{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:23:29Z","timestamp":1760059409063,"version":"build-2065373602"},"reference-count":62,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glycation is known as an important factor inducing human diseases, including diabetic complications. As oxidative stress contributes to procedures of glycation, antioxidants may inhibit glycation and delay the progression of diabetic complications. Our previous investigation of human aqueous humor after the intake of a lutein-containing supplement demonstrated increases in antioxidative activities and decreases in peroxidative products. This study enrolled 25 patients with diabetes (DM group) and 100 age-matched controls. Aqueous humor samples were collected during cataract surgery before and after 6 weeks of oral intake of the lutein-containing antioxidant supplement, Ocuvite + Lutein\u00ae. The carboxymethyl-lysine level (CML) was measured as an indicator of glycation. Levels of superoxide dismutase activities (SOD) and total hydroperoxide (TH) were measured as indicators of oxidation. Changes after intake and the differences between age-matched controls and the DM group were evaluated. CML decreased after intake among the DM group, while there were no changes among the age-matched controls. SOD was significantly lower and TH was significantly higher in the DM group as compared to the age-matched controls, both before and after intake. In line with the decreases in glycation, the intake of lutein-containing antioxidant supplements may inhibit diabetic complications in diabetic patients.<\/jats:p>","DOI":"10.3390\/ijms26125706","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T09:51:22Z","timestamp":1750067482000},"page":"5706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effects of Lutein-Containing Supplement Intake on Glycation Inhibition Among Diabetic Patients with Cataracts"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1575-3967","authenticated-orcid":false,"given":"Rijo","family":"Hayashi","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Saitama Medical Center, Dokkyo Medical University, Koshigaya 343-8555, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shimmin","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Saitama Medical Center, Dokkyo Medical University, Koshigaya 343-8555, Saitama, Japan"},{"name":"Lively Eye Clinic, Soka 340-0053, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeki","family":"Machida","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Saitama Medical Center, Dokkyo Medical University, Koshigaya 343-8555, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"ref_1","unstructured":"Vision Loss Expert Group of the Global Burden of Disease Study (2021). Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: The Right to Sight: An analysis for the Global Burden of Disease Study. Lancet Glob. Health, 9, e144\u2013e160."},{"key":"ref_2","unstructured":"Ministry of Health, Labour and Welfare (2024, June 30). Overview of National Medical Expenditures 2021, Available online: www.mhlw.go.jp\u203a toukei\u203a saikin\u203a k-iryohi\u203a data."},{"key":"ref_3","first-page":"1303","article-title":"The oxidative stress in the cataract formation","volume":"99","author":"Obara","year":"1995","journal-title":"Nippon. Ganka Gakkai Zasshi"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/S0021-5155(97)00030-0","article-title":"Pathophysiology of cataracts: Copper ion and peroxidation in diabetics","volume":"41","author":"Lin","year":"1997","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.exer.2004.12.007","article-title":"Age-related nuclear cataract-oxidation is the key","volume":"80","author":"Truscott","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9310","DOI":"10.12659\/MSM.917869","article-title":"Protective effect of \u03b2-glucogallin on damaged cataract against methylglyoxal induced oxidative stress in cultured lens epithelial cells","volume":"25","author":"Ma","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wojnar, W., Zych, M., Borymski, S., and Kaczmarczyl-Sedlak, I. (2020). Chrysin reduces oxidative stress but does not affect polyol pathway in the lenses of type 1 diabetic rats. Antioxidants, 9.","DOI":"10.3390\/antiox9020160"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1084\/jem.150.5.1098","article-title":"Nonenzymatic glycosylation, sulfhydryl oxidation and aggregation of lens proteins in experimental sugar cataracts","volume":"150","author":"Monnier","year":"1979","journal-title":"J. Exp. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0014-4835(87)80011-8","article-title":"Progressive changes in lens crystallin glycation and high-molecular-weight aggregate formation leading to cataract development in streptozotocin-diabetic rats","volume":"44","author":"Perry","year":"1987","journal-title":"Exp. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20781","DOI":"10.1074\/jbc.270.35.20781","article-title":"Role of glycine 1 and lysine 2 in the glycation of bovine gamma B-crystallin. Site-directed mutagenesis of lysine to threonine","volume":"270","author":"Casey","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1042\/BJ20070989","article-title":"Effect of glycation on alpha-crystallin structure and chaperone-like function","volume":"408","author":"Kumar","year":"2007","journal-title":"Biochem. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.exer.2018.08.017","article-title":"Too sweet: Problems of protein glycation in the eye","volume":"178","author":"Bejarano","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1196\/annals.1338.066","article-title":"The Maillard reaction in eye diseases","volume":"1043","author":"Stitt","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1432-1033.1994.00001.x","article-title":"Structure and modifications of the junior chaperone alpha-crystallin. From lens transparency to molecular pathology","volume":"225","author":"Groenen","year":"1994","journal-title":"Eur. J. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.2337\/diacare.22.9.1543","article-title":"Serum levels of advanced glycation end products are increased in patients with type 2 diabetes and coronary heart disease","volume":"22","author":"Kilhovd","year":"1999","journal-title":"Diabetes Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/S1262-3636(07)70006-X","article-title":"N(carboxymethyl)lysine as a biomarker for microvascular complications in type 2 diabetic patients","volume":"29","author":"Wautier","year":"2003","journal-title":"Diabetes Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/0014-5793(96)00142-1","article-title":"The presence of a glucose-derived Maillard reaction product in the human lens","volume":"382","author":"Nagaraj","year":"1996","journal-title":"FEBS Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9464","DOI":"10.1021\/bi00450a033","article-title":"Oxidation of glycated proteins: Age-dependent accumulation of N-(carboxymethyl) lysine in lens proteins","volume":"28","author":"Dunn","year":"1989","journal-title":"Biochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1023\/A:1007015416572","article-title":"Advanced glycation end products in human senile and diabetic cataractous lenses","volume":"210","author":"Zarina","year":"2000","journal-title":"Mol. Cell. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/s00417-002-0616-2","article-title":"Advanced glycation endproducts in human diabetic and non-diabetic cataractous lenses","volume":"241","author":"Pokupec","year":"2003","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Franke, S., Dawczynski, J., Strobel, J., Niwa, T., Stahl, P., and Stein, G. (2003). Increased levels of advanced glycation end products in human cataractous lenses. J. Cataract. Refract. Surg., 29.","DOI":"10.1016\/S0886-3350(02)01841-2"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s11357-010-9177-1","article-title":"Advanced glycation end products in diabetic and non-diabetic human subjects suffering from cataract","volume":"33","author":"Hashim","year":"2011","journal-title":"Age"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1753-4887.1989.tb02848.x","article-title":"Associations between nutrition and cataract","volume":"47","author":"Taylor","year":"1989","journal-title":"Nutr. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0748-5514(86)80010-1","article-title":"Delay of UV-induced eye lens protein damage in guinea pigs by dietary ascorbate","volume":"2","author":"Blondin","year":"1986","journal-title":"J. Free Radic. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e170","DOI":"10.1111\/aos.12688","article-title":"Association of vitamin C with the risk of age-related cataract: A meta-analysis","volume":"94","author":"Wei","year":"2016","journal-title":"Acta Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.freeradbiomed.2008.06.019","article-title":"The non-provitamin A carotenoid, lutein, inhibits HF-kappaB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase\/PTEN\/Akt and NF-kappaB-inducing kinase pathway: Role of H2O2 in NF-kappaB activation","volume":"45","author":"Kim","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1001\/archopht.126.3.354","article-title":"Association between age- related nuclear cataract and lutein and zeaxanthin in the diet and serum in the carotenoid in the Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women\u2019s Health Initiative","volume":"126","author":"Moeller","year":"2008","journal-title":"Arch Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1001\/archopht.126.1.102","article-title":"Dietary carotenoids, vitamins C and, D.; and risk of cataract in women: A prospective study","volume":"126","author":"Christen","year":"2008","journal-title":"Arch Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/ajcn\/nqy270","article-title":"Dietary vitamin and carotenoid intake and risk of age-related cataract","volume":"109","author":"Jiang","year":"2019","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.exer.2014.10.009","article-title":"The gender-differentiated antioxidant effects of a lutein-containing supplement in the aqueous humor of patients with senile cataracts","volume":"129","author":"Hayashi","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1126\/science.1355616","article-title":"Protein oxidation and aging","volume":"257","author":"Stadtman","year":"1992","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/35041687","article-title":"Oxidants, oxidative stress and the biology of ageing","volume":"408","author":"Finkel","year":"2000","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1093\/gerona\/62.4.427","article-title":"Circulating glycotoxins and dietary advanced glycation endproducts: Two links to inflammatory response, oxidative stress, and aging","volume":"62","author":"Uribarri","year":"2007","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1161\/CIRCULATIONAHA.105.581397","article-title":"Glycated proteins stimulate reactive oxygen species production in cardiac myocytes: Involvement of Nox2 (gp91phox)-containing NADPH oxidase","volume":"113","author":"Zhang","year":"2006","journal-title":"Circulation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.jhep.2009.12.007","article-title":"Advanced glycation end products induce production of reactive oxygen species via the activation of NADPH oxidase in murine hepatic stellate cells","volume":"52","author":"Guimaraes","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.diabet.2012.01.003","article-title":"Advanced glycation end-products induce injury to pancreatic beta cells through oxidative stress","volume":"38","author":"Lin","year":"2012","journal-title":"Diabetes Metab."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Moldogazieva, N.T., Mokhosoev, I.M., Mel\u2019nikova, T.I., Porozov, Y.B., and Terentiev, A.A. (2019). Oxidative stress and advanced lipoxidation and glycation end products (ALEs and AGEs) in aging and age-related diseases. Oxidative Med. Cell. Longev., 2019.","DOI":"10.1155\/2019\/3085756"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2337\/db09-0801","article-title":"Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands","volume":"59","author":"Yao","year":"2010","journal-title":"Diabetes"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.exer.2012.01.001","article-title":"Effects of antioxidant supplementation on mRNA expression of glucose-6-phosphate dehydrogenase, \u03b2-actin and 18S rRNA in the anterior capsule of the lens in cataract patients","volume":"96","author":"Hayashi","year":"2012","journal-title":"Exp. Eye Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.exer.2018.01.001","article-title":"Gender differences in mRNA expression of aquaporin 8 and glutathione peroxidase in cataractous lens following intake of an antioxidant supplement","volume":"168","author":"Hayashi","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0886-3350(02)01524-9","article-title":"Advanced glycation end-products in anterior chamber aqueous of cataractous patients","volume":"29","author":"Franke","year":"2003","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Chitra, P.S., Chaki, D., Boiroju, N.K., Mokalla, T.R., Gadde, A.K., Agraharam, S.G., and Reddy, G.B. (2020). Status of oxidative stress markers, advanced glycation index, and polyol pathway in age-related cataract subjects with and without diabetes. Exp. Eye Res., 200.","DOI":"10.1016\/j.exer.2020.108230"},{"key":"ref_43","first-page":"593","article-title":"Erythrocyte aldose reductase activity and sorbitol levels in diabetic retinopathy","volume":"14","author":"Reddy","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_44","first-page":"132","article-title":"Correlation between vitreous advanced glycation end products, and D-dimer with blood HbA1c levels in proliferative diabetic retinopathy","volume":"50","author":"Loho","year":"2018","journal-title":"Acta Medica Indones."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Hirai, T., Fujiyoshi, K., Yamada, S., Matsumoto, T., Kikuchi, J., Ishida, K., Ishida, M., Yamaoka-Tojo, M., Inomata, T., and Shigeta, K. (2022). Advanced glycation end products are associated with diabetes status and physical functions inpatients with cardiovascular disease. Nutrients, 14.","DOI":"10.3390\/nu14153032"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Christidis, G., K\u00fcppers, F., Karatayli, S.C., Karatayli, E., Weber, S.N., Lammert, F., and Krawczyk, M. (2024). Skin advanced glycation end-products as indicators of the metabolic profile in diabetes mellitus: Correlations with glycemic control, liver phenotypes and metabolic biomarkers. BMC Endocr. Disord., 24.","DOI":"10.1186\/s12902-024-01558-9"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.2353\/ajpath.2007.061281","article-title":"Reduced oxidant stress and extended lifespan in mice exposed to a low glycotoxin diet: Association with increased AGER1 expression","volume":"170","author":"Cai","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1159\/000517573","article-title":"Changes in macular pigment optical density among pseudophakic patients following intake of a lutein-containing supplement","volume":"64","author":"Hayashi","year":"2021","journal-title":"Ophthalmic Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0960-0760(93)90166-T","article-title":"Antioxidant properties of steroids","volume":"45","author":"Mooradian","year":"1993","journal-title":"Steroid Biochem. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1097\/00042192-200107000-00009","article-title":"Influence of estrogen replacement therapy on plasma lipid peroxidation","volume":"8","author":"Hinchado","year":"2001","journal-title":"Menopause"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0009-3084(00)00120-1","article-title":"Antioxidant activities of estrogens against aqueous and lipophilic radicals; differences between phenol and catechol estrogens","volume":"105","author":"Navarro","year":"2000","journal-title":"Chem. Phys. Lipids"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/j.1474-9726.2005.00151.x","article-title":"17\u03b2-Oestradiol up-regulates longevity-related, antioxidant enzyme expression via the ERK1 and ERK2(MAPK)\/NF\u03baB cascade","volume":"4","author":"Borras","year":"2005","journal-title":"Aging Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"9748","DOI":"10.1073\/pnas.85.24.9748","article-title":"Antioxidant defences and lipid peroxidation in human blood plasma","volume":"85","author":"Frei","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1056\/NEJM198604033141407","article-title":"New concepts in the biology and biochemistry of ascorbic acid","volume":"314","author":"Levine","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1096\/fasebj.1.6.3315807","article-title":"Free radical tissue damage: Protective role of antioxidant nutrients","volume":"1","author":"Machlin","year":"1987","journal-title":"FASEB J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/S0891-5849(02)00831-6","article-title":"Photoprotective potential of lycopene, beta-carotene, vitamin, E.; vitamin C and carnosic acid in UVA-irradiated human skin fibroblasts","volume":"32","author":"Offord","year":"2002","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1432-1033.1988.tb14105.x","article-title":"The protection by ascorbate and glutathione against microsomal lipid peroxidation is dependent on vitamin, E","volume":"174","author":"Wefers","year":"1988","journal-title":"Eur. J. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1001\/archopht.1991.01080020090051","article-title":"The lens opacities case-control study risk factors for cataract","volume":"109","author":"Leske","year":"1991","journal-title":"Arch. Ophthalmol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"788","DOI":"10.2105\/AJPH.84.5.788","article-title":"The use of vitamin supplements and the risk of cataract among US male physician","volume":"84","author":"Seddon","year":"1994","journal-title":"Am. J. Public Health"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1136\/bmj.305.6866.1392","article-title":"Serum antioxidants vitamins and risk of cataract","volume":"305","author":"Knekt","year":"1992","journal-title":"Br. Med. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1080\/02713683.2022.2059811","article-title":"Changes in aqueous humor lutein levels of patients with cataracts after a 6-week course of lutein-containing antioxidant supplementation","volume":"47","author":"Hayashi","year":"2022","journal-title":"Curr. Eye Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1001\/archopht.1993.01090060119035","article-title":"The lens opacities classification system III. The longitudinal study of cataract study group","volume":"111","author":"Chylack","year":"1993","journal-title":"Arch Ophthalmol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5706\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:51:55Z","timestamp":1760032315000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5706"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,13]]},"references-count":62,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125706"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125706","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,6,13]]}}}