Loading…

Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre-diabetes and type 2 diabetes mellitus

Aims The purpose of the current study was to investigate the characteristic expression of circular RNAs (circRNAs) in the peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potential as diagnostic biomarkers for pre-diabetes and T2DM. Methods CircRNAs in the peripheral blood from...

Full description

Saved in:
Bibliographic Details
Published in:Acta diabetologica 2017-03, Vol.54 (3), p.237-245
Main Authors: Zhao, Zhenzhou, Li, Xuejie, Jian, Dongdong, Hao, Peiyuan, Rao, Lixin, Li, Muwei
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-c503t-9885ac2709fc068cbd8baf88b39ba719b73170745df6d9da26e35442a746ae8e3
cites cdi_FETCH-LOGICAL-c503t-9885ac2709fc068cbd8baf88b39ba719b73170745df6d9da26e35442a746ae8e3
container_end_page 245
container_issue 3
container_start_page 237
container_title Acta diabetologica
container_volume 54
creator Zhao, Zhenzhou
Li, Xuejie
Jian, Dongdong
Hao, Peiyuan
Rao, Lixin
Li, Muwei
description Aims The purpose of the current study was to investigate the characteristic expression of circular RNAs (circRNAs) in the peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potential as diagnostic biomarkers for pre-diabetes and T2DM. Methods CircRNAs in the peripheral blood from six healthy individuals and six T2DM patients were collected for microarray analysis, and an independent cohort study consisting of 20 normal cases, 20 pre-diabetes patients and 20 T2DM patients was conducted to verify the five chosen circRNAs. We then tested hsa_circ_0054633 in a third cohort (control group, n  = 60; pre-diabetes group, n  = 63; and T2DM group, n  = 64) by quantitative real-time polymerase chain reaction (Q-PCR). Results In total, 489 circRNAs were discovered to be differentially expressed between the two groups, and of these, 78 were upregulated and 411 were downregulated in the T2DM group. Five circRNAs were then selected as candidate biomarkers and further verified in a second cohort. Hsa_circ_0054633 was found to have the largest area under the curve (AUC). The diagnostic capacity of hsa_circ_0054633 was tested in a third cohort. After introducing the risk factors of T2DM, the hsa_circ_0054633 AUCs for the diagnosis of pre-diabetes and T2DM slightly increased from 0.751 (95% confidence interval [0.666–0.835], P  
doi_str_mv 10.1007/s00592-016-0943-0
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5329094</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1843923193</sourcerecordid><originalsourceid>FETCH-LOGICAL-c503t-9885ac2709fc068cbd8baf88b39ba719b73170745df6d9da26e35442a746ae8e3</originalsourceid><addsrcrecordid>eNqNkk2LFDEQhoMo7jj6A7xIwMteWpNUupNcBFlWV1jwoueQpKtns8502qRb2X9vmlmHVRA8BaqeevPWByEvOXvDGVNvC2OtEQ3jXcOMhIY9IhsuQTStAHhMNjXImlYKc0aelXLLGBcK9FNyJpRWGjRsyM-r4myIOdiqJTsAGkc6YY7TDWa3p36fUk-DG6lHuhTsqSvU0T663ZjKHAP1MR1c_oaZpoFOGZua8zhjxcaezncTUkFPsQPu93FeynPyZHD7gi_u3y35-uHyy8VVc_3546eL99dNaBnMjdG6dUEoZobAOh18r70btPZgvFPceAVcMSXbfuh60zvRIbRSCqdk51AjbMm7o-60-AP2Ace5tmWnHKvpO5tctH9mxnhjd-mHbUGYdahbcn4vkNP3BctsD7GE2oUbMS3Fcq3qKLuu_R9UghHADVT09V_obVryWCexCkomhQZWKX6kQk6lZBxOvjmz6wXY4wXYegF2NWvXmlcPGz5V_F55BcQRKDU17jA_-Pqfqr8AmeW7Jg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1874042830</pqid></control><display><type>article</type><title>Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre-diabetes and type 2 diabetes mellitus</title><source>Springer Nature</source><creator>Zhao, Zhenzhou ; Li, Xuejie ; Jian, Dongdong ; Hao, Peiyuan ; Rao, Lixin ; Li, Muwei</creator><creatorcontrib>Zhao, Zhenzhou ; Li, Xuejie ; Jian, Dongdong ; Hao, Peiyuan ; Rao, Lixin ; Li, Muwei</creatorcontrib><description>Aims The purpose of the current study was to investigate the characteristic expression of circular RNAs (circRNAs) in the peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potential as diagnostic biomarkers for pre-diabetes and T2DM. Methods CircRNAs in the peripheral blood from six healthy individuals and six T2DM patients were collected for microarray analysis, and an independent cohort study consisting of 20 normal cases, 20 pre-diabetes patients and 20 T2DM patients was conducted to verify the five chosen circRNAs. We then tested hsa_circ_0054633 in a third cohort (control group, n  = 60; pre-diabetes group, n  = 63; and T2DM group, n  = 64) by quantitative real-time polymerase chain reaction (Q-PCR). Results In total, 489 circRNAs were discovered to be differentially expressed between the two groups, and of these, 78 were upregulated and 411 were downregulated in the T2DM group. Five circRNAs were then selected as candidate biomarkers and further verified in a second cohort. Hsa_circ_0054633 was found to have the largest area under the curve (AUC). The diagnostic capacity of hsa_circ_0054633 was tested in a third cohort. After introducing the risk factors of T2DM, the hsa_circ_0054633 AUCs for the diagnosis of pre-diabetes and T2DM slightly increased from 0.751 (95% confidence interval [0.666–0.835], P  &lt; 0.001) to 0.841 ([0.773–0.910], P  &lt; 0.001) and from 0.793 ([0.716–0.871], P  &lt; 0.001) to 0.834 ([0.762–0.905], P  &lt; 0.001), respectively. Conclusions Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.</description><identifier>ISSN: 0940-5429</identifier><identifier>EISSN: 1432-5233</identifier><identifier>DOI: 10.1007/s00592-016-0943-0</identifier><identifier>PMID: 27878383</identifier><identifier>CODEN: ACDAEZ</identifier><language>eng</language><publisher>Milan: Springer Milan</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biomarkers ; Biomarkers - blood ; Case-Control Studies ; Cohort Studies ; Diabetes ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - diagnosis ; Diabetes Mellitus, Type 2 - genetics ; Down-Regulation ; Female ; Humans ; Internal Medicine ; Male ; Medical diagnosis ; Medicine ; Medicine &amp; Public Health ; Metabolic Diseases ; Microarray Analysis ; Middle Aged ; Original ; Original Article ; Prediabetic State - blood ; Prediabetic State - diagnosis ; Prediabetic State - genetics ; Prognosis ; Ribonucleic acid ; RNA ; RNA - blood ; Sensitivity and Specificity</subject><ispartof>Acta diabetologica, 2017-03, Vol.54 (3), p.237-245</ispartof><rights>The Author(s) 2016</rights><rights>Acta Diabetologica is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-9885ac2709fc068cbd8baf88b39ba719b73170745df6d9da26e35442a746ae8e3</citedby><cites>FETCH-LOGICAL-c503t-9885ac2709fc068cbd8baf88b39ba719b73170745df6d9da26e35442a746ae8e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27878383$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Zhenzhou</creatorcontrib><creatorcontrib>Li, Xuejie</creatorcontrib><creatorcontrib>Jian, Dongdong</creatorcontrib><creatorcontrib>Hao, Peiyuan</creatorcontrib><creatorcontrib>Rao, Lixin</creatorcontrib><creatorcontrib>Li, Muwei</creatorcontrib><title>Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre-diabetes and type 2 diabetes mellitus</title><title>Acta diabetologica</title><addtitle>Acta Diabetol</addtitle><addtitle>Acta Diabetol</addtitle><description>Aims The purpose of the current study was to investigate the characteristic expression of circular RNAs (circRNAs) in the peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potential as diagnostic biomarkers for pre-diabetes and T2DM. Methods CircRNAs in the peripheral blood from six healthy individuals and six T2DM patients were collected for microarray analysis, and an independent cohort study consisting of 20 normal cases, 20 pre-diabetes patients and 20 T2DM patients was conducted to verify the five chosen circRNAs. We then tested hsa_circ_0054633 in a third cohort (control group, n  = 60; pre-diabetes group, n  = 63; and T2DM group, n  = 64) by quantitative real-time polymerase chain reaction (Q-PCR). Results In total, 489 circRNAs were discovered to be differentially expressed between the two groups, and of these, 78 were upregulated and 411 were downregulated in the T2DM group. Five circRNAs were then selected as candidate biomarkers and further verified in a second cohort. Hsa_circ_0054633 was found to have the largest area under the curve (AUC). The diagnostic capacity of hsa_circ_0054633 was tested in a third cohort. After introducing the risk factors of T2DM, the hsa_circ_0054633 AUCs for the diagnosis of pre-diabetes and T2DM slightly increased from 0.751 (95% confidence interval [0.666–0.835], P  &lt; 0.001) to 0.841 ([0.773–0.910], P  &lt; 0.001) and from 0.793 ([0.716–0.871], P  &lt; 0.001) to 0.834 ([0.762–0.905], P  &lt; 0.001), respectively. Conclusions Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Case-Control Studies</subject><subject>Cohort Studies</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - diagnosis</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Down-Regulation</subject><subject>Female</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medical diagnosis</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Metabolic Diseases</subject><subject>Microarray Analysis</subject><subject>Middle Aged</subject><subject>Original</subject><subject>Original Article</subject><subject>Prediabetic State - blood</subject><subject>Prediabetic State - diagnosis</subject><subject>Prediabetic State - genetics</subject><subject>Prognosis</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA - blood</subject><subject>Sensitivity and Specificity</subject><issn>0940-5429</issn><issn>1432-5233</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqNkk2LFDEQhoMo7jj6A7xIwMteWpNUupNcBFlWV1jwoueQpKtns8502qRb2X9vmlmHVRA8BaqeevPWByEvOXvDGVNvC2OtEQ3jXcOMhIY9IhsuQTStAHhMNjXImlYKc0aelXLLGBcK9FNyJpRWGjRsyM-r4myIOdiqJTsAGkc6YY7TDWa3p36fUk-DG6lHuhTsqSvU0T663ZjKHAP1MR1c_oaZpoFOGZua8zhjxcaezncTUkFPsQPu93FeynPyZHD7gi_u3y35-uHyy8VVc_3546eL99dNaBnMjdG6dUEoZobAOh18r70btPZgvFPceAVcMSXbfuh60zvRIbRSCqdk51AjbMm7o-60-AP2Ace5tmWnHKvpO5tctH9mxnhjd-mHbUGYdahbcn4vkNP3BctsD7GE2oUbMS3Fcq3qKLuu_R9UghHADVT09V_obVryWCexCkomhQZWKX6kQk6lZBxOvjmz6wXY4wXYegF2NWvXmlcPGz5V_F55BcQRKDU17jA_-Pqfqr8AmeW7Jg</recordid><startdate>20170301</startdate><enddate>20170301</enddate><creator>Zhao, Zhenzhou</creator><creator>Li, Xuejie</creator><creator>Jian, Dongdong</creator><creator>Hao, Peiyuan</creator><creator>Rao, Lixin</creator><creator>Li, Muwei</creator><general>Springer Milan</general><general>Springer Nature B.V</general><scope>C6C</scope><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>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170301</creationdate><title>Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre-diabetes and type 2 diabetes mellitus</title><author>Zhao, Zhenzhou ; Li, Xuejie ; Jian, Dongdong ; Hao, Peiyuan ; Rao, Lixin ; Li, Muwei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c503t-9885ac2709fc068cbd8baf88b39ba719b73170745df6d9da26e35442a746ae8e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Case-Control Studies</topic><topic>Cohort Studies</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes Mellitus, Type 2 - diagnosis</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Down-Regulation</topic><topic>Female</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medical diagnosis</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Metabolic Diseases</topic><topic>Microarray Analysis</topic><topic>Middle Aged</topic><topic>Original</topic><topic>Original Article</topic><topic>Prediabetic State - blood</topic><topic>Prediabetic State - diagnosis</topic><topic>Prediabetic State - genetics</topic><topic>Prognosis</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA - blood</topic><topic>Sensitivity and Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Zhenzhou</creatorcontrib><creatorcontrib>Li, Xuejie</creatorcontrib><creatorcontrib>Jian, Dongdong</creatorcontrib><creatorcontrib>Hao, Peiyuan</creatorcontrib><creatorcontrib>Rao, Lixin</creatorcontrib><creatorcontrib>Li, Muwei</creatorcontrib><collection>SpringerOpen</collection><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</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</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>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest research library</collection><collection>Research Library (Corporate)</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Acta diabetologica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Zhenzhou</au><au>Li, Xuejie</au><au>Jian, Dongdong</au><au>Hao, Peiyuan</au><au>Rao, Lixin</au><au>Li, Muwei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre-diabetes and type 2 diabetes mellitus</atitle><jtitle>Acta diabetologica</jtitle><stitle>Acta Diabetol</stitle><addtitle>Acta Diabetol</addtitle><date>2017-03-01</date><risdate>2017</risdate><volume>54</volume><issue>3</issue><spage>237</spage><epage>245</epage><pages>237-245</pages><issn>0940-5429</issn><eissn>1432-5233</eissn><coden>ACDAEZ</coden><abstract>Aims The purpose of the current study was to investigate the characteristic expression of circular RNAs (circRNAs) in the peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potential as diagnostic biomarkers for pre-diabetes and T2DM. Methods CircRNAs in the peripheral blood from six healthy individuals and six T2DM patients were collected for microarray analysis, and an independent cohort study consisting of 20 normal cases, 20 pre-diabetes patients and 20 T2DM patients was conducted to verify the five chosen circRNAs. We then tested hsa_circ_0054633 in a third cohort (control group, n  = 60; pre-diabetes group, n  = 63; and T2DM group, n  = 64) by quantitative real-time polymerase chain reaction (Q-PCR). Results In total, 489 circRNAs were discovered to be differentially expressed between the two groups, and of these, 78 were upregulated and 411 were downregulated in the T2DM group. Five circRNAs were then selected as candidate biomarkers and further verified in a second cohort. Hsa_circ_0054633 was found to have the largest area under the curve (AUC). The diagnostic capacity of hsa_circ_0054633 was tested in a third cohort. After introducing the risk factors of T2DM, the hsa_circ_0054633 AUCs for the diagnosis of pre-diabetes and T2DM slightly increased from 0.751 (95% confidence interval [0.666–0.835], P  &lt; 0.001) to 0.841 ([0.773–0.910], P  &lt; 0.001) and from 0.793 ([0.716–0.871], P  &lt; 0.001) to 0.834 ([0.762–0.905], P  &lt; 0.001), respectively. Conclusions Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.</abstract><cop>Milan</cop><pub>Springer Milan</pub><pmid>27878383</pmid><doi>10.1007/s00592-016-0943-0</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0940-5429
ispartof Acta diabetologica, 2017-03, Vol.54 (3), p.237-245
issn 0940-5429
1432-5233
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5329094
source Springer Nature
subjects Adult
Aged
Aged, 80 and over
Biomarkers
Biomarkers - blood
Case-Control Studies
Cohort Studies
Diabetes
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - diagnosis
Diabetes Mellitus, Type 2 - genetics
Down-Regulation
Female
Humans
Internal Medicine
Male
Medical diagnosis
Medicine
Medicine & Public Health
Metabolic Diseases
Microarray Analysis
Middle Aged
Original
Original Article
Prediabetic State - blood
Prediabetic State - diagnosis
Prediabetic State - genetics
Prognosis
Ribonucleic acid
RNA
RNA - blood
Sensitivity and Specificity
title Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre-diabetes and type 2 diabetes mellitus
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T09%3A56%3A52IST&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=Hsa_circ_0054633%20in%20peripheral%20blood%20can%20be%20used%20as%20a%20diagnostic%20biomarker%20of%20pre-diabetes%20and%20type%202%20diabetes%20mellitus&rft.jtitle=Acta%20diabetologica&rft.au=Zhao,%20Zhenzhou&rft.date=2017-03-01&rft.volume=54&rft.issue=3&rft.spage=237&rft.epage=245&rft.pages=237-245&rft.issn=0940-5429&rft.eissn=1432-5233&rft.coden=ACDAEZ&rft_id=info:doi/10.1007/s00592-016-0943-0&rft_dat=%3Cproquest_pubme%3E1843923193%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c503t-9885ac2709fc068cbd8baf88b39ba719b73170745df6d9da26e35442a746ae8e3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1874042830&rft_id=info:pmid/27878383&rfr_iscdi=true