Fatty Acid Binding Protein 7 Regulates Phagocytosis and Cytokine Production in Kupffer Cells during Liver Injury
Kupffer cells (KCs) are involved in the progression of liver diseases such as hepatitis and liver cancer. Several members of the fatty acid binding proteins (FABPs) are expressed by tissue macrophages, and FABP7 is localized only in KCs. To clarify the role of FABP7 in the regulation of KC function,...
Gespeichert in:
| Veröffentlicht in: | The American journal of pathology 2014-09, Vol.184 (9), p.2505-2515 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2515 |
|---|---|
| container_issue | 9 |
| container_start_page | 2505 |
| container_title | The American journal of pathology |
| container_volume | 184 |
| creator | Miyazaki, Hirofumi Sawada, Tomoo Kiyohira, Miwa Yu, Zhiqian Nakamura, Keiji Yasumoto, Yuki Kagawa, Yoshiteru Ebrahimi, Majid Islam, Ariful Sharifi, Kazem Kawamura, Saki Kodama, Takanori Yamamoto, Yui Adachi, Yasuhiro Tokuda, Nobuko Terai, Shuji Sakaida, Isao Ishikawa, Toshizo Owada, Yuji |
| description | Kupffer cells (KCs) are involved in the progression of liver diseases such as hepatitis and liver cancer. Several members of the fatty acid binding proteins (FABPs) are expressed by tissue macrophages, and FABP7 is localized only in KCs. To clarify the role of FABP7 in the regulation of KC function, we evaluated pathological changes of Fabp7 knockout mice during carbon tetrachloride-induced liver injury. During liver injury in Fabp7 knockout mice, serum liver enzymes were increased, cytokine expression (tumor necrosis factor-α, monocyte chemoattractant protein-1, and transforming growth factor-β) was decreased in the liver, and the number of KCs in the liver necrotic area was significantly decreased. Interestingly, in the FABP7-deficient KCs, phagocytosis of apoptotic cells was impaired, and expression of the scavenger receptor CD36 was markedly decreased. In chronic liver injury, Fabp7 knockout mice showed less fibrogenic response to carbon tetrachloride compared with wild-type mice. Taken together, FABP7 is involved in the liver injury process through its regulation of KC phagocytic activity and cytokine production. Such modulation of KC function by FABP7 may provide a novel therapeutic approach to the treatment of liver diseases. |
| doi_str_mv | 10.1016/j.ajpath.2014.05.015 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1554942123</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0002944014003174</els_id><sourcerecordid>1554942123</sourcerecordid><originalsourceid>FETCH-LOGICAL-c483t-526f75b607b8af3959d19e96ded3501db12a42d00ffb1722d4f7f5143b6ae0b73</originalsourceid><addsrcrecordid>eNqFkU9v1DAQxS0EokvhGyDkI5eEsWMnmwtSWVGoWImKP2fLsSdbp1lnsZ1K-fY42sKBCyePrffeeH5DyGsGJQNWvxtKPZx0uis5MFGCLIHJJ2TDJJcFZy17SjYAwItWCLggL2Ic8rWutvCcXHAJgm2l3JDTtU5poVfGWfrBeev8gd6GKaHztKHf8DCPOmGkt3f6MJklTdFFqr2lu1zfO4-r2s4mucnT7Pkyn_oeA93hOEZq57AG7t1DfrrxwxyWl-RZr8eIrx7PS_Lz-uOP3edi__XTze5qXxixrVIhed03squh6ba6r1rZWtZiW1u0lQRmO8a14Bag7zvWcG5F3_SSiaqrNULXVJfk7Tn3FKZfM8akji6a_CvtcZqjYlKKVnDGqywVZ6kJU4wBe3UK7qjDohiolbUa1Jm1WlkrkCqzzrY3jx3m7oj2r-kP3Cx4fxZgnvPBYVDROPQGrQtokrKT-1-HfwPM6LwzerzHBeMwzcFnhoqpyBWo7-u-13UzAVCxRlS_AVKVptI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1554942123</pqid></control><display><type>article</type><title>Fatty Acid Binding Protein 7 Regulates Phagocytosis and Cytokine Production in Kupffer Cells during Liver Injury</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Miyazaki, Hirofumi ; Sawada, Tomoo ; Kiyohira, Miwa ; Yu, Zhiqian ; Nakamura, Keiji ; Yasumoto, Yuki ; Kagawa, Yoshiteru ; Ebrahimi, Majid ; Islam, Ariful ; Sharifi, Kazem ; Kawamura, Saki ; Kodama, Takanori ; Yamamoto, Yui ; Adachi, Yasuhiro ; Tokuda, Nobuko ; Terai, Shuji ; Sakaida, Isao ; Ishikawa, Toshizo ; Owada, Yuji</creator><creatorcontrib>Miyazaki, Hirofumi ; Sawada, Tomoo ; Kiyohira, Miwa ; Yu, Zhiqian ; Nakamura, Keiji ; Yasumoto, Yuki ; Kagawa, Yoshiteru ; Ebrahimi, Majid ; Islam, Ariful ; Sharifi, Kazem ; Kawamura, Saki ; Kodama, Takanori ; Yamamoto, Yui ; Adachi, Yasuhiro ; Tokuda, Nobuko ; Terai, Shuji ; Sakaida, Isao ; Ishikawa, Toshizo ; Owada, Yuji</creatorcontrib><description>Kupffer cells (KCs) are involved in the progression of liver diseases such as hepatitis and liver cancer. Several members of the fatty acid binding proteins (FABPs) are expressed by tissue macrophages, and FABP7 is localized only in KCs. To clarify the role of FABP7 in the regulation of KC function, we evaluated pathological changes of Fabp7 knockout mice during carbon tetrachloride-induced liver injury. During liver injury in Fabp7 knockout mice, serum liver enzymes were increased, cytokine expression (tumor necrosis factor-α, monocyte chemoattractant protein-1, and transforming growth factor-β) was decreased in the liver, and the number of KCs in the liver necrotic area was significantly decreased. Interestingly, in the FABP7-deficient KCs, phagocytosis of apoptotic cells was impaired, and expression of the scavenger receptor CD36 was markedly decreased. In chronic liver injury, Fabp7 knockout mice showed less fibrogenic response to carbon tetrachloride compared with wild-type mice. Taken together, FABP7 is involved in the liver injury process through its regulation of KC phagocytic activity and cytokine production. Such modulation of KC function by FABP7 may provide a novel therapeutic approach to the treatment of liver diseases.</description><identifier>ISSN: 0002-9440</identifier><identifier>EISSN: 1525-2191</identifier><identifier>DOI: 10.1016/j.ajpath.2014.05.015</identifier><identifier>PMID: 25041855</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Blotting, Western ; Carbon Tetrachloride - toxicity ; Chemical and Drug Induced Liver Injury - metabolism ; Chemical and Drug Induced Liver Injury - pathology ; Cytokines - biosynthesis ; Enzyme-Linked Immunosorbent Assay ; Fatty Acid-Binding Protein 7 ; Fatty Acid-Binding Proteins - metabolism ; Flow Cytometry ; Fluorescent Antibody Technique ; Immunohistochemistry ; In Situ Nick-End Labeling ; Kupffer Cells - metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Tissue Proteins - metabolism ; Pathology ; Phagocytosis - physiology ; Reverse Transcriptase Polymerase Chain Reaction</subject><ispartof>The American journal of pathology, 2014-09, Vol.184 (9), p.2505-2515</ispartof><rights>American Society for Investigative Pathology</rights><rights>2014 American Society for Investigative Pathology</rights><rights>Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-526f75b607b8af3959d19e96ded3501db12a42d00ffb1722d4f7f5143b6ae0b73</citedby><cites>FETCH-LOGICAL-c483t-526f75b607b8af3959d19e96ded3501db12a42d00ffb1722d4f7f5143b6ae0b73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0002944014003174$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25041855$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miyazaki, Hirofumi</creatorcontrib><creatorcontrib>Sawada, Tomoo</creatorcontrib><creatorcontrib>Kiyohira, Miwa</creatorcontrib><creatorcontrib>Yu, Zhiqian</creatorcontrib><creatorcontrib>Nakamura, Keiji</creatorcontrib><creatorcontrib>Yasumoto, Yuki</creatorcontrib><creatorcontrib>Kagawa, Yoshiteru</creatorcontrib><creatorcontrib>Ebrahimi, Majid</creatorcontrib><creatorcontrib>Islam, Ariful</creatorcontrib><creatorcontrib>Sharifi, Kazem</creatorcontrib><creatorcontrib>Kawamura, Saki</creatorcontrib><creatorcontrib>Kodama, Takanori</creatorcontrib><creatorcontrib>Yamamoto, Yui</creatorcontrib><creatorcontrib>Adachi, Yasuhiro</creatorcontrib><creatorcontrib>Tokuda, Nobuko</creatorcontrib><creatorcontrib>Terai, Shuji</creatorcontrib><creatorcontrib>Sakaida, Isao</creatorcontrib><creatorcontrib>Ishikawa, Toshizo</creatorcontrib><creatorcontrib>Owada, Yuji</creatorcontrib><title>Fatty Acid Binding Protein 7 Regulates Phagocytosis and Cytokine Production in Kupffer Cells during Liver Injury</title><title>The American journal of pathology</title><addtitle>Am J Pathol</addtitle><description>Kupffer cells (KCs) are involved in the progression of liver diseases such as hepatitis and liver cancer. Several members of the fatty acid binding proteins (FABPs) are expressed by tissue macrophages, and FABP7 is localized only in KCs. To clarify the role of FABP7 in the regulation of KC function, we evaluated pathological changes of Fabp7 knockout mice during carbon tetrachloride-induced liver injury. During liver injury in Fabp7 knockout mice, serum liver enzymes were increased, cytokine expression (tumor necrosis factor-α, monocyte chemoattractant protein-1, and transforming growth factor-β) was decreased in the liver, and the number of KCs in the liver necrotic area was significantly decreased. Interestingly, in the FABP7-deficient KCs, phagocytosis of apoptotic cells was impaired, and expression of the scavenger receptor CD36 was markedly decreased. In chronic liver injury, Fabp7 knockout mice showed less fibrogenic response to carbon tetrachloride compared with wild-type mice. Taken together, FABP7 is involved in the liver injury process through its regulation of KC phagocytic activity and cytokine production. Such modulation of KC function by FABP7 may provide a novel therapeutic approach to the treatment of liver diseases.</description><subject>Animals</subject><subject>Blotting, Western</subject><subject>Carbon Tetrachloride - toxicity</subject><subject>Chemical and Drug Induced Liver Injury - metabolism</subject><subject>Chemical and Drug Induced Liver Injury - pathology</subject><subject>Cytokines - biosynthesis</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Fatty Acid-Binding Protein 7</subject><subject>Fatty Acid-Binding Proteins - metabolism</subject><subject>Flow Cytometry</subject><subject>Fluorescent Antibody Technique</subject><subject>Immunohistochemistry</subject><subject>In Situ Nick-End Labeling</subject><subject>Kupffer Cells - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Pathology</subject><subject>Phagocytosis - physiology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><issn>0002-9440</issn><issn>1525-2191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAQxS0EokvhGyDkI5eEsWMnmwtSWVGoWImKP2fLsSdbp1lnsZ1K-fY42sKBCyePrffeeH5DyGsGJQNWvxtKPZx0uis5MFGCLIHJJ2TDJJcFZy17SjYAwItWCLggL2Ic8rWutvCcXHAJgm2l3JDTtU5poVfGWfrBeev8gd6GKaHztKHf8DCPOmGkt3f6MJklTdFFqr2lu1zfO4-r2s4mucnT7Pkyn_oeA93hOEZq57AG7t1DfrrxwxyWl-RZr8eIrx7PS_Lz-uOP3edi__XTze5qXxixrVIhed03squh6ba6r1rZWtZiW1u0lQRmO8a14Bag7zvWcG5F3_SSiaqrNULXVJfk7Tn3FKZfM8akji6a_CvtcZqjYlKKVnDGqywVZ6kJU4wBe3UK7qjDohiolbUa1Jm1WlkrkCqzzrY3jx3m7oj2r-kP3Cx4fxZgnvPBYVDROPQGrQtokrKT-1-HfwPM6LwzerzHBeMwzcFnhoqpyBWo7-u-13UzAVCxRlS_AVKVptI</recordid><startdate>20140901</startdate><enddate>20140901</enddate><creator>Miyazaki, Hirofumi</creator><creator>Sawada, Tomoo</creator><creator>Kiyohira, Miwa</creator><creator>Yu, Zhiqian</creator><creator>Nakamura, Keiji</creator><creator>Yasumoto, Yuki</creator><creator>Kagawa, Yoshiteru</creator><creator>Ebrahimi, Majid</creator><creator>Islam, Ariful</creator><creator>Sharifi, Kazem</creator><creator>Kawamura, Saki</creator><creator>Kodama, Takanori</creator><creator>Yamamoto, Yui</creator><creator>Adachi, Yasuhiro</creator><creator>Tokuda, Nobuko</creator><creator>Terai, Shuji</creator><creator>Sakaida, Isao</creator><creator>Ishikawa, Toshizo</creator><creator>Owada, Yuji</creator><general>Elsevier 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>7X8</scope></search><sort><creationdate>20140901</creationdate><title>Fatty Acid Binding Protein 7 Regulates Phagocytosis and Cytokine Production in Kupffer Cells during Liver Injury</title><author>Miyazaki, Hirofumi ; Sawada, Tomoo ; Kiyohira, Miwa ; Yu, Zhiqian ; Nakamura, Keiji ; Yasumoto, Yuki ; Kagawa, Yoshiteru ; Ebrahimi, Majid ; Islam, Ariful ; Sharifi, Kazem ; Kawamura, Saki ; Kodama, Takanori ; Yamamoto, Yui ; Adachi, Yasuhiro ; Tokuda, Nobuko ; Terai, Shuji ; Sakaida, Isao ; Ishikawa, Toshizo ; Owada, Yuji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-526f75b607b8af3959d19e96ded3501db12a42d00ffb1722d4f7f5143b6ae0b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Blotting, Western</topic><topic>Carbon Tetrachloride - toxicity</topic><topic>Chemical and Drug Induced Liver Injury - metabolism</topic><topic>Chemical and Drug Induced Liver Injury - pathology</topic><topic>Cytokines - biosynthesis</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Fatty Acid-Binding Protein 7</topic><topic>Fatty Acid-Binding Proteins - metabolism</topic><topic>Flow Cytometry</topic><topic>Fluorescent Antibody Technique</topic><topic>Immunohistochemistry</topic><topic>In Situ Nick-End Labeling</topic><topic>Kupffer Cells - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Pathology</topic><topic>Phagocytosis - physiology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miyazaki, Hirofumi</creatorcontrib><creatorcontrib>Sawada, Tomoo</creatorcontrib><creatorcontrib>Kiyohira, Miwa</creatorcontrib><creatorcontrib>Yu, Zhiqian</creatorcontrib><creatorcontrib>Nakamura, Keiji</creatorcontrib><creatorcontrib>Yasumoto, Yuki</creatorcontrib><creatorcontrib>Kagawa, Yoshiteru</creatorcontrib><creatorcontrib>Ebrahimi, Majid</creatorcontrib><creatorcontrib>Islam, Ariful</creatorcontrib><creatorcontrib>Sharifi, Kazem</creatorcontrib><creatorcontrib>Kawamura, Saki</creatorcontrib><creatorcontrib>Kodama, Takanori</creatorcontrib><creatorcontrib>Yamamoto, Yui</creatorcontrib><creatorcontrib>Adachi, Yasuhiro</creatorcontrib><creatorcontrib>Tokuda, Nobuko</creatorcontrib><creatorcontrib>Terai, Shuji</creatorcontrib><creatorcontrib>Sakaida, Isao</creatorcontrib><creatorcontrib>Ishikawa, Toshizo</creatorcontrib><creatorcontrib>Owada, Yuji</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 American journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miyazaki, Hirofumi</au><au>Sawada, Tomoo</au><au>Kiyohira, Miwa</au><au>Yu, Zhiqian</au><au>Nakamura, Keiji</au><au>Yasumoto, Yuki</au><au>Kagawa, Yoshiteru</au><au>Ebrahimi, Majid</au><au>Islam, Ariful</au><au>Sharifi, Kazem</au><au>Kawamura, Saki</au><au>Kodama, Takanori</au><au>Yamamoto, Yui</au><au>Adachi, Yasuhiro</au><au>Tokuda, Nobuko</au><au>Terai, Shuji</au><au>Sakaida, Isao</au><au>Ishikawa, Toshizo</au><au>Owada, Yuji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fatty Acid Binding Protein 7 Regulates Phagocytosis and Cytokine Production in Kupffer Cells during Liver Injury</atitle><jtitle>The American journal of pathology</jtitle><addtitle>Am J Pathol</addtitle><date>2014-09-01</date><risdate>2014</risdate><volume>184</volume><issue>9</issue><spage>2505</spage><epage>2515</epage><pages>2505-2515</pages><issn>0002-9440</issn><eissn>1525-2191</eissn><abstract>Kupffer cells (KCs) are involved in the progression of liver diseases such as hepatitis and liver cancer. Several members of the fatty acid binding proteins (FABPs) are expressed by tissue macrophages, and FABP7 is localized only in KCs. To clarify the role of FABP7 in the regulation of KC function, we evaluated pathological changes of Fabp7 knockout mice during carbon tetrachloride-induced liver injury. During liver injury in Fabp7 knockout mice, serum liver enzymes were increased, cytokine expression (tumor necrosis factor-α, monocyte chemoattractant protein-1, and transforming growth factor-β) was decreased in the liver, and the number of KCs in the liver necrotic area was significantly decreased. Interestingly, in the FABP7-deficient KCs, phagocytosis of apoptotic cells was impaired, and expression of the scavenger receptor CD36 was markedly decreased. In chronic liver injury, Fabp7 knockout mice showed less fibrogenic response to carbon tetrachloride compared with wild-type mice. Taken together, FABP7 is involved in the liver injury process through its regulation of KC phagocytic activity and cytokine production. Such modulation of KC function by FABP7 may provide a novel therapeutic approach to the treatment of liver diseases.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25041855</pmid><doi>10.1016/j.ajpath.2014.05.015</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0002-9440 |
| ispartof | The American journal of pathology, 2014-09, Vol.184 (9), p.2505-2515 |
| issn | 0002-9440 1525-2191 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1554942123 |
| source | MEDLINE; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Blotting, Western Carbon Tetrachloride - toxicity Chemical and Drug Induced Liver Injury - metabolism Chemical and Drug Induced Liver Injury - pathology Cytokines - biosynthesis Enzyme-Linked Immunosorbent Assay Fatty Acid-Binding Protein 7 Fatty Acid-Binding Proteins - metabolism Flow Cytometry Fluorescent Antibody Technique Immunohistochemistry In Situ Nick-End Labeling Kupffer Cells - metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Nerve Tissue Proteins - metabolism Pathology Phagocytosis - physiology Reverse Transcriptase Polymerase Chain Reaction |
| title | Fatty Acid Binding Protein 7 Regulates Phagocytosis and Cytokine Production in Kupffer Cells during Liver Injury |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T04%3A34%3A56IST&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=Fatty%20Acid%20Binding%20Protein%207%20Regulates%20Phagocytosis%20and%20Cytokine%20Production%20in%20Kupffer%20Cells%20during%20Liver%20Injury&rft.jtitle=The%20American%20journal%20of%20pathology&rft.au=Miyazaki,%20Hirofumi&rft.date=2014-09-01&rft.volume=184&rft.issue=9&rft.spage=2505&rft.epage=2515&rft.pages=2505-2515&rft.issn=0002-9440&rft.eissn=1525-2191&rft_id=info:doi/10.1016/j.ajpath.2014.05.015&rft_dat=%3Cproquest_cross%3E1554942123%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=1554942123&rft_id=info:pmid/25041855&rft_els_id=1_s2_0_S0002944014003174&rfr_iscdi=true |