On-Site Monitoring of Postoperative Bile Leakage Using Bilirubin-Inducible Fluorescent Protein
Background Bile leakage is the most common postoperative complication associated with hepatobiliary and pancreatic surgery. Until now, however, a rapid, accurate diagnostic method for monitoring intraoperative and postoperative bile leakage had not been established. Method Bilirubin levels in draine...
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creator | Kono, Yoshiharu Ishizawa, Takeaki Kokudo, Norihiro Kuriki, Yugo Iwatate, Ryu J. Kamiya, Mako Urano, Yasuteru Kumagai, Akiko Kurokawa, Hiroshi Miyawaki, Atsushi Hasegawa, Kiyoshi |
description | Background
Bile leakage is the most common postoperative complication associated with hepatobiliary and pancreatic surgery. Until now, however, a rapid, accurate diagnostic method for monitoring intraoperative and postoperative bile leakage had not been established.
Method
Bilirubin levels in drained abdominal fluids collected from 23 patients who had undergone hepatectomy (
n
= 22) or liver transplantation (
n
= 1) were measured using a microplate reader with excitation/emission wavelengths of 497/527 nm after applying 5 µM of UnaG to the samples. UnaG was also sprayed directly on hepatic raw surfaces in swine hepatectomy models to identify bile leaks by fluorescence imaging.
Results
The bilirubin levels measured by UnaG fluorescence imaging showed favorable correlations with the results of the conventional light-absorptiometric methods (indirect bilirubin: rs = 0.939,
p
|
doi_str_mv | 10.1007/s00268-020-05774-x |
format | Article |
fullrecord | <record><control><sourceid>proquest_webof</sourceid><recordid>TN_cdi_webofscience_primary_000567764100001CitationCount</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2441609946</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5915-c5028db4b47d1556b46abc91fee5e656757d0d55c59b63baf386eee7e33fd0a3</originalsourceid><addsrcrecordid>eNqNkk1v1DAQhiMEokvhD3BAkbggoYC_veFQia5YKFrUSi3ihuUkk8Ulay92Utp_z4Qsy8cB9WJbnucdz8zrLHtMyQtKiH6ZCGFqXhBGCiK1FsX1nWxGBWcF44zfzWaEK4Fnyg-yByldEkK1Iup-dsBZSUrK5Cz7fOqLc9dD_iF414fo_DoPbX4WUh-2EG3vriA_dh3kK7Bf7Rryj2lk8MrFoXK-OPHNULsKiWU3hAipBt_nZzH04PzD7F5ruwSPdvthdrF8c7F4V6xO354sXq-KWpZU4krYvKlEJXRDpVSVULaqS9oCSFBSaakb0kiJdKV4ZVs-VwCggfO2IZYfZkdT2u1QbaAZK4i2M9voNjbemGCd-Tvi3RezDldGyxLfV5jg2S5BDN8GSL3ZOGyk66yHMCTDhKCKlKUY0af_oJdhiB67Q0pTqUUpNVJsouoYUorQ7ouhxIzumck9g-6Zn-6ZaxQ9-bONveSXXQjMJ-A7VKFNtQNfwx4jhOCotBKYH71euB7tC34RBt-j9PntpUi_2tFo_c0tajef3p8fLzGmxyr5JE7b8T9B_D2h_zT_A3HE2Xw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2471574957</pqid></control><display><type>article</type><title>On-Site Monitoring of Postoperative Bile Leakage Using Bilirubin-Inducible Fluorescent Protein</title><source>Wiley-Blackwell Journals</source><source>Springer journals</source><source>Web of Science - Science Citation Index Expanded - 2020<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /></source><creator>Kono, Yoshiharu ; Ishizawa, Takeaki ; Kokudo, Norihiro ; Kuriki, Yugo ; Iwatate, Ryu J. ; Kamiya, Mako ; Urano, Yasuteru ; Kumagai, Akiko ; Kurokawa, Hiroshi ; Miyawaki, Atsushi ; Hasegawa, Kiyoshi</creator><creatorcontrib>Kono, Yoshiharu ; Ishizawa, Takeaki ; Kokudo, Norihiro ; Kuriki, Yugo ; Iwatate, Ryu J. ; Kamiya, Mako ; Urano, Yasuteru ; Kumagai, Akiko ; Kurokawa, Hiroshi ; Miyawaki, Atsushi ; Hasegawa, Kiyoshi</creatorcontrib><description>Background
Bile leakage is the most common postoperative complication associated with hepatobiliary and pancreatic surgery. Until now, however, a rapid, accurate diagnostic method for monitoring intraoperative and postoperative bile leakage had not been established.
Method
Bilirubin levels in drained abdominal fluids collected from 23 patients who had undergone hepatectomy (
n
= 22) or liver transplantation (
n
= 1) were measured using a microplate reader with excitation/emission wavelengths of 497/527 nm after applying 5 µM of UnaG to the samples. UnaG was also sprayed directly on hepatic raw surfaces in swine hepatectomy models to identify bile leaks by fluorescence imaging.
Results
The bilirubin levels measured by UnaG fluorescence imaging showed favorable correlations with the results of the conventional light-absorptiometric methods (indirect bilirubin: rs = 0.939,
p
< 0.001; direct bilirubin: rs = 0.929,
p
< 0.001). Approximate time required for bilirubin measurements with UnaG was 15 min, whereas it took about 40 min with the conventional method at a hospital laboratory. Following administration of UnaG on hepatic surfaces, the fluorescence imaging identified bile leaks not only on the resected specimens but also in the abdominal cavity of the swine hepatectomy models.
Conclusion
Fluorescence imaging techniques using UnaG may enable real-time identification of bile leaks during hepatectomy and on-site rapid diagnosis of bile leaks after surgery.</description><identifier>ISSN: 0364-2313</identifier><identifier>EISSN: 1432-2323</identifier><identifier>DOI: 10.1007/s00268-020-05774-x</identifier><identifier>PMID: 32909125</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Abdomen ; Abdominal Surgery ; Animal models ; Bile ; Bilirubin ; Cardiac Surgery ; Computational fluid dynamics ; Diagnostic systems ; Fluids ; Fluorescence ; General Surgery ; Hepatectomy ; Hospitals ; Imaging techniques ; Laboratory animals ; Leakage ; Leaks ; Life Sciences & Biomedicine ; Ligands ; Liver ; Liver transplantation ; Livestock ; Medical imaging ; Medical research ; Medicine ; Medicine & Public Health ; Methods ; Monitoring ; Onsite ; Original Scientific Report with Video ; Pancreas ; Postoperative period ; Proteins ; R&D ; Research & development ; Science & Technology ; Surgery ; Swine ; Thoracic Surgery ; Transplantation ; Vascular Surgery ; Wavelengths</subject><ispartof>World journal of surgery, 2020-12, Vol.44 (12), p.4245-4253</ispartof><rights>The Author(s) 2020</rights><rights>2020 The Author(s)</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>1</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000567764100001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c5915-c5028db4b47d1556b46abc91fee5e656757d0d55c59b63baf386eee7e33fd0a3</citedby><cites>FETCH-LOGICAL-c5915-c5028db4b47d1556b46abc91fee5e656757d0d55c59b63baf386eee7e33fd0a3</cites><orcidid>0000-0001-8734-740X ; 0000-0002-2329-3235</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00268-020-05774-x$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00268-020-05774-x$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,1418,27929,27930,28253,41493,42562,45579,45580,51324</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32909125$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kono, Yoshiharu</creatorcontrib><creatorcontrib>Ishizawa, Takeaki</creatorcontrib><creatorcontrib>Kokudo, Norihiro</creatorcontrib><creatorcontrib>Kuriki, Yugo</creatorcontrib><creatorcontrib>Iwatate, Ryu J.</creatorcontrib><creatorcontrib>Kamiya, Mako</creatorcontrib><creatorcontrib>Urano, Yasuteru</creatorcontrib><creatorcontrib>Kumagai, Akiko</creatorcontrib><creatorcontrib>Kurokawa, Hiroshi</creatorcontrib><creatorcontrib>Miyawaki, Atsushi</creatorcontrib><creatorcontrib>Hasegawa, Kiyoshi</creatorcontrib><title>On-Site Monitoring of Postoperative Bile Leakage Using Bilirubin-Inducible Fluorescent Protein</title><title>World journal of surgery</title><addtitle>World J Surg</addtitle><addtitle>WORLD J SURG</addtitle><addtitle>World J Surg</addtitle><description>Background
Bile leakage is the most common postoperative complication associated with hepatobiliary and pancreatic surgery. Until now, however, a rapid, accurate diagnostic method for monitoring intraoperative and postoperative bile leakage had not been established.
Method
Bilirubin levels in drained abdominal fluids collected from 23 patients who had undergone hepatectomy (
n
= 22) or liver transplantation (
n
= 1) were measured using a microplate reader with excitation/emission wavelengths of 497/527 nm after applying 5 µM of UnaG to the samples. UnaG was also sprayed directly on hepatic raw surfaces in swine hepatectomy models to identify bile leaks by fluorescence imaging.
Results
The bilirubin levels measured by UnaG fluorescence imaging showed favorable correlations with the results of the conventional light-absorptiometric methods (indirect bilirubin: rs = 0.939,
p
< 0.001; direct bilirubin: rs = 0.929,
p
< 0.001). Approximate time required for bilirubin measurements with UnaG was 15 min, whereas it took about 40 min with the conventional method at a hospital laboratory. Following administration of UnaG on hepatic surfaces, the fluorescence imaging identified bile leaks not only on the resected specimens but also in the abdominal cavity of the swine hepatectomy models.
Conclusion
Fluorescence imaging techniques using UnaG may enable real-time identification of bile leaks during hepatectomy and on-site rapid diagnosis of bile leaks after surgery.</description><subject>Abdomen</subject><subject>Abdominal Surgery</subject><subject>Animal models</subject><subject>Bile</subject><subject>Bilirubin</subject><subject>Cardiac Surgery</subject><subject>Computational fluid dynamics</subject><subject>Diagnostic systems</subject><subject>Fluids</subject><subject>Fluorescence</subject><subject>General Surgery</subject><subject>Hepatectomy</subject><subject>Hospitals</subject><subject>Imaging techniques</subject><subject>Laboratory animals</subject><subject>Leakage</subject><subject>Leaks</subject><subject>Life Sciences & Biomedicine</subject><subject>Ligands</subject><subject>Liver</subject><subject>Liver transplantation</subject><subject>Livestock</subject><subject>Medical imaging</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Methods</subject><subject>Monitoring</subject><subject>Onsite</subject><subject>Original Scientific Report with Video</subject><subject>Pancreas</subject><subject>Postoperative period</subject><subject>Proteins</subject><subject>R&D</subject><subject>Research & development</subject><subject>Science & Technology</subject><subject>Surgery</subject><subject>Swine</subject><subject>Thoracic Surgery</subject><subject>Transplantation</subject><subject>Vascular Surgery</subject><subject>Wavelengths</subject><issn>0364-2313</issn><issn>1432-2323</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>AOWDO</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkk1v1DAQhiMEokvhD3BAkbggoYC_veFQia5YKFrUSi3ihuUkk8Ulay92Utp_z4Qsy8cB9WJbnucdz8zrLHtMyQtKiH6ZCGFqXhBGCiK1FsX1nWxGBWcF44zfzWaEK4Fnyg-yByldEkK1Iup-dsBZSUrK5Cz7fOqLc9dD_iF414fo_DoPbX4WUh-2EG3vriA_dh3kK7Bf7Rryj2lk8MrFoXK-OPHNULsKiWU3hAipBt_nZzH04PzD7F5ruwSPdvthdrF8c7F4V6xO354sXq-KWpZU4krYvKlEJXRDpVSVULaqS9oCSFBSaakb0kiJdKV4ZVs-VwCggfO2IZYfZkdT2u1QbaAZK4i2M9voNjbemGCd-Tvi3RezDldGyxLfV5jg2S5BDN8GSL3ZOGyk66yHMCTDhKCKlKUY0af_oJdhiB67Q0pTqUUpNVJsouoYUorQ7ouhxIzumck9g-6Zn-6ZaxQ9-bONveSXXQjMJ-A7VKFNtQNfwx4jhOCotBKYH71euB7tC34RBt-j9PntpUi_2tFo_c0tajef3p8fLzGmxyr5JE7b8T9B_D2h_zT_A3HE2Xw</recordid><startdate>202012</startdate><enddate>202012</enddate><creator>Kono, Yoshiharu</creator><creator>Ishizawa, Takeaki</creator><creator>Kokudo, Norihiro</creator><creator>Kuriki, Yugo</creator><creator>Iwatate, Ryu J.</creator><creator>Kamiya, Mako</creator><creator>Urano, Yasuteru</creator><creator>Kumagai, Akiko</creator><creator>Kurokawa, Hiroshi</creator><creator>Miyawaki, Atsushi</creator><creator>Hasegawa, Kiyoshi</creator><general>Springer International Publishing</general><general>Springer Nature</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>24P</scope><scope>WIN</scope><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QO</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8734-740X</orcidid><orcidid>https://orcid.org/0000-0002-2329-3235</orcidid></search><sort><creationdate>202012</creationdate><title>On-Site Monitoring of Postoperative Bile Leakage Using Bilirubin-Inducible Fluorescent Protein</title><author>Kono, Yoshiharu ; Ishizawa, Takeaki ; Kokudo, Norihiro ; Kuriki, Yugo ; Iwatate, Ryu J. ; Kamiya, Mako ; Urano, Yasuteru ; Kumagai, Akiko ; Kurokawa, Hiroshi ; Miyawaki, Atsushi ; Hasegawa, Kiyoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5915-c5028db4b47d1556b46abc91fee5e656757d0d55c59b63baf386eee7e33fd0a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Abdomen</topic><topic>Abdominal Surgery</topic><topic>Animal models</topic><topic>Bile</topic><topic>Bilirubin</topic><topic>Cardiac Surgery</topic><topic>Computational fluid dynamics</topic><topic>Diagnostic systems</topic><topic>Fluids</topic><topic>Fluorescence</topic><topic>General Surgery</topic><topic>Hepatectomy</topic><topic>Hospitals</topic><topic>Imaging techniques</topic><topic>Laboratory animals</topic><topic>Leakage</topic><topic>Leaks</topic><topic>Life Sciences & Biomedicine</topic><topic>Ligands</topic><topic>Liver</topic><topic>Liver transplantation</topic><topic>Livestock</topic><topic>Medical imaging</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Methods</topic><topic>Monitoring</topic><topic>Onsite</topic><topic>Original Scientific Report with Video</topic><topic>Pancreas</topic><topic>Postoperative period</topic><topic>Proteins</topic><topic>R&D</topic><topic>Research & development</topic><topic>Science & Technology</topic><topic>Surgery</topic><topic>Swine</topic><topic>Thoracic Surgery</topic><topic>Transplantation</topic><topic>Vascular Surgery</topic><topic>Wavelengths</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kono, Yoshiharu</creatorcontrib><creatorcontrib>Ishizawa, Takeaki</creatorcontrib><creatorcontrib>Kokudo, Norihiro</creatorcontrib><creatorcontrib>Kuriki, Yugo</creatorcontrib><creatorcontrib>Iwatate, Ryu J.</creatorcontrib><creatorcontrib>Kamiya, Mako</creatorcontrib><creatorcontrib>Urano, Yasuteru</creatorcontrib><creatorcontrib>Kumagai, Akiko</creatorcontrib><creatorcontrib>Kurokawa, Hiroshi</creatorcontrib><creatorcontrib>Miyawaki, Atsushi</creatorcontrib><creatorcontrib>Hasegawa, Kiyoshi</creatorcontrib><collection>SpringerOpen</collection><collection>Wiley-Blackwell Open Access Collection</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biotechnology and BioEngineering Abstracts</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>World journal of surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kono, Yoshiharu</au><au>Ishizawa, Takeaki</au><au>Kokudo, Norihiro</au><au>Kuriki, Yugo</au><au>Iwatate, Ryu J.</au><au>Kamiya, Mako</au><au>Urano, Yasuteru</au><au>Kumagai, Akiko</au><au>Kurokawa, Hiroshi</au><au>Miyawaki, Atsushi</au><au>Hasegawa, Kiyoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>On-Site Monitoring of Postoperative Bile Leakage Using Bilirubin-Inducible Fluorescent Protein</atitle><jtitle>World journal of surgery</jtitle><stitle>World J Surg</stitle><stitle>WORLD J SURG</stitle><addtitle>World J Surg</addtitle><date>2020-12</date><risdate>2020</risdate><volume>44</volume><issue>12</issue><spage>4245</spage><epage>4253</epage><pages>4245-4253</pages><issn>0364-2313</issn><eissn>1432-2323</eissn><abstract>Background
Bile leakage is the most common postoperative complication associated with hepatobiliary and pancreatic surgery. Until now, however, a rapid, accurate diagnostic method for monitoring intraoperative and postoperative bile leakage had not been established.
Method
Bilirubin levels in drained abdominal fluids collected from 23 patients who had undergone hepatectomy (
n
= 22) or liver transplantation (
n
= 1) were measured using a microplate reader with excitation/emission wavelengths of 497/527 nm after applying 5 µM of UnaG to the samples. UnaG was also sprayed directly on hepatic raw surfaces in swine hepatectomy models to identify bile leaks by fluorescence imaging.
Results
The bilirubin levels measured by UnaG fluorescence imaging showed favorable correlations with the results of the conventional light-absorptiometric methods (indirect bilirubin: rs = 0.939,
p
< 0.001; direct bilirubin: rs = 0.929,
p
< 0.001). Approximate time required for bilirubin measurements with UnaG was 15 min, whereas it took about 40 min with the conventional method at a hospital laboratory. Following administration of UnaG on hepatic surfaces, the fluorescence imaging identified bile leaks not only on the resected specimens but also in the abdominal cavity of the swine hepatectomy models.
Conclusion
Fluorescence imaging techniques using UnaG may enable real-time identification of bile leaks during hepatectomy and on-site rapid diagnosis of bile leaks after surgery.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>32909125</pmid><doi>10.1007/s00268-020-05774-x</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-8734-740X</orcidid><orcidid>https://orcid.org/0000-0002-2329-3235</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Abdomen Abdominal Surgery Animal models Bile Bilirubin Cardiac Surgery Computational fluid dynamics Diagnostic systems Fluids Fluorescence General Surgery Hepatectomy Hospitals Imaging techniques Laboratory animals Leakage Leaks Life Sciences & Biomedicine Ligands Liver Liver transplantation Livestock Medical imaging Medical research Medicine Medicine & Public Health Methods Monitoring Onsite Original Scientific Report with Video Pancreas Postoperative period Proteins R&D Research & development Science & Technology Surgery Swine Thoracic Surgery Transplantation Vascular Surgery Wavelengths |
title | On-Site Monitoring of Postoperative Bile Leakage Using Bilirubin-Inducible Fluorescent Protein |
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