Prognostic value of pneumococcal urinary antigen test in community-acquired pneumonia
The pneumococcal urinary antigen test (UAT) has been known to improve sensitivity and specificity for the diagnosis of pneumococcal pneumonia. Associations of UAT results with prognosis in community acquired pneumonia (CAP) are not known. We hypothesized that positive UAT is associated with a good p...
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| description | The pneumococcal urinary antigen test (UAT) has been known to improve sensitivity and specificity for the diagnosis of pneumococcal pneumonia. Associations of UAT results with prognosis in community acquired pneumonia (CAP) are not known. We hypothesized that positive UAT is associated with a good prognosis, and incorporation of UAT into CRB65 would improve its prognostic performance.
In this registry-based retrospective study, we analyzed CAP patients over a 10-year period beginning in April 2008. Patients who had UAT results were included in multivariable extended Cox-regression analyses to determine the association between UAT positivity and 30-day mortality. UAT results were incorporated for patients with a CRB65 score of 1 by subtracting 1 from the scoring system if the test was positive. The performance of the modified scoring systems was assessed with area under the receiver operating characteristic (AUROC) curves.
Among 5145 CAP patients, total 2280 patients had UAT results and were included in analyses. A positive UAT result was associated with a good prognosis after a week of hospitalization (aHR, 0.14; p = 0.007). After modification of CRB65 using UAT results, positive and negative predictive values for 30-day mortality were increased from 7.7 to 8.3 (p |
| doi_str_mv | 10.1371/journal.pone.0200620 |
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In this registry-based retrospective study, we analyzed CAP patients over a 10-year period beginning in April 2008. Patients who had UAT results were included in multivariable extended Cox-regression analyses to determine the association between UAT positivity and 30-day mortality. UAT results were incorporated for patients with a CRB65 score of 1 by subtracting 1 from the scoring system if the test was positive. The performance of the modified scoring systems was assessed with area under the receiver operating characteristic (AUROC) curves.
Among 5145 CAP patients, total 2280 patients had UAT results and were included in analyses. A positive UAT result was associated with a good prognosis after a week of hospitalization (aHR, 0.14; p = 0.007). After modification of CRB65 using UAT results, positive and negative predictive values for 30-day mortality were increased from 7.7 to 8.3 (p<0.001) and 98.9 to 99.1 (p = 0.010). The AUROC increased from 0.73 to 0.75 (p<0.001).
Positive results on UAT could be considered as a good prognostic factor in CAP. UAT could be used as a useful tool in deciding whether to refer patients to the hospital, especially in moderate CAP with a CRB score of 1.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0200620</identifier><identifier>PMID: 30028834</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Aged, 80 and over ; Analysis ; Antibiotics ; Antigens ; Antigens, Bacterial - urine ; Biology and Life Sciences ; Communities ; Community-Acquired Infections - diagnosis ; Community-Acquired Infections - microbiology ; Community-Acquired Infections - mortality ; Community-Acquired Infections - urine ; Diagnosis ; Emergency medical care ; Female ; Gram-negative bacteria ; Health aspects ; Hospitals ; Humans ; Infectious diseases ; Male ; Medical prognosis ; Medicine ; Medicine and Health Sciences ; Middle Aged ; Mortality ; Patients ; Pneumococcal pneumonia ; Pneumonia ; Pneumonia, Pneumococcal - diagnosis ; Pneumonia, Pneumococcal - microbiology ; Pneumonia, Pneumococcal - mortality ; Pneumonia, Pneumococcal - urine ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Regression analysis ; Republic of Korea - epidemiology ; Retrospective Studies ; ROC Curve ; Streptococcus infections ; Streptococcus pneumoniae - immunology ; Streptococcus pneumoniae - isolation & purification ; Studies ; Survival Rate ; Urinalysis ; Urine ; Variables ; Ventilators</subject><ispartof>PloS one, 2018-07, Vol.13 (7), p.e0200620-e0200620</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Kim 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>2018 Kim et al 2018 Kim et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-4a222c479b48c76323d3110dc6a9a81550dade21a16133109270586e2a2165343</citedby><cites>FETCH-LOGICAL-c692t-4a222c479b48c76323d3110dc6a9a81550dade21a16133109270586e2a2165343</cites><orcidid>0000-0001-5080-7097</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/PMC6054390/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054390/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30028834$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Byunghyun</creatorcontrib><creatorcontrib>Kim, Joonghee</creatorcontrib><creatorcontrib>Jo, You Hwan</creatorcontrib><creatorcontrib>Lee, Jae Hyuk</creatorcontrib><creatorcontrib>Hwang, Ji Eun</creatorcontrib><creatorcontrib>Park, Min Ji</creatorcontrib><creatorcontrib>Lee, Sihyung</creatorcontrib><title>Prognostic value of pneumococcal urinary antigen test in community-acquired pneumonia</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The pneumococcal urinary antigen test (UAT) has been known to improve sensitivity and specificity for the diagnosis of pneumococcal pneumonia. Associations of UAT results with prognosis in community acquired pneumonia (CAP) are not known. We hypothesized that positive UAT is associated with a good prognosis, and incorporation of UAT into CRB65 would improve its prognostic performance.
In this registry-based retrospective study, we analyzed CAP patients over a 10-year period beginning in April 2008. Patients who had UAT results were included in multivariable extended Cox-regression analyses to determine the association between UAT positivity and 30-day mortality. UAT results were incorporated for patients with a CRB65 score of 1 by subtracting 1 from the scoring system if the test was positive. The performance of the modified scoring systems was assessed with area under the receiver operating characteristic (AUROC) curves.
Among 5145 CAP patients, total 2280 patients had UAT results and were included in analyses. A positive UAT result was associated with a good prognosis after a week of hospitalization (aHR, 0.14; p = 0.007). After modification of CRB65 using UAT results, positive and negative predictive values for 30-day mortality were increased from 7.7 to 8.3 (p<0.001) and 98.9 to 99.1 (p = 0.010). The AUROC increased from 0.73 to 0.75 (p<0.001).
Positive results on UAT could be considered as a good prognostic factor in CAP. UAT could be used as a useful tool in deciding whether to refer patients to the hospital, especially in moderate CAP with a CRB score of 1.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Antibiotics</subject><subject>Antigens</subject><subject>Antigens, Bacterial - urine</subject><subject>Biology and Life Sciences</subject><subject>Communities</subject><subject>Community-Acquired Infections - diagnosis</subject><subject>Community-Acquired Infections - microbiology</subject><subject>Community-Acquired Infections - mortality</subject><subject>Community-Acquired Infections - urine</subject><subject>Diagnosis</subject><subject>Emergency medical care</subject><subject>Female</subject><subject>Gram-negative bacteria</subject><subject>Health aspects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Patients</subject><subject>Pneumococcal pneumonia</subject><subject>Pneumonia</subject><subject>Pneumonia, Pneumococcal - diagnosis</subject><subject>Pneumonia, Pneumococcal - microbiology</subject><subject>Pneumonia, Pneumococcal - mortality</subject><subject>Pneumonia, Pneumococcal - urine</subject><subject>Predictive Value of Tests</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Regression analysis</subject><subject>Republic of Korea - epidemiology</subject><subject>Retrospective Studies</subject><subject>ROC Curve</subject><subject>Streptococcus infections</subject><subject>Streptococcus pneumoniae - immunology</subject><subject>Streptococcus pneumoniae - isolation & purification</subject><subject>Studies</subject><subject>Survival Rate</subject><subject>Urinalysis</subject><subject>Urine</subject><subject>Variables</subject><subject>Ventilators</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1r2zAUhs1YWbts_2BshsFYL5Lpy7J1UyhlH4FCx7buVhxLiqNgS6lkl_XfT2ncEo9eDF9ISM95j97jN8veYLTAtMSfNn4IDtrF1juzQAQhTtCz7AQLSuZpS58f7I-zlzFuECpoxfmL7JgiRKqKspPs-nvwjfOxtyq_hXYwuV_lW2eGziuvFLT5EKyDcJeD621jXN6b2OfW5cp33eBsfzcHdTPYYPRY5yy8yo5W0Ebzelxn2fWXz78uvs0vr74uL84v54oL0s8ZEEIUK0XNKlVySqimGCOtOAiocFEgDdoQDJhjSjESpERFxQ0BgnlBGZ1l7_a629ZHOU4kSoJKwoUoS5GI5Z7QHjZyG2yXvEgPVt4f-NBICMl8ayShRmlUCwymZgyRWghd6LKoi1ogyiFpnY3dhrozWhnXB2gnotMbZ9ey8beSo4LRpDHLPo4Cwd8MaY6ys1GZtgVn_HD_bkpJhdjO2ft_0KfdjVQDyYB1K5_6qp2oPC9YmWaJ-K7t4gkqfdp0VqX4rGw6nxScTgoS05s_fQNDjHL588f_s1e_p-yHA3ZtoO3X0bdDb72LU5DtQRV8jMGsHoeMkdyl_2Eacpd-OaY_lb09_EGPRQ9xp38BQvb9-g</recordid><startdate>20180720</startdate><enddate>20180720</enddate><creator>Kim, Byunghyun</creator><creator>Kim, Joonghee</creator><creator>Jo, You Hwan</creator><creator>Lee, Jae Hyuk</creator><creator>Hwang, Ji Eun</creator><creator>Park, Min Ji</creator><creator>Lee, Sihyung</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/0000-0001-5080-7097</orcidid></search><sort><creationdate>20180720</creationdate><title>Prognostic value of pneumococcal urinary antigen test in community-acquired pneumonia</title><author>Kim, Byunghyun ; Kim, Joonghee ; Jo, You Hwan ; Lee, Jae Hyuk ; Hwang, Ji Eun ; Park, Min Ji ; Lee, Sihyung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-4a222c479b48c76323d3110dc6a9a81550dade21a16133109270586e2a2165343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Antibiotics</topic><topic>Antigens</topic><topic>Antigens, Bacterial - urine</topic><topic>Biology and Life Sciences</topic><topic>Communities</topic><topic>Community-Acquired Infections - diagnosis</topic><topic>Community-Acquired Infections - microbiology</topic><topic>Community-Acquired Infections - mortality</topic><topic>Community-Acquired Infections - urine</topic><topic>Diagnosis</topic><topic>Emergency medical care</topic><topic>Female</topic><topic>Gram-negative bacteria</topic><topic>Health aspects</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Patients</topic><topic>Pneumococcal pneumonia</topic><topic>Pneumonia</topic><topic>Pneumonia, Pneumococcal - diagnosis</topic><topic>Pneumonia, Pneumococcal - microbiology</topic><topic>Pneumonia, Pneumococcal - mortality</topic><topic>Pneumonia, Pneumococcal - urine</topic><topic>Predictive Value of Tests</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Regression analysis</topic><topic>Republic of Korea - epidemiology</topic><topic>Retrospective Studies</topic><topic>ROC Curve</topic><topic>Streptococcus infections</topic><topic>Streptococcus pneumoniae - immunology</topic><topic>Streptococcus pneumoniae - isolation & purification</topic><topic>Studies</topic><topic>Survival Rate</topic><topic>Urinalysis</topic><topic>Urine</topic><topic>Variables</topic><topic>Ventilators</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Byunghyun</creatorcontrib><creatorcontrib>Kim, Joonghee</creatorcontrib><creatorcontrib>Jo, You Hwan</creatorcontrib><creatorcontrib>Lee, Jae Hyuk</creatorcontrib><creatorcontrib>Hwang, Ji Eun</creatorcontrib><creatorcontrib>Park, Min Ji</creatorcontrib><creatorcontrib>Lee, Sihyung</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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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>Kim, Byunghyun</au><au>Kim, Joonghee</au><au>Jo, You Hwan</au><au>Lee, Jae Hyuk</au><au>Hwang, Ji Eun</au><au>Park, Min Ji</au><au>Lee, Sihyung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic value of pneumococcal urinary antigen test in community-acquired pneumonia</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-07-20</date><risdate>2018</risdate><volume>13</volume><issue>7</issue><spage>e0200620</spage><epage>e0200620</epage><pages>e0200620-e0200620</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The pneumococcal urinary antigen test (UAT) has been known to improve sensitivity and specificity for the diagnosis of pneumococcal pneumonia. Associations of UAT results with prognosis in community acquired pneumonia (CAP) are not known. We hypothesized that positive UAT is associated with a good prognosis, and incorporation of UAT into CRB65 would improve its prognostic performance.
In this registry-based retrospective study, we analyzed CAP patients over a 10-year period beginning in April 2008. Patients who had UAT results were included in multivariable extended Cox-regression analyses to determine the association between UAT positivity and 30-day mortality. UAT results were incorporated for patients with a CRB65 score of 1 by subtracting 1 from the scoring system if the test was positive. The performance of the modified scoring systems was assessed with area under the receiver operating characteristic (AUROC) curves.
Among 5145 CAP patients, total 2280 patients had UAT results and were included in analyses. A positive UAT result was associated with a good prognosis after a week of hospitalization (aHR, 0.14; p = 0.007). After modification of CRB65 using UAT results, positive and negative predictive values for 30-day mortality were increased from 7.7 to 8.3 (p<0.001) and 98.9 to 99.1 (p = 0.010). The AUROC increased from 0.73 to 0.75 (p<0.001).
Positive results on UAT could be considered as a good prognostic factor in CAP. UAT could be used as a useful tool in deciding whether to refer patients to the hospital, especially in moderate CAP with a CRB score of 1.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30028834</pmid><doi>10.1371/journal.pone.0200620</doi><orcidid>https://orcid.org/0000-0001-5080-7097</orcidid><oa>free_for_read</oa></addata></record> |
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| issn | 1932-6203 1932-6203 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Aged Aged, 80 and over Analysis Antibiotics Antigens Antigens, Bacterial - urine Biology and Life Sciences Communities Community-Acquired Infections - diagnosis Community-Acquired Infections - microbiology Community-Acquired Infections - mortality Community-Acquired Infections - urine Diagnosis Emergency medical care Female Gram-negative bacteria Health aspects Hospitals Humans Infectious diseases Male Medical prognosis Medicine Medicine and Health Sciences Middle Aged Mortality Patients Pneumococcal pneumonia Pneumonia Pneumonia, Pneumococcal - diagnosis Pneumonia, Pneumococcal - microbiology Pneumonia, Pneumococcal - mortality Pneumonia, Pneumococcal - urine Predictive Value of Tests Prognosis Prospective Studies Regression analysis Republic of Korea - epidemiology Retrospective Studies ROC Curve Streptococcus infections Streptococcus pneumoniae - immunology Streptococcus pneumoniae - isolation & purification Studies Survival Rate Urinalysis Urine Variables Ventilators |
| title | Prognostic value of pneumococcal urinary antigen test in community-acquired pneumonia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T13%3A52%3A09IST&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=Prognostic%20value%20of%20pneumococcal%20urinary%20antigen%20test%20in%20community-acquired%20pneumonia&rft.jtitle=PloS%20one&rft.au=Kim,%20Byunghyun&rft.date=2018-07-20&rft.volume=13&rft.issue=7&rft.spage=e0200620&rft.epage=e0200620&rft.pages=e0200620-e0200620&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0200620&rft_dat=%3Cgale_plos_%3EA547110060%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=2072699779&rft_id=info:pmid/30028834&rft_galeid=A547110060&rft_doaj_id=oai_doaj_org_article_23ecd0b91aeb4402b99d5d75b5b9036a&rfr_iscdi=true |