INPP4B is highly expressed in prostate intermediate cells and its loss of expression in prostate carcinoma predicts for recurrence and poor long term survival
BACKGROUND Phosphoinositide 3‐kinase (PI3K)/Akt pathway is frequently activated in prostate carcinoma due to the loss of tumor suppressor PTEN, which leads to increased Akt activity. Expression of INPP4B, another negative regulator of the PI3K/Akt pathway, is also reduced in prostate carcinoma. Howe...
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| Veröffentlicht in: | The Prostate 2015-01, Vol.75 (1), p.92-102 |
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| creator | Rynkiewicz, Natalie K. Fedele, Clare G. Chiam, Karen Gupta, Ruta Kench, James G. Ooms, Lisa M. McLean, Catriona A. Giles, Graham G. Horvath, Lisa G. Mitchell, Christina A. |
| description | BACKGROUND
Phosphoinositide 3‐kinase (PI3K)/Akt pathway is frequently activated in prostate carcinoma due to the loss of tumor suppressor PTEN, which leads to increased Akt activity. Expression of INPP4B, another negative regulator of the PI3K/Akt pathway, is also reduced in prostate carcinoma. However, uncertainty exists regarding the association of INPP4B expression and biochemical and clinical relapse of prostate carcinoma.
METHODS
INPP4B expression in benign prostate acini was analyzed by co‐immunofluorescence with cytokeratins (CK) 5, 8, 19, androgen receptor (AR), c‐MET, chromogranin A and Ki67. INPP4B expression in prostate carcinoma was analyzed in two independent cohorts (n = 406). The association of INPP4B with biochemical and clinical prostate carcinoma relapse was assessed by Kaplan–Meier and Cox proportional hazards modeling.
RESULTS
INPP4B was expressed in luminal epithelium within benign ducts, and was highly expressed in CK5+/CK8+/CK19+/AR−/c‐MET+/Ki67− intermediate cells in proliferative inflammatory atrophic acini. Overall, INPP4B expression was reduced in prostate carcinoma compared to benign epithelium. Absent/low INPP4B expression was associated with reduced biochemical relapse‐free survival (P = 0.01) and increased risk of clinical relapse (P = 0.01). Absence of INPP4B expression was an independent predictor of clinical relapse free survival (P = 0.004) when modeled with Gleason score (P = 0.027) and pathologic stage (P = 0.07).
CONCLUSIONS
INPP4B is highly expressed in intermediate cells within proliferative inflammatory atrophic ducts, and expression is reduced in prostate carcinoma. Absence of INPP4B expression is associated with poor outcome following radical prostatectomy, and represents an independent prognostic marker of prostate carcinoma clinical recurrence. Prostate 75:92–102, 2015. © 2014 Wiley Periodicals, Inc. |
| doi_str_mv | 10.1002/pros.22895 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1634281762</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1634281762</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3925-90f7a522bbb045943d05cff63fd756914f9559650fc9951ad389ea6195ef4e843</originalsourceid><addsrcrecordid>eNpdkc9O3DAQxq2qqCy0lz5AZamXXkL93_Gx0EKREKxoqx4tbzIG02y82AllX6bPWmcXkODk8fj3jWe-Qeg9JQeUEPZ5lWI-YKw28hWaUWJ0RYiQr9GMME0qQbneRXs53xBScMLeoF0mWS24UjP07_R8PheHOGR8Ha6uuzWG-1WCnKHFocdT6cENUOIB0hLaMF0a6LqMXV-QIeMu5oyjfxSG2D9TNi41oY9LV1JF3xSFjwknaMaUoG9gU2gVS66L_RWe_sF5THfhznVv0Y53XYZ3D-c--nX87efR9-rs4uT06MtZ1XDDZGWI104ytlgsyuRG8JbIxnvFfaulMlR4I6VRkvjGGEldy2sDTlEjwQsoVuyjT9u6pe3bEfJglyFPY7oe4pgtVVywmmrFCvrxBXoTx9SX7grFjGGKS1KoDw_UuCi22VUKS5fW9tH5AtAt8Dd0sH56p8ROO7WTfXazUzu_vPixiYqm2mpCHuD-SePSH6s019L-Pj-x5uuhlqSureD_AQm6pQA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1629926350</pqid></control><display><type>article</type><title>INPP4B is highly expressed in prostate intermediate cells and its loss of expression in prostate carcinoma predicts for recurrence and poor long term survival</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Rynkiewicz, Natalie K. ; Fedele, Clare G. ; Chiam, Karen ; Gupta, Ruta ; Kench, James G. ; Ooms, Lisa M. ; McLean, Catriona A. ; Giles, Graham G. ; Horvath, Lisa G. ; Mitchell, Christina A.</creator><creatorcontrib>Rynkiewicz, Natalie K. ; Fedele, Clare G. ; Chiam, Karen ; Gupta, Ruta ; Kench, James G. ; Ooms, Lisa M. ; McLean, Catriona A. ; Giles, Graham G. ; Horvath, Lisa G. ; Mitchell, Christina A.</creatorcontrib><description>BACKGROUND
Phosphoinositide 3‐kinase (PI3K)/Akt pathway is frequently activated in prostate carcinoma due to the loss of tumor suppressor PTEN, which leads to increased Akt activity. Expression of INPP4B, another negative regulator of the PI3K/Akt pathway, is also reduced in prostate carcinoma. However, uncertainty exists regarding the association of INPP4B expression and biochemical and clinical relapse of prostate carcinoma.
METHODS
INPP4B expression in benign prostate acini was analyzed by co‐immunofluorescence with cytokeratins (CK) 5, 8, 19, androgen receptor (AR), c‐MET, chromogranin A and Ki67. INPP4B expression in prostate carcinoma was analyzed in two independent cohorts (n = 406). The association of INPP4B with biochemical and clinical prostate carcinoma relapse was assessed by Kaplan–Meier and Cox proportional hazards modeling.
RESULTS
INPP4B was expressed in luminal epithelium within benign ducts, and was highly expressed in CK5+/CK8+/CK19+/AR−/c‐MET+/Ki67− intermediate cells in proliferative inflammatory atrophic acini. Overall, INPP4B expression was reduced in prostate carcinoma compared to benign epithelium. Absent/low INPP4B expression was associated with reduced biochemical relapse‐free survival (P = 0.01) and increased risk of clinical relapse (P = 0.01). Absence of INPP4B expression was an independent predictor of clinical relapse free survival (P = 0.004) when modeled with Gleason score (P = 0.027) and pathologic stage (P = 0.07).
CONCLUSIONS
INPP4B is highly expressed in intermediate cells within proliferative inflammatory atrophic ducts, and expression is reduced in prostate carcinoma. Absence of INPP4B expression is associated with poor outcome following radical prostatectomy, and represents an independent prognostic marker of prostate carcinoma clinical recurrence. Prostate 75:92–102, 2015. © 2014 Wiley Periodicals, Inc.</description><identifier>ISSN: 0270-4137</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.22895</identifier><identifier>PMID: 25284366</identifier><identifier>CODEN: PRSTDS</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Chromogranin A - metabolism ; Disease-Free Survival ; Fluorescent Antibody Technique ; Fluorescent Antibody Technique, Indirect ; Humans ; INPP4B ; Keratins - metabolism ; Ki-67 Antigen - metabolism ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Phosphoric Monoester Hydrolases - metabolism ; PI3K pathway ; Proportional Hazards Models ; prostate atrophy ; prostate carcinoma ; Prostatic Neoplasms - enzymology ; Prostatic Neoplasms - mortality ; Prostatic Neoplasms - pathology ; Proto-Oncogene Proteins c-met - metabolism ; Receptors, Androgen - metabolism ; Survival Analysis</subject><ispartof>The Prostate, 2015-01, Vol.75 (1), p.92-102</ispartof><rights>2014 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3925-90f7a522bbb045943d05cff63fd756914f9559650fc9951ad389ea6195ef4e843</citedby></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.22895$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpros.22895$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25284366$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rynkiewicz, Natalie K.</creatorcontrib><creatorcontrib>Fedele, Clare G.</creatorcontrib><creatorcontrib>Chiam, Karen</creatorcontrib><creatorcontrib>Gupta, Ruta</creatorcontrib><creatorcontrib>Kench, James G.</creatorcontrib><creatorcontrib>Ooms, Lisa M.</creatorcontrib><creatorcontrib>McLean, Catriona A.</creatorcontrib><creatorcontrib>Giles, Graham G.</creatorcontrib><creatorcontrib>Horvath, Lisa G.</creatorcontrib><creatorcontrib>Mitchell, Christina A.</creatorcontrib><title>INPP4B is highly expressed in prostate intermediate cells and its loss of expression in prostate carcinoma predicts for recurrence and poor long term survival</title><title>The Prostate</title><addtitle>Prostate</addtitle><description>BACKGROUND
Phosphoinositide 3‐kinase (PI3K)/Akt pathway is frequently activated in prostate carcinoma due to the loss of tumor suppressor PTEN, which leads to increased Akt activity. Expression of INPP4B, another negative regulator of the PI3K/Akt pathway, is also reduced in prostate carcinoma. However, uncertainty exists regarding the association of INPP4B expression and biochemical and clinical relapse of prostate carcinoma.
METHODS
INPP4B expression in benign prostate acini was analyzed by co‐immunofluorescence with cytokeratins (CK) 5, 8, 19, androgen receptor (AR), c‐MET, chromogranin A and Ki67. INPP4B expression in prostate carcinoma was analyzed in two independent cohorts (n = 406). The association of INPP4B with biochemical and clinical prostate carcinoma relapse was assessed by Kaplan–Meier and Cox proportional hazards modeling.
RESULTS
INPP4B was expressed in luminal epithelium within benign ducts, and was highly expressed in CK5+/CK8+/CK19+/AR−/c‐MET+/Ki67− intermediate cells in proliferative inflammatory atrophic acini. Overall, INPP4B expression was reduced in prostate carcinoma compared to benign epithelium. Absent/low INPP4B expression was associated with reduced biochemical relapse‐free survival (P = 0.01) and increased risk of clinical relapse (P = 0.01). Absence of INPP4B expression was an independent predictor of clinical relapse free survival (P = 0.004) when modeled with Gleason score (P = 0.027) and pathologic stage (P = 0.07).
CONCLUSIONS
INPP4B is highly expressed in intermediate cells within proliferative inflammatory atrophic ducts, and expression is reduced in prostate carcinoma. Absence of INPP4B expression is associated with poor outcome following radical prostatectomy, and represents an independent prognostic marker of prostate carcinoma clinical recurrence. Prostate 75:92–102, 2015. © 2014 Wiley Periodicals, Inc.</description><subject>Adult</subject><subject>Aged</subject><subject>Chromogranin A - metabolism</subject><subject>Disease-Free Survival</subject><subject>Fluorescent Antibody Technique</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Humans</subject><subject>INPP4B</subject><subject>Keratins - metabolism</subject><subject>Ki-67 Antigen - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Recurrence, Local</subject><subject>Phosphoric Monoester Hydrolases - metabolism</subject><subject>PI3K pathway</subject><subject>Proportional Hazards Models</subject><subject>prostate atrophy</subject><subject>prostate carcinoma</subject><subject>Prostatic Neoplasms - enzymology</subject><subject>Prostatic Neoplasms - mortality</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Proto-Oncogene Proteins c-met - metabolism</subject><subject>Receptors, Androgen - metabolism</subject><subject>Survival Analysis</subject><issn>0270-4137</issn><issn>1097-0045</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc9O3DAQxq2qqCy0lz5AZamXXkL93_Gx0EKREKxoqx4tbzIG02y82AllX6bPWmcXkODk8fj3jWe-Qeg9JQeUEPZ5lWI-YKw28hWaUWJ0RYiQr9GMME0qQbneRXs53xBScMLeoF0mWS24UjP07_R8PheHOGR8Ha6uuzWG-1WCnKHFocdT6cENUOIB0hLaMF0a6LqMXV-QIeMu5oyjfxSG2D9TNi41oY9LV1JF3xSFjwknaMaUoG9gU2gVS66L_RWe_sF5THfhznVv0Y53XYZ3D-c--nX87efR9-rs4uT06MtZ1XDDZGWI104ytlgsyuRG8JbIxnvFfaulMlR4I6VRkvjGGEldy2sDTlEjwQsoVuyjT9u6pe3bEfJglyFPY7oe4pgtVVywmmrFCvrxBXoTx9SX7grFjGGKS1KoDw_UuCi22VUKS5fW9tH5AtAt8Dd0sH56p8ROO7WTfXazUzu_vPixiYqm2mpCHuD-SePSH6s019L-Pj-x5uuhlqSureD_AQm6pQA</recordid><startdate>201501</startdate><enddate>201501</enddate><creator>Rynkiewicz, Natalie K.</creator><creator>Fedele, Clare G.</creator><creator>Chiam, Karen</creator><creator>Gupta, Ruta</creator><creator>Kench, James G.</creator><creator>Ooms, Lisa M.</creator><creator>McLean, Catriona A.</creator><creator>Giles, Graham G.</creator><creator>Horvath, Lisa G.</creator><creator>Mitchell, Christina A.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</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></search><sort><creationdate>201501</creationdate><title>INPP4B is highly expressed in prostate intermediate cells and its loss of expression in prostate carcinoma predicts for recurrence and poor long term survival</title><author>Rynkiewicz, Natalie K. ; Fedele, Clare G. ; Chiam, Karen ; Gupta, Ruta ; Kench, James G. ; Ooms, Lisa M. ; McLean, Catriona A. ; Giles, Graham G. ; Horvath, Lisa G. ; Mitchell, Christina A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3925-90f7a522bbb045943d05cff63fd756914f9559650fc9951ad389ea6195ef4e843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Chromogranin A - metabolism</topic><topic>Disease-Free Survival</topic><topic>Fluorescent Antibody Technique</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Humans</topic><topic>INPP4B</topic><topic>Keratins - metabolism</topic><topic>Ki-67 Antigen - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Recurrence, Local</topic><topic>Phosphoric Monoester Hydrolases - metabolism</topic><topic>PI3K pathway</topic><topic>Proportional Hazards Models</topic><topic>prostate atrophy</topic><topic>prostate carcinoma</topic><topic>Prostatic Neoplasms - enzymology</topic><topic>Prostatic Neoplasms - mortality</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Proto-Oncogene Proteins c-met - metabolism</topic><topic>Receptors, Androgen - metabolism</topic><topic>Survival Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rynkiewicz, Natalie K.</creatorcontrib><creatorcontrib>Fedele, Clare G.</creatorcontrib><creatorcontrib>Chiam, Karen</creatorcontrib><creatorcontrib>Gupta, Ruta</creatorcontrib><creatorcontrib>Kench, James G.</creatorcontrib><creatorcontrib>Ooms, Lisa M.</creatorcontrib><creatorcontrib>McLean, Catriona A.</creatorcontrib><creatorcontrib>Giles, Graham G.</creatorcontrib><creatorcontrib>Horvath, Lisa G.</creatorcontrib><creatorcontrib>Mitchell, Christina A.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</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><jtitle>The Prostate</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rynkiewicz, Natalie K.</au><au>Fedele, Clare G.</au><au>Chiam, Karen</au><au>Gupta, Ruta</au><au>Kench, James G.</au><au>Ooms, Lisa M.</au><au>McLean, Catriona A.</au><au>Giles, Graham G.</au><au>Horvath, Lisa G.</au><au>Mitchell, Christina A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>INPP4B is highly expressed in prostate intermediate cells and its loss of expression in prostate carcinoma predicts for recurrence and poor long term survival</atitle><jtitle>The Prostate</jtitle><addtitle>Prostate</addtitle><date>2015-01</date><risdate>2015</risdate><volume>75</volume><issue>1</issue><spage>92</spage><epage>102</epage><pages>92-102</pages><issn>0270-4137</issn><eissn>1097-0045</eissn><coden>PRSTDS</coden><abstract>BACKGROUND
Phosphoinositide 3‐kinase (PI3K)/Akt pathway is frequently activated in prostate carcinoma due to the loss of tumor suppressor PTEN, which leads to increased Akt activity. Expression of INPP4B, another negative regulator of the PI3K/Akt pathway, is also reduced in prostate carcinoma. However, uncertainty exists regarding the association of INPP4B expression and biochemical and clinical relapse of prostate carcinoma.
METHODS
INPP4B expression in benign prostate acini was analyzed by co‐immunofluorescence with cytokeratins (CK) 5, 8, 19, androgen receptor (AR), c‐MET, chromogranin A and Ki67. INPP4B expression in prostate carcinoma was analyzed in two independent cohorts (n = 406). The association of INPP4B with biochemical and clinical prostate carcinoma relapse was assessed by Kaplan–Meier and Cox proportional hazards modeling.
RESULTS
INPP4B was expressed in luminal epithelium within benign ducts, and was highly expressed in CK5+/CK8+/CK19+/AR−/c‐MET+/Ki67− intermediate cells in proliferative inflammatory atrophic acini. Overall, INPP4B expression was reduced in prostate carcinoma compared to benign epithelium. Absent/low INPP4B expression was associated with reduced biochemical relapse‐free survival (P = 0.01) and increased risk of clinical relapse (P = 0.01). Absence of INPP4B expression was an independent predictor of clinical relapse free survival (P = 0.004) when modeled with Gleason score (P = 0.027) and pathologic stage (P = 0.07).
CONCLUSIONS
INPP4B is highly expressed in intermediate cells within proliferative inflammatory atrophic ducts, and expression is reduced in prostate carcinoma. Absence of INPP4B expression is associated with poor outcome following radical prostatectomy, and represents an independent prognostic marker of prostate carcinoma clinical recurrence. Prostate 75:92–102, 2015. © 2014 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>25284366</pmid><doi>10.1002/pros.22895</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Chromogranin A - metabolism Disease-Free Survival Fluorescent Antibody Technique Fluorescent Antibody Technique, Indirect Humans INPP4B Keratins - metabolism Ki-67 Antigen - metabolism Male Middle Aged Neoplasm Recurrence, Local Phosphoric Monoester Hydrolases - metabolism PI3K pathway Proportional Hazards Models prostate atrophy prostate carcinoma Prostatic Neoplasms - enzymology Prostatic Neoplasms - mortality Prostatic Neoplasms - pathology Proto-Oncogene Proteins c-met - metabolism Receptors, Androgen - metabolism Survival Analysis |
| title | INPP4B is highly expressed in prostate intermediate cells and its loss of expression in prostate carcinoma predicts for recurrence and poor long term survival |
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