Loading…

Structural brain disconnectivity mapping of post-stroke fatigue

•We tested for associations between post stroke fatigue (PSF) and both lesion characteristics and brain structural disconnectome in 84 S patients.•Results provided no evidence supporting a simple association between PSF severity and lesion characteristics or disconnectivity.•PSF was strongly correla...

Full description

Saved in:
Bibliographic Details
Published in:NeuroImage clinical 2021-01, Vol.30, p.102635-102635, Article 102635
Main Authors: Ulrichsen, Kristine M., Kolskår, Knut K., Richard, Geneviève, Alnæs, Dag, Dørum, Erlend S., Sanders, Anne-Marthe, Tornås, Sveinung, Sánchez, Jennifer Monereo, Engvig, Andreas, Ihle-Hansen, Hege, de Schotten, Michel Thiebaut, Nordvik, Jan E., Westlye, Lars T.
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c579t-e6c2a673e6274e4097b9ceef831796de8e5719aa639f1a632d0bc67fca2214183
cites cdi_FETCH-LOGICAL-c579t-e6c2a673e6274e4097b9ceef831796de8e5719aa639f1a632d0bc67fca2214183
container_end_page 102635
container_issue
container_start_page 102635
container_title NeuroImage clinical
container_volume 30
creator Ulrichsen, Kristine M.
Kolskår, Knut K.
Richard, Geneviève
Alnæs, Dag
Dørum, Erlend S.
Sanders, Anne-Marthe
Tornås, Sveinung
Sánchez, Jennifer Monereo
Engvig, Andreas
Ihle-Hansen, Hege
de Schotten, Michel Thiebaut
Nordvik, Jan E.
Westlye, Lars T.
description •We tested for associations between post stroke fatigue (PSF) and both lesion characteristics and brain structural disconnectome in 84 S patients.•Results provided no evidence supporting a simple association between PSF severity and lesion characteristics or disconnectivity.•PSF was strongly correlated with depression.•Further studies including patients with more severe symptoms are needed to generalize the findings across a wider clinical spectrum. Stroke patients commonly suffer from post stroke fatigue (PSF). Despite a general consensus that brain perturbations constitute a precipitating event in the multifactorial etiology of PSF, the specific predictive value of conventional lesion characteristics such as size and localization remains unclear. The current study represents a novel approach to assess the neural correlates of PSF in chronic stroke patients. While previous research has focused primarily on lesion location or size, with mixed or inconclusive results, we targeted the extended structural network implicated by the lesion, and evaluated the added explanatory value of a structural disconnectivity approach with regards to the brain correlates of PSF. To this end, we estimated individual structural brain disconnectome maps in 84 S survivors in the chronic phase (≥3 months post stroke) using information about lesion location and normative white matter pathways obtained from 170 healthy individuals. PSF was measured by the Fatigue Severity Scale (FSS). Voxel wise analyses using non-parametric permutation-based inference were conducted on disconnectome maps to estimate regional effects of disconnectivity. Associations between PSF and global disconnectivity and clinical lesion characteristics were tested by linear models, and we estimated Bayes factor to quantify the evidence for the null and alternative hypotheses, respectively. The results revealed no significant associations between PSF and disconnectome measures or lesion characteristics, with moderate evidence in favor of the null hypothesis. These results suggest that symptoms of post-stroke fatigue among chronic stroke patients are not simply explained by lesion characteristics or the extent and distribution of structural brain disconnectome, and are discussed in light of methodological considerations.
doi_str_mv 10.1016/j.nicl.2021.102635
format article
fullrecord <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_2ed7ac4bee14427fb3f32c030ad13af2</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S2213158221000796</els_id><doaj_id>oai_doaj_org_article_2ed7ac4bee14427fb3f32c030ad13af2</doaj_id><sourcerecordid>2508563215</sourcerecordid><originalsourceid>FETCH-LOGICAL-c579t-e6c2a673e6274e4097b9ceef831796de8e5719aa639f1a632d0bc67fca2214183</originalsourceid><addsrcrecordid>eNp9UsFu1DAQjRCIVqU_wAFyhEMWe-zEiYSoqgraSitxAM6W44y3XnbtYDsr9e9xSFu1PeCDbY3fPM-8eUXxlpIVJbT5tF05q3crIEBzABpWvyiOASiraN3Cy0f3o-I0xi3JqyVENM3r4ogx0XUg6HFx9iOFSacpqF3ZB2VdOdiovXOokz3YdFvu1Thatym9KUcfUxVT8L-xNCrZzYRvildG7SKe3p0nxa9vX39eXFXr75fXF-frSteiSxU2GlQjGDYgOHLSib7TiKZlVHTNgC3WgnZKNawzNO8wkF43wmiV2-C0ZSfF9cI7eLWVY7B7FW6lV1b-C_iwkSqkrAhKwEEozXtEyjkI0zPDQBNG1ECZMpC5vixc49TvcdDoUm7_CenTF2dv5MYfZEs4F8AywceF4OZZ2tX5Ws4xkgUmwOFAM_b9gtXBxmSddD4oSUlbg2wFh7mcD3flBP9nwpjkPo8Adzvl0E9RQp3BWRJaZyjck_kYA5qH3ymRsy3kVs62kLMt5GKLnPTucbsPKfcmyIDPCwDzAA8Wg4zaotM42JBtkBW2_-P_C7t2xyw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2508563215</pqid></control><display><type>article</type><title>Structural brain disconnectivity mapping of post-stroke fatigue</title><source>Open Access: PubMed Central</source><source>NORA - Norwegian Open Research Archives</source><source>ScienceDirect Journals</source><creator>Ulrichsen, Kristine M. ; Kolskår, Knut K. ; Richard, Geneviève ; Alnæs, Dag ; Dørum, Erlend S. ; Sanders, Anne-Marthe ; Tornås, Sveinung ; Sánchez, Jennifer Monereo ; Engvig, Andreas ; Ihle-Hansen, Hege ; de Schotten, Michel Thiebaut ; Nordvik, Jan E. ; Westlye, Lars T.</creator><creatorcontrib>Ulrichsen, Kristine M. ; Kolskår, Knut K. ; Richard, Geneviève ; Alnæs, Dag ; Dørum, Erlend S. ; Sanders, Anne-Marthe ; Tornås, Sveinung ; Sánchez, Jennifer Monereo ; Engvig, Andreas ; Ihle-Hansen, Hege ; de Schotten, Michel Thiebaut ; Nordvik, Jan E. ; Westlye, Lars T.</creatorcontrib><description>•We tested for associations between post stroke fatigue (PSF) and both lesion characteristics and brain structural disconnectome in 84 S patients.•Results provided no evidence supporting a simple association between PSF severity and lesion characteristics or disconnectivity.•PSF was strongly correlated with depression.•Further studies including patients with more severe symptoms are needed to generalize the findings across a wider clinical spectrum. Stroke patients commonly suffer from post stroke fatigue (PSF). Despite a general consensus that brain perturbations constitute a precipitating event in the multifactorial etiology of PSF, the specific predictive value of conventional lesion characteristics such as size and localization remains unclear. The current study represents a novel approach to assess the neural correlates of PSF in chronic stroke patients. While previous research has focused primarily on lesion location or size, with mixed or inconclusive results, we targeted the extended structural network implicated by the lesion, and evaluated the added explanatory value of a structural disconnectivity approach with regards to the brain correlates of PSF. To this end, we estimated individual structural brain disconnectome maps in 84 S survivors in the chronic phase (≥3 months post stroke) using information about lesion location and normative white matter pathways obtained from 170 healthy individuals. PSF was measured by the Fatigue Severity Scale (FSS). Voxel wise analyses using non-parametric permutation-based inference were conducted on disconnectome maps to estimate regional effects of disconnectivity. Associations between PSF and global disconnectivity and clinical lesion characteristics were tested by linear models, and we estimated Bayes factor to quantify the evidence for the null and alternative hypotheses, respectively. The results revealed no significant associations between PSF and disconnectome measures or lesion characteristics, with moderate evidence in favor of the null hypothesis. These results suggest that symptoms of post-stroke fatigue among chronic stroke patients are not simply explained by lesion characteristics or the extent and distribution of structural brain disconnectome, and are discussed in light of methodological considerations.</description><identifier>ISSN: 2213-1582</identifier><identifier>EISSN: 2213-1582</identifier><identifier>DOI: 10.1016/j.nicl.2021.102635</identifier><identifier>PMID: 33799271</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Brain mapping ; Cognitive science ; Lesion ; MRI ; Post-stroke fatigue ; Regular ; Stroke ; Structural disconnectome</subject><ispartof>NeuroImage clinical, 2021-01, Vol.30, p.102635-102635, Article 102635</ispartof><rights>2021 The Author(s)</rights><rights>Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.</rights><rights>info:eu-repo/semantics/openAccess</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2021 The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c579t-e6c2a673e6274e4097b9ceef831796de8e5719aa639f1a632d0bc67fca2214183</citedby><cites>FETCH-LOGICAL-c579t-e6c2a673e6274e4097b9ceef831796de8e5719aa639f1a632d0bc67fca2214183</cites><orcidid>0000-0003-0981-648X ; 0000-0002-2638-2452 ; 0000-0001-6475-2576 ; 0000-0002-0329-1814</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044723/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S2213158221000796$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,3549,26567,27924,27925,45780,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33799271$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03370242$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Ulrichsen, Kristine M.</creatorcontrib><creatorcontrib>Kolskår, Knut K.</creatorcontrib><creatorcontrib>Richard, Geneviève</creatorcontrib><creatorcontrib>Alnæs, Dag</creatorcontrib><creatorcontrib>Dørum, Erlend S.</creatorcontrib><creatorcontrib>Sanders, Anne-Marthe</creatorcontrib><creatorcontrib>Tornås, Sveinung</creatorcontrib><creatorcontrib>Sánchez, Jennifer Monereo</creatorcontrib><creatorcontrib>Engvig, Andreas</creatorcontrib><creatorcontrib>Ihle-Hansen, Hege</creatorcontrib><creatorcontrib>de Schotten, Michel Thiebaut</creatorcontrib><creatorcontrib>Nordvik, Jan E.</creatorcontrib><creatorcontrib>Westlye, Lars T.</creatorcontrib><title>Structural brain disconnectivity mapping of post-stroke fatigue</title><title>NeuroImage clinical</title><addtitle>Neuroimage Clin</addtitle><description>•We tested for associations between post stroke fatigue (PSF) and both lesion characteristics and brain structural disconnectome in 84 S patients.•Results provided no evidence supporting a simple association between PSF severity and lesion characteristics or disconnectivity.•PSF was strongly correlated with depression.•Further studies including patients with more severe symptoms are needed to generalize the findings across a wider clinical spectrum. Stroke patients commonly suffer from post stroke fatigue (PSF). Despite a general consensus that brain perturbations constitute a precipitating event in the multifactorial etiology of PSF, the specific predictive value of conventional lesion characteristics such as size and localization remains unclear. The current study represents a novel approach to assess the neural correlates of PSF in chronic stroke patients. While previous research has focused primarily on lesion location or size, with mixed or inconclusive results, we targeted the extended structural network implicated by the lesion, and evaluated the added explanatory value of a structural disconnectivity approach with regards to the brain correlates of PSF. To this end, we estimated individual structural brain disconnectome maps in 84 S survivors in the chronic phase (≥3 months post stroke) using information about lesion location and normative white matter pathways obtained from 170 healthy individuals. PSF was measured by the Fatigue Severity Scale (FSS). Voxel wise analyses using non-parametric permutation-based inference were conducted on disconnectome maps to estimate regional effects of disconnectivity. Associations between PSF and global disconnectivity and clinical lesion characteristics were tested by linear models, and we estimated Bayes factor to quantify the evidence for the null and alternative hypotheses, respectively. The results revealed no significant associations between PSF and disconnectome measures or lesion characteristics, with moderate evidence in favor of the null hypothesis. These results suggest that symptoms of post-stroke fatigue among chronic stroke patients are not simply explained by lesion characteristics or the extent and distribution of structural brain disconnectome, and are discussed in light of methodological considerations.</description><subject>Brain mapping</subject><subject>Cognitive science</subject><subject>Lesion</subject><subject>MRI</subject><subject>Post-stroke fatigue</subject><subject>Regular</subject><subject>Stroke</subject><subject>Structural disconnectome</subject><issn>2213-1582</issn><issn>2213-1582</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>3HK</sourceid><sourceid>DOA</sourceid><recordid>eNp9UsFu1DAQjRCIVqU_wAFyhEMWe-zEiYSoqgraSitxAM6W44y3XnbtYDsr9e9xSFu1PeCDbY3fPM-8eUXxlpIVJbT5tF05q3crIEBzABpWvyiOASiraN3Cy0f3o-I0xi3JqyVENM3r4ogx0XUg6HFx9iOFSacpqF3ZB2VdOdiovXOokz3YdFvu1Thatym9KUcfUxVT8L-xNCrZzYRvildG7SKe3p0nxa9vX39eXFXr75fXF-frSteiSxU2GlQjGDYgOHLSib7TiKZlVHTNgC3WgnZKNawzNO8wkF43wmiV2-C0ZSfF9cI7eLWVY7B7FW6lV1b-C_iwkSqkrAhKwEEozXtEyjkI0zPDQBNG1ECZMpC5vixc49TvcdDoUm7_CenTF2dv5MYfZEs4F8AywceF4OZZ2tX5Ws4xkgUmwOFAM_b9gtXBxmSddD4oSUlbg2wFh7mcD3flBP9nwpjkPo8Adzvl0E9RQp3BWRJaZyjck_kYA5qH3ymRsy3kVs62kLMt5GKLnPTucbsPKfcmyIDPCwDzAA8Wg4zaotM42JBtkBW2_-P_C7t2xyw</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Ulrichsen, Kristine M.</creator><creator>Kolskår, Knut K.</creator><creator>Richard, Geneviève</creator><creator>Alnæs, Dag</creator><creator>Dørum, Erlend S.</creator><creator>Sanders, Anne-Marthe</creator><creator>Tornås, Sveinung</creator><creator>Sánchez, Jennifer Monereo</creator><creator>Engvig, Andreas</creator><creator>Ihle-Hansen, Hege</creator><creator>de Schotten, Michel Thiebaut</creator><creator>Nordvik, Jan E.</creator><creator>Westlye, Lars T.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>3HK</scope><scope>1XC</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-0981-648X</orcidid><orcidid>https://orcid.org/0000-0002-2638-2452</orcidid><orcidid>https://orcid.org/0000-0001-6475-2576</orcidid><orcidid>https://orcid.org/0000-0002-0329-1814</orcidid></search><sort><creationdate>20210101</creationdate><title>Structural brain disconnectivity mapping of post-stroke fatigue</title><author>Ulrichsen, Kristine M. ; Kolskår, Knut K. ; Richard, Geneviève ; Alnæs, Dag ; Dørum, Erlend S. ; Sanders, Anne-Marthe ; Tornås, Sveinung ; Sánchez, Jennifer Monereo ; Engvig, Andreas ; Ihle-Hansen, Hege ; de Schotten, Michel Thiebaut ; Nordvik, Jan E. ; Westlye, Lars T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c579t-e6c2a673e6274e4097b9ceef831796de8e5719aa639f1a632d0bc67fca2214183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Brain mapping</topic><topic>Cognitive science</topic><topic>Lesion</topic><topic>MRI</topic><topic>Post-stroke fatigue</topic><topic>Regular</topic><topic>Stroke</topic><topic>Structural disconnectome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ulrichsen, Kristine M.</creatorcontrib><creatorcontrib>Kolskår, Knut K.</creatorcontrib><creatorcontrib>Richard, Geneviève</creatorcontrib><creatorcontrib>Alnæs, Dag</creatorcontrib><creatorcontrib>Dørum, Erlend S.</creatorcontrib><creatorcontrib>Sanders, Anne-Marthe</creatorcontrib><creatorcontrib>Tornås, Sveinung</creatorcontrib><creatorcontrib>Sánchez, Jennifer Monereo</creatorcontrib><creatorcontrib>Engvig, Andreas</creatorcontrib><creatorcontrib>Ihle-Hansen, Hege</creatorcontrib><creatorcontrib>de Schotten, Michel Thiebaut</creatorcontrib><creatorcontrib>Nordvik, Jan E.</creatorcontrib><creatorcontrib>Westlye, Lars T.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>NORA - Norwegian Open Research Archives</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>NeuroImage clinical</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ulrichsen, Kristine M.</au><au>Kolskår, Knut K.</au><au>Richard, Geneviève</au><au>Alnæs, Dag</au><au>Dørum, Erlend S.</au><au>Sanders, Anne-Marthe</au><au>Tornås, Sveinung</au><au>Sánchez, Jennifer Monereo</au><au>Engvig, Andreas</au><au>Ihle-Hansen, Hege</au><au>de Schotten, Michel Thiebaut</au><au>Nordvik, Jan E.</au><au>Westlye, Lars T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural brain disconnectivity mapping of post-stroke fatigue</atitle><jtitle>NeuroImage clinical</jtitle><addtitle>Neuroimage Clin</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>30</volume><spage>102635</spage><epage>102635</epage><pages>102635-102635</pages><artnum>102635</artnum><issn>2213-1582</issn><eissn>2213-1582</eissn><abstract>•We tested for associations between post stroke fatigue (PSF) and both lesion characteristics and brain structural disconnectome in 84 S patients.•Results provided no evidence supporting a simple association between PSF severity and lesion characteristics or disconnectivity.•PSF was strongly correlated with depression.•Further studies including patients with more severe symptoms are needed to generalize the findings across a wider clinical spectrum. Stroke patients commonly suffer from post stroke fatigue (PSF). Despite a general consensus that brain perturbations constitute a precipitating event in the multifactorial etiology of PSF, the specific predictive value of conventional lesion characteristics such as size and localization remains unclear. The current study represents a novel approach to assess the neural correlates of PSF in chronic stroke patients. While previous research has focused primarily on lesion location or size, with mixed or inconclusive results, we targeted the extended structural network implicated by the lesion, and evaluated the added explanatory value of a structural disconnectivity approach with regards to the brain correlates of PSF. To this end, we estimated individual structural brain disconnectome maps in 84 S survivors in the chronic phase (≥3 months post stroke) using information about lesion location and normative white matter pathways obtained from 170 healthy individuals. PSF was measured by the Fatigue Severity Scale (FSS). Voxel wise analyses using non-parametric permutation-based inference were conducted on disconnectome maps to estimate regional effects of disconnectivity. Associations between PSF and global disconnectivity and clinical lesion characteristics were tested by linear models, and we estimated Bayes factor to quantify the evidence for the null and alternative hypotheses, respectively. The results revealed no significant associations between PSF and disconnectome measures or lesion characteristics, with moderate evidence in favor of the null hypothesis. These results suggest that symptoms of post-stroke fatigue among chronic stroke patients are not simply explained by lesion characteristics or the extent and distribution of structural brain disconnectome, and are discussed in light of methodological considerations.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>33799271</pmid><doi>10.1016/j.nicl.2021.102635</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-0981-648X</orcidid><orcidid>https://orcid.org/0000-0002-2638-2452</orcidid><orcidid>https://orcid.org/0000-0001-6475-2576</orcidid><orcidid>https://orcid.org/0000-0002-0329-1814</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2213-1582
ispartof NeuroImage clinical, 2021-01, Vol.30, p.102635-102635, Article 102635
issn 2213-1582
2213-1582
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_2ed7ac4bee14427fb3f32c030ad13af2
source Open Access: PubMed Central; NORA - Norwegian Open Research Archives; ScienceDirect Journals
subjects Brain mapping
Cognitive science
Lesion
MRI
Post-stroke fatigue
Regular
Stroke
Structural disconnectome
title Structural brain disconnectivity mapping of post-stroke fatigue
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T21%3A31%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Structural%20brain%20disconnectivity%20mapping%20of%20post-stroke%20fatigue&rft.jtitle=NeuroImage%20clinical&rft.au=Ulrichsen,%20Kristine%20M.&rft.date=2021-01-01&rft.volume=30&rft.spage=102635&rft.epage=102635&rft.pages=102635-102635&rft.artnum=102635&rft.issn=2213-1582&rft.eissn=2213-1582&rft_id=info:doi/10.1016/j.nicl.2021.102635&rft_dat=%3Cproquest_doaj_%3E2508563215%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c579t-e6c2a673e6274e4097b9ceef831796de8e5719aa639f1a632d0bc67fca2214183%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2508563215&rft_id=info:pmid/33799271&rfr_iscdi=true