Wound Healing Promotion by Hyaluronic Acid: Effect of Molecular Weight on Gene Expression and In Vivo Wound Closure
Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing proces...
Gespeichert in:
| Veröffentlicht in: | Pharmaceuticals (Basel, Switzerland) Switzerland), 2021-03, Vol.14 (4), p.301, Article 301 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 4 |
| container_start_page | 301 |
| container_title | Pharmaceuticals (Basel, Switzerland) |
| container_volume | 14 |
| creator | Kawano, Yayoi Patrulea, Viorica Sublet, Emmanuelle Borchard, Gerrit Iyoda, Takuya Kageyama, Rihoko Morita, Asa Seino, Satoshi Yoshida, Hideto Jordan, Olivier Hanawa, Takehisa |
| description | Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1 beta), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds. |
| doi_str_mv | 10.3390/ph14040301 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_crossref_primary_10_3390_ph14040301</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_60d78544f3f947008687cbbb2ee52276</doaj_id><sourcerecordid>2508575961</sourcerecordid><originalsourceid>FETCH-LOGICAL-c538t-7e964bd58340544b47ecfcb6f3531556fe837caa28bbb4816dd5c3a8415c71303</originalsourceid><addsrcrecordid>eNqNksGPEyEUxidG4-5WL_4BhsSLWVOFAQbGg8lmUrdN1uhB3SNhmEdLM4UuzKz2v5fate568sTj8eN7X-ArihcEv6W0xu-2K8IwwxSTR8UpYSWbypKJx_fqk-IspTXGXBBGnhYnlMq8kfK0SNdh9B2ag-6dX6IvMWzC4IJH7Q7Nd7ofY_DOoAvjuvdoZi2YAQWLPoUezNjriK7BLVe559EleECzn9sIKe0VdNZdePTd3QZ0mNL0IY0RnhVPrO4TPL9bJ8W3j7OvzXx69fly0VxcTQ2ncpgKqCvWdlxShjljLRNgrGkrSzklnFcWJBVG61K2bcskqbqOG6olI9wIQjGdFIuDbhf0Wm2j2-i4U0E79bsR4lLpODjTg6pwJ2QeYqmtmcBYVlKYLFsC8LIUVdb6cNDaju0GOgN-iLp_IPrwxLuVWoZbJXHF6-x4Ury-E4jhZoQ0qI1LBvpeewhjUiXHkgteVySjr_5B12GMPj9VpjguSYnx3tH5gTIxpBTBHs0QrPa5UH9zkeGX9-0f0T9ByIA8AD-gDTYZB97AEcN5IKOU8zpXmDRu0PuQNPlXh3z1zf9fpb8AJNTSiw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2550212006</pqid></control><display><type>article</type><title>Wound Healing Promotion by Hyaluronic Acid: Effect of Molecular Weight on Gene Expression and In Vivo Wound Closure</title><source>DOAJ Directory of Open Access Journals</source><source>PubMed Central Open Access</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /></source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Kawano, Yayoi ; Patrulea, Viorica ; Sublet, Emmanuelle ; Borchard, Gerrit ; Iyoda, Takuya ; Kageyama, Rihoko ; Morita, Asa ; Seino, Satoshi ; Yoshida, Hideto ; Jordan, Olivier ; Hanawa, Takehisa</creator><creatorcontrib>Kawano, Yayoi ; Patrulea, Viorica ; Sublet, Emmanuelle ; Borchard, Gerrit ; Iyoda, Takuya ; Kageyama, Rihoko ; Morita, Asa ; Seino, Satoshi ; Yoshida, Hideto ; Jordan, Olivier ; Hanawa, Takehisa</creatorcontrib><description>Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1 beta), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.</description><identifier>ISSN: 1424-8247</identifier><identifier>EISSN: 1424-8247</identifier><identifier>DOI: 10.3390/ph14040301</identifier><identifier>PMID: 33800588</identifier><language>eng</language><publisher>BASEL: Mdpi</publisher><subject>accelerated wound healing ; Angiogenesis ; Chemistry, Medicinal ; Cytokines ; epidermal cells ; Fibroblasts ; Gene expression ; Hyaluronic acid ; Inflammation ; Insulin-like growth factors ; Life Sciences & Biomedicine ; Molecular weight ; Pharmacology & Pharmacy ; Science & Technology ; Tumor necrosis factor-TNF ; Vascular endothelial growth factor ; Wound healing</subject><ispartof>Pharmaceuticals (Basel, Switzerland), 2021-03, Vol.14 (4), p.301, Article 301</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>61</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000643355900001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c538t-7e964bd58340544b47ecfcb6f3531556fe837caa28bbb4816dd5c3a8415c71303</citedby><cites>FETCH-LOGICAL-c538t-7e964bd58340544b47ecfcb6f3531556fe837caa28bbb4816dd5c3a8415c71303</cites><orcidid>0000-0002-3922-025X ; 0000-0003-3906-2041 ; 0000-0001-5241-3622 ; 0000-0002-3551-674X ; 0000-0003-3752-2198 ; 0000-0001-6268-2586</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/PMC8065935/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065935/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2115,27929,27930,39263,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33800588$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kawano, Yayoi</creatorcontrib><creatorcontrib>Patrulea, Viorica</creatorcontrib><creatorcontrib>Sublet, Emmanuelle</creatorcontrib><creatorcontrib>Borchard, Gerrit</creatorcontrib><creatorcontrib>Iyoda, Takuya</creatorcontrib><creatorcontrib>Kageyama, Rihoko</creatorcontrib><creatorcontrib>Morita, Asa</creatorcontrib><creatorcontrib>Seino, Satoshi</creatorcontrib><creatorcontrib>Yoshida, Hideto</creatorcontrib><creatorcontrib>Jordan, Olivier</creatorcontrib><creatorcontrib>Hanawa, Takehisa</creatorcontrib><title>Wound Healing Promotion by Hyaluronic Acid: Effect of Molecular Weight on Gene Expression and In Vivo Wound Closure</title><title>Pharmaceuticals (Basel, Switzerland)</title><addtitle>PHARMACEUTICALS-BASE</addtitle><addtitle>Pharmaceuticals (Basel)</addtitle><description>Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1 beta), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.</description><subject>accelerated wound healing</subject><subject>Angiogenesis</subject><subject>Chemistry, Medicinal</subject><subject>Cytokines</subject><subject>epidermal cells</subject><subject>Fibroblasts</subject><subject>Gene expression</subject><subject>Hyaluronic acid</subject><subject>Inflammation</subject><subject>Insulin-like growth factors</subject><subject>Life Sciences & Biomedicine</subject><subject>Molecular weight</subject><subject>Pharmacology & Pharmacy</subject><subject>Science & Technology</subject><subject>Tumor necrosis factor-TNF</subject><subject>Vascular endothelial growth factor</subject><subject>Wound healing</subject><issn>1424-8247</issn><issn>1424-8247</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</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><sourceid>DOA</sourceid><recordid>eNqNksGPEyEUxidG4-5WL_4BhsSLWVOFAQbGg8lmUrdN1uhB3SNhmEdLM4UuzKz2v5fate568sTj8eN7X-ArihcEv6W0xu-2K8IwwxSTR8UpYSWbypKJx_fqk-IspTXGXBBGnhYnlMq8kfK0SNdh9B2ag-6dX6IvMWzC4IJH7Q7Nd7ofY_DOoAvjuvdoZi2YAQWLPoUezNjriK7BLVe559EleECzn9sIKe0VdNZdePTd3QZ0mNL0IY0RnhVPrO4TPL9bJ8W3j7OvzXx69fly0VxcTQ2ncpgKqCvWdlxShjljLRNgrGkrSzklnFcWJBVG61K2bcskqbqOG6olI9wIQjGdFIuDbhf0Wm2j2-i4U0E79bsR4lLpODjTg6pwJ2QeYqmtmcBYVlKYLFsC8LIUVdb6cNDaju0GOgN-iLp_IPrwxLuVWoZbJXHF6-x4Ury-E4jhZoQ0qI1LBvpeewhjUiXHkgteVySjr_5B12GMPj9VpjguSYnx3tH5gTIxpBTBHs0QrPa5UH9zkeGX9-0f0T9ByIA8AD-gDTYZB97AEcN5IKOU8zpXmDRu0PuQNPlXh3z1zf9fpb8AJNTSiw</recordid><startdate>20210328</startdate><enddate>20210328</enddate><creator>Kawano, Yayoi</creator><creator>Patrulea, Viorica</creator><creator>Sublet, Emmanuelle</creator><creator>Borchard, Gerrit</creator><creator>Iyoda, Takuya</creator><creator>Kageyama, Rihoko</creator><creator>Morita, Asa</creator><creator>Seino, Satoshi</creator><creator>Yoshida, Hideto</creator><creator>Jordan, Olivier</creator><creator>Hanawa, Takehisa</creator><general>Mdpi</general><general>MDPI AG</general><general>MDPI</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7XB</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3922-025X</orcidid><orcidid>https://orcid.org/0000-0003-3906-2041</orcidid><orcidid>https://orcid.org/0000-0001-5241-3622</orcidid><orcidid>https://orcid.org/0000-0002-3551-674X</orcidid><orcidid>https://orcid.org/0000-0003-3752-2198</orcidid><orcidid>https://orcid.org/0000-0001-6268-2586</orcidid></search><sort><creationdate>20210328</creationdate><title>Wound Healing Promotion by Hyaluronic Acid: Effect of Molecular Weight on Gene Expression and In Vivo Wound Closure</title><author>Kawano, Yayoi ; Patrulea, Viorica ; Sublet, Emmanuelle ; Borchard, Gerrit ; Iyoda, Takuya ; Kageyama, Rihoko ; Morita, Asa ; Seino, Satoshi ; Yoshida, Hideto ; Jordan, Olivier ; Hanawa, Takehisa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c538t-7e964bd58340544b47ecfcb6f3531556fe837caa28bbb4816dd5c3a8415c71303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>accelerated wound healing</topic><topic>Angiogenesis</topic><topic>Chemistry, Medicinal</topic><topic>Cytokines</topic><topic>epidermal cells</topic><topic>Fibroblasts</topic><topic>Gene expression</topic><topic>Hyaluronic acid</topic><topic>Inflammation</topic><topic>Insulin-like growth factors</topic><topic>Life Sciences & Biomedicine</topic><topic>Molecular weight</topic><topic>Pharmacology & Pharmacy</topic><topic>Science & Technology</topic><topic>Tumor necrosis factor-TNF</topic><topic>Vascular endothelial growth factor</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kawano, Yayoi</creatorcontrib><creatorcontrib>Patrulea, Viorica</creatorcontrib><creatorcontrib>Sublet, Emmanuelle</creatorcontrib><creatorcontrib>Borchard, Gerrit</creatorcontrib><creatorcontrib>Iyoda, Takuya</creatorcontrib><creatorcontrib>Kageyama, Rihoko</creatorcontrib><creatorcontrib>Morita, Asa</creatorcontrib><creatorcontrib>Seino, Satoshi</creatorcontrib><creatorcontrib>Yoshida, Hideto</creatorcontrib><creatorcontrib>Jordan, Olivier</creatorcontrib><creatorcontrib>Hanawa, Takehisa</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Central (purchase pre-March 2016)</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>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Access via ProQuest (Open Access)</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 Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Pharmaceuticals (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kawano, Yayoi</au><au>Patrulea, Viorica</au><au>Sublet, Emmanuelle</au><au>Borchard, Gerrit</au><au>Iyoda, Takuya</au><au>Kageyama, Rihoko</au><au>Morita, Asa</au><au>Seino, Satoshi</au><au>Yoshida, Hideto</au><au>Jordan, Olivier</au><au>Hanawa, Takehisa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Wound Healing Promotion by Hyaluronic Acid: Effect of Molecular Weight on Gene Expression and In Vivo Wound Closure</atitle><jtitle>Pharmaceuticals (Basel, Switzerland)</jtitle><stitle>PHARMACEUTICALS-BASE</stitle><addtitle>Pharmaceuticals (Basel)</addtitle><date>2021-03-28</date><risdate>2021</risdate><volume>14</volume><issue>4</issue><spage>301</spage><pages>301-</pages><artnum>301</artnum><issn>1424-8247</issn><eissn>1424-8247</eissn><abstract>Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1 beta), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.</abstract><cop>BASEL</cop><pub>Mdpi</pub><pmid>33800588</pmid><doi>10.3390/ph14040301</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-3922-025X</orcidid><orcidid>https://orcid.org/0000-0003-3906-2041</orcidid><orcidid>https://orcid.org/0000-0001-5241-3622</orcidid><orcidid>https://orcid.org/0000-0002-3551-674X</orcidid><orcidid>https://orcid.org/0000-0003-3752-2198</orcidid><orcidid>https://orcid.org/0000-0001-6268-2586</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1424-8247 |
| ispartof | Pharmaceuticals (Basel, Switzerland), 2021-03, Vol.14 (4), p.301, Article 301 |
| issn | 1424-8247 1424-8247 |
| language | eng |
| recordid | cdi_crossref_primary_10_3390_ph14040301 |
| source | DOAJ Directory of Open Access Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | accelerated wound healing Angiogenesis Chemistry, Medicinal Cytokines epidermal cells Fibroblasts Gene expression Hyaluronic acid Inflammation Insulin-like growth factors Life Sciences & Biomedicine Molecular weight Pharmacology & Pharmacy Science & Technology Tumor necrosis factor-TNF Vascular endothelial growth factor Wound healing |
| title | Wound Healing Promotion by Hyaluronic Acid: Effect of Molecular Weight on Gene Expression and In Vivo Wound Closure |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-12T12%3A51%3A21IST&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=Wound%20Healing%20Promotion%20by%20Hyaluronic%20Acid:%20Effect%20of%20Molecular%20Weight%20on%20Gene%20Expression%20and%20In%20Vivo%20Wound%20Closure&rft.jtitle=Pharmaceuticals%20(Basel,%20Switzerland)&rft.au=Kawano,%20Yayoi&rft.date=2021-03-28&rft.volume=14&rft.issue=4&rft.spage=301&rft.pages=301-&rft.artnum=301&rft.issn=1424-8247&rft.eissn=1424-8247&rft_id=info:doi/10.3390/ph14040301&rft_dat=%3Cproquest_cross%3E2508575961%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=2550212006&rft_id=info:pmid/33800588&rft_doaj_id=oai_doaj_org_article_60d78544f3f947008687cbbb2ee52276&rfr_iscdi=true |