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Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors
A somatic deletion at the proximal end of canine chromosome 27 (CFA27) was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC...
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Published in: | PloS one 2015-07, Vol.10 (7), p.e0131280 |
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description | A somatic deletion at the proximal end of canine chromosome 27 (CFA27) was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors.
Droplet digital PCR for PFDN5 was performed in DNA from 102 malignant, 40 benign mammary tumors/dysplasias, 11 non-neoplastic mammary tissues and each corresponding genomic DNA from leukocytes. The copy number of PFDN5 was normalized to a reference amplicon on canine chromosome 32 (CFA32). Z-scores were calculated, based on Gaussian distributed normalized PFDN5 copy numbers of the leukocyte DNA. Z-scores ≤ -3.0 in tissue were considered as being indicative of the PFDN5 deletion and called as such. The Ki-67 proliferation index was assessed in a subset of 79 tissue samples by immunohistochemistry.
The deletion was confirmed in 24% of all malignant tumors, detected in only 7.5% of the benign tumors and was not present in any normal mammary tissue sample. The subgroup of solid carcinomas (n = 9) showed the highest frequency of the deletion (67%) and those malignomas without microscopical high fraction of benign tissue (n = 71) had a 32% frequency (p |
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Droplet digital PCR for PFDN5 was performed in DNA from 102 malignant, 40 benign mammary tumors/dysplasias, 11 non-neoplastic mammary tissues and each corresponding genomic DNA from leukocytes. The copy number of PFDN5 was normalized to a reference amplicon on canine chromosome 32 (CFA32). Z-scores were calculated, based on Gaussian distributed normalized PFDN5 copy numbers of the leukocyte DNA. Z-scores ≤ -3.0 in tissue were considered as being indicative of the PFDN5 deletion and called as such. The Ki-67 proliferation index was assessed in a subset of 79 tissue samples by immunohistochemistry.
The deletion was confirmed in 24% of all malignant tumors, detected in only 7.5% of the benign tumors and was not present in any normal mammary tissue sample. The subgroup of solid carcinomas (n = 9) showed the highest frequency of the deletion (67%) and those malignomas without microscopical high fraction of benign tissue (n = 71) had a 32% frequency (p<0.01 vs. benign samples). The Ki-67 score was found to be significantly higher (p<0.05) in the PFDN5-deleted group compared to malignant tumors without the deletion.
A somatic deletion of the PFDN5 gene is recurrently present in canine mammary cancer, supporting a potential role in carcinogenesis. The association of this deletion with higher Ki-67 indicates an increased proliferation rate and thus a link to tumor aggressiveness can be hypothesized. The confirmation of earlier results warrants further studies on PFDN5 as cancer-driver gene.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0131280</identifier><identifier>PMID: 26132936</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Benign ; Breast cancer ; c-Myc protein ; Cancer ; Cancer genetics ; Carcinogenesis ; Carcinogens ; Carcinoma ; Cell growth ; Chromosome deletion ; Chromosomes ; Copy number ; Deoxyribonucleic acid ; DNA ; Dogs ; Female ; Gene Deletion ; Genes ; Genomes ; Hematology ; Immunohistochemistry ; Leukocytes ; Mammary Neoplasms, Animal - genetics ; Mastectomy ; Medical research ; Molecular Chaperones - genetics ; Myc protein ; Oncology ; Palliative care ; Pathology ; Prevalence studies (Epidemiology) ; Protein Subunits - genetics ; Rodents ; Thyroid gland ; Tissues ; Tumor suppressor genes ; Tumors ; Veterinary medicine</subject><ispartof>PloS one, 2015-07, Vol.10 (7), p.e0131280</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Hennecke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Hennecke et al 2015 Hennecke et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-fe61dadd221a02fc76d1785cb22137ba3f2a63122e3f3a6fc11889508cbe99673</citedby><cites>FETCH-LOGICAL-c692t-fe61dadd221a02fc76d1785cb22137ba3f2a63122e3f3a6fc11889508cbe99673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1692759580/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1692759580?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26132936$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Liu, Xuefeng</contributor><creatorcontrib>Hennecke, Silvia</creatorcontrib><creatorcontrib>Beck, Julia</creatorcontrib><creatorcontrib>Bornemann-Kolatzki, Kirsten</creatorcontrib><creatorcontrib>Neumann, Stephan</creatorcontrib><creatorcontrib>Murua Escobar, Hugo</creatorcontrib><creatorcontrib>Nolte, Ingo</creatorcontrib><creatorcontrib>Hammer, Susanne Conradine</creatorcontrib><creatorcontrib>Hewicker-Trautwein, Marion</creatorcontrib><creatorcontrib>Junginger, Johannes</creatorcontrib><creatorcontrib>Kaup, Franz-Josef</creatorcontrib><creatorcontrib>Brenig, Bertram</creatorcontrib><creatorcontrib>Schütz, Ekkehard</creatorcontrib><title>Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>A somatic deletion at the proximal end of canine chromosome 27 (CFA27) was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors.
Droplet digital PCR for PFDN5 was performed in DNA from 102 malignant, 40 benign mammary tumors/dysplasias, 11 non-neoplastic mammary tissues and each corresponding genomic DNA from leukocytes. The copy number of PFDN5 was normalized to a reference amplicon on canine chromosome 32 (CFA32). Z-scores were calculated, based on Gaussian distributed normalized PFDN5 copy numbers of the leukocyte DNA. Z-scores ≤ -3.0 in tissue were considered as being indicative of the PFDN5 deletion and called as such. The Ki-67 proliferation index was assessed in a subset of 79 tissue samples by immunohistochemistry.
The deletion was confirmed in 24% of all malignant tumors, detected in only 7.5% of the benign tumors and was not present in any normal mammary tissue sample. The subgroup of solid carcinomas (n = 9) showed the highest frequency of the deletion (67%) and those malignomas without microscopical high fraction of benign tissue (n = 71) had a 32% frequency (p<0.01 vs. benign samples). The Ki-67 score was found to be significantly higher (p<0.05) in the PFDN5-deleted group compared to malignant tumors without the deletion.
A somatic deletion of the PFDN5 gene is recurrently present in canine mammary cancer, supporting a potential role in carcinogenesis. The association of this deletion with higher Ki-67 indicates an increased proliferation rate and thus a link to tumor aggressiveness can be hypothesized. The confirmation of earlier results warrants further studies on PFDN5 as cancer-driver gene.</description><subject>Animals</subject><subject>Benign</subject><subject>Breast cancer</subject><subject>c-Myc protein</subject><subject>Cancer</subject><subject>Cancer genetics</subject><subject>Carcinogenesis</subject><subject>Carcinogens</subject><subject>Carcinoma</subject><subject>Cell growth</subject><subject>Chromosome deletion</subject><subject>Chromosomes</subject><subject>Copy number</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Dogs</subject><subject>Female</subject><subject>Gene Deletion</subject><subject>Genes</subject><subject>Genomes</subject><subject>Hematology</subject><subject>Immunohistochemistry</subject><subject>Leukocytes</subject><subject>Mammary Neoplasms, Animal - genetics</subject><subject>Mastectomy</subject><subject>Medical research</subject><subject>Molecular Chaperones - genetics</subject><subject>Myc protein</subject><subject>Oncology</subject><subject>Palliative care</subject><subject>Pathology</subject><subject>Prevalence studies (Epidemiology)</subject><subject>Protein Subunits - genetics</subject><subject>Rodents</subject><subject>Thyroid gland</subject><subject>Tissues</subject><subject>Tumor suppressor genes</subject><subject>Tumors</subject><subject>Veterinary medicine</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl-L1DAUxYso7jr6DUQLguDDjPnTpOmLsIy6DoysuKuvIU1vZjK0ydiki357M053mYKC5KHh3N89vb09WfYcowWmJX6780PvVLvYewcLhCkmAj3IznFFyZwTRB-e3M-yJyHsEGJUcP44OyMcU1JRfp6tv_Rwq1pwGnJv8riFPCnGt411-fVQD87GnOWX4CB_Dy1E612eSkvlbJI-q65T_a_8Zuh8H55mj4xqAzwbn7Ps28cPN8tP8_XV5Wp5sZ5rXpE4N8Bxo5qGEKwQMbrkDS4F03USaFkraoji6XsIUEMVNxpjISqGhK6hqnhJZ9nLo---9UGOiwgSJ_eSVUygRKyOROPVTu57e5hSemXlH8H3G6n6aHULsiTUQJqB0kIVtaiEQZgRzhCqS2YQTV7vxrcNdQeNBhd71U5MpxVnt3Ljb2VRiKqgh3FfjQa9_zFAiP8YeaQ26XdI64xPZrqzQcuLgiBcFCy5zbLFX6h0GuisTlEwNumThjeThsRE-Bk3aghBrq6__j979X3Kvj5ht6DauA2-HQ4BCVOwOIK69yGkbN1vDiN5SPLdNuQhyXJMcmp7cbr1-6a76NLfNH7rvQ</recordid><startdate>20150701</startdate><enddate>20150701</enddate><creator>Hennecke, Silvia</creator><creator>Beck, Julia</creator><creator>Bornemann-Kolatzki, Kirsten</creator><creator>Neumann, Stephan</creator><creator>Murua Escobar, Hugo</creator><creator>Nolte, Ingo</creator><creator>Hammer, Susanne Conradine</creator><creator>Hewicker-Trautwein, Marion</creator><creator>Junginger, Johannes</creator><creator>Kaup, Franz-Josef</creator><creator>Brenig, Bertram</creator><creator>Schütz, Ekkehard</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150701</creationdate><title>Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors</title><author>Hennecke, Silvia ; Beck, Julia ; Bornemann-Kolatzki, Kirsten ; Neumann, Stephan ; Murua Escobar, Hugo ; Nolte, Ingo ; Hammer, Susanne Conradine ; Hewicker-Trautwein, Marion ; Junginger, Johannes ; Kaup, Franz-Josef ; Brenig, Bertram ; Schütz, Ekkehard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-fe61dadd221a02fc76d1785cb22137ba3f2a63122e3f3a6fc11889508cbe99673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Benign</topic><topic>Breast cancer</topic><topic>c-Myc protein</topic><topic>Cancer</topic><topic>Cancer genetics</topic><topic>Carcinogenesis</topic><topic>Carcinogens</topic><topic>Carcinoma</topic><topic>Cell growth</topic><topic>Chromosome deletion</topic><topic>Chromosomes</topic><topic>Copy number</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Dogs</topic><topic>Female</topic><topic>Gene Deletion</topic><topic>Genes</topic><topic>Genomes</topic><topic>Hematology</topic><topic>Immunohistochemistry</topic><topic>Leukocytes</topic><topic>Mammary Neoplasms, Animal - genetics</topic><topic>Mastectomy</topic><topic>Medical research</topic><topic>Molecular Chaperones - genetics</topic><topic>Myc protein</topic><topic>Oncology</topic><topic>Palliative care</topic><topic>Pathology</topic><topic>Prevalence studies (Epidemiology)</topic><topic>Protein Subunits - genetics</topic><topic>Rodents</topic><topic>Thyroid gland</topic><topic>Tissues</topic><topic>Tumor suppressor genes</topic><topic>Tumors</topic><topic>Veterinary medicine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hennecke, Silvia</creatorcontrib><creatorcontrib>Beck, Julia</creatorcontrib><creatorcontrib>Bornemann-Kolatzki, Kirsten</creatorcontrib><creatorcontrib>Neumann, Stephan</creatorcontrib><creatorcontrib>Murua Escobar, Hugo</creatorcontrib><creatorcontrib>Nolte, Ingo</creatorcontrib><creatorcontrib>Hammer, Susanne Conradine</creatorcontrib><creatorcontrib>Hewicker-Trautwein, Marion</creatorcontrib><creatorcontrib>Junginger, Johannes</creatorcontrib><creatorcontrib>Kaup, Franz-Josef</creatorcontrib><creatorcontrib>Brenig, Bertram</creatorcontrib><creatorcontrib>Schütz, Ekkehard</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Science in Context</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Agriculture & Environmental Science Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors.
Droplet digital PCR for PFDN5 was performed in DNA from 102 malignant, 40 benign mammary tumors/dysplasias, 11 non-neoplastic mammary tissues and each corresponding genomic DNA from leukocytes. The copy number of PFDN5 was normalized to a reference amplicon on canine chromosome 32 (CFA32). Z-scores were calculated, based on Gaussian distributed normalized PFDN5 copy numbers of the leukocyte DNA. Z-scores ≤ -3.0 in tissue were considered as being indicative of the PFDN5 deletion and called as such. The Ki-67 proliferation index was assessed in a subset of 79 tissue samples by immunohistochemistry.
The deletion was confirmed in 24% of all malignant tumors, detected in only 7.5% of the benign tumors and was not present in any normal mammary tissue sample. The subgroup of solid carcinomas (n = 9) showed the highest frequency of the deletion (67%) and those malignomas without microscopical high fraction of benign tissue (n = 71) had a 32% frequency (p<0.01 vs. benign samples). The Ki-67 score was found to be significantly higher (p<0.05) in the PFDN5-deleted group compared to malignant tumors without the deletion.
A somatic deletion of the PFDN5 gene is recurrently present in canine mammary cancer, supporting a potential role in carcinogenesis. The association of this deletion with higher Ki-67 indicates an increased proliferation rate and thus a link to tumor aggressiveness can be hypothesized. The confirmation of earlier results warrants further studies on PFDN5 as cancer-driver gene.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26132936</pmid><doi>10.1371/journal.pone.0131280</doi><oa>free_for_read</oa></addata></record> |
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subjects | Animals Benign Breast cancer c-Myc protein Cancer Cancer genetics Carcinogenesis Carcinogens Carcinoma Cell growth Chromosome deletion Chromosomes Copy number Deoxyribonucleic acid DNA Dogs Female Gene Deletion Genes Genomes Hematology Immunohistochemistry Leukocytes Mammary Neoplasms, Animal - genetics Mastectomy Medical research Molecular Chaperones - genetics Myc protein Oncology Palliative care Pathology Prevalence studies (Epidemiology) Protein Subunits - genetics Rodents Thyroid gland Tissues Tumor suppressor genes Tumors Veterinary medicine |
title | Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T20%3A47%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Prevalence%20of%20the%20Prefoldin%20Subunit%205%20Gene%20Deletion%20in%20Canine%20Mammary%20Tumors&rft.jtitle=PloS%20one&rft.au=Hennecke,%20Silvia&rft.date=2015-07-01&rft.volume=10&rft.issue=7&rft.spage=e0131280&rft.pages=e0131280-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0131280&rft_dat=%3Cgale_plos_%3EA420144594%3C/gale_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c692t-fe61dadd221a02fc76d1785cb22137ba3f2a63122e3f3a6fc11889508cbe99673%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1692759580&rft_id=info:pmid/26132936&rft_galeid=A420144594&rfr_iscdi=true |