Whole-Genome Sequencing for National Surveillance of Shiga Toxin–Producing Escherichia coli O157
Background. National surveillance of gastrointestinal pathogens, such as Shiga toxin–producing Escherichia coli O157 (STEC O157), is key to rapidly identifying linked cases in the distributed food network to facilitate public health interventions. In this study, we used whole-genome sequencing (WGS)...
Gespeichert in:
Veröffentlicht in: | Clinical infectious diseases 2015-08, Vol.61 (3), p.305-312 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 312 |
---|---|
container_issue | 3 |
container_start_page | 305 |
container_title | Clinical infectious diseases |
container_volume | 61 |
creator | Dallman, Timothy J. Byrne, Lisa Ashton, Philip M. Cowley, Lauren A. Perry, Neil T. Adak, Goutam Petrovska, Liljana Ellis, Richard J. Elson, Richard Underwood, Anthony Green, Jonathan Hanage, William P. Jenkins, Claire Grant, Kathie Wain, John |
description | Background. National surveillance of gastrointestinal pathogens, such as Shiga toxin–producing Escherichia coli O157 (STEC O157), is key to rapidly identifying linked cases in the distributed food network to facilitate public health interventions. In this study, we used whole-genome sequencing (WGS) as a tool to inform national surveillance of STEC O157 in terms of identifying linked cases and clusters and guiding epidemiological investigation. Methods. We retrospectively analyzed 334 isolates randomly sampled from 1002 strains of STEC O157 received by the Gastrointestinal Bacteria Reference Unit at Public Health England, Colindale, in 2012. The genetic distance between each isolate, as estimated by WGS, was calculated and phylogenetic methods were used to place strains in an evolutionary context. Results. Estimates of linked clusters representing STEC O157 outbreaks in England and Wales increased by 2-fold when WGS was used instead of traditional typing techniques. The previously unidentified clusters were often widely geographically distributed and small in size. Phylogenetic analysis facilitated identification of temporally distinct cases sharing common exposures and delineating those that shared epidemiological and temporal links. Comparison with multi locus variable number tandem repeat analysis (MLVA) showed that although MLVA is as sensitive as WGS, WGS provides a more timely resolution to outbreak clustering. Conclusions. WGS has come of age as a molecular typing tool to inform national surveillance of STEC O157; it can be used in real time to provide the highest strain-level resolution for outbreak investigation. WGS allows linked cases to be identified with unprecedented specificity and sensitivity that will facilitate targeted and appropriate public health investigations. |
doi_str_mv | 10.1093/cid/civ318 |
format | Article |
fullrecord | <record><control><sourceid>jstor_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4542925</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>26367996</jstor_id><sourcerecordid>26367996</sourcerecordid><originalsourceid>FETCH-LOGICAL-c425t-c78cb7fc0eb6a7383e7ccb29a67e0434a31e8cdeadebaeb99b00c62428f02dbf3</originalsourceid><addsrcrecordid>eNqFkcuKFDEUhgtRnItu3CsBN4NQmvtlI8gwjsLgCD3iMiSpU11pqitjUtXoznfwDX0Sq61xvGxcHHLg__In5_xV9Yjg5wQb9iLEZq4dI_pOdUgEU7UUhtydeyx0zTXTB9VRKRuMCdFY3K8OqNBaS0UPK_-xSz3U5zCkLaAVfJpgCHFYozZl9M6NMQ2uR6sp7yD2vRsCoNSiVRfXDl2lz3H4_vXb-5ya6eelsxI6yDF00aGQ-oguiVAPqnut6ws8vDmPqw-vz65O39QXl-dvT19d1IFTMdZB6eBVGzB46RTTDFQInhonFWDOuGMEdGjANeAdeGM8xkFSTnWLaeNbdly9XHyvJ7-FJsAwZtfb6xy3Ln-xyUX7tzLEzq7TznLBqaFiNji5Mchp3kMZ7TaWAPuxIU3FEqWkFJwR8n9UGkWJ5ETO6NN_0E2a8rzVhVKGML5_-9lChZxKydDe_ptgu0_ZzinbJeUZfvLnpLfor1hn4PECbMqY8m9dMqmMkewHTs-vvw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1697791345</pqid></control><display><type>article</type><title>Whole-Genome Sequencing for National Surveillance of Shiga Toxin–Producing Escherichia coli O157</title><source>MEDLINE</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><source>JSTOR</source><creator>Dallman, Timothy J. ; Byrne, Lisa ; Ashton, Philip M. ; Cowley, Lauren A. ; Perry, Neil T. ; Adak, Goutam ; Petrovska, Liljana ; Ellis, Richard J. ; Elson, Richard ; Underwood, Anthony ; Green, Jonathan ; Hanage, William P. ; Jenkins, Claire ; Grant, Kathie ; Wain, John</creator><creatorcontrib>Dallman, Timothy J. ; Byrne, Lisa ; Ashton, Philip M. ; Cowley, Lauren A. ; Perry, Neil T. ; Adak, Goutam ; Petrovska, Liljana ; Ellis, Richard J. ; Elson, Richard ; Underwood, Anthony ; Green, Jonathan ; Hanage, William P. ; Jenkins, Claire ; Grant, Kathie ; Wain, John</creatorcontrib><description>Background. National surveillance of gastrointestinal pathogens, such as Shiga toxin–producing Escherichia coli O157 (STEC O157), is key to rapidly identifying linked cases in the distributed food network to facilitate public health interventions. In this study, we used whole-genome sequencing (WGS) as a tool to inform national surveillance of STEC O157 in terms of identifying linked cases and clusters and guiding epidemiological investigation. Methods. We retrospectively analyzed 334 isolates randomly sampled from 1002 strains of STEC O157 received by the Gastrointestinal Bacteria Reference Unit at Public Health England, Colindale, in 2012. The genetic distance between each isolate, as estimated by WGS, was calculated and phylogenetic methods were used to place strains in an evolutionary context. Results. Estimates of linked clusters representing STEC O157 outbreaks in England and Wales increased by 2-fold when WGS was used instead of traditional typing techniques. The previously unidentified clusters were often widely geographically distributed and small in size. Phylogenetic analysis facilitated identification of temporally distinct cases sharing common exposures and delineating those that shared epidemiological and temporal links. Comparison with multi locus variable number tandem repeat analysis (MLVA) showed that although MLVA is as sensitive as WGS, WGS provides a more timely resolution to outbreak clustering. Conclusions. WGS has come of age as a molecular typing tool to inform national surveillance of STEC O157; it can be used in real time to provide the highest strain-level resolution for outbreak investigation. WGS allows linked cases to be identified with unprecedented specificity and sensitivity that will facilitate targeted and appropriate public health investigations.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1093/cid/civ318</identifier><identifier>PMID: 25888672</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>and Commentaries ; ARTICLES AND COMMENTARIES ; Disease Outbreaks ; DNA, Bacterial - analysis ; DNA, Bacterial - genetics ; E coli ; Epidemiology ; Escherichia coli Infections - microbiology ; Genome, Bacterial - genetics ; Genomes ; Humans ; Phylogenetics ; Phylogeny ; Public health ; Public Health Surveillance ; Retrospective Studies ; Sequence Analysis, DNA ; Shiga-Toxigenic Escherichia coli - classification ; Shiga-Toxigenic Escherichia coli - genetics ; Toxins</subject><ispartof>Clinical infectious diseases, 2015-08, Vol.61 (3), p.305-312</ispartof><rights>Copyright © 2015 Oxford University Press on behalf of the Infectious Diseases Society of America</rights><rights>The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.</rights><rights>Copyright Oxford University Press, UK Aug 1, 2015</rights><rights>The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: . 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c425t-c78cb7fc0eb6a7383e7ccb29a67e0434a31e8cdeadebaeb99b00c62428f02dbf3</citedby><cites>FETCH-LOGICAL-c425t-c78cb7fc0eb6a7383e7ccb29a67e0434a31e8cdeadebaeb99b00c62428f02dbf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26367996$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26367996$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,780,784,803,885,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25888672$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dallman, Timothy J.</creatorcontrib><creatorcontrib>Byrne, Lisa</creatorcontrib><creatorcontrib>Ashton, Philip M.</creatorcontrib><creatorcontrib>Cowley, Lauren A.</creatorcontrib><creatorcontrib>Perry, Neil T.</creatorcontrib><creatorcontrib>Adak, Goutam</creatorcontrib><creatorcontrib>Petrovska, Liljana</creatorcontrib><creatorcontrib>Ellis, Richard J.</creatorcontrib><creatorcontrib>Elson, Richard</creatorcontrib><creatorcontrib>Underwood, Anthony</creatorcontrib><creatorcontrib>Green, Jonathan</creatorcontrib><creatorcontrib>Hanage, William P.</creatorcontrib><creatorcontrib>Jenkins, Claire</creatorcontrib><creatorcontrib>Grant, Kathie</creatorcontrib><creatorcontrib>Wain, John</creatorcontrib><title>Whole-Genome Sequencing for National Surveillance of Shiga Toxin–Producing Escherichia coli O157</title><title>Clinical infectious diseases</title><addtitle>Clin Infect Dis</addtitle><description>Background. National surveillance of gastrointestinal pathogens, such as Shiga toxin–producing Escherichia coli O157 (STEC O157), is key to rapidly identifying linked cases in the distributed food network to facilitate public health interventions. In this study, we used whole-genome sequencing (WGS) as a tool to inform national surveillance of STEC O157 in terms of identifying linked cases and clusters and guiding epidemiological investigation. Methods. We retrospectively analyzed 334 isolates randomly sampled from 1002 strains of STEC O157 received by the Gastrointestinal Bacteria Reference Unit at Public Health England, Colindale, in 2012. The genetic distance between each isolate, as estimated by WGS, was calculated and phylogenetic methods were used to place strains in an evolutionary context. Results. Estimates of linked clusters representing STEC O157 outbreaks in England and Wales increased by 2-fold when WGS was used instead of traditional typing techniques. The previously unidentified clusters were often widely geographically distributed and small in size. Phylogenetic analysis facilitated identification of temporally distinct cases sharing common exposures and delineating those that shared epidemiological and temporal links. Comparison with multi locus variable number tandem repeat analysis (MLVA) showed that although MLVA is as sensitive as WGS, WGS provides a more timely resolution to outbreak clustering. Conclusions. WGS has come of age as a molecular typing tool to inform national surveillance of STEC O157; it can be used in real time to provide the highest strain-level resolution for outbreak investigation. WGS allows linked cases to be identified with unprecedented specificity and sensitivity that will facilitate targeted and appropriate public health investigations.</description><subject>and Commentaries</subject><subject>ARTICLES AND COMMENTARIES</subject><subject>Disease Outbreaks</subject><subject>DNA, Bacterial - analysis</subject><subject>DNA, Bacterial - genetics</subject><subject>E coli</subject><subject>Epidemiology</subject><subject>Escherichia coli Infections - microbiology</subject><subject>Genome, Bacterial - genetics</subject><subject>Genomes</subject><subject>Humans</subject><subject>Phylogenetics</subject><subject>Phylogeny</subject><subject>Public health</subject><subject>Public Health Surveillance</subject><subject>Retrospective Studies</subject><subject>Sequence Analysis, DNA</subject><subject>Shiga-Toxigenic Escherichia coli - classification</subject><subject>Shiga-Toxigenic Escherichia coli - genetics</subject><subject>Toxins</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuKFDEUhgtRnItu3CsBN4NQmvtlI8gwjsLgCD3iMiSpU11pqitjUtXoznfwDX0Sq61xvGxcHHLg__In5_xV9Yjg5wQb9iLEZq4dI_pOdUgEU7UUhtydeyx0zTXTB9VRKRuMCdFY3K8OqNBaS0UPK_-xSz3U5zCkLaAVfJpgCHFYozZl9M6NMQ2uR6sp7yD2vRsCoNSiVRfXDl2lz3H4_vXb-5ya6eelsxI6yDF00aGQ-oguiVAPqnut6ws8vDmPqw-vz65O39QXl-dvT19d1IFTMdZB6eBVGzB46RTTDFQInhonFWDOuGMEdGjANeAdeGM8xkFSTnWLaeNbdly9XHyvJ7-FJsAwZtfb6xy3Ln-xyUX7tzLEzq7TznLBqaFiNji5Mchp3kMZ7TaWAPuxIU3FEqWkFJwR8n9UGkWJ5ETO6NN_0E2a8rzVhVKGML5_-9lChZxKydDe_ptgu0_ZzinbJeUZfvLnpLfor1hn4PECbMqY8m9dMqmMkewHTs-vvw</recordid><startdate>20150801</startdate><enddate>20150801</enddate><creator>Dallman, Timothy J.</creator><creator>Byrne, Lisa</creator><creator>Ashton, Philip M.</creator><creator>Cowley, Lauren A.</creator><creator>Perry, Neil T.</creator><creator>Adak, Goutam</creator><creator>Petrovska, Liljana</creator><creator>Ellis, Richard J.</creator><creator>Elson, Richard</creator><creator>Underwood, Anthony</creator><creator>Green, Jonathan</creator><creator>Hanage, William P.</creator><creator>Jenkins, Claire</creator><creator>Grant, Kathie</creator><creator>Wain, John</creator><general>Oxford University Press</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>7T2</scope><scope>7T7</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150801</creationdate><title>Whole-Genome Sequencing for National Surveillance of Shiga Toxin–Producing Escherichia coli O157</title><author>Dallman, Timothy J. ; Byrne, Lisa ; Ashton, Philip M. ; Cowley, Lauren A. ; Perry, Neil T. ; Adak, Goutam ; Petrovska, Liljana ; Ellis, Richard J. ; Elson, Richard ; Underwood, Anthony ; Green, Jonathan ; Hanage, William P. ; Jenkins, Claire ; Grant, Kathie ; Wain, John</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c425t-c78cb7fc0eb6a7383e7ccb29a67e0434a31e8cdeadebaeb99b00c62428f02dbf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>and Commentaries</topic><topic>ARTICLES AND COMMENTARIES</topic><topic>Disease Outbreaks</topic><topic>DNA, Bacterial - analysis</topic><topic>DNA, Bacterial - genetics</topic><topic>E coli</topic><topic>Epidemiology</topic><topic>Escherichia coli Infections - microbiology</topic><topic>Genome, Bacterial - genetics</topic><topic>Genomes</topic><topic>Humans</topic><topic>Phylogenetics</topic><topic>Phylogeny</topic><topic>Public health</topic><topic>Public Health Surveillance</topic><topic>Retrospective Studies</topic><topic>Sequence Analysis, DNA</topic><topic>Shiga-Toxigenic Escherichia coli - classification</topic><topic>Shiga-Toxigenic Escherichia coli - genetics</topic><topic>Toxins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dallman, Timothy J.</creatorcontrib><creatorcontrib>Byrne, Lisa</creatorcontrib><creatorcontrib>Ashton, Philip M.</creatorcontrib><creatorcontrib>Cowley, Lauren A.</creatorcontrib><creatorcontrib>Perry, Neil T.</creatorcontrib><creatorcontrib>Adak, Goutam</creatorcontrib><creatorcontrib>Petrovska, Liljana</creatorcontrib><creatorcontrib>Ellis, Richard J.</creatorcontrib><creatorcontrib>Elson, Richard</creatorcontrib><creatorcontrib>Underwood, Anthony</creatorcontrib><creatorcontrib>Green, Jonathan</creatorcontrib><creatorcontrib>Hanage, William P.</creatorcontrib><creatorcontrib>Jenkins, Claire</creatorcontrib><creatorcontrib>Grant, Kathie</creatorcontrib><creatorcontrib>Wain, John</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>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dallman, Timothy J.</au><au>Byrne, Lisa</au><au>Ashton, Philip M.</au><au>Cowley, Lauren A.</au><au>Perry, Neil T.</au><au>Adak, Goutam</au><au>Petrovska, Liljana</au><au>Ellis, Richard J.</au><au>Elson, Richard</au><au>Underwood, Anthony</au><au>Green, Jonathan</au><au>Hanage, William P.</au><au>Jenkins, Claire</au><au>Grant, Kathie</au><au>Wain, John</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Whole-Genome Sequencing for National Surveillance of Shiga Toxin–Producing Escherichia coli O157</atitle><jtitle>Clinical infectious diseases</jtitle><addtitle>Clin Infect Dis</addtitle><date>2015-08-01</date><risdate>2015</risdate><volume>61</volume><issue>3</issue><spage>305</spage><epage>312</epage><pages>305-312</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><abstract>Background. National surveillance of gastrointestinal pathogens, such as Shiga toxin–producing Escherichia coli O157 (STEC O157), is key to rapidly identifying linked cases in the distributed food network to facilitate public health interventions. In this study, we used whole-genome sequencing (WGS) as a tool to inform national surveillance of STEC O157 in terms of identifying linked cases and clusters and guiding epidemiological investigation. Methods. We retrospectively analyzed 334 isolates randomly sampled from 1002 strains of STEC O157 received by the Gastrointestinal Bacteria Reference Unit at Public Health England, Colindale, in 2012. The genetic distance between each isolate, as estimated by WGS, was calculated and phylogenetic methods were used to place strains in an evolutionary context. Results. Estimates of linked clusters representing STEC O157 outbreaks in England and Wales increased by 2-fold when WGS was used instead of traditional typing techniques. The previously unidentified clusters were often widely geographically distributed and small in size. Phylogenetic analysis facilitated identification of temporally distinct cases sharing common exposures and delineating those that shared epidemiological and temporal links. Comparison with multi locus variable number tandem repeat analysis (MLVA) showed that although MLVA is as sensitive as WGS, WGS provides a more timely resolution to outbreak clustering. Conclusions. WGS has come of age as a molecular typing tool to inform national surveillance of STEC O157; it can be used in real time to provide the highest strain-level resolution for outbreak investigation. WGS allows linked cases to be identified with unprecedented specificity and sensitivity that will facilitate targeted and appropriate public health investigations.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>25888672</pmid><doi>10.1093/cid/civ318</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1058-4838 |
ispartof | Clinical infectious diseases, 2015-08, Vol.61 (3), p.305-312 |
issn | 1058-4838 1537-6591 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4542925 |
source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; JSTOR |
subjects | and Commentaries ARTICLES AND COMMENTARIES Disease Outbreaks DNA, Bacterial - analysis DNA, Bacterial - genetics E coli Epidemiology Escherichia coli Infections - microbiology Genome, Bacterial - genetics Genomes Humans Phylogenetics Phylogeny Public health Public Health Surveillance Retrospective Studies Sequence Analysis, DNA Shiga-Toxigenic Escherichia coli - classification Shiga-Toxigenic Escherichia coli - genetics Toxins |
title | Whole-Genome Sequencing for National Surveillance of Shiga Toxin–Producing Escherichia coli O157 |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T13%3A50%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Whole-Genome%20Sequencing%20for%20National%20Surveillance%20of%20Shiga%20Toxin%E2%80%93Producing%20Escherichia%20coli%20O157&rft.jtitle=Clinical%20infectious%20diseases&rft.au=Dallman,%20Timothy%20J.&rft.date=2015-08-01&rft.volume=61&rft.issue=3&rft.spage=305&rft.epage=312&rft.pages=305-312&rft.issn=1058-4838&rft.eissn=1537-6591&rft_id=info:doi/10.1093/cid/civ318&rft_dat=%3Cjstor_pubme%3E26367996%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1697791345&rft_id=info:pmid/25888672&rft_jstor_id=26367996&rfr_iscdi=true |