The relationship between dioxins exposure and risk of prostate cancer with steroid hormone and age in Vietnamese men

Although Vietnam's massive herbicide exposure in 1960s and 1970s was clearly injurious to health, not all causal relationships have been clarified. We therefore explored associations among dioxins, steroid hormones, age and prostate cancer risk in men. We compared serum levels of dioxin, steroi...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The Science of the total environment 2017-10, Vol.595, p.842-848
Hauptverfasser: Sun, Xian Liang, Kido, Teruhiko, Honma, Seijiro, Koh, Eitetsu, Okamoto, Rie, Manh, Ho Dung, Maruzeni, Shoko, Nishijo, Muneko, Nakagawa, Hideaki, Nakano, Takeshi, Takasuga, Takumi, Nhu, Dang Duc, Hung, Nguyen Ngoc, Son, Le Ke
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 848
container_issue
container_start_page 842
container_title The Science of the total environment
container_volume 595
creator Sun, Xian Liang
Kido, Teruhiko
Honma, Seijiro
Koh, Eitetsu
Okamoto, Rie
Manh, Ho Dung
Maruzeni, Shoko
Nishijo, Muneko
Nakagawa, Hideaki
Nakano, Takeshi
Takasuga, Takumi
Nhu, Dang Duc
Hung, Nguyen Ngoc
Son, Le Ke
description Although Vietnam's massive herbicide exposure in 1960s and 1970s was clearly injurious to health, not all causal relationships have been clarified. We therefore explored associations among dioxins, steroid hormones, age and prostate cancer risk in men. We compared serum levels of dioxin, steroid hormones and prostate specific antigen (PSA) in men aged 56–81years from herbicide-exposed hotspots (n=50) with those from non-sprayed regions (n=48). Mean serum levels of dioxin congeners in the hotspot group were 1.5–11.3 times higher than the non-sprayed group depending on specific compound. Levels of testosterone, estradiol and 3β-hydroxysteroid dehydrogenase (3β-HSD) activity in the hotspot group were also significantly higher than in non-sprayed group. Estradiol levels were significantly related to levels of several specific dioxin derivatives in both group. Significant positive correlations were also found between DHT and 1234678-HpCDD or 1234678-HpCDF; and between 3β-HSD activity and 123678-HxCDD, 123478-HxCDF, 123678-HxCDF, or HxCB#169. After adjusting for age, body mass index, and tobacco use, multiple linear regressions showed levels of dihydrotestosterone (DHT), estradiol, testosterone and 3β-HSD activity were not associated with dioxins in the two groups; however, levels of DHT, testosterone and 3β-HSD activity increased significantly with age in the hotspot group. The hotspot and non-sprayed groups did not significantly differ in PSA levels. But six of the hotspot subjects had PSA levels >3ng/mL, 3 of whom were suspected to have prostate cancer (PC) after digital rectal examination. Our findings suggest that dioxin exposure can lead to increased levels of several sex steroid hormones with age. The correlation of dioxin with steroid hormone levels and prostate cancer risk should be studied further. [Display omitted] •In the hotspot group, sex hormone levels were significantly increased with age.•Mean 3β-HSD activity levels were higher in the hotspot than the non-sprayed group.•In the hotspot group, 3β-HSD activity levels were significantly increased with age.
doi_str_mv 10.1016/j.scitotenv.2017.04.013
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1888955875</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0048969717308409</els_id><sourcerecordid>1888955875</sourcerecordid><originalsourceid>FETCH-LOGICAL-c371t-15f590d787a1b618a4dfe8cf267577fc16e5d325928b9018459a267bef03bc383</originalsourceid><addsrcrecordid>eNqFkEFv2zAMhYWhw5J2-wudjrvYE23Lko9FsW4FAvTS7SrIEr0ojaVMUpru31dB2l7LCw98j-T7CPkKrAYG_fdNnYzLIaN_rBsGomZdzaD9QJYgxVABa_ozsmSsk9XQD2JBzlPasFJCwieyaGQHTc_bJcn3a6QRtzq74NPa7eiI-YDoqXXhyflE8WkX0j4i1d7S6NIDDRPdxZCyzkiN9gYjPbi8piljDM7SdYhz8CeD_ovUefrHYfZ6xoR0Rv-ZfJz0NuGXl35Bft_8uL_-Va3uft5eX60q0wrIFfCJD8wKKTSMPUjd2QmlmZpecCEmAz1y2zZ8aOQ4MJAdH3SZjTixdjStbC_It9Pe8u6_PaasZpcMbrfaY9gnBVLKgXMpeJGKk9SUZCnipHbRzTr-V8DUEbnaqDfk6ohcsU4V5MV5-XJkP85o33yvjIvg6iTAEvXRYTwuwoLNuogmKxvcu0eeAf_pmLA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1888955875</pqid></control><display><type>article</type><title>The relationship between dioxins exposure and risk of prostate cancer with steroid hormone and age in Vietnamese men</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Sun, Xian Liang ; Kido, Teruhiko ; Honma, Seijiro ; Koh, Eitetsu ; Okamoto, Rie ; Manh, Ho Dung ; Maruzeni, Shoko ; Nishijo, Muneko ; Nakagawa, Hideaki ; Nakano, Takeshi ; Takasuga, Takumi ; Nhu, Dang Duc ; Hung, Nguyen Ngoc ; Son, Le Ke</creator><creatorcontrib>Sun, Xian Liang ; Kido, Teruhiko ; Honma, Seijiro ; Koh, Eitetsu ; Okamoto, Rie ; Manh, Ho Dung ; Maruzeni, Shoko ; Nishijo, Muneko ; Nakagawa, Hideaki ; Nakano, Takeshi ; Takasuga, Takumi ; Nhu, Dang Duc ; Hung, Nguyen Ngoc ; Son, Le Ke</creatorcontrib><description>Although Vietnam's massive herbicide exposure in 1960s and 1970s was clearly injurious to health, not all causal relationships have been clarified. We therefore explored associations among dioxins, steroid hormones, age and prostate cancer risk in men. We compared serum levels of dioxin, steroid hormones and prostate specific antigen (PSA) in men aged 56–81years from herbicide-exposed hotspots (n=50) with those from non-sprayed regions (n=48). Mean serum levels of dioxin congeners in the hotspot group were 1.5–11.3 times higher than the non-sprayed group depending on specific compound. Levels of testosterone, estradiol and 3β-hydroxysteroid dehydrogenase (3β-HSD) activity in the hotspot group were also significantly higher than in non-sprayed group. Estradiol levels were significantly related to levels of several specific dioxin derivatives in both group. Significant positive correlations were also found between DHT and 1234678-HpCDD or 1234678-HpCDF; and between 3β-HSD activity and 123678-HxCDD, 123478-HxCDF, 123678-HxCDF, or HxCB#169. After adjusting for age, body mass index, and tobacco use, multiple linear regressions showed levels of dihydrotestosterone (DHT), estradiol, testosterone and 3β-HSD activity were not associated with dioxins in the two groups; however, levels of DHT, testosterone and 3β-HSD activity increased significantly with age in the hotspot group. The hotspot and non-sprayed groups did not significantly differ in PSA levels. But six of the hotspot subjects had PSA levels &gt;3ng/mL, 3 of whom were suspected to have prostate cancer (PC) after digital rectal examination. Our findings suggest that dioxin exposure can lead to increased levels of several sex steroid hormones with age. The correlation of dioxin with steroid hormone levels and prostate cancer risk should be studied further. [Display omitted] •In the hotspot group, sex hormone levels were significantly increased with age.•Mean 3β-HSD activity levels were higher in the hotspot than the non-sprayed group.•In the hotspot group, 3β-HSD activity levels were significantly increased with age.</description><identifier>ISSN: 0048-9697</identifier><identifier>EISSN: 1879-1026</identifier><identifier>DOI: 10.1016/j.scitotenv.2017.04.013</identifier><identifier>PMID: 28412653</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>3-Hydroxysteroid Dehydrogenases - blood ; 3β-Hydroxysteroid dehydrogenase activity ; Age Factors ; Aged ; Aged, 80 and over ; Dihydrotestosterone - blood ; Dioxins - toxicity ; Estradiol - blood ; Gonadal Steroid Hormones - blood ; Hotspot ; Humans ; Male ; Middle Aged ; Polychlorinated dibenzodioxins ; Polychlorinated dibenzofurans ; Prostatic Neoplasms - blood ; Prostatic Neoplasms - epidemiology ; Testosterone ; Testosterone - blood ; Vietnam</subject><ispartof>The Science of the total environment, 2017-10, Vol.595, p.842-848</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c371t-15f590d787a1b618a4dfe8cf267577fc16e5d325928b9018459a267bef03bc383</citedby><cites>FETCH-LOGICAL-c371t-15f590d787a1b618a4dfe8cf267577fc16e5d325928b9018459a267bef03bc383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.scitotenv.2017.04.013$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27928,27929,45999</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28412653$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Xian Liang</creatorcontrib><creatorcontrib>Kido, Teruhiko</creatorcontrib><creatorcontrib>Honma, Seijiro</creatorcontrib><creatorcontrib>Koh, Eitetsu</creatorcontrib><creatorcontrib>Okamoto, Rie</creatorcontrib><creatorcontrib>Manh, Ho Dung</creatorcontrib><creatorcontrib>Maruzeni, Shoko</creatorcontrib><creatorcontrib>Nishijo, Muneko</creatorcontrib><creatorcontrib>Nakagawa, Hideaki</creatorcontrib><creatorcontrib>Nakano, Takeshi</creatorcontrib><creatorcontrib>Takasuga, Takumi</creatorcontrib><creatorcontrib>Nhu, Dang Duc</creatorcontrib><creatorcontrib>Hung, Nguyen Ngoc</creatorcontrib><creatorcontrib>Son, Le Ke</creatorcontrib><title>The relationship between dioxins exposure and risk of prostate cancer with steroid hormone and age in Vietnamese men</title><title>The Science of the total environment</title><addtitle>Sci Total Environ</addtitle><description>Although Vietnam's massive herbicide exposure in 1960s and 1970s was clearly injurious to health, not all causal relationships have been clarified. We therefore explored associations among dioxins, steroid hormones, age and prostate cancer risk in men. We compared serum levels of dioxin, steroid hormones and prostate specific antigen (PSA) in men aged 56–81years from herbicide-exposed hotspots (n=50) with those from non-sprayed regions (n=48). Mean serum levels of dioxin congeners in the hotspot group were 1.5–11.3 times higher than the non-sprayed group depending on specific compound. Levels of testosterone, estradiol and 3β-hydroxysteroid dehydrogenase (3β-HSD) activity in the hotspot group were also significantly higher than in non-sprayed group. Estradiol levels were significantly related to levels of several specific dioxin derivatives in both group. Significant positive correlations were also found between DHT and 1234678-HpCDD or 1234678-HpCDF; and between 3β-HSD activity and 123678-HxCDD, 123478-HxCDF, 123678-HxCDF, or HxCB#169. After adjusting for age, body mass index, and tobacco use, multiple linear regressions showed levels of dihydrotestosterone (DHT), estradiol, testosterone and 3β-HSD activity were not associated with dioxins in the two groups; however, levels of DHT, testosterone and 3β-HSD activity increased significantly with age in the hotspot group. The hotspot and non-sprayed groups did not significantly differ in PSA levels. But six of the hotspot subjects had PSA levels &gt;3ng/mL, 3 of whom were suspected to have prostate cancer (PC) after digital rectal examination. Our findings suggest that dioxin exposure can lead to increased levels of several sex steroid hormones with age. The correlation of dioxin with steroid hormone levels and prostate cancer risk should be studied further. [Display omitted] •In the hotspot group, sex hormone levels were significantly increased with age.•Mean 3β-HSD activity levels were higher in the hotspot than the non-sprayed group.•In the hotspot group, 3β-HSD activity levels were significantly increased with age.</description><subject>3-Hydroxysteroid Dehydrogenases - blood</subject><subject>3β-Hydroxysteroid dehydrogenase activity</subject><subject>Age Factors</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Dihydrotestosterone - blood</subject><subject>Dioxins - toxicity</subject><subject>Estradiol - blood</subject><subject>Gonadal Steroid Hormones - blood</subject><subject>Hotspot</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Polychlorinated dibenzodioxins</subject><subject>Polychlorinated dibenzofurans</subject><subject>Prostatic Neoplasms - blood</subject><subject>Prostatic Neoplasms - epidemiology</subject><subject>Testosterone</subject><subject>Testosterone - blood</subject><subject>Vietnam</subject><issn>0048-9697</issn><issn>1879-1026</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEFv2zAMhYWhw5J2-wudjrvYE23Lko9FsW4FAvTS7SrIEr0ojaVMUpru31dB2l7LCw98j-T7CPkKrAYG_fdNnYzLIaN_rBsGomZdzaD9QJYgxVABa_ozsmSsk9XQD2JBzlPasFJCwieyaGQHTc_bJcn3a6QRtzq74NPa7eiI-YDoqXXhyflE8WkX0j4i1d7S6NIDDRPdxZCyzkiN9gYjPbi8piljDM7SdYhz8CeD_ovUefrHYfZ6xoR0Rv-ZfJz0NuGXl35Bft_8uL_-Va3uft5eX60q0wrIFfCJD8wKKTSMPUjd2QmlmZpecCEmAz1y2zZ8aOQ4MJAdH3SZjTixdjStbC_It9Pe8u6_PaasZpcMbrfaY9gnBVLKgXMpeJGKk9SUZCnipHbRzTr-V8DUEbnaqDfk6ohcsU4V5MV5-XJkP85o33yvjIvg6iTAEvXRYTwuwoLNuogmKxvcu0eeAf_pmLA</recordid><startdate>20171001</startdate><enddate>20171001</enddate><creator>Sun, Xian Liang</creator><creator>Kido, Teruhiko</creator><creator>Honma, Seijiro</creator><creator>Koh, Eitetsu</creator><creator>Okamoto, Rie</creator><creator>Manh, Ho Dung</creator><creator>Maruzeni, Shoko</creator><creator>Nishijo, Muneko</creator><creator>Nakagawa, Hideaki</creator><creator>Nakano, Takeshi</creator><creator>Takasuga, Takumi</creator><creator>Nhu, Dang Duc</creator><creator>Hung, Nguyen Ngoc</creator><creator>Son, Le Ke</creator><general>Elsevier 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>7X8</scope></search><sort><creationdate>20171001</creationdate><title>The relationship between dioxins exposure and risk of prostate cancer with steroid hormone and age in Vietnamese men</title><author>Sun, Xian Liang ; Kido, Teruhiko ; Honma, Seijiro ; Koh, Eitetsu ; Okamoto, Rie ; Manh, Ho Dung ; Maruzeni, Shoko ; Nishijo, Muneko ; Nakagawa, Hideaki ; Nakano, Takeshi ; Takasuga, Takumi ; Nhu, Dang Duc ; Hung, Nguyen Ngoc ; Son, Le Ke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-15f590d787a1b618a4dfe8cf267577fc16e5d325928b9018459a267bef03bc383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>3-Hydroxysteroid Dehydrogenases - blood</topic><topic>3β-Hydroxysteroid dehydrogenase activity</topic><topic>Age Factors</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Dihydrotestosterone - blood</topic><topic>Dioxins - toxicity</topic><topic>Estradiol - blood</topic><topic>Gonadal Steroid Hormones - blood</topic><topic>Hotspot</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Polychlorinated dibenzodioxins</topic><topic>Polychlorinated dibenzofurans</topic><topic>Prostatic Neoplasms - blood</topic><topic>Prostatic Neoplasms - epidemiology</topic><topic>Testosterone</topic><topic>Testosterone - blood</topic><topic>Vietnam</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Xian Liang</creatorcontrib><creatorcontrib>Kido, Teruhiko</creatorcontrib><creatorcontrib>Honma, Seijiro</creatorcontrib><creatorcontrib>Koh, Eitetsu</creatorcontrib><creatorcontrib>Okamoto, Rie</creatorcontrib><creatorcontrib>Manh, Ho Dung</creatorcontrib><creatorcontrib>Maruzeni, Shoko</creatorcontrib><creatorcontrib>Nishijo, Muneko</creatorcontrib><creatorcontrib>Nakagawa, Hideaki</creatorcontrib><creatorcontrib>Nakano, Takeshi</creatorcontrib><creatorcontrib>Takasuga, Takumi</creatorcontrib><creatorcontrib>Nhu, Dang Duc</creatorcontrib><creatorcontrib>Hung, Nguyen Ngoc</creatorcontrib><creatorcontrib>Son, Le Ke</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Science of the total environment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Xian Liang</au><au>Kido, Teruhiko</au><au>Honma, Seijiro</au><au>Koh, Eitetsu</au><au>Okamoto, Rie</au><au>Manh, Ho Dung</au><au>Maruzeni, Shoko</au><au>Nishijo, Muneko</au><au>Nakagawa, Hideaki</au><au>Nakano, Takeshi</au><au>Takasuga, Takumi</au><au>Nhu, Dang Duc</au><au>Hung, Nguyen Ngoc</au><au>Son, Le Ke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The relationship between dioxins exposure and risk of prostate cancer with steroid hormone and age in Vietnamese men</atitle><jtitle>The Science of the total environment</jtitle><addtitle>Sci Total Environ</addtitle><date>2017-10-01</date><risdate>2017</risdate><volume>595</volume><spage>842</spage><epage>848</epage><pages>842-848</pages><issn>0048-9697</issn><eissn>1879-1026</eissn><abstract>Although Vietnam's massive herbicide exposure in 1960s and 1970s was clearly injurious to health, not all causal relationships have been clarified. We therefore explored associations among dioxins, steroid hormones, age and prostate cancer risk in men. We compared serum levels of dioxin, steroid hormones and prostate specific antigen (PSA) in men aged 56–81years from herbicide-exposed hotspots (n=50) with those from non-sprayed regions (n=48). Mean serum levels of dioxin congeners in the hotspot group were 1.5–11.3 times higher than the non-sprayed group depending on specific compound. Levels of testosterone, estradiol and 3β-hydroxysteroid dehydrogenase (3β-HSD) activity in the hotspot group were also significantly higher than in non-sprayed group. Estradiol levels were significantly related to levels of several specific dioxin derivatives in both group. Significant positive correlations were also found between DHT and 1234678-HpCDD or 1234678-HpCDF; and between 3β-HSD activity and 123678-HxCDD, 123478-HxCDF, 123678-HxCDF, or HxCB#169. After adjusting for age, body mass index, and tobacco use, multiple linear regressions showed levels of dihydrotestosterone (DHT), estradiol, testosterone and 3β-HSD activity were not associated with dioxins in the two groups; however, levels of DHT, testosterone and 3β-HSD activity increased significantly with age in the hotspot group. The hotspot and non-sprayed groups did not significantly differ in PSA levels. But six of the hotspot subjects had PSA levels &gt;3ng/mL, 3 of whom were suspected to have prostate cancer (PC) after digital rectal examination. Our findings suggest that dioxin exposure can lead to increased levels of several sex steroid hormones with age. The correlation of dioxin with steroid hormone levels and prostate cancer risk should be studied further. [Display omitted] •In the hotspot group, sex hormone levels were significantly increased with age.•Mean 3β-HSD activity levels were higher in the hotspot than the non-sprayed group.•In the hotspot group, 3β-HSD activity levels were significantly increased with age.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28412653</pmid><doi>10.1016/j.scitotenv.2017.04.013</doi><tpages>7</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0048-9697
ispartof The Science of the total environment, 2017-10, Vol.595, p.842-848
issn 0048-9697
1879-1026
language eng
recordid cdi_proquest_miscellaneous_1888955875
source MEDLINE; Access via ScienceDirect (Elsevier)
subjects 3-Hydroxysteroid Dehydrogenases - blood
3β-Hydroxysteroid dehydrogenase activity
Age Factors
Aged
Aged, 80 and over
Dihydrotestosterone - blood
Dioxins - toxicity
Estradiol - blood
Gonadal Steroid Hormones - blood
Hotspot
Humans
Male
Middle Aged
Polychlorinated dibenzodioxins
Polychlorinated dibenzofurans
Prostatic Neoplasms - blood
Prostatic Neoplasms - epidemiology
Testosterone
Testosterone - blood
Vietnam
title The relationship between dioxins exposure and risk of prostate cancer with steroid hormone and age in Vietnamese men
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T09%3A49%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20relationship%20between%20dioxins%20exposure%20and%20risk%20of%20prostate%20cancer%20with%20steroid%20hormone%20and%20age%20in%20Vietnamese%20men&rft.jtitle=The%20Science%20of%20the%20total%20environment&rft.au=Sun,%20Xian%20Liang&rft.date=2017-10-01&rft.volume=595&rft.spage=842&rft.epage=848&rft.pages=842-848&rft.issn=0048-9697&rft.eissn=1879-1026&rft_id=info:doi/10.1016/j.scitotenv.2017.04.013&rft_dat=%3Cproquest_cross%3E1888955875%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1888955875&rft_id=info:pmid/28412653&rft_els_id=S0048969717308409&rfr_iscdi=true