{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:09:24Z","timestamp":1780391364968,"version":"3.54.1"},"reference-count":41,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["JP21ek0109524"],"award-info":[{"award-number":["JP21ek0109524"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JST FOREST Program"},{"name":"JSPS KAKENHI","award":["20K08859"],"award-info":[{"award-number":["20K08859"]}]},{"name":"JSPS KAKENHI","award":["19K07427"],"award-info":[{"award-number":["19K07427"]}]},{"DOI":"10.13039\/501100005694","name":"Hori Sciences and Arts Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005694","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Toyoaki Scholarship Foundation"},{"DOI":"10.13039\/100015120","name":"Daiko Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015120","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nitto Foundation"},{"DOI":"10.13039\/100007434","name":"Suzuken Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007434","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008965","name":"Takahashi Industrial and Economic Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008965","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Prolactin (PRL), a hormone involved in lactation, is mainly produced and secreted by the lactotrophs of the anterior pituitary (AP) gland. We previously reported a method to generate functional adrenocorticotropic hormone-producing cells by differentiating the AP and hypothalamus simultaneously from human induced pluripotent stem cells (iPSCs). However, PRL-producing cells in the induced AP have not been investigated. Here, we confirmed the presence of PRL-producing cells and evaluated their endocrine functions. We differentiated pituitary cells from human iPSCs using serum-free floating culture of embryoid-like aggregates with quick reaggregation (SFEB-q) method and evaluated the appearance and function of PRL-producing cells. Secretion of PRL from the differentiated aggregates was confirmed, which increased with further culture. Fluorescence immunostaining and immunoelectron microscopy revealed PRL-producing cells and PRL-positive secretory granules, respectively. PRL secretion was promoted by various prolactin secretagogues such as thyrotropin-releasing hormone, vasoactive intestinal peptide, and prolactin-releasing peptide, and inhibited by bromocriptine. Moreover, the presence of tyrosine hydroxylase-positive dopaminergic nerves in the hypothalamic tissue area around the center of the aggregates connecting to PRL-producing cells indicated the possibility of recapitulating PRL regulatory mechanisms through the hypothalamus. In conclusion, we generated pituitary lactotrophs from human iPSCs; these displayed similar secretory responsiveness as human pituitary cells in vivo. In the future, this is expected to be used as a model of human PRL-producing cells for various studies, such as drug discovery, prediction of side effects, and elucidation of tumorigenic mechanisms using disease-specific iPSCs. Furthermore, it may help to develop regenerative medicine for the pituitary gland.<\/jats:p>","DOI":"10.1210\/endocr\/bqac004","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T17:11:42Z","timestamp":1643303502000},"source":"Crossref","is-referenced-by-count":6,"title":["Functional Lactotrophs in Induced Adenohypophysis Differentiated From Human iPS Cells"],"prefix":"10.1210","volume":"163","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4539-4798","authenticated-orcid":false,"given":"Natsuki","family":"Miyake","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1924-7639","authenticated-orcid":false,"given":"Hidetaka","family":"Suga","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Osuka","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takatoshi","family":"Kasai","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayu","family":"Sakakibara","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Soen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Miwata","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyoshi","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayuko","family":"Kano","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Muraoka","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuki","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Miyata","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Onoue","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Hagiwara","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-0337","authenticated-orcid":false,"given":"Shintaro","family":"Iwama","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Iwase","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Inoshita","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo 173-0015, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Arima","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0493-1825","authenticated-orcid":false,"given":"Hiroaki","family":"Kajiyama","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2022,1,27]]},"reference":[{"issue":"2","key":"2022020820053006200_CIT0001","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1210\/jc.2010-1692","article-title":"Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline","volume":"96","author":"Melmed","year":"2011","journal-title":"J Clin Endocrinol Metab."},{"issue":"4","key":"2022020820053006200_CIT0002","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1007\/BF03346292","article-title":"Acquired prolactin deficiency in patients with disorders of the hypothalamic-pituitary axis","volume":"30","author":"Toledano","year":"2007","journal-title":"J Endocrinol Invest."},{"issue":"10","key":"2022020820053006200_CIT0003","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1210\/jc.2013-2411","article-title":"Isolated prolactin deficiency associated with serum autoantibodies against prolactin-secreting cells","volume":"98","author":"Iwama","year":"2013","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2022020820053006200_CIT0004","doi-asserted-by":"crossref","first-page":"ORSFc1","DOI":"10.1167\/iovs.15-18681","article-title":"Subretinal transplantation of embryonic stem cell-derived retinal pigment epithelium for the treatment of macular degeneration: an assessment at 4 years","volume":"57","author":"Schwartz","year":"2016","journal-title":"Invest Ophthalmol Vis Sci."},{"issue":"11","key":"2022020820053006200_CIT0005","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1056\/NEJMoa1608368","article-title":"Autologous induced stem-cell\u2013derived retinal cells for macular degeneration","volume":"376","author":"Mandai","year":"2017","journal-title":"N Engl J Med."},{"issue":"1","key":"2022020820053006200_CIT0006","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1038\/s41467-020-17165-w","article-title":"Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson\u2019s disease","volume":"11","author":"Doi","year":"2020","journal-title":"Nat Commun."},{"issue":"1","key":"2022020820053006200_CIT0007","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/cr.2012.171","article-title":"Cell transplantation therapies for spinal cord injury focusing on induced pluripotent stem cells","volume":"23","author":"Nakamura","year":"2013","journal-title":"Cell Res."},{"issue":"33","key":"2022020820053006200_CIT0008","doi-asserted-by":"crossref","first-page":"11796","DOI":"10.1073\/pnas.0803078105","article-title":"Minimization of exogenous signals in ES cell culture induces rostral hypothalamic differentiation","volume":"105","author":"Wataya","year":"2008","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"7375","key":"2022020820053006200_CIT0009","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature10637","article-title":"Self-formation of functional adenohypophysis in three-dimensional culture","volume":"480","author":"Suga","year":"2011","journal-title":"Nature."},{"issue":"7","key":"2022020820053006200_CIT0010","doi-asserted-by":"crossref","first-page":"10351","DOI":"10.1038\/ncomms10351","article-title":"Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells","author":"Ozone","year":"2016","journal-title":"Nat Commun."},{"issue":"1","key":"2022020820053006200_CIT0011","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.celrep.2019.12.009","article-title":"Hypothalamic contribution to pituitary functions is recapitulated in vitro using 3D-cultured human iPS cells","volume":"30","author":"Kasai","year":"2020","journal-title":"Cell Rep."},{"issue":"5","key":"2022020820053006200_CIT0012","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.stem.2008.09.002","article-title":"Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals","volume":"3","author":"Eiraku","year":"2008","journal-title":"Cell Stem Cell."},{"issue":"5","key":"2022020820053006200_CIT0013","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/j.celrep.2013.10.048","article-title":"Specification of functional cranial placode derivatives from human pluripotent stem cells","volume":"5","author":"Dincer","year":"2013","journal-title":"Cell Rep."},{"issue":"6","key":"2022020820053006200_CIT0014","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.stemcr.2016.05.005","article-title":"Derivation of diverse hormone-releasing pituitary cells from human pluripotent stem cells","volume":"6","author":"Zimmer","year":"2016","journal-title":"Stem Cell Rep."},{"issue":"5","key":"2022020820053006200_CIT0015","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell."},{"key":"2022020820053006200_CIT0016"},{"key":"2022020820053006200_CIT0017"},{"key":"2022020820053006200_CIT0018"},{"key":"2022020820053006200_CIT0019"},{"key":"2022020820053006200_CIT0020"},{"key":"2022020820053006200_CIT0021"},{"key":"2022020820053006200_CIT0022"},{"key":"2022020820053006200_CIT0023"},{"key":"2022020820053006200_CIT0024"},{"key":"2022020820053006200_CIT0025"},{"key":"2022020820053006200_CIT0026"},{"issue":"4","key":"2022020820053006200_CIT0027","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1152\/physrev.2000.80.4.1523","article-title":"Prolactin: structure, function, and regulation of secretion","volume":"80","author":"Freeman","year":"2000","journal-title":"Physiol Rev."},{"issue":"6682","key":"2022020820053006200_CIT0028","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/30515","article-title":"A prolactin-releasing peptide in the brain","volume":"393","author":"Hinuma","year":"1998","journal-title":"Nature."},{"issue":"8","key":"2022020820053006200_CIT0029","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1111\/j.1365-2826.2007.01567.x","article-title":"Thyrotrophin-releasing hormone, vasoactive intestinal peptide, prolactin-releasing peptide and dopamine regulation of prolactin secretion by different lactotroph morphological subtypes in the rat","volume":"19","author":"Christian","year":"2007","journal-title":"J Neuroendocrinol."},{"issue":"3","key":"2022020820053006200_CIT0030","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s00795-018-0180-4","article-title":"Characteristics of pericytes in diethylstilbestrol (DES)-induced pituitary prolactinoma in rats","volume":"51","author":"Jindatip","year":"2018","journal-title":"Med Mol Morphol."},{"issue":"5","key":"2022020820053006200_CIT0031","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1530\/ERC-18-0409","article-title":"mPRs represent a novel target for PRL inhibition in experimental prolactinomas","volume":"26","author":"Camilletti","year":"2019","journal-title":"Endocr Relat Cancer."},{"issue":"2","key":"2022020820053006200_CIT0032","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1530\/JOE-19-0326","article-title":"Activin-inhibitory action on lactotrophs is decreased in lactotroph hyperplasia","volume":"244","author":"Faraoni","year":"2020","journal-title":"J Endocrinol."},{"issue":"11 Pt 2","key":"2022020820053006200_CIT0033","first-page":"5722","article-title":"Establishment and characterization of an new human cultured cell line from a prolactin-secreting pituitary adenoma","volume":"45","author":"Kikuchi","year":"1985","journal-title":"Cancer Res."},{"issue":"(1)","key":"2022020820053006200_CIT0034","doi-asserted-by":"crossref","first-page":"110679","DOI":"10.1016\/j.mce.2019.110679","article-title":"Patterns of prolactin secretion","volume":"502","author":"Phillipps","year":"2020","journal-title":"Mol Cell Endocrinol."},{"issue":"6","key":"2022020820053006200_CIT0035","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1159\/000125961","article-title":"Attenuation of the suckling-induced prolactin release and the high afternoon oscillations of plasma prolactin secretion of lactating rats by antiserum to vasopressin","volume":"54","author":"Nagy","year":"1991","journal-title":"Neuroendocrinology."},{"issue":"1","key":"2022020820053006200_CIT0036","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1210\/endo-122-1-341","article-title":"Role of oxytocin on prolactin secretion during proestrus and in different physiological or pharmacological paradigms","volume":"122","author":"Johnston","year":"1988","journal-title":"Endocrinology."},{"issue":"2","key":"2022020820053006200_CIT0037","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1210\/endo-119-2-554","article-title":"Evidence for a physiological role for oxytocin in the control of prolactin secretion","volume":"119","author":"Samson","year":"1986","journal-title":"Endocrinology."},{"issue":"(1)","key":"2022020820053006200_CIT0038","doi-asserted-by":"crossref","first-page":"591501","DOI":"10.3389\/fendo.2020.591501","article-title":"Phenotypes associated with MEN1 syndrome: a focus on genotype-phenotype correlations","volume":"11","author":"Mele","year":"2020","journal-title":"Front Endocrinol (Lausanne)."},{"issue":"(1)","key":"2022020820053006200_CIT0039","doi-asserted-by":"crossref","first-page":"101846","DOI":"10.1016\/j.scr.2020.101846","article-title":"Generation of three induced pluripotent stem cell (iPSC) lines from a multiple endocrine neoplasia type 1 (MEN1) patient and three iPSC lines from an unaffected relative of the patient","volume":"46","author":"Yoshida","year":"2020","journal-title":"Stem Cell Res."},{"issue":"12","key":"2022020820053006200_CIT0040","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2147\/IJGM.S188525","article-title":"The relation of serum prolactin levels and Toxoplasma infection in humans","volume":"20","author":"Mohammadpour","year":"2018","journal-title":"Int J Gen Med."},{"issue":"6","key":"2022020820053006200_CIT0041","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1111\/j.1365-2826.2008.01736.x","article-title":"Prolactin: a pleiotropic neuroendocrine hormone","volume":"20","author":"Grattan","year":"2008","journal-title":"J Neuroendocrinol."}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/endo\/advance-article-pdf\/doi\/10.1210\/endocr\/bqac004\/42308467\/bqac004.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/163\/3\/bqac004\/42370064\/bqac004.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/163\/3\/bqac004\/42370064\/bqac004.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T20:06:12Z","timestamp":1644350772000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/doi\/10.1210\/endocr\/bqac004\/6516050"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,27]]},"references-count":41,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3,1]]}},"URL":"https:\/\/doi.org\/10.1210\/endocr\/bqac004","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,3,1]]},"published":{"date-parts":[[2022,1,27]]},"article-number":"bqac004"}}