Loading…
Benzonidazole treatment has a beneficial effect on cells infected with the Colombian strain of Trypanosoma cruzi
Benznidazole (Bz) is the recommended drug for the treatment of Chagas disease; however, its efficacy may vary according to the sensitivity of Trypanosoma cruzi strains to the drug and host immune background. The study evaluated the immune response of peripheral blood mononuclear cells (PBMC) that we...
Saved in:
Published in: | Parasite immunology 2023-06, Vol.45 (6), p.e12983-n/a |
---|---|
Main Authors: | , , , , , , , , , , , |
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-c3533-b1bf6397a3ddd4b3254196e9c554e7fd02d059d58ecfc42cd106059e26012793 |
---|---|
cites | cdi_FETCH-LOGICAL-c3533-b1bf6397a3ddd4b3254196e9c554e7fd02d059d58ecfc42cd106059e26012793 |
container_end_page | n/a |
container_issue | 6 |
container_start_page | e12983 |
container_title | Parasite immunology |
container_volume | 45 |
creator | Rafael Moreira, Leyllane Santos Oliveira, Kamila Kássia Torres, Diego José Lira Silva Barros, Michelle Arruda, Tiago Ribeiro Nascimento, Amanda Vasconcelos Soares, Ana Karine Araújo Higino, Taciana Mirely Maciel Diniz, George Tadeu Nunes Souza, Valdênia Maria Oliveira Morais, Clarice Neuenschwander Lins Lorena, Virginia Maria Barros |
description | Benznidazole (Bz) is the recommended drug for the treatment of Chagas disease; however, its efficacy may vary according to the sensitivity of Trypanosoma cruzi strains to the drug and host immune background. The study evaluated the immune response of peripheral blood mononuclear cells (PBMC) that were infected in vitro with the Colombian strain (Col) and treated with Bz. The co‐cultures were incubated for 24 h, 5 and 10 days, where cytokine dosage was performed in the supernatant and evaluation of the cells for CD28+ and CTLA‐4+ molecules in CD4+ and CD8+ lymphocytes, and CD80+, CD86+ and HLA‐DR+ in CD14+ cells. The results showed that Col induced a strong inflammatory response, with an increase in IFN‐γ and TNF early in the infection (24 h), however, from 5 days of infection on, TNF production declined, and IL‐10 production increased, which may be associated with a control mechanism of the exacerbated inflammatory response. The Bz treatment did not significantly alter the frequencies of the phenotypes evaluated both T cell subsets and CD14+ cells. Therefore, this study reinforces the need for typing the patient's strain to guide therapy and promote individualized treatment protocols due to the heterogeneous genetic background among T. cruzi strains. |
doi_str_mv | 10.1111/pim.12983 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2802424558</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2814410505</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3533-b1bf6397a3ddd4b3254196e9c554e7fd02d059d58ecfc42cd106059e26012793</originalsourceid><addsrcrecordid>eNp1kUtrGzEUhUVISFy3i_6BIsgmWUys5zyWjUnaQEK68H7QSFdYYUaaSjME-9dHrtMuCrmbyz18HC7nIPSVkhuaZzW64YaypuYnaEF5KQtOmDhFC0IFLbJcX6BPKb0QQjkr-Tm64BUpy0o0CzTegt8H74zahx7wFEFNA_gJb1XCCnfgwTrtVI_BWtATDh5r6PuEnT_cYPCrm7Z42gJehz4MnVMepykq53GweBN3o_IhhUFhHee9-4zOrOoTfHnfS7S5v9usfxaPzz8e1t8fC80l50VHO1vyplLcGCM6zqSgTQmNllJAZQ1hhsjGyBq01YJpQ0mZBWAloaxq-BJdHW3HGH7PkKZ2cOnwuPIQ5tSyOkfEhJR1Ri__Q1_CHH1-LlNUCEokkZm6PlI6hpQi2HaMblBx11LSHlpocwvtnxYy--3dce4GMP_Iv7FnYHUEXl0Pu4-d2l8PT0fLN8jFkU4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2814410505</pqid></control><display><type>article</type><title>Benzonidazole treatment has a beneficial effect on cells infected with the Colombian strain of Trypanosoma cruzi</title><source>Wiley</source><creator>Rafael Moreira, Leyllane ; Santos Oliveira, Kamila Kássia ; Torres, Diego José Lira ; Silva Barros, Michelle ; Arruda, Tiago Ribeiro ; Nascimento, Amanda Vasconcelos ; Soares, Ana Karine Araújo ; Higino, Taciana Mirely Maciel ; Diniz, George Tadeu Nunes ; Souza, Valdênia Maria Oliveira ; Morais, Clarice Neuenschwander Lins ; Lorena, Virginia Maria Barros</creator><creatorcontrib>Rafael Moreira, Leyllane ; Santos Oliveira, Kamila Kássia ; Torres, Diego José Lira ; Silva Barros, Michelle ; Arruda, Tiago Ribeiro ; Nascimento, Amanda Vasconcelos ; Soares, Ana Karine Araújo ; Higino, Taciana Mirely Maciel ; Diniz, George Tadeu Nunes ; Souza, Valdênia Maria Oliveira ; Morais, Clarice Neuenschwander Lins ; Lorena, Virginia Maria Barros</creatorcontrib><description>Benznidazole (Bz) is the recommended drug for the treatment of Chagas disease; however, its efficacy may vary according to the sensitivity of Trypanosoma cruzi strains to the drug and host immune background. The study evaluated the immune response of peripheral blood mononuclear cells (PBMC) that were infected in vitro with the Colombian strain (Col) and treated with Bz. The co‐cultures were incubated for 24 h, 5 and 10 days, where cytokine dosage was performed in the supernatant and evaluation of the cells for CD28+ and CTLA‐4+ molecules in CD4+ and CD8+ lymphocytes, and CD80+, CD86+ and HLA‐DR+ in CD14+ cells. The results showed that Col induced a strong inflammatory response, with an increase in IFN‐γ and TNF early in the infection (24 h), however, from 5 days of infection on, TNF production declined, and IL‐10 production increased, which may be associated with a control mechanism of the exacerbated inflammatory response. The Bz treatment did not significantly alter the frequencies of the phenotypes evaluated both T cell subsets and CD14+ cells. Therefore, this study reinforces the need for typing the patient's strain to guide therapy and promote individualized treatment protocols due to the heterogeneous genetic background among T. cruzi strains.</description><identifier>ISSN: 0141-9838</identifier><identifier>EISSN: 1365-3024</identifier><identifier>DOI: 10.1111/pim.12983</identifier><identifier>PMID: 37066749</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Benznidazole ; CD14 antigen ; CD28 antigen ; CD4 antigen ; CD8 antigen ; CD80 antigen ; CD86 antigen ; Chagas disease ; Chagas Disease - drug therapy ; Colombia ; DTU ; Humans ; immune response ; immunomodulation ; Inflammation ; Leukocytes, Mononuclear ; Lymphocytes T ; Nitroimidazoles - pharmacology ; Nitroimidazoles - therapeutic use ; Peripheral blood mononuclear cells ; Phenotypes ; Protozoa ; Tissue typing ; Trypanocidal Agents - pharmacology ; Trypanocidal Agents - therapeutic use ; Trypanosoma cruzi</subject><ispartof>Parasite immunology, 2023-06, Vol.45 (6), p.e12983-n/a</ispartof><rights>2023 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3533-b1bf6397a3ddd4b3254196e9c554e7fd02d059d58ecfc42cd106059e26012793</citedby><cites>FETCH-LOGICAL-c3533-b1bf6397a3ddd4b3254196e9c554e7fd02d059d58ecfc42cd106059e26012793</cites><orcidid>0000-0001-6704-2393 ; 0000-0001-5625-1907 ; 0000-0002-0887-8163 ; 0000-0003-0663-236X ; 0000-0001-7888-7922 ; 0000-0002-4976-009X ; 0000-0002-5542-0171 ; 0000-0002-9620-2621 ; 0000-0003-1173-1119 ; 0000-0003-3342-8671 ; 0000-0001-5836-3208</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37066749$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rafael Moreira, Leyllane</creatorcontrib><creatorcontrib>Santos Oliveira, Kamila Kássia</creatorcontrib><creatorcontrib>Torres, Diego José Lira</creatorcontrib><creatorcontrib>Silva Barros, Michelle</creatorcontrib><creatorcontrib>Arruda, Tiago Ribeiro</creatorcontrib><creatorcontrib>Nascimento, Amanda Vasconcelos</creatorcontrib><creatorcontrib>Soares, Ana Karine Araújo</creatorcontrib><creatorcontrib>Higino, Taciana Mirely Maciel</creatorcontrib><creatorcontrib>Diniz, George Tadeu Nunes</creatorcontrib><creatorcontrib>Souza, Valdênia Maria Oliveira</creatorcontrib><creatorcontrib>Morais, Clarice Neuenschwander Lins</creatorcontrib><creatorcontrib>Lorena, Virginia Maria Barros</creatorcontrib><title>Benzonidazole treatment has a beneficial effect on cells infected with the Colombian strain of Trypanosoma cruzi</title><title>Parasite immunology</title><addtitle>Parasite Immunol</addtitle><description>Benznidazole (Bz) is the recommended drug for the treatment of Chagas disease; however, its efficacy may vary according to the sensitivity of Trypanosoma cruzi strains to the drug and host immune background. The study evaluated the immune response of peripheral blood mononuclear cells (PBMC) that were infected in vitro with the Colombian strain (Col) and treated with Bz. The co‐cultures were incubated for 24 h, 5 and 10 days, where cytokine dosage was performed in the supernatant and evaluation of the cells for CD28+ and CTLA‐4+ molecules in CD4+ and CD8+ lymphocytes, and CD80+, CD86+ and HLA‐DR+ in CD14+ cells. The results showed that Col induced a strong inflammatory response, with an increase in IFN‐γ and TNF early in the infection (24 h), however, from 5 days of infection on, TNF production declined, and IL‐10 production increased, which may be associated with a control mechanism of the exacerbated inflammatory response. The Bz treatment did not significantly alter the frequencies of the phenotypes evaluated both T cell subsets and CD14+ cells. Therefore, this study reinforces the need for typing the patient's strain to guide therapy and promote individualized treatment protocols due to the heterogeneous genetic background among T. cruzi strains.</description><subject>Benznidazole</subject><subject>CD14 antigen</subject><subject>CD28 antigen</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>CD80 antigen</subject><subject>CD86 antigen</subject><subject>Chagas disease</subject><subject>Chagas Disease - drug therapy</subject><subject>Colombia</subject><subject>DTU</subject><subject>Humans</subject><subject>immune response</subject><subject>immunomodulation</subject><subject>Inflammation</subject><subject>Leukocytes, Mononuclear</subject><subject>Lymphocytes T</subject><subject>Nitroimidazoles - pharmacology</subject><subject>Nitroimidazoles - therapeutic use</subject><subject>Peripheral blood mononuclear cells</subject><subject>Phenotypes</subject><subject>Protozoa</subject><subject>Tissue typing</subject><subject>Trypanocidal Agents - pharmacology</subject><subject>Trypanocidal Agents - therapeutic use</subject><subject>Trypanosoma cruzi</subject><issn>0141-9838</issn><issn>1365-3024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp1kUtrGzEUhUVISFy3i_6BIsgmWUys5zyWjUnaQEK68H7QSFdYYUaaSjME-9dHrtMuCrmbyz18HC7nIPSVkhuaZzW64YaypuYnaEF5KQtOmDhFC0IFLbJcX6BPKb0QQjkr-Tm64BUpy0o0CzTegt8H74zahx7wFEFNA_gJb1XCCnfgwTrtVI_BWtATDh5r6PuEnT_cYPCrm7Z42gJehz4MnVMepykq53GweBN3o_IhhUFhHee9-4zOrOoTfHnfS7S5v9usfxaPzz8e1t8fC80l50VHO1vyplLcGCM6zqSgTQmNllJAZQ1hhsjGyBq01YJpQ0mZBWAloaxq-BJdHW3HGH7PkKZ2cOnwuPIQ5tSyOkfEhJR1Ri__Q1_CHH1-LlNUCEokkZm6PlI6hpQi2HaMblBx11LSHlpocwvtnxYy--3dce4GMP_Iv7FnYHUEXl0Pu4-d2l8PT0fLN8jFkU4</recordid><startdate>202306</startdate><enddate>202306</enddate><creator>Rafael Moreira, Leyllane</creator><creator>Santos Oliveira, Kamila Kássia</creator><creator>Torres, Diego José Lira</creator><creator>Silva Barros, Michelle</creator><creator>Arruda, Tiago Ribeiro</creator><creator>Nascimento, Amanda Vasconcelos</creator><creator>Soares, Ana Karine Araújo</creator><creator>Higino, Taciana Mirely Maciel</creator><creator>Diniz, George Tadeu Nunes</creator><creator>Souza, Valdênia Maria Oliveira</creator><creator>Morais, Clarice Neuenschwander Lins</creator><creator>Lorena, Virginia Maria Barros</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>7T5</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6704-2393</orcidid><orcidid>https://orcid.org/0000-0001-5625-1907</orcidid><orcidid>https://orcid.org/0000-0002-0887-8163</orcidid><orcidid>https://orcid.org/0000-0003-0663-236X</orcidid><orcidid>https://orcid.org/0000-0001-7888-7922</orcidid><orcidid>https://orcid.org/0000-0002-4976-009X</orcidid><orcidid>https://orcid.org/0000-0002-5542-0171</orcidid><orcidid>https://orcid.org/0000-0002-9620-2621</orcidid><orcidid>https://orcid.org/0000-0003-1173-1119</orcidid><orcidid>https://orcid.org/0000-0003-3342-8671</orcidid><orcidid>https://orcid.org/0000-0001-5836-3208</orcidid></search><sort><creationdate>202306</creationdate><title>Benzonidazole treatment has a beneficial effect on cells infected with the Colombian strain of Trypanosoma cruzi</title><author>Rafael Moreira, Leyllane ; Santos Oliveira, Kamila Kássia ; Torres, Diego José Lira ; Silva Barros, Michelle ; Arruda, Tiago Ribeiro ; Nascimento, Amanda Vasconcelos ; Soares, Ana Karine Araújo ; Higino, Taciana Mirely Maciel ; Diniz, George Tadeu Nunes ; Souza, Valdênia Maria Oliveira ; Morais, Clarice Neuenschwander Lins ; Lorena, Virginia Maria Barros</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3533-b1bf6397a3ddd4b3254196e9c554e7fd02d059d58ecfc42cd106059e26012793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Benznidazole</topic><topic>CD14 antigen</topic><topic>CD28 antigen</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>CD80 antigen</topic><topic>CD86 antigen</topic><topic>Chagas disease</topic><topic>Chagas Disease - drug therapy</topic><topic>Colombia</topic><topic>DTU</topic><topic>Humans</topic><topic>immune response</topic><topic>immunomodulation</topic><topic>Inflammation</topic><topic>Leukocytes, Mononuclear</topic><topic>Lymphocytes T</topic><topic>Nitroimidazoles - pharmacology</topic><topic>Nitroimidazoles - therapeutic use</topic><topic>Peripheral blood mononuclear cells</topic><topic>Phenotypes</topic><topic>Protozoa</topic><topic>Tissue typing</topic><topic>Trypanocidal Agents - pharmacology</topic><topic>Trypanocidal Agents - therapeutic use</topic><topic>Trypanosoma cruzi</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rafael Moreira, Leyllane</creatorcontrib><creatorcontrib>Santos Oliveira, Kamila Kássia</creatorcontrib><creatorcontrib>Torres, Diego José Lira</creatorcontrib><creatorcontrib>Silva Barros, Michelle</creatorcontrib><creatorcontrib>Arruda, Tiago Ribeiro</creatorcontrib><creatorcontrib>Nascimento, Amanda Vasconcelos</creatorcontrib><creatorcontrib>Soares, Ana Karine Araújo</creatorcontrib><creatorcontrib>Higino, Taciana Mirely Maciel</creatorcontrib><creatorcontrib>Diniz, George Tadeu Nunes</creatorcontrib><creatorcontrib>Souza, Valdênia Maria Oliveira</creatorcontrib><creatorcontrib>Morais, Clarice Neuenschwander Lins</creatorcontrib><creatorcontrib>Lorena, Virginia Maria Barros</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Parasite immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rafael Moreira, Leyllane</au><au>Santos Oliveira, Kamila Kássia</au><au>Torres, Diego José Lira</au><au>Silva Barros, Michelle</au><au>Arruda, Tiago Ribeiro</au><au>Nascimento, Amanda Vasconcelos</au><au>Soares, Ana Karine Araújo</au><au>Higino, Taciana Mirely Maciel</au><au>Diniz, George Tadeu Nunes</au><au>Souza, Valdênia Maria Oliveira</au><au>Morais, Clarice Neuenschwander Lins</au><au>Lorena, Virginia Maria Barros</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Benzonidazole treatment has a beneficial effect on cells infected with the Colombian strain of Trypanosoma cruzi</atitle><jtitle>Parasite immunology</jtitle><addtitle>Parasite Immunol</addtitle><date>2023-06</date><risdate>2023</risdate><volume>45</volume><issue>6</issue><spage>e12983</spage><epage>n/a</epage><pages>e12983-n/a</pages><issn>0141-9838</issn><eissn>1365-3024</eissn><abstract>Benznidazole (Bz) is the recommended drug for the treatment of Chagas disease; however, its efficacy may vary according to the sensitivity of Trypanosoma cruzi strains to the drug and host immune background. The study evaluated the immune response of peripheral blood mononuclear cells (PBMC) that were infected in vitro with the Colombian strain (Col) and treated with Bz. The co‐cultures were incubated for 24 h, 5 and 10 days, where cytokine dosage was performed in the supernatant and evaluation of the cells for CD28+ and CTLA‐4+ molecules in CD4+ and CD8+ lymphocytes, and CD80+, CD86+ and HLA‐DR+ in CD14+ cells. The results showed that Col induced a strong inflammatory response, with an increase in IFN‐γ and TNF early in the infection (24 h), however, from 5 days of infection on, TNF production declined, and IL‐10 production increased, which may be associated with a control mechanism of the exacerbated inflammatory response. The Bz treatment did not significantly alter the frequencies of the phenotypes evaluated both T cell subsets and CD14+ cells. Therefore, this study reinforces the need for typing the patient's strain to guide therapy and promote individualized treatment protocols due to the heterogeneous genetic background among T. cruzi strains.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37066749</pmid><doi>10.1111/pim.12983</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-6704-2393</orcidid><orcidid>https://orcid.org/0000-0001-5625-1907</orcidid><orcidid>https://orcid.org/0000-0002-0887-8163</orcidid><orcidid>https://orcid.org/0000-0003-0663-236X</orcidid><orcidid>https://orcid.org/0000-0001-7888-7922</orcidid><orcidid>https://orcid.org/0000-0002-4976-009X</orcidid><orcidid>https://orcid.org/0000-0002-5542-0171</orcidid><orcidid>https://orcid.org/0000-0002-9620-2621</orcidid><orcidid>https://orcid.org/0000-0003-1173-1119</orcidid><orcidid>https://orcid.org/0000-0003-3342-8671</orcidid><orcidid>https://orcid.org/0000-0001-5836-3208</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0141-9838 |
ispartof | Parasite immunology, 2023-06, Vol.45 (6), p.e12983-n/a |
issn | 0141-9838 1365-3024 |
language | eng |
recordid | cdi_proquest_miscellaneous_2802424558 |
source | Wiley |
subjects | Benznidazole CD14 antigen CD28 antigen CD4 antigen CD8 antigen CD80 antigen CD86 antigen Chagas disease Chagas Disease - drug therapy Colombia DTU Humans immune response immunomodulation Inflammation Leukocytes, Mononuclear Lymphocytes T Nitroimidazoles - pharmacology Nitroimidazoles - therapeutic use Peripheral blood mononuclear cells Phenotypes Protozoa Tissue typing Trypanocidal Agents - pharmacology Trypanocidal Agents - therapeutic use Trypanosoma cruzi |
title | Benzonidazole treatment has a beneficial effect on cells infected with the Colombian strain of Trypanosoma cruzi |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T17%3A22%3A27IST&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=Benzonidazole%20treatment%20has%20a%20beneficial%20effect%20on%20cells%20infected%20with%20the%20Colombian%20strain%20of%20Trypanosoma%20cruzi&rft.jtitle=Parasite%20immunology&rft.au=Rafael%20Moreira,%20Leyllane&rft.date=2023-06&rft.volume=45&rft.issue=6&rft.spage=e12983&rft.epage=n/a&rft.pages=e12983-n/a&rft.issn=0141-9838&rft.eissn=1365-3024&rft_id=info:doi/10.1111/pim.12983&rft_dat=%3Cproquest_cross%3E2814410505%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c3533-b1bf6397a3ddd4b3254196e9c554e7fd02d059d58ecfc42cd106059e26012793%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2814410505&rft_id=info:pmid/37066749&rfr_iscdi=true |