{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:01:28Z","timestamp":1787238088120,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Donald W. Reynolds Foundation","award":["UL1TR001105"],"award-info":[{"award-number":["UL1TR001105"]}]},{"name":"Donald W. Reynolds Foundation","award":["R01 AG057571"],"award-info":[{"award-number":["R01 AG057571"]}]},{"DOI":"10.13039\/100000002","name":"National Center for Advancing Translational Sciences of the NIH","doi-asserted-by":"publisher","award":["UL1TR001105"],"award-info":[{"award-number":["UL1TR001105"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Center for Advancing Translational Sciences of the NIH","doi-asserted-by":"publisher","award":["R01 AG057571"],"award-info":[{"award-number":["R01 AG057571"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UT Southwestern O\u2019Brien Kidney Center","award":["UL1TR001105"],"award-info":[{"award-number":["UL1TR001105"]}]},{"name":"UT Southwestern O\u2019Brien Kidney Center","award":["R01 AG057571"],"award-info":[{"award-number":["R01 AG057571"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objective: High-density lipoprotein cholesterol efflux function may prevent brain amyloid beta deposition and neurodegeneration. However, the relevance of this finding has not been established in the diverse middle-aged population. Methods: We examined 1826 adults (47% Black adults) who participated in the Dallas Heart Study to determine associations between high-density lipoprotein (HDL) measures and brain structure and function. White matter hyperintensities (WMH) and whole-brain grey matter volume (GMV) were measured using brain MRI, and the Montreal Cognitive Assessment (MoCA) was used to measure neurocognitive function. HDL cholesterol efflux capacity (HDL-CEC) was assessed using fluorescence-labeled cholesterol efflux from J774 macrophages, and HDL particle size measures were assessed using nuclear magnetic resonance (NMR) spectroscopy (LipoScience). Multivariable linear regressions were performed to elucidate associations between HDL-CEC and brain and cognitive phenotypes after adjustment for traditional risk factors such as age, smoking status, time spent in daily physical activity, and education level. Results: Higher HDL-CEC and small HDL particle (HDL-P) concentration were positively associated with higher GMV normalized to total cranial volume (TCV) (GMV\/TCV) after adjustment for relevant risk factors (\u03b2 = 0.078 [95% CI: 0.029, 0.126], p = 0.002, and \u03b2 = 0.063 [95% CI: 0.014, 0.111], p = 0.012, respectively). Conversely, there were no associations between HDL measures and WMH or MoCA (all p &gt; 0.05). Associations of HDL-CEC and small HDL-P with GMV\/TCV were not modified by ApoE-\u03b54 status or race\/ethnicity. Interpretation: Higher HDL cholesterol efflux and higher plasma concentration of small HDL-P were associated with higher GMV\/TCV. Additional studies are needed to explore the potential neuroprotective functions of HDL.<\/jats:p>","DOI":"10.3390\/jcm13206218","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T06:46:52Z","timestamp":1729234012000},"page":"6218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Associations Between High-Density Lipoprotein Cholesterol Efflux and Brain Grey Matter Volume"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0334-9876","authenticated-orcid":false,"given":"John M.","family":"Giacona","sequence":"first","affiliation":[{"name":"Hypertension Section, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA"},{"name":"Department of Applied Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA"},{"name":"Cardiology Division, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2882-7520","authenticated-orcid":false,"given":"Jijia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Applied Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas, TX 75235, USA"},{"name":"Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3440-5191","authenticated-orcid":false,"given":"Brendan J.","family":"Kelley","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihab","family":"Hajjar","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3882-3251","authenticated-orcid":false,"given":"Binu P.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang F.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"de Lemos","sequence":"additional","affiliation":[{"name":"Cardiology Division, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0164-2382","authenticated-orcid":false,"given":"Anand","family":"Rohatgi","sequence":"additional","affiliation":[{"name":"Cardiology Division, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanpen","family":"Vongpatanasin","sequence":"additional","affiliation":[{"name":"Hypertension Section, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA"},{"name":"Cardiology Division, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1161\/CIRCULATIONAHA.113.004798","article-title":"Early Adult to Midlife Cardiovascular Risk Factors and Cognitive Function","volume":"129","author":"Yaffe","year":"2014","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1001\/jama.2017.3090","article-title":"Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition","volume":"317","author":"Gottesman","year":"2017","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1136\/bmj.322.7300.1447","article-title":"Midlife vascular risk factors and Alzheimer\u2019s disease in later life: Longitudinal, population based study","volume":"322","author":"Kivipelto","year":"2001","journal-title":"BMJ"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1159\/000231980","article-title":"Midlife Serum Cholesterol and Increased Risk of Alzheimer\u2019s and Vascular Dementia Three Decades Later","volume":"28","author":"Solomon","year":"2009","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1080\/00207454.2016.1182527","article-title":"Serum high-density lipoprotein is associated with better cognitive function in a cross-sectional study of aging women","volume":"127","author":"Bates","year":"2016","journal-title":"Int. J. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1017\/S1355617714000885","article-title":"Higher HDL Cholesterol Is Associated with Better Cognitive Function: The Maine-Syracuse Study","volume":"20","author":"Crichton","year":"2014","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Iqbal, G., Braidy, N., and Ahmed, T. (2020). Blood-Based Biomarkers for Predictive Diagnosis of Cognitive Impairment in a Pakistani Population. Front. Aging Neurosci., 12.","DOI":"10.3389\/fnagi.2020.00223"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1001\/jamaneurol.2013.5390","article-title":"Associations Between Serum Cholesterol Levels and Cerebral Amyloidosis","volume":"71","author":"Reed","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.neurobiolaging.2018.10.024","article-title":"Predictors of neurodegeneration differ between cognitively normal and subsequently impaired older adults","volume":"75","author":"Armstrong","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Turri, M., Marchi, C., Adorni, M.P., Calabresi, L., and Zimetti, F. (2022). Emerging role of HDL in brain cholesterol metabolism and neurodegenerative disorders. Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids, 1867.","DOI":"10.1016\/j.bbalip.2022.159123"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1159\/000519452","article-title":"Evaluation of High Cholesterol and Risk of Dementia and Cognitive Decline in Older Adults Using Individual Patient Meta-Analysis","volume":"50","author":"Peters","year":"2021","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e498","DOI":"10.1016\/S2666-7568(21)00150-1","article-title":"Blood cholesterol and risk of dementia in more than 1\u00b78 million people over two decades: A retrospective cohort study","volume":"2","author":"Iwagami","year":"2021","journal-title":"Lancet Health. Longev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Schilling, S., Tzourio, C., Soumar\u00e9, A., Kaffashian, S., Dartigues, J.-F., Ancelin, M.-L., Samieri, C., Dufouil, C., and Debette, S. (2017). Differential associations of plasma lipids with incident dementia and dementia subtypes in the 3C Study: A longitudinal, population-based prospective cohort study. PLoS Med., 14.","DOI":"10.1371\/journal.pmed.1002265"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1161\/CIRCULATIONAHA.120.044221","article-title":"HDL in the 21st Century: A Multifunctional Roadmap for Future HDL Research","volume":"143","author":"Rohatgi","year":"2021","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1056\/NEJMoa1409065","article-title":"HDL Cholesterol Efflux Capacity and Incident Cardiovascular Events","volume":"371","author":"Rohatgi","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1097\/MCA.0000000000000886","article-title":"Cholesterol efflux capacity in coronary artery disease: A meta-analysis","volume":"31","author":"Ye","year":"2020","journal-title":"Coron. Artery Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1111\/j.1474-9726.2011.00685.x","article-title":"Membrane cholesterol content plays a key role in the neurotoxicity of \u03b2-amyloid: Implications for Alzheimer\u2019s disease","volume":"10","author":"Abramov","year":"2011","journal-title":"Aging Cell"},{"key":"ref_18","first-page":"1","article-title":"ApoJ\/Clusterin concentrations are determinants of cerebrospinal fluid cholesterol efflux capacity and reduced levels are associated with Alzheimer\u2019s disease","volume":"14","author":"Ko","year":"2022","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1194\/jlr.P091033","article-title":"ABCA1- and ABCG1-mediated cholesterol efflux capacity of cerebrospinal fluid is impaired in Alzheimer\u2019s disease","volume":"60","author":"Marchi","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yassine, H.N., Feng, Q., Chiang, J., Petrosspour, L.M., Fonteh, A.N., Chui, H.C., and Harrington, M.G. (2016). ABCA1-Mediated Cholesterol Efflux Capacity to Cerebrospinal Fluid Is Reduced in Patients With Mild Cognitive Impairment and Alzheimer\u2019s Disease. J. Am. Hear. Assoc., 5.","DOI":"10.1161\/JAHA.115.002886"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1249\/MSS.0000000000000211","article-title":"Ethnic Differences in Physical Activity and Metabolic Risk","volume":"46","author":"Lakoski","year":"2014","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/j.amjcard.2004.02.058","article-title":"The Dallas Heart Study: A population-based probability sample for the multidisciplinary study of ethnic differences in cardiovascular health","volume":"93","author":"Victor","year":"2004","journal-title":"Am. J. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1194\/jlr.D018051","article-title":"A sensitive assay for ABCA1-mediated cholesterol efflux using BODIPY-cholesterol","volume":"52","author":"Sankaranarayanan","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1001\/jamaneurol.2014.3418","article-title":"Association of 3.0-T Brain Magnetic Resonance Imaging Biomarkers With Cognitive Function in the Dallas Heart Study","volume":"72","author":"Gupta","year":"2015","journal-title":"JAMA Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S173","DOI":"10.1016\/j.neuroimage.2008.10.055","article-title":"Bayesian analysis of neuroimaging data in FSL","volume":"45","author":"Woolrich","year":"2009","journal-title":"NeuroImage"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S208","DOI":"10.1016\/j.neuroimage.2004.07.051","article-title":"Advances in functional and structural MR image analysis and implementation as FSL","volume":"23","author":"Smith","year":"2004","journal-title":"NeuroImage"},{"key":"ref_27","first-page":"238","article-title":"Montreal Cognitive Assessment Performance among Community-Dwelling African Americans","volume":"32","author":"Rossetti","year":"2016","journal-title":"Arch. Clin. Neuropsychol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1161\/CIRCULATIONAHA.119.042502","article-title":"Cumulative Blood Pressure Exposure During Young Adulthood and Mobility and Cognitive Function in Midlife","volume":"141","author":"Mahinrad","year":"2020","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1161\/CIRCULATIONAHA.114.012477","article-title":"Hyperlipidemia in Early Adulthood Increases Long-Term Risk of Coronary Heart Disease","volume":"131","author":"Peterson","year":"2015","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1136\/jnnp.74.11.1530","article-title":"Serum lipids and memory in a population based cohort of middle age women","volume":"74","author":"Henderson","year":"2003","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1159\/000115847","article-title":"Plasma Lipid Levels in the Elderly Are Not Associated with the Risk of Mild Cognitive Impairment","volume":"25","author":"Reitz","year":"2008","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"S\u00e1iz-Vazquez, O., Puente-Mart\u00ednez, A., Ubillos-Landa, S., Pacheco-Bonrostro, J., and Santab\u00e1rbara, J. (2020). Cholesterol and Alzheimer\u2019s Disease Risk: A Meta-Meta-Analysis. Brain Sci., 10.","DOI":"10.3390\/brainsci10060386"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1001\/archneurol.2010.297","article-title":"Association of Higher Levels of High-Density Lipoprotein Cholesterol in Elderly Individuals and Lower Risk of Late-Onset Alzheimer Disease","volume":"67","author":"Reitz","year":"2010","journal-title":"Arch. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"705","DOI":"10.3233\/JAD-210173","article-title":"Grey Matter Loss at Different Stages of Cognitive Decline: A Role for the Thalamus in Developing Alzheimer\u2019s Disease","volume":"83","author":"Initiative","year":"2021","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/alz.12649","article-title":"The small HDL particle hypothesis of Alzheimer\u2019s disease","volume":"19","author":"Martinez","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Borr\u00e0s, C., Mercer, A., Sirisi, S., Alcolea, D., Escol\u00e0-Gil, J.C., Blanco-Vaca, F., and Tondo, M. (2022). HDL-like-Mediated Cell Cholesterol Trafficking in the Central Nervous System and Alzheimer\u2019s Disease Pathogenesis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169356"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1159\/000017234","article-title":"Cholesterol Modulates the Membrane- Disordering Effects of Beta-Amyloid Peptides in the Hippocampus: Specific Changes in Alzheimer\u2019s Disease","volume":"11","author":"Eckert","year":"2000","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wang, H., Kulas, J.A., Wang, C., Holtzman, D.M., Ferris, H.A., and Hansen, S.B. (2021). Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol. Proc. Natl. Acad. Sci. USA, 118.","DOI":"10.1073\/pnas.2102191118"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1096\/fj.00-0815fje","article-title":"Essential role for cholesterol in synaptic plasticity and neuronal degeneration","volume":"15","author":"Koudinov","year":"2001","journal-title":"FASEB J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"733","DOI":"10.3233\/JAD-200291","article-title":"Plasma High Density Lipoprotein Small Subclass is Reduced in Alzheimer\u2019s Disease Patients and Correlates with Cognitive Performance","volume":"77","author":"Pedrini","year":"2020","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_42","first-page":"001140","article-title":"What are White Matter Hyperintensities Made of?","volume":"4","author":"Wardlaw","year":"2015","journal-title":"J. Am. Hear. Assoc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.neuroimage.2004.07.006","article-title":"Global and local gray matter loss in mild cognitive impairment and Alzheimer\u2019s disease","volume":"23","author":"Karas","year":"2004","journal-title":"NeuroImage"},{"key":"ref_44","unstructured":"European Alzheimer\u2019s & Dementia Biobank Mendelian Randomization (EADB-MR) Collaboration, Luo, J., Thomassen, J.Q., Bellenguez, C., Grenier-Boley, B., de Rojas, I., Castillo, A., Parveen, K., K\u00fc\u00e7\u00fckali, F., and Nicolas, A. (2023). Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease. JAMA Netw. Open, 6."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E2172","DOI":"10.1212\/WNL.0000000000207876","article-title":"Low- and High-Density Lipoprotein Cholesterol and Dementia Risk Over 17 Years of Follow-up Among Members of a Large Health Care Plan","volume":"101","author":"Ferguson","year":"2023","journal-title":"Neurology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100140","DOI":"10.1016\/j.ynirp.2022.100140","article-title":"Longitudinal changes in grey matter and cognitive performance over four years of healthy aging","volume":"2","author":"Neufeld","year":"2022","journal-title":"Neuroimage Rep."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/20\/6218\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:15:59Z","timestamp":1760112959000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/20\/6218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,18]]},"references-count":46,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["jcm13206218"],"URL":"https:\/\/doi.org\/10.3390\/jcm13206218","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,18]]}}}