Loading…

Differential Gene Expression Pattern of Importin β3 and NS5 in C6/36 Cells Acutely and Persistently Infected with Dengue Virus 2

The establishment of persistent dengue virus infection within the cells of the mosquito vector is an essential requirement for viral transmission to a new human host. The mechanisms involved in the establishment and maintenance of persistent infection are not well understood, but it has been suggest...

Full description

Saved in:
Bibliographic Details
Published in:Pathogens (Basel) 2023-01, Vol.12 (2), p.191
Main Authors: Ávila-Ramírez, María Leticia, Reyes-Reyes, Ana Laura, Avila-Bonilla, Rodolfo Gamaliel, Salas-Benito, Mariana, Cerecedo, Doris, Ramírez-Moreno, María Esther, Villagrán-Herrera, María Elena, Mercado-Curiel, Ricardo Francisco, Salas-Benito, Juan Santiago
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by
cites cdi_FETCH-LOGICAL-c512t-78cdb6b65c54f9734c7f09afc363f6e804285054d3f1f8933082d15d8235bc5c3
container_end_page
container_issue 2
container_start_page 191
container_title Pathogens (Basel)
container_volume 12
creator Ávila-Ramírez, María Leticia
Reyes-Reyes, Ana Laura
Avila-Bonilla, Rodolfo Gamaliel
Salas-Benito, Mariana
Cerecedo, Doris
Ramírez-Moreno, María Esther
Villagrán-Herrera, María Elena
Mercado-Curiel, Ricardo Francisco
Salas-Benito, Juan Santiago
description The establishment of persistent dengue virus infection within the cells of the mosquito vector is an essential requirement for viral transmission to a new human host. The mechanisms involved in the establishment and maintenance of persistent infection are not well understood, but it has been suggested that both viral and cellular factors might play an important role. In the present work, we evaluated differential gene expression in cells acutely (C6/36-HT) and persistently infected (C6-L) with Dengue virus 2 by cDNA-AFLP. We observed that importin β3 was upregulated in noninfected cells compared with C6-L cells. Using RT-qPCR and plaque assays, we observed that Dengue virus levels in C6-L cells essentially do not vary over time, and peak viral titers in acutely infected cells are observed at 72 and 120 h postinfection. The expression level of importin β3 was higher in acutely infected cells than in persistently infected cells; this correlates with higher levels of NS5 in the nucleus of the cell. The differential pattern of importin β3 expression between acute and persistent infection with Dengue virus 2 could be a mechanism to maintain viral infection over time, reducing the antiviral response of the cell and the viral replicative rate.
doi_str_mv 10.3390/pathogens12020191
format article
fullrecord <record><control><sourceid>gale_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_bd5a32e0cfe34ca2b621d92e58c2db9e</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A743326698</galeid><doaj_id>oai_doaj_org_article_bd5a32e0cfe34ca2b621d92e58c2db9e</doaj_id><sourcerecordid>A743326698</sourcerecordid><originalsourceid>FETCH-LOGICAL-c512t-78cdb6b65c54f9734c7f09afc363f6e804285054d3f1f8933082d15d8235bc5c3</originalsourceid><addsrcrecordid>eNptUs1uEzEQXiEQrUofgAuyxIVLWq-99q4vSFFaSqQKKvFztbz2OHG0sYPtLfTIK_EgPBNOU0oD2Ad7Zr7vG894qup5jU8oFfh0o_IyLMCnmmCCa1E_qg4JbvkEd3X7-MH9oDpOaYXL6vDWflodUN5R0XB6WH0_c9ZCBJ-dGtAFeEDn3zYRUnLBoyuVM0SPgkXz9SbE7Dz6-YMi5Q1694GhYs74KeVoBsOQ0FSPGYab2_AVxORSLsLFMfcWdAaDvrq8RGfgFyOgzy6OCZFn1ROrhgTHd-dR9enN-cfZ28nl-4v5bHo50awmedJ22vS850yzxoqWNrq1WCirKaeWQ4cb0jHMGkNtbTtBKe6IqZnpCGW9ZpoeVfOdrglqJTfRrVW8kUE5eesIcSFVKVAPIHvDFCWAtYWSR5Gek9oIAqzTxPQCitbrndZm7NdgdKkyqmFPdD_i3VIuwrUUgvPy9iLw6k4ghi8jpCzXLunSROUhjEmStvxVgbZtgb78C7oKY_SlVQXVCk44w80f1EKVApy3oeTVW1E5bRtKCeeiK6iT_6DKNrB2Oniwrvj3CPWOoGNIKYK9r7HGcjuG8p8xLJwXD5tzz_g9dPQXvZrZgw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2779626504</pqid></control><display><type>article</type><title>Differential Gene Expression Pattern of Importin β3 and NS5 in C6/36 Cells Acutely and Persistently Infected with Dengue Virus 2</title><source>PubMed Central Free</source><source>Publicly Available Content Database</source><creator>Ávila-Ramírez, María Leticia ; Reyes-Reyes, Ana Laura ; Avila-Bonilla, Rodolfo Gamaliel ; Salas-Benito, Mariana ; Cerecedo, Doris ; Ramírez-Moreno, María Esther ; Villagrán-Herrera, María Elena ; Mercado-Curiel, Ricardo Francisco ; Salas-Benito, Juan Santiago</creator><creatorcontrib>Ávila-Ramírez, María Leticia ; Reyes-Reyes, Ana Laura ; Avila-Bonilla, Rodolfo Gamaliel ; Salas-Benito, Mariana ; Cerecedo, Doris ; Ramírez-Moreno, María Esther ; Villagrán-Herrera, María Elena ; Mercado-Curiel, Ricardo Francisco ; Salas-Benito, Juan Santiago</creatorcontrib><description>The establishment of persistent dengue virus infection within the cells of the mosquito vector is an essential requirement for viral transmission to a new human host. The mechanisms involved in the establishment and maintenance of persistent infection are not well understood, but it has been suggested that both viral and cellular factors might play an important role. In the present work, we evaluated differential gene expression in cells acutely (C6/36-HT) and persistently infected (C6-L) with Dengue virus 2 by cDNA-AFLP. We observed that importin β3 was upregulated in noninfected cells compared with C6-L cells. Using RT-qPCR and plaque assays, we observed that Dengue virus levels in C6-L cells essentially do not vary over time, and peak viral titers in acutely infected cells are observed at 72 and 120 h postinfection. The expression level of importin β3 was higher in acutely infected cells than in persistently infected cells; this correlates with higher levels of NS5 in the nucleus of the cell. The differential pattern of importin β3 expression between acute and persistent infection with Dengue virus 2 could be a mechanism to maintain viral infection over time, reducing the antiviral response of the cell and the viral replicative rate.</description><identifier>ISSN: 2076-0817</identifier><identifier>EISSN: 2076-0817</identifier><identifier>DOI: 10.3390/pathogens12020191</identifier><identifier>PMID: 36839463</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Aedes albopictus ; Amplified fragment length polymorphism ; Aquatic insects ; Carrier proteins ; Dengue ; Dengue fever ; Dengue virus ; Dengue viruses ; Development and progression ; DNA polymerase ; Gene expression ; Genetic aspects ; Genomes ; Hypotheses ; importin ; Infections ; L cells ; Mosquitoes ; nuclear transport ; Persistent infection ; Physiological aspects ; Proteins ; Vector-borne diseases ; Viral infections ; viral persistence ; Viral proteins ; Virus research ; Viruses</subject><ispartof>Pathogens (Basel), 2023-01, Vol.12 (2), p.191</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 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>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c512t-78cdb6b65c54f9734c7f09afc363f6e804285054d3f1f8933082d15d8235bc5c3</cites><orcidid>0000-0002-0015-8081 ; 0000-0002-0582-0046 ; 0000-0001-7002-0881 ; 0000-0002-4096-0079</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2779626504/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2779626504?pq-origsite=primo$$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/36839463$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ávila-Ramírez, María Leticia</creatorcontrib><creatorcontrib>Reyes-Reyes, Ana Laura</creatorcontrib><creatorcontrib>Avila-Bonilla, Rodolfo Gamaliel</creatorcontrib><creatorcontrib>Salas-Benito, Mariana</creatorcontrib><creatorcontrib>Cerecedo, Doris</creatorcontrib><creatorcontrib>Ramírez-Moreno, María Esther</creatorcontrib><creatorcontrib>Villagrán-Herrera, María Elena</creatorcontrib><creatorcontrib>Mercado-Curiel, Ricardo Francisco</creatorcontrib><creatorcontrib>Salas-Benito, Juan Santiago</creatorcontrib><title>Differential Gene Expression Pattern of Importin β3 and NS5 in C6/36 Cells Acutely and Persistently Infected with Dengue Virus 2</title><title>Pathogens (Basel)</title><addtitle>Pathogens</addtitle><description>The establishment of persistent dengue virus infection within the cells of the mosquito vector is an essential requirement for viral transmission to a new human host. The mechanisms involved in the establishment and maintenance of persistent infection are not well understood, but it has been suggested that both viral and cellular factors might play an important role. In the present work, we evaluated differential gene expression in cells acutely (C6/36-HT) and persistently infected (C6-L) with Dengue virus 2 by cDNA-AFLP. We observed that importin β3 was upregulated in noninfected cells compared with C6-L cells. Using RT-qPCR and plaque assays, we observed that Dengue virus levels in C6-L cells essentially do not vary over time, and peak viral titers in acutely infected cells are observed at 72 and 120 h postinfection. The expression level of importin β3 was higher in acutely infected cells than in persistently infected cells; this correlates with higher levels of NS5 in the nucleus of the cell. The differential pattern of importin β3 expression between acute and persistent infection with Dengue virus 2 could be a mechanism to maintain viral infection over time, reducing the antiviral response of the cell and the viral replicative rate.</description><subject>Aedes albopictus</subject><subject>Amplified fragment length polymorphism</subject><subject>Aquatic insects</subject><subject>Carrier proteins</subject><subject>Dengue</subject><subject>Dengue fever</subject><subject>Dengue virus</subject><subject>Dengue viruses</subject><subject>Development and progression</subject><subject>DNA polymerase</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Hypotheses</subject><subject>importin</subject><subject>Infections</subject><subject>L cells</subject><subject>Mosquitoes</subject><subject>nuclear transport</subject><subject>Persistent infection</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Vector-borne diseases</subject><subject>Viral infections</subject><subject>viral persistence</subject><subject>Viral proteins</subject><subject>Virus research</subject><subject>Viruses</subject><issn>2076-0817</issn><issn>2076-0817</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptUs1uEzEQXiEQrUofgAuyxIVLWq-99q4vSFFaSqQKKvFztbz2OHG0sYPtLfTIK_EgPBNOU0oD2Ad7Zr7vG894qup5jU8oFfh0o_IyLMCnmmCCa1E_qg4JbvkEd3X7-MH9oDpOaYXL6vDWflodUN5R0XB6WH0_c9ZCBJ-dGtAFeEDn3zYRUnLBoyuVM0SPgkXz9SbE7Dz6-YMi5Q1694GhYs74KeVoBsOQ0FSPGYab2_AVxORSLsLFMfcWdAaDvrq8RGfgFyOgzy6OCZFn1ROrhgTHd-dR9enN-cfZ28nl-4v5bHo50awmedJ22vS850yzxoqWNrq1WCirKaeWQ4cb0jHMGkNtbTtBKe6IqZnpCGW9ZpoeVfOdrglqJTfRrVW8kUE5eesIcSFVKVAPIHvDFCWAtYWSR5Gek9oIAqzTxPQCitbrndZm7NdgdKkyqmFPdD_i3VIuwrUUgvPy9iLw6k4ghi8jpCzXLunSROUhjEmStvxVgbZtgb78C7oKY_SlVQXVCk44w80f1EKVApy3oeTVW1E5bRtKCeeiK6iT_6DKNrB2Oniwrvj3CPWOoGNIKYK9r7HGcjuG8p8xLJwXD5tzz_g9dPQXvZrZgw</recordid><startdate>20230127</startdate><enddate>20230127</enddate><creator>Ávila-Ramírez, María Leticia</creator><creator>Reyes-Reyes, Ana Laura</creator><creator>Avila-Bonilla, Rodolfo Gamaliel</creator><creator>Salas-Benito, Mariana</creator><creator>Cerecedo, Doris</creator><creator>Ramírez-Moreno, María Esther</creator><creator>Villagrán-Herrera, María Elena</creator><creator>Mercado-Curiel, Ricardo Francisco</creator><creator>Salas-Benito, Juan Santiago</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T7</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-0015-8081</orcidid><orcidid>https://orcid.org/0000-0002-0582-0046</orcidid><orcidid>https://orcid.org/0000-0001-7002-0881</orcidid><orcidid>https://orcid.org/0000-0002-4096-0079</orcidid></search><sort><creationdate>20230127</creationdate><title>Differential Gene Expression Pattern of Importin β3 and NS5 in C6/36 Cells Acutely and Persistently Infected with Dengue Virus 2</title><author>Ávila-Ramírez, María Leticia ; Reyes-Reyes, Ana Laura ; Avila-Bonilla, Rodolfo Gamaliel ; Salas-Benito, Mariana ; Cerecedo, Doris ; Ramírez-Moreno, María Esther ; Villagrán-Herrera, María Elena ; Mercado-Curiel, Ricardo Francisco ; Salas-Benito, Juan Santiago</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c512t-78cdb6b65c54f9734c7f09afc363f6e804285054d3f1f8933082d15d8235bc5c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Aedes albopictus</topic><topic>Amplified fragment length polymorphism</topic><topic>Aquatic insects</topic><topic>Carrier proteins</topic><topic>Dengue</topic><topic>Dengue fever</topic><topic>Dengue virus</topic><topic>Dengue viruses</topic><topic>Development and progression</topic><topic>DNA polymerase</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Hypotheses</topic><topic>importin</topic><topic>Infections</topic><topic>L cells</topic><topic>Mosquitoes</topic><topic>nuclear transport</topic><topic>Persistent infection</topic><topic>Physiological aspects</topic><topic>Proteins</topic><topic>Vector-borne diseases</topic><topic>Viral infections</topic><topic>viral persistence</topic><topic>Viral proteins</topic><topic>Virus research</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ávila-Ramírez, María Leticia</creatorcontrib><creatorcontrib>Reyes-Reyes, Ana Laura</creatorcontrib><creatorcontrib>Avila-Bonilla, Rodolfo Gamaliel</creatorcontrib><creatorcontrib>Salas-Benito, Mariana</creatorcontrib><creatorcontrib>Cerecedo, Doris</creatorcontrib><creatorcontrib>Ramírez-Moreno, María Esther</creatorcontrib><creatorcontrib>Villagrán-Herrera, María Elena</creatorcontrib><creatorcontrib>Mercado-Curiel, Ricardo Francisco</creatorcontrib><creatorcontrib>Salas-Benito, Juan Santiago</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>ProQuest Biological Science Journals</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ</collection><jtitle>Pathogens (Basel)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ávila-Ramírez, María Leticia</au><au>Reyes-Reyes, Ana Laura</au><au>Avila-Bonilla, Rodolfo Gamaliel</au><au>Salas-Benito, Mariana</au><au>Cerecedo, Doris</au><au>Ramírez-Moreno, María Esther</au><au>Villagrán-Herrera, María Elena</au><au>Mercado-Curiel, Ricardo Francisco</au><au>Salas-Benito, Juan Santiago</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential Gene Expression Pattern of Importin β3 and NS5 in C6/36 Cells Acutely and Persistently Infected with Dengue Virus 2</atitle><jtitle>Pathogens (Basel)</jtitle><addtitle>Pathogens</addtitle><date>2023-01-27</date><risdate>2023</risdate><volume>12</volume><issue>2</issue><spage>191</spage><pages>191-</pages><issn>2076-0817</issn><eissn>2076-0817</eissn><abstract>The establishment of persistent dengue virus infection within the cells of the mosquito vector is an essential requirement for viral transmission to a new human host. The mechanisms involved in the establishment and maintenance of persistent infection are not well understood, but it has been suggested that both viral and cellular factors might play an important role. In the present work, we evaluated differential gene expression in cells acutely (C6/36-HT) and persistently infected (C6-L) with Dengue virus 2 by cDNA-AFLP. We observed that importin β3 was upregulated in noninfected cells compared with C6-L cells. Using RT-qPCR and plaque assays, we observed that Dengue virus levels in C6-L cells essentially do not vary over time, and peak viral titers in acutely infected cells are observed at 72 and 120 h postinfection. The expression level of importin β3 was higher in acutely infected cells than in persistently infected cells; this correlates with higher levels of NS5 in the nucleus of the cell. The differential pattern of importin β3 expression between acute and persistent infection with Dengue virus 2 could be a mechanism to maintain viral infection over time, reducing the antiviral response of the cell and the viral replicative rate.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36839463</pmid><doi>10.3390/pathogens12020191</doi><orcidid>https://orcid.org/0000-0002-0015-8081</orcidid><orcidid>https://orcid.org/0000-0002-0582-0046</orcidid><orcidid>https://orcid.org/0000-0001-7002-0881</orcidid><orcidid>https://orcid.org/0000-0002-4096-0079</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2076-0817
ispartof Pathogens (Basel), 2023-01, Vol.12 (2), p.191
issn 2076-0817
2076-0817
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_bd5a32e0cfe34ca2b621d92e58c2db9e
source PubMed Central Free; Publicly Available Content Database
subjects Aedes albopictus
Amplified fragment length polymorphism
Aquatic insects
Carrier proteins
Dengue
Dengue fever
Dengue virus
Dengue viruses
Development and progression
DNA polymerase
Gene expression
Genetic aspects
Genomes
Hypotheses
importin
Infections
L cells
Mosquitoes
nuclear transport
Persistent infection
Physiological aspects
Proteins
Vector-borne diseases
Viral infections
viral persistence
Viral proteins
Virus research
Viruses
title Differential Gene Expression Pattern of Importin β3 and NS5 in C6/36 Cells Acutely and Persistently Infected with Dengue Virus 2
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T03%3A22%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Differential%20Gene%20Expression%20Pattern%20of%20Importin%20%CE%B23%20and%20NS5%20in%20C6/36%20Cells%20Acutely%20and%20Persistently%20Infected%20with%20Dengue%20Virus%202&rft.jtitle=Pathogens%20(Basel)&rft.au=%C3%81vila-Ram%C3%ADrez,%20Mar%C3%ADa%20Leticia&rft.date=2023-01-27&rft.volume=12&rft.issue=2&rft.spage=191&rft.pages=191-&rft.issn=2076-0817&rft.eissn=2076-0817&rft_id=info:doi/10.3390/pathogens12020191&rft_dat=%3Cgale_doaj_%3EA743326698%3C/gale_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c512t-78cdb6b65c54f9734c7f09afc363f6e804285054d3f1f8933082d15d8235bc5c3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2779626504&rft_id=info:pmid/36839463&rft_galeid=A743326698&rfr_iscdi=true