Overexpression of MHCII by hepatocytes in Alcoholic Hepatitis (AH) compared to Non-alcoholic Steatohepatitis (NASH) and normal controls
AbstractPreviously we have shown that in autoimmune hepatitis CD4 positive lymphocytes form an immunologic synapse with hepatocytes, leading to gradual diminishing and elimination of the hepatocyte. We wondered whether a similar mechanism may occur in alcoholic hepatitis (AH) and non-alcoholic steat...
Gespeichert in:
| Veröffentlicht in: | Alcohol (Fayetteville, N.Y.) N.Y.), 2020-05, Vol.84, p.27-32 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 32 |
|---|---|
| container_issue | |
| container_start_page | 27 |
| container_title | Alcohol (Fayetteville, N.Y.) |
| container_volume | 84 |
| creator | Lu, Jiajie G Iyasu, Askalu French, Barbara Tillman, Brittany French, Samuel W M.D |
| description | AbstractPreviously we have shown that in autoimmune hepatitis CD4 positive lymphocytes form an immunologic synapse with hepatocytes, leading to gradual diminishing and elimination of the hepatocyte. We wondered whether a similar mechanism may occur in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH). We conducted immunofluorescence studies of expression of MHCII, the binding partner of CD4, on patient liver biopsies of AH, NASH, and normal controls. In cases of alcoholic hepatitis, there was prominent sinusoidal expression of MHC II; In NASH biopsies there was comparatively lower expression of MHC II, but still more than control tissue. Immunohistochemical stain for CD4 showed CD4 positive lymphocytes closely associated with hepatocytes in AH biopsies. Furthermore, expression levels of the multifunctional cytokine IL-1α was higher in AH compared to NASH and control biopsies. These results underlie the more severe nature of alcoholic hepatitis and underscore the autoimmune mechanisms involved in the liver damage found in alcoholic hepatitis. |
| doi_str_mv | 10.1016/j.alcohol.2019.08.008 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2425656484</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0741832919300679</els_id><sourcerecordid>2425656484</sourcerecordid><originalsourceid>FETCH-LOGICAL-c495t-fe2cb2e691eeb6322744b182d40c789d035ae23d5e28afbdcafffff03cd4ce7f3</originalsourceid><addsrcrecordid>eNqFks2O0zAUhS0EYjoDjwCyxIZZJPgvib0BVRXQSsPMorC2HPtGdUnjYqcj-gS8No5aisQGb-7C3zlX5-gi9IqSkhJav9uWprdhE_qSEapKIktC5BM0o7LhRS0Zf4pmpBG0kJypK3Sd0pYQ0jSNeo6uOBVKsErN0K-HR4jwcx8hJR8GHDr8ZblYrXB7xBvYmzHY4wgJ-wHPT_u8xcvpw48-4bfz5S22Ybc3ERweA74PQ2Eu4HqE7LD5i9_P11lgBoeHEHemz9phjKFPL9CzzvQJXp7nDfr26ePXxbK4e_i8WszvCitUNRYdMNsyqBUFaGvOWCNESyVzgthGKkd4ZYBxVwGTpmudNd30CLdOWGg6foPenHz3Mfw4QBr1NhzikFdqlhupq1pIkanqRNkYUorQ6X30OxOPmhI91a-3-pxST_VrInWuP-ten90P7Q7cRfWn7wx8OAGQMz56iDpZD4MF5yPYUbvg_7vi_T8OtveDt6b_DkdIlzRUJ6aJXk83MJ0AVZyQulH8N3p8r7c</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2425656484</pqid></control><display><type>article</type><title>Overexpression of MHCII by hepatocytes in Alcoholic Hepatitis (AH) compared to Non-alcoholic Steatohepatitis (NASH) and normal controls</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><source>ProQuest Central UK/Ireland</source><creator>Lu, Jiajie G ; Iyasu, Askalu ; French, Barbara ; Tillman, Brittany ; French, Samuel W ; M.D</creator><creatorcontrib>Lu, Jiajie G ; Iyasu, Askalu ; French, Barbara ; Tillman, Brittany ; French, Samuel W ; M.D</creatorcontrib><description>AbstractPreviously we have shown that in autoimmune hepatitis CD4 positive lymphocytes form an immunologic synapse with hepatocytes, leading to gradual diminishing and elimination of the hepatocyte. We wondered whether a similar mechanism may occur in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH). We conducted immunofluorescence studies of expression of MHCII, the binding partner of CD4, on patient liver biopsies of AH, NASH, and normal controls. In cases of alcoholic hepatitis, there was prominent sinusoidal expression of MHC II; In NASH biopsies there was comparatively lower expression of MHC II, but still more than control tissue. Immunohistochemical stain for CD4 showed CD4 positive lymphocytes closely associated with hepatocytes in AH biopsies. Furthermore, expression levels of the multifunctional cytokine IL-1α was higher in AH compared to NASH and control biopsies. These results underlie the more severe nature of alcoholic hepatitis and underscore the autoimmune mechanisms involved in the liver damage found in alcoholic hepatitis.</description><identifier>ISSN: 0741-8329</identifier><identifier>EISSN: 1873-6823</identifier><identifier>DOI: 10.1016/j.alcohol.2019.08.008</identifier><identifier>PMID: 31494259</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alcohol use ; Alcoholic hepatitis ; Alcoholism ; Antibodies ; Antigens ; Biopsy ; CD4 ; CD4 antigen ; CD4-Positive T-Lymphocytes - immunology ; Cytokines ; Cytotoxicity ; Fluorescent Antibody Technique ; Hepatitis ; Hepatitis, Alcoholic - immunology ; Hepatocytes ; Hepatocytes - pathology ; Histocompatibility Antigens Class II - immunology ; Humans ; Immune synapse ; Immunofluorescence ; Immunohistochemistry ; Immunology ; Interleukin-1alpha - immunology ; Liver ; Lymphocytes ; Major histocompatibility complex ; MHCII ; Microscopy ; Neutrophils ; Non-alcoholic Fatty Liver Disease - immunology ; Non-alcoholic steatohepatitis ; Proteins ; Psychiatric/Mental Health ; Synapses</subject><ispartof>Alcohol (Fayetteville, N.Y.), 2020-05, Vol.84, p.27-32</ispartof><rights>2019 The Authors</rights><rights>Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>2019. The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-fe2cb2e691eeb6322744b182d40c789d035ae23d5e28afbdcafffff03cd4ce7f3</citedby><cites>FETCH-LOGICAL-c495t-fe2cb2e691eeb6322744b182d40c789d035ae23d5e28afbdcafffff03cd4ce7f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2425656484?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,64361,64365,65309,72215</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31494259$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Jiajie G</creatorcontrib><creatorcontrib>Iyasu, Askalu</creatorcontrib><creatorcontrib>French, Barbara</creatorcontrib><creatorcontrib>Tillman, Brittany</creatorcontrib><creatorcontrib>French, Samuel W</creatorcontrib><creatorcontrib>M.D</creatorcontrib><title>Overexpression of MHCII by hepatocytes in Alcoholic Hepatitis (AH) compared to Non-alcoholic Steatohepatitis (NASH) and normal controls</title><title>Alcohol (Fayetteville, N.Y.)</title><addtitle>Alcohol</addtitle><description>AbstractPreviously we have shown that in autoimmune hepatitis CD4 positive lymphocytes form an immunologic synapse with hepatocytes, leading to gradual diminishing and elimination of the hepatocyte. We wondered whether a similar mechanism may occur in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH). We conducted immunofluorescence studies of expression of MHCII, the binding partner of CD4, on patient liver biopsies of AH, NASH, and normal controls. In cases of alcoholic hepatitis, there was prominent sinusoidal expression of MHC II; In NASH biopsies there was comparatively lower expression of MHC II, but still more than control tissue. Immunohistochemical stain for CD4 showed CD4 positive lymphocytes closely associated with hepatocytes in AH biopsies. Furthermore, expression levels of the multifunctional cytokine IL-1α was higher in AH compared to NASH and control biopsies. These results underlie the more severe nature of alcoholic hepatitis and underscore the autoimmune mechanisms involved in the liver damage found in alcoholic hepatitis.</description><subject>Alcohol use</subject><subject>Alcoholic hepatitis</subject><subject>Alcoholism</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Biopsy</subject><subject>CD4</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Fluorescent Antibody Technique</subject><subject>Hepatitis</subject><subject>Hepatitis, Alcoholic - immunology</subject><subject>Hepatocytes</subject><subject>Hepatocytes - pathology</subject><subject>Histocompatibility Antigens Class II - immunology</subject><subject>Humans</subject><subject>Immune synapse</subject><subject>Immunofluorescence</subject><subject>Immunohistochemistry</subject><subject>Immunology</subject><subject>Interleukin-1alpha - immunology</subject><subject>Liver</subject><subject>Lymphocytes</subject><subject>Major histocompatibility complex</subject><subject>MHCII</subject><subject>Microscopy</subject><subject>Neutrophils</subject><subject>Non-alcoholic Fatty Liver Disease - immunology</subject><subject>Non-alcoholic steatohepatitis</subject><subject>Proteins</subject><subject>Psychiatric/Mental Health</subject><subject>Synapses</subject><issn>0741-8329</issn><issn>1873-6823</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFks2O0zAUhS0EYjoDjwCyxIZZJPgvib0BVRXQSsPMorC2HPtGdUnjYqcj-gS8No5aisQGb-7C3zlX5-gi9IqSkhJav9uWprdhE_qSEapKIktC5BM0o7LhRS0Zf4pmpBG0kJypK3Sd0pYQ0jSNeo6uOBVKsErN0K-HR4jwcx8hJR8GHDr8ZblYrXB7xBvYmzHY4wgJ-wHPT_u8xcvpw48-4bfz5S22Ybc3ERweA74PQ2Eu4HqE7LD5i9_P11lgBoeHEHemz9phjKFPL9CzzvQJXp7nDfr26ePXxbK4e_i8WszvCitUNRYdMNsyqBUFaGvOWCNESyVzgthGKkd4ZYBxVwGTpmudNd30CLdOWGg6foPenHz3Mfw4QBr1NhzikFdqlhupq1pIkanqRNkYUorQ6X30OxOPmhI91a-3-pxST_VrInWuP-ten90P7Q7cRfWn7wx8OAGQMz56iDpZD4MF5yPYUbvg_7vi_T8OtveDt6b_DkdIlzRUJ6aJXk83MJ0AVZyQulH8N3p8r7c</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>Lu, Jiajie G</creator><creator>Iyasu, Askalu</creator><creator>French, Barbara</creator><creator>Tillman, Brittany</creator><creator>French, Samuel W</creator><creator>M.D</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0-V</scope><scope>3V.</scope><scope>7QG</scope><scope>7RV</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AM</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ALSLI</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGRYB</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K7.</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0O</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope></search><sort><creationdate>20200501</creationdate><title>Overexpression of MHCII by hepatocytes in Alcoholic Hepatitis (AH) compared to Non-alcoholic Steatohepatitis (NASH) and normal controls</title><author>Lu, Jiajie G ; Iyasu, Askalu ; French, Barbara ; Tillman, Brittany ; French, Samuel W ; M.D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-fe2cb2e691eeb6322744b182d40c789d035ae23d5e28afbdcafffff03cd4ce7f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alcohol use</topic><topic>Alcoholic hepatitis</topic><topic>Alcoholism</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Biopsy</topic><topic>CD4</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>Cytokines</topic><topic>Cytotoxicity</topic><topic>Fluorescent Antibody Technique</topic><topic>Hepatitis</topic><topic>Hepatitis, Alcoholic - immunology</topic><topic>Hepatocytes</topic><topic>Hepatocytes - pathology</topic><topic>Histocompatibility Antigens Class II - immunology</topic><topic>Humans</topic><topic>Immune synapse</topic><topic>Immunofluorescence</topic><topic>Immunohistochemistry</topic><topic>Immunology</topic><topic>Interleukin-1alpha - immunology</topic><topic>Liver</topic><topic>Lymphocytes</topic><topic>Major histocompatibility complex</topic><topic>MHCII</topic><topic>Microscopy</topic><topic>Neutrophils</topic><topic>Non-alcoholic Fatty Liver Disease - immunology</topic><topic>Non-alcoholic steatohepatitis</topic><topic>Proteins</topic><topic>Psychiatric/Mental Health</topic><topic>Synapses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Jiajie G</creatorcontrib><creatorcontrib>Iyasu, Askalu</creatorcontrib><creatorcontrib>French, Barbara</creatorcontrib><creatorcontrib>Tillman, Brittany</creatorcontrib><creatorcontrib>French, Samuel W</creatorcontrib><creatorcontrib>M.D</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Social Sciences Premium Collection</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Criminal Justice Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Social Science Premium Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Criminology Collection</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Criminal Justice (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>ProQuest Criminal Justice</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><jtitle>Alcohol (Fayetteville, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Jiajie G</au><au>Iyasu, Askalu</au><au>French, Barbara</au><au>Tillman, Brittany</au><au>French, Samuel W</au><au>M.D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of MHCII by hepatocytes in Alcoholic Hepatitis (AH) compared to Non-alcoholic Steatohepatitis (NASH) and normal controls</atitle><jtitle>Alcohol (Fayetteville, N.Y.)</jtitle><addtitle>Alcohol</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>84</volume><spage>27</spage><epage>32</epage><pages>27-32</pages><issn>0741-8329</issn><eissn>1873-6823</eissn><abstract>AbstractPreviously we have shown that in autoimmune hepatitis CD4 positive lymphocytes form an immunologic synapse with hepatocytes, leading to gradual diminishing and elimination of the hepatocyte. We wondered whether a similar mechanism may occur in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH). We conducted immunofluorescence studies of expression of MHCII, the binding partner of CD4, on patient liver biopsies of AH, NASH, and normal controls. In cases of alcoholic hepatitis, there was prominent sinusoidal expression of MHC II; In NASH biopsies there was comparatively lower expression of MHC II, but still more than control tissue. Immunohistochemical stain for CD4 showed CD4 positive lymphocytes closely associated with hepatocytes in AH biopsies. Furthermore, expression levels of the multifunctional cytokine IL-1α was higher in AH compared to NASH and control biopsies. These results underlie the more severe nature of alcoholic hepatitis and underscore the autoimmune mechanisms involved in the liver damage found in alcoholic hepatitis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>31494259</pmid><doi>10.1016/j.alcohol.2019.08.008</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0741-8329 |
| ispartof | Alcohol (Fayetteville, N.Y.), 2020-05, Vol.84, p.27-32 |
| issn | 0741-8329 1873-6823 |
| language | eng |
| recordid | cdi_proquest_journals_2425656484 |
| source | MEDLINE; Elsevier ScienceDirect Journals; ProQuest Central UK/Ireland |
| subjects | Alcohol use Alcoholic hepatitis Alcoholism Antibodies Antigens Biopsy CD4 CD4 antigen CD4-Positive T-Lymphocytes - immunology Cytokines Cytotoxicity Fluorescent Antibody Technique Hepatitis Hepatitis, Alcoholic - immunology Hepatocytes Hepatocytes - pathology Histocompatibility Antigens Class II - immunology Humans Immune synapse Immunofluorescence Immunohistochemistry Immunology Interleukin-1alpha - immunology Liver Lymphocytes Major histocompatibility complex MHCII Microscopy Neutrophils Non-alcoholic Fatty Liver Disease - immunology Non-alcoholic steatohepatitis Proteins Psychiatric/Mental Health Synapses |
| title | Overexpression of MHCII by hepatocytes in Alcoholic Hepatitis (AH) compared to Non-alcoholic Steatohepatitis (NASH) and normal controls |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T11%3A03%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Overexpression%20of%20MHCII%20by%20hepatocytes%20in%20Alcoholic%20Hepatitis%20(AH)%20compared%20to%20Non-alcoholic%20Steatohepatitis%20(NASH)%20and%20normal%20controls&rft.jtitle=Alcohol%20(Fayetteville,%20N.Y.)&rft.au=Lu,%20Jiajie%20G&rft.date=2020-05-01&rft.volume=84&rft.spage=27&rft.epage=32&rft.pages=27-32&rft.issn=0741-8329&rft.eissn=1873-6823&rft_id=info:doi/10.1016/j.alcohol.2019.08.008&rft_dat=%3Cproquest_cross%3E2425656484%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2425656484&rft_id=info:pmid/31494259&rft_els_id=S0741832919300679&rfr_iscdi=true |