Human Sarcopenic Myoblasts Can Be Rescued by Pharmacological Reactivation of HIF-1α
Sarcopenia, an age-related decline in muscle mass and strength, is associated with metabolic disease and increased risk of cardiovascular morbidity and mortality. It is associated with decreased tissue vascularization and muscle atrophy. In this work, we investigated the role of the hypoxia inducibl...
Gespeichert in:
| Veröffentlicht in: | International journal of molecular sciences 2022-07, Vol.23 (13), p.7114 |
|---|---|
| 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 | 13 |
| container_start_page | 7114 |
| container_title | International journal of molecular sciences |
| container_volume | 23 |
| creator | Cirillo, Federica Mangiavini, Laura La Rocca, Paolo Piccoli, Marco Ghiroldi, Andrea Rota, Paola Tarantino, Adriana Canciani, Barbara Coviello, Simona Messina, Carmelo Ciconte, Giuseppe Pappone, Carlo Peretti, Giuseppe Maria Anastasia, Luigi |
| description | Sarcopenia, an age-related decline in muscle mass and strength, is associated with metabolic disease and increased risk of cardiovascular morbidity and mortality. It is associated with decreased tissue vascularization and muscle atrophy. In this work, we investigated the role of the hypoxia inducible factor HIF-1α in sarcopenia. To this end, we obtained skeletal muscle biopsies from elderly sarcopenic patients and compared them with those from young individuals. We found a decrease in the expression of HIF-1α and its target genes in sarcopenia, as well as of PAX7, the major stem cell marker of satellite cells, whereas the atrophy marker MURF1 was increased. We also isolated satellite cells from muscle biopsies and cultured them in vitro. We found that a pharmacological activation of HIF-1α and its target genes caused a reduction in skeletal muscle atrophy and activation of PAX7 gene expression. In conclusion, in this work we found that HIF-1α plays a role in sarcopenia and is involved in satellite cell homeostasis. These results support further studies to test whether pharmacological reactivation of HIF-1α could prevent and counteract sarcopenia. |
| doi_str_mv | 10.3390/ijms23137114 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9267002</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2687720614</sourcerecordid><originalsourceid>FETCH-LOGICAL-c389t-95e47189aad44143fd731205352575a0d6cc7b9df8d2ec90a21c3006e8d46aec3</originalsourceid><addsrcrecordid>eNpdkc1Kw0AUhQdRbK3ufICAGxdG5yfJZDaCFmuFiqJ1PdxMJu2UJFNnkkIfyxfxmUxpkerqXjgfh3vuQeic4GvGBL4xi8pTRhgnJDpAfRJRGmKc8MO9vYdOvF9gTBmNxTHqsTjFCSGij6bjtoI6eAen7FLXRgXPa5uV4BsfDDvhXgdv2qtW50G2Dl7n4CpQtrQzo6DsJFCNWUFjbB3YIhg_jULy_XWKjgoovT7bzQH6GD1Mh-Nw8vL4NLybhIqloglFrCNOUgGQRxGJWJFzRiiOWUxjHgPOE6V4JvIizalWAgMlinVxdJpHCWjFBuh267tss0rnSteNg1IunanAraUFI_8qtZnLmV1JQRO--cYAXe4MnP1stW9kZbzSZQm1tq2XNEk5p92rog69-IcubOvqLt6GSghmFKcddbWllLPeO138HkOw3NQl9-tiP8lIhsY</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2686103208</pqid></control><display><type>article</type><title>Human Sarcopenic Myoblasts Can Be Rescued by Pharmacological Reactivation of HIF-1α</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Cirillo, Federica ; Mangiavini, Laura ; La Rocca, Paolo ; Piccoli, Marco ; Ghiroldi, Andrea ; Rota, Paola ; Tarantino, Adriana ; Canciani, Barbara ; Coviello, Simona ; Messina, Carmelo ; Ciconte, Giuseppe ; Pappone, Carlo ; Peretti, Giuseppe Maria ; Anastasia, Luigi</creator><creatorcontrib>Cirillo, Federica ; Mangiavini, Laura ; La Rocca, Paolo ; Piccoli, Marco ; Ghiroldi, Andrea ; Rota, Paola ; Tarantino, Adriana ; Canciani, Barbara ; Coviello, Simona ; Messina, Carmelo ; Ciconte, Giuseppe ; Pappone, Carlo ; Peretti, Giuseppe Maria ; Anastasia, Luigi</creatorcontrib><description>Sarcopenia, an age-related decline in muscle mass and strength, is associated with metabolic disease and increased risk of cardiovascular morbidity and mortality. It is associated with decreased tissue vascularization and muscle atrophy. In this work, we investigated the role of the hypoxia inducible factor HIF-1α in sarcopenia. To this end, we obtained skeletal muscle biopsies from elderly sarcopenic patients and compared them with those from young individuals. We found a decrease in the expression of HIF-1α and its target genes in sarcopenia, as well as of PAX7, the major stem cell marker of satellite cells, whereas the atrophy marker MURF1 was increased. We also isolated satellite cells from muscle biopsies and cultured them in vitro. We found that a pharmacological activation of HIF-1α and its target genes caused a reduction in skeletal muscle atrophy and activation of PAX7 gene expression. In conclusion, in this work we found that HIF-1α plays a role in sarcopenia and is involved in satellite cell homeostasis. These results support further studies to test whether pharmacological reactivation of HIF-1α could prevent and counteract sarcopenia.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms23137114</identifier><identifier>PMID: 35806119</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Age ; Aging ; Angiogenesis ; Atrophy ; Biopsy ; Blood vessels ; Cardiovascular diseases ; Cell cycle ; Gene expression ; Genes ; Genotype & phenotype ; Homeostasis ; Hypoxia ; Hypoxia-inducible factor 1a ; Metabolic disorders ; Morbidity ; Muscles ; Musculoskeletal system ; Myoblasts ; Older people ; Pharmacology ; Population ; Proteins ; Public health ; Sarcopenia ; Satellite cells ; Skeletal muscle ; Stem cells ; Vascularization</subject><ispartof>International journal of molecular sciences, 2022-07, Vol.23 (13), p.7114</ispartof><rights>2022 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 (https://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>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-95e47189aad44143fd731205352575a0d6cc7b9df8d2ec90a21c3006e8d46aec3</citedby><cites>FETCH-LOGICAL-c389t-95e47189aad44143fd731205352575a0d6cc7b9df8d2ec90a21c3006e8d46aec3</cites><orcidid>0000-0002-1859-130X ; 0000-0002-0196-5977 ; 0000-0001-5795-4989 ; 0000-0002-2896-7390 ; 0000-0001-9341-7187 ; 0000-0002-1872-9524 ; 0000-0001-7518-5773 ; 0000-0002-0712-2161</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/PMC9267002/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267002/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids></links><search><creatorcontrib>Cirillo, Federica</creatorcontrib><creatorcontrib>Mangiavini, Laura</creatorcontrib><creatorcontrib>La Rocca, Paolo</creatorcontrib><creatorcontrib>Piccoli, Marco</creatorcontrib><creatorcontrib>Ghiroldi, Andrea</creatorcontrib><creatorcontrib>Rota, Paola</creatorcontrib><creatorcontrib>Tarantino, Adriana</creatorcontrib><creatorcontrib>Canciani, Barbara</creatorcontrib><creatorcontrib>Coviello, Simona</creatorcontrib><creatorcontrib>Messina, Carmelo</creatorcontrib><creatorcontrib>Ciconte, Giuseppe</creatorcontrib><creatorcontrib>Pappone, Carlo</creatorcontrib><creatorcontrib>Peretti, Giuseppe Maria</creatorcontrib><creatorcontrib>Anastasia, Luigi</creatorcontrib><title>Human Sarcopenic Myoblasts Can Be Rescued by Pharmacological Reactivation of HIF-1α</title><title>International journal of molecular sciences</title><description>Sarcopenia, an age-related decline in muscle mass and strength, is associated with metabolic disease and increased risk of cardiovascular morbidity and mortality. It is associated with decreased tissue vascularization and muscle atrophy. In this work, we investigated the role of the hypoxia inducible factor HIF-1α in sarcopenia. To this end, we obtained skeletal muscle biopsies from elderly sarcopenic patients and compared them with those from young individuals. We found a decrease in the expression of HIF-1α and its target genes in sarcopenia, as well as of PAX7, the major stem cell marker of satellite cells, whereas the atrophy marker MURF1 was increased. We also isolated satellite cells from muscle biopsies and cultured them in vitro. We found that a pharmacological activation of HIF-1α and its target genes caused a reduction in skeletal muscle atrophy and activation of PAX7 gene expression. In conclusion, in this work we found that HIF-1α plays a role in sarcopenia and is involved in satellite cell homeostasis. These results support further studies to test whether pharmacological reactivation of HIF-1α could prevent and counteract sarcopenia.</description><subject>Age</subject><subject>Aging</subject><subject>Angiogenesis</subject><subject>Atrophy</subject><subject>Biopsy</subject><subject>Blood vessels</subject><subject>Cardiovascular diseases</subject><subject>Cell cycle</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genotype & phenotype</subject><subject>Homeostasis</subject><subject>Hypoxia</subject><subject>Hypoxia-inducible factor 1a</subject><subject>Metabolic disorders</subject><subject>Morbidity</subject><subject>Muscles</subject><subject>Musculoskeletal system</subject><subject>Myoblasts</subject><subject>Older people</subject><subject>Pharmacology</subject><subject>Population</subject><subject>Proteins</subject><subject>Public health</subject><subject>Sarcopenia</subject><subject>Satellite cells</subject><subject>Skeletal muscle</subject><subject>Stem cells</subject><subject>Vascularization</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkc1Kw0AUhQdRbK3ufICAGxdG5yfJZDaCFmuFiqJ1PdxMJu2UJFNnkkIfyxfxmUxpkerqXjgfh3vuQeic4GvGBL4xi8pTRhgnJDpAfRJRGmKc8MO9vYdOvF9gTBmNxTHqsTjFCSGij6bjtoI6eAen7FLXRgXPa5uV4BsfDDvhXgdv2qtW50G2Dl7n4CpQtrQzo6DsJFCNWUFjbB3YIhg_jULy_XWKjgoovT7bzQH6GD1Mh-Nw8vL4NLybhIqloglFrCNOUgGQRxGJWJFzRiiOWUxjHgPOE6V4JvIizalWAgMlinVxdJpHCWjFBuh267tss0rnSteNg1IunanAraUFI_8qtZnLmV1JQRO--cYAXe4MnP1stW9kZbzSZQm1tq2XNEk5p92rog69-IcubOvqLt6GSghmFKcddbWllLPeO138HkOw3NQl9-tiP8lIhsY</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Cirillo, Federica</creator><creator>Mangiavini, Laura</creator><creator>La Rocca, Paolo</creator><creator>Piccoli, Marco</creator><creator>Ghiroldi, Andrea</creator><creator>Rota, Paola</creator><creator>Tarantino, Adriana</creator><creator>Canciani, Barbara</creator><creator>Coviello, Simona</creator><creator>Messina, Carmelo</creator><creator>Ciconte, Giuseppe</creator><creator>Pappone, Carlo</creator><creator>Peretti, Giuseppe Maria</creator><creator>Anastasia, Luigi</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</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>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</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><orcidid>https://orcid.org/0000-0002-1859-130X</orcidid><orcidid>https://orcid.org/0000-0002-0196-5977</orcidid><orcidid>https://orcid.org/0000-0001-5795-4989</orcidid><orcidid>https://orcid.org/0000-0002-2896-7390</orcidid><orcidid>https://orcid.org/0000-0001-9341-7187</orcidid><orcidid>https://orcid.org/0000-0002-1872-9524</orcidid><orcidid>https://orcid.org/0000-0001-7518-5773</orcidid><orcidid>https://orcid.org/0000-0002-0712-2161</orcidid></search><sort><creationdate>20220701</creationdate><title>Human Sarcopenic Myoblasts Can Be Rescued by Pharmacological Reactivation of HIF-1α</title><author>Cirillo, Federica ; Mangiavini, Laura ; La Rocca, Paolo ; Piccoli, Marco ; Ghiroldi, Andrea ; Rota, Paola ; Tarantino, Adriana ; Canciani, Barbara ; Coviello, Simona ; Messina, Carmelo ; Ciconte, Giuseppe ; Pappone, Carlo ; Peretti, Giuseppe Maria ; Anastasia, Luigi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-95e47189aad44143fd731205352575a0d6cc7b9df8d2ec90a21c3006e8d46aec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Age</topic><topic>Aging</topic><topic>Angiogenesis</topic><topic>Atrophy</topic><topic>Biopsy</topic><topic>Blood vessels</topic><topic>Cardiovascular diseases</topic><topic>Cell cycle</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genotype & phenotype</topic><topic>Homeostasis</topic><topic>Hypoxia</topic><topic>Hypoxia-inducible factor 1a</topic><topic>Metabolic disorders</topic><topic>Morbidity</topic><topic>Muscles</topic><topic>Musculoskeletal system</topic><topic>Myoblasts</topic><topic>Older people</topic><topic>Pharmacology</topic><topic>Population</topic><topic>Proteins</topic><topic>Public health</topic><topic>Sarcopenia</topic><topic>Satellite cells</topic><topic>Skeletal muscle</topic><topic>Stem cells</topic><topic>Vascularization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cirillo, Federica</creatorcontrib><creatorcontrib>Mangiavini, Laura</creatorcontrib><creatorcontrib>La Rocca, Paolo</creatorcontrib><creatorcontrib>Piccoli, Marco</creatorcontrib><creatorcontrib>Ghiroldi, Andrea</creatorcontrib><creatorcontrib>Rota, Paola</creatorcontrib><creatorcontrib>Tarantino, Adriana</creatorcontrib><creatorcontrib>Canciani, Barbara</creatorcontrib><creatorcontrib>Coviello, Simona</creatorcontrib><creatorcontrib>Messina, Carmelo</creatorcontrib><creatorcontrib>Ciconte, Giuseppe</creatorcontrib><creatorcontrib>Pappone, Carlo</creatorcontrib><creatorcontrib>Peretti, Giuseppe Maria</creatorcontrib><creatorcontrib>Anastasia, Luigi</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>ProQuest Central Essentials</collection><collection>ProQuest Central</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</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><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cirillo, Federica</au><au>Mangiavini, Laura</au><au>La Rocca, Paolo</au><au>Piccoli, Marco</au><au>Ghiroldi, Andrea</au><au>Rota, Paola</au><au>Tarantino, Adriana</au><au>Canciani, Barbara</au><au>Coviello, Simona</au><au>Messina, Carmelo</au><au>Ciconte, Giuseppe</au><au>Pappone, Carlo</au><au>Peretti, Giuseppe Maria</au><au>Anastasia, Luigi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human Sarcopenic Myoblasts Can Be Rescued by Pharmacological Reactivation of HIF-1α</atitle><jtitle>International journal of molecular sciences</jtitle><date>2022-07-01</date><risdate>2022</risdate><volume>23</volume><issue>13</issue><spage>7114</spage><pages>7114-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Sarcopenia, an age-related decline in muscle mass and strength, is associated with metabolic disease and increased risk of cardiovascular morbidity and mortality. It is associated with decreased tissue vascularization and muscle atrophy. In this work, we investigated the role of the hypoxia inducible factor HIF-1α in sarcopenia. To this end, we obtained skeletal muscle biopsies from elderly sarcopenic patients and compared them with those from young individuals. We found a decrease in the expression of HIF-1α and its target genes in sarcopenia, as well as of PAX7, the major stem cell marker of satellite cells, whereas the atrophy marker MURF1 was increased. We also isolated satellite cells from muscle biopsies and cultured them in vitro. We found that a pharmacological activation of HIF-1α and its target genes caused a reduction in skeletal muscle atrophy and activation of PAX7 gene expression. In conclusion, in this work we found that HIF-1α plays a role in sarcopenia and is involved in satellite cell homeostasis. These results support further studies to test whether pharmacological reactivation of HIF-1α could prevent and counteract sarcopenia.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>35806119</pmid><doi>10.3390/ijms23137114</doi><orcidid>https://orcid.org/0000-0002-1859-130X</orcidid><orcidid>https://orcid.org/0000-0002-0196-5977</orcidid><orcidid>https://orcid.org/0000-0001-5795-4989</orcidid><orcidid>https://orcid.org/0000-0002-2896-7390</orcidid><orcidid>https://orcid.org/0000-0001-9341-7187</orcidid><orcidid>https://orcid.org/0000-0002-1872-9524</orcidid><orcidid>https://orcid.org/0000-0001-7518-5773</orcidid><orcidid>https://orcid.org/0000-0002-0712-2161</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1422-0067 |
| ispartof | International journal of molecular sciences, 2022-07, Vol.23 (13), p.7114 |
| issn | 1422-0067 1661-6596 1422-0067 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9267002 |
| source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Age Aging Angiogenesis Atrophy Biopsy Blood vessels Cardiovascular diseases Cell cycle Gene expression Genes Genotype & phenotype Homeostasis Hypoxia Hypoxia-inducible factor 1a Metabolic disorders Morbidity Muscles Musculoskeletal system Myoblasts Older people Pharmacology Population Proteins Public health Sarcopenia Satellite cells Skeletal muscle Stem cells Vascularization |
| title | Human Sarcopenic Myoblasts Can Be Rescued by Pharmacological Reactivation of HIF-1α |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T21%3A56%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Human%20Sarcopenic%20Myoblasts%20Can%20Be%20Rescued%20by%20Pharmacological%20Reactivation%20of%20HIF-1%CE%B1&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Cirillo,%20Federica&rft.date=2022-07-01&rft.volume=23&rft.issue=13&rft.spage=7114&rft.pages=7114-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms23137114&rft_dat=%3Cproquest_pubme%3E2687720614%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2686103208&rft_id=info:pmid/35806119&rfr_iscdi=true |