Loading…

Maternal crack cocaine use in rats leads to depressive- and anxiety-like behavior, memory impairment, and increased seizure susceptibility in the offspring

•Crack cocaine exposure during pregnancy induced anxiety-like behavior in offspring.•Crack cocaine exposure during pregnancy lead to the development of depression in offspring.•Crack cocaine exposure during pregnancy lead to memory impairment in offspring.•Crack cocaine exposure during pregnancy inc...

Full description

Saved in:
Bibliographic Details
Published in:European neuropsychopharmacology 2021-03, Vol.44, p.34-50
Main Authors: Pacheco, Amanda Larissa Dias, de Melo, Igor Santana, de Souza, Fernanda Maria Araújo, Nicácio, Dannyele Cynthia Santos Pimentel, Freitas-Santos, Jucilene, Oliveira dos Santos, Yngrid Mickaelli, Costa, Maisa de Araújo, Cavalcante, Cibelle de Melo Bastos, Gomes dos Santos Neto, José, Gitaí, Daniel Leite Góes, Sabino-Silva, Robinson, Torres de Miranda, Cláudio, Borbely, Alexandre Urban, Duzzioni, Marcelo, Shetty, Ashok K., de Castro, Olagide Wagner
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-c371t-1f965b3abba552362422a8d3bd935710576b8173ef46ee6b396ed82711f99313
cites cdi_FETCH-LOGICAL-c371t-1f965b3abba552362422a8d3bd935710576b8173ef46ee6b396ed82711f99313
container_end_page 50
container_issue
container_start_page 34
container_title European neuropsychopharmacology
container_volume 44
creator Pacheco, Amanda Larissa Dias
de Melo, Igor Santana
de Souza, Fernanda Maria Araújo
Nicácio, Dannyele Cynthia Santos Pimentel
Freitas-Santos, Jucilene
Oliveira dos Santos, Yngrid Mickaelli
Costa, Maisa de Araújo
Cavalcante, Cibelle de Melo Bastos
Gomes dos Santos Neto, José
Gitaí, Daniel Leite Góes
Sabino-Silva, Robinson
Torres de Miranda, Cláudio
Borbely, Alexandre Urban
Duzzioni, Marcelo
Shetty, Ashok K.
de Castro, Olagide Wagner
description •Crack cocaine exposure during pregnancy induced anxiety-like behavior in offspring.•Crack cocaine exposure during pregnancy lead to the development of depression in offspring.•Crack cocaine exposure during pregnancy lead to memory impairment in offspring.•Crack cocaine exposure during pregnancy increase seizure susceptibility in offspring.•Reduced threshold of seizures in offspring is associated with neuronal death. Crack users suffer the effects of cocaine present in the drug and the action of other active compounds from its pyrolysis. An emergent fact is an increase in the number of pregnant crack cocaine users. Studies suggest that crack cocaine and its metabolites cross the placenta, promoting premature birth, fever, irritability, sweating, and seizures in the early months of life. In children, the effects of crack cocaine have been associated with cognitive deficits, difficulty in verbalization, aggressiveness, and depression, besides enhancing the susceptibility to epileptic seizures, including status epilepticus (SE) in adulthood. Therefore, we investigated the effect of maternal exposure to smoke crack cocaine on several behavioral parameters in the offspring during adulthood. A series of behavioral tests and intrahippocampal pilocarpine (H-PILO) microinjection at sub-convulsive and convulsive doses in a rat model demonstrated that exposure to crack cocaine during the embryonic period leads to anxiogenic-like behavior and long-term memory impairment in both genders and promotes depressive-like behavior in the female. Besides, crack cocaine offspring exposed to a sub-convulsive H-PILO dose showed higher susceptibility to SE, increased seizure frequency, and neurodegeneration, while animals that received a convulsive dose of H-PILO displayed no alteration in SE severity. Taken together, our data suggest that crack cocaine exposure during the gestational period leads to an increased predilection for anxiety and depression, long-term memory deficits, and reduction in the threshold for developing epileptic seizures associated with neuronal death, which predispose crack cocaine babies to develop neuropsychological disorders.
doi_str_mv 10.1016/j.euroneuro.2020.12.011
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2478775033</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0924977X21000018</els_id><sourcerecordid>2478775033</sourcerecordid><originalsourceid>FETCH-LOGICAL-c371t-1f965b3abba552362422a8d3bd935710576b8173ef46ee6b396ed82711f99313</originalsourceid><addsrcrecordid>eNqFkc1u1DAURi0EotPCK4CXLJrBP0mcLKsKKFIRmy7YWY59Q-80sYPtjBhehZfFw5RuWdiWrPP5u9Yh5C1nW854-363hTUGf9y2golyK7aM82dkwzslK9W14jnZsF7UVa_UtzNyntKOMd5I2b8kZ1LWTc3rfkN-fzEZojcTtdHYB2qDNeiBrgkoehpNTnQC4xLNgTpYIqSEe6io8a6snwj5UE34AHSAe7PHEC_pDHOIB4rzYjDO4PPlXxq9jWASOJoAf60RaFqThSXjgBPmw7Ev3wMN45iWiP77K_JiNFOC14_nBbn7-OHu-qa6_frp8_XVbWWl4rniY982gzTDYJpGyFbUQpjOycH1slGcNaodOq4kjHUL0A6yb8F1QvES7CWXF-Td6dklhh8rpKxnLHNNk_EQ1qRFrTqlGiZlQdUJtTGkFGHUZdDZxIPmTB_F6J1-EqOPYjQXuogpyTePJeswg3vK_TNRgKsTAOWne4Sok0XwFhxGsFm7gP8t-QPuO6bC</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2478775033</pqid></control><display><type>article</type><title>Maternal crack cocaine use in rats leads to depressive- and anxiety-like behavior, memory impairment, and increased seizure susceptibility in the offspring</title><source>ScienceDirect Freedom Collection 2022-2024</source><creator>Pacheco, Amanda Larissa Dias ; de Melo, Igor Santana ; de Souza, Fernanda Maria Araújo ; Nicácio, Dannyele Cynthia Santos Pimentel ; Freitas-Santos, Jucilene ; Oliveira dos Santos, Yngrid Mickaelli ; Costa, Maisa de Araújo ; Cavalcante, Cibelle de Melo Bastos ; Gomes dos Santos Neto, José ; Gitaí, Daniel Leite Góes ; Sabino-Silva, Robinson ; Torres de Miranda, Cláudio ; Borbely, Alexandre Urban ; Duzzioni, Marcelo ; Shetty, Ashok K. ; de Castro, Olagide Wagner</creator><creatorcontrib>Pacheco, Amanda Larissa Dias ; de Melo, Igor Santana ; de Souza, Fernanda Maria Araújo ; Nicácio, Dannyele Cynthia Santos Pimentel ; Freitas-Santos, Jucilene ; Oliveira dos Santos, Yngrid Mickaelli ; Costa, Maisa de Araújo ; Cavalcante, Cibelle de Melo Bastos ; Gomes dos Santos Neto, José ; Gitaí, Daniel Leite Góes ; Sabino-Silva, Robinson ; Torres de Miranda, Cláudio ; Borbely, Alexandre Urban ; Duzzioni, Marcelo ; Shetty, Ashok K. ; de Castro, Olagide Wagner</creatorcontrib><description>•Crack cocaine exposure during pregnancy induced anxiety-like behavior in offspring.•Crack cocaine exposure during pregnancy lead to the development of depression in offspring.•Crack cocaine exposure during pregnancy lead to memory impairment in offspring.•Crack cocaine exposure during pregnancy increase seizure susceptibility in offspring.•Reduced threshold of seizures in offspring is associated with neuronal death. Crack users suffer the effects of cocaine present in the drug and the action of other active compounds from its pyrolysis. An emergent fact is an increase in the number of pregnant crack cocaine users. Studies suggest that crack cocaine and its metabolites cross the placenta, promoting premature birth, fever, irritability, sweating, and seizures in the early months of life. In children, the effects of crack cocaine have been associated with cognitive deficits, difficulty in verbalization, aggressiveness, and depression, besides enhancing the susceptibility to epileptic seizures, including status epilepticus (SE) in adulthood. Therefore, we investigated the effect of maternal exposure to smoke crack cocaine on several behavioral parameters in the offspring during adulthood. A series of behavioral tests and intrahippocampal pilocarpine (H-PILO) microinjection at sub-convulsive and convulsive doses in a rat model demonstrated that exposure to crack cocaine during the embryonic period leads to anxiogenic-like behavior and long-term memory impairment in both genders and promotes depressive-like behavior in the female. Besides, crack cocaine offspring exposed to a sub-convulsive H-PILO dose showed higher susceptibility to SE, increased seizure frequency, and neurodegeneration, while animals that received a convulsive dose of H-PILO displayed no alteration in SE severity. Taken together, our data suggest that crack cocaine exposure during the gestational period leads to an increased predilection for anxiety and depression, long-term memory deficits, and reduction in the threshold for developing epileptic seizures associated with neuronal death, which predispose crack cocaine babies to develop neuropsychological disorders.</description><identifier>ISSN: 0924-977X</identifier><identifier>EISSN: 1873-7862</identifier><identifier>DOI: 10.1016/j.euroneuro.2020.12.011</identifier><identifier>PMID: 33454149</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Anxiety ; Crack cocaine ; Depression ; Epilepsy ; Gestational</subject><ispartof>European neuropsychopharmacology, 2021-03, Vol.44, p.34-50</ispartof><rights>2021</rights><rights>Copyright © 2021. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c371t-1f965b3abba552362422a8d3bd935710576b8173ef46ee6b396ed82711f99313</citedby><cites>FETCH-LOGICAL-c371t-1f965b3abba552362422a8d3bd935710576b8173ef46ee6b396ed82711f99313</cites></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/33454149$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pacheco, Amanda Larissa Dias</creatorcontrib><creatorcontrib>de Melo, Igor Santana</creatorcontrib><creatorcontrib>de Souza, Fernanda Maria Araújo</creatorcontrib><creatorcontrib>Nicácio, Dannyele Cynthia Santos Pimentel</creatorcontrib><creatorcontrib>Freitas-Santos, Jucilene</creatorcontrib><creatorcontrib>Oliveira dos Santos, Yngrid Mickaelli</creatorcontrib><creatorcontrib>Costa, Maisa de Araújo</creatorcontrib><creatorcontrib>Cavalcante, Cibelle de Melo Bastos</creatorcontrib><creatorcontrib>Gomes dos Santos Neto, José</creatorcontrib><creatorcontrib>Gitaí, Daniel Leite Góes</creatorcontrib><creatorcontrib>Sabino-Silva, Robinson</creatorcontrib><creatorcontrib>Torres de Miranda, Cláudio</creatorcontrib><creatorcontrib>Borbely, Alexandre Urban</creatorcontrib><creatorcontrib>Duzzioni, Marcelo</creatorcontrib><creatorcontrib>Shetty, Ashok K.</creatorcontrib><creatorcontrib>de Castro, Olagide Wagner</creatorcontrib><title>Maternal crack cocaine use in rats leads to depressive- and anxiety-like behavior, memory impairment, and increased seizure susceptibility in the offspring</title><title>European neuropsychopharmacology</title><addtitle>Eur Neuropsychopharmacol</addtitle><description>•Crack cocaine exposure during pregnancy induced anxiety-like behavior in offspring.•Crack cocaine exposure during pregnancy lead to the development of depression in offspring.•Crack cocaine exposure during pregnancy lead to memory impairment in offspring.•Crack cocaine exposure during pregnancy increase seizure susceptibility in offspring.•Reduced threshold of seizures in offspring is associated with neuronal death. Crack users suffer the effects of cocaine present in the drug and the action of other active compounds from its pyrolysis. An emergent fact is an increase in the number of pregnant crack cocaine users. Studies suggest that crack cocaine and its metabolites cross the placenta, promoting premature birth, fever, irritability, sweating, and seizures in the early months of life. In children, the effects of crack cocaine have been associated with cognitive deficits, difficulty in verbalization, aggressiveness, and depression, besides enhancing the susceptibility to epileptic seizures, including status epilepticus (SE) in adulthood. Therefore, we investigated the effect of maternal exposure to smoke crack cocaine on several behavioral parameters in the offspring during adulthood. A series of behavioral tests and intrahippocampal pilocarpine (H-PILO) microinjection at sub-convulsive and convulsive doses in a rat model demonstrated that exposure to crack cocaine during the embryonic period leads to anxiogenic-like behavior and long-term memory impairment in both genders and promotes depressive-like behavior in the female. Besides, crack cocaine offspring exposed to a sub-convulsive H-PILO dose showed higher susceptibility to SE, increased seizure frequency, and neurodegeneration, while animals that received a convulsive dose of H-PILO displayed no alteration in SE severity. Taken together, our data suggest that crack cocaine exposure during the gestational period leads to an increased predilection for anxiety and depression, long-term memory deficits, and reduction in the threshold for developing epileptic seizures associated with neuronal death, which predispose crack cocaine babies to develop neuropsychological disorders.</description><subject>Anxiety</subject><subject>Crack cocaine</subject><subject>Depression</subject><subject>Epilepsy</subject><subject>Gestational</subject><issn>0924-977X</issn><issn>1873-7862</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqFkc1u1DAURi0EotPCK4CXLJrBP0mcLKsKKFIRmy7YWY59Q-80sYPtjBhehZfFw5RuWdiWrPP5u9Yh5C1nW854-363hTUGf9y2golyK7aM82dkwzslK9W14jnZsF7UVa_UtzNyntKOMd5I2b8kZ1LWTc3rfkN-fzEZojcTtdHYB2qDNeiBrgkoehpNTnQC4xLNgTpYIqSEe6io8a6snwj5UE34AHSAe7PHEC_pDHOIB4rzYjDO4PPlXxq9jWASOJoAf60RaFqThSXjgBPmw7Ev3wMN45iWiP77K_JiNFOC14_nBbn7-OHu-qa6_frp8_XVbWWl4rniY982gzTDYJpGyFbUQpjOycH1slGcNaodOq4kjHUL0A6yb8F1QvES7CWXF-Td6dklhh8rpKxnLHNNk_EQ1qRFrTqlGiZlQdUJtTGkFGHUZdDZxIPmTB_F6J1-EqOPYjQXuogpyTePJeswg3vK_TNRgKsTAOWne4Sok0XwFhxGsFm7gP8t-QPuO6bC</recordid><startdate>202103</startdate><enddate>202103</enddate><creator>Pacheco, Amanda Larissa Dias</creator><creator>de Melo, Igor Santana</creator><creator>de Souza, Fernanda Maria Araújo</creator><creator>Nicácio, Dannyele Cynthia Santos Pimentel</creator><creator>Freitas-Santos, Jucilene</creator><creator>Oliveira dos Santos, Yngrid Mickaelli</creator><creator>Costa, Maisa de Araújo</creator><creator>Cavalcante, Cibelle de Melo Bastos</creator><creator>Gomes dos Santos Neto, José</creator><creator>Gitaí, Daniel Leite Góes</creator><creator>Sabino-Silva, Robinson</creator><creator>Torres de Miranda, Cláudio</creator><creator>Borbely, Alexandre Urban</creator><creator>Duzzioni, Marcelo</creator><creator>Shetty, Ashok K.</creator><creator>de Castro, Olagide Wagner</creator><general>Elsevier B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202103</creationdate><title>Maternal crack cocaine use in rats leads to depressive- and anxiety-like behavior, memory impairment, and increased seizure susceptibility in the offspring</title><author>Pacheco, Amanda Larissa Dias ; de Melo, Igor Santana ; de Souza, Fernanda Maria Araújo ; Nicácio, Dannyele Cynthia Santos Pimentel ; Freitas-Santos, Jucilene ; Oliveira dos Santos, Yngrid Mickaelli ; Costa, Maisa de Araújo ; Cavalcante, Cibelle de Melo Bastos ; Gomes dos Santos Neto, José ; Gitaí, Daniel Leite Góes ; Sabino-Silva, Robinson ; Torres de Miranda, Cláudio ; Borbely, Alexandre Urban ; Duzzioni, Marcelo ; Shetty, Ashok K. ; de Castro, Olagide Wagner</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-1f965b3abba552362422a8d3bd935710576b8173ef46ee6b396ed82711f99313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Anxiety</topic><topic>Crack cocaine</topic><topic>Depression</topic><topic>Epilepsy</topic><topic>Gestational</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pacheco, Amanda Larissa Dias</creatorcontrib><creatorcontrib>de Melo, Igor Santana</creatorcontrib><creatorcontrib>de Souza, Fernanda Maria Araújo</creatorcontrib><creatorcontrib>Nicácio, Dannyele Cynthia Santos Pimentel</creatorcontrib><creatorcontrib>Freitas-Santos, Jucilene</creatorcontrib><creatorcontrib>Oliveira dos Santos, Yngrid Mickaelli</creatorcontrib><creatorcontrib>Costa, Maisa de Araújo</creatorcontrib><creatorcontrib>Cavalcante, Cibelle de Melo Bastos</creatorcontrib><creatorcontrib>Gomes dos Santos Neto, José</creatorcontrib><creatorcontrib>Gitaí, Daniel Leite Góes</creatorcontrib><creatorcontrib>Sabino-Silva, Robinson</creatorcontrib><creatorcontrib>Torres de Miranda, Cláudio</creatorcontrib><creatorcontrib>Borbely, Alexandre Urban</creatorcontrib><creatorcontrib>Duzzioni, Marcelo</creatorcontrib><creatorcontrib>Shetty, Ashok K.</creatorcontrib><creatorcontrib>de Castro, Olagide Wagner</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European neuropsychopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pacheco, Amanda Larissa Dias</au><au>de Melo, Igor Santana</au><au>de Souza, Fernanda Maria Araújo</au><au>Nicácio, Dannyele Cynthia Santos Pimentel</au><au>Freitas-Santos, Jucilene</au><au>Oliveira dos Santos, Yngrid Mickaelli</au><au>Costa, Maisa de Araújo</au><au>Cavalcante, Cibelle de Melo Bastos</au><au>Gomes dos Santos Neto, José</au><au>Gitaí, Daniel Leite Góes</au><au>Sabino-Silva, Robinson</au><au>Torres de Miranda, Cláudio</au><au>Borbely, Alexandre Urban</au><au>Duzzioni, Marcelo</au><au>Shetty, Ashok K.</au><au>de Castro, Olagide Wagner</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Maternal crack cocaine use in rats leads to depressive- and anxiety-like behavior, memory impairment, and increased seizure susceptibility in the offspring</atitle><jtitle>European neuropsychopharmacology</jtitle><addtitle>Eur Neuropsychopharmacol</addtitle><date>2021-03</date><risdate>2021</risdate><volume>44</volume><spage>34</spage><epage>50</epage><pages>34-50</pages><issn>0924-977X</issn><eissn>1873-7862</eissn><abstract>•Crack cocaine exposure during pregnancy induced anxiety-like behavior in offspring.•Crack cocaine exposure during pregnancy lead to the development of depression in offspring.•Crack cocaine exposure during pregnancy lead to memory impairment in offspring.•Crack cocaine exposure during pregnancy increase seizure susceptibility in offspring.•Reduced threshold of seizures in offspring is associated with neuronal death. Crack users suffer the effects of cocaine present in the drug and the action of other active compounds from its pyrolysis. An emergent fact is an increase in the number of pregnant crack cocaine users. Studies suggest that crack cocaine and its metabolites cross the placenta, promoting premature birth, fever, irritability, sweating, and seizures in the early months of life. In children, the effects of crack cocaine have been associated with cognitive deficits, difficulty in verbalization, aggressiveness, and depression, besides enhancing the susceptibility to epileptic seizures, including status epilepticus (SE) in adulthood. Therefore, we investigated the effect of maternal exposure to smoke crack cocaine on several behavioral parameters in the offspring during adulthood. A series of behavioral tests and intrahippocampal pilocarpine (H-PILO) microinjection at sub-convulsive and convulsive doses in a rat model demonstrated that exposure to crack cocaine during the embryonic period leads to anxiogenic-like behavior and long-term memory impairment in both genders and promotes depressive-like behavior in the female. Besides, crack cocaine offspring exposed to a sub-convulsive H-PILO dose showed higher susceptibility to SE, increased seizure frequency, and neurodegeneration, while animals that received a convulsive dose of H-PILO displayed no alteration in SE severity. Taken together, our data suggest that crack cocaine exposure during the gestational period leads to an increased predilection for anxiety and depression, long-term memory deficits, and reduction in the threshold for developing epileptic seizures associated with neuronal death, which predispose crack cocaine babies to develop neuropsychological disorders.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>33454149</pmid><doi>10.1016/j.euroneuro.2020.12.011</doi><tpages>17</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0924-977X
ispartof European neuropsychopharmacology, 2021-03, Vol.44, p.34-50
issn 0924-977X
1873-7862
language eng
recordid cdi_proquest_miscellaneous_2478775033
source ScienceDirect Freedom Collection 2022-2024
subjects Anxiety
Crack cocaine
Depression
Epilepsy
Gestational
title Maternal crack cocaine use in rats leads to depressive- and anxiety-like behavior, memory impairment, and increased seizure susceptibility in the offspring
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T11%3A55%3A12IST&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=Maternal%20crack%20cocaine%20use%20in%20rats%20leads%20to%20depressive-%20and%20anxiety-like%20behavior,%20memory%20impairment,%20and%20increased%20seizure%20susceptibility%20in%20the%20offspring&rft.jtitle=European%20neuropsychopharmacology&rft.au=Pacheco,%20Amanda%20Larissa%20Dias&rft.date=2021-03&rft.volume=44&rft.spage=34&rft.epage=50&rft.pages=34-50&rft.issn=0924-977X&rft.eissn=1873-7862&rft_id=info:doi/10.1016/j.euroneuro.2020.12.011&rft_dat=%3Cproquest_cross%3E2478775033%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c371t-1f965b3abba552362422a8d3bd935710576b8173ef46ee6b396ed82711f99313%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2478775033&rft_id=info:pmid/33454149&rfr_iscdi=true