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Karakousis, Petros C., M.D.

Petros Karakousis, M.D.

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Karakousis Lab

Petros Karakousis, M.D.

Associate Professor of Medicine
Division of Infectious Diseases

Dr. Karakousis’ primary research interest is the molecular basis of Mycobacterium tuberculosis latency and reactivation. Secondary interests include preclinical screening of novel TB drugs and drug combinations in animal models of caseous necrosis, as well as development of novel molecular assays for the rapid diagnosis of latent TB infection and active TB disease, and for the detection of drug resistance.

Major research activities include studying the adaptation of M. tuberculosis to stress conditions believed to be important in the infected human host, as well as the phenomenon of phenotypic tolerance to antibiotics. In particular, the regulatory cascade involved in the mycobacterial stringent response is under active investigation. Dr. Karakousis, in collaboration with Dr. Joel Bader of the JHU Whiting School of Engineering, has undertaken a systems biology-based approach, including the use of several novel animal models of latency in combination with transcriptional, proteomic, genetic, imaging, and computational techniques, to identify host cytokine networks responsible for immunological control of M. tuberculosis growth, as well as M. tuberculosis regulatory and metabolic pathways required for bacillary growth restriction and reactivation.

The guinea pig model of TB, which forms necrotic lesions histologically resembling its human counterparts, is also being used to study the sterilizing activity of novel drugs and drug combinations against persisters, with the ultimate goal of shortening antituberculous chemotherapy. Molecular assays using blood, sputum, and urine samples are being investigated with the goal of developing rapid, sensitive, and specific point-of-care tests for TB diagnosis and detection of drug resistance. In collaboration with the Gorgas Memorial Institute of Health Studies (ICGES) in Panama, the sensitivity and specificity of Multiplex Allele-Specific PCR (MAS-PCR) is being studied for the rapid detection of isoniazid and rifampin resistance in archived, MDR-TB clinical isolates.

Dr. Karakousis received his undergraduate degree in 1994 from the Johns Hopkins University and his medical degree in 1998 from Washington University School of Medicine in St. Louis.  He completed residency training in Internal Medicine in 2001 at the Hospital of the University of Pennsylvania.  After completing fellowship training in Infectious Diseases at Johns Hopkins University School of Medicine, he joined the Department of Medicine faculty in 2005.

Business Address:

Center for Tuberculosis Research
Dept. of Medicine, Div. of Infectious Diseases
Johns Hopkins University School of Medicine
1550 Orleans St., Room 110
Baltimore, MD 21231                                      
Tel: 410-502-8233
Fax: 410-614-8173
E-mail: petros@jhmi.edu

Publications: To read some of these publications online, click here. Please note that to read the full text of some of these articles requires that you have an online subscription to the journal.

Selected Peer-reviewed articles:

1: Zhou A, Ni J, Xu Z, Wang Y, Lu S, Sha W, Karakousis PC, Yao YF. Application of (1)h NMR spectroscopy-based metabolomics to sera of tuberculosis patients. J Proteome Res. 2013 Oct 4;12(10):4642-9. doi: 10.1021/pr4007359. Epub 2013 Sep 10.  PMID: 23980697.

2: Subbian S, Bandyopadhyay N, Tsenova L, O Brien P, Khetani V, Kushner NL, Peixoto B, Soteropoulos P, Bader JS, Karakousis PC, Fallows D, Kaplan G. Early innate immunity determines outcome of Mycobacterium tuberculosis pulmonary infection in rabbits. Cell Commun Signal. 2013 Aug 19;11(1):60. [Epub ahead of print]  PMID: 23958185;  PMCID: PMC3765177.

3: Lanzas F,  , Sacchettini JC, Ioerger TR. Multidrug-Resistant Tuberculosis in Panama Is Driven by Clonal Expansion of a Multidrug-Resistant Mycobacterium tuberculosis Strain Related to the KZN Extensively Drug-Resistant M. tuberculosis Strain from South Africa. J Clin Microbiol. 2013 Oct;51(10):3277-85. doi: 10.1128/JCM.01122-13. Epub 2013 Jul 24.  PMID: 23884993.

4: Skerry C, Pokkali S, Pinn M, Be NA, Harper J, Karakousis PC, Jain SK. Vaccination with recombinant Mycobacterium tuberculosis PknD attenuates bacterial dissemination to the brain in guinea pigs. PLoS One. 2013 Jun 11;8(6):e66310. doi: 10.1371/journal.pone.0066310. Print 2013.  PMID: 23776655;  PMCID: PMC3679071.

5: Dutta NK, Alsultan A, Gniadek TJ, Belchis DA, Pinn ML, Mdluli KE, Nuermberger  EL, Peloquin CA, Karakousis PC. Potent rifamycin-sparing regimen cures guinea pig tuberculosis as rapidly as the standard regimen. Antimicrob Agents Chemother. 2013 Aug;57(8):3910-6. doi: 10.1128/AAC.00761-13. Epub 2013 Jun 3.  PMID: 23733473;  PMCID: PMC3719725.

6: Chuang YM, Belchis DA, Karakousis PC. The polyphosphate kinase gene ppk2 is required for Mycobacterium tuberculosis inorganic polyphosphate regulation and virulence. MBio. 2013 May 21;4(3):e00039-13. doi: 10.1128/mBio.00039-13.  PMID: 23695835;  PMCID: PMC3663568.

7: Dutta NK, Pinn ML, Zhao M, Rudek MA, Karakousis PC. Thioridazine lacks bactericidal activity in an animal model of extracellular tuberculosis. J Antimicrob Chemother. 2013 Jun;68(6):1327-30. doi: 10.1093/jac/dkt037. Epub 2013  Mar 5.  PMID: 23463208;  PMCID: PMC3654222.

8: Subbian S, O'Brien P, Kushner NL, Yang G, Tsenova L, Peixoto B, Bandyopadhyay  N, Bader JS, Karakousis PC, Fallows D, Kaplan G. Molecular immunologic correlates of spontaneous latency in a rabbit model of pulmonary tuberculosis. Cell Commun Signal. 2013 Feb 28;11(1):16. doi: 10.1186/1478-811X-11-16.  PMID: 23448601;  PMCID: PMC3598925.

9: Klinkenberg LG, Karakousis PC. Rv1894c is a novel hypoxia-induced nitronate monooxygenase required for Mycobacterium tuberculosis virulence. J Infect Dis. 2013 May 15;207(10):1525-34. doi: 10.1093/infdis/jit049. Epub 2013 Feb 13.  PMID: 23408846;  PMCID: PMC3627198.

10: Nuermberger EL, Rosenthal IM, Tasneen R, Peloquin CA, Mdluli KE, Karakousis PC, Grosset JH. Reply to "Contradictory results with high-dosage rifamycin in mice and humans". Antimicrob Agents Chemother. 2013 Feb;57(2):1104-5. doi: 10.1128/AAC.02216-12.  PMID: 23341430;  PMCID: PMC3553677.

11: Dutta NK, Alsultan A, Peloquin CA, Karakousis PC. Preliminary pharmacokinetic study of repeated doses of rifampin and rifapentine in guinea pigs. Antimicrob Agents Chemother. 2013 Mar;57(3):1535-7. doi: 10.1128/AAC.01933-12. Epub 2013 Jan 7.  PMID: 23295923;  PMCID: PMC3591898.

12: Albini TA, Karakousis PC, Abbey AM, Bartlett JG, Flynn HW Jr. Association between oral fluoroquinolones and retinal detachment. Am J Ophthalmol. 2012 Dec;154(6):919-921.e1. doi: 10.1016/j.ajo.2012.09.016.  PMID: 23149367.

13: Bisson GP, Mehaffy C, Broeckling C, Prenni J, Rifat D, Lun DS, Burgos M, Weissman D, Karakousis PC, Dobos K. Upregulation of the phthiocerol dimycocerosate biosynthetic pathway by rifampin-resistant, rpoB mutant Mycobacterium tuberculosis. J Bacteriol. 2012 Dec;194(23):6441-52. doi: 10.1128/JB.01013-12. Epub 2012 Sep 21.  PMID: 23002228;  PMCID: PMC3497527.

14: Dutta NK, Karakousis PC. Tuberculosis chemotherapy : present situation, possible solutions, and progress towards a TB-free world. Indian J Med Microbiol. 2012 Jul-Sep;30(3):261-3. doi: 10.4103/0255-0857.99481.  PMID: 22885189.

15: Thayil SM, Ho YC, Bollinger RC, Blankson JN, Siliciano RF, Karakousis PC, Page KR. Mycobacterium tuberculosis complex enhances susceptibility of CD4 T cells to HIV through a TLR2-mediated pathway. PLoS One. 2012;7(7):e41093. doi: 10.1371/journal.pone.0041093. Epub 2012 Jul 23.  PMID: 22844428;  PMCID: PMC3402510.

16: Chia BS, Lanzas F, Rifat D, Herrera A, Kim EY, Sailer C, Torres-Chavolla E, Narayanaswamy P, Einarsson V, Bravo J, Pascale JM, Ioerger TR, Sacchettini JC, Karakousis PC. Use of multiplex allele-specific polymerase chain reaction (MAS-PCR) to detect multidrug-resistant tuberculosis in Panama. PLoS One. 2012;7(7):e40456. doi: 10.1371/journal.pone.0040456. Epub 2012 Jul 6.  PMID: 22792333;  PMCID: PMC3391257.

17: Singh PP, Smith VL, Karakousis PC, Schorey JS. Exosomes isolated from mycobacteria-infected mice or cultured macrophages can recruit and activate immune cells in vitro and in vivo. J Immunol. 2012 Jul 15;189(2):777-85. doi: 10.4049/jimmunol.1103638. Epub 2012 Jun 20.  PMID: 22723519;  PMCID: PMC3685416.

18: Rosenthal IM, Tasneen R, Peloquin CA, Zhang M, Almeida D, Mdluli KE, Karakousis PC, Grosset JH, Nuermberger EL. Dose-ranging comparison of rifampin and rifapentine in two pathologically distinct murine models of tuberculosis. Antimicrob Agents Chemother. 2012 Aug;56(8):4331-40. doi: 10.1128/AAC.00912-12. Epub 2012 Jun 4.  PMID: 22664964;  PMCID: PMC3421552.

19: Dutta NK, Illei PB, Peloquin CA, Pinn ML, Mdluli KE, Nuermberger EL, Grosset  JH, Karakousis PC. Rifapentine is not more active than rifampin against chronic tuberculosis in guinea pigs. Antimicrob Agents Chemother. 2012 Jul;56(7):3726-31. doi: 10.1128/AAC.00500-12. Epub 2012 Apr 30.  PMID: 22547623;  PMCID: PMC3393407.

20: Thayil SM, Albini TA, Nazari H, Moshfeghi AA, Parel JM, Rao NA, Karakousis PC. Local ischemia and increased expression of vascular endothelial growth factor following ocular dissemination of Mycobacterium tuberculosis. PLoS One. 2011;6(12):e28383. doi: 10.1371/journal.pone.0028383. Epub 2011 Dec 5.  PMID: 22162767;  PMCID: PMC3230586.

21: Thayil SM, Morrison N, Schechter N, Rubin H, Karakousis PC. The role of the novel exopolyphosphatase MT0516 in Mycobacterium tuberculosis drug tolerance and  persistence. PLoS One. 2011;6(11):e28076. doi: 10.1371/journal.pone.0028076. Epub 2011 Nov 21.  PMID: 22132215;  PMCID: PMC3221697.

22: Be NA, Klinkenberg LG, Bishai WR, Karakousis PC, Jain SK. Strain-dependent CNS dissemination in guinea pigs after Mycobacterium tuberculosis aerosol challenge. Tuberculosis (Edinb). 2011 Sep;91(5):386-9. doi: 10.1016/j.tube.2011.07.003. Epub 2011 Aug 9.  PMID: 21831713;  PMCID: PMC3172348.

23: Ahmad Z, Fraig MM, Pinn ML, Tyagi S, Nuermberger EL, Grosset JH, Karakousis PC. Effectiveness of tuberculosis chemotherapy correlates with resistance to Mycobacterium tuberculosis infection in animal models. J Antimicrob Chemother. 2011 Jul;66(7):1560-6. doi: 10.1093/jac/dkr188. Epub 2011 May 20.  PMID: 21602551;  PMCID: PMC3112031.

24: Abomoelak B, Marcus SA, Ward SK, Karakousis PC, Steinberg H, Talaat AM. Characterization of a novel heat shock protein (Hsp22.5) involved in the pathogenesis of Mycobacterium tuberculosis. J Bacteriol. 2011 Jul;193(14):3497-505. doi: 10.1128/JB.01536-10. Epub 2011 May 20.  PMID: 21602349;  PMCID: PMC3133320.

25: Dutta NK, Mazumdar K, Dastidar SG, Karakousis PC, Amaral L. New patentable use of an old neuroleptic compound thioridazine to combat tuberculosis: a gene regulation perspective. Recent Pat Antiinfect Drug Discov. 2011 May;6(2):128-38.  Review.  PMID: 21517741.

26: Zhou A, Nawaz M, Xue X, Karakousis PC, Yao Y, Xu J. Molecular genotyping of Mycobacterium tuberculosis in Xi'an, China, using MIRU-VNTR typing. Int J Tuberc  Lung Dis. 2011 Apr;15(4):517-22. doi: 10.5588/ijtld.10.0495.  PMID: 21396212.

27: Ahmad Z, Fraig MM, Bisson GP, Nuermberger EL, Grosset JH, Karakousis PC. Dose-dependent activity of pyrazinamide in animal models of intracellular and extracellular tuberculosis infections. Antimicrob Agents Chemother. 2011 Apr;55(4):1527-32. doi: 10.1128/AAC.01524-10. Epub 2011 Jan 31.  PMID: 21282447;  PMCID: PMC3067197.

28: Piggott DA, Karakousis PC. Timing of antiretroviral therapy for HIV in the setting of TB treatment. Clin Dev Immunol. 2011;2011:103917. doi: 10.1155/2011/103917. Epub 2010 Dec 27. Review.  PMID: 21234380;  PMCID: PMC3017895.

29: Klinkenberg LG, Lee JH, Bishai WR, Karakousis PC. The stringent response is required for full virulence of Mycobacterium tuberculosis in guinea pigs. J Infect Dis. 2010 Nov 1;202(9):1397-404. doi: 10.1086/656524.  PMID: 20863231;  PMCID: PMC2949470.

30: Ahmad Z, Pinn ML, Nuermberger EL, Peloquin CA, Grosset JH, Karakousis PC. The potent bactericidal activity of streptomycin in the guinea pig model of tuberculosis ceases due to the presence of persisters. J Antimicrob Chemother. 2010 Oct;65(10):2172-5. doi: 10.1093/jac/dkq277. Epub 2010 Aug 6.  PMID: 20693172;  PMCID: PMC2941674.

31: Cutrufello NJ, Karakousis PC, Fishler J, Albini TA. Intraocular tuberculosis. Ocul Immunol Inflamm. 2010 Aug;18(4):281-91. doi: 10.3109/09273948.2010.489729. Review.  PMID: 20662660.

32: Converse PJ, Eisenach KD, Theus SA, Nuermberger EL, Tyagi S, Ly LH, Geiman DE, Guo H, Nolan ST, Akar NC, Klinkenberg LG, Gupta R, Lun S, Karakousis PC, Lamichhane G, McMurray DN, Grosset JH, Bishai WR. The impact of mouse passaging of Mycobacterium tuberculosis strains prior to virulence testing in the mouse and guinea pig aerosol models. PLoS One. 2010 Apr 21;5(4):e10289. doi: 10.1371/journal.pone.0010289.  PMID: 20422019;  PMCID: PMC2858211.

33: Ahmad Z, Nuermberger EL, Tasneen R, Pinn ML, Williams KN, Peloquin CA, Grosset JH, Karakousis PC. Comparison of the 'Denver regimen' against acute tuberculosis in the mouse and guinea pig. J Antimicrob Chemother. 2010 Apr;65(4):729-34. doi: 10.1093/jac/dkq007. Epub 2010 Jan 31.  PMID: 20123722;  PMCID: PMC2837551.

34: Rao NA, Albini TA, Kumaradas M, Pinn ML, Fraig MM, Karakousis PC. Experimental ocular tuberculosis in guinea pigs. Arch Ophthalmol. 2009 Sep;127(9):1162-6. doi: 10.1001/archophthalmol.2009.220.  PMID: 19752425;  PMCID: PMC3062475.

35: Ahmad Z, Klinkenberg LG, Pinn ML, Fraig MM, Peloquin CA, Bishai WR, Nuermberger EL, Grosset JH, Karakousis PC. Biphasic kill curve of isoniazid reveals the presence of drug-tolerant, not drug-resistant, Mycobacterium tuberculosis in the guinea pig. J Infect Dis. 2009 Oct 1;200(7):1136-43. doi: 10.1086/605605.  PMID: 19686043.

36: Rifat D, Bishai WR, Karakousis PC. Phosphate depletion: a novel trigger for Mycobacterium tuberculosis persistence. J Infect Dis. 2009 Oct 1;200(7):1126-35.  doi: 10.1086/605700.  PMID: 19686042.

37: Converse PJ, Karakousis PC, Klinkenberg LG, Kesavan AK, Ly LH, Allen SS, Grosset JH, Jain SK, Lamichhane G, Manabe YC, McMurray DN, Nuermberger EL, Bishai WR. Role of the dosR-dosS two-component regulatory system in Mycobacterium tuberculosis virulence in three animal models. Infect Immun. 2009 Mar;77(3):1230-7. doi: 10.1128/IAI.01117-08. Epub 2008 Dec 22.  PMID: 19103767;  PMCID: PMC2643651.

38: Albini TA, Karakousis PC, Rao NA. Interferon-gamma release assays in the diagnosis of tuberculous uveitis. Am J Ophthalmol. 2008 Oct;146(4):486-8. doi: 10.1016/j.ajo.2008.06.021.  PMID: 18804561.

39: Klinkenberg LG, Sutherland LA, Bishai WR, Karakousis PC. Metronidazole lacks  activity against Mycobacterium tuberculosis in an in vivo hypoxic granuloma model of latency. J Infect Dis. 2008 Jul 15;198(2):275-83. doi: 10.1086/589515.   PMID: 18491971;  PMCID: PMC2647800.

40: Karakousis PC, Williams EP, Bishai WR. Altered expression of isoniazid-regulated genes in drug-treated dormant Mycobacterium tuberculosis. J Antimicrob Chemother. 2008 Feb;61(2):323-31. Epub 2007 Dec 21.  PMID: 18156607.

41: Lee JH, Karakousis PC, Bishai WR. Roles of SigB and SigF in the Mycobacterium tuberculosis sigma factor network. J Bacteriol. 2008 Jan;190(2):699-707. Epub 2007 Nov 9.  PMID: 17993538;  PMCID: PMC2223694.

42: Riddell J 4th, Kaul DR, Karakousis PC, Gallant JE, Mitty J, Kazanjian PH. Mycobacterium avium complex immune reconstitution inflammatory syndrome: long term outcomes. J Transl Med. 2007 Oct 15;5:50.  PMID: 17937815;  PMCID: PMC2213635.

43: Karakousis PC, Sifakis FG, de Oca RM, Amorosa VC, Page KR, Manabe YC, Campbell JD. U.S. medical resident familiarity with national tuberculosis guidelines. BMC Infect Dis. 2007 Aug 2;7:89.  PMID: 17678548;  PMCID: PMC1976424.

44: Jain SK, Hernandez-Abanto SM, Cheng QJ, Singh P, Ly LH, Klinkenberg LG, Morrison NE, Converse PJ, Nuermberger E, Grosset J, McMurray DN, Karakousis PC, Lamichhane G, Bishai WR. Accelerated detection of Mycobacterium tuberculosis genes essential for bacterial survival in guinea pigs, compared with mice. J Infect Dis. 2007 Jun 1;195(11):1634-42. Epub 2007 Apr 23.  PMID: 17471433.

45: Williams EP, Lee JH, Bishai WR, Colantuoni C, Karakousis PC. Mycobacterium tuberculosis SigF regulates genes encoding cell wall-associated proteins and directly regulates the transcriptional regulatory gene phoY1. J Bacteriol. 2007 Jun;189(11):4234-42. Epub 2007 Mar 23.  PMID: 17384187;  PMCID: PMC1913405.

46: Karakousis PC, Magill SS, Gupta A. Paraplegia caused by invasive spinal aspergillosis. Neurology. 2007 Jan 9;68(2):158. Erratum in: Neurology. 2007 Jul 10;69(2):225.  PMID: 17210900.

47: Brastianos PK, Swanson JW, Torbenson M, Sperati J, Karakousis PC. Tuberculosis-associated haemophagocytic syndrome. Lancet Infect Dis. 2006 Jul;6(7):447-54. Review.  PMID: 16790385.

48: Karakousis PC, Trucksis M, Dumler JS. Chronic Q fever in the United States. J Clin Microbiol. 2006 Jun;44(6):2283-7. Review.  PMID: 16757641;  PMCID: PMC1489455.

49: Karakousis PC, Yoshimatsu T, Lamichhane G, Woolwine SC, Nuermberger EL, Grosset J, Bishai WR. Dormancy phenotype displayed by extracellular Mycobacterium tuberculosis within artificial granulomas in mice. J Exp Med. 2004 Sep 6;200(5):647-57.  PMID: 15353557;  PMCID: PMC2212740.

50: Karakousis PC, Moore RD, Chaisson RE. Mycobacterium avium complex in patients with HIV infection in the era of highly active antiretroviral therapy. Lancet Infect Dis. 2004 Sep;4(9):557-65. Review.  PMID: 15336223.

51: Coppola AG, Karakousis PC, Metz DC, Go MF, Mhokashi M, Howden CW, Raufman JP, Sharma VK. Hepatitis C knowledge among primary care residents: is our teaching adequate for the times? Am J Gastroenterol. 2004 Sep;99(9):1720-5.  PMID: 15330909.

52: Karakousis PC, Page KR, Bishai WR. From the Infectious Diseases Society of America (IDSA) meeting - important new findings in HIV treatment and pathogenesis, 2003. Hopkins HIV Rep. 2004 Jan;16(1):2-3. Erratum in: Hopkins HIV  Rep. 2004 Mar;16(2):4.  PMID: 14989191.

53: Karakousis PC, Bishai WR, Dorman SE. Mycobacterium tuberculosis cell envelope lipids and the host immune response. Cell Microbiol. 2004 Feb;6(2):105-16. Review.  PMID: 14706097.

54: Page KR, Karakousis PC, Maslow JN. Postoperative pneumococcal cellulitis in systemic lupus erythematosus. Scand J Infect Dis. 2003;35(2):141-3. Review.  PMID: 12693569.

55: Karakousis PC, Lee MS, Grostern RJ, Nichols CW. The role of conjunctival biopsy in the diagnosis of Wegener's granulomatosis: a case report. Can J Ophthalmol. 2002 Apr;37(3):179-81.  PMID: 12083477.

56: Karakousis PC, Page KR, Varello MA, Howlett PJ, Stieritz DD. Waterhouse-Friderichsen syndrome after infection with group A streptococcus. Mayo Clin Proc. 2001 Nov;76(11):1167-70.  PMID: 11702906.

57: Karakousis PC, Tomaszewski JE. Ulcerating subcutaneous nodules and advanced renal failure: is it time for a new liver? Nephrol Dial Transplant. 2001 Oct;16(10):2095-6.  PMID: 11572906.

58: Karakousis PC, John SK, Behling KC, Surace EM, Smith JE, Hendrickson A, Tang  WX, Bennett J, Milam AH. Localization of pigment epithelium derived factor (PEDF) in developing and adult human ocular tissues. Mol Vis. 2001 Jun 30;7:154-63.  PMID: 11438800.

59: Canning BJ, Undem BJ, Karakousis PC, Dey RD. Effects of organotypic culture on parasympathetic innervation of guinea pig trachealis. Am J Physiol. 1996 Nov;271(5 Pt 1):L698-706.  PMID: 8944712. 

 

Book Chapters:

Karakousis PC, Chaisson RE. Mycobacterial infections and HIV infection. In: Fishman's Pulmonary Diseases and Disorders, 4th edition, Fishman AP, Elias JA, Fishman JA, Grippi MA, Senior RM, Pack AI, ed. New York: McGraw Hill, 2008:2487-2497.

Karakousis PC. Mechanisms of Action and Resistance of the Antimycobacterial Agents. In: Antimicrobial Drug Resistance, Mayers D, ed. New York: Humana Press, 2009:271-291

Kolyva A, Karakousis PC. Old and New TB Drugs: Mechanisms of Action and Resistance. In: Mycobacterium tuberculosis/Book 2, Cardona P-J, ed. InTech, 2011.

 

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