13 results on '"Manschreck C"'
Search Results
2. A Founder Mutation in Regulator of Telomere Elongation Helicase 1, RTEL1, Underlies Severe Immunodeficiency and Features of Hoyeraal Hreidarsson Syndrome
- Author
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Ballew BJ, Joesph V, De S, Sarek G, Vannier JB, Stracker T, Small T, O’Reilly R, Offit K, Schrader KA, Manschreck C, Harlan MH, Sullivan J, Stratton K, Yeager M, Jacobs K, Giri N, Alter BP, Boland J, Burdett L, Boulton SJ, and Savage SA & Petrini JHJ
- Published
- 2013
3. An analysis of the association between prostate cancer risk loci, PSA levels, disease aggressiveness and disease-specific mortality
- Author
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Sullivan, J, primary, Kopp, R, additional, Stratton, K, additional, Manschreck, C, additional, Corines, M, additional, Rau-Murthy, R, additional, Hayes, J, additional, Lincon, A, additional, Ashraf, A, additional, Thomas, T, additional, Schrader, K, additional, Gallagher, D, additional, Hamilton, R, additional, Scher, H, additional, Lilja, H, additional, Scardino, P, additional, Eastham, J, additional, Offit, K, additional, Vijai, J, additional, and Klein, R J, additional
- Published
- 2015
- Full Text
- View/download PDF
4. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia
- Author
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Shah, S., Schrader, K.A., Waanders, E., Timms, A.E., Vijai, J., Miething, C., Wechsler, J., Yang, J., Hayes, J., Klein, R.J., Zhang, J., Wei, L., Wu, G., Rusch, M., Nagahawatte, P., Ma, J, Chen, S.C., Song, G., Cheng, J., Meyers, P., Bhojwani, D., Jhanwar, S., Maslak, P., Fleisher, M., Littman, J., Offit, L., Rau-Murthy, R., Fleischut, M.H., Corines, M., Murali, R., Gao, X., Manschreck, C., Kitzing, T., Murty, V.V., Raimondi, S.C., Kuiper, R.P., Simons, A., Schiffman, J.D., Onel, K., Plon, S.E., Wheeler, D.A., Ritter, D., Ziegler, D.S., Tucker, K., Sutton, R., Chenevix-Trench, G., Li, J., Huntsman, D.G., Hansford, S., Senz, J., Walsh, T., Lee (Helen Dowling Instituut), M. van der, Hahn, C.N., Roberts, K.G., King, M.C., Lo, S.M., Levine, R.L., Viale, A., Socci, N.D., Nathanson, K.L., Scott, H.S., Daly, M., Lipkin, S.M., Lowe, S.W., Downing, J.R., Altshuler, D., Sandlund, J.T., Horwitz, M.S., Mullighan, C.G., Offit, K., Shah, S., Schrader, K.A., Waanders, E., Timms, A.E., Vijai, J., Miething, C., Wechsler, J., Yang, J., Hayes, J., Klein, R.J., Zhang, J., Wei, L., Wu, G., Rusch, M., Nagahawatte, P., Ma, J, Chen, S.C., Song, G., Cheng, J., Meyers, P., Bhojwani, D., Jhanwar, S., Maslak, P., Fleisher, M., Littman, J., Offit, L., Rau-Murthy, R., Fleischut, M.H., Corines, M., Murali, R., Gao, X., Manschreck, C., Kitzing, T., Murty, V.V., Raimondi, S.C., Kuiper, R.P., Simons, A., Schiffman, J.D., Onel, K., Plon, S.E., Wheeler, D.A., Ritter, D., Ziegler, D.S., Tucker, K., Sutton, R., Chenevix-Trench, G., Li, J., Huntsman, D.G., Hansford, S., Senz, J., Walsh, T., Lee (Helen Dowling Instituut), M. van der, Hahn, C.N., Roberts, K.G., King, M.C., Lo, S.M., Levine, R.L., Viale, A., Socci, N.D., Nathanson, K.L., Scott, H.S., Daly, M., Lipkin, S.M., Lowe, S.W., Downing, J.R., Altshuler, D., Sandlund, J.T., Horwitz, M.S., Mullighan, C.G., and Offit, K.
- Abstract
Contains fulltext : 126772.pdf (publisher's version ) (Closed access), Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL), but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly183Ser), affecting the octapeptide domain of PAX5 that was found to segregate with disease in two unrelated kindreds with autosomal dominant B-ALL. Leukemic cells from all affected individuals in both families exhibited 9p deletion, with loss of heterozygosity and retention of the mutant PAX5 allele at 9p13. Two additional sporadic ALL cases with 9p loss harbored somatic PAX5 substitutions affecting Gly183. Functional and gene expression analysis of the PAX5 mutation demonstrated that it had significantly reduced transcriptional activity. These data extend the role of PAX5 alterations in the pathogenesis of pre-B cell ALL and implicate PAX5 in a new syndrome of susceptibility to pre-B cell neoplasia.
- Published
- 2013
5. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia
- Author
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Shah, S, Schrader, KA, Vijai, J, Miething, C, Hayes, J, Klein, RJ, Gao, X, Kitzing, T, Lowe, SW, Offit, K, Littman, J, Offit, L, Rau-Murthy, R, Fleischut, MH, Corines, M, Manschreck, C, Waanders, E, Wei, L, Ma, J, Chen, S-C, Song, G, Cheng, J, Raimondi, SC, Roberts, KG, Downing, JR, Mullighan, CG, Kuiper, RP, Simons, A, Timms, AE, Wechsler, J, Horwitz, MS, Yang, J, Zhang, J, Wu, G, Rusch, M, Nagahawatte, P, Meyers, P, Bhojwani, D, Sandlund, JT, Jhanwar, S, Murali, R, Maslak, P, Fleisher, M, Murty, VV, Schiffman, JD, Onel, K, Plon, SE, Wheeler, DA, Ritter, D, Ziegler, DS, Sutton, R, Tucker, K, Chenevix-Trench, G, Li, J, Huntsman, DG, Hansford, S, Senz, J, Walsh, T, Lee, M, King, M-C, Hahn, CN, Scott, HS, Lo, SM, Levine, RL, Viale, A, Socci, ND, Nathanson, KL, Daly, M, Lipkin, SM, Altshuler, D, Shah, S, Schrader, KA, Vijai, J, Miething, C, Hayes, J, Klein, RJ, Gao, X, Kitzing, T, Lowe, SW, Offit, K, Littman, J, Offit, L, Rau-Murthy, R, Fleischut, MH, Corines, M, Manschreck, C, Waanders, E, Wei, L, Ma, J, Chen, S-C, Song, G, Cheng, J, Raimondi, SC, Roberts, KG, Downing, JR, Mullighan, CG, Kuiper, RP, Simons, A, Timms, AE, Wechsler, J, Horwitz, MS, Yang, J, Zhang, J, Wu, G, Rusch, M, Nagahawatte, P, Meyers, P, Bhojwani, D, Sandlund, JT, Jhanwar, S, Murali, R, Maslak, P, Fleisher, M, Murty, VV, Schiffman, JD, Onel, K, Plon, SE, Wheeler, DA, Ritter, D, Ziegler, DS, Sutton, R, Tucker, K, Chenevix-Trench, G, Li, J, Huntsman, DG, Hansford, S, Senz, J, Walsh, T, Lee, M, King, M-C, Hahn, CN, Scott, HS, Lo, SM, Levine, RL, Viale, A, Socci, ND, Nathanson, KL, Daly, M, Lipkin, SM, and Altshuler, D
- Abstract
Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL), but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly183Ser), affecting the octapeptide domain of PAX5 that was found to segregate with disease in two unrelated kindreds with autosomal dominant B-ALL. Leukemic cells from all affected individuals in both families exhibited 9p deletion, with loss of heterozygosity and retention of the mutant PAX5 allele at 9p13. Two additional sporadic ALL cases with 9p loss harbored somatic PAX5 substitutions affecting Gly183. Functional and gene expression analysis of the PAX5 mutation demonstrated that it had significantly reduced transcriptional activity. These data extend the role of PAX5 alterations in the pathogenesis of pre-B cell ALL and implicate PAX5 in a new syndrome of susceptibility to pre-B cell neoplasia. © 2013 Nature America, Inc. All rights reserved.
- Published
- 2013
6. Common breast cancer risk alleles and lobular carcinoma in situ (LCIS)
- Author
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Koslow, S., Manschreck, C., Patil, S., Vijai, J., Muhsen, S., Anna Park, Robson, M., and King, T.
7. Clinical Evaluation of Cisplatin Sensitivity of Germline Polymorphisms in Neoadjuvant Chemotherapy for Urothelial Cancer.
- Author
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O'Donnell PH, Alanee S, Stratton KL, Garcia-Grossman IR, Cao H, Ostrovnaya I, Plimack ER, Manschreck C, Ganshert C, Smith ND, Steinberg GD, Vijai J, Offit K, Stadler WM, and Bajorin DF
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents pharmacology, Carcinoma, Transitional Cell genetics, Carcinoma, Transitional Cell pathology, Cisplatin pharmacology, Female, Humans, Male, Middle Aged, Neoadjuvant Therapy, Neoplasm Staging, Pharmacogenomic Variants, Survival Analysis, Treatment Outcome, Antineoplastic Agents administration & dosage, Carcinoma, Transitional Cell drug therapy, Cisplatin administration & dosage, Germ-Line Mutation, Polymorphism, Single Nucleotide
- Abstract
Background: Level 1 evidence has demonstrated increased overall survival with cisplatin-based neoadjuvant chemotherapy for patients with muscle-invasive urothelial cancer. Usage remains low, however, in part because neoadjuvant chemotherapy will not be effective for every patient. To identify the patients most likely to benefit, we evaluated germline pharmacogenomic markers for association with neoadjuvant chemotherapy sensitivity in 2 large cohorts of patients with urothelial cancer., Patients and Methods: Patients receiving neoadjuvant cisplatin-based chemotherapy for muscle-invasive urothelial cancer were eligible. Nine germline single nucleotide polymorphisms (SNPs) potentially conferring platinum sensitivity were tested for an association with a complete pathologic response to neoadjuvant chemotherapy (pT0) or elimination of muscle-invasive cancer (
- Published
- 2016
- Full Text
- View/download PDF
8. Genome Sequencing of Multiple Primary Tumors Reveals a Novel PALB2 Variant.
- Author
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Schrader KA, Stratton KL, Murali R, Laitman Y, Cavallone L, Offit L, Wen YH, Thomas T, Shah S, Rau-Murthy R, Manschreck C, Salo-Mullen E, Otegbeye E, Corines M, Zhang L, Norton L, Hudis C, Klein RJ, Kauff ND, Robson M, Stadler ZK, Haber DA, Lipkin SM, Friedman E, Foulkes WD, Altshuler D, Vijai J, and Offit K
- Subjects
- Aged, Fanconi Anemia Complementation Group N Protein, Female, Genome, Human, Humans, Neoplasms, Multiple Primary genetics, Nuclear Proteins genetics, Ovarian Neoplasms genetics, Tumor Suppressor Proteins genetics
- Published
- 2016
- Full Text
- View/download PDF
9. A Germline Variant on Chromosome 4q31.1 Associates with Susceptibility to Developing Colon Cancer Metastasis.
- Author
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Markowitz SD, Nock NL, Schmit SL, Stadler ZK, Joseph V, Zhang L, Willis JE, Scacheri P, Veigl M, Adams MD, Raskin L, Sullivan JF, Stratton K, Shia J, Ellis N, Rennert HS, Manschreck C, Li L, Offit K, Elston RC, Rennert G, and Gruber SB
- Subjects
- Aged, Cohort Studies, Colonic Neoplasms ethnology, Female, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Genotype, Haplotypes, Humans, Jews, Linkage Disequilibrium, Male, Middle Aged, Models, Statistical, Neoplasm Metastasis pathology, Odds Ratio, Polymorphism, Single Nucleotide, Chromosomes, Human, Pair 4 genetics, Colonic Neoplasms genetics, Colonic Neoplasms pathology, Germ-Line Mutation, Neoplasm Metastasis genetics
- Abstract
We tested for germline variants showing association to colon cancer metastasis using a genome-wide association study that compared Ashkenazi Jewish individuals with stage IV metastatic colon cancers versus those with stage I or II non-metastatic colon cancers. In a two-stage study design, we demonstrated significant association to developing metastatic disease for rs60745952, that in Ashkenazi discovery and validation cohorts, respectively, showed an odds ratio (OR) = 2.3 (P = 2.73E-06) and OR = 1.89 (P = 8.05E-04) (exceeding validation threshold of 0.0044). Significant association to metastatic colon cancer was further confirmed by a meta-analysis of rs60745952 in these datasets plus an additional Ashkenazi validation cohort (OR = 1.92; 95% CI: 1.28-2.87), and by a permutation test that demonstrated a significantly longer haplotype surrounding rs60745952 in the stage IV samples. rs60745952, located in an intergenic region on chromosome 4q31.1, and not previously associated with cancer, is, thus, a germline genetic marker for susceptibility to developing colon cancer metastases among Ashkenazi Jews.
- Published
- 2016
- Full Text
- View/download PDF
10. Prevalence of HOXB13 mutation in a population of Ashkenazi Jewish men treated for prostate cancer.
- Author
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Alanee S, Shah S, Vijai J, Schrader K, Hamilton R, Rau-Murthy R, Sarrel K, Manschreck C, Eastham J, and Offit K
- Subjects
- Aged, Case-Control Studies, Follow-Up Studies, Genetic Predisposition to Disease, Genotype, Humans, Jews, Male, Middle Aged, Neoplasm Grading, Neoplasm Metastasis, Neoplasm Staging, New York epidemiology, Prevalence, Prognosis, Prostatic Neoplasms therapy, Homeodomain Proteins genetics, Mutation genetics, Prostatic Neoplasms epidemiology, Prostatic Neoplasms genetics
- Abstract
We performed a retrospective analysis of germline DNA samples from Ashkenazi Jewish men and a comparison group of non-Ashkenazi men treated for prostate cancer at our institution to determine the prevalence of HOXB13 G84E mutation in prostate cancer patients of Ashkenazi Jewish heritage, an ethnic group common to the New York City area. Patients were genotyped for G84E using a TaqMan assay (Applied Biosystems). Positive cases were confirmed using Sanger sequencing. Median age at prostate cancer diagnosis was 68 years for 889 Ashkenazi Jewish patients, 64 years for 920 non-Ashkenazi Jewish patients. The median follow up was 9 years for Ashkenazi Jewish patients and 8.8 years for non-Ashkenazi Jewish patients. Only 4 patients were found to be heterozygous carriers of G84E. They were all of non-Ashkenazi Jewish ancestry and were diagnosed at 70, 66, 78, and 49 years of age. Two of them presented with high-risk prostate cancer. The prevalence of G84E in the non-Ashkenazi sample was 0.4%. HOXB13 G84E mutation was not observed in prostate cancer patients of Ashkenazi Jewish ancestry treated at our institution. Screening for G84E, therefore, may be unnecessary in Ashkenazi Jewish men if these results are validated by other studies.
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- 2013
- Full Text
- View/download PDF
11. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia.
- Author
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Shah S, Schrader KA, Waanders E, Timms AE, Vijai J, Miething C, Wechsler J, Yang J, Hayes J, Klein RJ, Zhang J, Wei L, Wu G, Rusch M, Nagahawatte P, Ma J, Chen SC, Song G, Cheng J, Meyers P, Bhojwani D, Jhanwar S, Maslak P, Fleisher M, Littman J, Offit L, Rau-Murthy R, Fleischut MH, Corines M, Murali R, Gao X, Manschreck C, Kitzing T, Murty VV, Raimondi S, Kuiper RP, Simons A, Schiffman JD, Onel K, Plon SE, Wheeler D, Ritter D, Ziegler DS, Tucker K, Sutton R, Chenevix-Trench G, Li J, Huntsman DG, Hansford S, Senz J, Walsh T, Lee M, Hahn CN, Roberts K, King MC, Lo SM, Levine RL, Viale A, Socci ND, Nathanson KL, Scott HS, Daly M, Lipkin SM, Lowe SW, Downing JR, Altshuler D, Sandlund JT, Horwitz MS, Mullighan CG, and Offit K
- Subjects
- Humans, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Germ-Line Mutation, PAX5 Transcription Factor genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL), but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly183Ser), affecting the octapeptide domain of PAX5 that was found to segregate with disease in two unrelated kindreds with autosomal dominant B-ALL. Leukemic cells from all affected individuals in both families exhibited 9p deletion, with loss of heterozygosity and retention of the mutant PAX5 allele at 9p13. Two additional sporadic ALL cases with 9p loss harbored somatic PAX5 substitutions affecting Gly183. Functional and gene expression analysis of the PAX5 mutation demonstrated that it had significantly reduced transcriptional activity. These data extend the role of PAX5 alterations in the pathogenesis of pre-B cell ALL and implicate PAX5 in a new syndrome of susceptibility to pre-B cell neoplasia.
- Published
- 2013
- Full Text
- View/download PDF
12. A recessive founder mutation in regulator of telomere elongation helicase 1, RTEL1, underlies severe immunodeficiency and features of Hoyeraal Hreidarsson syndrome.
- Author
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Ballew BJ, Joseph V, De S, Sarek G, Vannier JB, Stracker T, Schrader KA, Small TN, O'Reilly R, Manschreck C, Harlan Fleischut MM, Zhang L, Sullivan J, Stratton K, Yeager M, Jacobs K, Giri N, Alter BP, Boland J, Burdett L, Offit K, Boulton SJ, Savage SA, and Petrini JH
- Subjects
- Adult, Dyskeratosis Congenita etiology, Female, Fetal Growth Retardation etiology, Genes, Recessive, Germ-Line Mutation, Homozygote, Humans, Immunologic Deficiency Syndromes genetics, Intellectual Disability etiology, Jews, Microcephaly etiology, Molecular Sequence Data, Mutation, Phenotype, Telomerase genetics, Telomere genetics, DNA Helicases genetics, Dyskeratosis Congenita genetics, Dyskeratosis Congenita pathology, Fetal Growth Retardation genetics, Fetal Growth Retardation pathology, Immunologic Deficiency Syndromes pathology, Intellectual Disability genetics, Intellectual Disability pathology, Microcephaly genetics, Microcephaly pathology
- Abstract
Dyskeratosis congenita (DC) is a heterogeneous inherited bone marrow failure and cancer predisposition syndrome in which germline mutations in telomere biology genes account for approximately one-half of known families. Hoyeraal Hreidarsson syndrome (HH) is a clinically severe variant of DC in which patients also have cerebellar hypoplasia and may present with severe immunodeficiency and enteropathy. We discovered a germline autosomal recessive mutation in RTEL1, a helicase with critical telomeric functions, in two unrelated families of Ashkenazi Jewish (AJ) ancestry. The affected individuals in these families are homozygous for the same mutation, R1264H, which affects three isoforms of RTEL1. Each parent was a heterozygous carrier of one mutant allele. Patient-derived cell lines revealed evidence of telomere dysfunction, including significantly decreased telomere length, telomere length heterogeneity, and the presence of extra-chromosomal circular telomeric DNA. In addition, RTEL1 mutant cells exhibited enhanced sensitivity to the interstrand cross-linking agent mitomycin C. The molecular data and the patterns of inheritance are consistent with a hypomorphic mutation in RTEL1 as the underlying basis of the clinical and cellular phenotypes. This study further implicates RTEL1 in the etiology of DC/HH and immunodeficiency, and identifies the first known homozygous autosomal recessive disease-associated mutation in RTEL1., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2013
- Full Text
- View/download PDF
13. Susceptibility loci associated with specific and shared subtypes of lymphoid malignancies.
- Author
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Vijai J, Kirchhoff T, Schrader KA, Brown J, Dutra-Clarke AV, Manschreck C, Hansen N, Rau-Murthy R, Sarrel K, Przybylo J, Shah S, Cheguri S, Stadler Z, Zhang L, Paltiel O, Ben-Yehuda D, Viale A, Portlock C, Straus D, Lipkin SM, Lacher M, Robson M, Klein RJ, Zelenetz A, and Offit K
- Subjects
- Alleles, Cell Line, Tumor, Chromosomes, Human, Pair 11, Gene Expression, Humans, Leukemia, Lymphoid pathology, Lymphoma, Follicular, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Genome-Wide Association Study, Leukemia, Lymphoid genetics, Quantitative Trait Loci
- Abstract
The genetics of lymphoma susceptibility reflect the marked heterogeneity of diseases that comprise this broad phenotype. However, multiple subtypes of lymphoma are observed in some families, suggesting shared pathways of genetic predisposition to these pathologically distinct entities. Using a two-stage GWAS, we tested 530,583 SNPs in 944 cases of lymphoma, including 282 familial cases, and 4,044 public shared controls, followed by genotyping of 50 SNPs in 1,245 cases and 2,596 controls. A novel region on 11q12.1 showed association with combined lymphoma (LYM) subtypes. SNPs in this region included rs12289961 near LPXN, (P(LYM) = 3.89×10(-8), OR = 1.29) and rs948562 (P(LYM) = 5.85×10(-7), OR = 1.29). A SNP in a novel non-HLA region on 6p23 (rs707824, P(NHL) = 5.72×10(-7)) was suggestive of an association conferring susceptibility to lymphoma. Four SNPs, all in a previously reported HLA region, 6p21.32, showed genome-wide significant associations with follicular lymphoma. The most significant association with follicular lymphoma was for rs4530903 (P(FL) = 2.69×10(-12), OR = 1.93). Three novel SNPs near the HLA locus, rs9268853, rs2647046, and rs2621416, demonstrated additional variation contributing toward genetic susceptibility to FL associated with this region. Genes implicated by GWAS were also found to be cis-eQTLs in lymphoblastoid cell lines; candidate genes in these regions have been implicated in hematopoiesis and immune function. These results, showing novel susceptibility regions and allelic heterogeneity, point to the existence of pathways of susceptibility to both shared as well as specific subtypes of lymphoid malignancy., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2013
- Full Text
- View/download PDF
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