Association Between Ex Vivo Human Ulcerative Colitis Explant Protein Secretion Profiles and Disease Behaviour
Background The clinical course of ulcerative colitis (UC) is variable. There is an unmet clinical need for biomarkers of UC disease behaviour. We aimed to evaluate the association between ex vivo human UC explant conditioned media (explant-CM) secreted protein profiles and UC disease behaviour. Meth...
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| Veröffentlicht in: | Digestive diseases and sciences 2022-12, Vol.67 (12), p.5540-5550 |
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| creator | Corcoran, R. M. MacDonagh, P. O’Connell, F. Morrissey, M. E. Dunne, M. R. Argue, R. O’Sullivan, J. Kevans, D. |
| description | Background
The clinical course of ulcerative colitis (UC) is variable. There is an unmet clinical need for biomarkers of UC disease behaviour. We aimed to evaluate the association between ex vivo human UC explant conditioned media (explant-CM) secreted protein profiles and UC disease behaviour.
Methods
UC patients undergoing endoscopy were prospectively recruited. Endoscopic biopsies were collected and explant-CM generated. Association between explant-CM protein secretion profiles and disease progression was evaluated. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent. Association between explant-CM secreted protein profiles and anti-TNF failure status was also evaluated.
p
values |
| doi_str_mv | 10.1007/s10620-022-07411-0 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9652171</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A726308247</galeid><sourcerecordid>A726308247</sourcerecordid><originalsourceid>FETCH-LOGICAL-c541t-32027f764ea9a80ccaa119c7f2506c90bb7af484daf56423b30fd824c10c36493</originalsourceid><addsrcrecordid>eNp9kkFv1DAQhS0EotvCH-CALHHhkjK2Ezu5IG2XQpEqgQTlanmdydZVYi92stB_j9MtLUUI-WDLfvPNPOsR8oLBMQNQbxIDyaEAzgtQJWMFPCILVilR8ErWj8kCmMxnxuQBOUzpCgAaxeRTciAqXtc1bxZkWKYUrDOjC56e4PgD0dPTn_Sb2wV6Ng3G04veYsyCHdJV6N3oUhZse-NH-jmGEZ2nX9BGvEHkm871mKjxLX3nEpqEmXtpdi5M8Rl50pk-4fPb_YhcvD_9ujorzj99-Lhanhe2KtlYCA5cdUqWaBpTg7XGMNZY1fEKpG1gvVamK-uyNV0lSy7WArq25qVlYIUsG3FE3u6522k9YGvRj9H0ehvdYOK1Dsbphy_eXepN2OlGVpwplgGvbwExfJ8wjXpwyWKfXWOYkuZSNJzn3nOvV39Jr7JTn-1prkT2I6SEe9XG9Kid70Lua2eoXqpMgzy-yqrjf6jyanFwNnic__ZhAd8X2BhSitjdeWSg55DofUh0Dom-CYmeZ3n55-_clfxORRaIvSDlJ7_BeG_pP9hfZ93G2w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2735413660</pqid></control><display><type>article</type><title>Association Between Ex Vivo Human Ulcerative Colitis Explant Protein Secretion Profiles and Disease Behaviour</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Corcoran, R. M. ; MacDonagh, P. ; O’Connell, F. ; Morrissey, M. E. ; Dunne, M. R. ; Argue, R. ; O’Sullivan, J. ; Kevans, D.</creator><creatorcontrib>Corcoran, R. M. ; MacDonagh, P. ; O’Connell, F. ; Morrissey, M. E. ; Dunne, M. R. ; Argue, R. ; O’Sullivan, J. ; Kevans, D.</creatorcontrib><description>Background
The clinical course of ulcerative colitis (UC) is variable. There is an unmet clinical need for biomarkers of UC disease behaviour. We aimed to evaluate the association between ex vivo human UC explant conditioned media (explant-CM) secreted protein profiles and UC disease behaviour.
Methods
UC patients undergoing endoscopy were prospectively recruited. Endoscopic biopsies were collected and explant-CM generated. Association between explant-CM protein secretion profiles and disease progression was evaluated. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent. Association between explant-CM secreted protein profiles and anti-TNF failure status was also evaluated.
p
values < 0.05 were considered significant in analyses.
Results
Twenty-four UC patients were included (age [median, range]) 55 [21–72] years; 50% female. Disease progression during follow-up occurred in twelve (50%) patients. Multivariate analysis, including endoscopic remission status, demonstrated reduced IL-2 secretion to be independently associated with UC disease progression,
p
= 0.01. In univariate analysis, anti-TNF failure status was associated with significantly increased IL-17A/F (
p
= 0.015) and IL-12 / IL-23p40 (
p
= 0.044) concentrations. In multivariate analysis, there was a trend towards an association between IL-17A/F and anti-TNF failure status (
p
= 0.069); FLT-1 was demonstrated to be independently associated with anti-TNF failure status (
p
= 0.016).
Conclusion
Reduced explant-CM secreted IL-2 is associated with UC disease progression. Increased secretion of IL-23 pathway-associated cytokines was observed in anti-TNF failure status consistent with previous reports. Ex vivo human UC explants, generated from endoscopic biopsies, have potential as precision medicine tools in inflammatory bowel disease.</description><identifier>ISSN: 0163-2116</identifier><identifier>EISSN: 1573-2568</identifier><identifier>DOI: 10.1007/s10620-022-07411-0</identifier><identifier>PMID: 35288829</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Analysis ; Biochemistry ; Biopsy ; Colitis, Ulcerative - pathology ; Corticosteroids ; Development and progression ; Disease Progression ; Endoscopy ; Female ; Gastroenterology ; Hepatology ; Humans ; Inflammatory bowel disease ; Interleukin-17 ; Interleukin-2 - therapeutic use ; Male ; Medical colleges ; Medicine ; Medicine & Public Health ; Middle Aged ; Multivariate analysis ; Oncology ; Original ; Original Article ; Proteins ; Transplant Surgery ; Tumor necrosis factor ; Tumor Necrosis Factor Inhibitors ; Ulcerative colitis</subject><ispartof>Digestive diseases and sciences, 2022-12, Vol.67 (12), p.5540-5550</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>COPYRIGHT 2022 Springer</rights><rights>The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c541t-32027f764ea9a80ccaa119c7f2506c90bb7af484daf56423b30fd824c10c36493</citedby><cites>FETCH-LOGICAL-c541t-32027f764ea9a80ccaa119c7f2506c90bb7af484daf56423b30fd824c10c36493</cites><orcidid>0000-0002-9720-0273</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10620-022-07411-0$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10620-022-07411-0$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,27926,27927,41490,42559,51321</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35288829$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Corcoran, R. M.</creatorcontrib><creatorcontrib>MacDonagh, P.</creatorcontrib><creatorcontrib>O’Connell, F.</creatorcontrib><creatorcontrib>Morrissey, M. E.</creatorcontrib><creatorcontrib>Dunne, M. R.</creatorcontrib><creatorcontrib>Argue, R.</creatorcontrib><creatorcontrib>O’Sullivan, J.</creatorcontrib><creatorcontrib>Kevans, D.</creatorcontrib><title>Association Between Ex Vivo Human Ulcerative Colitis Explant Protein Secretion Profiles and Disease Behaviour</title><title>Digestive diseases and sciences</title><addtitle>Dig Dis Sci</addtitle><addtitle>Dig Dis Sci</addtitle><description>Background
The clinical course of ulcerative colitis (UC) is variable. There is an unmet clinical need for biomarkers of UC disease behaviour. We aimed to evaluate the association between ex vivo human UC explant conditioned media (explant-CM) secreted protein profiles and UC disease behaviour.
Methods
UC patients undergoing endoscopy were prospectively recruited. Endoscopic biopsies were collected and explant-CM generated. Association between explant-CM protein secretion profiles and disease progression was evaluated. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent. Association between explant-CM secreted protein profiles and anti-TNF failure status was also evaluated.
p
values < 0.05 were considered significant in analyses.
Results
Twenty-four UC patients were included (age [median, range]) 55 [21–72] years; 50% female. Disease progression during follow-up occurred in twelve (50%) patients. Multivariate analysis, including endoscopic remission status, demonstrated reduced IL-2 secretion to be independently associated with UC disease progression,
p
= 0.01. In univariate analysis, anti-TNF failure status was associated with significantly increased IL-17A/F (
p
= 0.015) and IL-12 / IL-23p40 (
p
= 0.044) concentrations. In multivariate analysis, there was a trend towards an association between IL-17A/F and anti-TNF failure status (
p
= 0.069); FLT-1 was demonstrated to be independently associated with anti-TNF failure status (
p
= 0.016).
Conclusion
Reduced explant-CM secreted IL-2 is associated with UC disease progression. Increased secretion of IL-23 pathway-associated cytokines was observed in anti-TNF failure status consistent with previous reports. Ex vivo human UC explants, generated from endoscopic biopsies, have potential as precision medicine tools in inflammatory bowel disease.</description><subject>Analysis</subject><subject>Biochemistry</subject><subject>Biopsy</subject><subject>Colitis, Ulcerative - pathology</subject><subject>Corticosteroids</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>Endoscopy</subject><subject>Female</subject><subject>Gastroenterology</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Inflammatory bowel disease</subject><subject>Interleukin-17</subject><subject>Interleukin-2 - therapeutic use</subject><subject>Male</subject><subject>Medical colleges</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Multivariate analysis</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Proteins</subject><subject>Transplant Surgery</subject><subject>Tumor necrosis factor</subject><subject>Tumor Necrosis Factor Inhibitors</subject><subject>Ulcerative colitis</subject><issn>0163-2116</issn><issn>1573-2568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kkFv1DAQhS0EotvCH-CALHHhkjK2Ezu5IG2XQpEqgQTlanmdydZVYi92stB_j9MtLUUI-WDLfvPNPOsR8oLBMQNQbxIDyaEAzgtQJWMFPCILVilR8ErWj8kCmMxnxuQBOUzpCgAaxeRTciAqXtc1bxZkWKYUrDOjC56e4PgD0dPTn_Sb2wV6Ng3G04veYsyCHdJV6N3oUhZse-NH-jmGEZ2nX9BGvEHkm871mKjxLX3nEpqEmXtpdi5M8Rl50pk-4fPb_YhcvD_9ujorzj99-Lhanhe2KtlYCA5cdUqWaBpTg7XGMNZY1fEKpG1gvVamK-uyNV0lSy7WArq25qVlYIUsG3FE3u6522k9YGvRj9H0ehvdYOK1Dsbphy_eXepN2OlGVpwplgGvbwExfJ8wjXpwyWKfXWOYkuZSNJzn3nOvV39Jr7JTn-1prkT2I6SEe9XG9Kid70Lua2eoXqpMgzy-yqrjf6jyanFwNnic__ZhAd8X2BhSitjdeWSg55DofUh0Dom-CYmeZ3n55-_clfxORRaIvSDlJ7_BeG_pP9hfZ93G2w</recordid><startdate>20221201</startdate><enddate>20221201</enddate><creator>Corcoran, R. M.</creator><creator>MacDonagh, P.</creator><creator>O’Connell, F.</creator><creator>Morrissey, M. E.</creator><creator>Dunne, M. R.</creator><creator>Argue, R.</creator><creator>O’Sullivan, J.</creator><creator>Kevans, D.</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>C6C</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9720-0273</orcidid></search><sort><creationdate>20221201</creationdate><title>Association Between Ex Vivo Human Ulcerative Colitis Explant Protein Secretion Profiles and Disease Behaviour</title><author>Corcoran, R. M. ; MacDonagh, P. ; O’Connell, F. ; Morrissey, M. E. ; Dunne, M. R. ; Argue, R. ; O’Sullivan, J. ; Kevans, D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c541t-32027f764ea9a80ccaa119c7f2506c90bb7af484daf56423b30fd824c10c36493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Analysis</topic><topic>Biochemistry</topic><topic>Biopsy</topic><topic>Colitis, Ulcerative - pathology</topic><topic>Corticosteroids</topic><topic>Development and progression</topic><topic>Disease Progression</topic><topic>Endoscopy</topic><topic>Female</topic><topic>Gastroenterology</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Inflammatory bowel disease</topic><topic>Interleukin-17</topic><topic>Interleukin-2 - therapeutic use</topic><topic>Male</topic><topic>Medical colleges</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Multivariate analysis</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Proteins</topic><topic>Transplant Surgery</topic><topic>Tumor necrosis factor</topic><topic>Tumor Necrosis Factor Inhibitors</topic><topic>Ulcerative colitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Corcoran, R. M.</creatorcontrib><creatorcontrib>MacDonagh, P.</creatorcontrib><creatorcontrib>O’Connell, F.</creatorcontrib><creatorcontrib>Morrissey, M. E.</creatorcontrib><creatorcontrib>Dunne, M. R.</creatorcontrib><creatorcontrib>Argue, R.</creatorcontrib><creatorcontrib>O’Sullivan, J.</creatorcontrib><creatorcontrib>Kevans, D.</creatorcontrib><collection>Springer Nature OA Free Journals</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 Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Digestive diseases and sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Corcoran, R. M.</au><au>MacDonagh, P.</au><au>O’Connell, F.</au><au>Morrissey, M. E.</au><au>Dunne, M. R.</au><au>Argue, R.</au><au>O’Sullivan, J.</au><au>Kevans, D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association Between Ex Vivo Human Ulcerative Colitis Explant Protein Secretion Profiles and Disease Behaviour</atitle><jtitle>Digestive diseases and sciences</jtitle><stitle>Dig Dis Sci</stitle><addtitle>Dig Dis Sci</addtitle><date>2022-12-01</date><risdate>2022</risdate><volume>67</volume><issue>12</issue><spage>5540</spage><epage>5550</epage><pages>5540-5550</pages><issn>0163-2116</issn><eissn>1573-2568</eissn><abstract>Background
The clinical course of ulcerative colitis (UC) is variable. There is an unmet clinical need for biomarkers of UC disease behaviour. We aimed to evaluate the association between ex vivo human UC explant conditioned media (explant-CM) secreted protein profiles and UC disease behaviour.
Methods
UC patients undergoing endoscopy were prospectively recruited. Endoscopic biopsies were collected and explant-CM generated. Association between explant-CM protein secretion profiles and disease progression was evaluated. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent. Association between explant-CM secreted protein profiles and anti-TNF failure status was also evaluated.
p
values < 0.05 were considered significant in analyses.
Results
Twenty-four UC patients were included (age [median, range]) 55 [21–72] years; 50% female. Disease progression during follow-up occurred in twelve (50%) patients. Multivariate analysis, including endoscopic remission status, demonstrated reduced IL-2 secretion to be independently associated with UC disease progression,
p
= 0.01. In univariate analysis, anti-TNF failure status was associated with significantly increased IL-17A/F (
p
= 0.015) and IL-12 / IL-23p40 (
p
= 0.044) concentrations. In multivariate analysis, there was a trend towards an association between IL-17A/F and anti-TNF failure status (
p
= 0.069); FLT-1 was demonstrated to be independently associated with anti-TNF failure status (
p
= 0.016).
Conclusion
Reduced explant-CM secreted IL-2 is associated with UC disease progression. Increased secretion of IL-23 pathway-associated cytokines was observed in anti-TNF failure status consistent with previous reports. Ex vivo human UC explants, generated from endoscopic biopsies, have potential as precision medicine tools in inflammatory bowel disease.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>35288829</pmid><doi>10.1007/s10620-022-07411-0</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-9720-0273</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0163-2116 |
| ispartof | Digestive diseases and sciences, 2022-12, Vol.67 (12), p.5540-5550 |
| issn | 0163-2116 1573-2568 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9652171 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Analysis Biochemistry Biopsy Colitis, Ulcerative - pathology Corticosteroids Development and progression Disease Progression Endoscopy Female Gastroenterology Hepatology Humans Inflammatory bowel disease Interleukin-17 Interleukin-2 - therapeutic use Male Medical colleges Medicine Medicine & Public Health Middle Aged Multivariate analysis Oncology Original Original Article Proteins Transplant Surgery Tumor necrosis factor Tumor Necrosis Factor Inhibitors Ulcerative colitis |
| title | Association Between Ex Vivo Human Ulcerative Colitis Explant Protein Secretion Profiles and Disease Behaviour |
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