Loading…

Immunoglobulin G4 (IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection

Interactions between pancreatic cancer cells and inflammatory cells play crucial roles in the biological behavior of pancreatic cancer. Abundant infiltration of immunoglobulin G4 (IgG4)-positive plasma cells in the pancreas is the most significant feature of autoimmune pancreatitis; however, the cli...

Full description

Saved in:
Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2016-08, Vol.65 (8), p.931-940
Main Authors: Liu, Qiaofei, Niu, Zheyu, Li, Yuan, Wang, Mengyi, Pan, Boju, Lu, Zhaohui, Liao, Quan, Zhao, Yupei
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-c461t-1ee86391c7ca725c44807af635f640237b7eadc5d01e649590c7f599c356c4333
cites cdi_FETCH-LOGICAL-c461t-1ee86391c7ca725c44807af635f640237b7eadc5d01e649590c7f599c356c4333
container_end_page 940
container_issue 8
container_start_page 931
container_title Cancer Immunology, Immunotherapy
container_volume 65
creator Liu, Qiaofei
Niu, Zheyu
Li, Yuan
Wang, Mengyi
Pan, Boju
Lu, Zhaohui
Liao, Quan
Zhao, Yupei
description Interactions between pancreatic cancer cells and inflammatory cells play crucial roles in the biological behavior of pancreatic cancer. Abundant infiltration of immunoglobulin G4 (IgG4)-positive plasma cells in the pancreas is the most significant feature of autoimmune pancreatitis; however, the clinical significance of IgG4-positive plasma cell infiltration in pancreatic cancer has not previously been reported. Herein, we analyzed intratumoral and peritumoral infiltrations of IgG4-positive plasma cells in 95 pancreatic cancer cases after curative resection. The correlations between IgG4-positive plasma cell infiltration and the clinicopathologic traits and overall survival of pancreatic cancer were investigated. IgG4-positive plasma cells were found in 86 % of tumor tissue samples compared with 69 % of peritumoral tissue samples ( P  = 0.0063). The high-level infiltration of intratumoral IgG4-positive plasma cells was positively correlated with poor histological grade ( P  = 0.017). The high-level infiltration of intratumoral IgG4-positive plasma cells was significantly correlated with worse prognosis ( P  = 0.01) in multivariate analysis. We further found that intratumoral M2-polarized tumor-associated macrophages (TAMs) were positively, linearly correlated with IgG4-positive plasma cells. In conclusion, IgG4-positive plasma cell infiltration is correlated with the clinicopathologic traits and overall survival of pancreatic cancer. High-level intratumoral infiltration of IgG4-positive plasma cells is an independent predictor for poor overall survival in pancreatic cancer patients after curative resection. Intratumoral M2-polarized TAMs probably induce IgG4-positive plasma cells.
doi_str_mv 10.1007/s00262-016-1853-2
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11028508</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1811899197</sourcerecordid><originalsourceid>FETCH-LOGICAL-c461t-1ee86391c7ca725c44807af635f640237b7eadc5d01e649590c7f599c356c4333</originalsourceid><addsrcrecordid>eNqNksuKFDEUhgtRnHb0AdxIwM24KM09lZXIoG3DgBtdh3Q6VZ2hKimT1Igv5HN6yh6HURDcJCHnP9-58DfNc4JfE4zVm4IxlbTFRLakE6ylD5oN4Qx-OkEeNhvMOG4VxvyseVLKNTwo1vpxc0YVVUQIsml-7KZpiWkY034ZQ0Rbji52w5a_audUQg03Hs2jLZNFzo8jCrEPY822hhRRKMiWklyw1R_Qt1CPqB49csAJLs22HtOYhuAQJIQK4nhAc05DBHJBqUezjS57gDnk4Okzsn2F0y1rBSidffFurfW0edTbsfhnt_d58-XD-8-XH9urT9vd5bur1nFJaku87yTTxClnFRWO8w4r20smeskxZWqvvD04ccDES66Fxk71QmvHhHScMXbevD1x52U_-YPzEXofzZzDZPN3k2wwf0ZiOJoh3RhCMO0E7oBwcUvI6eviSzVTKOvubPRpKYZ0hHRaE63-Q4olh660BOnLv6TXackRVvELSBiHCUBFTiqXUynZ93eNE2xWx5iTYww4xqyOMRRyXtyf-C7jt0VAQE-CAqE4-Hyv9D-pPwEHNM6U</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1811134356</pqid></control><display><type>article</type><title>Immunoglobulin G4 (IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection</title><source>Springer Nature</source><source>PubMed Central</source><creator>Liu, Qiaofei ; Niu, Zheyu ; Li, Yuan ; Wang, Mengyi ; Pan, Boju ; Lu, Zhaohui ; Liao, Quan ; Zhao, Yupei</creator><creatorcontrib>Liu, Qiaofei ; Niu, Zheyu ; Li, Yuan ; Wang, Mengyi ; Pan, Boju ; Lu, Zhaohui ; Liao, Quan ; Zhao, Yupei</creatorcontrib><description>Interactions between pancreatic cancer cells and inflammatory cells play crucial roles in the biological behavior of pancreatic cancer. Abundant infiltration of immunoglobulin G4 (IgG4)-positive plasma cells in the pancreas is the most significant feature of autoimmune pancreatitis; however, the clinical significance of IgG4-positive plasma cell infiltration in pancreatic cancer has not previously been reported. Herein, we analyzed intratumoral and peritumoral infiltrations of IgG4-positive plasma cells in 95 pancreatic cancer cases after curative resection. The correlations between IgG4-positive plasma cell infiltration and the clinicopathologic traits and overall survival of pancreatic cancer were investigated. IgG4-positive plasma cells were found in 86 % of tumor tissue samples compared with 69 % of peritumoral tissue samples ( P  = 0.0063). The high-level infiltration of intratumoral IgG4-positive plasma cells was positively correlated with poor histological grade ( P  = 0.017). The high-level infiltration of intratumoral IgG4-positive plasma cells was significantly correlated with worse prognosis ( P  = 0.01) in multivariate analysis. We further found that intratumoral M2-polarized tumor-associated macrophages (TAMs) were positively, linearly correlated with IgG4-positive plasma cells. In conclusion, IgG4-positive plasma cell infiltration is correlated with the clinicopathologic traits and overall survival of pancreatic cancer. High-level intratumoral infiltration of IgG4-positive plasma cells is an independent predictor for poor overall survival in pancreatic cancer patients after curative resection. Intratumoral M2-polarized TAMs probably induce IgG4-positive plasma cells.</description><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-016-1853-2</identifier><identifier>PMID: 27271551</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Aged ; Cancer Research ; Female ; Humans ; Immunoglobulin G - immunology ; Immunology ; Macrophages - immunology ; Male ; Medicine ; Medicine &amp; Public Health ; Oncology ; Original ; Original Article ; Pancreatic cancer ; Pancreatic Neoplasms - immunology ; Pancreatic Neoplasms - pathology ; Pancreatic Neoplasms - surgery ; Prognosis ; Survival Rate</subject><ispartof>Cancer Immunology, Immunotherapy, 2016-08, Vol.65 (8), p.931-940</ispartof><rights>Springer-Verlag Berlin Heidelberg 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c461t-1ee86391c7ca725c44807af635f640237b7eadc5d01e649590c7f599c356c4333</citedby><cites>FETCH-LOGICAL-c461t-1ee86391c7ca725c44807af635f640237b7eadc5d01e649590c7f599c356c4333</cites><orcidid>0000-0001-7148-2850</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/PMC11028508/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11028508/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27271551$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Qiaofei</creatorcontrib><creatorcontrib>Niu, Zheyu</creatorcontrib><creatorcontrib>Li, Yuan</creatorcontrib><creatorcontrib>Wang, Mengyi</creatorcontrib><creatorcontrib>Pan, Boju</creatorcontrib><creatorcontrib>Lu, Zhaohui</creatorcontrib><creatorcontrib>Liao, Quan</creatorcontrib><creatorcontrib>Zhao, Yupei</creatorcontrib><title>Immunoglobulin G4 (IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection</title><title>Cancer Immunology, Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Interactions between pancreatic cancer cells and inflammatory cells play crucial roles in the biological behavior of pancreatic cancer. Abundant infiltration of immunoglobulin G4 (IgG4)-positive plasma cells in the pancreas is the most significant feature of autoimmune pancreatitis; however, the clinical significance of IgG4-positive plasma cell infiltration in pancreatic cancer has not previously been reported. Herein, we analyzed intratumoral and peritumoral infiltrations of IgG4-positive plasma cells in 95 pancreatic cancer cases after curative resection. The correlations between IgG4-positive plasma cell infiltration and the clinicopathologic traits and overall survival of pancreatic cancer were investigated. IgG4-positive plasma cells were found in 86 % of tumor tissue samples compared with 69 % of peritumoral tissue samples ( P  = 0.0063). The high-level infiltration of intratumoral IgG4-positive plasma cells was positively correlated with poor histological grade ( P  = 0.017). The high-level infiltration of intratumoral IgG4-positive plasma cells was significantly correlated with worse prognosis ( P  = 0.01) in multivariate analysis. We further found that intratumoral M2-polarized tumor-associated macrophages (TAMs) were positively, linearly correlated with IgG4-positive plasma cells. In conclusion, IgG4-positive plasma cell infiltration is correlated with the clinicopathologic traits and overall survival of pancreatic cancer. High-level intratumoral infiltration of IgG4-positive plasma cells is an independent predictor for poor overall survival in pancreatic cancer patients after curative resection. Intratumoral M2-polarized TAMs probably induce IgG4-positive plasma cells.</description><subject>Aged</subject><subject>Cancer Research</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunology</subject><subject>Macrophages - immunology</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - immunology</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Pancreatic Neoplasms - surgery</subject><subject>Prognosis</subject><subject>Survival Rate</subject><issn>0340-7004</issn><issn>1432-0851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNqNksuKFDEUhgtRnHb0AdxIwM24KM09lZXIoG3DgBtdh3Q6VZ2hKimT1Igv5HN6yh6HURDcJCHnP9-58DfNc4JfE4zVm4IxlbTFRLakE6ylD5oN4Qx-OkEeNhvMOG4VxvyseVLKNTwo1vpxc0YVVUQIsml-7KZpiWkY034ZQ0Rbji52w5a_audUQg03Hs2jLZNFzo8jCrEPY822hhRRKMiWklyw1R_Qt1CPqB49csAJLs22HtOYhuAQJIQK4nhAc05DBHJBqUezjS57gDnk4Okzsn2F0y1rBSidffFurfW0edTbsfhnt_d58-XD-8-XH9urT9vd5bur1nFJaku87yTTxClnFRWO8w4r20smeskxZWqvvD04ccDES66Fxk71QmvHhHScMXbevD1x52U_-YPzEXofzZzDZPN3k2wwf0ZiOJoh3RhCMO0E7oBwcUvI6eviSzVTKOvubPRpKYZ0hHRaE63-Q4olh660BOnLv6TXackRVvELSBiHCUBFTiqXUynZ93eNE2xWx5iTYww4xqyOMRRyXtyf-C7jt0VAQE-CAqE4-Hyv9D-pPwEHNM6U</recordid><startdate>20160801</startdate><enddate>20160801</enddate><creator>Liu, Qiaofei</creator><creator>Niu, Zheyu</creator><creator>Li, Yuan</creator><creator>Wang, Mengyi</creator><creator>Pan, Boju</creator><creator>Lu, Zhaohui</creator><creator>Liao, Quan</creator><creator>Zhao, Yupei</creator><general>Springer Berlin Heidelberg</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7148-2850</orcidid></search><sort><creationdate>20160801</creationdate><title>Immunoglobulin G4 (IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection</title><author>Liu, Qiaofei ; Niu, Zheyu ; Li, Yuan ; Wang, Mengyi ; Pan, Boju ; Lu, Zhaohui ; Liao, Quan ; Zhao, Yupei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c461t-1ee86391c7ca725c44807af635f640237b7eadc5d01e649590c7f599c356c4333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aged</topic><topic>Cancer Research</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoglobulin G - immunology</topic><topic>Immunology</topic><topic>Macrophages - immunology</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - immunology</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Pancreatic Neoplasms - surgery</topic><topic>Prognosis</topic><topic>Survival Rate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Qiaofei</creatorcontrib><creatorcontrib>Niu, Zheyu</creatorcontrib><creatorcontrib>Li, Yuan</creatorcontrib><creatorcontrib>Wang, Mengyi</creatorcontrib><creatorcontrib>Pan, Boju</creatorcontrib><creatorcontrib>Lu, Zhaohui</creatorcontrib><creatorcontrib>Liao, Quan</creatorcontrib><creatorcontrib>Zhao, Yupei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health &amp; Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</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 (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science 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>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer Immunology, Immunotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Qiaofei</au><au>Niu, Zheyu</au><au>Li, Yuan</au><au>Wang, Mengyi</au><au>Pan, Boju</au><au>Lu, Zhaohui</au><au>Liao, Quan</au><au>Zhao, Yupei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunoglobulin G4 (IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection</atitle><jtitle>Cancer Immunology, Immunotherapy</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2016-08-01</date><risdate>2016</risdate><volume>65</volume><issue>8</issue><spage>931</spage><epage>940</epage><pages>931-940</pages><issn>0340-7004</issn><eissn>1432-0851</eissn><abstract>Interactions between pancreatic cancer cells and inflammatory cells play crucial roles in the biological behavior of pancreatic cancer. Abundant infiltration of immunoglobulin G4 (IgG4)-positive plasma cells in the pancreas is the most significant feature of autoimmune pancreatitis; however, the clinical significance of IgG4-positive plasma cell infiltration in pancreatic cancer has not previously been reported. Herein, we analyzed intratumoral and peritumoral infiltrations of IgG4-positive plasma cells in 95 pancreatic cancer cases after curative resection. The correlations between IgG4-positive plasma cell infiltration and the clinicopathologic traits and overall survival of pancreatic cancer were investigated. IgG4-positive plasma cells were found in 86 % of tumor tissue samples compared with 69 % of peritumoral tissue samples ( P  = 0.0063). The high-level infiltration of intratumoral IgG4-positive plasma cells was positively correlated with poor histological grade ( P  = 0.017). The high-level infiltration of intratumoral IgG4-positive plasma cells was significantly correlated with worse prognosis ( P  = 0.01) in multivariate analysis. We further found that intratumoral M2-polarized tumor-associated macrophages (TAMs) were positively, linearly correlated with IgG4-positive plasma cells. In conclusion, IgG4-positive plasma cell infiltration is correlated with the clinicopathologic traits and overall survival of pancreatic cancer. High-level intratumoral infiltration of IgG4-positive plasma cells is an independent predictor for poor overall survival in pancreatic cancer patients after curative resection. Intratumoral M2-polarized TAMs probably induce IgG4-positive plasma cells.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>27271551</pmid><doi>10.1007/s00262-016-1853-2</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-7148-2850</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0340-7004
ispartof Cancer Immunology, Immunotherapy, 2016-08, Vol.65 (8), p.931-940
issn 0340-7004
1432-0851
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11028508
source Springer Nature; PubMed Central
subjects Aged
Cancer Research
Female
Humans
Immunoglobulin G - immunology
Immunology
Macrophages - immunology
Male
Medicine
Medicine & Public Health
Oncology
Original
Original Article
Pancreatic cancer
Pancreatic Neoplasms - immunology
Pancreatic Neoplasms - pathology
Pancreatic Neoplasms - surgery
Prognosis
Survival Rate
title Immunoglobulin G4 (IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T17%3A33%3A05IST&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=Immunoglobulin%20G4%20(IgG4)-positive%20plasma%20cell%20infiltration%20is%20associated%20with%20the%20clinicopathologic%20traits%20and%20prognosis%20of%20pancreatic%20cancer%20after%20curative%20resection&rft.jtitle=Cancer%20Immunology,%20Immunotherapy&rft.au=Liu,%20Qiaofei&rft.date=2016-08-01&rft.volume=65&rft.issue=8&rft.spage=931&rft.epage=940&rft.pages=931-940&rft.issn=0340-7004&rft.eissn=1432-0851&rft_id=info:doi/10.1007/s00262-016-1853-2&rft_dat=%3Cproquest_pubme%3E1811899197%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c461t-1ee86391c7ca725c44807af635f640237b7eadc5d01e649590c7f599c356c4333%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1811134356&rft_id=info:pmid/27271551&rfr_iscdi=true