{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:35:59Z","timestamp":1790948159978,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alterations in apoptosis, as reflected by circulating Cytokeratin 18 (CK18), are involved in the progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis and atherogenesis. We aimed to explore the discriminant accuracy of Cytokeratin 18 (CK18, including M65 and M30 forms) for an elevated fatty liver index (FLI) as a validated proxy of NAFLD, and cardiovascular disease (CVD) risk in the general population. Both serum CK18 forms were measured using a commercial immunoassay in randomly selected samples from 312 participants of the PREVEND general population cohort. FLI \u2265 60 was used to indicate NAFLD. Framingham Risk Score (FRS) and the SCORE2 were used to estimate the 10-year risk of CVD. The Receiver Operating Characteristic (ROC) curve, linear\/logistic regression models, and Spearman\u2019s correlations were used. Intricate associations were found between CK18, FLI, and CVD risk scores. While M30 was the only independent predictor of FLI \u2265 60, M65 best discriminated NAFLD individuals at very-high 10-year CVD risk according to SCORE2 (AUC: 0.71; p = 0.001). Values above the predefined manufacturer cutoff (400 U\/L) were associated with an independent 5-fold increased risk (adjusted odds ratio: 5.44, p = 0.01), with a negative predictive value of 93%. Confirming that NAFLD is associated with an increased CVD risk, our results in a European general population-based cohort suggest that CK18 M65 may represent a candidate biomarker to identify NAFLD individuals at low CVD risk.<\/jats:p>","DOI":"10.3390\/biom13071128","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T08:35:47Z","timestamp":1689323747000},"page":"1128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Serum Level of Cytokeratin 18 (M65) as a Prognostic Marker of High Cardiovascular Disease Risk in Individuals with Non-Alcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7075-1182","authenticated-orcid":false,"given":"Sabrina","family":"Pagano","sequence":"first","affiliation":[{"name":"Division of Laboratory Medicine, Diagnostics Department, Geneva University Hospitals, 1205 Geneva, Switzerland"},{"name":"Department of Medicine Specialties, Medical Faculty, Geneva University, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3356-6791","authenticated-orcid":false,"given":"Stephan J. L.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Juillard","sequence":"additional","affiliation":[{"name":"Department of Medicine Specialties, Medical Faculty, Geneva University, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3844-5254","authenticated-orcid":false,"given":"Robin P. F.","family":"Dullaart","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Vuilleumier","sequence":"additional","affiliation":[{"name":"Division of Laboratory Medicine, Diagnostics Department, Geneva University Hospitals, 1205 Geneva, Switzerland"},{"name":"Department of Medicine Specialties, Medical Faculty, Geneva University, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global Burden of Nafld and Nash: Trends, Predictions, Risk Factors and Prevention","volume":"15","author":"Younossi","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1002\/hep.28785","article-title":"The Economic and Clinical Burden of Nonalcoholic Fatty Liver Disease in the United States and Europe","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"715","DOI":"10.4254\/wjh.v9.i16.715","article-title":"Non-Alcoholic Fatty Liver Disease: An Expanded Review","volume":"9","author":"Benedict","year":"2017","journal-title":"World J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/nrgastro.2013.171","article-title":"The Global Nafld Epidemic","volume":"10","author":"Loomba","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_6","first-page":"774079","article-title":"Mafld\/Nafld Biopsy-Free Scoring Systems for Hepatic Steatosis, Nash, and Fibrosis Diagnosis","volume":"8","year":"2021","journal-title":"Front. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bedogni, G., Bellentani, S., Miglioli, L., Masutti, F., Passalacqua, M., Castiglione, A., and Tiribelli, C. (2006). The Fatty Liver Index: A Simple and Accurate Predictor of Hepatic Steatosis in the General Population. BMC Gastroenterol., 6.","DOI":"10.1186\/1471-230X-6-33"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1002\/hep.22845","article-title":"Fatty Liver Is Associated with Insulin Resistance, Risk of Coronary Heart Disease, and Early Atherosclerosis in a Large European Population","volume":"49","author":"Gastaldelli","year":"2009","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"van den Berg, E.H., Amini, M., Schreuder, T.C., Dullaart, R.P., Faber, K.N., Alizadeh, B.Z., and Blokzijl, H. (2017). Prevalence and Determinants of Non-Alcoholic Fatty Liver Disease in Lifelines: A Large Dutch Population Cohort. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171502"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1002\/hep.26717","article-title":"Extrahepatic Complications of Nonalcoholic Fatty Liver Disease","volume":"59","author":"Armstrong","year":"2014","journal-title":"Hepatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/S2468-1253(21)00020-0","article-title":"Non-Alcoholic Fatty Liver Disease: A Multisystem Disease Requiring a Multidisciplinary and Holistic Approach","volume":"6","author":"Targher","year":"2021","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"van den Berg, E.H., Flores-Guerrero, J.L., Gruppen, E.G., de Borst, M.H., Wolak-Dinsmore, J., Connelly, M.A., Bakker, S.J.L., and Dullaart, R.P.F. (2019). Non-Alcoholic Fatty Liver Disease and Risk of Incident Type 2 Diabetes: Role of Circulating Branched-Chain Amino Acids. Nutrients, 11.","DOI":"10.3390\/nu11030705"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1056\/NEJMra0912063","article-title":"Risk of Cardiovascular Disease in Patients with Nonalcoholic Fatty Liver Disease","volume":"363","author":"Targher","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.jhep.2013.12.026","article-title":"Biomarkers of Liver Cell Death","volume":"60","author":"Eguchi","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S359","DOI":"10.1016\/S0753-3322(05)80078-2","article-title":"Detection of Epithelial Cell Death in the Body by Cytokeratin 18 Measurement","volume":"59","author":"Ueno","year":"2005","journal-title":"Biomed. Pharmacother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.yexcr.2004.02.019","article-title":"Keratin 8\/18 Breakdown and Reorganization During Apoptosis","volume":"297","author":"Schutte","year":"2004","journal-title":"Exp. Cell. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s00280-007-0437-4","article-title":"Qualification of M30 and M65 Elisas as Surrogate Biomarkers of Cell Death: Long Term Antigen Stability in Cancer Patient Plasma","volume":"60","author":"Cummings","year":"2007","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1038\/sj.bjc.6603129","article-title":"Docetaxel Induces Apoptosis in Hormone Refractory Prostate Carcinomas During Multiple Treatment Cycles","volume":"94","author":"Kramer","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Monserrat-Mesquida, M., Quetglas-Llabres, M., Abbate, M., Montemayor, S., Mascaro, C.M., Casares, M., Tejada, S., Abete, I., Zulet, M.A., and Tur, J.A. (2020). Oxidative Stress and Pro-Inflammatory Status in Patients with Non-Alcoholic Fatty Liver Disease. Antioxidants, 9.","DOI":"10.3390\/antiox9080759"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1002\/jcp.25779","article-title":"Novel Circulating Biomarkers for Non-Alcoholic Fatty Liver Disease: A Systematic Review","volume":"233","author":"Sahebkar","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9252536","DOI":"10.1155\/2018\/9252536","article-title":"Relationship between Serum Cytokeratin-18, Control Attenuation Parameter, Nafld Fibrosis Score, and Liver Steatosis in Nonalcoholic Fatty Liver Disease","volume":"2018","author":"Kosasih","year":"2018","journal-title":"Int. J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1432-0436.1989.tb00813.x","article-title":"High Frequency of Cytokeratin-Producing Smooth Muscle Cells in Human Atherosclerotic Plaques","volume":"40","author":"Jahn","year":"1989","journal-title":"Differentiation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1097\/MCA.0b013e328330d56a","article-title":"Serial Changes in Circulating M30 Antigen, a Biomarker of Apoptosis, in Patients with Acute Coronary Syndromes: Relationship with the Severity of Coronary Artery Disease","volume":"20","author":"Senturk","year":"2009","journal-title":"Coron. Artery Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.cca.2010.12.030","article-title":"Increased Total Cytokeratin-18 Serum and Urine Levels in Chronic Kidney Disease","volume":"412","author":"Roth","year":"2011","journal-title":"Clin. Chim. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1177\/0004563218796259","article-title":"Elevated Serum Cytokeratin-18 Concentration in Patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease","volume":"56","author":"Chang","year":"2019","journal-title":"Ann. Clin. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1038\/cdd.2013.138","article-title":"Cell Death and Diseases Related to Oxidative Stress: 4-Hydroxynonenal (Hne) in the Balance","volume":"20","author":"Dalleau","year":"2013","journal-title":"Cell. Death Differ."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1146\/annurev-med-043010-144749","article-title":"Role of Endoplasmic Reticulum Stress in Metabolic Disease and Other Disorders","volume":"63","author":"Ozcan","year":"2012","journal-title":"Annu. Rev. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3389\/fgene.2017.00021","article-title":"Metabolic Stress and Compromised Identity of Pancreatic Beta Cells","volume":"8","author":"Swisa","year":"2017","journal-title":"Front. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5198359","DOI":"10.1155\/2020\/5198359","article-title":"Elevated Serum Level of Cytokeratin 18 M65ed Is an Independent Indicator of Cardiometabolic Disorders","volume":"2020","author":"Qian","year":"2020","journal-title":"J. Diabetes Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/j.1365-2796.2010.02323.x","article-title":"Apolipoprotein B\/a-I and Total Cholesterol\/High-Density Lipoprotein Cholesterol Ratios Both Predict Cardiovascular Events in the General Population Independently of Nonlipid Risk Factors, Albuminuria and C-Reactive Protein","volume":"269","author":"Kappelle","year":"2011","journal-title":"J. Intern. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1111\/liv.14562","article-title":"Oxidative Stress Is Associated with Suspected Non-Alcoholic Fatty Liver Disease and All-Cause Mortality in the General Population","volume":"40","author":"Damba","year":"2020","journal-title":"Liver Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e13627","DOI":"10.1111\/eci.13627","article-title":"Nonalcoholic Fatty Liver Disease, Circulating Ketone Bodies and All-Cause Mortality in a General Population-Based Cohort","volume":"51","author":"Post","year":"2021","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1161\/CIRCULATIONAHA.107.699579","article-title":"General Cardiovascular Risk Profile for Use in Primary Care: The Framingham Heart Study","volume":"117","author":"Vasan","year":"2008","journal-title":"Circulation"},{"key":"ref_34","unstructured":"SCORE2 working group and ESC Cardiovascular risk collaboration (2021). Cardiovascular risk. Score2 Risk Prediction Algorithms: New Models to Estimate 10-Year Risk of Cardiovascular Disease in Europe. Eur. Heart J., 42, 2439\u20132454."},{"key":"ref_35","first-page":"417","article-title":"Practical Use of the Framingham Risk Score in Primary Prevention: Canadian Perspective","volume":"57","author":"Bosomworth","year":"2011","journal-title":"Can. Fam. Physician"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"246","DOI":"10.4162\/nrp.2012.6.3.246","article-title":"The Framingham Risk Score, Diet, and Inflammatory Markers in Korean Men with Metabolic Syndrome","volume":"6","author":"Sohn","year":"2012","journal-title":"Nutr. Res. Pract."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lee, J., Vali, Y., Boursier, J., Duffin, K., Verheij, J., Brosnan, M.J., Zwinderman, K., Anstee, Q.M., Bossuyt, P.M., and Zafarmand, M.H. (2020). Accuracy of Cytokeratin 18 (M30 and M65) in Detecting Non-Alcoholic Steatohepatitis and Fibrosis: A Systematic Review and Meta-Analysis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0238717"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"837","DOI":"10.5604\/16652681.1171767","article-title":"Correlation between Serum Cytokeratin-18 and the Progression or Regression of Non-Alcoholic Fatty Liver Disease","volume":"14","author":"Kawanaka","year":"2015","journal-title":"Ann. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/eurheartj\/ehy653","article-title":"Emerging Risk Factors, Collaboration. Equalization of Four Cardiovascular Risk Algorithms after Systematic Recalibration: Individual-Participant Meta-Analysis of 86 Prospective Studies","volume":"40","author":"Pennells","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver, European Association for the Study of Diabetes, and European Association for the Study of Obesity (2016). Easl-Easd-Easo Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease. J. Hepatol., 64, 1388\u20131402.","DOI":"10.1016\/j.jhep.2015.11.004"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"387","DOI":"10.12669\/pjms.36.3.1674","article-title":"Association of Liver Biomarkers and Cytokeratin-18 in Nonalcoholic Fatty Liver Disease Patients","volume":"36","author":"Altaf","year":"2020","journal-title":"Pak. J. Med. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s00392-020-01709-7","article-title":"Nafld and Cardiovascular Diseases: A Clinical Review","volume":"110","author":"Kasper","year":"2021","journal-title":"Clin. Res. Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1136\/gutjnl-2020-320622","article-title":"Nafld and Increased Risk of Cardiovascular Disease: Clinical Associations, Pathophysiological Mechanisms and Pharmacological Implications","volume":"69","author":"Targher","year":"2020","journal-title":"Gut"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12933-020-01025-4","article-title":"Fatty Liver Index and Development of Cardiovascular Disease in Koreans without Pre-Existing Myocardial Infarction and Ischemic Stroke: A Large Population-Based Study","volume":"19","author":"Kim","year":"2020","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.cca.2017.01.008","article-title":"Associations of the Fatty Liver and Hepatic Steatosis Indices with Risk of Cardiovascular Disease: Interrelationship with Age","volume":"466","author":"Kunutsor","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"177","DOI":"10.4103\/ajprhc.ajprhc_42_22","article-title":"Correlation of Cytokeratin-18 as a Marker of Cardiovascular Risk Assessment in Nonalcoholic Fatty Liver Disease in Nonobese and Nondiabetic Patients: Two Years Prospective Study","volume":"14","author":"Rasool","year":"2022","journal-title":"Asian J. Pharm. Res. Health Care"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Goralska, J., Razny, U., Gruca, A., Zdzienicka, A., Micek, A., Dembinska-Kiec, A., Solnica, B., and Malczewska-Malec, M. (2023). Plasma Cytokeratin-18 Fragment Level Reflects the Metabolic Phenotype in Obesity. Biomolecules, 13.","DOI":"10.3390\/biom13040675"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.jacc.2018.11.050","article-title":"Nonalcoholic Fatty Liver Disease and the Heart: Jacc State-of-the-Art Review","volume":"73","author":"Stahl","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1161\/CIRCRESAHA.118.314032","article-title":"Endothelial Sirt6 Is Vital to Prevent Hypertension and Associated Cardiorenal Injury through Targeting Nkx3.2-Gata5 Signaling","volume":"124","author":"Guo","year":"2019","journal-title":"Circ. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1006\/jmcc.1994.1115","article-title":"Hypothesis-Apoptosis May Be a Mechanism for the Transition to Heart-Failure with Chronic Pressure-Overload","volume":"26","author":"Bing","year":"1994","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1056\/NEJM199610173351603","article-title":"Apoptosis in Myocytes in End-Stage Heart Failure","volume":"335","author":"Narula","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Yang, M.C., Liu, H.K., Su, Y.T., Tsai, C.C., and Wu, J.R. (2019). Serum Apoptotic Marker M30 Is Positively Correlated with Early Diastolic Dysfunction in Adolescent Obesity. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0217429"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1097\/MCA.0000000000000416","article-title":"The Predictive Value of M30 and Oxidative Stress for Left Ventricular Remodeling in Patients with Anterior St-Segment Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention","volume":"27","author":"Turkoglu","year":"2016","journal-title":"Coron. Artery Dis."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/7\/1128\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:11:51Z","timestamp":1760127111000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/7\/1128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,14]]},"references-count":53,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["biom13071128"],"URL":"https:\/\/doi.org\/10.3390\/biom13071128","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,14]]}}}