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Protective efficacy of pirfenidone in rats with pulmonary fibrosis induced by bleomycin
Bleomycin causes increased production of reactive oxygen species, leads to pulmonary toxicity, fibroblast activation, and fibrosis.BACKGROUNDBleomycin causes increased production of reactive oxygen species, leads to pulmonary toxicity, fibroblast activation, and fibrosis.This study aimed to evaluate...
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Published in: | Sarcoidosis, vasculitis, and diffuse lung diseases vasculitis, and diffuse lung diseases, 2023-01, Vol.40 (3), p.e2023036 |
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creator | Demirkol, Baris Gul, Sule Cörtük, Mustafa Akanıl Fener, Neslihan Yavuzsan, Eminegül Eren, Ramazan Baydili, Kursad Nuri Çekmen, Mustafa Baki Cetinkaya, Erdogan |
description | Bleomycin causes increased production of reactive oxygen species, leads to pulmonary toxicity, fibroblast activation, and fibrosis.BACKGROUNDBleomycin causes increased production of reactive oxygen species, leads to pulmonary toxicity, fibroblast activation, and fibrosis.This study aimed to evaluate the protective effect of pirfenidone on bleomycin-induced lung toxicity in rats.OBJECTIVESThis study aimed to evaluate the protective effect of pirfenidone on bleomycin-induced lung toxicity in rats.Twenty-eight adult rats were randomly divided into 3 groups; Bleomycin (B group, n=10), Bleomycin and Pirfenidone (B-PND group, n=13), and the control group (n=5). The bleomycin regimen was administered for 9 weeks. Pirfenidone was administered at 100 mg/kg daily. Total antioxidant level (TAS), total oxidant level (TOS), tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1), matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor (PAI) levels were studied. Histopathologically, sections were stained with Hematoxylin-eosin and Masson-trichrome for grading-scoring according to the Ashcroft score.METHODSTwenty-eight adult rats were randomly divided into 3 groups; Bleomycin (B group, n=10), Bleomycin and Pirfenidone (B-PND group, n=13), and the control group (n=5). The bleomycin regimen was administered for 9 weeks. Pirfenidone was administered at 100 mg/kg daily. Total antioxidant level (TAS), total oxidant level (TOS), tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1), matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor (PAI) levels were studied. Histopathologically, sections were stained with Hematoxylin-eosin and Masson-trichrome for grading-scoring according to the Ashcroft score.Stage 3 fibrosis was observed in 50% of the B group rats, stage 3 and higher fibrosis was never detected in the B-PND group and the difference was statistically significant (p=0.003). When evaluating tissue inflammation, the inflammation was higher in the B-PND group than in the other groups (p |
doi_str_mv | 10.36141/svdld.v40i3.13847 |
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The bleomycin regimen was administered for 9 weeks. Pirfenidone was administered at 100 mg/kg daily. Total antioxidant level (TAS), total oxidant level (TOS), tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1), matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor (PAI) levels were studied. Histopathologically, sections were stained with Hematoxylin-eosin and Masson-trichrome for grading-scoring according to the Ashcroft score.METHODSTwenty-eight adult rats were randomly divided into 3 groups; Bleomycin (B group, n=10), Bleomycin and Pirfenidone (B-PND group, n=13), and the control group (n=5). The bleomycin regimen was administered for 9 weeks. Pirfenidone was administered at 100 mg/kg daily. Total antioxidant level (TAS), total oxidant level (TOS), tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1), matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor (PAI) levels were studied. Histopathologically, sections were stained with Hematoxylin-eosin and Masson-trichrome for grading-scoring according to the Ashcroft score.Stage 3 fibrosis was observed in 50% of the B group rats, stage 3 and higher fibrosis was never detected in the B-PND group and the difference was statistically significant (p=0.003). When evaluating tissue inflammation, the inflammation was higher in the B-PND group than in the other groups (p<0.001). Pleuritis was detected in all rats in group B, while was not observed in B-PND and control group (p<0.001). The TAS level was found to be significantly higher in group B than in group B-PND (p=0.034), while no difference was found between TOS, TNF-α, MMP-2, PAI, TGF-β1.RESULTSStage 3 fibrosis was observed in 50% of the B group rats, stage 3 and higher fibrosis was never detected in the B-PND group and the difference was statistically significant (p=0.003). When evaluating tissue inflammation, the inflammation was higher in the B-PND group than in the other groups (p<0.001). Pleuritis was detected in all rats in group B, while was not observed in B-PND and control group (p<0.001). The TAS level was found to be significantly higher in group B than in group B-PND (p=0.034), while no difference was found between TOS, TNF-α, MMP-2, PAI, TGF-β1.Pirfenidone had a statistically significant protective effect in bleomycin-induced lung fibrosis and pleuritis in rats. Despite the presence of inflammation in the tissue, no significant changes were observed in inflammation markers in the peripheral blood. Novel serum biomarkers are needed to indicate the presence of inflammation and fibrosis in the lung.CONCLUSIONSPirfenidone had a statistically significant protective effect in bleomycin-induced lung fibrosis and pleuritis in rats. Despite the presence of inflammation in the tissue, no significant changes were observed in inflammation markers in the peripheral blood. Novel serum biomarkers are needed to indicate the presence of inflammation and fibrosis in the lung.</description><identifier>ISSN: 2532-179X</identifier><identifier>ISSN: 1124-0490</identifier><identifier>EISSN: 2532-179X</identifier><identifier>DOI: 10.36141/svdld.v40i3.13847</identifier><identifier>PMID: 37712376</identifier><language>eng</language><publisher>Italy: Mattioli 1885</publisher><subject>Original</subject><ispartof>Sarcoidosis, vasculitis, and diffuse lung diseases, 2023-01, Vol.40 (3), p.e2023036</ispartof><rights>Copyright: © 2023 SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c293t-9137d4b0df520f54f81cf3768f717da4804ec2e8e94509e75536a0a52f4000033</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10540724/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10540724/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids></links><search><creatorcontrib>Demirkol, Baris</creatorcontrib><creatorcontrib>Gul, Sule</creatorcontrib><creatorcontrib>Cörtük, Mustafa</creatorcontrib><creatorcontrib>Akanıl Fener, Neslihan</creatorcontrib><creatorcontrib>Yavuzsan, Eminegül</creatorcontrib><creatorcontrib>Eren, Ramazan</creatorcontrib><creatorcontrib>Baydili, Kursad Nuri</creatorcontrib><creatorcontrib>Çekmen, Mustafa Baki</creatorcontrib><creatorcontrib>Cetinkaya, Erdogan</creatorcontrib><title>Protective efficacy of pirfenidone in rats with pulmonary fibrosis induced by bleomycin</title><title>Sarcoidosis, vasculitis, and diffuse lung diseases</title><description>Bleomycin causes increased production of reactive oxygen species, leads to pulmonary toxicity, fibroblast activation, and fibrosis.BACKGROUNDBleomycin causes increased production of reactive oxygen species, leads to pulmonary toxicity, fibroblast activation, and fibrosis.This study aimed to evaluate the protective effect of pirfenidone on bleomycin-induced lung toxicity in rats.OBJECTIVESThis study aimed to evaluate the protective effect of pirfenidone on bleomycin-induced lung toxicity in rats.Twenty-eight adult rats were randomly divided into 3 groups; Bleomycin (B group, n=10), Bleomycin and Pirfenidone (B-PND group, n=13), and the control group (n=5). The bleomycin regimen was administered for 9 weeks. Pirfenidone was administered at 100 mg/kg daily. Total antioxidant level (TAS), total oxidant level (TOS), tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1), matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor (PAI) levels were studied. Histopathologically, sections were stained with Hematoxylin-eosin and Masson-trichrome for grading-scoring according to the Ashcroft score.METHODSTwenty-eight adult rats were randomly divided into 3 groups; Bleomycin (B group, n=10), Bleomycin and Pirfenidone (B-PND group, n=13), and the control group (n=5). The bleomycin regimen was administered for 9 weeks. Pirfenidone was administered at 100 mg/kg daily. Total antioxidant level (TAS), total oxidant level (TOS), tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1), matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor (PAI) levels were studied. Histopathologically, sections were stained with Hematoxylin-eosin and Masson-trichrome for grading-scoring according to the Ashcroft score.Stage 3 fibrosis was observed in 50% of the B group rats, stage 3 and higher fibrosis was never detected in the B-PND group and the difference was statistically significant (p=0.003). When evaluating tissue inflammation, the inflammation was higher in the B-PND group than in the other groups (p<0.001). Pleuritis was detected in all rats in group B, while was not observed in B-PND and control group (p<0.001). The TAS level was found to be significantly higher in group B than in group B-PND (p=0.034), while no difference was found between TOS, TNF-α, MMP-2, PAI, TGF-β1.RESULTSStage 3 fibrosis was observed in 50% of the B group rats, stage 3 and higher fibrosis was never detected in the B-PND group and the difference was statistically significant (p=0.003). When evaluating tissue inflammation, the inflammation was higher in the B-PND group than in the other groups (p<0.001). Pleuritis was detected in all rats in group B, while was not observed in B-PND and control group (p<0.001). The TAS level was found to be significantly higher in group B than in group B-PND (p=0.034), while no difference was found between TOS, TNF-α, MMP-2, PAI, TGF-β1.Pirfenidone had a statistically significant protective effect in bleomycin-induced lung fibrosis and pleuritis in rats. Despite the presence of inflammation in the tissue, no significant changes were observed in inflammation markers in the peripheral blood. Novel serum biomarkers are needed to indicate the presence of inflammation and fibrosis in the lung.CONCLUSIONSPirfenidone had a statistically significant protective effect in bleomycin-induced lung fibrosis and pleuritis in rats. Despite the presence of inflammation in the tissue, no significant changes were observed in inflammation markers in the peripheral blood. Novel serum biomarkers are needed to indicate the presence of inflammation and fibrosis in the lung.</description><subject>Original</subject><issn>2532-179X</issn><issn>1124-0490</issn><issn>2532-179X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNpVjktLxDAYRYMozjj6B1xl6WbGPJt0JTL4ggFdKLorafLFibRNbdpK_70FXejd3AsHDhehc0o2PKOCXqbRVW4zChL4hnIt1AFaMsnZmqr87fDPXqCTlD4IybQk5BgtuFKUcZUt0etTF3uwfRgBg_fBGjvh6HEbOg9NcLEBHBrcmT7hr9DvcTtUdWxMN2Efyi6mkGbuBgsOlxMuK4j1ZENzio68qRKc_fYKvdzePG_v17vHu4ft9W5tWc77dU65cqIkzktGvBReU-vnY9orqpwRmgiwDDTkQpIclJQ8M8RI5gWZw_kKXf1426GswVlo-s5URduFev5YRBOK_6QJ--I9jgUlUhDFxGy4-DV08XOA1Bd1SBaqyjQQh1QwnUmlheYZ_wZdoXDc</recordid><startdate>20230101</startdate><enddate>20230101</enddate><creator>Demirkol, Baris</creator><creator>Gul, Sule</creator><creator>Cörtük, Mustafa</creator><creator>Akanıl Fener, Neslihan</creator><creator>Yavuzsan, Eminegül</creator><creator>Eren, Ramazan</creator><creator>Baydili, Kursad Nuri</creator><creator>Çekmen, Mustafa Baki</creator><creator>Cetinkaya, Erdogan</creator><general>Mattioli 1885</general><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20230101</creationdate><title>Protective efficacy of pirfenidone in rats with pulmonary fibrosis induced by bleomycin</title><author>Demirkol, Baris ; Gul, Sule ; Cörtük, Mustafa ; Akanıl Fener, Neslihan ; Yavuzsan, Eminegül ; Eren, Ramazan ; Baydili, Kursad Nuri ; Çekmen, Mustafa Baki ; Cetinkaya, Erdogan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c293t-9137d4b0df520f54f81cf3768f717da4804ec2e8e94509e75536a0a52f4000033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Original</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Demirkol, Baris</creatorcontrib><creatorcontrib>Gul, Sule</creatorcontrib><creatorcontrib>Cörtük, Mustafa</creatorcontrib><creatorcontrib>Akanıl Fener, Neslihan</creatorcontrib><creatorcontrib>Yavuzsan, Eminegül</creatorcontrib><creatorcontrib>Eren, Ramazan</creatorcontrib><creatorcontrib>Baydili, Kursad Nuri</creatorcontrib><creatorcontrib>Çekmen, Mustafa Baki</creatorcontrib><creatorcontrib>Cetinkaya, Erdogan</creatorcontrib><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Sarcoidosis, vasculitis, and diffuse lung diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Demirkol, Baris</au><au>Gul, Sule</au><au>Cörtük, Mustafa</au><au>Akanıl Fener, Neslihan</au><au>Yavuzsan, Eminegül</au><au>Eren, Ramazan</au><au>Baydili, Kursad Nuri</au><au>Çekmen, Mustafa Baki</au><au>Cetinkaya, Erdogan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective efficacy of pirfenidone in rats with pulmonary fibrosis induced by bleomycin</atitle><jtitle>Sarcoidosis, vasculitis, and diffuse lung diseases</jtitle><date>2023-01-01</date><risdate>2023</risdate><volume>40</volume><issue>3</issue><spage>e2023036</spage><pages>e2023036-</pages><issn>2532-179X</issn><issn>1124-0490</issn><eissn>2532-179X</eissn><abstract>Bleomycin causes increased production of reactive oxygen species, leads to pulmonary toxicity, fibroblast activation, and fibrosis.BACKGROUNDBleomycin causes increased production of reactive oxygen species, leads to pulmonary toxicity, fibroblast activation, and fibrosis.This study aimed to evaluate the protective effect of pirfenidone on bleomycin-induced lung toxicity in rats.OBJECTIVESThis study aimed to evaluate the protective effect of pirfenidone on bleomycin-induced lung toxicity in rats.Twenty-eight adult rats were randomly divided into 3 groups; Bleomycin (B group, n=10), Bleomycin and Pirfenidone (B-PND group, n=13), and the control group (n=5). The bleomycin regimen was administered for 9 weeks. Pirfenidone was administered at 100 mg/kg daily. Total antioxidant level (TAS), total oxidant level (TOS), tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1), matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor (PAI) levels were studied. Histopathologically, sections were stained with Hematoxylin-eosin and Masson-trichrome for grading-scoring according to the Ashcroft score.METHODSTwenty-eight adult rats were randomly divided into 3 groups; Bleomycin (B group, n=10), Bleomycin and Pirfenidone (B-PND group, n=13), and the control group (n=5). The bleomycin regimen was administered for 9 weeks. Pirfenidone was administered at 100 mg/kg daily. Total antioxidant level (TAS), total oxidant level (TOS), tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1), matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor (PAI) levels were studied. Histopathologically, sections were stained with Hematoxylin-eosin and Masson-trichrome for grading-scoring according to the Ashcroft score.Stage 3 fibrosis was observed in 50% of the B group rats, stage 3 and higher fibrosis was never detected in the B-PND group and the difference was statistically significant (p=0.003). When evaluating tissue inflammation, the inflammation was higher in the B-PND group than in the other groups (p<0.001). Pleuritis was detected in all rats in group B, while was not observed in B-PND and control group (p<0.001). The TAS level was found to be significantly higher in group B than in group B-PND (p=0.034), while no difference was found between TOS, TNF-α, MMP-2, PAI, TGF-β1.RESULTSStage 3 fibrosis was observed in 50% of the B group rats, stage 3 and higher fibrosis was never detected in the B-PND group and the difference was statistically significant (p=0.003). When evaluating tissue inflammation, the inflammation was higher in the B-PND group than in the other groups (p<0.001). Pleuritis was detected in all rats in group B, while was not observed in B-PND and control group (p<0.001). The TAS level was found to be significantly higher in group B than in group B-PND (p=0.034), while no difference was found between TOS, TNF-α, MMP-2, PAI, TGF-β1.Pirfenidone had a statistically significant protective effect in bleomycin-induced lung fibrosis and pleuritis in rats. Despite the presence of inflammation in the tissue, no significant changes were observed in inflammation markers in the peripheral blood. Novel serum biomarkers are needed to indicate the presence of inflammation and fibrosis in the lung.CONCLUSIONSPirfenidone had a statistically significant protective effect in bleomycin-induced lung fibrosis and pleuritis in rats. Despite the presence of inflammation in the tissue, no significant changes were observed in inflammation markers in the peripheral blood. Novel serum biomarkers are needed to indicate the presence of inflammation and fibrosis in the lung.</abstract><cop>Italy</cop><pub>Mattioli 1885</pub><pmid>37712376</pmid><doi>10.36141/svdld.v40i3.13847</doi><oa>free_for_read</oa></addata></record> |
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title | Protective efficacy of pirfenidone in rats with pulmonary fibrosis induced by bleomycin |
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