{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:50:45Z","timestamp":1793152245391,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Purpose: To investigate the relationship between the apolipoprotein E (APOE) \u03b54 allele and retinal structural and vascular characteristics in older adult participants from several research studies. We also studied the relationship between these structural and vascular characteristics with multifocal visual evoked potential (mfVEP) indices, neuropsychological parameters and MRI brain volumes in these participants. Methods: In this study, 109 participants with a mean (SD) age of 67.1 (9.0) years were recruited. Participants were classified as APOE \u03b54 carriers or non-carriers based on the presence or absence of the \u03b54 allele. Baseline measurements included peripapillary retinal nerve fibre layer optical coherence tomography (RNFL OCT), and OCT\u2013angiography (OCT-A) for evaluation of the retinal layer thickness and vessel density (VD) parameters. A multifocal visual evoked potential (mfVEP) test, including amplitude and latency, was used to assess the visual pathway function. Finally, cognitive function was evaluated using a battery of neuropsychological tests. OCT-A images were analysed in ImageJ to quantify VD in the superficial and deep vascular plexus and the size of the foveal avascular zone (FAZ). The relationship between carriers of APOE \u03b54 allele and these ocular parameters was analysed using generalised estimating equation (GEE) models and data adjusted for age, sex and inter-eye differences as within-subject variables (p &lt; 0.05). Results: Twenty-four participants were APOE \u03b54 carriers. Temporal RNFL thickness was decreased in APOE \u03b54 carriers (p &lt; 0.01). Vessel density between carriers and non-carriers was not significantly different at either the superficial or deep level. The FAZ area was significantly smaller in \u03b54 carriers in both superficial (p &lt; 0.01) and deep layers (p &lt; 0.003). Conclusions: Retinal abnormalities were present in participants with increased genetic risk of dementia due to presence of the \u03b54 allele. These findings provide preliminary evidence for their potential role in the diagnosis of dementia.<\/jats:p>","DOI":"10.3390\/jcm12196219","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T03:49:14Z","timestamp":1695786554000},"page":"6219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Association of APOE \u03b54 Allele with Retinal Layer Thickness and Microvasculature in Older Adults: Optic Nerve Decline and Cognitive Change Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Samran","family":"Sheriff","sequence":"first","affiliation":[{"name":"Macquarie Medical School, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0057-232X","authenticated-orcid":false,"given":"Ting","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital (Shanghai First People\u2019s Hospital), School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danit","family":"Saks","sequence":"additional","affiliation":[{"name":"Macquarie Medical School, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Schultz","sequence":"additional","affiliation":[{"name":"Macquarie Medical School, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-7782","authenticated-orcid":false,"given":"Heather","family":"Francis","sequence":"additional","affiliation":[{"name":"School of Psychological Sciences, Macquarie University, Sydney, NSW 2019, Australia"},{"name":"Neurology Department, Royal North Shore Hospital, Sydney, NSW 2065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wen","sequence":"additional","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2147-6302","authenticated-orcid":false,"given":"Jiyang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Mirzaei","sequence":"additional","affiliation":[{"name":"Macquarie Medical School, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veer","family":"Gupta","sequence":"additional","affiliation":[{"name":"School of Medicine, Deakin University, Melbourne, VIC 3125, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-8707","authenticated-orcid":false,"given":"Maria","family":"Fiatarone Singh","sequence":"additional","affiliation":[{"name":"Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA 02131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9595-3220","authenticated-orcid":false,"given":"Perminder S.","family":"Sachdev","sequence":"additional","affiliation":[{"name":"Centre for Healthy Brain Ageing, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart L.","family":"Graham","sequence":"additional","affiliation":[{"name":"Macquarie Medical School, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0202-7843","authenticated-orcid":false,"given":"Vivek","family":"Gupta","sequence":"additional","affiliation":[{"name":"Macquarie Medical School, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0140-6736(20)30367-6","article-title":"Dementia prevention, intervention, and care: 2020 report of the Lancet Commission","volume":"396","author":"Livingston","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Cuenca, I., de Hoz, R., Salobrar-Garc\u00eda, E., Elvira-Hurtado, L., Rojas, P., Fern\u00e1ndez-Albarral, J.A., and Ram\u00edrez, J.M. (2020). Macular thickness decrease in asymptomatic subjects at high genetic risk of developing Alzheimer\u2019s disease: An OCT study. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061728"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.neuron.2020.10.008","article-title":"Apolipoprotein E: Structural insights and links to Alzheimer disease pathogenesis","volume":"109","author":"Chen","year":"2021","journal-title":"Neuron"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1037\/0882-7974.19.4.592","article-title":"Apolipoprotein E and cognitive performance: A meta-analysis","volume":"19","author":"Small","year":"2004","journal-title":"Psychol. Aging"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1136\/jnnp.73.6.672","article-title":"The apolipoprotein E \u03b52 allele and decline in episodic memory","volume":"73","author":"Wilson","year":"2002","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_6","first-page":"e12181","article-title":"Retinal imaging demonstrates reduced capillary density in clinically unimpaired APOE \u03b54 gene carriers","volume":"13","author":"Elahi","year":"2021","journal-title":"Alzheimer\u2019s Dement. Diagn. Assess. Dis. Monit."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Salobrar-Garcia, E., M\u00e9ndez-Hern\u00e1ndez, C., Hoz, R.D., Ram\u00edrez, A.I., L\u00f3pez-Cuenca, I., Fern\u00e1ndez-Albarral, J.A., and Ram\u00edrez, J.M. (2020). Ocular vascular changes in mild alzheimer\u2019s disease patients: Foveal avascular zone, choroidal thickness, and onh hemoglobin analysis. J. Pers. Med., 10.","DOI":"10.3390\/jpm10040231"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1001\/jamaneurol.2017.1658","article-title":"Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) cohort","volume":"74","author":"Gottesman","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s10654-022-00864-7","article-title":"APOE \u03b54 and late-life cognition: Mediation by structural brain imaging markers","volume":"37","author":"Ma","year":"2022","journal-title":"Eur. J. Epidemiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1111\/ceo.14134","article-title":"Quantification of localised vascular wedge-shaped defects in glaucoma","volume":"50","author":"Saks","year":"2022","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"572484","DOI":"10.3389\/fnagi.2020.572484","article-title":"Decreased retinal vascular density in Alzheimer\u2019s disease (AD) and mild cognitive impairment (MCI): An optical coherence tomography angiography (OCTA) study","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Jiang, H., Liu, Y., Wei, Y., Shi, Y., Wright, C.B., Sun, X., and Wang, J. (2018). Impaired retinal microcirculation in patients with Alzheimer\u2019s disease. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192154"},{"key":"ref_13","first-page":"49","article-title":"Retinal thickness correlates with parietal cortical atrophy in early-onset Alzheimer\u2019s disease and controls","volume":"10","author":"Janssen","year":"2018","journal-title":"Alzheimer\u2019s Dement. Diagn. Assess. Dis. Monit."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"440","DOI":"10.3928\/23258160-20180601-09","article-title":"Assessment of differences in retinal microvasculature using OCT angiography in Alzheimer\u2019s disease: A twin discordance report","volume":"49","author":"Grewal","year":"2018","journal-title":"Ophthalmic Surg. Lasers Imaging Retin."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Cuenca, I., Salobrar-Garc\u00eda, E., Elvira-Hurtado, L., Fern\u00e1ndez-Albarral, J.A., S\u00e1nchez-Puebla, L., Salazar, J.J., and de Hoz, R. (2021). The value of oct and octa as potential biomarkers for preclinical Alzheimer\u2019s disease: A review study. Life, 11.","DOI":"10.3390\/life11070712"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100049","DOI":"10.1016\/j.nbas.2022.100049","article-title":"Evaluating associations of RNFL thickness and multifocal VEP with cognitive assessment and brain MRI volumes in older adults: Optic nerve decline and cognitive change (ONDCC) initiative","volume":"2","author":"Shen","year":"2022","journal-title":"Aging Brain"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tewarie, P., Balk, L., Costello, F., Green, A., Martin, R., Schippling, S., and Petzold, A. (2012). The OSCAR-IB consensus criteria for retinal OCT quality assessment. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034823"},{"key":"ref_18","unstructured":"Elfarnawany, M.H.E.-K. (2015). Signal Processing Methods for Quantitative Power Doppler Microvascular Angiography, The University of Western Ontario."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1080\/09602011.2016.1231121","article-title":"The National Adult Reading Test: Restandardisation against the Wechsler adult intelligence scale\u2014Fourth edition","volume":"28","author":"Bright","year":"2018","journal-title":"Neuropsychol. Rehabil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1037\/0022-006X.56.1.123","article-title":"Integrating clinical assessment with cognitive neuroscience: Construct validation of the California Verbal Learning Test","volume":"56","author":"Delis","year":"1988","journal-title":"J. Consult. Clin. Psychol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.30773\/pi.2019.0061e","article-title":"Normative Data for the Logical Memory Subtest of the Wechsler Memory Scale-IV in Middle-Aged and Elderly Korean People","volume":"17","author":"Ahn","year":"2020","journal-title":"Psychiatry Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.acn.2007.01.026","article-title":"The reliability and validity of qualitative scores for the Controlled Oral Word Association Test","volume":"22","author":"Ross","year":"2007","journal-title":"Arch. Clin. Neuropsychol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Smith, A. (1973). Symbol Digit Modalities Test, Western Psychological Services Los Angeles.","DOI":"10.1037\/t27513-000"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1038\/nprot.2006.390","article-title":"Administration and interpretation of the Trail Making Test","volume":"1","author":"Bowie","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wechsler, D. (1997). Wechsler Adult Intelligence Scale, Psychological Corporation. [3rd ed.]. (WAIS-III).","DOI":"10.1037\/t49755-000"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1037\/pne0000140","article-title":"Digit span sequencing as a neurocognitive screening tool in an aging, veteran population","volume":"12","author":"Lumpkin","year":"2019","journal-title":"Psychol. Neurosci."},{"key":"ref_27","unstructured":"Kaplan, E.F., Goodglass, H., and Weintraub, S. (1982). The Boston Naming Test, Lea&Febiger. [2nd ed.]."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1080\/13803395.2015.1075473","article-title":"Examining Rey complex figure test organization in healthy adults","volume":"37","author":"Wilson","year":"2015","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J. Psychiatr. Res."},{"key":"ref_30","first-page":"1","article-title":"The geriatric depression scale (GDS)","volume":"4","author":"Greenberg","year":"2012","journal-title":"Best Pract. Nurs. Care Older Adults"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.ophtha.2018.06.022","article-title":"Differing structural and functional patterns of optic nerve damage in multiple sclerosis and neuromyelitis optica spectrum disorder","volume":"126","author":"Shen","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.scijus.2015.01.005","article-title":"An evaluation of the performance of five extraction methods: Chelex\u00ae 100, QIAamp\u00ae DNA blood mini kit, QIAamp\u00ae DNA investigator kit, QIAsymphony\u00ae DNA Investigator\u00ae kit and DNA IQ\u2122","volume":"55","author":"Ip","year":"2015","journal-title":"Sci. Justice"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12877-021-02471-9","article-title":"Cognitive function assessed by Mini-mental state examination and risk of all-cause mortality: A community-based prospective cohort study","volume":"21","author":"Su","year":"2021","journal-title":"BMC Geriatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1212\/WNL.46.2.413","article-title":"Clinical and neuropsychological characteristics in familial and sporadic Alzheimer\u2019s disease: Relation to apolipoprotein E polymorphism","volume":"46","author":"Lehtovirta","year":"1996","journal-title":"Neurology"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Salobrar-Garc\u00eda, E., Rodrigues-Neves, A.C., Ram\u00edrez, A.I., de Hoz, R., Fern\u00e1ndez-Albarral, J.A., and L\u00f3pez-Cuenca, I. (2020). Microglial activation in the retina of a triple-transgenic alzheimer\u2019s disease mouse model (3xTg-AD). Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030816"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3447","DOI":"10.1167\/iovs.19-27028","article-title":"Comparison of retinal microvasculature in patients with Alzheimer\u2019s disease and primary open-angle glaucoma by optical coherence tomography angiography","volume":"60","author":"Zabel","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100159","DOI":"10.1016\/j.xops.2022.100159","article-title":"The APOE E4 allele is associated with faster rates of neuroretinal thinning in a prospective cohort study of suspect and early glaucoma","volume":"2","author":"Mullany","year":"2022","journal-title":"Ophthalmol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"211","DOI":"10.15252\/emmm.201404524","article-title":"Apolipoprotein E promotes subretinal mononuclear phagocyte survival and chronic inflammation in age-related macular degeneration","volume":"7","author":"Levy","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1212\/WNL.0000000000000431","article-title":"Amyloid and APOE \u03b54 interact to influence short-term decline in preclinical Alzheimer disease","volume":"82","author":"Mormino","year":"2014","journal-title":"Neurology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.archger.2014.10.011","article-title":"Abnormal retinal nerve fiber layer thickness and macula lutea in patients with mild cognitive impairment and Alzheimer\u2019s disease","volume":"60","author":"Gao","year":"2015","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Shi, Z., Cao, X., Hu, J., Jiang, L., Mei, X., and Zheng, H. (2020). Retinal nerve fiber layer thickness is associated with hippocampus and lingual gyrus volumes in nondemented older adults. Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 99.","DOI":"10.1016\/j.pnpbp.2019.109824"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1016\/j.neuroimage.2010.05.036","article-title":"Alterations in multiple measures of white matter integrity in normal women at high risk for Alzheimer\u2019s disease","volume":"52","author":"Gold","year":"2010","journal-title":"Neuroimage"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.neurobiolaging.2008.03.013","article-title":"White matter pathology isolates the hippocampal formation in Alzheimer\u2019s disease","volume":"31","author":"Salat","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S0002-9394(02)02003-2","article-title":"Evaluation of the glaucomatous damage on retinal nerve fiber layer thickness measured by optical coherence tomography","volume":"135","author":"Kanamori","year":"2003","journal-title":"Am. J. Ophthalmol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1016\/j.ophtha.2014.01.017","article-title":"Rates of retinal nerve fiber layer thinning in glaucoma suspect eyes","volume":"121","author":"Miki","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.ophtha.2016.02.017","article-title":"Risk of visual field progression in glaucoma patients with progressive retinal nerve fiber layer thinning: A 5-year prospective study","volume":"123","author":"Yu","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1212\/WNL.0b013e31827deb39","article-title":"Axonal loss in non\u2013optic neuritis eyes of patients with multiple sclerosis linked to delayed visual evoked potential","volume":"80","author":"Klistorner","year":"2013","journal-title":"Neurology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy","volume":"9","author":"Liu","year":"2013","journal-title":"Nat. Rev. Neurol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/19\/6219\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:59:07Z","timestamp":1760129947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/19\/6219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,27]]},"references-count":48,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["jcm12196219"],"URL":"https:\/\/doi.org\/10.3390\/jcm12196219","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,27]]}}}