Oxidative Stress and Cellular Response to Doxorubicin: A Common Factor in the Complex Milieu of Anthracycline Cardiotoxicity
The production of reactive species is a core of the redox cycling profile of anthracyclines. However, these molecular characteristics can be viewed as a double-edged sword acting not only on neoplastic cells but also on multiple cellular targets throughout the body. This phenomenon translates into a...
Gespeichert in:
| Veröffentlicht in: | Oxidative medicine and cellular longevity 2017-01, Vol.2017 (2017), p.1-13 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 13 |
|---|---|
| container_issue | 2017 |
| container_start_page | 1 |
| container_title | Oxidative medicine and cellular longevity |
| container_volume | 2017 |
| creator | Urbanek, Konrad Naviglio, Silvio Rossi, Francesco Quaini, F. Illiano, Michela Prezioso, Lucia Sapio, Luigi De Angelis, A. Cappetta, Donato Berrino, L. |
| description | The production of reactive species is a core of the redox cycling profile of anthracyclines. However, these molecular characteristics can be viewed as a double-edged sword acting not only on neoplastic cells but also on multiple cellular targets throughout the body. This phenomenon translates into anthracycline cardiotoxicity that is a serious problem in the growing population of paediatric and adult cancer survivors. Therefore, better understanding of cellular processes that operate within but also go beyond cardiomyocytes is a necessary step to develop more effective tools for the prevention and treatment of progressive and often severe cardiomyopathy experienced by otherwise successfully treated oncologic patients. In this review, we focus on oxidative stress-triggered cellular events such as DNA damage, senescence, and cell death implicated in anthracycline cardiovascular toxicity. The involvement of progenitor cells of cardiac and extracardiac origin as well as different cardiac cell types is discussed, pointing to molecular signals that impact on cell longevity and functional competence. |
| doi_str_mv | 10.1155/2017/1521020 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5664340</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A555850384</galeid><sourcerecordid>A555850384</sourcerecordid><originalsourceid>FETCH-LOGICAL-c565t-2eddc0338c87907a7361a6195e94fbf95e9bc3c378b5be3b117fcb7d753bb4f03</originalsourceid><addsrcrecordid>eNqNkcuLFDEQhxtR3IfePEvAi7COm0en0_EgDKOrwsqCj3NI0tU7WXqS2SS9zoB_vGlmnFVPniqkPr5U5VdVzwh-TQjn5xQTcU44JZjiB9UxkTWdYSnrh4czxkfVSUo3GDeM1uRxdUQlaQmh9Lj6ebVxnc7uDtDXHCElpH2HFjAM46Aj-gJpHXwClAN6FzYhjsZZ59-gOVqE1Sp4dKFtDhE5j_ISpsv1ABv02Q0ORhR6NPd5GbXd2sH50texcyGHTbHk7ZPqUa-HBE_39bT6fvH-2-Lj7PLqw6fF_HJmecPzjELXWcxYa1shsdCCNUQ3RHKQdW_6qRrLLBOt4QaYIUT01ohOcGZM3WN2Wr3dedejWUFnweeoB7WObqXjVgXt1N8d75bqOtwp3jQ1qyfBy70ghtsRUlYrl2z5JO0hjEkR2UhJSwBtQV_8g96EMfqyXqG4IBLXQt5T13oA5Xwfyrt2kqo557zlmLV1oV7tKBtDShH6w8gEqyl8NYWv9uEX_Pmfax7g32kX4GwHLJ3v9A_3nzooDPT6niayTNewX8_ywSs</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1957190479</pqid></control><display><type>article</type><title>Oxidative Stress and Cellular Response to Doxorubicin: A Common Factor in the Complex Milieu of Anthracycline Cardiotoxicity</title><source>MEDLINE</source><source>Wiley-Blackwell Open Access Titles</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>PubMed Central Open Access</source><creator>Urbanek, Konrad ; Naviglio, Silvio ; Rossi, Francesco ; Quaini, F. ; Illiano, Michela ; Prezioso, Lucia ; Sapio, Luigi ; De Angelis, A. ; Cappetta, Donato ; Berrino, L.</creator><contributor>Ameri, Pietro</contributor><creatorcontrib>Urbanek, Konrad ; Naviglio, Silvio ; Rossi, Francesco ; Quaini, F. ; Illiano, Michela ; Prezioso, Lucia ; Sapio, Luigi ; De Angelis, A. ; Cappetta, Donato ; Berrino, L. ; Ameri, Pietro</creatorcontrib><description>The production of reactive species is a core of the redox cycling profile of anthracyclines. However, these molecular characteristics can be viewed as a double-edged sword acting not only on neoplastic cells but also on multiple cellular targets throughout the body. This phenomenon translates into anthracycline cardiotoxicity that is a serious problem in the growing population of paediatric and adult cancer survivors. Therefore, better understanding of cellular processes that operate within but also go beyond cardiomyocytes is a necessary step to develop more effective tools for the prevention and treatment of progressive and often severe cardiomyopathy experienced by otherwise successfully treated oncologic patients. In this review, we focus on oxidative stress-triggered cellular events such as DNA damage, senescence, and cell death implicated in anthracycline cardiovascular toxicity. The involvement of progenitor cells of cardiac and extracardiac origin as well as different cardiac cell types is discussed, pointing to molecular signals that impact on cell longevity and functional competence.</description><identifier>ISSN: 1942-0900</identifier><identifier>ISSN: 1942-0994</identifier><identifier>EISSN: 1942-0994</identifier><identifier>DOI: 10.1155/2017/1521020</identifier><identifier>PMID: 29181122</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Anthracyclines - adverse effects ; Antibiotics, Antineoplastic - pharmacology ; Antibiotics, Antineoplastic - therapeutic use ; Cancer ; Cardiomyocytes ; Cardiomyopathy ; Cardiotoxicity - drug therapy ; Doxorubicin ; Doxorubicin - pharmacology ; Doxorubicin - therapeutic use ; Enzymes ; Humans ; Hydrogen peroxide ; Mitochondria ; Oxidative stress ; Oxidative Stress - drug effects ; Review ; Signal transduction ; Toxicity</subject><ispartof>Oxidative medicine and cellular longevity, 2017-01, Vol.2017 (2017), p.1-13</ispartof><rights>Copyright © 2017 Donato Cappetta et al.</rights><rights>COPYRIGHT 2017 John Wiley & Sons, Inc.</rights><rights>Copyright © 2017 Donato Cappetta et al.; This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2017 Donato Cappetta et al. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c565t-2eddc0338c87907a7361a6195e94fbf95e9bc3c378b5be3b117fcb7d753bb4f03</citedby><cites>FETCH-LOGICAL-c565t-2eddc0338c87907a7361a6195e94fbf95e9bc3c378b5be3b117fcb7d753bb4f03</cites><orcidid>0000-0001-8469-3403 ; 0000-0003-1771-8265 ; 0000-0001-6359-0974</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664340/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664340/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29181122$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ameri, Pietro</contributor><creatorcontrib>Urbanek, Konrad</creatorcontrib><creatorcontrib>Naviglio, Silvio</creatorcontrib><creatorcontrib>Rossi, Francesco</creatorcontrib><creatorcontrib>Quaini, F.</creatorcontrib><creatorcontrib>Illiano, Michela</creatorcontrib><creatorcontrib>Prezioso, Lucia</creatorcontrib><creatorcontrib>Sapio, Luigi</creatorcontrib><creatorcontrib>De Angelis, A.</creatorcontrib><creatorcontrib>Cappetta, Donato</creatorcontrib><creatorcontrib>Berrino, L.</creatorcontrib><title>Oxidative Stress and Cellular Response to Doxorubicin: A Common Factor in the Complex Milieu of Anthracycline Cardiotoxicity</title><title>Oxidative medicine and cellular longevity</title><addtitle>Oxid Med Cell Longev</addtitle><description>The production of reactive species is a core of the redox cycling profile of anthracyclines. However, these molecular characteristics can be viewed as a double-edged sword acting not only on neoplastic cells but also on multiple cellular targets throughout the body. This phenomenon translates into anthracycline cardiotoxicity that is a serious problem in the growing population of paediatric and adult cancer survivors. Therefore, better understanding of cellular processes that operate within but also go beyond cardiomyocytes is a necessary step to develop more effective tools for the prevention and treatment of progressive and often severe cardiomyopathy experienced by otherwise successfully treated oncologic patients. In this review, we focus on oxidative stress-triggered cellular events such as DNA damage, senescence, and cell death implicated in anthracycline cardiovascular toxicity. The involvement of progenitor cells of cardiac and extracardiac origin as well as different cardiac cell types is discussed, pointing to molecular signals that impact on cell longevity and functional competence.</description><subject>Anthracyclines - adverse effects</subject><subject>Antibiotics, Antineoplastic - pharmacology</subject><subject>Antibiotics, Antineoplastic - therapeutic use</subject><subject>Cancer</subject><subject>Cardiomyocytes</subject><subject>Cardiomyopathy</subject><subject>Cardiotoxicity - drug therapy</subject><subject>Doxorubicin</subject><subject>Doxorubicin - pharmacology</subject><subject>Doxorubicin - therapeutic use</subject><subject>Enzymes</subject><subject>Humans</subject><subject>Hydrogen peroxide</subject><subject>Mitochondria</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Review</subject><subject>Signal transduction</subject><subject>Toxicity</subject><issn>1942-0900</issn><issn>1942-0994</issn><issn>1942-0994</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkcuLFDEQhxtR3IfePEvAi7COm0en0_EgDKOrwsqCj3NI0tU7WXqS2SS9zoB_vGlmnFVPniqkPr5U5VdVzwh-TQjn5xQTcU44JZjiB9UxkTWdYSnrh4czxkfVSUo3GDeM1uRxdUQlaQmh9Lj6ebVxnc7uDtDXHCElpH2HFjAM46Aj-gJpHXwClAN6FzYhjsZZ59-gOVqE1Sp4dKFtDhE5j_ISpsv1ABv02Q0ORhR6NPd5GbXd2sH50texcyGHTbHk7ZPqUa-HBE_39bT6fvH-2-Lj7PLqw6fF_HJmecPzjELXWcxYa1shsdCCNUQ3RHKQdW_6qRrLLBOt4QaYIUT01ohOcGZM3WN2Wr3dedejWUFnweeoB7WObqXjVgXt1N8d75bqOtwp3jQ1qyfBy70ghtsRUlYrl2z5JO0hjEkR2UhJSwBtQV_8g96EMfqyXqG4IBLXQt5T13oA5Xwfyrt2kqo557zlmLV1oV7tKBtDShH6w8gEqyl8NYWv9uEX_Pmfax7g32kX4GwHLJ3v9A_3nzooDPT6niayTNewX8_ywSs</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>Urbanek, Konrad</creator><creator>Naviglio, Silvio</creator><creator>Rossi, Francesco</creator><creator>Quaini, F.</creator><creator>Illiano, Michela</creator><creator>Prezioso, Lucia</creator><creator>Sapio, Luigi</creator><creator>De Angelis, A.</creator><creator>Cappetta, Donato</creator><creator>Berrino, L.</creator><general>Hindawi Publishing Corporation</general><general>Hindawi</general><general>John Wiley & Sons, Inc</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</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>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8469-3403</orcidid><orcidid>https://orcid.org/0000-0003-1771-8265</orcidid><orcidid>https://orcid.org/0000-0001-6359-0974</orcidid></search><sort><creationdate>20170101</creationdate><title>Oxidative Stress and Cellular Response to Doxorubicin: A Common Factor in the Complex Milieu of Anthracycline Cardiotoxicity</title><author>Urbanek, Konrad ; Naviglio, Silvio ; Rossi, Francesco ; Quaini, F. ; Illiano, Michela ; Prezioso, Lucia ; Sapio, Luigi ; De Angelis, A. ; Cappetta, Donato ; Berrino, L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c565t-2eddc0338c87907a7361a6195e94fbf95e9bc3c378b5be3b117fcb7d753bb4f03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Anthracyclines - adverse effects</topic><topic>Antibiotics, Antineoplastic - pharmacology</topic><topic>Antibiotics, Antineoplastic - therapeutic use</topic><topic>Cancer</topic><topic>Cardiomyocytes</topic><topic>Cardiomyopathy</topic><topic>Cardiotoxicity - drug therapy</topic><topic>Doxorubicin</topic><topic>Doxorubicin - pharmacology</topic><topic>Doxorubicin - therapeutic use</topic><topic>Enzymes</topic><topic>Humans</topic><topic>Hydrogen peroxide</topic><topic>Mitochondria</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Review</topic><topic>Signal transduction</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Urbanek, Konrad</creatorcontrib><creatorcontrib>Naviglio, Silvio</creatorcontrib><creatorcontrib>Rossi, Francesco</creatorcontrib><creatorcontrib>Quaini, F.</creatorcontrib><creatorcontrib>Illiano, Michela</creatorcontrib><creatorcontrib>Prezioso, Lucia</creatorcontrib><creatorcontrib>Sapio, Luigi</creatorcontrib><creatorcontrib>De Angelis, A.</creatorcontrib><creatorcontrib>Cappetta, Donato</creatorcontrib><creatorcontrib>Berrino, L.</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical Periodicals</collection><collection>معرفة - المحتوى العربي الأكاديمي المتكامل - e-Marefa Academic Complete</collection><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</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>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</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>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</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 China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oxidative medicine and cellular longevity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Urbanek, Konrad</au><au>Naviglio, Silvio</au><au>Rossi, Francesco</au><au>Quaini, F.</au><au>Illiano, Michela</au><au>Prezioso, Lucia</au><au>Sapio, Luigi</au><au>De Angelis, A.</au><au>Cappetta, Donato</au><au>Berrino, L.</au><au>Ameri, Pietro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oxidative Stress and Cellular Response to Doxorubicin: A Common Factor in the Complex Milieu of Anthracycline Cardiotoxicity</atitle><jtitle>Oxidative medicine and cellular longevity</jtitle><addtitle>Oxid Med Cell Longev</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>2017</volume><issue>2017</issue><spage>1</spage><epage>13</epage><pages>1-13</pages><issn>1942-0900</issn><issn>1942-0994</issn><eissn>1942-0994</eissn><abstract>The production of reactive species is a core of the redox cycling profile of anthracyclines. However, these molecular characteristics can be viewed as a double-edged sword acting not only on neoplastic cells but also on multiple cellular targets throughout the body. This phenomenon translates into anthracycline cardiotoxicity that is a serious problem in the growing population of paediatric and adult cancer survivors. Therefore, better understanding of cellular processes that operate within but also go beyond cardiomyocytes is a necessary step to develop more effective tools for the prevention and treatment of progressive and often severe cardiomyopathy experienced by otherwise successfully treated oncologic patients. In this review, we focus on oxidative stress-triggered cellular events such as DNA damage, senescence, and cell death implicated in anthracycline cardiovascular toxicity. The involvement of progenitor cells of cardiac and extracardiac origin as well as different cardiac cell types is discussed, pointing to molecular signals that impact on cell longevity and functional competence.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>29181122</pmid><doi>10.1155/2017/1521020</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-8469-3403</orcidid><orcidid>https://orcid.org/0000-0003-1771-8265</orcidid><orcidid>https://orcid.org/0000-0001-6359-0974</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1942-0900 |
| ispartof | Oxidative medicine and cellular longevity, 2017-01, Vol.2017 (2017), p.1-13 |
| issn | 1942-0900 1942-0994 1942-0994 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5664340 |
| source | MEDLINE; Wiley-Blackwell Open Access Titles; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; PubMed Central Open Access |
| subjects | Anthracyclines - adverse effects Antibiotics, Antineoplastic - pharmacology Antibiotics, Antineoplastic - therapeutic use Cancer Cardiomyocytes Cardiomyopathy Cardiotoxicity - drug therapy Doxorubicin Doxorubicin - pharmacology Doxorubicin - therapeutic use Enzymes Humans Hydrogen peroxide Mitochondria Oxidative stress Oxidative Stress - drug effects Review Signal transduction Toxicity |
| title | Oxidative Stress and Cellular Response to Doxorubicin: A Common Factor in the Complex Milieu of Anthracycline Cardiotoxicity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T17%3A33%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Oxidative%20Stress%20and%20Cellular%20Response%20to%20Doxorubicin:%20A%20Common%20Factor%20in%20the%20Complex%20Milieu%20of%20Anthracycline%20Cardiotoxicity&rft.jtitle=Oxidative%20medicine%20and%20cellular%20longevity&rft.au=Urbanek,%20Konrad&rft.date=2017-01-01&rft.volume=2017&rft.issue=2017&rft.spage=1&rft.epage=13&rft.pages=1-13&rft.issn=1942-0900&rft.eissn=1942-0994&rft_id=info:doi/10.1155/2017/1521020&rft_dat=%3Cgale_pubme%3EA555850384%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1957190479&rft_id=info:pmid/29181122&rft_galeid=A555850384&rfr_iscdi=true |