{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T23:35:50Z","timestamp":1767137750675,"version":"build-2238731810"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T00:00:00Z","timestamp":1657238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Laryngoscope Investig Oto"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective\/Hypothesis<\/jats:title>\n                    <jats:p>\n                      Middle ear cholesteatoma is characterized by abnormal growth of the keratinizing squamous epithelium of the temporal bone.\n                      <jats:sc>d<\/jats:sc>\n                      \u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010aspartic acid is the major isomer of\n                      <jats:sc>d<\/jats:sc>\n                      \u2010aspartic acid found in elderly tissue. We assessed the immunoreactivity to k\u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010aspartic acid of congenital and acquired middle ear cholesteatomas.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>Case\u2013control studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>\n                      Tissue samples were collected from 21 patients comprising 21 ears with congenital middle ear cholesteatoma and 26 patients comprising 29 ears with acquired type. Their clinical and histopathological features were investigated. We divided the middle ear cholesteatoma samples into three layers: the perimatrix, matrix, and cystic contents. The patterns of immunoreactivity to\n                      <jats:sc>d<\/jats:sc>\n                      \u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010aspartic acid expression were then assessed immunohistochemically.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two patterns of immunoreactivity to\n                      <jats:sc>d<\/jats:sc>\n                      \u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010aspartic acid were detected in middle ear cholesteatoma: infiltrative and diffuse. In congenital middle ear cholesteatoma,\n                      <jats:sc>d<\/jats:sc>\n                      \u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010aspartic acid expression was observed throughout all the layers (perimatrix, matrix, and cystic contents), and immunoreactivity to\n                      <jats:sc>d<\/jats:sc>\n                      \u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010aspartic acid was dramatically strong in all layers. The expression levels of\n                      <jats:sc>d<\/jats:sc>\n                      \u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010aspartic acid to the cystic content and perimatrix were significantly higher in congenital middle ear cholesteatoma than in the acquired type.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study showed the expression levels of\n                      <jats:sc>d<\/jats:sc>\n                      \u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010aspartic acid in middle ear cholesteatoma to differ significantly between congenital and acquired middle ear cholesteatoma. Our results indicate that overexpression of\n                      <jats:sc>d<\/jats:sc>\n                      \u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010aspartic acid is likely to be involved in the pathogenesis of cholesteatoma, and we speculate that\n                      <jats:sc>d<\/jats:sc>\n                      \u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010aspartic acid could be a novel biomarker for, and a therapeutic target in, congenital and acquired middle ear cholesteatoma.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence<\/jats:title>\n                    <jats:p>4<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lio2.856","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T06:24:20Z","timestamp":1657261460000},"page":"1155-1163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunohistochemical localization of\n                    <scp>d<\/scp>\n                    \u2010\n                    <i>\u03b2<\/i>\n                    \u2010aspartic acid in congenital and acquired middle ear cholesteatoma"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7238-1338","authenticated-orcid":false,"given":"Shiori","family":"Kitaya","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery Tohoku University Hospital  Sendai Japan"},{"name":"Division of Otolaryngology Tohoku Medical and Pharmaceutical University Hospital  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0076-6092","authenticated-orcid":false,"given":"Ryoukichi","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery Tohoku University Hospital  Sendai Japan"},{"name":"Center for Otologic Surgery Sen\u2010en Rifu Hospital  Rifu Miyagi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery Tohoku University Hospital  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidetoshi","family":"Oshima","sequence":"additional","affiliation":[{"name":"Center for Otologic Surgery Sen\u2010en Rifu Hospital  Rifu Miyagi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri","family":"Nomura","sequence":"additional","affiliation":[{"name":"Center for Otologic Surgery Sen\u2010en Rifu Hospital  Rifu Miyagi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Kusano","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery Tohoku University Hospital  Sendai Japan"},{"name":"Center for Otologic Surgery Sen\u2010en Rifu Hospital  Rifu Miyagi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2821-6976","authenticated-orcid":false,"given":"Nobuo","family":"Ohta","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology Tohoku Medical and Pharmaceutical University Hospital  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuaki","family":"Kawase","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery Tohoku University Hospital  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazue","family":"Ise","sequence":"additional","affiliation":[{"name":"Technical Services Division Tohoku Medical and Pharmaceutical University  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Murakami","sequence":"additional","affiliation":[{"name":"Division of Pathology Tohoku Medical and Pharmaceutical University Hospital  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Division of Pathology Tohoku Medical and Pharmaceutical University Hospital  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironobu","family":"Sasano","sequence":"additional","affiliation":[{"name":"Department of Pathology Tohoku University School of Medicine  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukio","family":"Katori","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery Tohoku University Hospital  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otc.2006.08.003"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.25834"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-018-0915-5"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.5152\/iao.2017.3363"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5876(88)90050-X"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1279"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00597-1"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(92)90132-Z"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-1284"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(87)90797-2"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00414-002-0355-2"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/268071a0"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-005-0047-y"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2015.01.057"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0022215109992763"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4838(94)90003-5"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0303-6987.2004.0144.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1288\/00005537-198809000-00008"}],"updated-by":[{"DOI":"10.1002\/lio2.1052","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000}}],"container-title":["Laryngoscope Investigative Otolaryngology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lio2.856","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/lio2.856","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lio2.856","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T01:29:11Z","timestamp":1726190951000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/lio2.856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,8]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1002\/lio2.856"],"URL":"https:\/\/doi.org\/10.1002\/lio2.856","archive":["Portico"],"relation":{},"ISSN":["2378-8038","2378-8038"],"issn-type":[{"value":"2378-8038","type":"print"},{"value":"2378-8038","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,8]]},"assertion":[{"value":"2022-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}