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Volumn 35, Issue 23, 2017, Pages 2700-2707

Neurocognitive functioning of children treated for high-risk B-acute lymphoblastic leukemia randomly assigned to different methotrexate and corticosteroid treatment strategies: A report from the children's oncology group

(15)  Hardy, Kristina K b   Embry, Leanne c   Kairalla, John A d   Helian, Shanjun f   Devidas, Meenakshi d   Armstrong, Daniel e   Hunger, Stephen g   Carroll, William L i   Larsen, Eric j   Raetz, Elizabeth A k   Loh, Mignon L l   Yang, Wenjian m   Relling, Mary V m   Noll, Robert B h   Winick, Naomi a  


Author keywords

[No Author keywords available]

Indexed keywords

ASPARAGINASE MACROGOL; CYTARABINE; DEXAMETHASONE; FOLINIC ACID; METHOTREXATE; PREDNISONE; ANTINEOPLASTIC AGENT; ASPARAGINASE; CORTICOSTEROID; MACROGOL DERIVATIVE;

EID: 85028762924     PISSN: 0732183X     EISSN: 15277755     Source Type: Journal    
DOI: 10.1200/JCO.2016.71.7587     Document Type: Article
Times cited : (43)

References (48)
  • 1
    • 34249799306 scopus 로고    scopus 로고
    • A meta-analysis of the neurocognitive sequelae of treatment for childhood acute lymphocytic leukemia
    • Campbell LK, Scaduto M, Sharp W, et al: A meta-analysis of the neurocognitive sequelae of treatment for childhood acute lymphocytic leukemia. Pediatr Blood Cancer 49:65-73, 2007
    • (2007) Pediatr Blood Cancer , vol.49 , pp. 65-73
    • Campbell, L.K.1    Scaduto, M.2    Sharp, W.3
  • 2
    • 18144383863 scopus 로고    scopus 로고
    • Attention and information processing in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only
    • Mennes M, Stiers P, Vandenbussche E, et al: Attention and information processing in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only. Pediatr Blood Cancer 44: 478-486, 2005
    • (2005) Pediatr Blood Cancer , vol.44 , pp. 478-486
    • Mennes, M.1    Stiers, P.2    Vandenbussche, E.3
  • 3
    • 84963490924 scopus 로고    scopus 로고
    • Longitudinal assessment of neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia treated on a contemporary chemotherapy protocol
    • Jacola LM, Krull KR, Pui C-H, et al: Longitudinal assessment of neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia treated on a contemporary chemotherapy protocol. J Clin Oncol 34:1239-1247, 2016
    • (2016) J Clin Oncol , vol.34 , pp. 1239-1247
    • Jacola, L.M.1    Krull, K.R.2    Pui, C.-H.3
  • 4
    • 44149110403 scopus 로고    scopus 로고
    • A meta-analysis of the neuropsychological sequelae of chemotherapy-only treatment for pediatric acute lymphoblastic leukemia
    • Peterson CC, Johnson CE, Ramirez LY, et al: A meta-analysis of the neuropsychological sequelae of chemotherapy-only treatment for pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer 51: 99-104, 2008
    • (2008) Pediatr Blood Cancer , vol.51 , pp. 99-104
    • Peterson, C.C.1    Johnson, C.E.2    Ramirez, L.Y.3
  • 5
    • 84897643050 scopus 로고    scopus 로고
    • Visuomotor function in children treated for acute lymphoblastic leukaemia with chemotherapy only
    • Knight S, McCarthy M, Anderson V, et al: Visuomotor function in children treated for acute lymphoblastic leukaemia with chemotherapy only. Dev Neuropsychol 39:101-112, 2014
    • (2014) Dev Neuropsychol , vol.39 , pp. 101-112
    • Knight, S.1    McCarthy, M.2    Anderson, V.3
  • 6
    • 84937775292 scopus 로고    scopus 로고
    • Chemotherapy-only treatment effects on long-term neurocognitive functioning in childhood ALL survivors: A review and meta-analysis
    • Iyer NS, Balsamo LM, Bracken MB, et al: Chemotherapy-only treatment effects on long-term neurocognitive functioning in childhood ALL survivors: A review and meta-analysis. Blood 126: 346-353, 2015
    • (2015) Blood , vol.126 , pp. 346-353
    • Iyer, N.S.1    Balsamo, L.M.2    Bracken, M.B.3
  • 7
    • 67649410242 scopus 로고    scopus 로고
    • Treating childhood acute lymphoblastic leukemia without cranial irradiation
    • Pui C-H, Campana D, Pei D, et al: Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med 360:2730-2741, 2009
    • (2009) N Engl J Med , vol.360 , pp. 2730-2741
    • Pui, C.-H.1    Campana, D.2    Pei, D.3
  • 8
    • 84866652995 scopus 로고    scopus 로고
    • Cognitive outcomes following contemporary treatment without cranial irradiation for childhood acute lymphoblastic leukemia
    • Conklin HM, Krull KR, Reddick WE, et al: Cognitive outcomes following contemporary treatment without cranial irradiation for childhood acute lymphoblastic leukemia. J Natl Cancer Inst 104: 1386-1395, 2012
    • (2012) J Natl Cancer Inst , vol.104 , pp. 1386-1395
    • Conklin, H.M.1    Krull, K.R.2    Reddick, W.E.3
  • 9
    • 80053924320 scopus 로고    scopus 로고
    • The impact of therapy for childhood acute lymphoblastic leukaemia on intelligence quotients: Results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI
    • Halsey C, Buck G, Richards S, et al: The impact of therapy for childhood acute lymphoblastic leukaemia on intelligence quotients: Results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI. J Hematol Oncol 4:42, 2011
    • (2011) J Hematol Oncol , vol.4 , pp. 42
    • Halsey, C.1    Buck, G.2    Richards, S.3
  • 10
    • 70149093900 scopus 로고    scopus 로고
    • Sex-specific attention problems in long-term survivors of pediatric acute lymphoblastic leukemia
    • Jain N, Brouwers P, Okcu MF, et al: Sex-specific attention problems in long-term survivors of pediatric acute lymphoblastic leukemia. Cancer 115:4238-4245, 2009
    • (2009) Cancer , vol.115 , pp. 4238-4245
    • Jain, N.1    Brouwers, P.2    Okcu, M.F.3
  • 11
    • 84881531512 scopus 로고    scopus 로고
    • Neurocognitive and behavioral outcomes in Latino childhood cancer survivors
    • Patel SK, Lo TTY, Dennis JM, et al: Neurocognitive and behavioral outcomes in Latino childhood cancer survivors. Pediatr Blood Cancer 60: 1696-1702, 2013
    • (2013) Pediatr Blood Cancer , vol.60 , pp. 1696-1702
    • Patel, S.K.1    Lo, T.T.Y.2    Dennis, J.M.3
  • 12
    • 84885175761 scopus 로고    scopus 로고
    • Intellectual functioning and multi-dimensional attentional processes in long-term survivors of a central nervous system related pediatric malignancy
    • Butler RW, Fairclough DL, Katz ER, et al: Intellectual functioning and multi-dimensional attentional processes in long-term survivors of a central nervous system related pediatric malignancy. Life Sci 93:611-616, 2013
    • (2013) Life Sci , vol.93 , pp. 611-616
    • Butler, R.W.1    Fairclough, D.L.2    Katz, E.R.3
  • 13
    • 80053920543 scopus 로고    scopus 로고
    • Predictors of independent living status in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study
    • Kunin-Batson A, Kadan-Lottick N, Zhu L, et al: Predictors of independent living status in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 57:1197-1203, 2011
    • (2011) Pediatr Blood Cancer , vol.57 , pp. 1197-1203
    • Kunin-Batson, A.1    Kadan-Lottick, N.2    Zhu, L.3
  • 14
    • 67349281455 scopus 로고    scopus 로고
    • White matter fractional anisotropy correlates with speed of processing and motor speed in young childhood cancer survivors
    • Aukema EJ, Caan MWA, Oudhuis N, et al: White matter fractional anisotropy correlates with speed of processing and motor speed in young childhood cancer survivors. Int J Radiat Oncol Biol Phys 74:837-843, 2009
    • (2009) Int J Radiat Oncol Biol Phys , vol.74 , pp. 837-843
    • Aukema, E.J.1    Caan, M.W.A.2    Oudhuis, N.3
  • 15
    • 84887140959 scopus 로고    scopus 로고
    • Genetic mediators of neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia
    • Krull KR, Bhojwani D, Conklin HM, et al: Genetic mediators of neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia. J Clin Oncol 31:2182-2188, 2013
    • (2013) J Clin Oncol , vol.31 , pp. 2182-2188
    • Krull, K.R.1    Bhojwani, D.2    Conklin, H.M.3
  • 16
    • 84879570527 scopus 로고    scopus 로고
    • Intellectual functioning of childhood leukemia survivors–relation to Tau protein–A marker of white matter injury
    • Krawczuk-Rybak M, Grabowska A, Protas PT, et al: Intellectual functioning of childhood leukemia survivors–relation to Tau protein–A marker of white matter injury. Adv Med Sci 57: 266-272, 2012
    • (2012) Adv Med Sci , vol.57 , pp. 266-272
    • Krawczuk-Rybak, M.1    Grabowska, A.2    Protas, P.T.3
  • 17
    • 33845584082 scopus 로고    scopus 로고
    • Very high-dose methotrexate (33.6 g/m2) as central nervous system preventive therapy for childhood acute lymphoblastic leukemia: Results of National Cancer Institute/Children's Cancer Group trials CCG-191P, CCG-134P and CCG-144P
    • Nathan PC, Whitcomb T, Wolters PL, et al: Very high-dose methotrexate (33.6 g/m2) as central nervous system preventive therapy for childhood acute lymphoblastic leukemia: Results of National Cancer Institute/Children's Cancer Group trials CCG-191P, CCG-134P and CCG-144P. Leuk Lymphoma 47:2488-2504, 2006
    • (2006) Leuk Lymphoma , vol.47 , pp. 2488-2504
    • Nathan, P.C.1    Whitcomb, T.2    Wolters, P.L.3
  • 18
    • 84883828379 scopus 로고    scopus 로고
    • Neuropsychological outcomes of a randomized trial of prednisone versus dexamethasone in acute lymphoblastic leukemia: Findings from Dana-Farber Cancer Institute All Consortium Protocol 00-01
    • Waber DP, McCabe M, Sebree M, et al: Neuropsychological outcomes of a randomized trial of prednisone versus dexamethasone in acute lymphoblastic leukemia: Findings from Dana-Farber Cancer Institute All Consortium Protocol 00-01. Pediatr Blood Cancer 60:1785-1791, 2013
    • (2013) Pediatr Blood Cancer , vol.60 , pp. 1785-1791
    • Waber, D.P.1    McCabe, M.2    Sebree, M.3
  • 19
    • 84977505620 scopus 로고    scopus 로고
    • Dexamethasone and high-dose methotrexate improve outcome for children and young adults with high-risk B-acute lymphoblastic leukemia: A report from Children's Oncology Group Study AALL0232
    • Larsen EC, Devidas M, Chen S, et al: Dexamethasone and high-dose methotrexate improve outcome for children and young adults with high-risk B-acute lymphoblastic leukemia: A report from Children's Oncology Group Study AALL0232. J Clin Oncol 34:2380-2388, 2016
    • (2016) J Clin Oncol , vol.34 , pp. 2380-2388
    • Larsen, E.C.1    Devidas, M.2    Chen, S.3
  • 20
    • 84863878048 scopus 로고    scopus 로고
    • Implementation of multi-site neurocognitive assessments within a pediatric cooperative group: Can it be done?
    • Embry L, Annett RD, Kunin-Batson A, et al: Implementation of multi-site neurocognitive assessments within a pediatric cooperative group: Can it be done? Pediatr Blood Cancer 59:536-539, 2012
    • (2012) Pediatr Blood Cancer , vol.59 , pp. 536-539
    • Embry, L.1    Annett, R.D.2    Kunin-Batson, A.3
  • 21
    • 84984608981 scopus 로고    scopus 로고
    • Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia
    • Karol SE, Yang W, Van Driest SL, et al: Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia. Blood 126:1770-1776, 2015
    • (2015) Blood , vol.126 , pp. 1770-1776
    • Karol, S.E.1    Yang, W.2    Van Driest, S.L.3
  • 26
    • 84936969259 scopus 로고    scopus 로고
    • Polymorphisms in genes related to oxidative stress are associated with inferior cognitive function after therapy for childhood acute lymphoblastic leukemia
    • Cole PD, Finkelstein Y, Stevenson KE, et al: Polymorphisms in genes related to oxidative stress are associated with inferior cognitive function after therapy for childhood acute lymphoblastic leukemia. J Clin Oncol 33:2205-2211, 2015
    • (2015) J Clin Oncol , vol.33 , pp. 2205-2211
    • Cole, P.D.1    Finkelstein, Y.2    Stevenson, K.E.3
  • 27
    • 79960174296 scopus 로고    scopus 로고
    • Folate pathway polymorphisms predict deficits in attention and processing speed after childhood leukemia therapy
    • Kamdar KY, Krull KR, El-Zein RA, et al: Folate pathway polymorphisms predict deficits in attention and processing speed after childhood leukemia therapy. Pediatr Blood Cancer 57:454-460, 2011
    • (2011) Pediatr Blood Cancer , vol.57 , pp. 454-460
    • Kamdar, K.Y.1    Krull, K.R.2    El-Zein, R.A.3
  • 28
    • 37249044154 scopus 로고    scopus 로고
    • Folate pathway genetic polymorphisms are related to attention disorders in childhood leukemia survivors
    • Krull KR, Brouwers P, Jain N, et al: Folate pathway genetic polymorphisms are related to attention disorders in childhood leukemia survivors. J Pediatr 152:101-105, 2008
    • (2008) J Pediatr , vol.152 , pp. 101-105
    • Krull, K.R.1    Brouwers, P.2    Jain, N.3
  • 29
    • 84927664690 scopus 로고    scopus 로고
    • Neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on contemporary treatment protocols: A systematic review
    • Cheung YT, Krull KR: Neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on contemporary treatment protocols: A systematic review. Neurosci Biobehav Rev 53:108-120, 2015
    • (2015) Neurosci Biobehav Rev , vol.53 , pp. 108-120
    • Cheung, Y.T.1    Krull, K.R.2
  • 30
    • 84899638189 scopus 로고    scopus 로고
    • Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia
    • Bhojwani D, Sabin ND, Pei D, et al: Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia. J Clin Oncol 32:949-959, 2014
    • (2014) J Clin Oncol , vol.32 , pp. 949-959
    • Bhojwani, D.1    Sabin, N.D.2    Pei, D.3
  • 31
    • 0026525903 scopus 로고
    • Unexpected acute neurologic toxicity in the treatment of children with acute lymphoblastic leukemia
    • Winick NJ, Bowman WP, Kamen BA, et al: Unexpected acute neurologic toxicity in the treatment of children with acute lymphoblastic leukemia. J Natl Cancer Inst 84:252-256, 1992
    • (1992) J Natl Cancer Inst , vol.84 , pp. 252-256
    • Winick, N.J.1    Bowman, W.P.2    Kamen, B.A.3
  • 32
    • 70350703428 scopus 로고    scopus 로고
    • Posterior reversible encephalopathy syndrome associated with methotrexate neurotoxicity: Conventional magnetic resonance and diffusion-weighted imaging findings
    • Dicuonzo F, Salvati A, Palma M, et al: Posterior reversible encephalopathy syndrome associated with methotrexate neurotoxicity: Conventional magnetic resonance and diffusion-weighted imaging findings. J Child Neurol 24:1013-1018, 2009
    • (2009) J Child Neurol , vol.24 , pp. 1013-1018
    • Dicuonzo, F.1    Salvati, A.2    Palma, M.3
  • 33
    • 77953486368 scopus 로고    scopus 로고
    • Central nervous system complications during treatment of acute lymphoblastic leukemia in a single pediatric institution
    • Parasole R, Petruzziello F, Menna G, et al: Central nervous system complications during treatment of acute lymphoblastic leukemia in a single pediatric institution. Leuk Lymphoma 51:1063-1071, 2010
    • (2010) Leuk Lymphoma , vol.51 , pp. 1063-1071
    • Parasole, R.1    Petruzziello, F.2    Menna, G.3
  • 34
    • 0344542098 scopus 로고    scopus 로고
    • Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: An association with intermediate-dose intravenous methotrexate and intrathecal triple therapy—A Pediatric Oncology Group study
    • Mahoney DH, Jr, Shuster JJ, Nitschke R, et al: Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: An association with intermediate-dose intravenous methotrexate and intrathecal triple therapy—A Pediatric Oncology Group study. J Clin Oncol 16:1712-1722, 1998
    • (1998) J Clin Oncol , vol.16 , pp. 1712-1722
    • Mahoney, D.H.1    Shuster, J.J.2    Nitschke, R.3
  • 35
    • 70349247009 scopus 로고    scopus 로고
    • A comparison of neurocognitive functioning in children previously randomized to dexamethasone or prednisone in the treatment of childhood acute lymphoblastic leukemia
    • Kadan-Lottick NS, Brouwers P, Breiger D, et al: A comparison of neurocognitive functioning in children previously randomized to dexamethasone or prednisone in the treatment of childhood acute lymphoblastic leukemia. Blood 114:1746-1752, 2009
    • (2009) Blood , vol.114 , pp. 1746-1752
    • Kadan-Lottick, N.S.1    Brouwers, P.2    Breiger, D.3
  • 36
    • 23044452435 scopus 로고    scopus 로고
    • The influence of the parents' educational level on the development of executive functions
    • Ardila A, Rosselli M, Matute E, et al: The influence of the parents' educational level on the development of executive functions. Dev Neuropsychol 28:539-560, 2005
    • (2005) Dev Neuropsychol , vol.28 , pp. 539-560
    • Ardila, A.1    Rosselli, M.2    Matute, E.3
  • 37
    • 0742323508 scopus 로고    scopus 로고
    • Critical periods of brain growth and cognitive function in children
    • Gale CR, O'Callaghan FJ, Godfrey KM, et al: Critical periods of brain growth and cognitive function in children. Brain 127:321-329, 2004
    • (2004) Brain , vol.127 , pp. 321-329
    • Gale, C.R.1    O'Callaghan, F.J.2    Godfrey, K.M.3
  • 38
    • 33645453807 scopus 로고    scopus 로고
    • Intellectual ability and cortical development in children and adolescents
    • Shaw P, Greenstein D, Lerch J, et al: Intellectual ability and cortical development in children and adolescents. Nature 440:676-679, 2006
    • (2006) Nature , vol.440 , pp. 676-679
    • Shaw, P.1    Greenstein, D.2    Lerch, J.3
  • 39
    • 0031400410 scopus 로고    scopus 로고
    • The effects of poverty on children
    • Brooks-Gunn J, Duncan GJ: The effects of poverty on children. Future Child 7:55-71, 1997
    • (1997) Future Child , vol.7 , pp. 55-71
    • Brooks-Gunn, J.1    Duncan, G.J.2
  • 40
    • 0028414307 scopus 로고
    • Economic deprivation and early childhood development
    • Duncan GJ, Brooks-Gunn J, Klebanov PK: Economic deprivation and early childhood development. Child Dev 65:296-318, 1994
    • (1994) Child Dev , vol.65 , pp. 296-318
    • Duncan, G.J.1    Brooks-Gunn, J.2    Klebanov, P.K.3
  • 41
    • 34648836403 scopus 로고    scopus 로고
    • Measurement of socioeconomic status in health disparities research
    • Shavers VL: Measurement of socioeconomic status in health disparities research. J Natl Med Assoc 99:1013-1023, 2007
    • (2007) J Natl Med Assoc , vol.99 , pp. 1013-1023
    • Shavers, V.L.1
  • 42
    • 84862248334 scopus 로고    scopus 로고
    • Mathematics intervention for prevention of neurocognitive deficits in childhood leukemia
    • Moore IM, Hockenberry MJ, Anhalt C, et al: Mathematics intervention for prevention of neurocognitive deficits in childhood leukemia. Pediatr Blood Cancer 59:278-284, 2012
    • (2012) Pediatr Blood Cancer , vol.59 , pp. 278-284
    • Moore, I.M.1    Hockenberry, M.J.2    Anhalt, C.3
  • 43
    • 84948466457 scopus 로고    scopus 로고
    • Computerized cognitive training for amelioration of cognitive late effects among childhood cancer survivors: A randomized controlled trial
    • Conklin HM, Ogg RJ, Ashford JM, et al: Computerized cognitive training for amelioration of cognitive late effects among childhood cancer survivors: A randomized controlled trial. J Clin Oncol 33: 3894-3902, 2015
    • (2015) J Clin Oncol , vol.33 , pp. 3894-3902
    • Conklin, H.M.1    Ogg, R.J.2    Ashford, J.M.3
  • 44
    • 84880697461 scopus 로고    scopus 로고
    • Working memory training in survivors of pediatric cancer: A randomized pilot study
    • Hardy KK, Willard VW, Allen TM, et al: Working memory training in survivors of pediatric cancer: A randomized pilot study. Psychooncology 22: 1856-1865, 2013
    • (2013) Psychooncology , vol.22 , pp. 1856-1865
    • Hardy, K.K.1    Willard, V.W.2    Allen, T.M.3
  • 45
    • 44949130841 scopus 로고    scopus 로고
    • A multicenter, randomized clinical trial of a cognitive remediation program for childhood survivors of a pediatric malignancy
    • Butler RW, Copeland DR, Fairclough DL, et al: A multicenter, randomized clinical trial of a cognitive remediation program for childhood survivors of a pediatric malignancy. J Consult Clin Psychol 76: 367-378, 2008
    • (2008) J Consult Clin Psychol , vol.76 , pp. 367-378
    • Butler, R.W.1    Copeland, D.R.2    Fairclough, D.L.3
  • 46
    • 14044255978 scopus 로고    scopus 로고
    • Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans
    • Lee S-G, Joo Y, Kim B, et al: Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans. Hum Genet 116:319-328, 2005
    • (2005) Hum Genet , vol.116 , pp. 319-328
    • Lee, S.-G.1    Joo, Y.2    Kim, B.3
  • 47
    • 0036913209 scopus 로고    scopus 로고
    • A highly significant association between a COMT haplotype and schizophrenia
    • Shifman S, Bronstein M, Sternfeld M, et al: A highly significant association between a COMT haplotype and schizophrenia. Am J Hum Genet 71: 1296-1302, 2002
    • (2002) Am J Hum Genet , vol.71 , pp. 1296-1302
    • Shifman, S.1    Bronstein, M.2    Sternfeld, M.3
  • 48
    • 4644248763 scopus 로고    scopus 로고
    • COMT haplotypes suggest P2 promoter region relevance for schizophrenia
    • Palmatier MA, Pakstis AJ, Speed W, et al: COMT haplotypes suggest P2 promoter region relevance for schizophrenia. Mol Psychiatry 9:859-870, 2004
    • (2004) Mol Psychiatry , vol.9 , pp. 859-870
    • Palmatier, M.A.1    Pakstis, A.J.2    Speed, W.3


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