{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:42:32Z","timestamp":1772152952089,"version":"3.50.1"},"reference-count":59,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Several studies suggest the complex relationship between Endothelin-1 (ET-1) levels with various types of glaucoma. This systematic review and meta-analysis explore ET-1 levels in plasma and aqueous humor among different types of glaucoma. Materials and Methods: A literature search (PubMed, ScienceDirect, Cochrane Library) was made up to April 2024 (PROSPERO: CRD42023430471). The results were synthesized according to PRISMA Guidelines. Results were presented as standardized mean differences (SMD) with 95% confidence intervals (CI). Results: A total of 2597 subjects (1513 patients with glaucoma vs. 1084 healthy controls) from 23 studies were included in a meta-analysis. Notably, patients with glaucoma reported significantly higher plasma levels of ET-1 compared to controls (SMD: 1.21, 95% CI: 0.59\u20131.82, p &lt; 0.001). Particularly, plasma ET-1 levels were higher in primary open-angle glaucoma (POAG) (SMD: 0.87, 95% CI: 0.09\u20131.65, p &lt; 0.05), normal-tension glaucoma (SMD: 0.86, 95% CI: 0.27\u20131.46, p = 0.05), and angle-closure glaucoma patients (SMD: 1.03, 95% CI: 0.43\u20131.63, p &lt; 0.001) compared to healthy controls. Moreover, ET-1 aqueous humor levels were significantly higher in patients with glaucoma compared to controls (SMD: 1.60, 95% CI: 1.04\u20132.15, p &lt; 0.001). In particular, aqueous humor levels were higher in POAG patients (SMD: 2.03 95% CI: 1.00\u20133.14, p &lt; 0.001), and pseudoexfoliative glaucoma patients (SMD: 2.03, 95% CI: 1.00\u20133.07, p &lt; 0.001) compared to controls. Conclusions: This meta-analysis indicates that elevated levels of ET-1 plasma and aqueous humor are significantly associated with different types of glaucoma. The pathogenesis of ET-1-related mechanisms may vary across different glaucoma types, indicating that possible therapeutic approaches targeting ET-1 pathways should be tailored to each specific glaucoma type.<\/jats:p>","DOI":"10.3390\/medicina60071117","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T13:34:38Z","timestamp":1720618478000},"page":"1117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Endothelin-1 Plasma and Aqueous Humor Levels in Different Types of Glaucoma: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6481-0000","authenticated-orcid":false,"given":"Stamatios","family":"Lampsas","sequence":"first","affiliation":[{"name":"Second Department of Ophthalmology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2912-7438","authenticated-orcid":false,"given":"Stylianos A.","family":"Kandarakis","sequence":"additional","affiliation":[{"name":"First Department of Ophthalmology, \u201cG. Gennimatas\u201d Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0204-8919","authenticated-orcid":false,"given":"Dionysios G.","family":"Vakalopoulos","sequence":"additional","affiliation":[{"name":"First Department of Ophthalmology, \u201cG. Gennimatas\u201d Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aikaterini","family":"Lampsa","sequence":"additional","affiliation":[{"name":"Second Department of Ophthalmology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evangelos","family":"Oikonomou","sequence":"additional","affiliation":[{"name":"Third Department of Cardiology, Thoracic Diseases General Hospital Sotiria, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerasimos","family":"Siasos","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Harvard Medical School, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George D.","family":"Kymionis","sequence":"additional","affiliation":[{"name":"First Department of Ophthalmology, \u201cG. Gennimatas\u201d Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1136\/bjo.86.2.238","article-title":"The definition and classification of glaucoma in prevalence surveys","volume":"86","author":"Foster","year":"2002","journal-title":"Br. J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/bs.pbr.2015.04.007","article-title":"Emerging risk factors for glaucoma onset and progression","volume":"221","author":"Blumberg","year":"2015","journal-title":"Prog. Brain Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1097\/ICU.0000000000000245","article-title":"Vascular and autonomic dysregulation in primary open-angle glaucoma","volume":"27","author":"Pasquale","year":"2016","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S51","DOI":"10.1016\/S0039-6257(99)00026-0","article-title":"Potential role of nitric oxide and endothelin in the pathogenesis of glaucoma","volume":"43","author":"Haefliger","year":"1999","journal-title":"Surv. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1076\/ceyr.16.7.687.5065","article-title":"Effects of endothelin-1 (ET-1) on ocular hemodynamics","volume":"16","author":"Schmetterer","year":"1997","journal-title":"Curr. Eye Res."},{"key":"ref_7","first-page":"864","article-title":"Endothelin-1 contributes to hyperoxia-induced vasoconstriction in the human retina","volume":"41","author":"Dallinger","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_8","first-page":"103","article-title":"Localization of endothelin-1 mRNA expression and immunoreactivity in the anterior segment of human eye: Expression of ETA and ETB receptors","volume":"9","author":"Rollin","year":"2003","journal-title":"Mol. Vis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1001\/archopht.120.3.348","article-title":"Partial antagonism of endothelin 1-induced vasoconstriction in the human choroid by topical unoprostone isopropyl","volume":"120","author":"Polska","year":"2002","journal-title":"Arch. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S0009-9236(98)90121-7","article-title":"Reversal of endothelin-1-induced ocular hemodynamic effects by low-dose nifedipine in humans","volume":"63","author":"Strenn","year":"1998","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1089\/jop.2012.0198","article-title":"Black currant anthocyanins normalized abnormal levels of serum concentrations of endothelin-1 in patients with glaucoma","volume":"29","author":"Yoshida","year":"2013","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1089\/jop.1996.12.75","article-title":"Effects of endothelin-1 on optic nerve head blood flow in cats","volume":"12","author":"Nishimura","year":"1996","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_13","first-page":"1081","article-title":"Effects of endothelin-1 and flunarizine on human trabecular meshwork cell contraction","volume":"231","author":"Cellini","year":"2006","journal-title":"Exp. Biol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s10654-010-9491-z","article-title":"Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses","volume":"25","author":"Stang","year":"2010","journal-title":"Eur. J. Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wan, X., Wang, W., Liu, J., and Tong, T. (2014). Estimating the sample mean and standard deviation from the sample size, median, range and\/or interquartile range. BMC Med. Res. Methodol., 14.","DOI":"10.1186\/1471-2288-14-135"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1097\/IJG.0000000000000553","article-title":"Klotho and Endothelin-1 in Pseudoexfoliation Syndrome and Glaucoma","volume":"25","author":"Ahoor","year":"2016","journal-title":"J. Glaucoma"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1600-0420.1997.tb00448.x","article-title":"Color Doppler imaging and plasma levels of endothelin-1 in low-tension glaucoma","volume":"75","author":"Cellini","year":"1997","journal-title":"Acta Ophthalmol. Scand. Suppl."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.lfs.2012.02.013","article-title":"Endothelin-1 plasma levels and vascular endothelial dysfunction in primary open angle glaucoma","volume":"91","author":"Cellini","year":"2012","journal-title":"Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1097\/IJG.0b013e31822e8c65","article-title":"Association between plasma endothelin-1 and severity of different types of glaucoma","volume":"22","author":"Chen","year":"2013","journal-title":"J. Glaucoma"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7336","DOI":"10.1167\/iovs.12-10216","article-title":"Correlation of endothelin-1 concentration in aqueous humor with intraocular pressure in primary open angle and pseudoexfoliation glaucoma","volume":"53","author":"Choritz","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4467","DOI":"10.1167\/iovs.10-6710","article-title":"Systemic vascular dysregulation and retrobulbar hemodynamics in normal-tension glaucoma","volume":"52","author":"Galassi","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1159\/000323584","article-title":"Endothelin-1 and nitric oxide levels in patients with glaucoma","volume":"46","author":"Ghanem","year":"2011","journal-title":"Ophthalmic Res."},{"key":"ref_24","first-page":"105","article-title":"Cold pressor test and plasma endothelin-1 concentration in primary open-angle and capsular glaucoma","volume":"7","author":"Hollo","year":"1998","journal-title":"J. Glaucoma"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"287","DOI":"10.3109\/02713680903545315","article-title":"Aqueous humor endothelin-1 (Et-1), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) levels in Mexican glaucomatous patients","volume":"35","author":"Iwabe","year":"2010","journal-title":"Curr. Eye Res."},{"key":"ref_26","first-page":"5542","article-title":"Correlations of TIMP2 and TIMP3 gene polymorphisms with primary open-angle glaucoma","volume":"23","author":"Ji","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1007\/BF00183429","article-title":"Endothelin-1 plasma levels in normal-tension glaucoma: Abnormal response to postural changes","volume":"233","author":"Kaiser","year":"1995","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1136\/bjo.2003.028290","article-title":"Endothelin-1 concentration is increased in the aqueous humour of patients with exfoliation syndrome","volume":"88","author":"Koliakos","year":"2004","journal-title":"Br. J. Ophthalmol."},{"key":"ref_29","first-page":"905","article-title":"Age dependence of plasma endothelin levels in glaucoma patients","volume":"71","author":"Konieczka","year":"2020","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.2147\/OPTH.S155551","article-title":"Retrobulbar hemodynamics and aqueous humor levels of endothelin-1 in exfoliation syndrome and exfoliation glaucoma","volume":"12","author":"Koukoula","year":"2018","journal-title":"Clin. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1080\/02713680600837382","article-title":"Plasma endothelin-1 level in Japanese normal tension glaucoma patients","volume":"31","author":"Kunimatsu","year":"2006","journal-title":"Curr. Eye Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.3109\/02713683.2012.725798","article-title":"Analysis of systemic endothelin-1, matrix metalloproteinase-9, macrophage chemoattractant protein-1, and high-sensitivity C-reactive protein in normal-tension glaucoma","volume":"37","author":"Lee","year":"2012","journal-title":"Curr. Eye Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11801","DOI":"10.1038\/s41598-022-15401-5","article-title":"Elevated endothelin-1 levels as risk factor for an impaired ocular blood flow measured by OCT-A in glaucoma","volume":"12","author":"Lommatzsch","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s10792-014-9979-8","article-title":"Endothelin-1 levels and biomarkers of oxidative stress in glaucoma patients","volume":"35","author":"Villalba","year":"2015","journal-title":"Int. Ophthalmol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1167\/iovs.02-0913","article-title":"Effects of cold-induced vasospasm in glaucoma: The role of endothelin-1","volume":"44","author":"Nicolela","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/BF00947082","article-title":"Endothelin-like immunoreactivity in aqueous humor of patients with primary open-angle glaucoma and cataract","volume":"235","author":"Noske","year":"1997","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Pinazo-Duran, M.D., Zanon-Moreno, V., Garcia-Villanueva, C., Martucci, A., Peris-Martinez, C., Vila-Arteaga, J., Garcia-Medina, J.J., Andres-Blasco, I., Gallego-Martinez, A., and Nucci, C. (2023). Biochemical-molecular-genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patients. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1157773"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1097\/IJG.0b013e3182312047","article-title":"Aqueous vascular endothelial growth factor and endothelin-1 levels in branch retinal vein occlusion associated with normal tension glaucoma","volume":"22","author":"Sin","year":"2013","journal-title":"J. Glaucoma"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1016\/S0039-6257(05)80073-6","article-title":"Association of endothelin-1 with normal tension glaucoma: Clinical and fundamental studies","volume":"39","author":"Sugiyama","year":"1995","journal-title":"Surv. Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2678017","DOI":"10.1155\/2016\/2678017","article-title":"Elevated Plasma Endothelin-1 Levels in Normal Tension Glaucoma and Primary Open-Angle Glaucoma: A Meta-Analysis","volume":"2016","author":"Li","year":"2016","journal-title":"J. Ophthalmol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e3055","DOI":"10.1097\/MD.0000000000003055","article-title":"Association Between Peripheral Vascular Endothelial Function and Progression of Open-Angle Glaucoma","volume":"95","author":"Liu","year":"2016","journal-title":"Medicine"},{"key":"ref_42","first-page":"201","article-title":"Investigation into the vasospastic mechanisms in the pathogenesis of glaucomatous neuropathy","volume":"113","year":"2011","journal-title":"Klin. Oczna"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1001\/2013.jamaophthalmol.1","article-title":"Primary open-angle glaucoma vs normal-tension glaucoma: The vascular perspective","volume":"131","author":"Mroczkowska","year":"2013","journal-title":"JAMA Ophthalmol."},{"key":"ref_44","first-page":"568","article-title":"Vascular reactivity of optic nerve head and retinal blood vessels in glaucoma\u2014A review","volume":"17","author":"Venkataraman","year":"2010","journal-title":"Microcirculation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1089\/jop.2011.0081","article-title":"Peak intraocular pressure and glaucomatous progression in primary open-angle glaucoma","volume":"28","author":"Konstas","year":"2012","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"337","DOI":"10.4103\/ijo.IJO_330_17","article-title":"Evaluating ocular blood flow","volume":"65","author":"Maram","year":"2017","journal-title":"Indian. J. Ophthalmol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100036","DOI":"10.1016\/j.aopr.2022.100036","article-title":"Role of ocular blood flow in normal tension glaucoma","volume":"2","author":"Wu","year":"2022","journal-title":"Adv. Ophthalmol. Pract. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/APO.0000000000000183","article-title":"Ocular Blood Flow and Influencing Factors for Glaucoma","volume":"5","author":"Nakazawa","year":"2016","journal-title":"Asia Pac. J. Ophthalmol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/j.1440-1681.1995.tb02008.x","article-title":"Endothelin-1 and the regulation of vascular tone","volume":"22","author":"La","year":"1995","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/FJC.0b013e31826f32c1","article-title":"Endothelin(A)-endothelin(B) receptor cross talk in endothelin-1-induced contraction of smooth muscle","volume":"60","author":"Rapoport","year":"2012","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.metabol.2014.04.007","article-title":"Metabolic syndrome and endothelin-1 mediated vasoconstrictor tone in overweight\/obese adults","volume":"63","author":"Rocha","year":"2014","journal-title":"Metabolism"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1097\/IJG.0000000000000106","article-title":"The trabecular meshwork in normal eyes and in exfoliation glaucoma","volume":"23","author":"Rasmussen","year":"2014","journal-title":"J. Glaucoma"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.exer.2009.01.008","article-title":"Connective tissue growth factor induces extracellular matrix deposition in human trabecular meshwork cells","volume":"88","author":"Junglas","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Nordahl, K.M.L., Fedulov, V., Holm, A., and Haanes, K.A. (2023). Intraocular Adeno-Associated Virus-Mediated Transgene Endothelin-1 Delivery to the Rat Eye Induces Functional Changes Indicative of Retinal Ischemia-A Potential Chronic Glaucoma Model. Cells, 12.","DOI":"10.3390\/cells12151987"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3571","DOI":"10.1038\/s41598-020-60558-6","article-title":"Endothelin-1 Mediated Decrease in Mitochondrial Gene Expression and Bioenergetics Contribute to Neurodegeneration of Retinal Ganglion Cells","volume":"10","author":"Chaphalkar","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1007\/s10792-023-02733-y","article-title":"The effect of ET1-CTGF mediated pathway on the accumulation of extracellular matrix in the trabecular meshwork and its contribution to the increase in IOP","volume":"43","author":"Wang","year":"2023","journal-title":"Int. Ophthalmol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Lu, R., Soden, P.A., and Lee, E. (2020). Tissue-Engineered Models for Glaucoma Research. Micromachines, 11.","DOI":"10.3390\/mi11060612"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"107996","DOI":"10.1016\/j.exer.2020.107996","article-title":"Magnesium acetyltaurate protects against endothelin-1 induced RGC loss by reducing neuroinflammation in Sprague dawley rats","volume":"194","author":"Agarwal","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1080\/02713683.2018.1467933","article-title":"Effect of Magnesium Acetyltaurate and Taurine on Endothelin1-Induced Retinal Nitrosative Stress in Rats","volume":"43","author":"Agarwal","year":"2018","journal-title":"Curr. Eye Res."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/7\/1117\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:12:41Z","timestamp":1760109161000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/7\/1117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,10]]},"references-count":59,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["medicina60071117"],"URL":"https:\/\/doi.org\/10.3390\/medicina60071117","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,10]]}}}