{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T08:36:28Z","timestamp":1784363788976,"version":"3.55.0"},"reference-count":63,"publisher":"ASME International","issue":"6","license":[{"start":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T00:00:00Z","timestamp":1649980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.asme.org\/publications-submissions\/publishing-information\/legal-policies"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["194777"],"award-info":[{"award-number":["194777"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asmedigitalcollection.asme.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Higher reproductive age is associated with an increased risk of gestational diabetes, pre-eclampsia, and severe vaginal tearing during delivery. Further, menopause is associated with vaginal stiffening. However, the mechanical properties of the vagina during reproductive aging before the onset of menopause are unknown. Therefore, the first objective of this study was to quantify the biaxial mechanical properties of the nulliparous murine vagina with reproductive aging. Menopause is further associated with a decrease in elastic fiber content, which may contribute to vaginal stiffening. Hence, our second objective was to determine the effect of elastic fiber disruption on the biaxial vaginal mechanical properties. To accomplish this, vaginal samples from CD-1 mice aged 2\u201314\u2009months underwent extension-inflation testing protocols (n\u2009=\u200964 total; n\u2009=\u200916\/age group). Then, half of the samples were randomly allocated to undergo elastic fiber fragmentation via elastase digestion (n\u2009=\u200932 total; 8\/age group) to evaluate the role of elastic fibers. The material stiffness increased with reproductive age in both the circumferential and axial directions within the control and elastase-treated vaginas. The vagina demonstrated anisotropic mechanical behavior, and anisotropy increased with age. In summary, vaginal remodeling with reproductive age included increased direction-dependent material stiffness, which further increased following elastic fiber disruption. Further work is needed to quantify vaginal remodeling during pregnancy and postpartum with reproductive aging to better understand how age-related vaginal remodeling may contribute to an increased risk of vaginal tearing.<\/jats:p>","DOI":"10.1115\/1.4054362","type":"journal-article","created":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T08:31:48Z","timestamp":1650011508000},"update-policy":"https:\/\/doi.org\/10.1115\/crossmarkpolicy-asme","source":"Crossref","is-referenced-by-count":10,"title":["Biaxial Murine Vaginal Remodeling With Reproductive Aging"],"prefix":"10.1115","volume":"144","author":[{"given":"Shelby E.","family":"White","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Tulane University , 6823\u2009St Charles Ave, New Orleans, LA 70118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine X.","family":"Kiley","sequence":"additional","affiliation":[{"name":"Department of Biology, Tulane University , 6823\u2009St Charles Ave, New Orleans, LA 70118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna","family":"Visniauskas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Tulane University , 1430 Tulane Ave, New Orleans, LA 70118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah H.","family":"Lindsey","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Tulane University , 1430 Tulane Ave, New Orleans, LA 70118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin S.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tulane University , 6823\u2009St Charles Ave, New Orleans, LA 70118"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"33","published-online":{"date-parts":[[2022,4,22]]},"reference":[{"issue":"1","key":"2023042200103607500_bib1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1117\/1.JBO.19.1.016004","article-title":"Label-Free Photoacoustic Microscopy of Peripheral Nerves","volume":"19","year":"2014","journal-title":"J. Biomed. Optics"},{"issue":"4","key":"2023042200103607500_bib2","first-page":"451.e451","article-title":"The Association Between Maternal Age at First Delivery and Risk of Obstetric Trauma","volume":"215","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"4","key":"2023042200103607500_bib3","doi-asserted-by":"crossref","first-page":"948","DOI":"10.2337\/diacare.29.04.06.dc05-2568","article-title":"Maternal Age and Prevalence of Gestational Diabetes Mellitus","volume":"29","year":"2006","journal-title":"Diabetes Care"},{"issue":"9","key":"2023042200103607500_bib4","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/ajh.2011.95","article-title":"Maternal Age During Pregnancy is Associated With Third Trimester Blood Pressure Level: The Generation R Study","volume":"24","year":"2011","journal-title":"Am. J. Hypertens."},{"issue":"1","key":"2023042200103607500_bib5","first-page":"44","article-title":"Maternal Factors in Predicting Low Birth Weight Babies","volume":"68","year":"2013","journal-title":"Med. J. Malays."},{"issue":"8","key":"2023042200103607500_bib6","first-page":"CD001500","article-title":"Local Oestrogen for Vaginal Atrophy in Postmenopausal Women","volume":"2016","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"issue":"1","key":"2023042200103607500_bib7","first-page":"46","article-title":"Management of Post-Menopausal Vaginal Atrophy and Atrophic Vaginitis","volume":"52","year":"2005","journal-title":"Maturitas"},{"issue":"2","key":"2023042200103607500_bib8","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1093\/cvr\/cvr195","article-title":"Mechanical Assessment of Elastin Integrity in Fibrillin-1-Deficient Carotid Arteries: Implication for Marfan Syndrome","volume":"92","year":"2011","journal-title":"Cardiovasc. Res."},{"issue":"3","key":"2023042200103607500_bib9","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.ajog.2003.08.040","article-title":"Impact of Menopause on Collagen Subtypes in the Arcus Tendineous Fasciae Pelvis","volume":"190","year":"2004","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"1","key":"2023042200103607500_bib10","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/GME.0000000000001166","article-title":"The Histological Microstructure and In Vitro Mechanical Properties of Pregnant and Postmenopausal Ewe Perineal Body","volume":"26","year":"2019","journal-title":"Menopause (NY)"},{"issue":"1","key":"2023042200103607500_bib11","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/GME.0000000000001209","article-title":"The Mysteries of Menopause and Urogynecologic Health: Clinical and Scientific Gaps","volume":"26","year":"2019","journal-title":"Menopause"},{"issue":"7","key":"2023042200103607500_bib12","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1097\/GME.0000000000000840","article-title":"Vaginal Estrogen: A Dual-Edged Sword in Postoperative Healing of the Vaginal Wall","volume":"24","year":"2017","journal-title":"North Am. Menopause Soc."},{"issue":"2","key":"2023042200103607500_bib13","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1258\/002367793780810397","article-title":"Genetic Variation Within and Between Strains of Outbred Swiss Mice","volume":"27","year":"1993","journal-title":"Lab Anim."},{"key":"2023042200103607500_bib14","first-page":"327","article-title":"A Longitudinal Study of Estrous Cyclicity in Aging C57\/6J Mice: Cycle, Frequency, Length, and Vaginal Cytology","year":"1982","journal-title":"Biol. Reprod."},{"issue":"1","key":"2023042200103607500_bib15","first-page":"244","article-title":"Men and Mice: Relating Their Ages","volume":"152","year":"2016","journal-title":"Life Sci."},{"key":"2023042200103607500_bib16","volume-title":"The Mouse in Biomedical Research","year":"2007"},{"issue":"6","key":"2023042200103607500_bib17","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1113\/JP273350","article-title":"Effect of Reproductive Ageing on Pregnant Mouse Uterus and Cervix: Effect of Reproductive Ageing on Pregnant Uterus and Cervix","volume":"595","year":"2017","journal-title":"J. Physiol."},{"issue":"5743","key":"2023042200103607500_bib18","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/283157a0","article-title":"Genetic Variance of Laboratory Outbred Swiss Mice","volume":"283","year":"1980","journal-title":"Nature"},{"issue":"11","key":"2023042200103607500_bib19","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1038\/ng1665","article-title":"The Origins and Uses of Mouse Outbred Stocks","volume":"37","year":"2005","journal-title":"Nat. Genet."},{"issue":"12","key":"2023042200103607500_bib20","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1007\/s00192-007-0387-8","article-title":"Vaginal Pressure During Lifting, Floor Exercises, Jogging, and Use of Hydraulic Exercise Machines","volume":"18","year":"2007","journal-title":"Int. Urogynecol. J."},{"issue":"2","key":"2023042200103607500_bib21","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s001920200019","article-title":"Biomechanical Properties of Prolapsed Vaginal Tissue in Pre- and Postmenopausal Women","volume":"13","year":"2002","journal-title":"Int. Urogynecol. J. Pelvic Floor Dysfunct."},{"issue":"5","key":"2023042200103607500_bib22","first-page":"590.e591","article-title":"Biomechanical Properties of the Vaginal Wall: Effect of Pregnancy, Elastic Fiber Deficiency, and Pelvic Organ Prolapse","volume":"198","year":"2008","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"3","key":"2023042200103607500_bib23","first-page":"317","article-title":"Prediction of Nonlinear Elastic Behavior of Vaginal Tissue: Experimental Results and Model Formation","volume":"13","year":"2010","journal-title":"Comput. Methods Biomech. Biomed. Eng."},{"issue":"1","key":"2023042200103607500_bib24","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1007\/s10439-018-02117-9","article-title":"Anisotropy of the Passive and Active Rat Vagina Under Biaxial Loading","volume":"47","year":"2019","journal-title":"Ann. Biomed. Eng."},{"issue":"1","key":"2023042200103607500_bib25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3109\/03008209109006992","article-title":"Three-Dimensional Structures of Uterine Elastic Fibers: Scanning Electron Microscopic Studies","volume":"27","year":"1991","journal-title":"Connect. Tissue Res."},{"issue":"4","key":"2023042200103607500_bib26","first-page":"305","article-title":"Tissue Elasticity and the Ageing Elastic Fibre","volume":"31","year":"2009","journal-title":"Off. J. Am. Aging Assoc."},{"issue":"3","key":"2023042200103607500_bib27","first-page":"621","article-title":"Aging Might Increase Myocardial Ischemia\/Reperfusion-Induced Apoptosis in Humans and Rats","volume":"34","year":"2012","journal-title":"Off. J. Am. Aging Assoc."},{"issue":"4","key":"2023042200103607500_bib28","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00192-008-0737-1","article-title":"Changes in Connective Tissue in Patients With Pelvic Organ Prolapse-a Review of the Current Literature","volume":"20","year":"2009","journal-title":"Int. Urogynecol. J."},{"issue":"2","key":"2023042200103607500_bib29","article-title":"Effects of Elastase Digestion on the Murine Vaginal Wall Biaxial Mechanical Response","volume":"141","year":"2019","journal-title":"ASME J. Biomech. Eng."},{"issue":"4","key":"2023042200103607500_bib30","doi-asserted-by":"crossref","first-page":"20190025","DOI":"10.1098\/rsfs.2019.0025","article-title":"Smooth Muscle Regional Contribution to Vaginal Wall Function","volume":"9","year":"2019","journal-title":"Interface Focus"},{"issue":"4","key":"2023042200103607500_bib31","first-page":"484","article-title":"Failure of Elastin or Collagen as Possible Critical Connective Tissue Alterations Underlying Aneurysmal Dilatation","volume":"2","year":"1994","journal-title":"Cardiovas. Surg."},{"issue":"6","key":"2023042200103607500_bib32","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1161\/HYPERTENSIONAHA.113.01177","article-title":"Body Fat is Associated With Reduced Aortic Stiffness Until Middle Age","volume":"61","year":"2013","journal-title":"Hypertension"},{"issue":"4","key":"2023042200103607500_bib33","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s00192-014-2525-4","article-title":"Influence of Body Mass Index on the Biomechanical Properties of the Human Prolapsed Anterior Vaginal Wall","volume":"26","year":"2015","journal-title":"Int. Urogynecol. J."},{"issue":"4","key":"2023042200103607500_bib34","doi-asserted-by":"crossref","first-page":"e35538","DOI":"10.1371\/journal.pone.0035538","article-title":"Mouse Estrous Cycle Identification Tool and Images","volume":"7","year":"2012","journal-title":"PLoS ONE"},{"key":"2023042200103607500_bib35","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jbiomech.2019.07.011","article-title":"Biaxial Biomechanical Properties of the Nonpregnant Murine Cervix and Uterus","volume":"94","year":"2019","journal-title":"J. Biomech."},{"issue":"10","key":"2023042200103607500_bib36","doi-asserted-by":"crossref","first-page":"104504","DOI":"10.1115\/1.4037559","article-title":"Biaxial Mechanical Assessment of the Murine Vaginal Wall Using Extension-Inflation Testing","volume":"139","year":"2017","journal-title":"ASME J. Biomech. Eng."},{"issue":"108","key":"2023042200103607500_bib37","doi-asserted-by":"crossref","first-page":"20150280","DOI":"10.1098\/rsif.2015.0280","article-title":"Quantification of the Passive and Active Biaxial Mechanical Behavior and Microstructural Organization of Rat Thoracic Ducts","volume":"12","year":"2015","journal-title":"R. Soc. Interface"},{"issue":"6","key":"2023042200103607500_bib38","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s00192-006-0214-7","article-title":"Biomechanical Properties of Prolapsed Vaginal Tissue in Pre- and Postmenopausal Women","volume":"18","year":"2007","journal-title":"Int. Urogynecol. J."},{"issue":"5","key":"2023042200103607500_bib39","doi-asserted-by":"crossref","first-page":"051008","DOI":"10.1115\/1.4032938","article-title":"Reduced Biaxial Contractility in the Descending Thoracic Aorta of Fibulin-5 Deficent Mice","volume":"138","year":"2016","journal-title":"ASME J. Biomech. Eng."},{"issue":"60","key":"2023042200103607500_bib40","article-title":"Mechanical Testing of Mouse Carotid Arteries: From Newborn to Adult","year":"2012","journal-title":"J. Vis. Exp."},{"issue":"7","key":"2023042200103607500_bib41","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1007\/s10439-013-0799-1","article-title":"Biomechanical Phenotyping of Central Arteries in Health and Disease: Advantages of and Methods for Murine Models","volume":"41","year":"2013","journal-title":"Ann. Biomed. Eng."},{"issue":"10","key":"2023042200103607500_bib42","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1007\/s00192-010-1183-4","article-title":"Ultrasound Measurement of Vaginal Wall Thickness: A Novel and Reliable Technique","volume":"21","year":"2010","journal-title":"Int. Urogynecol. J."},{"key":"2023042200103607500_bib43","volume-title":"Cardiovascular Solid Mechanics: Cells, Tissues, and Organs","year":"2002"},{"issue":"3","key":"2023042200103607500_bib44","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1007\/s12265-012-9349-8","article-title":"Elastin in Large Artery Stiffness and Hypertension","volume":"5","year":"2012","journal-title":"J. Cardiovas. Transl. Res."},{"issue":"2","key":"2023042200103607500_bib45","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1037\/a0022658","article-title":"Effect Size Measures for Mediation Models: Quantitative Strategies for Communicating Indirect Effects","volume":"16","year":"2011","journal-title":"Psychol. Methods"},{"key":"2023042200103607500_bib46","doi-asserted-by":"crossref","first-page":"109436","DOI":"10.1016\/j.jbiomech.2019.109436","article-title":"Age-Associated Changes in the Mechanical Properties of Human Cadaveric Pelvic Floor Muscles","volume":"98","year":"2020","journal-title":"J. Biomech."},{"issue":"11","key":"2023042200103607500_bib47","doi-asserted-by":"crossref","first-page":"e13259","DOI":"10.1111\/acel.13259","article-title":"Ovarian Stiffness Increases With Age in the Mammalian Ovary and Depends on Collagen and Hyaluronan Matrices","volume":"19","year":"2020","journal-title":"Aging Cell"},{"issue":"3","key":"2023042200103607500_bib48","first-page":"245","article-title":"Reproductive Age-Associated Fibrosis in the Stroma of the Mammalian Ovary","volume":"152","year":"2016","journal-title":"Reproduction (Cambridge, UK)"},{"issue":"3","key":"2023042200103607500_bib49","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1158\/1078-0432.CCR-19-0603","article-title":"Metformin Abrogates Age-Associated Ovarian Fibrosis","volume":"26","year":"2020","journal-title":"Clin. Cancer Res."},{"issue":"1","key":"2023042200103607500_bib50","first-page":"134","article-title":"Factors Associated With Increased Intra-Abdominal Pressure in Patients Undergoing Cardiac Surgery","volume":"28","year":"2020","journal-title":"T\u00fcrk G\u00f6\u011f\u00fcs Kalp Damar Cerrahisi Dergisi"},{"issue":"4","key":"2023042200103607500_bib51","first-page":"228","article-title":"Postmenopausal Vaginal Atrophy and Atrophic Vaginitis","volume":"314","year":"1997","journal-title":"Am. J. Med. Sci."},{"issue":"Suppl","key":"2023042200103607500_bib52","first-page":"31S","article-title":"Sexuality and Menopause","volume":"75","year":"1990","journal-title":"Obstet. Gynecol."},{"issue":"2","key":"2023042200103607500_bib53","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/j.1464-410X.2007.06998.x","article-title":"Elastin Expression and Elastic Fibre Width in the Anterior Vaginal Wall of Postmenopausal Women With and Without Prolapse","volume":"100","year":"2007","journal-title":"BJU Int."},{"issue":"1","key":"2023042200103607500_bib54","doi-asserted-by":"crossref","first-page":"12354","DOI":"10.1038\/s41598-019-48527-0","article-title":"Effect of Protease Inhibitors in Healing of the Vaginal Wall","volume":"9","year":"2019","journal-title":"Sci. Rep."},{"issue":"5","key":"2023042200103607500_bib55","first-page":"512.e511","article-title":"Pelvic Muscles' Mechanical Response to Strains in the Absence and Presence of Pregnancy-Induced Adaptations in a Rat Model","volume":"218","year":"2018","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"2","key":"2023042200103607500_bib56","first-page":"191.e191","article-title":"Pregnancy-Induced Adaptations in the Intrinsic Structure of Rat Pelvic Floor Muscles","volume":"213","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"2023042200103607500_bib57","article-title":"Uncovering Changes in Proteomic Signature of Rat Pelvic Floor Muscles in Pregnancy","volume-title":"Am. J. Obstet. Gynecol.","year":"2019"},{"issue":"4","key":"2023042200103607500_bib58","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.repbio.2017.09.001","article-title":"The Decline of Pregnancy Rate and Abnormal Uterine Responsiveness of Steroid Hormones in Aging Mice","volume":"17","year":"2017","journal-title":"Reprod. Biol."},{"issue":"5","key":"2023042200103607500_bib59","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1111\/j.1365-2133.2004.06203.x","article-title":"Ovariectomy is Sufficient to Accelerate Spontaneous Skin Ageing and to Stimulate Ultraviolet Irradiation-Induced Photoageing of Murine Skin","volume":"151","year":"2004","journal-title":"Br. J. Dermatol. (1951)"},{"issue":"C","key":"2023042200103607500_bib60","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.artres.2016.04.001","article-title":"Loss of Elastic Fiber Integrity Compromises Common Carotid Artery Function: Implications for Vascular Aging","volume":"14","year":"2016","journal-title":"Artery Res."},{"issue":"2","key":"2023042200103607500_bib61","first-page":"210.e211","article-title":"Pregnancy-Induced Adaptations in Intramuscular Extracellular Matrix of Rat Pelvic Floor Muscles","volume":"215","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"12","key":"2023042200103607500_bib62","doi-asserted-by":"crossref","first-page":"121008","DOI":"10.1115\/1.4052365","article-title":"Investigation of Murine Vaginal Creep Response to Altered Mechanical Loads","volume":"143","year":"2021","journal-title":"ASME J. Biomech. Eng."},{"issue":"1","key":"2023042200103607500_bib63","doi-asserted-by":"crossref","first-page":"20956","DOI":"10.1038\/s41598-021-00351-1","article-title":"Role of Fibulin-5 Insufficiency and Prolapse Progression on Murine Vaginal Biomechanical Function","volume":"11","year":"2021","journal-title":"Sci. Rep."}],"container-title":["Journal of Biomechanical Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/asmedigitalcollection.asme.org\/biomechanical\/article-pdf\/144\/6\/061010\/6873622\/bio_144_06_061010.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/asmedigitalcollection.asme.org\/biomechanical\/article-pdf\/144\/6\/061010\/6873622\/bio_144_06_061010.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T01:35:23Z","timestamp":1700444123000},"score":1,"resource":{"primary":{"URL":"https:\/\/asmedigitalcollection.asme.org\/biomechanical\/article\/144\/6\/061010\/1140227\/Biaxial-Murine-Vaginal-Remodeling-With"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,22]]},"references-count":63,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6,1]]}},"URL":"https:\/\/doi.org\/10.1115\/1.4054362","relation":{},"ISSN":["0148-0731","1528-8951"],"issn-type":[{"value":"0148-0731","type":"print"},{"value":"1528-8951","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,22]]},"article-number":"061010"}}