":"Biology Open"},{"key":"pone.0258158.ref014","doi-asserted-by":"crossref","first-page":"e101409","DOI":"10.15252\/embj.2018101409","article-title":"Cul3-Klhl18 ubiquitin ligase modulates rod transducin translocation during light-dark adaptation","volume":"38","author":"T Chaya","year":"2019","journal-title":"EMBO J"},{"key":"pone.0258158.ref015","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature10163","article-title":"A conditional knockout resource for the genome-wide study of mouse gene function","volume":"474","author":"WC Skarnes","year":"2011","journal-title":"Nature"},{"key":"pone.0258158.ref016","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/9780470942390.mo110059","article-title":"Using the Auditory Brainstem Response (ABR) to Determine Hearing Sensitivity in Mutant Mice","volume":"1","author":"NJ Ingham","year":"2011","journal-title":"Curr. Protocols. Mouse Biol"},{"key":"pone.0258158.ref017","doi-asserted-by":"crossref","first-page":"e3447","DOI":"10.21769\/BioProtoc.3447","article-title":"Evoked potential recordings of auditory brainstem activity in the mouse: An optimized method for the assessment of hearing function of mice","volume":"9","author":"NJ Ingham","year":"2019","journal-title":"Bio-Protocol"},{"key":"pone.0258158.ref018","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1242\/dev.107.3.453","article-title":"Another role for melanocytes: their importance for normal stria vascularis development in the mammalian inner ear","volume":"107","author":"KP Steel","year":"1989","journal-title":"Development"},{"key":"pone.0258158.ref019","first-page":"28964","article-title":"S1PR2 variants associated with auditory function in humans and endocochlear potential decline in mouse","volume":"6","author":"NJ Ingham","year":"2016","journal-title":"Sci. Reports"},{"key":"pone.0258158.ref020","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/0378-5955(92)90044-N","article-title":"The development and interpretation of the summating potential response","volume":"61","author":"D Harvey","year":"1992","journal-title":"Hear. Res"},{"key":"pone.0258158.ref021","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.heares.2004.08.011","article-title":"A physiological place-frequency map of the cochlea in the CBA\/J mouse","volume":"202","author":"M M\u00fcller","year":"2005","journal-title":"Hear. Res"},{"issue":"sup351","key":"pone.0258158.ref022","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3109\/00016487809122718","article-title":"A technique for preparation of cochlear specimens for assessment with the scanning electron microscope","volume":"85","author":"IM Hunter-Duvar","year":"1978","journal-title":"Acto Oto-Laryngol."},{"key":"pone.0258158.ref023","first-page":"1","volume-title":"Active Processes and Otoacoustic Emissions in Hearing","author":"DT Kemp","year":"2008"},{"key":"pone.0258158.ref024","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1121\/1.381214","article-title":"Analysis of compound action potential responses to tone bursts in the human and guinea pig cochlea","volume":"60","author":"JJ Eggermont","year":"1976","journal-title":"J. Acoust. Soc. Am"},{"key":"pone.0258158.ref025","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1113\/jphysiol.1987.sp016428","article-title":"The responses of hair cells in the basal turn of the guinea-pig cochlea to tones","volume":"383","author":"AR Cody","year":"1987","journal-title":"J. Physiol"},{"key":"pone.0258158.ref026","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/0378-5955(86)90096-1","article-title":"The responses of inner and outer hair cells in the basal turn of the guinea-pig cochlea and in the mouse cochlea grown in vitro","volume":"22","author":"IJ Russell","year":"1986","journal-title":"Hear. Res"},{"key":"pone.0258158.ref027","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1038\/s41467-020-16113-y","article-title":"Characterization of the development of the mouse cochlear epithelium at the single cell level","volume":"11","author":"L Kolla","year":"2020","journal-title":"Nat Commun"},{"key":"pone.0258158.ref028","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1016\/j.celrep.2019.02.053","article-title":"Insights into the Biology of Hearing and Deafness Revealed by Single-Cell RNA Sequencing","volume":"26","author":"PT Ranum","year":"2019","journal-title":"Cell Rep"},{"key":"pone.0258158.ref029","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nn1828","article-title":"Sharpened cochlear tuning in a mouse with a genetically modified tectorial membrane","volume":"10","author":"IJ Russell","year":"2007","journal-title":"Nat. Neurosci"},{"key":"pone.0258158.ref030","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1007\/s00335-004-2344-x","article-title":"A Myo7a mutation cosegregates with stereocilia defects and low-frequency hearing impairment","volume":"15","author":"CR Rhodes","year":"2004","journal-title":"Mamm. Genome"},{"key":"pone.0258158.ref031","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/hmg\/ddn311","article-title":"Hearing loss in a mouse model of Meunke Syndrome","volume":"18","author":"SL Mansour","year":"2009","journal-title":"Hum. Molec. Gen."},{"key":"pone.0258158.ref032","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1126\/science.278.5341.1315","article-title":"Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous","volume":"278","author":"ED Lynch","year":"1997","journal-title":"Science"},{"issue":"22","key":"pone.0258158.ref033","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1093\/hmg\/10.22.2501","article-title":"Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss","volume":"10","author":"IN Bespalova","year":"2001","journal-title":"Hum Mol Genet"},{"key":"pone.0258158.ref034","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s00418-003-0495-6","article-title":"The WFS1 gene, responsible for low frequency sensorineural hearing loss and Wolfram syndrome, is expressed in a variety of inner ear cells","volume":"119","author":"K Cryns","year":"2003","journal-title":"Histochem. Cell Biol"},{"key":"pone.0258158.ref035","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jcg.2011.01.001","article-title":"Identification of two novel missense WFS1 mutations, H696Y and R703H, in patients with non-syndromic low-frequency sensorineural hearing loss","volume":"38","author":"Y Sun","year":"2011","journal-title":"J. Genet. Genom"},{"key":"pone.0258158.ref036","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3233\/VES-150549","article-title":"Diagnostic criteria for Meni\u00e8re\u2019s disease","volume":"25","author":"JA Lopez-Escamez","year":"2015","journal-title":"J. Vestib. Res"},{"key":"pone.0258158.ref037","doi-asserted-by":"crossref","first-page":"14487","DOI":"10.1038\/ncomms14487","article-title":"Transient auditory nerve demyelination as a new mechanism for hidden hearing loss","volume":"8","author":"G Wan","year":"2017","journal-title":"Nat. Commun"},{"key":"pone.0258158.ref038","doi-asserted-by":"crossref","first-page":"14077","DOI":"10.1523\/JNEUROSCI.2845-09.2009","article-title":"Adding insult to injury: cochlear nerve degeneration after \"temporary\" noise-induced hearing loss","volume":"29","author":"SG Kujawa","year":"2009","journal-title":"J. Neurosci"},{"key":"pone.0258158.ref039","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1038\/s41598-019-39119-z","article-title":"Sodium-activated potassium channels shape peripheral auditory function and activity of the primary auditory neurons in mice","volume":"9","author":"DOJ Reijntjes","year":"2019","journal-title":"Sci. Rep"},{"key":"pone.0258158.ref040","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0962-8924(99)01673-6","article-title":"The kelch repeat superfamily of proteins: propellers of cell function","volume":"10","author":"J Adams","year":"2000","journal-title":"Trends in Cell Biol"},{"key":"pone.0258158.ref041","doi-asserted-by":"crossref","first-page":"e1002032","DOI":"10.1371\/journal.pgen.1002032","article-title":"Roles of the Espin Actin-Bundling Proteins in the Morphogenesis and Stabilization of Hair Cell Stereocilia Revealed in CBA\/CaJ Congenic Jerker Mice","volume":"7","author":"G Sekerkov\u00e1","year":"2011","journal-title":"PLOS Genetics"},{"key":"pone.0258158.ref042","doi-asserted-by":"crossref","first-page":"10833","DOI":"10.1038\/ncomms10833","article-title":"Stereocilia-staircase spacing is influenced by myosin III motors and their cargoes espin-1 and espin-like","volume":"7","author":"S Ebrahim","year":"2016","journal-title":"Nature Communications"},{"key":"pone.0258158.ref043","first-page":"e08627","volume":"4","author":"Q Fang","year":"2015","journal-title":"The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing eLife"},{"key":"pone.0258158.ref044","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/hmg\/ddu417","article-title":"Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice","volume":"24","author":"R Taylor","year":"2015","journal-title":"Hum. Molec. Genetics"},{"key":"pone.0258158.ref045","doi-asserted-by":"crossref","first-page":"13989","DOI":"10.1073\/pnas.1304644110","article-title":"Progressive hearing loss and gradual deterioration of sensory hair bundles in the ears of mice lacking the actin-binding protein Eps8L2","volume":"110","author":"DN Furness","year":"2013","journal-title":"PNAS"},{"key":"pone.0258158.ref046","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/cm.10025","article-title":"A human homologue of Drosophila kelch associates with myosin-VIIa in specialized adhesion junctions","volume":"51","author":"M Velichkova","year":"2002","journal-title":"Cell Motil Cytoskeleton"},{"key":"pone.0258158.ref047","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1242\/dev.125.4.557","article-title":"Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells","volume":"125","author":"T Self","year":"1998","journal-title":"Development"},{"key":"pone.0258158.ref048","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1128\/MCB.01282-07","article-title":"Bradley. Mosaic complementation demonstrates a regulatory role for myosin VIIa in actin dynamics of stereocilia","volume":"28","author":"HM Prosser","year":"2008","journal-title":"Mol Cell Biol"},{"key":"pone.0258158.ref049","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1152\/jn.00006.2019","article-title":"Hair cell and neural contributions to the cochlear summating potential","volume":"121","author":"AK Pappa","year":"2019","journal-title":"J. Neurophysiol"},{"key":"pone.0258158.ref050","doi-asserted-by":"crossref","first-page":"E4716","DOI":"10.1073\/pnas.1605737113","article-title":"Hair cells use active zones with different voltage dependence of Ca2+ influx to decompose sounds into complementary neural codes","volume":"113","author":"TL Ohn","year":"2016","journal-title":"PNAS"},{"key":"pone.0258158.ref051","doi-asserted-by":"crossref","first-page":"10832","DOI":"10.1523\/JNEUROSCI.23-34-10832.2003","article-title":"CaV1.3 Channels Are Essential for Development and Presynaptic Activity of Cochlear Inner Hair Cells","volume":"23","author":"A Brandt","year":"2003","journal-title":"J. Neurosci"},{"key":"pone.0258158.ref052","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.3390\/jcm9041074","article-title":"Auditory Neuropathy Spectrum Disorders: from diagnosis to treatment","volume":"9","author":"RD De Siati","year":"2020","journal-title":"J. Clin. Med."},{"key":"pone.0258158.ref053","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/nrneurol.2016.10","article-title":"Auditory neuropathy\u2013neural and synaptic mechanisms","volume":"12","author":"T Moser","year":"2016","journal-title":"Nature Reviews Neurology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258158","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T15:30:41Z","timestamp":1633102241000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258158"}},"subtitle":[],"editor":[{"given":"Olivia","family":"Bermingham-McDonogh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,10,1]]},"references-count":53,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0258158","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.03.09.434536","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,1]]}}}