Genomic predictive model for recurrence and metastasis development in head and neck squamous cell carcinoma patients
The head and neck squamous cell carcinoma (HNSCC) population consists mainly of high-risk for recurrence and locally advanced stage patients. Increased knowledge of the HNSCC genomic profile can improve early diagnosis and treatment outcomes. The development of models to identify consistent genomic...
Gespeichert in:
| Veröffentlicht in: | Scientific reports 2017-10, Vol.7 (1), p.13897-8, Article 13897 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 8 |
|---|---|
| container_issue | 1 |
| container_start_page | 13897 |
| container_title | Scientific reports |
| container_volume | 7 |
| creator | Ribeiro, Ilda Patrícia Caramelo, Francisco Esteves, Luísa Menoita, Joana Marques, Francisco Barroso, Leonor Miguéis, Jorge Melo, Joana Barbosa Carreira, Isabel Marques |
| description | The head and neck squamous cell carcinoma (HNSCC) population consists mainly of high-risk for recurrence and locally advanced stage patients. Increased knowledge of the HNSCC genomic profile can improve early diagnosis and treatment outcomes. The development of models to identify consistent genomic patterns that distinguish HNSCC patients that will recur and/or develop metastasis after treatment is of utmost importance to decrease mortality and improve survival rates. In this study, we used array comparative genomic hybridization data from HNSCC patients to implement a robust model to predict HNSCC recurrence/metastasis. This predictive model showed a good accuracy (>80%) and was validated in an independent population from TCGA data portal. This predictive genomic model comprises chromosomal regions from 5p, 6p, 8p, 9p, 11q, 12q, 15q and 17p, where several upstream and downstream members of signaling pathways that lead to an increase in cell proliferation and invasion are mapped. The introduction of genomic predictive models in clinical practice might contribute to a more individualized clinical management of the HNSCC patients, reducing recurrences and improving patients’ quality of life. The power of this genomic model to predict the recurrence and metastases development should be evaluated in other HNSCC populations. |
| doi_str_mv | 10.1038/s41598-017-14377-x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5654944</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1955027561</sourcerecordid><originalsourceid>FETCH-LOGICAL-c540t-175d28975e471d20d07a0a23a5d9469ce2a55da27b895704fa1640e989c55dc43</originalsourceid><addsrcrecordid>eNp1kUFrHSEUhaW0NCHNH-iiCN10M6k6Oo6bQglpGghkk67lRu9LTGd0ojOP5N_H914aXgsVQfF-91wPh5CPnJ1w1vZfi-TK9A3juuGy1bp5fEMOBZOqEa0Qb_fuB-S4lHtWlxJGcvOeHAjDuk6r_pDM5xjTGBydMvrg5rBGOiaPA12lTDO6JWeMDilET0ecodQdCvW4xiFNI8aZhkjvEPwWieh-0_KwwJiWQh0OA3WQXahDgE4wh9pQPpB3KxgKHr-cR-TXj7Pr05_N5dX5xen3y8YpyeaGa-VFb7RCqbkXzDMNDEQLyhvZGYcClPIg9E1vlGZyBbyTDE1vXH13sj0i33a603Izond1dobBTjmMkJ9sgmD_rsRwZ2_T2qpOSSM3Al9eBHJ6WLDMdgxlYwoiVn-WG6U6xky3QT__g96nJcdqb0sxoVXHKyV2lMuplIyr189wZje52l2utuZqt7nax9r0ad_Ga8ufFCvQ7oBSS_EW897s_8s-AzNOsG0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1955027561</pqid></control><display><type>article</type><title>Genomic predictive model for recurrence and metastasis development in head and neck squamous cell carcinoma patients</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Springer Nature OA Free Journals</source><source>Nature Free</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Ribeiro, Ilda Patrícia ; Caramelo, Francisco ; Esteves, Luísa ; Menoita, Joana ; Marques, Francisco ; Barroso, Leonor ; Miguéis, Jorge ; Melo, Joana Barbosa ; Carreira, Isabel Marques</creator><creatorcontrib>Ribeiro, Ilda Patrícia ; Caramelo, Francisco ; Esteves, Luísa ; Menoita, Joana ; Marques, Francisco ; Barroso, Leonor ; Miguéis, Jorge ; Melo, Joana Barbosa ; Carreira, Isabel Marques</creatorcontrib><description>The head and neck squamous cell carcinoma (HNSCC) population consists mainly of high-risk for recurrence and locally advanced stage patients. Increased knowledge of the HNSCC genomic profile can improve early diagnosis and treatment outcomes. The development of models to identify consistent genomic patterns that distinguish HNSCC patients that will recur and/or develop metastasis after treatment is of utmost importance to decrease mortality and improve survival rates. In this study, we used array comparative genomic hybridization data from HNSCC patients to implement a robust model to predict HNSCC recurrence/metastasis. This predictive model showed a good accuracy (>80%) and was validated in an independent population from TCGA data portal. This predictive genomic model comprises chromosomal regions from 5p, 6p, 8p, 9p, 11q, 12q, 15q and 17p, where several upstream and downstream members of signaling pathways that lead to an increase in cell proliferation and invasion are mapped. The introduction of genomic predictive models in clinical practice might contribute to a more individualized clinical management of the HNSCC patients, reducing recurrences and improving patients’ quality of life. The power of this genomic model to predict the recurrence and metastases development should be evaluated in other HNSCC populations.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-017-14377-x</identifier><identifier>PMID: 29066758</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45 ; 45/61 ; 692/4028/67/69 ; 692/53/2422 ; Adult ; Cell proliferation ; Chromosomes, Human - genetics ; Cohort Studies ; Comparative Genomic Hybridization ; Female ; Genomics ; Head & neck cancer ; Humanities and Social Sciences ; Humans ; Hybridization ; Male ; Metastases ; Metastasis ; Middle Aged ; Models, Statistical ; multidisciplinary ; Neoplasm Metastasis ; Prediction models ; Prognosis ; Quality of life ; Recurrence ; Science ; Science (multidisciplinary) ; Squamous cell carcinoma ; Squamous Cell Carcinoma of Head and Neck - diagnostic imaging ; Squamous Cell Carcinoma of Head and Neck - genetics ; Squamous Cell Carcinoma of Head and Neck - pathology ; Survival</subject><ispartof>Scientific reports, 2017-10, Vol.7 (1), p.13897-8, Article 13897</ispartof><rights>The Author(s) 2017</rights><rights>2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-175d28975e471d20d07a0a23a5d9469ce2a55da27b895704fa1640e989c55dc43</citedby><cites>FETCH-LOGICAL-c540t-175d28975e471d20d07a0a23a5d9469ce2a55da27b895704fa1640e989c55dc43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654944/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654944/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29066758$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ribeiro, Ilda Patrícia</creatorcontrib><creatorcontrib>Caramelo, Francisco</creatorcontrib><creatorcontrib>Esteves, Luísa</creatorcontrib><creatorcontrib>Menoita, Joana</creatorcontrib><creatorcontrib>Marques, Francisco</creatorcontrib><creatorcontrib>Barroso, Leonor</creatorcontrib><creatorcontrib>Miguéis, Jorge</creatorcontrib><creatorcontrib>Melo, Joana Barbosa</creatorcontrib><creatorcontrib>Carreira, Isabel Marques</creatorcontrib><title>Genomic predictive model for recurrence and metastasis development in head and neck squamous cell carcinoma patients</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The head and neck squamous cell carcinoma (HNSCC) population consists mainly of high-risk for recurrence and locally advanced stage patients. Increased knowledge of the HNSCC genomic profile can improve early diagnosis and treatment outcomes. The development of models to identify consistent genomic patterns that distinguish HNSCC patients that will recur and/or develop metastasis after treatment is of utmost importance to decrease mortality and improve survival rates. In this study, we used array comparative genomic hybridization data from HNSCC patients to implement a robust model to predict HNSCC recurrence/metastasis. This predictive model showed a good accuracy (>80%) and was validated in an independent population from TCGA data portal. This predictive genomic model comprises chromosomal regions from 5p, 6p, 8p, 9p, 11q, 12q, 15q and 17p, where several upstream and downstream members of signaling pathways that lead to an increase in cell proliferation and invasion are mapped. The introduction of genomic predictive models in clinical practice might contribute to a more individualized clinical management of the HNSCC patients, reducing recurrences and improving patients’ quality of life. The power of this genomic model to predict the recurrence and metastases development should be evaluated in other HNSCC populations.</description><subject>45</subject><subject>45/61</subject><subject>692/4028/67/69</subject><subject>692/53/2422</subject><subject>Adult</subject><subject>Cell proliferation</subject><subject>Chromosomes, Human - genetics</subject><subject>Cohort Studies</subject><subject>Comparative Genomic Hybridization</subject><subject>Female</subject><subject>Genomics</subject><subject>Head & neck cancer</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hybridization</subject><subject>Male</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Models, Statistical</subject><subject>multidisciplinary</subject><subject>Neoplasm Metastasis</subject><subject>Prediction models</subject><subject>Prognosis</subject><subject>Quality of life</subject><subject>Recurrence</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Squamous cell carcinoma</subject><subject>Squamous Cell Carcinoma of Head and Neck - diagnostic imaging</subject><subject>Squamous Cell Carcinoma of Head and Neck - genetics</subject><subject>Squamous Cell Carcinoma of Head and Neck - pathology</subject><subject>Survival</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kUFrHSEUhaW0NCHNH-iiCN10M6k6Oo6bQglpGghkk67lRu9LTGd0ojOP5N_H914aXgsVQfF-91wPh5CPnJ1w1vZfi-TK9A3juuGy1bp5fEMOBZOqEa0Qb_fuB-S4lHtWlxJGcvOeHAjDuk6r_pDM5xjTGBydMvrg5rBGOiaPA12lTDO6JWeMDilET0ecodQdCvW4xiFNI8aZhkjvEPwWieh-0_KwwJiWQh0OA3WQXahDgE4wh9pQPpB3KxgKHr-cR-TXj7Pr05_N5dX5xen3y8YpyeaGa-VFb7RCqbkXzDMNDEQLyhvZGYcClPIg9E1vlGZyBbyTDE1vXH13sj0i33a603Izond1dobBTjmMkJ9sgmD_rsRwZ2_T2qpOSSM3Al9eBHJ6WLDMdgxlYwoiVn-WG6U6xky3QT__g96nJcdqb0sxoVXHKyV2lMuplIyr189wZje52l2utuZqt7nax9r0ad_Ga8ufFCvQ7oBSS_EW897s_8s-AzNOsG0</recordid><startdate>20171024</startdate><enddate>20171024</enddate><creator>Ribeiro, Ilda Patrícia</creator><creator>Caramelo, Francisco</creator><creator>Esteves, Luísa</creator><creator>Menoita, Joana</creator><creator>Marques, Francisco</creator><creator>Barroso, Leonor</creator><creator>Miguéis, Jorge</creator><creator>Melo, Joana Barbosa</creator><creator>Carreira, Isabel Marques</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</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>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20171024</creationdate><title>Genomic predictive model for recurrence and metastasis development in head and neck squamous cell carcinoma patients</title><author>Ribeiro, Ilda Patrícia ; Caramelo, Francisco ; Esteves, Luísa ; Menoita, Joana ; Marques, Francisco ; Barroso, Leonor ; Miguéis, Jorge ; Melo, Joana Barbosa ; Carreira, Isabel Marques</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-175d28975e471d20d07a0a23a5d9469ce2a55da27b895704fa1640e989c55dc43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>45</topic><topic>45/61</topic><topic>692/4028/67/69</topic><topic>692/53/2422</topic><topic>Adult</topic><topic>Cell proliferation</topic><topic>Chromosomes, Human - genetics</topic><topic>Cohort Studies</topic><topic>Comparative Genomic Hybridization</topic><topic>Female</topic><topic>Genomics</topic><topic>Head & neck cancer</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Hybridization</topic><topic>Male</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Models, Statistical</topic><topic>multidisciplinary</topic><topic>Neoplasm Metastasis</topic><topic>Prediction models</topic><topic>Prognosis</topic><topic>Quality of life</topic><topic>Recurrence</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Squamous cell carcinoma</topic><topic>Squamous Cell Carcinoma of Head and Neck - diagnostic imaging</topic><topic>Squamous Cell Carcinoma of Head and Neck - genetics</topic><topic>Squamous Cell Carcinoma of Head and Neck - pathology</topic><topic>Survival</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ribeiro, Ilda Patrícia</creatorcontrib><creatorcontrib>Caramelo, Francisco</creatorcontrib><creatorcontrib>Esteves, Luísa</creatorcontrib><creatorcontrib>Menoita, Joana</creatorcontrib><creatorcontrib>Marques, Francisco</creatorcontrib><creatorcontrib>Barroso, Leonor</creatorcontrib><creatorcontrib>Miguéis, Jorge</creatorcontrib><creatorcontrib>Melo, Joana Barbosa</creatorcontrib><creatorcontrib>Carreira, Isabel Marques</creatorcontrib><collection>Springer Nature OA Free Journals</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content 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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ribeiro, Ilda Patrícia</au><au>Caramelo, Francisco</au><au>Esteves, Luísa</au><au>Menoita, Joana</au><au>Marques, Francisco</au><au>Barroso, Leonor</au><au>Miguéis, Jorge</au><au>Melo, Joana Barbosa</au><au>Carreira, Isabel Marques</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomic predictive model for recurrence and metastasis development in head and neck squamous cell carcinoma patients</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2017-10-24</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>13897</spage><epage>8</epage><pages>13897-8</pages><artnum>13897</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The head and neck squamous cell carcinoma (HNSCC) population consists mainly of high-risk for recurrence and locally advanced stage patients. Increased knowledge of the HNSCC genomic profile can improve early diagnosis and treatment outcomes. The development of models to identify consistent genomic patterns that distinguish HNSCC patients that will recur and/or develop metastasis after treatment is of utmost importance to decrease mortality and improve survival rates. In this study, we used array comparative genomic hybridization data from HNSCC patients to implement a robust model to predict HNSCC recurrence/metastasis. This predictive model showed a good accuracy (>80%) and was validated in an independent population from TCGA data portal. This predictive genomic model comprises chromosomal regions from 5p, 6p, 8p, 9p, 11q, 12q, 15q and 17p, where several upstream and downstream members of signaling pathways that lead to an increase in cell proliferation and invasion are mapped. The introduction of genomic predictive models in clinical practice might contribute to a more individualized clinical management of the HNSCC patients, reducing recurrences and improving patients’ quality of life. The power of this genomic model to predict the recurrence and metastases development should be evaluated in other HNSCC populations.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29066758</pmid><doi>10.1038/s41598-017-14377-x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2045-2322 |
| ispartof | Scientific reports, 2017-10, Vol.7 (1), p.13897-8, Article 13897 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5654944 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 45 45/61 692/4028/67/69 692/53/2422 Adult Cell proliferation Chromosomes, Human - genetics Cohort Studies Comparative Genomic Hybridization Female Genomics Head & neck cancer Humanities and Social Sciences Humans Hybridization Male Metastases Metastasis Middle Aged Models, Statistical multidisciplinary Neoplasm Metastasis Prediction models Prognosis Quality of life Recurrence Science Science (multidisciplinary) Squamous cell carcinoma Squamous Cell Carcinoma of Head and Neck - diagnostic imaging Squamous Cell Carcinoma of Head and Neck - genetics Squamous Cell Carcinoma of Head and Neck - pathology Survival |
| title | Genomic predictive model for recurrence and metastasis development in head and neck squamous cell carcinoma patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T04%3A32%3A42IST&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=Genomic%20predictive%20model%20for%20recurrence%20and%20metastasis%20development%20in%20head%20and%20neck%20squamous%20cell%20carcinoma%20patients&rft.jtitle=Scientific%20reports&rft.au=Ribeiro,%20Ilda%20Patr%C3%ADcia&rft.date=2017-10-24&rft.volume=7&rft.issue=1&rft.spage=13897&rft.epage=8&rft.pages=13897-8&rft.artnum=13897&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-017-14377-x&rft_dat=%3Cproquest_pubme%3E1955027561%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1955027561&rft_id=info:pmid/29066758&rfr_iscdi=true |