Clinical significance of IgG antimitochondrial M2 antibody levels in primary biliary cholangitis: A single center study from China
The relationship between antimitochondrial antibody (AMA) levels and the severity or prognosis of primary biliary cholangitis (PBC) is unclear. This study explored the clinical significance of serum IgG antimitochondrial M2 antibody (IgG-M2) levels. From 2008 to 2017, a retrospective analysis was co...
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| creator | Feng, Lina Dong, Kaihui Zhang, Xiaoxue Ma, Bo Chen, Lin Yang, Qianqian Chen, Qingling Wen, Xiaoyu Jin, Qinglong |
| description | The relationship between antimitochondrial antibody (AMA) levels and the severity or prognosis of primary biliary cholangitis (PBC) is unclear. This study explored the clinical significance of serum IgG antimitochondrial M2 antibody (IgG-M2) levels.
From 2008 to 2017, a retrospective analysis was conducted with PBC patients who had available quantitative values of serum IgG-M2 levels obtained with ELISA based on triple expression hybrid clones. The patients were divided into two groups based on high and low concentrations of IgG-M2. Baseline parameters, the incidence of adverse events, and prognosis were compared.
Among the 530 PBC patients, the levels of albumin, cholinesterase, hemoglobin, fibrinogen and triglycerides and the red blood cell count were significantly lower in the high-concentration group than in the low-concentration group (n = 263, 49.6%). The red cell distribution width (RDW) and levels of serum immunoglobulin (Ig) G, IgM and IgA were significantly higher in the high-concentration group than in the low-concentration group. Spearman's correlation analysis suggested that the correlation between the above baseline indicators and IgG-M2 levels was statistically significant but weak (r < 0.2, P < 0.05). In total, 203 patients were followed up, of whom 87 (42.9%) were in the high-concentration group. During the median follow-up period of 52 months (range: 28-75), 121 (59.6%) experienced hepatic decompensation, and 37 (18.2%) died or underwent liver transplantation. There was no significant difference in the incidence of complications or survival (log-rank test: P = 0.079) between the two groups. One year after ursodeoxycholic acid (UDCA) treatment, the two groups had similar responses. In addition, the levels of IgG-M2 did not fluctuate significantly during treatment.
IgG-M2 levels were not related to the disease severity, prognosis or efficacy of UDCA. The levels of IgG-M2 did not change significantly during treatment. |
| doi_str_mv | 10.1371/journal.pone.0242164 |
| format | Article |
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From 2008 to 2017, a retrospective analysis was conducted with PBC patients who had available quantitative values of serum IgG-M2 levels obtained with ELISA based on triple expression hybrid clones. The patients were divided into two groups based on high and low concentrations of IgG-M2. Baseline parameters, the incidence of adverse events, and prognosis were compared.
Among the 530 PBC patients, the levels of albumin, cholinesterase, hemoglobin, fibrinogen and triglycerides and the red blood cell count were significantly lower in the high-concentration group than in the low-concentration group (n = 263, 49.6%). The red cell distribution width (RDW) and levels of serum immunoglobulin (Ig) G, IgM and IgA were significantly higher in the high-concentration group than in the low-concentration group. Spearman's correlation analysis suggested that the correlation between the above baseline indicators and IgG-M2 levels was statistically significant but weak (r < 0.2, P < 0.05). In total, 203 patients were followed up, of whom 87 (42.9%) were in the high-concentration group. During the median follow-up period of 52 months (range: 28-75), 121 (59.6%) experienced hepatic decompensation, and 37 (18.2%) died or underwent liver transplantation. There was no significant difference in the incidence of complications or survival (log-rank test: P = 0.079) between the two groups. One year after ursodeoxycholic acid (UDCA) treatment, the two groups had similar responses. In addition, the levels of IgG-M2 did not fluctuate significantly during treatment.
IgG-M2 levels were not related to the disease severity, prognosis or efficacy of UDCA. The levels of IgG-M2 did not change significantly during treatment.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0242164</identifier><identifier>PMID: 33180817</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Albumins ; Antibodies ; Ascites ; Autoantibodies ; Autoantigens - blood ; Autoantigens - immunology ; Biology and Life Sciences ; Biomarkers - blood ; Causes of ; Cholangitis ; Cholinesterase ; Clinical significance ; Complications ; Correlation ; Correlation analysis ; Dehydrogenases ; Drug therapy ; Enzyme-linked immunosorbent assay ; Erythrocytes ; Female ; Fibrinogen ; Gallbladder diseases ; Health aspects ; Health services ; Hemoglobin ; Hepatology ; Histology ; Hospitals ; Humans ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin G - blood ; Immunoglobulin G - immunology ; Immunoglobulin M ; Liver cancer ; Liver cirrhosis ; Liver Cirrhosis, Biliary - immunology ; Liver Cirrhosis, Biliary - pathology ; Liver diseases ; Liver transplantation ; Low concentrations ; Male ; Medical prognosis ; Medical research ; Medicine and Health Sciences ; Middle Aged ; Mitochondrial Proteins - immunology ; Patients ; Prognosis ; Rank tests ; Research and Analysis Methods ; Statistical analysis ; Transplantation ; Transplants & implants ; Triglycerides ; Ursodeoxycholic acid</subject><ispartof>PloS one, 2020-11, Vol.15 (11), p.e0242164-e0242164</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Feng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Feng et al 2020 Feng et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-8e4ed7894fffb8bc85d36d459a8733ef78d26f0cc4cb0db9d91437c934589473</citedby><cites>FETCH-LOGICAL-c692t-8e4ed7894fffb8bc85d36d459a8733ef78d26f0cc4cb0db9d91437c934589473</cites><orcidid>0000-0003-3486-2795</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/PMC7661052/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661052/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33180817$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Barbier, Olivier</contributor><creatorcontrib>Feng, Lina</creatorcontrib><creatorcontrib>Dong, Kaihui</creatorcontrib><creatorcontrib>Zhang, Xiaoxue</creatorcontrib><creatorcontrib>Ma, Bo</creatorcontrib><creatorcontrib>Chen, Lin</creatorcontrib><creatorcontrib>Yang, Qianqian</creatorcontrib><creatorcontrib>Chen, Qingling</creatorcontrib><creatorcontrib>Wen, Xiaoyu</creatorcontrib><creatorcontrib>Jin, Qinglong</creatorcontrib><title>Clinical significance of IgG antimitochondrial M2 antibody levels in primary biliary cholangitis: A single center study from China</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The relationship between antimitochondrial antibody (AMA) levels and the severity or prognosis of primary biliary cholangitis (PBC) is unclear. This study explored the clinical significance of serum IgG antimitochondrial M2 antibody (IgG-M2) levels.
From 2008 to 2017, a retrospective analysis was conducted with PBC patients who had available quantitative values of serum IgG-M2 levels obtained with ELISA based on triple expression hybrid clones. The patients were divided into two groups based on high and low concentrations of IgG-M2. Baseline parameters, the incidence of adverse events, and prognosis were compared.
Among the 530 PBC patients, the levels of albumin, cholinesterase, hemoglobin, fibrinogen and triglycerides and the red blood cell count were significantly lower in the high-concentration group than in the low-concentration group (n = 263, 49.6%). The red cell distribution width (RDW) and levels of serum immunoglobulin (Ig) G, IgM and IgA were significantly higher in the high-concentration group than in the low-concentration group. Spearman's correlation analysis suggested that the correlation between the above baseline indicators and IgG-M2 levels was statistically significant but weak (r < 0.2, P < 0.05). In total, 203 patients were followed up, of whom 87 (42.9%) were in the high-concentration group. During the median follow-up period of 52 months (range: 28-75), 121 (59.6%) experienced hepatic decompensation, and 37 (18.2%) died or underwent liver transplantation. There was no significant difference in the incidence of complications or survival (log-rank test: P = 0.079) between the two groups. One year after ursodeoxycholic acid (UDCA) treatment, the two groups had similar responses. In addition, the levels of IgG-M2 did not fluctuate significantly during treatment.
IgG-M2 levels were not related to the disease severity, prognosis or efficacy of UDCA. The levels of IgG-M2 did not change significantly during treatment.</description><subject>Aged</subject><subject>Albumins</subject><subject>Antibodies</subject><subject>Ascites</subject><subject>Autoantibodies</subject><subject>Autoantigens - blood</subject><subject>Autoantigens - immunology</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers - blood</subject><subject>Causes of</subject><subject>Cholangitis</subject><subject>Cholinesterase</subject><subject>Clinical significance</subject><subject>Complications</subject><subject>Correlation</subject><subject>Correlation analysis</subject><subject>Dehydrogenases</subject><subject>Drug therapy</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Erythrocytes</subject><subject>Female</subject><subject>Fibrinogen</subject><subject>Gallbladder diseases</subject><subject>Health aspects</subject><subject>Health services</subject><subject>Hemoglobin</subject><subject>Hepatology</subject><subject>Histology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunoglobulin A</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunoglobulin M</subject><subject>Liver cancer</subject><subject>Liver cirrhosis</subject><subject>Liver Cirrhosis, Biliary - immunology</subject><subject>Liver Cirrhosis, Biliary - pathology</subject><subject>Liver diseases</subject><subject>Liver transplantation</subject><subject>Low concentrations</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Mitochondrial Proteins - immunology</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Rank tests</subject><subject>Research and Analysis Methods</subject><subject>Statistical analysis</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><subject>Triglycerides</subject><subject>Ursodeoxycholic acid</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99qFDEUxgdRbK2-gWhAEL3YNf8mk_FCWBatC5WCFm9DJsnMpmSSdTJT7LUv4rP4ZGa607IjvZBcJJz8vi85JzlZ9hzBJSIFencZhs5Lt9wFb5YQU4wYfZAdo5LgBcOQPDxYH2VPYryEMCecscfZESGIQ46K4-zX2llvlXQg2sbbOi29MiDUYNOcAul729o-qG3wurPS_fn9Bd9Eq6CvgTNXxkVgPdh1tpXdNaiss-OcBE76xvY2vger5O0bZ4AyvjcdiP2QxHUXWrDeWi-fZo9q6aJ5Ns0n2cWnjxfrz4uz89PNenW2UKzE_YIbanTBS1rXdcUrxXNNmKZ5KXlBiKkLrjGroVJUVVBXpS4RJYUqCc2TqCAn2cu97c6FKKbyRYEpg5CXZUkTsdkTOshLMeUkgrTiJhC6Rsiut8oZQTiGmhliCsKowpAXONfSlJAgiDTCyevDdNpQtUaPqXfSzUznO95uRROuRMEYgvlo8GYy6MKPwcRetDYq41JdTRj29y5YSSlM6Kt_0Puzm6hGpgSsr0M6V42mYsUoIhTznCRqeQ-VhjatVemv1TbFZ4K3M0FievOzb-QQo9h8-_r_7Pn3Ofv6gN0a6fptDG7obfBxDtI9qLoQY2fquyIjKMZWua2GGFtFTK2SZC8OH-hOdNsb5C_MmQ-o</recordid><startdate>20201112</startdate><enddate>20201112</enddate><creator>Feng, Lina</creator><creator>Dong, Kaihui</creator><creator>Zhang, Xiaoxue</creator><creator>Ma, Bo</creator><creator>Chen, Lin</creator><creator>Yang, Qianqian</creator><creator>Chen, Qingling</creator><creator>Wen, Xiaoyu</creator><creator>Jin, Qinglong</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-3486-2795</orcidid></search><sort><creationdate>20201112</creationdate><title>Clinical significance of IgG antimitochondrial M2 antibody levels in primary biliary cholangitis: A single center study from China</title><author>Feng, Lina ; Dong, Kaihui ; Zhang, Xiaoxue ; Ma, Bo ; Chen, Lin ; Yang, Qianqian ; Chen, Qingling ; Wen, Xiaoyu ; Jin, Qinglong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-8e4ed7894fffb8bc85d36d459a8733ef78d26f0cc4cb0db9d91437c934589473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aged</topic><topic>Albumins</topic><topic>Antibodies</topic><topic>Ascites</topic><topic>Autoantibodies</topic><topic>Autoantigens - blood</topic><topic>Autoantigens - immunology</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers - blood</topic><topic>Causes of</topic><topic>Cholangitis</topic><topic>Cholinesterase</topic><topic>Clinical significance</topic><topic>Complications</topic><topic>Correlation</topic><topic>Correlation analysis</topic><topic>Dehydrogenases</topic><topic>Drug therapy</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Erythrocytes</topic><topic>Female</topic><topic>Fibrinogen</topic><topic>Gallbladder diseases</topic><topic>Health aspects</topic><topic>Health services</topic><topic>Hemoglobin</topic><topic>Hepatology</topic><topic>Histology</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immunoglobulin A</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulin G - blood</topic><topic>Immunoglobulin G - immunology</topic><topic>Immunoglobulin M</topic><topic>Liver cancer</topic><topic>Liver cirrhosis</topic><topic>Liver Cirrhosis, Biliary - immunology</topic><topic>Liver Cirrhosis, Biliary - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Feng, Lina</au><au>Dong, Kaihui</au><au>Zhang, Xiaoxue</au><au>Ma, Bo</au><au>Chen, Lin</au><au>Yang, Qianqian</au><au>Chen, Qingling</au><au>Wen, Xiaoyu</au><au>Jin, Qinglong</au><au>Barbier, Olivier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical significance of IgG antimitochondrial M2 antibody levels in primary biliary cholangitis: A single center study from China</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-11-12</date><risdate>2020</risdate><volume>15</volume><issue>11</issue><spage>e0242164</spage><epage>e0242164</epage><pages>e0242164-e0242164</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The relationship between antimitochondrial antibody (AMA) levels and the severity or prognosis of primary biliary cholangitis (PBC) is unclear. This study explored the clinical significance of serum IgG antimitochondrial M2 antibody (IgG-M2) levels.
From 2008 to 2017, a retrospective analysis was conducted with PBC patients who had available quantitative values of serum IgG-M2 levels obtained with ELISA based on triple expression hybrid clones. The patients were divided into two groups based on high and low concentrations of IgG-M2. Baseline parameters, the incidence of adverse events, and prognosis were compared.
Among the 530 PBC patients, the levels of albumin, cholinesterase, hemoglobin, fibrinogen and triglycerides and the red blood cell count were significantly lower in the high-concentration group than in the low-concentration group (n = 263, 49.6%). The red cell distribution width (RDW) and levels of serum immunoglobulin (Ig) G, IgM and IgA were significantly higher in the high-concentration group than in the low-concentration group. Spearman's correlation analysis suggested that the correlation between the above baseline indicators and IgG-M2 levels was statistically significant but weak (r < 0.2, P < 0.05). In total, 203 patients were followed up, of whom 87 (42.9%) were in the high-concentration group. During the median follow-up period of 52 months (range: 28-75), 121 (59.6%) experienced hepatic decompensation, and 37 (18.2%) died or underwent liver transplantation. There was no significant difference in the incidence of complications or survival (log-rank test: P = 0.079) between the two groups. One year after ursodeoxycholic acid (UDCA) treatment, the two groups had similar responses. In addition, the levels of IgG-M2 did not fluctuate significantly during treatment.
IgG-M2 levels were not related to the disease severity, prognosis or efficacy of UDCA. The levels of IgG-M2 did not change significantly during treatment.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33180817</pmid><doi>10.1371/journal.pone.0242164</doi><tpages>e0242164</tpages><orcidid>https://orcid.org/0000-0003-3486-2795</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-11, Vol.15 (11), p.e0242164-e0242164 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2460089994 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aged Albumins Antibodies Ascites Autoantibodies Autoantigens - blood Autoantigens - immunology Biology and Life Sciences Biomarkers - blood Causes of Cholangitis Cholinesterase Clinical significance Complications Correlation Correlation analysis Dehydrogenases Drug therapy Enzyme-linked immunosorbent assay Erythrocytes Female Fibrinogen Gallbladder diseases Health aspects Health services Hemoglobin Hepatology Histology Hospitals Humans Immunoglobulin A Immunoglobulin G Immunoglobulin G - blood Immunoglobulin G - immunology Immunoglobulin M Liver cancer Liver cirrhosis Liver Cirrhosis, Biliary - immunology Liver Cirrhosis, Biliary - pathology Liver diseases Liver transplantation Low concentrations Male Medical prognosis Medical research Medicine and Health Sciences Middle Aged Mitochondrial Proteins - immunology Patients Prognosis Rank tests Research and Analysis Methods Statistical analysis Transplantation Transplants & implants Triglycerides Ursodeoxycholic acid |
| title | Clinical significance of IgG antimitochondrial M2 antibody levels in primary biliary cholangitis: A single center study from China |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T04%3A42%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Clinical%20significance%20of%20IgG%20antimitochondrial%C2%A0M2%20antibody%20levels%20in%20primary%20biliary%20cholangitis:%20A%20single%20center%20study%20from%20China&rft.jtitle=PloS%20one&rft.au=Feng,%20Lina&rft.date=2020-11-12&rft.volume=15&rft.issue=11&rft.spage=e0242164&rft.epage=e0242164&rft.pages=e0242164-e0242164&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0242164&rft_dat=%3Cgale_plos_%3EA641342853%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2460089994&rft_id=info:pmid/33180817&rft_galeid=A641342853&rft_doaj_id=oai_doaj_org_article_3820d6e3e7364c208725dae903101d12&rfr_iscdi=true |