vaccine contamination
Updated: 12-22-2004
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[Items with a PMID number will usually have abstracts available to read. Go to the PubMed website: http://www4.ncbi.nlm.nih.gov/entrez/query.fcgi and enter the accession number into the search box.]

1. Trijzelaar B. Regulatory affairs and biotechnology in Europe: III. Introduction into good regulatory practice--validation of virus removal and inactivation. Biotherapy 1993; 6(2):93-102. PMID 8398576.

2. Vilcek S. Identification of pestiviruses contaminating cell lines and fetal calf sera. Acta Virol 2001 Apr;45(2):81-6. PMID 11719986.

3. Barkema HW, Bartels CJ, van Wuijckhuise L, Hesselink JW, Holzhauer M, Weber MF, Franken P, Kock PA, Bruschke CJ, Zimmer GM. Outbreak of bovine virus diarrhea on Dutch dairy farms induced by a bovine herpesvirus 1 marker vaccine contaminated with bovine virus diarrhea virus type 2. Tijdschr Diergeneeskd 2001 Mar 15;126(6):158-65. PMID 11285633.

4. Rolleston WB. Bovine serum: reducing the variables through the use of donor herds. Dev Biol Stand 1999;99:79-86. PMID 10404879.

5. Bolin SR, Matthews PJ, Ridpath JF. Methods for detection and frequency of contamination of fetal calf serum with bovine viral diarrhea virus and antibodies against bovine viral diarrhea virus. : J Vet Diagn Invest 1991 Jul;3(3):199-203. PMID 1655059.

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7. Yanagi M, Bukh J, Emerson SU, Purcell RH. Contamination of commercially available fetal bovine sera with bovine viral diarrhea virus genomes: implications for the study of hepatitis C virus in cell cultures. J Infect Dis 1996 Dec;174(6):1324-7. PMID 8940226.

8. Giangaspero M, Harasawa R, Verhulst A. Genotypic analysis of the 5'-untranslated region of a pestivirus strain isolated from human leucocytes. Microbiol Immunol 1997;41(10):829-34. PMID 9403511.

9. Harasawa R, Mizusawa H. Demonstration and genotyping of pestivirus RNA from mammalian cell lines. Microbiol Immunol 1995;39(12):979-85. PMID 8789057.

10. Brock, KV. Pathogenesis of BVDV Infections. http://www.vetmed.auburn.edu/~brockkv/path.htm  and http://www.vetmed.auburn.edu/~brockkv/terms.htm

11. Stoffregen B, Bolin SR, Ridpath JF, Pohlenz J. Morphologic lesions in type 2 BVDV infections experimentally induced by strain BVDV2-1373 recovered from a field case. Vet Microbiol 2000 Nov 15;77(1-2):157-62. PMID 11042409.

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15. Potts BJ, Sever JL, Tzan NR, Huddleston D, Elder GA. Possible role of pestiviruses in microcephaly. Lancet 1987 Apr 25;1(8539):972-3.

16. Harasawa R. Latent Risk in Bovine Serums Used for Biopharmaceutic Production. http://www.asmusa.org/pcsrc/sum02.htm

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20. Harasawa R, Mizusawa H. Detection of Pestiviruses from Mammalian Cell Cultures by the Polymerase Chain Reaction. Proceedings of 3rd Internet World Congress on Biomedical Sciences 1996.12.9-20 Riken, Tsukuba, Japan. http://www.3iwc.riken.go.jp/CONGRESS
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21. Contreras G, Bather R, Furesz J, Becker BC. Activation of metastatic potential in African green monkey kidney cell lines by prolonged in vitro culture. In Vitro Cell Dev Biol 1985 Nov;21(11):649-52. PMID 4066602.

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23. Furesz J, Fanok A, Contreras G, Becker B. Tumorigenicity testing of various cell substrates for production of biologicals. Dev Biol Stand 1989;70:233-43. PMID 2759351.

24. Letter to Sponsors Using Vero Cells as a Cell Substrate for Investigational Vaccines. Department of Health and Human Services, Public Health Service, Food and Drug Administration, Division of Vaccines and Related Products Applications, March 12, 2001. www.fda.gov/cber/ltr/vero031301.htm

25. U.S. Dept. of Health and Human Services, Public Health Service, Food and Drug Administration, Center for Biologics Evaluation and Research. Evolving Scientific and Regulatory Perspectives on Cell Substrates for Vaccine Development. http://www.fda.gov/cber/minutes/0907evolv.txt

26. Lewis AM Jr. Developing an approach to evaluate the use of neoplastic cells as vaccine substrates. Dev Biol (Basel) 2001;106:37-42; discussion 42-3. PMID 11761251.

27. Purcell DF. Pathogenesis of replication competent retroviruses derived from mouse cells in immuno suppressed primates: implications for use of neoplastic cells as vaccine substrates. Dev Biol (Basel) 2001;106:187-98; discussion 199, 253-63. PMID 11761231.

28. Amosenko FA, Svitkin YV, Popova VD, Terletskaya EN, Timofeev AV, Elbert LB, Lashkevich VA, Drozdov SG. Use of protamine sulphate for elimination of substrate DNA in polio vaccines produced on continuous cell lines. Vaccine 1991 Mar;9(3):207-9. PMID 1645900.

29. Thyagarajan B, McCormick-Graham M, Romero DP, Campbell C. Characterization of homologous DNA recombination activity in normal and immortal mammalian cells. Nucleic Acids Res 1996 Oct 15;24(20):4084-91. PMID 8918816 (full text article available free at this link).

30. Ruscetti SK. Generation of mink cell focus-inducing retroviruses: a model for understanding how viral-viral and viral-cellular interactions can result in biological consequences. Dev Biol (Basel) 2001;106:163-7; discussion 167-8, 253-63. PMID 11761228.

31. Hilleman MR. History, precedent, and progress in the development of mammalian cell culture systems for preparing vaccines: safety considerations revisited. J Med Virol 1990 May;31(1):5-12. PMID 2198327.

32. Butel JS, Lednicky JA. Cell and molecular biology of simian virus 40: implications for human infections and disease. J Natl Cancer Inst 1999 Jan 20;91(2):119-34. PMID 9923853.

33. Arrington AS, Lednicky JA, Butel JS. Molecular characterization of SV40 DNA in multiple samples from a human mesothelioma. Anticancer Res 2000 Mar-Apr;20(2A):879-84. PMID 10810370.

34. Vilchez RA, Madden CR, Kozinetz CA, Halvorson SJ, White ZS, Jorgensen JL, Finch CJ, Butel JS. Association between simian virus 40 and non-Hodgkin lymphoma. Lancet 2002 Mar 9;359(9309):817-23. PMID 11897278.

35. Shivapurkar N, Harada K, Reddy J, Scheuermann RH, Xu Y, McKenna RW, Milchgrub S, Kroft SH, Feng Z, Gazdar AF. Presence of simian virus 40 DNA sequences in human lymphomas. Lancet 2002 Mar 9;359(9309):851-2. PMID 11897287.

36. Bu X, Zhang X, Zhang X, et Al. A study of simian virus 40 infection and its origin in human brain tumors. Zhonghua Liu Xing Bing Xue Za Zhi 2000 Feb;21(1):19-21. PMID 11860751.

37. Butel JS, Jafar S, Wong C, Arrington AS, Opekun AR, Finegold MJ, Adam E. Evidence of SV40 infections in hospitalized children. Hum Pathol 1999 Dec;30(12):1496-502. PMID 10667429.

38. von Mettenheim AE. Studies on simian viruses as possible contaminants of inactivated virus vaccines. I. Direct and serologic detection of simian adenovirus SV20. Zentralbl Bakteriol [Orig A] 1975 Jul;232(2-3):131-40. PMID 1179876.

39. Schuurman R, van Steenis B, Sol C. Bovine polyomavirus, a frequent contaminant of calf serum. Biologicals 1991 Oct;19(4):265-70. PMID 1665699.

40. Nettleton PF, Rweyemamu MM. The association of calf serum with the contamination of BHK21 clone 13 suspension cells by a parvovirus serologically related to the minute virus of mice (MVM). Arch Virol 1980;64(4):359-74. PMID 7396725.

41. Fong CK, Gross PA, Hsiung GD, Swack NS. Use of electron microscopy for detection of viral and other microbial contaminants in bovine sera. J Clin Microbiol 1975 Feb;1(2):219-24. PMID 51855.

42. Erickson GA, Bolin SR, Landgraf JG. Viral contamination of fetal bovine serum used for tissue culture: risks and concerns. Dev Biol Stand 1991;75:173-5. PMID 1665460.

43. Kniazeff AJ, Wopschall LJ, Hopps HE, Morris CS. Detection of bovine viruses in fetal bovine serum used in cell culture. In Vitro 1975 Nov-Dec;11(6):400-3. PMID 172434.

44. Michalski FJ, Dietz A, Hsiung GD. Growth characteristics of bovine herpesvirus 1 (infectious bovine rhinotracheitis) in human diploid cell strain WI-38. Proc Soc Exp Biol Med 1976 Feb;151(2):407-10. PMID 175382.

45. Egyed L. Bovine herpesvirus type 4: a special herpesvirus (review article). Acta Vet Hung 2000;48(4):501-13. PMID 11402667.

46. Egyed L. Replication of bovine herpesvirus type 4 in human cells in vitro. J Clin Microbiol 1998 Jul;36(7):2109-11. PMID 9650976.

47. Johnson ES. Poultry oncogenic retroviruses and humans. Cancer Detect Prev 1994;18(1):9-30. PMID 8162609.

48. For example, see Nevins JR, “Cell Transformation by Viruses”, in Knipe DM et al (ed.), 2001. Fields Virology (4th ed), Vol. I, chapter 10, p.245-283. Lippincott. Also see Joklik WK, “Tumor Viruses”, in Joklik WK et al, 1992. Zinsser Microbiology (20th ed), chapter 59, p.869-905. Appleton & Lange.

49. Felder MP, Eychene A, Laugier D, Marx M, Dezelee P, Calothy G. Steps and mechanisms of oncogene transduction by retroviruses. Folia Biol (Praha) 1994;40(5):225-35. PMID 7895853.

50. Harris RJ, Dougherty RM, Biggs PM, Payne LN, Goffe AP, Churchill AE, Mortimer R. Contaminant viruses in two live virus vaccines produced in chick cells. J Hyg (Lond) 1966 Mar;64(1):1-7. PMID 4286627.

51. Payne LN, Biggs PM, Chubb RC, Bowden RS. Contamination of egg-adapted canine distemper vaccine by avian leukosis virus. Vet Rec 1966 Jan 8;78(2):45-8. PMID 4285488.

52. Knipe DM et al (ed.) 2001. Fields Virology (4th ed), Vol. I, p.1103. Lippincott.

53. Johnson JA, Heneine W. Characterization of endogenous avian leukosis viruses in chicken embryonic fibroblast substrates used in production of measles and mumps vaccines. J Virol 2001 Apr;75(8):3605-12. PMID 11264350.

54. Maudru T, Peden KW. Analysis of a coded panel of licensed vaccines by polymerase chain reaction-based reverse transcriptase assays: a collaborative study. J Clin Virol 1998 Jul 24;11(1):19-28. PMID 9784140.

55. Tsang SX, Switzer WM, Shanmugam V, Johnson JA, Goldsmith C, Wright A, Fadly A, Thea D, Jaffe H, Folks TM, Heneine W. Evidence of avian leukosis virus subgroup E and endogenous avian virus in measles and mumps vaccines derived from chicken cells: investigation of transmission to vaccine recipients. J Virol 1999 Jul;73(7):5843-51. PMID 10364336.

56. Hussain AI, Shanmugam V, Switzer WM, Tsang SX, Fadly A, Thea D, Helfand R, Bellini WJ, Folks TM, Heneine W. Lack of evidence of endogenous avian leukosis virus and endogenous avian retrovirus transmission to measles, mumps, and rubella vaccine recipients. Emerg Infect Dis 2001 Jan-Feb;7(1):66-72. PMID 11266296. Full article text available at www.cdc.gov/ncidod/eid/vol7no1/hussain.htm

57. Arshad SS, Howes K, Barron GS, Smith LM, Russell PH, Payne LN. Tissue tropism of the HPRS-103 strain of J subgroup avian leukosis virus and of a derivative acutely transforming virus. Vet Pathol 1997 Mar;34(2):127-37. PMID 9066079.

58. Johnson ES, Overby L, Philpot R. Detection of antibodies to avian leukosis/sarcoma viruses and reticuloendotheliosis viruses in humans by western blot assay. Cancer Detect Prev 1995;19(6):472-86. PMID 8925516.

59. Raines MA, Maihle NJ, Moscovici C, Crittenden L, Kung HJ. Mechanism of c-erbB transduction: newly released transducing viruses retain poly(A) tracts of erbB transcripts and encode C-terminally intact erbB proteins. J Virol 1988 Jul;62(7):2437-43. PMID 2897475.

60. Joklik WK, “Tumor Viruses”, in Joklik WK et al, 1992. Zinsser Microbiology (20th ed.), chapter 59, p.889. Appleton & Lange.

61. Geier MR, Stanbro H, Merril CR. Endotoxins in commercial vaccines. Appl Environ Microbiol 1978 Sep;36(3):445-9. PMID 727776.

62. Kreeftenberg JG, Loggen HG, van Ramshorst JD, Beuvery EC. The limulus amebocyte lysate test micromethod and application in the control of sera and vaccines. Dev Biol Stand 1977;34:15-20. PMID 838139.

63. Sharma SK. Endotoxin detection and elimination in biotechnology. Biotechnol Appl Biochem 1986 Feb;8(1):5-22. PMID 3548752.

64. Fumarola D, Panaro A, Palma R, Mazzone A. Endotoxic contamination of biological products (ribosomal vaccines, viral vaccines and interferon). G Batteriol Virol Immunol 1979 Jan-Jun;72(1-6):72-7. PMID 95449.

65. Cussler K, Godau H, Gyra H. Investigation of the endotoxin content of veterinary vaccines. ALTEX 1994;11(5):24-29. PMID 11178403.

66. Whitaker AM, Smith EM. Effect of bacterial toxins in serum on the chromosomes of WI-38. Dev Biol Stand 1976 Dec 13-15;37:185-90. PMID 801471.

67. See “What are nanobacteria?” at http://www.nanobaclabs.com/
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68. Breitschwerdt EB, Sontakke S, Cannedy A, Hancock SI, Bradley JM. Infection with Bartonella weissii and detection of Nanobacterium antigens in a North Carolina beef herd. J Clin Microbiol 2001 Mar;39(3):879-82. PMID 11230398. Full article text available at http://jcm.asm.org/cgi/content/
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69. Nanobacteria detected in vaccines. NanoNews 2001 July;1(2). Article available at http://www.nanobaclabs.com/Files/Newsletter/JulyNANONEWS1.pdf

70. Cell Culture Contamination Example. Mycoplasma. http://www.unc.edu/depts/tcf/mycoplasma.htm

71. Prasad E, Lim-Fong R. Mycoplasmas. http://www2.provlab.ab.ca/bugs/biologos/9702mypl.htm

72. Mycoplasma Detection Kit. http://www.atcc.org/Products/MycoplasmaDetectKit.cfm

73. Mattman LH, 2001. Cell wall deficient forms: stealth pathogens (3rd ed.). CRC Press.

74. Uphoff CC, Drexler HG. Prevention of mycoplasma contamination in leukemia-lymphoma cell lines. Hum Cell 2001 Sep;14(3):244-7. PMID 11774744.

75. Mycoplasma Detection and Elimination. http://www.dsmz.de/mutz/mutzmyco.htm

76. Mycoplasma Detection Kit. http://www.biovalley.fr/anglais/biology/mob_cc.htm

77. Kojima A, Takahashi T, Kijima M, Ogikubo Y, Tamura Y, Harasawa R. Detection of mycoplasma DNA in veterinary live virus vaccines by the polymerase chain reaction. J Vet Med Sci 1996 Oct;58(10):1045-8. PMID 8916012.

78. Kojima A, Takahashi T, Kijima M, Ogikubo Y, Nishimura M, Nishimura S, Harasawa R, Tamura Y. Detection of Mycoplasma in avian live virus vaccines by polymerase chain reaction. Biologicals 1997 Dec;25(4):365-71. PMID 9467032.

79. Benisheva T, Sovova V, Ivanov I, Opalchenova G. Comparison of methods used for detection of mycoplasma contamination in cell cultures, sera, and live-virus vaccines. Folia Biol (Praha) 1993;39(5):270-6. PMID 8206173.

80. Nicolson GL, Nass M, Nicolson N. Anthrax vaccine: controversy over safety and efficacy. Antimicrobics and Infectious Disease Newsletter (Elsevier Science) 2000. Article located at http://www.flatlandbooks.com/anthrax.html

81. Thornton DH. A survey of mycoplasma detection in veterinary vaccines. Vaccine 1986 Dec;4(4):237-40. PMID 3799018.

82. Kong F, James G, Gordon S, Zelynski A, Gilbert GL. Species-specific PCR for identification of common contaminant mollicutes in cell culture. Appl Environ Microbiol 2001 Jul;67(7):3195-200. PMID 11425741.

83. Mycoplasma testing by PCR. http://locus.umdnj.edu/nia/qc/myco.html

84. Mycoplasma sp. Reagent Set. http://www.euroclone.net/mol_biology/mycoplasma.htm

85. Macomber PB. Cancer and cell wall deficient bacteria. Med Hypotheses 1990 May;32(1):1-9. PMID 2190063.

86. Baseman JB, Tully JG. Mycoplasmas: sophisticated, reemerging, and burdened by their notoriety. Emerg Infect Dis 1997 Jan-Mar;3(1):21-32. PMID 9126441. Full text article available at http://www.cdc.gov/ncidod/eid/vol3no1/baseman.htm

87. Gartler SM. Apparent Hela cell contamination of human heteroploid cell lines. Nature 1968 Feb 24;217(5130):750-1. PMID 5641128.

88. Lavappa KS. Survey of ATCC stocks of human cell lines for HeLa contamination. In Vitro 1978 May;14(5):469-75. PMID 566722.

89. Nelson-Rees WA, Daniels DW, Flandermeyer RR. Cross-contamination of cells in culture. Science 1981 Apr 24;212(4493):446-52. PMID 6451928.

90. Gold M. The cells that would not die. Science 81 1981 April; 29-35.

91. Gold M, 1986. A Conspiracy of Cells: One Woman's Immortal Legacy and the Medical Scandal It Caused. State University of New York Press.

92. Demidova SA, Tsareva AA, Mikhailova GR, Perekrest VV, Gushchin BV. Several methodologic problems in the control of cell cultures. Vopr Virusol 1976 May-Jun;(3):371-9. PMID 983006.

93. Hukku B, Halton DM, Mally M, Peterson WD Jr. Cell characterization by use of multiple genetic markers. Adv Exp Med Biol 1984;172:13-31. PMID 6328905.

94. MacLeod RA, Dirks WG, Matsuo Y, Kaufmann M, Milch H, Drexler HG. Widespread intraspecies cross-contamination of human tumor cell lines arising at source. Int J Cancer 1999 Nov 12;83(4):555-63. PMID 10508494.

95. Stacey GN. Cell contamination leads to inaccurate data: we must take action now. Nature 2000 Jan 27;403(6768):356. PMID 10667765.

96. Kniss DA, Xie Y, Li Y, Kumar S, Linton EA, Cohen P, Fan-Havard P, Redman CW, Sargent IL. ED(27) Trophoblast-like Cells Isolated from First-trimester Chorionic Villi are Genetically Identical to HeLa Cells Yet Exhibit a Distinct Phenotype. Placenta 2002 Jan;23(1):32-43. PMID 11869090.

97. Buttner M, Oehmig A, Weiland F, Rziha HJ, Pfaff E. Detection of virus or virus specific nucleic acid in foodstuff or bioproducts--hazards and risk assessment. Arch Virol Suppl 1997;13:57-66. PMID 9413526.

98. Monath TP, Cropp CB, Harrison AK. Mode of entry of a neurotropic arbovirus into the central nervous system. Reinvestigation of an old controversy. Lab Invest 1983 Apr;48(4):399-410. PMID 6300550.

99. Burke DS, Monath TP, “Flaviviruses”, in Knipe DM et al (ed.), 2001. Fields Virology (4th ed), Vol. I, chapter 33, p.1057. Lippincott.

100. Hoffman PN, Abuknesha RA, Andrews NJ, Samuel D, Lloyd JS. A model to assess the infection potential of jet injectors used in mass immunisation. Vaccine 2001 Jul 16;19(28-29):4020-7. PMID 11427278.

101. Canter J, Mackey K, Good LS, Roberto RR, Chin J, Bond WW, Alter MJ, Horan JM. An outbreak of hepatitis B associated with jet injections in a weight reduction clinic. Arch Intern Med 1990 Sep;150(9):1923-7. PMID 2393323.

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103. McAleer WJ, Buynak EB, Maigetter RZ, Wampler DE, Miller WJ, Hilleman MR. Human hepatitis B vaccine from recombinant yeast. Nature 1984 Jan 12-18;307(5947):178-80. PMID 6318124.

104. Hilleman MR. Yeast recombinant hepatitis B vaccine. Infection 1987 Jan-Feb;15(1):3-7. PMID 2437037.

105. Points to Consider on Plasmid DNA Vaccines for Preventive Infectious Disease Indications. Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Vaccine Research and Review, December 1996. Full article available at http://www.fda.gov/cber/gdlns/plasmid.txt

106. Ho M, Ryan A, Cummins J, Traavik T. Slipping through the regulatory net: 'Naked' and 'free' nucleic acids. TWN Biotechnology and Biosafety Series No. 5, 2001. Available at http://www.twnside.org.sg/title/biod5.htm

107. Petricciani JC. Safety issues relating to the use of mammalian cells as hosts. Dev Biol Stand 1985;59:149-53. PMID 3891461.

108. Phillips A. Dispelling vaccination myths: an internationally published, referenced report. 1998. Report available at http://www.unc.edu/~aphillip/www/chf/myths/dvm1.htm  For statistics regarding adverse events, see the link at http://www.unc.edu/~aphillip/www/chf/myths/dvm11.htm

109. See a discussion of issues surrounding proposed forced smallpox vaccination at: Fisher, BL. Smallpox and forced vaccination: what every American needs to know. The Vaccine Reaction, Winter 2002. Article available at http://www.909shot.com/smallpoxspecialrpt.htm.  The entire text of the Model State Emergency Health Powers Act, currently being considered by the various U.S. state governments is available at http://www.publichealthlaw.net/MSEHPA/MSEHPA2.pdf

110. National Vaccine Program Office, Vaccine Fact Sheets: Vaccine Product Approval Process. Article available at http://www.cdc.gov/od/nvpo/fs_tableII_doc2.htm

111. Garnick RL. Raw materials as a source of contamination in large-scale cell culture. Dev Biol Stand 1998;93:21-9. PMID 9737373.

112. Fadly AM, Smith EJ. Isolation and some characteristics of a subgroup J-like avian leukosis virus associated with myeloid leukosis in meat-type chickens in the United States. Avian Dis 1999 Jul-Sep;43(3):391-400. PMID 10494407.

113. Grunder AA, Benkel BF, Chambers JR, Sabour MP, Gavora JS, Dickie JW. Characterization of four endogenous viral genes in semi-congenic lines of meat chickens. Poult Sci 1999 Jun;78(6):873-7. PMID 10438132.

114. Pham TD, Spencer JL, Johnson ES. Detection of avian leukosis virus in albumen of chicken eggs using reverse transcription polymerase chain reaction. J Virol Methods 1999 Mar;78(1-2):1-11. PMID 10204692.

115. http://www.worldnetdaily.com
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116. Kopelovich L. Are all normal diploid human cell strains alike? Relevance to carcinogenic mechanisms in vitro. Exp Cell Biol 1982;50(5):266-70. PMID

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