The effects of nitric oxide on coagulation and inflammation in ex vivo models of extracorporeal membrane oxygenation and cardiopulmonary bypass

Extracorporeal life support (ECLS) has extensive applications in managing patients with acute cardiac and pulmonary failure. Two primary modalities of ECLS, cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO), include several similarities in their composition, complications,...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Artificial organs 2023-10, Vol.47 (10), p.1581-1591
Hauptverfasser: Malfertheiner, Maximilian V, Garrett, Ashlen, Passmore, Margaret, Haymet, Andrew B, Webb, Richard I, Von Bahr, Viktor, Millar, Jonathan E, Schneider, Bailey A, Obonyo, Nchafatso G, Black, Debra, Bouquet, Mahe, Bartnikowski, Nicole, Suen, Jacky Y, Fraser, John F
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1591
container_issue 10
container_start_page 1581
container_title Artificial organs
container_volume 47
creator Malfertheiner, Maximilian V
Garrett, Ashlen
Passmore, Margaret
Haymet, Andrew B
Webb, Richard I
Von Bahr, Viktor
Millar, Jonathan E
Schneider, Bailey A
Obonyo, Nchafatso G
Black, Debra
Bouquet, Mahe
Bartnikowski, Nicole
Suen, Jacky Y
Fraser, John F
description Extracorporeal life support (ECLS) has extensive applications in managing patients with acute cardiac and pulmonary failure. Two primary modalities of ECLS, cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO), include several similarities in their composition, complications, and patient outcomes. Both CPB and ECMO pose a high risk of thrombus formation and platelet activation due to the large surface area of the devices and bleeding due to system anticoagulation. Therefore, novel methods of anticoagulation are needed to reduce the morbidity and mortality associated with extracorporeal support. Nitric oxide (NO) has potent antiplatelet properties and presents a promising alternative or addition to anticoagulation with heparin during extracorporeal support. We developed two ex vivo models of CPB and ECMO to investigate NO effects on anticoagulation and inflammation in these systems. Sole addition of NO as an anticoagulant was not successful in preventing thrombus formation in the ex vivo setups, therefore a combination of low-level heparin with NO was used. Antiplatelet effects were observed in the ex vivo ECMO model when NO was delivered at 80 ppm. Platelet count was preserved after 480 min when NO was delivered at 30 ppm. Combined delivery of NO and heparin did not improve haemocompatibility in either ex vivo model of CPB and ECMO. Anti-inflammatory effects of NO in ECMO systems have to be evaluated further.
doi_str_mv 10.1111/aor.14608
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2832842701</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2882285159</sourcerecordid><originalsourceid>FETCH-LOGICAL-c348t-102d591c0b39201dfbdd607b8372a14ae3d27a1e52d0d6d67bceb7f68ad43ec43</originalsourceid><addsrcrecordid>eNpdkU9LHDEYh4NU3O22h36BEuilHkbzdzJ7LGJtQfCi4G3IJO9ss0ySaTIju5_Cr2x0bQVzSQgPD7_3_SH0hZIzWs65jumMipo0R2hJJZMVlWvxAS0JrUkla3G_QB9z3hJClCD1CVpwxddScblEj7d_AEPfg5kyjj0ObkrO4LhzFnAM2ES9mQc9ufLWwWIX-kF7f_hwAcMOP7iHiH20MLwYYDclbWIaYwI9YA--SzoU2W6_gfBmMjpZF8d58DHotMfdftQ5f0LHvR4yfH69V-ju5-Xtxa_q-ubq98WP68pw0UwVJczKNTWk42tGqO07a2uiuoYrpqnQwC1TmoJkltja1qoz0Km-brQVHIzgK_T94B1T_DtDnlrvsoFhKFHjnFvWcNYIpggt6Ld36DbOKZR0hWoYa2RZd6FOD5RJMecEfTsm58tgLSXtc0ttaal9aamwX1-Nc-fB_if_1cKfACqnkF8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2882285159</pqid></control><display><type>article</type><title>The effects of nitric oxide on coagulation and inflammation in ex vivo models of extracorporeal membrane oxygenation and cardiopulmonary bypass</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Malfertheiner, Maximilian V ; Garrett, Ashlen ; Passmore, Margaret ; Haymet, Andrew B ; Webb, Richard I ; Von Bahr, Viktor ; Millar, Jonathan E ; Schneider, Bailey A ; Obonyo, Nchafatso G ; Black, Debra ; Bouquet, Mahe ; Bartnikowski, Nicole ; Suen, Jacky Y ; Fraser, John F</creator><creatorcontrib>Malfertheiner, Maximilian V ; Garrett, Ashlen ; Passmore, Margaret ; Haymet, Andrew B ; Webb, Richard I ; Von Bahr, Viktor ; Millar, Jonathan E ; Schneider, Bailey A ; Obonyo, Nchafatso G ; Black, Debra ; Bouquet, Mahe ; Bartnikowski, Nicole ; Suen, Jacky Y ; Fraser, John F</creatorcontrib><description>Extracorporeal life support (ECLS) has extensive applications in managing patients with acute cardiac and pulmonary failure. Two primary modalities of ECLS, cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO), include several similarities in their composition, complications, and patient outcomes. Both CPB and ECMO pose a high risk of thrombus formation and platelet activation due to the large surface area of the devices and bleeding due to system anticoagulation. Therefore, novel methods of anticoagulation are needed to reduce the morbidity and mortality associated with extracorporeal support. Nitric oxide (NO) has potent antiplatelet properties and presents a promising alternative or addition to anticoagulation with heparin during extracorporeal support. We developed two ex vivo models of CPB and ECMO to investigate NO effects on anticoagulation and inflammation in these systems. Sole addition of NO as an anticoagulant was not successful in preventing thrombus formation in the ex vivo setups, therefore a combination of low-level heparin with NO was used. Antiplatelet effects were observed in the ex vivo ECMO model when NO was delivered at 80 ppm. Platelet count was preserved after 480 min when NO was delivered at 30 ppm. Combined delivery of NO and heparin did not improve haemocompatibility in either ex vivo model of CPB and ECMO. Anti-inflammatory effects of NO in ECMO systems have to be evaluated further.</description><identifier>ISSN: 0160-564X</identifier><identifier>ISSN: 1525-1594</identifier><identifier>EISSN: 1525-1594</identifier><identifier>DOI: 10.1111/aor.14608</identifier><identifier>PMID: 37395735</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Anticoagulants ; Anticoagulants - pharmacology ; Anticoagulants - therapeutic use ; Blood clots ; Cardiopulmonary Bypass - adverse effects ; Cardiopulmonary Bypass - methods ; Coagulation ; Complications ; Extracorporeal membrane oxygenation ; Extracorporeal Membrane Oxygenation - adverse effects ; Extracorporeal Membrane Oxygenation - methods ; Heart surgery ; Heparin ; Heparin - pharmacology ; Heparin - therapeutic use ; Humans ; Inflammation ; Inflammation - etiology ; Inflammation - prevention &amp; control ; Membranes ; Morbidity ; Nitric oxide ; Nitric Oxide - therapeutic use ; Oxygenation ; Platelets ; Thrombosis ; Thrombosis - etiology ; Thrombosis - prevention &amp; control</subject><ispartof>Artificial organs, 2023-10, Vol.47 (10), p.1581-1591</ispartof><rights>2023 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.</rights><rights>2023. This article 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-c348t-102d591c0b39201dfbdd607b8372a14ae3d27a1e52d0d6d67bceb7f68ad43ec43</citedby><cites>FETCH-LOGICAL-c348t-102d591c0b39201dfbdd607b8372a14ae3d27a1e52d0d6d67bceb7f68ad43ec43</cites><orcidid>0000-0002-0859-8882 ; 0000-0002-6245-2614 ; 0000-0002-5040-4359 ; 0000-0001-6511-0081</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37395735$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Malfertheiner, Maximilian V</creatorcontrib><creatorcontrib>Garrett, Ashlen</creatorcontrib><creatorcontrib>Passmore, Margaret</creatorcontrib><creatorcontrib>Haymet, Andrew B</creatorcontrib><creatorcontrib>Webb, Richard I</creatorcontrib><creatorcontrib>Von Bahr, Viktor</creatorcontrib><creatorcontrib>Millar, Jonathan E</creatorcontrib><creatorcontrib>Schneider, Bailey A</creatorcontrib><creatorcontrib>Obonyo, Nchafatso G</creatorcontrib><creatorcontrib>Black, Debra</creatorcontrib><creatorcontrib>Bouquet, Mahe</creatorcontrib><creatorcontrib>Bartnikowski, Nicole</creatorcontrib><creatorcontrib>Suen, Jacky Y</creatorcontrib><creatorcontrib>Fraser, John F</creatorcontrib><title>The effects of nitric oxide on coagulation and inflammation in ex vivo models of extracorporeal membrane oxygenation and cardiopulmonary bypass</title><title>Artificial organs</title><addtitle>Artif Organs</addtitle><description>Extracorporeal life support (ECLS) has extensive applications in managing patients with acute cardiac and pulmonary failure. Two primary modalities of ECLS, cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO), include several similarities in their composition, complications, and patient outcomes. Both CPB and ECMO pose a high risk of thrombus formation and platelet activation due to the large surface area of the devices and bleeding due to system anticoagulation. Therefore, novel methods of anticoagulation are needed to reduce the morbidity and mortality associated with extracorporeal support. Nitric oxide (NO) has potent antiplatelet properties and presents a promising alternative or addition to anticoagulation with heparin during extracorporeal support. We developed two ex vivo models of CPB and ECMO to investigate NO effects on anticoagulation and inflammation in these systems. Sole addition of NO as an anticoagulant was not successful in preventing thrombus formation in the ex vivo setups, therefore a combination of low-level heparin with NO was used. Antiplatelet effects were observed in the ex vivo ECMO model when NO was delivered at 80 ppm. Platelet count was preserved after 480 min when NO was delivered at 30 ppm. Combined delivery of NO and heparin did not improve haemocompatibility in either ex vivo model of CPB and ECMO. Anti-inflammatory effects of NO in ECMO systems have to be evaluated further.</description><subject>Anticoagulants</subject><subject>Anticoagulants - pharmacology</subject><subject>Anticoagulants - therapeutic use</subject><subject>Blood clots</subject><subject>Cardiopulmonary Bypass - adverse effects</subject><subject>Cardiopulmonary Bypass - methods</subject><subject>Coagulation</subject><subject>Complications</subject><subject>Extracorporeal membrane oxygenation</subject><subject>Extracorporeal Membrane Oxygenation - adverse effects</subject><subject>Extracorporeal Membrane Oxygenation - methods</subject><subject>Heart surgery</subject><subject>Heparin</subject><subject>Heparin - pharmacology</subject><subject>Heparin - therapeutic use</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation - etiology</subject><subject>Inflammation - prevention &amp; control</subject><subject>Membranes</subject><subject>Morbidity</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - therapeutic use</subject><subject>Oxygenation</subject><subject>Platelets</subject><subject>Thrombosis</subject><subject>Thrombosis - etiology</subject><subject>Thrombosis - prevention &amp; control</subject><issn>0160-564X</issn><issn>1525-1594</issn><issn>1525-1594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU9LHDEYh4NU3O22h36BEuilHkbzdzJ7LGJtQfCi4G3IJO9ss0ySaTIju5_Cr2x0bQVzSQgPD7_3_SH0hZIzWs65jumMipo0R2hJJZMVlWvxAS0JrUkla3G_QB9z3hJClCD1CVpwxddScblEj7d_AEPfg5kyjj0ObkrO4LhzFnAM2ES9mQc9ufLWwWIX-kF7f_hwAcMOP7iHiH20MLwYYDclbWIaYwI9YA--SzoU2W6_gfBmMjpZF8d58DHotMfdftQ5f0LHvR4yfH69V-ju5-Xtxa_q-ubq98WP68pw0UwVJczKNTWk42tGqO07a2uiuoYrpqnQwC1TmoJkltja1qoz0Km-brQVHIzgK_T94B1T_DtDnlrvsoFhKFHjnFvWcNYIpggt6Ld36DbOKZR0hWoYa2RZd6FOD5RJMecEfTsm58tgLSXtc0ttaal9aamwX1-Nc-fB_if_1cKfACqnkF8</recordid><startdate>202310</startdate><enddate>202310</enddate><creator>Malfertheiner, Maximilian V</creator><creator>Garrett, Ashlen</creator><creator>Passmore, Margaret</creator><creator>Haymet, Andrew B</creator><creator>Webb, Richard I</creator><creator>Von Bahr, Viktor</creator><creator>Millar, Jonathan E</creator><creator>Schneider, Bailey A</creator><creator>Obonyo, Nchafatso G</creator><creator>Black, Debra</creator><creator>Bouquet, Mahe</creator><creator>Bartnikowski, Nicole</creator><creator>Suen, Jacky Y</creator><creator>Fraser, John F</creator><general>Wiley Subscription Services, Inc</general><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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0859-8882</orcidid><orcidid>https://orcid.org/0000-0002-6245-2614</orcidid><orcidid>https://orcid.org/0000-0002-5040-4359</orcidid><orcidid>https://orcid.org/0000-0001-6511-0081</orcidid></search><sort><creationdate>202310</creationdate><title>The effects of nitric oxide on coagulation and inflammation in ex vivo models of extracorporeal membrane oxygenation and cardiopulmonary bypass</title><author>Malfertheiner, Maximilian V ; Garrett, Ashlen ; Passmore, Margaret ; Haymet, Andrew B ; Webb, Richard I ; Von Bahr, Viktor ; Millar, Jonathan E ; Schneider, Bailey A ; Obonyo, Nchafatso G ; Black, Debra ; Bouquet, Mahe ; Bartnikowski, Nicole ; Suen, Jacky Y ; Fraser, John F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c348t-102d591c0b39201dfbdd607b8372a14ae3d27a1e52d0d6d67bceb7f68ad43ec43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Anticoagulants</topic><topic>Anticoagulants - pharmacology</topic><topic>Anticoagulants - therapeutic use</topic><topic>Blood clots</topic><topic>Cardiopulmonary Bypass - adverse effects</topic><topic>Cardiopulmonary Bypass - methods</topic><topic>Coagulation</topic><topic>Complications</topic><topic>Extracorporeal membrane oxygenation</topic><topic>Extracorporeal Membrane Oxygenation - adverse effects</topic><topic>Extracorporeal Membrane Oxygenation - methods</topic><topic>Heart surgery</topic><topic>Heparin</topic><topic>Heparin - pharmacology</topic><topic>Heparin - therapeutic use</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammation - etiology</topic><topic>Inflammation - prevention &amp; control</topic><topic>Membranes</topic><topic>Morbidity</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - therapeutic use</topic><topic>Oxygenation</topic><topic>Platelets</topic><topic>Thrombosis</topic><topic>Thrombosis - etiology</topic><topic>Thrombosis - prevention &amp; control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Malfertheiner, Maximilian V</creatorcontrib><creatorcontrib>Garrett, Ashlen</creatorcontrib><creatorcontrib>Passmore, Margaret</creatorcontrib><creatorcontrib>Haymet, Andrew B</creatorcontrib><creatorcontrib>Webb, Richard I</creatorcontrib><creatorcontrib>Von Bahr, Viktor</creatorcontrib><creatorcontrib>Millar, Jonathan E</creatorcontrib><creatorcontrib>Schneider, Bailey A</creatorcontrib><creatorcontrib>Obonyo, Nchafatso G</creatorcontrib><creatorcontrib>Black, Debra</creatorcontrib><creatorcontrib>Bouquet, Mahe</creatorcontrib><creatorcontrib>Bartnikowski, Nicole</creatorcontrib><creatorcontrib>Suen, Jacky Y</creatorcontrib><creatorcontrib>Fraser, John F</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Artificial organs</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Malfertheiner, Maximilian V</au><au>Garrett, Ashlen</au><au>Passmore, Margaret</au><au>Haymet, Andrew B</au><au>Webb, Richard I</au><au>Von Bahr, Viktor</au><au>Millar, Jonathan E</au><au>Schneider, Bailey A</au><au>Obonyo, Nchafatso G</au><au>Black, Debra</au><au>Bouquet, Mahe</au><au>Bartnikowski, Nicole</au><au>Suen, Jacky Y</au><au>Fraser, John F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effects of nitric oxide on coagulation and inflammation in ex vivo models of extracorporeal membrane oxygenation and cardiopulmonary bypass</atitle><jtitle>Artificial organs</jtitle><addtitle>Artif Organs</addtitle><date>2023-10</date><risdate>2023</risdate><volume>47</volume><issue>10</issue><spage>1581</spage><epage>1591</epage><pages>1581-1591</pages><issn>0160-564X</issn><issn>1525-1594</issn><eissn>1525-1594</eissn><abstract>Extracorporeal life support (ECLS) has extensive applications in managing patients with acute cardiac and pulmonary failure. Two primary modalities of ECLS, cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO), include several similarities in their composition, complications, and patient outcomes. Both CPB and ECMO pose a high risk of thrombus formation and platelet activation due to the large surface area of the devices and bleeding due to system anticoagulation. Therefore, novel methods of anticoagulation are needed to reduce the morbidity and mortality associated with extracorporeal support. Nitric oxide (NO) has potent antiplatelet properties and presents a promising alternative or addition to anticoagulation with heparin during extracorporeal support. We developed two ex vivo models of CPB and ECMO to investigate NO effects on anticoagulation and inflammation in these systems. Sole addition of NO as an anticoagulant was not successful in preventing thrombus formation in the ex vivo setups, therefore a combination of low-level heparin with NO was used. Antiplatelet effects were observed in the ex vivo ECMO model when NO was delivered at 80 ppm. Platelet count was preserved after 480 min when NO was delivered at 30 ppm. Combined delivery of NO and heparin did not improve haemocompatibility in either ex vivo model of CPB and ECMO. Anti-inflammatory effects of NO in ECMO systems have to be evaluated further.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37395735</pmid><doi>10.1111/aor.14608</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-0859-8882</orcidid><orcidid>https://orcid.org/0000-0002-6245-2614</orcidid><orcidid>https://orcid.org/0000-0002-5040-4359</orcidid><orcidid>https://orcid.org/0000-0001-6511-0081</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0160-564X
ispartof Artificial organs, 2023-10, Vol.47 (10), p.1581-1591
issn 0160-564X
1525-1594
1525-1594
language eng
recordid cdi_proquest_miscellaneous_2832842701
source MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects Anticoagulants
Anticoagulants - pharmacology
Anticoagulants - therapeutic use
Blood clots
Cardiopulmonary Bypass - adverse effects
Cardiopulmonary Bypass - methods
Coagulation
Complications
Extracorporeal membrane oxygenation
Extracorporeal Membrane Oxygenation - adverse effects
Extracorporeal Membrane Oxygenation - methods
Heart surgery
Heparin
Heparin - pharmacology
Heparin - therapeutic use
Humans
Inflammation
Inflammation - etiology
Inflammation - prevention & control
Membranes
Morbidity
Nitric oxide
Nitric Oxide - therapeutic use
Oxygenation
Platelets
Thrombosis
Thrombosis - etiology
Thrombosis - prevention & control
title The effects of nitric oxide on coagulation and inflammation in ex vivo models of extracorporeal membrane oxygenation and cardiopulmonary bypass
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T19%3A19%3A58IST&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=The%20effects%20of%20nitric%20oxide%20on%20coagulation%20and%20inflammation%20in%20ex%20vivo%20models%20of%20extracorporeal%20membrane%20oxygenation%20and%20cardiopulmonary%20bypass&rft.jtitle=Artificial%20organs&rft.au=Malfertheiner,%20Maximilian%20V&rft.date=2023-10&rft.volume=47&rft.issue=10&rft.spage=1581&rft.epage=1591&rft.pages=1581-1591&rft.issn=0160-564X&rft.eissn=1525-1594&rft_id=info:doi/10.1111/aor.14608&rft_dat=%3Cproquest_cross%3E2882285159%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=2882285159&rft_id=info:pmid/37395735&rfr_iscdi=true