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Stem cellâ derived models to improve mechanistic understanding and prediction of human drugâ induced liver injury

dc.contributor.authorGoldring, Christopher
dc.contributor.authorAntoine, Daniel J.
dc.contributor.authorBonner, Frank
dc.contributor.authorCrozier, Jonathan
dc.contributor.authorDenning, Chris
dc.contributor.authorFontana, Robert J.
dc.contributor.authorHanley, Neil A.
dc.contributor.authorHay, David C.
dc.contributor.authorIngelman‐sundberg, Magnus
dc.contributor.authorJuhila, Satu
dc.contributor.authorKitteringham, Neil
dc.contributor.authorSilva‐lima, Beatriz
dc.contributor.authorNorris, Alan
dc.contributor.authorPridgeon, Chris
dc.contributor.authorRoss, James A.
dc.contributor.authorYoung, Rowena Sison
dc.contributor.authorTagle, Danilo
dc.contributor.authorTornesi, Belen
dc.contributor.authorvan de Water, Bob
dc.contributor.authorWeaver, Richard J.
dc.contributor.authorZhang, Fang
dc.contributor.authorPark, B. Kevin
dc.date.accessioned2017-02-02T22:00:51Z
dc.date.available2018-04-02T18:03:23Zen
dc.date.issued2017-02
dc.identifier.citationGoldring, Christopher; Antoine, Daniel J.; Bonner, Frank; Crozier, Jonathan; Denning, Chris; Fontana, Robert J.; Hanley, Neil A.; Hay, David C.; Ingelman‐sundberg, Magnus ; Juhila, Satu; Kitteringham, Neil; Silva‐lima, Beatriz ; Norris, Alan; Pridgeon, Chris; Ross, James A.; Young, Rowena Sison; Tagle, Danilo; Tornesi, Belen; van de Water, Bob; Weaver, Richard J.; Zhang, Fang; Park, B. Kevin (2017). "Stem cellâ derived models to improve mechanistic understanding and prediction of human drugâ induced liver injury." Hepatology 65(2): 710-721.
dc.identifier.issn0270-9139
dc.identifier.issn1527-3350
dc.identifier.urihttps://hdl.handle.net/2027.42/135984
dc.publisherWiley Periodicals, Inc.
dc.titleStem cellâ derived models to improve mechanistic understanding and prediction of human drugâ induced liver injury
dc.typeArticleen_US
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelInternal Medicine and Specialties
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/135984/1/hep28886.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/135984/2/hep28886_am.pdf
dc.identifier.doi10.1002/hep.28886
dc.identifier.sourceHepatology
dc.identifier.citedreferenceShan J, Schwartz RE, Ross NT, Logan DJ, Thomas D, Duncan SA, et al. Identification of small molecules for human hepatocyte expansion and iPS differentiation. Nat Chem Biol 2013; 9: 514 â 520.
dc.identifier.citedreferenceGieseck RL 3rd, Hannan NR, Bort R, Hanley NA, Drake RA, Cameron GW, et al. Maturation of induced pluripotent stem cell derived hepatocytes by 3Dâ culture. PLoS One 2014; 9: e86372.
dc.identifier.citedreferenceJia B, Chen S, Zhao Z, Liu P, Cai J, Qin D, et al. Modeling of hemophilia A using patientâ specific induced pluripotent stem cells derived from urine cells. Life Sci 2014; 108: 22 â 29.
dc.identifier.citedreferenceAvior Y, Levy G, Zimerman M, Kitsberg D, Schwartz R, Sadeh R, et al. Microbialâ derived lithocholic acid and vitamin K2 drive the metabolic maturation of pluripotent stem cellâ derived and fetal hepatocytes. Hepatology 2015; 62: 265 â 278.
dc.identifier.citedreferenceChien Y, Chang YL, Li HY, Larsson M, Wu WW, Chien CS, et al. Synergistic effects of carboxymethylâ hexanoyl chitosan, cationic polyurethaneâ short branch PEI in miR122 gene delivery: accelerated differentiation of iPSCs into mature hepatocyteâ like cells and improved stem cell therapy in a hepatic failure model. Acta Biomater 2015; 13: 228 â 244.
dc.identifier.citedreferenceUlvestad M, Nordell P, Asplund A, Rehnstrom M, Jacobsson S, Holmgren G, et al. Drug metabolizing enzyme and transporter protein profiles of hepatocytes derived from human embryonic and induced pluripotent stem cells. Biochem Pharmacol 2013; 86: 691 â 702.
dc.identifier.citedreferenceTakayama K, Morisaki Y, Kuno S, Nagamoto Y, Harada K, Furukawa N, et al. Prediction of interindividual differences in hepatic functions and drug sensitivity by using human iPSâ derived hepatocytes. Proc Natl Acad Sci USA 2014; 111: 16772 â 16777.
dc.identifier.citedreferencePark BK, Boobis A, Clarke S, Goldring CE, Jones D, Kenna JG, et al. Managing the challenge of chemically reactive metabolites in drug development. Nat Rev Drug Discov 2011; 10: 292 â 306.
dc.identifier.citedreferenceBerger DR, Ware BR, Davidson MD, Allsup SR, Khetani SR. Enhancing the functional maturity of induced pluripotent stem cellâ derived human hepatocytes by controlled presentation of cellâ cell interactions in vitro. Hepatology 2015; 61: 1370 â 1381.
dc.identifier.citedreferenceDavidson MD, Ware BR, Khetani SR. Stem cellâ derived liver cells for drug testing and disease modeling. Discov Med 2015; 19: 349 â 358.
dc.identifier.citedreferenceAusma J, Borgers M. Dedifferentiation of atrial cardiomyocytes: from in vivo to in vitro. Cardiovasc Res 2002; 55: 9 â 12.
dc.identifier.citedreferenceYusa K, Rashid ST, Strickâ Marchand H, Varela I, Liu PQ, Paschon DE, et al. Targeted gene correction of alpha1â antitrypsin deficiency in induced pluripotent stem cells. Nature 2011; 478: 391 â 394.
dc.identifier.citedreferenceWare BR, Berger DR, Khetani SR. Prediction of drugâ induced liver injury in micropatterned coâ cultures containing iPSCâ derived human hepatocytes. Toxicol Sci 2015; 145: 252 â 262.
dc.identifier.citedreferenceLahti AL, Kujala VJ, Chapman H, Koivisto AP, Pekkanenâ Mattila M, Kerkela E, et al. Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture. Dis Model Mech 2012; 5: 220 â 230.
dc.identifier.citedreferenceMatsa E, Rajamohan D, Dick E, Young L, Mellor I, Staniforth A, et al. Drug evaluation in cardiomyocytes derived from human induced pluripotent stem cells carrying a long QT syndrome type 2 mutation. Eur Heart J 2011; 32: 952 â 962.
dc.identifier.citedreferenceItzhaki I, Maizels L, Huber I, Gepstein A, Arbel G, Caspi O, et al. Modeling of catecholaminergic polymorphic ventricular tachycardia with patientâ specific humanâ induced pluripotent stem cells. J Am Coll Cardiol 2012; 60: 990 â 1000.
dc.identifier.citedreferenceKaplowitz N. Idiosyncratic drug hepatotoxicity. Nat Rev Drug Discov 2005; 4: 489 â 499.
dc.identifier.citedreferenceForce T, Kolaja KL. Cardiotoxicity of kinase inhibitors: the prediction and translation of preclinical models to clinical outcomes. Nat Rev Drug Discov 2011; 10: 111 â 126.
dc.identifier.citedreferenceDenning C, Borgdorff V, Crutchley J, Firth KS, George V, Kalra S, et al. Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform. Biochim Biophys Acta 2016; 1863: 1728 â 1748.
dc.identifier.citedreferenceSengupta S, Johnson BP, Swanson SA, Stewart R, Bradfield CA, Thomson JA. Aggregate culture of human embryonic stem cellâ derived hepatocytes in suspension are an improved in vitro model for drug metabolism and toxicity testing. Toxicol Sci 2014; 140: 236 â 245.
dc.identifier.citedreferenceMa X, Duan Y, Tschudyâ Seney B, Roll G, Behbahan IS, Ahuja TP, et al. Highly efficient differentiation of functional hepatocytes from human induced pluripotent stem cells. Stem Cells Transl Med 2013; 2: 409 â 419.
dc.identifier.citedreferenceKitteringham NR, Jenkins RE, Lane CS, Elliott VL, Park BK. Multiple reaction monitoring for quantitative biomarker analysis in proteomics and metabolomics. J Chromatogr B Analyt Technol Biomed Life Sci 2009; 877: 1229 â 1239.
dc.identifier.citedreferenceSchwanhausser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, et al. Global quantification of mammalian gene expression control. Nature 2011; 473: 337 â 342.
dc.identifier.citedreferenceStarkey Lewis PJ, Dear J, Platt V, Simpson KJ, Craig DG, Antoine DJ, et al. Circulating microRNAs as potential markers of human drugâ induced liver injury. Hepatology 2011; 54: 1767 â 1776.
dc.identifier.citedreferenceWillett C, Caverly Rae J, Goyak KO, Minsavage G, Westmoreland C, Andersen M, et al. Building shared experience to advance practical application of pathwayâ based toxicology: liver toxicity modeâ ofâ action. ALTEX 2014; 31: 500 â 519.
dc.identifier.citedreferenceHerpers B, Wink S, Fredriksson L, Di Z, Hendriks G, Vrieling H, et al. Activation of the Nrf2 response by intrinsic hepatotoxic drugs correlates with suppression of NFâ kappaB activation and sensitizes toward TNFalphaâ induced cytotoxicity. Arch Toxicol 2016; 90: 1163 â 1179.
dc.identifier.citedreferenceFredriksson L, Wink S, Herpers B, Benedetti G, Hadi M, de Bont H, et al. Drugâ induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNFalphaâ mediated hepatotoxicity. Toxicol Sci 2014; 140: 144 â 159.
dc.identifier.citedreferenceWink S, Hiemstra S, Huppelschoten S, Danen E, Niemeijer M, Hendriks G, et al. Quantitative high content imaging of cellular adaptive stress response pathways in toxicity for chemical safety assessment. Chem Res Toxicol 2014; 27: 338 â 355.
dc.identifier.citedreferenceElaut G, Henkens T, Papeleu P, Snykers S, Vinken M, Vanhaecke T, et al. Molecular mechanisms underlying the dedifferentiation process of isolated hepatocytes and their cultures. Curr Drug Metab 2006; 7: 629 â 660.
dc.identifier.citedreferenceBhatia SN, Balis UJ, Yarmush ML, Toner M. Probing heterotypic cell interactions: hepatocyte function in microfabricated coâ cultures. J Biomater Sci Polym Ed 1998; 9: 1137 â 1160.
dc.identifier.citedreferenceZinchenko YS, Schrum LW, Clemens M, Coger RN. Hepatocyte and Kupffer cells coâ cultured on micropatterned surfaces to optimize hepatocyte function. Tissue Eng 2006; 12: 751 â 761.
dc.identifier.citedreferenceRowe C, Gerrard DT, Jenkins R, Berry A, Durkin K, Sundstrom L, et al. Proteomeâ wide analyses of human hepatocytes during differentiation and dedifferentiation. Hepatology 2013; 58: 799 â 809.
dc.identifier.citedreferenceMa X, Qu X, Zhu W, Li YS, Yuan S, Zhang H, et al. Deterministically patterned biomimetic human iPSCâ derived hepatic model via rapid 3D bioprinting. Proc Natl Acad Sci USA 2016; 113: 2206 â 2211.
dc.identifier.citedreferenceTakebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, et al. Vascularized and functional human liver from an iPSCâ derived organ bud transplant. Nature 2013; 499: 481 â 484.
dc.identifier.citedreferenceNguyen TV, Ukairo O, Khetani SR, McVay M, Kanchagar C, Seghezzi W, et al. Establishment of a hepatocyteâ Kupffer cell coculture model for assessment of proinflammatory cytokine effects on metabolizing enzymes and drug transporters. Drug Metab Dispos 2015; 43: 774 â 785.
dc.identifier.citedreferencePirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 2004; 329: 15 â 19.
dc.identifier.citedreferenceWaring MJ, Arrowsmith J, Leach AR, Leeson PD, Mandrell S, Owen RM, et al. An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nat Rev Drug Discov 2015; 14: 475 â 486.
dc.identifier.citedreferenceOstapowicz G, Fontana RJ, Schiodt FV, Larson A, Davern TJ, Han SH, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002; 137: 947 â 954.
dc.identifier.citedreferenceSpanhaak S, Cook D, Barnes J, Reynolds J. Species concordance for liver injury. BioWisdom 2008. http://bioblog.instem.com/downloads/SIP_Board_Species_Concordance.pdf.
dc.identifier.citedreferenceVerma S, Kaplowitz N. Diagnosis, management and prevention of drugâ induced liver injury. Gut 2009; 58: 1555 â 1564.
dc.identifier.citedreferenceTolosa L, Pinto S, Donato MT, Lahoz A, Castell JV, O’Connor JE, et al. Development of a multiparametric cellâ based protocol to screen and classify the hepatotoxicity potential of drugs. Toxicol Sci 2012; 127: 187 â 198.
dc.identifier.citedreferenceXu JJ, Henstock PV, Dunn MC, Smith AR, Chabot JR, de Graaf D. Cellular imaging predictions of clinical drugâ induced liver injury. Toxicol Sci 2008; 105: 97 â 105.
dc.identifier.citedreferenceTolosa L, Gomezâ Lechon MJ, Lopez S, Guzman C, Castell JV, Donato MT, et al. Human upcyte hepatocytes: characterization of the hepatic phenotype and evaluation for acute and longâ term hepatotoxicity routine testing. Toxicol Sci 2016; 152: 214 â 229.
dc.identifier.citedreferenceKhetani SR, Kanchagar C, Ukairo O, Krzyzewski S, Moore A, Shi J, et al. Use of micropatterned cocultures to detect compounds that cause drugâ induced liver injury in humans. Toxicol Sci 2013; 132: 107 â 117.
dc.identifier.citedreferenceGerets HH, Tilmant K, Gerin B, Chanteux H, Depelchin BO, Dhalluin S, et al. Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins. Cell Biol Toxicol 2012; 28: 69 â 87.
dc.identifier.citedreferenceGuillouzo A, Corlu A, Aninat C, Glaise D, Morel F, Guguenâ Guillouzo C. The human hepatoma HepaRG cells: a highly differentiated model for studies of liver metabolism and toxicity of xenobiotics. Chem Biol Interact 2007; 168: 66 â 73.
dc.identifier.citedreferenceBaxter M, Withey S, Harrison S, Segeritz CP, Zhang F, Atkinsonâ Dell R, et al. Phenotypic and functional analyses show stem cellâ derived hepatocyteâ like cells better mimic fetal rather than adult hepatocytes. J Hepatol 2015; 62: 581 â 589.
dc.identifier.citedreferenceCameron K, Tan R, Schmidtâ Heck W, Campos G, Lyall MJ, Wang Y, et al. Recombinant laminins drive the differentiation and selfâ organization of hESCâ derived hepatocytes. Stem Cell Reports 2015; 5: 1250 â 1262.
dc.identifier.citedreferenceGodoy P, Schmidtâ Heck W, Natarajan K, Lucendoâ Villarin B, Szkolnicka D, Asplund A, et al. Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyteâ like cells. J Hepatol 2015; 63: 934 â 942.
dc.identifier.citedreferenceLiu J, Brzeszczynska J, Samuel K, Black J, Palakkan A, Anderson RA, et al. Efficient episomal reprogramming of blood mononuclear cells and differentiation to hepatocytes with functional drug metabolism. Exp Cell Res 2015; 338: 203 â 213.
dc.identifier.citedreferenceKia R, Sison RL, Heslop J, Kitteringham NR, Hanley N, Mills JS, et al. Stem cellâ derived hepatocytes as a predictive model for drugâ induced liver injury: are we there yet? Br J Clin Pharmacol 2013; 75: 885 â 896.
dc.identifier.citedreferenceCai J, Zhao Y, Liu Y, Ye F, Song Z, Qin H, et al. Directed differentiation of human embryonic stem cells into functional hepatic cells. Hepatology 2007; 45: 1229 â 1239.
dc.identifier.citedreferenceEk M, Soderdahl T, Kuppersâ Munther B, Edsbagge J, Andersson TB, Bjorquist P, et al. Expression of drug metabolizing enzymes in hepatocyteâ like cells derived from human embryonic stem cells. Biochem Pharmacol 2007; 74: 496 â 503.
dc.identifier.citedreferenceSoderdahl T, Kuppersâ Munther B, Heins N, Edsbagge J, Bjorquist P, Cotgreave I, et al. Glutathione transferases in hepatocyteâ like cells derived from human embryonic stem cells. Toxicol In Vitro 2007; 21: 929 â 937.
dc.identifier.citedreferenceHay DC, Fletcher J, Payne C, Terrace JD, Gallagher RC, Snoeys J, et al. Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling. Proc Natl Acad Sci USA 2008; 105: 12301 â 12306.
dc.identifier.citedreferenceShiraki N, Umeda K, Sakashita N, Takeya M, Kume K, Kume S. Differentiation of mouse and human embryonic stem cells into hepatic lineages. Genes Cells 2008; 13: 731 â 746.
dc.identifier.citedreferenceAgarwal S, Holton KL, Lanza R. Efficient differentiation of functional hepatocytes from human embryonic stem cells. Stem Cells 2008; 26: 1117 â 1127.
dc.identifier.citedreferenceMoore RN, Moghe PV. Expedited growth factorâ mediated specification of human embryonic stem cells toward the hepatic lineage. Stem Cell Res 2009; 3: 51 â 62.
dc.identifier.citedreferenceBasma H, Sotoâ Gutierrez A, Yannam GR, Liu L, Ito R, Yamamoto T, et al. Differentiation and transplantation of human embryonic stem cellâ derived hepatocytes. Gastroenterology 2009; 136: 990 â 999.
dc.identifier.citedreferenceSong Z, Cai J, Liu Y, Zhao D, Yong J, Duo S, et al. Efficient generation of hepatocyteâ like cells from human induced pluripotent stem cells. Cell Res 2009; 19: 1233 â 1242.
dc.identifier.citedreferenceDuan Y, Ma X, Zou W, Wang C, Bahbahan IS, Ahuja TP, et al. Differentiation and characterization of metabolically functioning hepatocytes from human embryonic stem cells. Stem Cells 2010; 28: 674 â 686.
dc.identifier.citedreferenceSynnergren J, Heins N, Brolen G, Eriksson G, Lindahl A, Hyllner J, et al. Transcriptional profiling of human embryonic stem cells differentiating to definitive and primitive endoderm and further toward the hepatic lineage. Stem Cells Dev 2010; 19: 961 â 978.
dc.identifier.citedreferenceTouboul T, Hannan NR, Corbineau S, Martinez A, Martinet C, Branchereau S, et al. Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development. Hepatology 2010; 51: 1754 â 1765.
dc.identifier.citedreferenceBrolen G, Sivertsson L, Bjorquist P, Eriksson G, Ek M, Semb H, et al. Hepatocyteâ like cells derived from human embryonic stem cells specifically via definitive endoderm and a progenitor stage. J Biotechnol 2010; 145: 284 â 294.
dc.identifier.citedreferenceGhodsizadeh A, Taei A, Totonchi M, Seifinejad A, Gourabi H, Pournasr B, et al. Generation of liver diseaseâ specific induced pluripotent stem cells along with efficient differentiation to functional hepatocyteâ like cells. Stem Cell Rev 2010; 6: 622 â 632.
dc.identifier.citedreferenceLiu H, Ye Z, Kim Y, Sharkis S, Jang YY. Generation of endodermâ derived human induced pluripotent stem cells from primary hepatocytes. Hepatology 2010; 51: 1810 â 1819.
dc.identifier.citedreferenceSiâ Tayeb K, Noto FK, Nagaoka M, Li J, Battle MA, Duris C, et al. Highly efficient generation of human hepatocyteâ like cells from induced pluripotent stem cells. Hepatology 2010; 51: 297 â 305.
dc.identifier.citedreferenceSullivan GJ, Hay DC, Park IH, Fletcher J, Hannoun Z, Payne CM, et al. Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology 2010; 51: 329 â 335.
dc.identifier.citedreferenceRashid ST, Corbineau S, Hannan N, Marciniak SJ, Miranda E, Alexander G, et al. Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J Clin Invest 2010; 120: 3127 â 3136.
dc.identifier.citedreferenceZhang S, Chen S, Li W, Guo X, Zhao P, Xu J, et al. Rescue of ATP7B function in hepatocyteâ like cells from Wilson’s disease induced pluripotent stem cells using gene therapy or the chaperone drug curcumin. Hum Mol Genet 2011; 20: 3176 â 3187.
dc.identifier.citedreferenceBone HK, Nelson AS, Goldring CE, Tosh D, Welham MJ. A novel chemically directed route for the generation of definitive endoderm from human embryonic stem cells based on inhibition of GSKâ 3. J Cell Sci 2011; 124: 1992 â 2000.
dc.identifier.citedreferenceYildirimman R, Brolen G, Vilardell M, Eriksson G, Synnergren J, Gmuender H, et al. Human embryonic stem cell derived hepatocyteâ like cells as a tool for in vitro hazard assessment of chemical carcinogenicity. Toxicol Sci 2011; 124: 278 â 290.
dc.identifier.citedreferenceChen YF, Tseng CY, Wang HW, Kuo HC, Yang VW, Lee OK. Rapid generation of mature hepatocyteâ like cells from human induced pluripotent stem cells by an efficient threeâ step protocol. Hepatology 2012; 55: 1193 â 1203.
dc.identifier.citedreferenceCayo MA, Cai J, DeLaForest A, Noto FK, Nagaoka M, Clark BS, et al. JD induced pluripotent stem cellâ derived hepatocytes faithfully recapitulate the pathophysiology of familial hypercholesterolemia. Hepatology 2012; 56: 2163 â 2171.
dc.identifier.citedreferenceSchwartz RE, Trehan K, Andrus L, Sheahan TP, Ploss A, Duncan SA, et al. Modeling hepatitis C virus infection using human induced pluripotent stem cells. Proc Natl Acad Sci USA 2012; 109: 2544 â 2548.
dc.identifier.citedreferenceTakayama K, Inamura M, Kawabata K, Katayama K, Higuchi M, Tashiro K, et al. Efficient generation of functional hepatocytes from human embryonic stem cells and induced pluripotent stem cells by HNF4alpha transduction. Mol Ther 2012; 20: 127 â 137.
dc.identifier.citedreferenceChoi SM, Kim Y, Shim JS, Park JT, Wang RH, Leach SD, et al. Efficient drug screening and gene correction for treating liver disease using patientâ specific stem cells. Hepatology 2013; 57: 2458 â 2468.
dc.identifier.citedreferenceRamasamy TS, Yu JS, Selden C, Hodgson H, Cui W. Application of threeâ dimensional culture conditions to human embryonic stem cellâ derived definitive endoderm cells enhances hepatocyte differentiation and functionality. Tissue Eng Part A 2013; 19: 360 â 367.
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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