{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:43:40Z","timestamp":1790671420953,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["1RO1EY023557-01"],"award-info":[{"award-number":["1RO1EY023557-01"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30 EY001583"],"award-info":[{"award-number":["P30 EY001583"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001205","name":"F. 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Kirby Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100001205","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UPenn Hospital Board of Women Visitors","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Paul and Evanina Bell Mackall Foundation Trust","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100009857","name":"Regeneron (United States)","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100009857","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>(1) Background: Vertical cup-to-disc ratio (CDR) is an important measure for evaluating damage to the optic nerve head (ONH) in glaucoma patients. However, this measure often does not fully capture the irregular cupping observed in glaucomatous nerves. We developed and evaluated a method to measure cup-to-disc ratio (CDR) at all 360 degrees of the ONH. (2) Methods: Non-physician graders from the Scheie Reading Center outlined the cup and disc on digital stereo color disc images from African American patients enrolled in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. After converting the resultant coordinates into polar representation, the CDR at each 360-degree location of the ONH was obtained. We compared grader VCDR values with clinical VCDR values, using Spearman correlation analysis, and validated significant genetic associations with clinical VCDR, using grader VCDR values. (3) Results: Graders delineated outlines of the cup contour and disc boundaries twice in each of 1815 stereo disc images. For both cases and controls, the mean CDR was highest at the horizontal bisector, particularly in the temporal region, as compared to other degree locations. There was a good correlation between grader CDR at the vertical bisector and clinical VCDR (Spearman Correlation OD: r = 0.78 [95% CI: 0.76\u20130.79]). An SNP in the MPDZ gene, associated with clinical VCDR in a prior genome-wide association study, showed a significant association with grader VCDR (p = 0.01) and grader CDR area ratio (p = 0.02). (4) Conclusions: The CDR of both glaucomatous and non-glaucomatous eyes varies by degree location, with the highest measurements in the temporal region of the eye. This method can be useful for capturing innate eccentric ONH morphology, tracking disease progression, and identifying genetic associations.<\/jats:p>","DOI":"10.3390\/genes12121961","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T21:46:58Z","timestamp":1639086418000},"page":"1961","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Precise Method to Evaluate 360 Degree Measures of Optic Cup and Disc Morphology in an African American Cohort and Its Genetic Applications"],"prefix":"10.3390","volume":"12","author":[{"given":"Victoria","family":"Addis","sequence":"first","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Zorger","sequence":"additional","affiliation":[{"name":"Penn Vision Research Center, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Salowe","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebenezer","family":"Daniel","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Lee","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxwell","family":"Pistilli","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinpeng","family":"Gao","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen G.","family":"Maguire","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian","family":"Chan","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harini V.","family":"Gudiseva","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selam","family":"Zenebe-Gete","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayaka","family":"Merriam","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli J.","family":"Smith","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Revell","family":"Martin","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candace","family":"Parker Ostroff","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Gee","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi N.","family":"Cui","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eydie","family":"Miller-Ellis","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan M.","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prithvi S.","family":"Sankar","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16067","DOI":"10.1038\/nrdp.2016.67","article-title":"Primary open-angle glaucoma","volume":"2","author":"Weinreb","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/S0140-6736(10)61423-7","article-title":"Glaucoma","volume":"377","author":"Quigley","year":"2011","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1001\/archopht.1982.01030030137016","article-title":"Optic nerve damage in human glaucoma. III. Quantitative correlation of nerve fiber loss and visual field defect in glaucoma, ischemic neuropathy, papilledema, and toxic neuropathy","volume":"100","author":"Quigley","year":"1982","journal-title":"Arch. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1001\/archopht.1991.01080010079037","article-title":"Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous field loss","volume":"109","author":"Sommer","year":"1991","journal-title":"Arch. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1001\/archopht.120.6.701","article-title":"The Ocular Hypertension Treatment Study: A randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma","volume":"120","author":"Kass","year":"2002","journal-title":"Arch. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/1471-2415-14-118","article-title":"Use of the structure-function relationship in detecting glaucoma progression in early glaucoma","volume":"14","author":"Hirooka","year":"2014","journal-title":"BMC Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/jnr.10198","article-title":"Synucleins in glaucoma: Implication of \u03b3-synuclein in glaucomatous alterations in the optic nerve","volume":"68","author":"Surgucheva","year":"2002","journal-title":"J. Neurosci. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1109\/TMI.2013.2247770","article-title":"Superpixel classification based optic disc and optic cup segmentation for glaucoma screening","volume":"32","author":"Cheng","year":"2013","journal-title":"IEEE Trans. Med. Imaging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/j.1475-1313.1993.tb00495.x","article-title":"Optic disc interpretation in glaucoma: Is confidence misplaced?","volume":"13","author":"Montgomery","year":"1993","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_10","first-page":"79","article-title":"Analytic methods in assessment of optic nerve cupping","volume":"70","author":"Jindra","year":"2014","journal-title":"Cesk. Slov. Oftalmol."},{"key":"ref_11","first-page":"3309","article-title":"Changing views on open-angle glaucoma: Definitions and prevalences--The Rotterdam Study","volume":"41","author":"Wolfs","year":"2000","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1001\/archopht.1980.01020041024003","article-title":"Alternative definitions of open-angle glaucoma. Effect on prevalence and associations in the Framingham eye study","volume":"98","author":"Kahn","year":"1980","journal-title":"Arch. Ophthalmol."},{"key":"ref_13","first-page":"532","article-title":"Variability of expert observers in evaluating the optic disc","volume":"74","author":"Lichter","year":"1976","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1016\/S0161-6420(94)31118-3","article-title":"Agreement among optometrists, ophthalmologists, and residents in evaluating the optic disc for glaucoma","volume":"101","author":"Abrams","year":"1994","journal-title":"Ophthalmology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1046\/j.1475-1313.2000.00528.x","article-title":"Observer variability in optic disc assessment, implications for glaucoma shared care","volume":"20","author":"Harper","year":"2000","journal-title":"Ophthalmic. Physiol. Opt."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/S0002-9394(01)01254-5","article-title":"Agreement among clinicians in the recognition of patterns of optic disk damage in glaucoma","volume":"132","author":"Nicolela","year":"2001","journal-title":"Am. J. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.ophtha.2009.09.026","article-title":"Clinical assessment of stereoscopic optic disc photographs for glaucoma, the European Optic Disc Assessment Trial","volume":"117","author":"Reus","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0161-6420(92)31990-6","article-title":"Expert agreement in evaluating the optic disc for glaucoma","volume":"99","author":"Varma","year":"1992","journal-title":"Ophthalmology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/S0161-6420(88)33177-5","article-title":"Intraobserver and interobserver agreement in measurement of optic disc characteristics","volume":"95","author":"Tielsch","year":"1988","journal-title":"Ophthalmology"},{"key":"ref_20","first-page":"177","article-title":"The Advanced Glaucoma Intervention Study (AGIS): 10. Variability among academic glaucoma subspecialists in assessing optic disc notching","volume":"99","author":"Gaasterland","year":"2001","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.ophtha.2010.08.019","article-title":"Agreement and accuracy of non-expert ophthalmologists in assessing glaucomatous changes in serial stereo optic disc photographs","volume":"118","author":"Breusegem","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/s41433-018-0332-8","article-title":"Non-physician grader reliability in measuring morphological features of the optic nerve head in stereo digital images","volume":"33","author":"Addis","year":"2019","journal-title":"Eye"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.ophtha.2011.09.045","article-title":"Trends in use of ancillary glaucoma tests for patients with open-angle glaucoma from 2001 to 2009","volume":"119","author":"Stein","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.ophtha.2016.01.041","article-title":"Can Automated Imaging for Optic Disc and Retinal Nerve Fiber Layer Analysis Aid Glaucoma Detection?","volume":"123","author":"Banister","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_25","first-page":"2266","article-title":"Level-set based automatic cup-to-disc ratio determination using retinal fundus images in ARGALI","volume":"2008","author":"Wong","year":"2008","journal-title":"Conf. Proc. IEEE Eng. Med. Biol. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5348","DOI":"10.1167\/iovs.06-0579","article-title":"Automated analysis of heidelberg retina tomograph optic disc images by glaucoma probability score","volume":"47","author":"Coops","year":"2006","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1016\/S0161-6420(98)98047-2","article-title":"Identification of early glaucoma cases with the scanning laser ophthalmoscope","volume":"105","author":"Wollstein","year":"1998","journal-title":"Ophthalmology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1097\/IJG.0000000000000155","article-title":"Cup-to-Disc Ratio From Heidelberg Retina Tomograph 3 and High-Definition Optical Coherence Tomography Agrees Poorly With Clinical Assessment","volume":"25","author":"Perera","year":"2016","journal-title":"J. Glaucoma"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1167\/iovs.06-1081","article-title":"Automated segmentation of the optic disc from stereo color photographs using physiologically plausible features","volume":"48","author":"Abramoff","year":"2007","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.cmpb.2010.04.006","article-title":"Automated segmentation of optic disc region on retinal fundus photographs: Comparison of contour modeling and pixel classification methods","volume":"101","author":"Muramatsu","year":"2011","journal-title":"Comput. Methods Programs Biomed."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1109\/TMI.2010.2053042","article-title":"Detecting the optic disc boundary in digital fundus images using morphological, edge detection, and feature extraction techniques","volume":"29","author":"Aquino","year":"2010","journal-title":"IEEE Trans. Med. Imaging."},{"key":"ref_32","first-page":"2626","article-title":"Model-based optic nerve head segmentation on retinal fundus images","volume":"2011","author":"Yin","year":"2011","journal-title":"Conf. Proc. IEEE Eng. Med. Biol. Soc."},{"key":"ref_33","first-page":"75","article-title":"Optic disc and cup segmentation from color fundus photograph using graph cut with priors","volume":"16","author":"Zheng","year":"2013","journal-title":"Med. Image. Comput. Comput. Assist. Interv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.ophtha.2014.11.015","article-title":"The primary open-angle african american glaucoma genetics study: Baseline demographics","volume":"122","author":"Charlson","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1097\/IJG.0b013e3181e87f20","article-title":"Presence of an optic disc notch and glaucoma","volume":"24","author":"Healey","year":"2015","journal-title":"J Glaucoma."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gudiseva, H.V., Verma, S.S., and Chavali, V.R.M. (2020). Genome wide-association study identifies novel loci in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. bioRxiv, 968156, [Preprint].","DOI":"10.1101\/2020.02.27.968156"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1093\/hmg\/ddr463","article-title":"Identification of four novel variants that influence central corneal thickness in multi-ethnic Asian populations","volume":"21","author":"Cornes","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/09286586.2017.1320413","article-title":"Tutorial on Biostatistics: Statistical Analysis for Correlated Binary Eye Data","volume":"25","author":"Ying","year":"2018","journal-title":"Ophthalmic. Epidemiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1080\/09286586.2016.1259636","article-title":"Tutorial on Biostatistics: Linear Regression Analysis of Continuous Correlated Eye Data","volume":"24","author":"Ying","year":"2017","journal-title":"Ophthalmic. Epidemiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1111\/j.1755-3768.1976.tb01801.x","article-title":"The variation and covariation of cup and disc diameters","volume":"54","author":"Bengtsson","year":"1976","journal-title":"Acta Ophthalmol"},{"key":"ref_41","first-page":"1151","article-title":"Optic disc, cup and neuroretinal rim size, configuration and correlations in normal eyes","volume":"29","author":"Jonas","year":"1988","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1001\/jama.1991.03470030069026","article-title":"Racial variations in the prevalence of primary open-angle glaucoma. The Baltimore Eye Survey","volume":"266","author":"Tielsch","year":"1991","journal-title":"JAMA."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1167\/iovs.07-0866","article-title":"Estimating the rate of progressive visual field damage in those with open-angle glaucoma, from cross-sectional data","volume":"49","author":"Broman","year":"2008","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1001\/archopht.124.11.1579","article-title":"The ISNT rule and differentiation of normal from glaucomatous eyes","volume":"124","author":"Harizman","year":"2006","journal-title":"Arch. Ophthalmol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"MacCormick, I.J.C., Williams, B.M., and Zheng, Y. (2019). Accurate, fast, data efficient and interpretable glaucoma diagnosis with automated spatial analysis of the whole cup to disc profile. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0215056"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/12\/1961\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:44:14Z","timestamp":1760168654000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/12\/1961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,9]]},"references-count":45,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["genes12121961"],"URL":"https:\/\/doi.org\/10.3390\/genes12121961","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,9]]}}}