Loading…

Decreased classical monocytes and CD163 expression in TB patients: an indicator of drug resistance

Tuberculosis (TB) is a disease instigated by Mycobacterium tuberculosis . Peripheral blood monocytes represent highly efficient effector cells of innate immunity against TB. Little is known about monocyte subsets and their potential involvement in the development of M. tuberculosis drug resistance i...

Full description

Saved in:
Bibliographic Details
Published in:Brazilian journal of microbiology 2021-06, Vol.52 (2), p.607-617
Main Authors: Shahzad, Faheem, Bashir, Noman, Ali, Atia, Jabeen, Shagufta, Kashif, Mohammad, Javaid, Khursheed, Tahir, Romeeza, Abbas, Afia, Jahan, Shah, Afzal, Nadeem
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-c474t-d3a0c12e450e646e1015f2f3d9faf2fed5fface33303f259242f00316b7a38223
cites cdi_FETCH-LOGICAL-c474t-d3a0c12e450e646e1015f2f3d9faf2fed5fface33303f259242f00316b7a38223
container_end_page 617
container_issue 2
container_start_page 607
container_title Brazilian journal of microbiology
container_volume 52
creator Shahzad, Faheem
Bashir, Noman
Ali, Atia
Jabeen, Shagufta
Kashif, Mohammad
Javaid, Khursheed
Tahir, Romeeza
Abbas, Afia
Jahan, Shah
Afzal, Nadeem
description Tuberculosis (TB) is a disease instigated by Mycobacterium tuberculosis . Peripheral blood monocytes represent highly efficient effector cells of innate immunity against TB. Little is known about monocyte subsets and their potential involvement in the development of M. tuberculosis drug resistance in patients with TB. This study was conducted to investigate alterations in monocyte subsets, CD163 expression on monocytes, and its serum level in patients without and with rifampicin resistance TB (RR-TB) and healthy controls. A total of 164 patients with TB (84 without RR-TB and 80 patients with RR-TB) and 85 healthy controls were enrolled in this study. The percentages of various monocyte subsets and surface expression of CD163 on monocytes were quantitatively determined using flow cytometry. The serum level of CD163 was determined by commercially available ELISA kits. Decreased frequency of classical monocytes was detected in patients with RR-TB. Non-classical monocytes were decreased in patients without RR-TB; however, intermediate monocytes were raised in patients with RR-TB. The serum level of CD163 was decreased in patients of RR-TB that showsed a positive correlation with the frequency of CD14 ++ CD16 – CD163 + and CD14 ++ CD16 + CD163 + monocytes. It is concluded that decreased classical monocytes and sCD163 in patients with RR-TB could be an indicator of drug resistance.
doi_str_mv 10.1007/s42770-021-00454-x
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8105472</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2523141381</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-d3a0c12e450e646e1015f2f3d9faf2fed5fface33303f259242f00316b7a38223</originalsourceid><addsrcrecordid>eNp9kU1P3DAQhq2qqHz-gR4qS730kjL-ShwOlWChgITEBc6W1xlvg7L2Yido-fc1LKWlB05j-X3mnRm9hHxm8J0BNIdZ8qaBCjirAKSS1foD2WF1oyspQX0sb8WaSgvNt8luzncAXIHkn8i2EErX0ModMj9Fl9Bm7KgbbM69swNdxhDd44iZ2tDR2SmrBcX1KmHRY6B9oDcndGXHHsOYjwpUvrrSOcZEo6ddmha0wH0ebXC4T7a8HTIevNQ9cvvz7GZ2UV1dn1_Ojq8qJxs5Vp2w4BhHqQBrWSMDpjz3omu9LRU75b11KIQA4blqueQeQLB63thyIhd75MfGdzXNl9i5slyyg1mlfmnTo4m2N2-V0P8yi_hgNAMlmyeDby8GKd5PmEez7LPDYbAB45QNl7pVrZagC_r1P_QuTimU8wxXXDDJhGaF4hvKpZhzQv-6DAPzFKHZRGhKhOY5QrMuTV_-PeO15U9mBRAbIBcpLDD9nf2O7W_Cjafh</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2523141381</pqid></control><display><type>article</type><title>Decreased classical monocytes and CD163 expression in TB patients: an indicator of drug resistance</title><source>PubMed (Medline)</source><source>Springer Link</source><creator>Shahzad, Faheem ; Bashir, Noman ; Ali, Atia ; Jabeen, Shagufta ; Kashif, Mohammad ; Javaid, Khursheed ; Tahir, Romeeza ; Abbas, Afia ; Jahan, Shah ; Afzal, Nadeem</creator><creatorcontrib>Shahzad, Faheem ; Bashir, Noman ; Ali, Atia ; Jabeen, Shagufta ; Kashif, Mohammad ; Javaid, Khursheed ; Tahir, Romeeza ; Abbas, Afia ; Jahan, Shah ; Afzal, Nadeem</creatorcontrib><description>Tuberculosis (TB) is a disease instigated by Mycobacterium tuberculosis . Peripheral blood monocytes represent highly efficient effector cells of innate immunity against TB. Little is known about monocyte subsets and their potential involvement in the development of M. tuberculosis drug resistance in patients with TB. This study was conducted to investigate alterations in monocyte subsets, CD163 expression on monocytes, and its serum level in patients without and with rifampicin resistance TB (RR-TB) and healthy controls. A total of 164 patients with TB (84 without RR-TB and 80 patients with RR-TB) and 85 healthy controls were enrolled in this study. The percentages of various monocyte subsets and surface expression of CD163 on monocytes were quantitatively determined using flow cytometry. The serum level of CD163 was determined by commercially available ELISA kits. Decreased frequency of classical monocytes was detected in patients with RR-TB. Non-classical monocytes were decreased in patients without RR-TB; however, intermediate monocytes were raised in patients with RR-TB. The serum level of CD163 was decreased in patients of RR-TB that showsed a positive correlation with the frequency of CD14 ++ CD16 – CD163 + and CD14 ++ CD16 + CD163 + monocytes. It is concluded that decreased classical monocytes and sCD163 in patients with RR-TB could be an indicator of drug resistance.</description><identifier>ISSN: 1517-8382</identifier><identifier>EISSN: 1678-4405</identifier><identifier>DOI: 10.1007/s42770-021-00454-x</identifier><identifier>PMID: 33586094</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Adult ; Antigens, CD - blood ; Antigens, CD - economics ; Antigens, Differentiation, Myelomonocytic - blood ; Antigens, Differentiation, Myelomonocytic - economics ; Antitubercular Agents - pharmacology ; Biomedical and Life Sciences ; CD14 antigen ; CD16 antigen ; CD163 antigen ; Clinical Microbiology - Research Paper ; Drug resistance ; Drug Resistance, Bacterial ; Effector cells ; Female ; Flow cytometry ; Food Microbiology ; Humans ; Innate immunity ; Life Sciences ; Male ; Medical Microbiology ; Microbial Ecology ; Microbial Genetics and Genomics ; Microbiology ; Middle Aged ; Monocytes ; Monocytes - metabolism ; Mycobacterium tuberculosis - drug effects ; Mycobacterium tuberculosis - genetics ; Mycobacterium tuberculosis - physiology ; Mycology ; Peripheral blood ; Receptors, Cell Surface - blood ; Rifampin ; Rifampin - pharmacology ; Tuberculosis ; Tuberculosis - blood ; Tuberculosis - drug therapy ; Tuberculosis - microbiology</subject><ispartof>Brazilian journal of microbiology, 2021-06, Vol.52 (2), p.607-617</ispartof><rights>Sociedade Brasileira de Microbiologia 2021</rights><rights>Sociedade Brasileira de Microbiologia 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-d3a0c12e450e646e1015f2f3d9faf2fed5fface33303f259242f00316b7a38223</citedby><cites>FETCH-LOGICAL-c474t-d3a0c12e450e646e1015f2f3d9faf2fed5fface33303f259242f00316b7a38223</cites><orcidid>0000-0002-2238-5912</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105472/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105472/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,733,786,790,891,27957,27958,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33586094$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shahzad, Faheem</creatorcontrib><creatorcontrib>Bashir, Noman</creatorcontrib><creatorcontrib>Ali, Atia</creatorcontrib><creatorcontrib>Jabeen, Shagufta</creatorcontrib><creatorcontrib>Kashif, Mohammad</creatorcontrib><creatorcontrib>Javaid, Khursheed</creatorcontrib><creatorcontrib>Tahir, Romeeza</creatorcontrib><creatorcontrib>Abbas, Afia</creatorcontrib><creatorcontrib>Jahan, Shah</creatorcontrib><creatorcontrib>Afzal, Nadeem</creatorcontrib><title>Decreased classical monocytes and CD163 expression in TB patients: an indicator of drug resistance</title><title>Brazilian journal of microbiology</title><addtitle>Braz J Microbiol</addtitle><addtitle>Braz J Microbiol</addtitle><description>Tuberculosis (TB) is a disease instigated by Mycobacterium tuberculosis . Peripheral blood monocytes represent highly efficient effector cells of innate immunity against TB. Little is known about monocyte subsets and their potential involvement in the development of M. tuberculosis drug resistance in patients with TB. This study was conducted to investigate alterations in monocyte subsets, CD163 expression on monocytes, and its serum level in patients without and with rifampicin resistance TB (RR-TB) and healthy controls. A total of 164 patients with TB (84 without RR-TB and 80 patients with RR-TB) and 85 healthy controls were enrolled in this study. The percentages of various monocyte subsets and surface expression of CD163 on monocytes were quantitatively determined using flow cytometry. The serum level of CD163 was determined by commercially available ELISA kits. Decreased frequency of classical monocytes was detected in patients with RR-TB. Non-classical monocytes were decreased in patients without RR-TB; however, intermediate monocytes were raised in patients with RR-TB. The serum level of CD163 was decreased in patients of RR-TB that showsed a positive correlation with the frequency of CD14 ++ CD16 – CD163 + and CD14 ++ CD16 + CD163 + monocytes. It is concluded that decreased classical monocytes and sCD163 in patients with RR-TB could be an indicator of drug resistance.</description><subject>Adult</subject><subject>Antigens, CD - blood</subject><subject>Antigens, CD - economics</subject><subject>Antigens, Differentiation, Myelomonocytic - blood</subject><subject>Antigens, Differentiation, Myelomonocytic - economics</subject><subject>Antitubercular Agents - pharmacology</subject><subject>Biomedical and Life Sciences</subject><subject>CD14 antigen</subject><subject>CD16 antigen</subject><subject>CD163 antigen</subject><subject>Clinical Microbiology - Research Paper</subject><subject>Drug resistance</subject><subject>Drug Resistance, Bacterial</subject><subject>Effector cells</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Food Microbiology</subject><subject>Humans</subject><subject>Innate immunity</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Medical Microbiology</subject><subject>Microbial Ecology</subject><subject>Microbial Genetics and Genomics</subject><subject>Microbiology</subject><subject>Middle Aged</subject><subject>Monocytes</subject><subject>Monocytes - metabolism</subject><subject>Mycobacterium tuberculosis - drug effects</subject><subject>Mycobacterium tuberculosis - genetics</subject><subject>Mycobacterium tuberculosis - physiology</subject><subject>Mycology</subject><subject>Peripheral blood</subject><subject>Receptors, Cell Surface - blood</subject><subject>Rifampin</subject><subject>Rifampin - pharmacology</subject><subject>Tuberculosis</subject><subject>Tuberculosis - blood</subject><subject>Tuberculosis - drug therapy</subject><subject>Tuberculosis - microbiology</subject><issn>1517-8382</issn><issn>1678-4405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kU1P3DAQhq2qqHz-gR4qS730kjL-ShwOlWChgITEBc6W1xlvg7L2Yido-fc1LKWlB05j-X3mnRm9hHxm8J0BNIdZ8qaBCjirAKSS1foD2WF1oyspQX0sb8WaSgvNt8luzncAXIHkn8i2EErX0ModMj9Fl9Bm7KgbbM69swNdxhDd44iZ2tDR2SmrBcX1KmHRY6B9oDcndGXHHsOYjwpUvrrSOcZEo6ddmha0wH0ebXC4T7a8HTIevNQ9cvvz7GZ2UV1dn1_Ojq8qJxs5Vp2w4BhHqQBrWSMDpjz3omu9LRU75b11KIQA4blqueQeQLB63thyIhd75MfGdzXNl9i5slyyg1mlfmnTo4m2N2-V0P8yi_hgNAMlmyeDby8GKd5PmEez7LPDYbAB45QNl7pVrZagC_r1P_QuTimU8wxXXDDJhGaF4hvKpZhzQv-6DAPzFKHZRGhKhOY5QrMuTV_-PeO15U9mBRAbIBcpLDD9nf2O7W_Cjafh</recordid><startdate>20210601</startdate><enddate>20210601</enddate><creator>Shahzad, Faheem</creator><creator>Bashir, Noman</creator><creator>Ali, Atia</creator><creator>Jabeen, Shagufta</creator><creator>Kashif, Mohammad</creator><creator>Javaid, Khursheed</creator><creator>Tahir, Romeeza</creator><creator>Abbas, Afia</creator><creator>Jahan, Shah</creator><creator>Afzal, Nadeem</creator><general>Springer International Publishing</general><general>Springer Nature B.V</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>7QL</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2238-5912</orcidid></search><sort><creationdate>20210601</creationdate><title>Decreased classical monocytes and CD163 expression in TB patients: an indicator of drug resistance</title><author>Shahzad, Faheem ; Bashir, Noman ; Ali, Atia ; Jabeen, Shagufta ; Kashif, Mohammad ; Javaid, Khursheed ; Tahir, Romeeza ; Abbas, Afia ; Jahan, Shah ; Afzal, Nadeem</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-d3a0c12e450e646e1015f2f3d9faf2fed5fface33303f259242f00316b7a38223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Antigens, CD - blood</topic><topic>Antigens, CD - economics</topic><topic>Antigens, Differentiation, Myelomonocytic - blood</topic><topic>Antigens, Differentiation, Myelomonocytic - economics</topic><topic>Antitubercular Agents - pharmacology</topic><topic>Biomedical and Life Sciences</topic><topic>CD14 antigen</topic><topic>CD16 antigen</topic><topic>CD163 antigen</topic><topic>Clinical Microbiology - Research Paper</topic><topic>Drug resistance</topic><topic>Drug Resistance, Bacterial</topic><topic>Effector cells</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Food Microbiology</topic><topic>Humans</topic><topic>Innate immunity</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Medical Microbiology</topic><topic>Microbial Ecology</topic><topic>Microbial Genetics and Genomics</topic><topic>Microbiology</topic><topic>Middle Aged</topic><topic>Monocytes</topic><topic>Monocytes - metabolism</topic><topic>Mycobacterium tuberculosis - drug effects</topic><topic>Mycobacterium tuberculosis - genetics</topic><topic>Mycobacterium tuberculosis - physiology</topic><topic>Mycology</topic><topic>Peripheral blood</topic><topic>Receptors, Cell Surface - blood</topic><topic>Rifampin</topic><topic>Rifampin - pharmacology</topic><topic>Tuberculosis</topic><topic>Tuberculosis - blood</topic><topic>Tuberculosis - drug therapy</topic><topic>Tuberculosis - microbiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shahzad, Faheem</creatorcontrib><creatorcontrib>Bashir, Noman</creatorcontrib><creatorcontrib>Ali, Atia</creatorcontrib><creatorcontrib>Jabeen, Shagufta</creatorcontrib><creatorcontrib>Kashif, Mohammad</creatorcontrib><creatorcontrib>Javaid, Khursheed</creatorcontrib><creatorcontrib>Tahir, Romeeza</creatorcontrib><creatorcontrib>Abbas, Afia</creatorcontrib><creatorcontrib>Jahan, Shah</creatorcontrib><creatorcontrib>Afzal, Nadeem</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Brazilian journal of microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shahzad, Faheem</au><au>Bashir, Noman</au><au>Ali, Atia</au><au>Jabeen, Shagufta</au><au>Kashif, Mohammad</au><au>Javaid, Khursheed</au><au>Tahir, Romeeza</au><au>Abbas, Afia</au><au>Jahan, Shah</au><au>Afzal, Nadeem</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased classical monocytes and CD163 expression in TB patients: an indicator of drug resistance</atitle><jtitle>Brazilian journal of microbiology</jtitle><stitle>Braz J Microbiol</stitle><addtitle>Braz J Microbiol</addtitle><date>2021-06-01</date><risdate>2021</risdate><volume>52</volume><issue>2</issue><spage>607</spage><epage>617</epage><pages>607-617</pages><issn>1517-8382</issn><eissn>1678-4405</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>Responsible Editor: Fernando R. Pavan</notes><abstract>Tuberculosis (TB) is a disease instigated by Mycobacterium tuberculosis . Peripheral blood monocytes represent highly efficient effector cells of innate immunity against TB. Little is known about monocyte subsets and their potential involvement in the development of M. tuberculosis drug resistance in patients with TB. This study was conducted to investigate alterations in monocyte subsets, CD163 expression on monocytes, and its serum level in patients without and with rifampicin resistance TB (RR-TB) and healthy controls. A total of 164 patients with TB (84 without RR-TB and 80 patients with RR-TB) and 85 healthy controls were enrolled in this study. The percentages of various monocyte subsets and surface expression of CD163 on monocytes were quantitatively determined using flow cytometry. The serum level of CD163 was determined by commercially available ELISA kits. Decreased frequency of classical monocytes was detected in patients with RR-TB. Non-classical monocytes were decreased in patients without RR-TB; however, intermediate monocytes were raised in patients with RR-TB. The serum level of CD163 was decreased in patients of RR-TB that showsed a positive correlation with the frequency of CD14 ++ CD16 – CD163 + and CD14 ++ CD16 + CD163 + monocytes. It is concluded that decreased classical monocytes and sCD163 in patients with RR-TB could be an indicator of drug resistance.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>33586094</pmid><doi>10.1007/s42770-021-00454-x</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-2238-5912</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1517-8382
ispartof Brazilian journal of microbiology, 2021-06, Vol.52 (2), p.607-617
issn 1517-8382
1678-4405
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8105472
source PubMed (Medline); Springer Link
subjects Adult
Antigens, CD - blood
Antigens, CD - economics
Antigens, Differentiation, Myelomonocytic - blood
Antigens, Differentiation, Myelomonocytic - economics
Antitubercular Agents - pharmacology
Biomedical and Life Sciences
CD14 antigen
CD16 antigen
CD163 antigen
Clinical Microbiology - Research Paper
Drug resistance
Drug Resistance, Bacterial
Effector cells
Female
Flow cytometry
Food Microbiology
Humans
Innate immunity
Life Sciences
Male
Medical Microbiology
Microbial Ecology
Microbial Genetics and Genomics
Microbiology
Middle Aged
Monocytes
Monocytes - metabolism
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - physiology
Mycology
Peripheral blood
Receptors, Cell Surface - blood
Rifampin
Rifampin - pharmacology
Tuberculosis
Tuberculosis - blood
Tuberculosis - drug therapy
Tuberculosis - microbiology
title Decreased classical monocytes and CD163 expression in TB patients: an indicator of drug resistance
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-22T20%3A23%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Decreased%20classical%20monocytes%20and%20CD163%20expression%20in%20TB%20patients:%20an%20indicator%20of%20drug%20resistance&rft.jtitle=Brazilian%20journal%20of%20microbiology&rft.au=Shahzad,%20Faheem&rft.date=2021-06-01&rft.volume=52&rft.issue=2&rft.spage=607&rft.epage=617&rft.pages=607-617&rft.issn=1517-8382&rft.eissn=1678-4405&rft_id=info:doi/10.1007/s42770-021-00454-x&rft_dat=%3Cproquest_pubme%3E2523141381%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c474t-d3a0c12e450e646e1015f2f3d9faf2fed5fface33303f259242f00316b7a38223%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2523141381&rft_id=info:pmid/33586094&rfr_iscdi=true