Loading…

Susceptibility and Pathology in Juvenile Atlantic Cod Gadus morhua to a Marine Viral Haemorrhagic Septicaemia Virus Isolated from Diseased Rainbow Trout Oncorhynchus mykiss

The first known outbreak caused by a viral haemorrhagic septicaemia virus (VHSV) strain of genotype III in rainbow trout occurred in 2007 at a marine farm in Storfjorden, Norway. The source of the virus is unknown, and cod and other marine fish around the farms are suspected as a possible reservoir....

Full description

Saved in:
Bibliographic Details
Published in:Animals (Basel) 2021-12, Vol.11 (12), p.3523
Main Authors: Sandlund, Nina, Johansen, Renate, Fiksdal, Ingrid U, Einen, Ann Cathrine B, Modahl, Ingebjørg, Gjerset, Britt, Bergh, Øivind
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-c475t-923a656792ea3dd6f91674faba1191dc62a61eb92d54815f41abd8f1bfa609713
cites cdi_FETCH-LOGICAL-c475t-923a656792ea3dd6f91674faba1191dc62a61eb92d54815f41abd8f1bfa609713
container_end_page
container_issue 12
container_start_page 3523
container_title Animals (Basel)
container_volume 11
creator Sandlund, Nina
Johansen, Renate
Fiksdal, Ingrid U
Einen, Ann Cathrine B
Modahl, Ingebjørg
Gjerset, Britt
Bergh, Øivind
description The first known outbreak caused by a viral haemorrhagic septicaemia virus (VHSV) strain of genotype III in rainbow trout occurred in 2007 at a marine farm in Storfjorden, Norway. The source of the virus is unknown, and cod and other marine fish around the farms are suspected as a possible reservoir. The main objective of this study was to test the susceptibility of juvenile Atlantic cod to the VHSV isolate from Storfjorden. As the pathology of VHS in cod is sparsely described, an additional aim of the study was to give a histopathological description of the disease. Two separate challenge experiments were carried out, using both intra peritoneal (ip) injection and cohabitation as challenge methods. Mortality in the ip injection experiment leveled at approximately 50% three weeks post challenge. Both immunohistochemical and rRT-PCR analysis of organs sampled from diseased and surviving fish confirmed VHSV infection. No VHSV was detected in the cohabitants. The results indicate that Atlantic cod has a low natural susceptibility to this VHSV genotype III strain. One of the most extensive pathological changes was degeneration of cardiac myocytes. Immunohistochemistry confirmed that the lesions were related to VHSV. In some fish, the hematopoietic tissue of spleen and kidney showed degeneration and immunostaining, classical signs of VHS, as described in rainbow trout. Positive immunostaining of the capillaries of the gills, suggests this organ as a useful alternative when screening for VHSV.
doi_str_mv 10.3390/ani11123523
format article
fullrecord <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_5903ee5799024abb89b02a104e0aba53</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_5903ee5799024abb89b02a104e0aba53</doaj_id><sourcerecordid>2614245904</sourcerecordid><originalsourceid>FETCH-LOGICAL-c475t-923a656792ea3dd6f91674faba1191dc62a61eb92d54815f41abd8f1bfa609713</originalsourceid><addsrcrecordid>eNpdkk1vEzEQhlcIRKvSE3dkiQsSCvh71xekKkAbVFREC1drdu1NHDZ2sL1F-U_8SLykVCm-2J55_cx4ZqrqOcFvGFP4LXhHCKFMUPaoOqa4ljMqiXh8cD6qTlNa47JqwYggT6sjxhXnVDXH1e_rMXV2m13rBpd3CLxBXyCvwhCWO-Q8-jTeWu8Gi87yAD67Ds2DQedgxoQ2Ia5GQDkgQJ8hOm_RdxdhQBdgiy-uYFn01xO-KxYHk7u8W6QwQLYG9TFs0HuXLKRy-wrOt-EXuolhzOjKdwW_891qirT74VJ6Vj3pYUj29G4_qb59_HAzv5hdXp0v5meXs47XIs8UZSCFrBW1wIyRvSKy5j20QIgippMUJLGtokbwhoieE2hN05O2B4lVTdhJtdhzTYC13ka3gbjTAZz-awhxqSGWPw1WC4WZtaJWClMObduoFlMgmFtc4glWWO_2rO3YbqzprM-lQg-gDz3erfQy3OpGqgZLWQCv7gAx_BxtynrjSsuG0g0bxqRLiznlJQ9epC__k67DGH0p1aSiNRVCThm93qu6GFKKtr9PhmA9DZU-GKqifnGY_7323wixP7-Vyns</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2612725563</pqid></control><display><type>article</type><title>Susceptibility and Pathology in Juvenile Atlantic Cod Gadus morhua to a Marine Viral Haemorrhagic Septicaemia Virus Isolated from Diseased Rainbow Trout Oncorhynchus mykiss</title><source>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</source><source>PubMed Central (Open access)</source><creator>Sandlund, Nina ; Johansen, Renate ; Fiksdal, Ingrid U ; Einen, Ann Cathrine B ; Modahl, Ingebjørg ; Gjerset, Britt ; Bergh, Øivind</creator><creatorcontrib>Sandlund, Nina ; Johansen, Renate ; Fiksdal, Ingrid U ; Einen, Ann Cathrine B ; Modahl, Ingebjørg ; Gjerset, Britt ; Bergh, Øivind</creatorcontrib><description>The first known outbreak caused by a viral haemorrhagic septicaemia virus (VHSV) strain of genotype III in rainbow trout occurred in 2007 at a marine farm in Storfjorden, Norway. The source of the virus is unknown, and cod and other marine fish around the farms are suspected as a possible reservoir. The main objective of this study was to test the susceptibility of juvenile Atlantic cod to the VHSV isolate from Storfjorden. As the pathology of VHS in cod is sparsely described, an additional aim of the study was to give a histopathological description of the disease. Two separate challenge experiments were carried out, using both intra peritoneal (ip) injection and cohabitation as challenge methods. Mortality in the ip injection experiment leveled at approximately 50% three weeks post challenge. Both immunohistochemical and rRT-PCR analysis of organs sampled from diseased and surviving fish confirmed VHSV infection. No VHSV was detected in the cohabitants. The results indicate that Atlantic cod has a low natural susceptibility to this VHSV genotype III strain. One of the most extensive pathological changes was degeneration of cardiac myocytes. Immunohistochemistry confirmed that the lesions were related to VHSV. In some fish, the hematopoietic tissue of spleen and kidney showed degeneration and immunostaining, classical signs of VHS, as described in rainbow trout. Positive immunostaining of the capillaries of the gills, suggests this organ as a useful alternative when screening for VHSV.</description><identifier>ISSN: 2076-2615</identifier><identifier>EISSN: 2076-2615</identifier><identifier>DOI: 10.3390/ani11123523</identifier><identifier>PMID: 34944298</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animal tissues ; Aquaculture ; Capillaries ; Cardiomyocytes ; Cell growth ; Cod ; Cohabitation ; Degeneration ; experimental challenge ; Experiments ; farmed fish ; Farming ; Fish ; Fish farms ; fish rhabdovirus ; Freshwater fish ; Gadus morhua ; Genotype &amp; phenotype ; Genotypes ; Gills ; Hemorrhagic septicemia ; Immunohistochemistry ; Injection ; Marine fish ; Mortality ; Myocytes ; Oncorhynchus mykiss ; Organs ; Outbreaks ; Pathology ; Salmon ; Spleen ; Standard deviation ; Susceptibility ; Trout ; Vaccines ; VHSV genotype III ; Virulence ; Viruses</subject><ispartof>Animals (Basel), 2021-12, Vol.11 (12), p.3523</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 (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>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-923a656792ea3dd6f91674faba1191dc62a61eb92d54815f41abd8f1bfa609713</citedby><cites>FETCH-LOGICAL-c475t-923a656792ea3dd6f91674faba1191dc62a61eb92d54815f41abd8f1bfa609713</cites><orcidid>0000-0002-9849-025X ; 0000-0002-3398-6940 ; 0009-0005-6209-3024</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2612725563/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2612725563?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34944298$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sandlund, Nina</creatorcontrib><creatorcontrib>Johansen, Renate</creatorcontrib><creatorcontrib>Fiksdal, Ingrid U</creatorcontrib><creatorcontrib>Einen, Ann Cathrine B</creatorcontrib><creatorcontrib>Modahl, Ingebjørg</creatorcontrib><creatorcontrib>Gjerset, Britt</creatorcontrib><creatorcontrib>Bergh, Øivind</creatorcontrib><title>Susceptibility and Pathology in Juvenile Atlantic Cod Gadus morhua to a Marine Viral Haemorrhagic Septicaemia Virus Isolated from Diseased Rainbow Trout Oncorhynchus mykiss</title><title>Animals (Basel)</title><addtitle>Animals (Basel)</addtitle><description>The first known outbreak caused by a viral haemorrhagic septicaemia virus (VHSV) strain of genotype III in rainbow trout occurred in 2007 at a marine farm in Storfjorden, Norway. The source of the virus is unknown, and cod and other marine fish around the farms are suspected as a possible reservoir. The main objective of this study was to test the susceptibility of juvenile Atlantic cod to the VHSV isolate from Storfjorden. As the pathology of VHS in cod is sparsely described, an additional aim of the study was to give a histopathological description of the disease. Two separate challenge experiments were carried out, using both intra peritoneal (ip) injection and cohabitation as challenge methods. Mortality in the ip injection experiment leveled at approximately 50% three weeks post challenge. Both immunohistochemical and rRT-PCR analysis of organs sampled from diseased and surviving fish confirmed VHSV infection. No VHSV was detected in the cohabitants. The results indicate that Atlantic cod has a low natural susceptibility to this VHSV genotype III strain. One of the most extensive pathological changes was degeneration of cardiac myocytes. Immunohistochemistry confirmed that the lesions were related to VHSV. In some fish, the hematopoietic tissue of spleen and kidney showed degeneration and immunostaining, classical signs of VHS, as described in rainbow trout. Positive immunostaining of the capillaries of the gills, suggests this organ as a useful alternative when screening for VHSV.</description><subject>Animal tissues</subject><subject>Aquaculture</subject><subject>Capillaries</subject><subject>Cardiomyocytes</subject><subject>Cell growth</subject><subject>Cod</subject><subject>Cohabitation</subject><subject>Degeneration</subject><subject>experimental challenge</subject><subject>Experiments</subject><subject>farmed fish</subject><subject>Farming</subject><subject>Fish</subject><subject>Fish farms</subject><subject>fish rhabdovirus</subject><subject>Freshwater fish</subject><subject>Gadus morhua</subject><subject>Genotype &amp; phenotype</subject><subject>Genotypes</subject><subject>Gills</subject><subject>Hemorrhagic septicemia</subject><subject>Immunohistochemistry</subject><subject>Injection</subject><subject>Marine fish</subject><subject>Mortality</subject><subject>Myocytes</subject><subject>Oncorhynchus mykiss</subject><subject>Organs</subject><subject>Outbreaks</subject><subject>Pathology</subject><subject>Salmon</subject><subject>Spleen</subject><subject>Standard deviation</subject><subject>Susceptibility</subject><subject>Trout</subject><subject>Vaccines</subject><subject>VHSV genotype III</subject><subject>Virulence</subject><subject>Viruses</subject><issn>2076-2615</issn><issn>2076-2615</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkk1vEzEQhlcIRKvSE3dkiQsSCvh71xekKkAbVFREC1drdu1NHDZ2sL1F-U_8SLykVCm-2J55_cx4ZqrqOcFvGFP4LXhHCKFMUPaoOqa4ljMqiXh8cD6qTlNa47JqwYggT6sjxhXnVDXH1e_rMXV2m13rBpd3CLxBXyCvwhCWO-Q8-jTeWu8Gi87yAD67Ds2DQedgxoQ2Ia5GQDkgQJ8hOm_RdxdhQBdgiy-uYFn01xO-KxYHk7u8W6QwQLYG9TFs0HuXLKRy-wrOt-EXuolhzOjKdwW_891qirT74VJ6Vj3pYUj29G4_qb59_HAzv5hdXp0v5meXs47XIs8UZSCFrBW1wIyRvSKy5j20QIgippMUJLGtokbwhoieE2hN05O2B4lVTdhJtdhzTYC13ka3gbjTAZz-awhxqSGWPw1WC4WZtaJWClMObduoFlMgmFtc4glWWO_2rO3YbqzprM-lQg-gDz3erfQy3OpGqgZLWQCv7gAx_BxtynrjSsuG0g0bxqRLiznlJQ9epC__k67DGH0p1aSiNRVCThm93qu6GFKKtr9PhmA9DZU-GKqifnGY_7323wixP7-Vyns</recordid><startdate>20211210</startdate><enddate>20211210</enddate><creator>Sandlund, Nina</creator><creator>Johansen, Renate</creator><creator>Fiksdal, Ingrid U</creator><creator>Einen, Ann Cathrine B</creator><creator>Modahl, Ingebjørg</creator><creator>Gjerset, Britt</creator><creator>Bergh, Øivind</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-9849-025X</orcidid><orcidid>https://orcid.org/0000-0002-3398-6940</orcidid><orcidid>https://orcid.org/0009-0005-6209-3024</orcidid></search><sort><creationdate>20211210</creationdate><title>Susceptibility and Pathology in Juvenile Atlantic Cod Gadus morhua to a Marine Viral Haemorrhagic Septicaemia Virus Isolated from Diseased Rainbow Trout Oncorhynchus mykiss</title><author>Sandlund, Nina ; Johansen, Renate ; Fiksdal, Ingrid U ; Einen, Ann Cathrine B ; Modahl, Ingebjørg ; Gjerset, Britt ; Bergh, Øivind</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-923a656792ea3dd6f91674faba1191dc62a61eb92d54815f41abd8f1bfa609713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animal tissues</topic><topic>Aquaculture</topic><topic>Capillaries</topic><topic>Cardiomyocytes</topic><topic>Cell growth</topic><topic>Cod</topic><topic>Cohabitation</topic><topic>Degeneration</topic><topic>experimental challenge</topic><topic>Experiments</topic><topic>farmed fish</topic><topic>Farming</topic><topic>Fish</topic><topic>Fish farms</topic><topic>fish rhabdovirus</topic><topic>Freshwater fish</topic><topic>Gadus morhua</topic><topic>Genotype &amp; phenotype</topic><topic>Genotypes</topic><topic>Gills</topic><topic>Hemorrhagic septicemia</topic><topic>Immunohistochemistry</topic><topic>Injection</topic><topic>Marine fish</topic><topic>Mortality</topic><topic>Myocytes</topic><topic>Oncorhynchus mykiss</topic><topic>Organs</topic><topic>Outbreaks</topic><topic>Pathology</topic><topic>Salmon</topic><topic>Spleen</topic><topic>Standard deviation</topic><topic>Susceptibility</topic><topic>Trout</topic><topic>Vaccines</topic><topic>VHSV genotype III</topic><topic>Virulence</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sandlund, Nina</creatorcontrib><creatorcontrib>Johansen, Renate</creatorcontrib><creatorcontrib>Fiksdal, Ingrid U</creatorcontrib><creatorcontrib>Einen, Ann Cathrine B</creatorcontrib><creatorcontrib>Modahl, Ingebjørg</creatorcontrib><creatorcontrib>Gjerset, Britt</creatorcontrib><creatorcontrib>Bergh, Øivind</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Animals (Basel)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sandlund, Nina</au><au>Johansen, Renate</au><au>Fiksdal, Ingrid U</au><au>Einen, Ann Cathrine B</au><au>Modahl, Ingebjørg</au><au>Gjerset, Britt</au><au>Bergh, Øivind</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Susceptibility and Pathology in Juvenile Atlantic Cod Gadus morhua to a Marine Viral Haemorrhagic Septicaemia Virus Isolated from Diseased Rainbow Trout Oncorhynchus mykiss</atitle><jtitle>Animals (Basel)</jtitle><addtitle>Animals (Basel)</addtitle><date>2021-12-10</date><risdate>2021</risdate><volume>11</volume><issue>12</issue><spage>3523</spage><pages>3523-</pages><issn>2076-2615</issn><eissn>2076-2615</eissn><abstract>The first known outbreak caused by a viral haemorrhagic septicaemia virus (VHSV) strain of genotype III in rainbow trout occurred in 2007 at a marine farm in Storfjorden, Norway. The source of the virus is unknown, and cod and other marine fish around the farms are suspected as a possible reservoir. The main objective of this study was to test the susceptibility of juvenile Atlantic cod to the VHSV isolate from Storfjorden. As the pathology of VHS in cod is sparsely described, an additional aim of the study was to give a histopathological description of the disease. Two separate challenge experiments were carried out, using both intra peritoneal (ip) injection and cohabitation as challenge methods. Mortality in the ip injection experiment leveled at approximately 50% three weeks post challenge. Both immunohistochemical and rRT-PCR analysis of organs sampled from diseased and surviving fish confirmed VHSV infection. No VHSV was detected in the cohabitants. The results indicate that Atlantic cod has a low natural susceptibility to this VHSV genotype III strain. One of the most extensive pathological changes was degeneration of cardiac myocytes. Immunohistochemistry confirmed that the lesions were related to VHSV. In some fish, the hematopoietic tissue of spleen and kidney showed degeneration and immunostaining, classical signs of VHS, as described in rainbow trout. Positive immunostaining of the capillaries of the gills, suggests this organ as a useful alternative when screening for VHSV.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>34944298</pmid><doi>10.3390/ani11123523</doi><orcidid>https://orcid.org/0000-0002-9849-025X</orcidid><orcidid>https://orcid.org/0000-0002-3398-6940</orcidid><orcidid>https://orcid.org/0009-0005-6209-3024</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2076-2615
ispartof Animals (Basel), 2021-12, Vol.11 (12), p.3523
issn 2076-2615
2076-2615
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_5903ee5799024abb89b02a104e0aba53
source Publicly Available Content Database (Proquest) (PQ_SDU_P3); PubMed Central (Open access)
subjects Animal tissues
Aquaculture
Capillaries
Cardiomyocytes
Cell growth
Cod
Cohabitation
Degeneration
experimental challenge
Experiments
farmed fish
Farming
Fish
Fish farms
fish rhabdovirus
Freshwater fish
Gadus morhua
Genotype & phenotype
Genotypes
Gills
Hemorrhagic septicemia
Immunohistochemistry
Injection
Marine fish
Mortality
Myocytes
Oncorhynchus mykiss
Organs
Outbreaks
Pathology
Salmon
Spleen
Standard deviation
Susceptibility
Trout
Vaccines
VHSV genotype III
Virulence
Viruses
title Susceptibility and Pathology in Juvenile Atlantic Cod Gadus morhua to a Marine Viral Haemorrhagic Septicaemia Virus Isolated from Diseased Rainbow Trout Oncorhynchus mykiss
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T12%3A42%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Susceptibility%20and%20Pathology%20in%20Juvenile%20Atlantic%20Cod%20Gadus%20morhua%20to%20a%20Marine%20Viral%20Haemorrhagic%20Septicaemia%20Virus%20Isolated%20from%20Diseased%20Rainbow%20Trout%20Oncorhynchus%20mykiss&rft.jtitle=Animals%20(Basel)&rft.au=Sandlund,%20Nina&rft.date=2021-12-10&rft.volume=11&rft.issue=12&rft.spage=3523&rft.pages=3523-&rft.issn=2076-2615&rft.eissn=2076-2615&rft_id=info:doi/10.3390/ani11123523&rft_dat=%3Cproquest_doaj_%3E2614245904%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c475t-923a656792ea3dd6f91674faba1191dc62a61eb92d54815f41abd8f1bfa609713%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2612725563&rft_id=info:pmid/34944298&rfr_iscdi=true