Detection of prostate cancer‐specific transcripts in extracellular vesicles isolated from post‐DRE urine
Background: The measurement of gene expression in post‐digital rectal examination (DRE) urine specimens provides a non‐invasive method to determine a patient's risk of prostate cancer. Many currently available assays use whole urine or cell pellets for the analysis of prostate cancer‐associated...
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| Veröffentlicht in: | The Prostate 2017-06, Vol.77 (9), p.990-999 |
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| creator | Pellegrini, Kathryn L. Patil, Dattatraya Douglas, Kristen J.S. Lee, Grace Wehrmeyer, Kathryn Torlak, Mersiha Clark, Jeremy Cooper, Colin S. Moreno, Carlos S. Sanda, Martin G. |
| description | Background: The measurement of gene expression in post‐digital rectal examination (DRE) urine specimens provides a non‐invasive method to determine a patient's risk of prostate cancer. Many currently available assays use whole urine or cell pellets for the analysis of prostate cancer‐associated genes, although the use of extracellular vesicles (EVs) has also recently been of interest. We investigated the expression of prostate‐, kidney‐, and bladder‐specific transcripts and known prostate cancer biomarkers in urine EVs.
Methods: Cell pellets and EVs were recovered from post‐DRE urine specimens, with the total RNA yield and quality determined by Bioanalyzer. The levels of prostate, kidney, and bladder‐associated transcripts in EVs were assessed by TaqMan qPCR and targeted sequencing.
Results: RNA was more consistently recovered from the urine EV specimens, with over 80% of the patients demonstrating higher RNA yields in the EV fraction as compared to urine cell pellets. The median EV RNA yield of 36.4 ng was significantly higher than the median urine cell pellet RNA yield of 4.8 ng. Analysis of the post‐DRE urine EVs indicated that prostate‐specific transcripts were more abundant than kidney‐ or bladder‐specific transcripts. Additionally, patients with prostate cancer had significantly higher levels of the prostate cancer‐associated genes PCA3 and ERG.
Conclusions: Post‐DRE urine EVs are a viable source of prostate‐derived RNAs for biomarker discovery and prostate cancer status can be distinguished from analysis of these specimens. Continued analysis of urine EVs offers the potential discovery of novel biomarkers for pre‐biopsy prostate cancer detection. |
| doi_str_mv | 10.1002/pros.23355 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5907935</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1896178922</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4485-7660de09905f3e2051f20d5de2b7e41d8abe11357af4e59f0015497212a4a993</originalsourceid><addsrcrecordid>eNp9kdFqFTEQhoMo9rR64wNIwBsRtk6yycnmRpC2VqFQqb0POdmJpuxJ1mS32jsfoc_okzTH0xbrhVeBzDcf888Q8oLBPgPgb8ecyj5vWykfkQUDrRoAIR-TBXAFjWCt2iG7pVwAVBz4U7LDO8G0FN2CDIc4oZtCijR5ujFNdkLqbHSYf_-6LiO64IOjU7axuBzGqdAQKf6sHw6HYR5sppdYghuwVkoaan9PfU5rOlZbdRyeHdE5h4jPyBNvh4LPb989cv7h6PzgY3Nyevzp4P1J44ToZKOWS-gRtAbpW-QgmefQyx75SqFgfWdXyFgrlfUCpfY1lxRaccatsFq3e-TdVjvOqzX2DmOddTBjDmubr0yywTysxPDNfE2XRmpQupVV8PpWkNP3Gctk1qFswtqIaS6GdZ1WXavVsqKv_kEv0pxjTVcpvWSq05xX6s2WcnXBJaO_H4aB2dzQbDZv_tywwi__Hv8evTtaBdgW-BEGvPqPynw-O_2yld4AMcmrJw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1896178922</pqid></control><display><type>article</type><title>Detection of prostate cancer‐specific transcripts in extracellular vesicles isolated from post‐DRE urine</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Pellegrini, Kathryn L. ; Patil, Dattatraya ; Douglas, Kristen J.S. ; Lee, Grace ; Wehrmeyer, Kathryn ; Torlak, Mersiha ; Clark, Jeremy ; Cooper, Colin S. ; Moreno, Carlos S. ; Sanda, Martin G.</creator><creatorcontrib>Pellegrini, Kathryn L. ; Patil, Dattatraya ; Douglas, Kristen J.S. ; Lee, Grace ; Wehrmeyer, Kathryn ; Torlak, Mersiha ; Clark, Jeremy ; Cooper, Colin S. ; Moreno, Carlos S. ; Sanda, Martin G.</creatorcontrib><description>Background: The measurement of gene expression in post‐digital rectal examination (DRE) urine specimens provides a non‐invasive method to determine a patient's risk of prostate cancer. Many currently available assays use whole urine or cell pellets for the analysis of prostate cancer‐associated genes, although the use of extracellular vesicles (EVs) has also recently been of interest. We investigated the expression of prostate‐, kidney‐, and bladder‐specific transcripts and known prostate cancer biomarkers in urine EVs.
Methods: Cell pellets and EVs were recovered from post‐DRE urine specimens, with the total RNA yield and quality determined by Bioanalyzer. The levels of prostate, kidney, and bladder‐associated transcripts in EVs were assessed by TaqMan qPCR and targeted sequencing.
Results: RNA was more consistently recovered from the urine EV specimens, with over 80% of the patients demonstrating higher RNA yields in the EV fraction as compared to urine cell pellets. The median EV RNA yield of 36.4 ng was significantly higher than the median urine cell pellet RNA yield of 4.8 ng. Analysis of the post‐DRE urine EVs indicated that prostate‐specific transcripts were more abundant than kidney‐ or bladder‐specific transcripts. Additionally, patients with prostate cancer had significantly higher levels of the prostate cancer‐associated genes PCA3 and ERG.
Conclusions: Post‐DRE urine EVs are a viable source of prostate‐derived RNAs for biomarker discovery and prostate cancer status can be distinguished from analysis of these specimens. Continued analysis of urine EVs offers the potential discovery of novel biomarkers for pre‐biopsy prostate cancer detection.</description><identifier>ISSN: 0270-4137</identifier><identifier>ISSN: 1097-0045</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.23355</identifier><identifier>PMID: 28419548</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Antigens, Neoplasm - genetics ; Antigens, Neoplasm - urine ; Biomarkers ; Biomarkers, Tumor - urine ; Biopsy ; Bladder ; Digital Rectal Examination - methods ; Early Detection of Cancer - methods ; ERG ; Extracellular vesicles ; Extracellular Vesicles - metabolism ; Extracellular Vesicles - pathology ; Gene expression ; Gene Expression Profiling ; Humans ; Kidneys ; Male ; Middle Aged ; PCA3 ; Prostate - metabolism ; Prostate - pathology ; Prostate cancer ; Prostatic Neoplasms - diagnosis ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - urine ; Rectum ; Reproducibility of Results ; Ribonucleic acid ; RNA ; Transcriptional Regulator ERG - genetics ; Transcriptional Regulator ERG - urine ; Urinalysis - methods ; Urinary bladder ; Urine</subject><ispartof>The Prostate, 2017-06, Vol.77 (9), p.990-999</ispartof><rights>2017 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4485-7660de09905f3e2051f20d5de2b7e41d8abe11357af4e59f0015497212a4a993</citedby><cites>FETCH-LOGICAL-c4485-7660de09905f3e2051f20d5de2b7e41d8abe11357af4e59f0015497212a4a993</cites><orcidid>0000-0002-5089-5477</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpros.23355$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpros.23355$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28419548$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pellegrini, Kathryn L.</creatorcontrib><creatorcontrib>Patil, Dattatraya</creatorcontrib><creatorcontrib>Douglas, Kristen J.S.</creatorcontrib><creatorcontrib>Lee, Grace</creatorcontrib><creatorcontrib>Wehrmeyer, Kathryn</creatorcontrib><creatorcontrib>Torlak, Mersiha</creatorcontrib><creatorcontrib>Clark, Jeremy</creatorcontrib><creatorcontrib>Cooper, Colin S.</creatorcontrib><creatorcontrib>Moreno, Carlos S.</creatorcontrib><creatorcontrib>Sanda, Martin G.</creatorcontrib><title>Detection of prostate cancer‐specific transcripts in extracellular vesicles isolated from post‐DRE urine</title><title>The Prostate</title><addtitle>Prostate</addtitle><description>Background: The measurement of gene expression in post‐digital rectal examination (DRE) urine specimens provides a non‐invasive method to determine a patient's risk of prostate cancer. Many currently available assays use whole urine or cell pellets for the analysis of prostate cancer‐associated genes, although the use of extracellular vesicles (EVs) has also recently been of interest. We investigated the expression of prostate‐, kidney‐, and bladder‐specific transcripts and known prostate cancer biomarkers in urine EVs.
Methods: Cell pellets and EVs were recovered from post‐DRE urine specimens, with the total RNA yield and quality determined by Bioanalyzer. The levels of prostate, kidney, and bladder‐associated transcripts in EVs were assessed by TaqMan qPCR and targeted sequencing.
Results: RNA was more consistently recovered from the urine EV specimens, with over 80% of the patients demonstrating higher RNA yields in the EV fraction as compared to urine cell pellets. The median EV RNA yield of 36.4 ng was significantly higher than the median urine cell pellet RNA yield of 4.8 ng. Analysis of the post‐DRE urine EVs indicated that prostate‐specific transcripts were more abundant than kidney‐ or bladder‐specific transcripts. Additionally, patients with prostate cancer had significantly higher levels of the prostate cancer‐associated genes PCA3 and ERG.
Conclusions: Post‐DRE urine EVs are a viable source of prostate‐derived RNAs for biomarker discovery and prostate cancer status can be distinguished from analysis of these specimens. Continued analysis of urine EVs offers the potential discovery of novel biomarkers for pre‐biopsy prostate cancer detection.</description><subject>Adult</subject><subject>Aged</subject><subject>Antigens, Neoplasm - genetics</subject><subject>Antigens, Neoplasm - urine</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - urine</subject><subject>Biopsy</subject><subject>Bladder</subject><subject>Digital Rectal Examination - methods</subject><subject>Early Detection of Cancer - methods</subject><subject>ERG</subject><subject>Extracellular vesicles</subject><subject>Extracellular Vesicles - metabolism</subject><subject>Extracellular Vesicles - pathology</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Humans</subject><subject>Kidneys</subject><subject>Male</subject><subject>Middle Aged</subject><subject>PCA3</subject><subject>Prostate - metabolism</subject><subject>Prostate - pathology</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - diagnosis</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Prostatic Neoplasms - urine</subject><subject>Rectum</subject><subject>Reproducibility of Results</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Transcriptional Regulator ERG - genetics</subject><subject>Transcriptional Regulator ERG - urine</subject><subject>Urinalysis - methods</subject><subject>Urinary bladder</subject><subject>Urine</subject><issn>0270-4137</issn><issn>1097-0045</issn><issn>1097-0045</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kdFqFTEQhoMo9rR64wNIwBsRtk6yycnmRpC2VqFQqb0POdmJpuxJ1mS32jsfoc_okzTH0xbrhVeBzDcf888Q8oLBPgPgb8ecyj5vWykfkQUDrRoAIR-TBXAFjWCt2iG7pVwAVBz4U7LDO8G0FN2CDIc4oZtCijR5ujFNdkLqbHSYf_-6LiO64IOjU7axuBzGqdAQKf6sHw6HYR5sppdYghuwVkoaan9PfU5rOlZbdRyeHdE5h4jPyBNvh4LPb989cv7h6PzgY3Nyevzp4P1J44ToZKOWS-gRtAbpW-QgmefQyx75SqFgfWdXyFgrlfUCpfY1lxRaccatsFq3e-TdVjvOqzX2DmOddTBjDmubr0yywTysxPDNfE2XRmpQupVV8PpWkNP3Gctk1qFswtqIaS6GdZ1WXavVsqKv_kEv0pxjTVcpvWSq05xX6s2WcnXBJaO_H4aB2dzQbDZv_tywwi__Hv8evTtaBdgW-BEGvPqPynw-O_2yld4AMcmrJw</recordid><startdate>201706</startdate><enddate>201706</enddate><creator>Pellegrini, Kathryn L.</creator><creator>Patil, Dattatraya</creator><creator>Douglas, Kristen J.S.</creator><creator>Lee, Grace</creator><creator>Wehrmeyer, Kathryn</creator><creator>Torlak, Mersiha</creator><creator>Clark, Jeremy</creator><creator>Cooper, Colin S.</creator><creator>Moreno, Carlos S.</creator><creator>Sanda, Martin G.</creator><general>Wiley Subscription Services, Inc</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>7T5</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5089-5477</orcidid></search><sort><creationdate>201706</creationdate><title>Detection of prostate cancer‐specific transcripts in extracellular vesicles isolated from post‐DRE urine</title><author>Pellegrini, Kathryn L. ; Patil, Dattatraya ; Douglas, Kristen J.S. ; Lee, Grace ; Wehrmeyer, Kathryn ; Torlak, Mersiha ; Clark, Jeremy ; Cooper, Colin S. ; Moreno, Carlos S. ; Sanda, Martin G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4485-7660de09905f3e2051f20d5de2b7e41d8abe11357af4e59f0015497212a4a993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antigens, Neoplasm - genetics</topic><topic>Antigens, Neoplasm - urine</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - urine</topic><topic>Biopsy</topic><topic>Bladder</topic><topic>Digital Rectal Examination - methods</topic><topic>Early Detection of Cancer - methods</topic><topic>ERG</topic><topic>Extracellular vesicles</topic><topic>Extracellular Vesicles - metabolism</topic><topic>Extracellular Vesicles - pathology</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Humans</topic><topic>Kidneys</topic><topic>Male</topic><topic>Middle Aged</topic><topic>PCA3</topic><topic>Prostate - metabolism</topic><topic>Prostate - pathology</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - diagnosis</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms - urine</topic><topic>Rectum</topic><topic>Reproducibility of Results</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Transcriptional Regulator ERG - genetics</topic><topic>Transcriptional Regulator ERG - urine</topic><topic>Urinalysis - methods</topic><topic>Urinary bladder</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pellegrini, Kathryn L.</creatorcontrib><creatorcontrib>Patil, Dattatraya</creatorcontrib><creatorcontrib>Douglas, Kristen J.S.</creatorcontrib><creatorcontrib>Lee, Grace</creatorcontrib><creatorcontrib>Wehrmeyer, Kathryn</creatorcontrib><creatorcontrib>Torlak, Mersiha</creatorcontrib><creatorcontrib>Clark, Jeremy</creatorcontrib><creatorcontrib>Cooper, Colin S.</creatorcontrib><creatorcontrib>Moreno, Carlos S.</creatorcontrib><creatorcontrib>Sanda, Martin G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Prostate</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pellegrini, Kathryn L.</au><au>Patil, Dattatraya</au><au>Douglas, Kristen J.S.</au><au>Lee, Grace</au><au>Wehrmeyer, Kathryn</au><au>Torlak, Mersiha</au><au>Clark, Jeremy</au><au>Cooper, Colin S.</au><au>Moreno, Carlos S.</au><au>Sanda, Martin G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Detection of prostate cancer‐specific transcripts in extracellular vesicles isolated from post‐DRE urine</atitle><jtitle>The Prostate</jtitle><addtitle>Prostate</addtitle><date>2017-06</date><risdate>2017</risdate><volume>77</volume><issue>9</issue><spage>990</spage><epage>999</epage><pages>990-999</pages><issn>0270-4137</issn><issn>1097-0045</issn><eissn>1097-0045</eissn><abstract>Background: The measurement of gene expression in post‐digital rectal examination (DRE) urine specimens provides a non‐invasive method to determine a patient's risk of prostate cancer. Many currently available assays use whole urine or cell pellets for the analysis of prostate cancer‐associated genes, although the use of extracellular vesicles (EVs) has also recently been of interest. We investigated the expression of prostate‐, kidney‐, and bladder‐specific transcripts and known prostate cancer biomarkers in urine EVs.
Methods: Cell pellets and EVs were recovered from post‐DRE urine specimens, with the total RNA yield and quality determined by Bioanalyzer. The levels of prostate, kidney, and bladder‐associated transcripts in EVs were assessed by TaqMan qPCR and targeted sequencing.
Results: RNA was more consistently recovered from the urine EV specimens, with over 80% of the patients demonstrating higher RNA yields in the EV fraction as compared to urine cell pellets. The median EV RNA yield of 36.4 ng was significantly higher than the median urine cell pellet RNA yield of 4.8 ng. Analysis of the post‐DRE urine EVs indicated that prostate‐specific transcripts were more abundant than kidney‐ or bladder‐specific transcripts. Additionally, patients with prostate cancer had significantly higher levels of the prostate cancer‐associated genes PCA3 and ERG.
Conclusions: Post‐DRE urine EVs are a viable source of prostate‐derived RNAs for biomarker discovery and prostate cancer status can be distinguished from analysis of these specimens. Continued analysis of urine EVs offers the potential discovery of novel biomarkers for pre‐biopsy prostate cancer detection.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28419548</pmid><doi>10.1002/pros.23355</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-5089-5477</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | The Prostate, 2017-06, Vol.77 (9), p.990-999 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult Aged Antigens, Neoplasm - genetics Antigens, Neoplasm - urine Biomarkers Biomarkers, Tumor - urine Biopsy Bladder Digital Rectal Examination - methods Early Detection of Cancer - methods ERG Extracellular vesicles Extracellular Vesicles - metabolism Extracellular Vesicles - pathology Gene expression Gene Expression Profiling Humans Kidneys Male Middle Aged PCA3 Prostate - metabolism Prostate - pathology Prostate cancer Prostatic Neoplasms - diagnosis Prostatic Neoplasms - genetics Prostatic Neoplasms - pathology Prostatic Neoplasms - urine Rectum Reproducibility of Results Ribonucleic acid RNA Transcriptional Regulator ERG - genetics Transcriptional Regulator ERG - urine Urinalysis - methods Urinary bladder Urine |
| title | Detection of prostate cancer‐specific transcripts in extracellular vesicles isolated from post‐DRE urine |
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