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Volumn 6, Issue SUPPL.1, 2012, Pages

Insights into the pathogenesis of axial spondyloarthropathy from network and pathway analysis

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; DNA MICROARRAY; GENETIC DATABASE; GENETICS; HUMAN; METABOLISM; METHODOLOGY; PROTEIN PROTEIN INTERACTION; PROTEOMICS; SPONDYLOARTHROPATHY; SYSTEMS BIOLOGY;

EID: 84866441413     PISSN: None     EISSN: 17520509     Source Type: Journal    
DOI: 10.1186/1752-0509-6-S1-S4     Document Type: Article
Times cited : (11)

References (59)
  • 1
    • 34247164611 scopus 로고    scopus 로고
    • Ankylosing spondylitis
    • 10.1016/S0140-6736(07)60635-7, 17448825
    • Braun J, Sieper J. Ankylosing spondylitis. Lancet 2007, 369:1379-1390. 10.1016/S0140-6736(07)60635-7, 17448825.
    • (2007) Lancet , vol.369 , pp. 1379-1390
    • Braun, J.1    Sieper, J.2
  • 2
    • 57049110395 scopus 로고    scopus 로고
    • Pathophysiology of ankylosing spondylitis: What's new?
    • 10.1016/j.jbspin.2008.09.003, 19036625
    • Pham T. Pathophysiology of ankylosing spondylitis: What's new?. Joint Bone Spine 2008, 75:656-660. 10.1016/j.jbspin.2008.09.003, 19036625.
    • (2008) Joint Bone Spine , vol.75 , pp. 656-660
    • Pham, T.1
  • 3
    • 42649086788 scopus 로고    scopus 로고
    • From gene expression to disease risk
    • 10.1038/ng0508-492, 18443581
    • Dermitzakis E. From gene expression to disease risk. Nature Genetics 2008, 40:492-493. 10.1038/ng0508-492, 18443581.
    • (2008) Nature Genetics , vol.40 , pp. 492-493
    • Dermitzakis, E.1
  • 5
    • 4243073059 scopus 로고    scopus 로고
    • Gene expression in juvenile arthritis and spondyloarthropathy: pro-angiogenic ELR+ chemokine genes relate to course of arthritis
    • 10.1093/rheumatology/keh224, 15150433
    • Barnes MG, Aronow BJ, Luyrink LK, Moroldo MB, Pavlidis P, Passo MH, Grom AA, Hirsch R, Giannini EH, Colbert RA, et al. Gene expression in juvenile arthritis and spondyloarthropathy: pro-angiogenic ELR+ chemokine genes relate to course of arthritis. Rheumatology 2004, 43(8):973-979. 10.1093/rheumatology/keh224, 15150433.
    • (2004) Rheumatology , vol.43 , Issue.8 , pp. 973-979
    • Barnes, M.G.1    Aronow, B.J.2    Luyrink, L.K.3    Moroldo, M.B.4    Pavlidis, P.5    Passo, M.H.6    Grom, A.A.7    Hirsch, R.8    Giannini, E.H.9    Colbert, R.A.10
  • 9
    • 33747035889 scopus 로고    scopus 로고
    • Predicting disease genes using protein-protein interactions
    • 10.1136/jmg.2006.041376, 2564594, 16611749
    • Oti M, Snel B, Huynen MA, Brunner HG. Predicting disease genes using protein-protein interactions. Journal of Medical Genetics 2006, 43(8):691-698. 10.1136/jmg.2006.041376, 2564594, 16611749.
    • (2006) Journal of Medical Genetics , vol.43 , Issue.8 , pp. 691-698
    • Oti, M.1    Snel, B.2    Huynen, M.A.3    Brunner, H.G.4
  • 10
    • 41549139527 scopus 로고    scopus 로고
    • Walking the Interactome for Prioritization of Candidate Disease Genes
    • 10.1016/j.ajhg.2008.02.013, 2427257, 18371930
    • Köhler S, Bauer S, Horn D, Robinson PN. Walking the Interactome for Prioritization of Candidate Disease Genes. Am J Hum Genet 2008, 82(4):949-958. 10.1016/j.ajhg.2008.02.013, 2427257, 18371930.
    • (2008) Am J Hum Genet , vol.82 , Issue.4 , pp. 949-958
    • Köhler, S.1    Bauer, S.2    Horn, D.3    Robinson, P.N.4
  • 11
    • 62849126285 scopus 로고    scopus 로고
    • Disease candidate gene identification and prioritization using protein interaction networks
    • 10.1186/1471-2105-10-73, 2657789, 19245720
    • Chen J, Aronow B, Jegga A. Disease candidate gene identification and prioritization using protein interaction networks. BMC Bioinformatics 2009, 10(1):73. 10.1186/1471-2105-10-73, 2657789, 19245720.
    • (2009) BMC Bioinformatics , vol.10 , Issue.1 , pp. 73
    • Chen, J.1    Aronow, B.2    Jegga, A.3
  • 12
    • 77951952127 scopus 로고    scopus 로고
    • The power of protein interaction networks for associating genes with diseases
    • 10.1093/bioinformatics/btq076, 2853684, 20185403
    • Navlakha S, Kingsford C. The power of protein interaction networks for associating genes with diseases. Bioinformatics 2010, 26(8):1057-1063. 10.1093/bioinformatics/btq076, 2853684, 20185403.
    • (2010) Bioinformatics , vol.26 , Issue.8 , pp. 1057-1063
    • Navlakha, S.1    Kingsford, C.2
  • 13
    • 59649125020 scopus 로고    scopus 로고
    • A Network-Based Method for Predicting Disease-Causing Genes
    • 10.1089/cmb.2008.05TT, 19193144
    • Karni S, Soreq H, Sharan R. A Network-Based Method for Predicting Disease-Causing Genes. Journal of Computational Biology 2009, 16(2):181-189. 10.1089/cmb.2008.05TT, 19193144.
    • (2009) Journal of Computational Biology , vol.16 , Issue.2 , pp. 181-189
    • Karni, S.1    Soreq, H.2    Sharan, R.3
  • 14
    • 65849165004 scopus 로고    scopus 로고
    • Network Analysis of Differential Expression for the Identification of Disease-Causing Genes
    • 10.1371/journal.pone.0005526, 2677677, 19436755
    • Nitsch D, Tranchevent L-C, Thienpont B, Thorrez L, Van Esch H, Devriendt K, Moreau Y. Network Analysis of Differential Expression for the Identification of Disease-Causing Genes. PLoS ONE 2009, 4(5):e5526. 10.1371/journal.pone.0005526, 2677677, 19436755.
    • (2009) PLoS ONE , vol.4 , Issue.5
    • Nitsch, D.1    Tranchevent, L.-C.2    Thienpont, B.3    Thorrez, L.4    Van Esch, H.5    Devriendt, K.6    Moreau, Y.7
  • 15
    • 80052398216 scopus 로고    scopus 로고
    • Ranking Candidate Disease Genes from Gene Expression and Protein Interaction: A Katz-Centrality Based Approach
    • 10.1371/journal.pone.0024306, 3166320, 21912686
    • Zhao J, Yang T-H, Huang Y, Holme P. Ranking Candidate Disease Genes from Gene Expression and Protein Interaction: A Katz-Centrality Based Approach. PLoS ONE 2011, 6(9):e24306. 10.1371/journal.pone.0024306, 3166320, 21912686.
    • (2011) PLoS ONE , vol.6 , Issue.9
    • Zhao, J.1    Yang, T.-H.2    Huang, Y.3    Holme, P.4
  • 17
    • 52149123619 scopus 로고    scopus 로고
    • Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
    • 10.1126/science.1164368, 2848990, 18772397
    • Jones S, Zhang X, Parsons D, Lin J-H, Leary R, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A. Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses. Science 2008, 321:1801-1806. 10.1126/science.1164368, 2848990, 18772397.
    • (2008) Science , vol.321 , pp. 1801-1806
    • Jones, S.1    Zhang, X.2    Parsons, D.3    Lin, J.-H.4    Leary, R.5    Angenendt, P.6    Mankoo, P.7    Carter, H.8    Kamiyama, H.9    Jimeno, A.10
  • 19
    • 33646687963 scopus 로고    scopus 로고
    • A Protein-Protein Interaction Network for Human Inherited Ataxias and Disorders of Purkinje Cell Degeneration
    • 10.1016/j.cell.2006.03.032, 16713569
    • Lim J, Hao T, Shaw C, Patel AJ, Szab G, Rual J-F, Fisk CJ, Li N, Smolyar A, Hill DE, et al. A Protein-Protein Interaction Network for Human Inherited Ataxias and Disorders of Purkinje Cell Degeneration. Cell 2006, 125(4):801-814. 10.1016/j.cell.2006.03.032, 16713569.
    • (2006) Cell , vol.125 , Issue.4 , pp. 801-814
    • Lim, J.1    Hao, T.2    Shaw, C.3    Patel, A.J.4    Szab, G.5    Rual, J.-F.6    Fisk, C.J.7    Li, N.8    Smolyar, A.9    Hill, D.E.10
  • 22
    • 54549108740 scopus 로고    scopus 로고
    • Comprehensive genomic characterization defines human glioblastoma genes and core pathways
    • 10.1038/nature07385, 2671642, 18772890
    • Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008, 455(7216):1061-1068. 10.1038/nature07385, 2671642, 18772890.
    • (2008) Nature , vol.455 , Issue.7216 , pp. 1061-1068
  • 23
    • 49249134279 scopus 로고    scopus 로고
    • Meta-Analysis Approach identifies Candidate Genes and associated Molecular Networks for Type-2 Diabetes Mellitus
    • 10.1186/1471-2164-9-310, 2515154, 18590522
    • Rasche A, Al-Hasani H, Herwig R. Meta-Analysis Approach identifies Candidate Genes and associated Molecular Networks for Type-2 Diabetes Mellitus. BMC Genomics 2008, 9(1):310. 10.1186/1471-2164-9-310, 2515154, 18590522.
    • (2008) BMC Genomics , vol.9 , Issue.1 , pp. 310
    • Rasche, A.1    Al-Hasani, H.2    Herwig, R.3
  • 24
    • 44449119819 scopus 로고    scopus 로고
    • A protein interaction network associated with asthma
    • 10.1016/j.jtbi.2008.02.011, 18395227
    • Hwang S, Son S-W, Kim SC, Kim YJ, Jeong H, Lee D. A protein interaction network associated with asthma. Journal of Theoretical Biology 2008, 252(4):722-731. 10.1016/j.jtbi.2008.02.011, 18395227.
    • (2008) Journal of Theoretical Biology , vol.252 , Issue.4 , pp. 722-731
    • Hwang, S.1    Son, S.-W.2    Kim, S.C.3    Kim, Y.J.4    Jeong, H.5    Lee, D.6
  • 25
    • 39049189899 scopus 로고    scopus 로고
    • Mining Alzheimer Disease Relevant Proteins from Integrated Protein Interactome Data
    • Chen J, Shen C, Sivachenko A. Mining Alzheimer Disease Relevant Proteins from Integrated Protein Interactome Data. Pac Symp Biocomput 2006, 367-378.
    • (2006) Pac Symp Biocomput , pp. 367-378
    • Chen, J.1    Shen, C.2    Sivachenko, A.3
  • 26
    • 44449144053 scopus 로고    scopus 로고
    • Linking Gene Expression and Functional Network Data in Human Heart Failure
    • 10.1371/journal.pone.0001347, 2147076, 18094754
    • Camargo A, Azuaje F. Linking Gene Expression and Functional Network Data in Human Heart Failure. PLoS ONE 2007, 2:e1347. 10.1371/journal.pone.0001347, 2147076, 18094754.
    • (2007) PLoS ONE , vol.2
    • Camargo, A.1    Azuaje, F.2
  • 27
    • 77349088313 scopus 로고    scopus 로고
    • Detecting disease associated modules and prioritizing active genes based on high throughput data
    • 10.1186/1471-2105-11-26, 2825224, 20070902
    • Qiu Y-Q, Zhang S, Zhang X-S, Chen L. Detecting disease associated modules and prioritizing active genes based on high throughput data. BMC Bioinformatics 2010, 11(1):26. 10.1186/1471-2105-11-26, 2825224, 20070902.
    • (2010) BMC Bioinformatics , vol.11 , Issue.1 , pp. 26
    • Qiu, Y.-Q.1    Zhang, S.2    Zhang, X.-S.3    Chen, L.4
  • 28
    • 84885684657 scopus 로고    scopus 로고
    • Biocarta
    • Biocarta. , http://www.biocarta.com/
  • 29
    • 84894205892 scopus 로고    scopus 로고
    • KEGG pathway
    • KEGG pathway. , http://www.genome.jp/kegg/pathway.html
  • 30
    • 13444266370 scopus 로고    scopus 로고
    • Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders
    • 539987, 15608251
    • Hamosh A, Scott AF, Amberger JS, Bocchini CA, McKusick VA. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res 2005, 33:D514-517. 539987, 15608251.
    • (2005) Nucleic Acids Res , vol.33
    • Hamosh, A.1    Scott, A.F.2    Amberger, J.S.3    Bocchini, C.A.4    McKusick, V.A.5
  • 31
    • 77955039434 scopus 로고    scopus 로고
    • Molecular networks for the study of TCM pharmacology
    • 10.1093/bib/bbp063, 20038567
    • Zhao J, Jiang P, Zhang W. Molecular networks for the study of TCM pharmacology. Briefings in Bioinformatics 2010, 11(4):417-430. 10.1093/bib/bbp063, 20038567.
    • (2010) Briefings in Bioinformatics , vol.11 , Issue.4 , pp. 417-430
    • Zhao, J.1    Jiang, P.2    Zhang, W.3
  • 32
    • 77951240586 scopus 로고    scopus 로고
    • Network properties of complex human disease genes identified through genome-wide association studies
    • 10.1371/journal.pone.0008090, 2779513, 19956617
    • Barrenas F, Chavali S, Holme P, Mobini R, Benson M. Network properties of complex human disease genes identified through genome-wide association studies. PLoS ONE 2009, 4:e8090. 10.1371/journal.pone.0008090, 2779513, 19956617.
    • (2009) PLoS ONE , vol.4
    • Barrenas, F.1    Chavali, S.2    Holme, P.3    Mobini, R.4    Benson, M.5
  • 33
    • 0002827622 scopus 로고
    • A new status index derived from sociometric analysis
    • Katz L. A new status index derived from sociometric analysis. Psychometrika 1953, 18:39-43.
    • (1953) Psychometrika , vol.18 , pp. 39-43
    • Katz, L.1
  • 35
    • 13844310836 scopus 로고    scopus 로고
    • Peeling the yeast protein network
    • 10.1002/pmic.200400962, 15627958
    • Wuchty S, Almaas E. Peeling the yeast protein network. Proteomics 2005, 5:444-449. 10.1002/pmic.200400962, 15627958.
    • (2005) Proteomics , vol.5 , pp. 444-449
    • Wuchty, S.1    Almaas, E.2
  • 36
    • 33244492393 scopus 로고    scopus 로고
    • Core-periphery organization of complex networks
    • Holme P. Core-periphery organization of complex networks. Phys Rev E Stat Nonlin Soft Matter Phys 2005, 72:046111.
    • (2005) Phys Rev E Stat Nonlin Soft Matter Phys , vol.72 , pp. 046111
    • Holme, P.1
  • 39
    • 0036024683 scopus 로고    scopus 로고
    • Therapy of ankylosing spondylitis and other spondyloarthritides: established medical treatment, anti-TNF-alpha therapy and other novel approaches
    • 10.1186/ar592, 128942, 12223105
    • Braun J, Sieper J. Therapy of ankylosing spondylitis and other spondyloarthritides: established medical treatment, anti-TNF-alpha therapy and other novel approaches. Arthritis Res 2002, 4(5):307-321. 10.1186/ar592, 128942, 12223105.
    • (2002) Arthritis Res , vol.4 , Issue.5 , pp. 307-321
    • Braun, J.1    Sieper, J.2
  • 42
    • 64349094767 scopus 로고    scopus 로고
    • Tissue specificity and the human protein interaction network
    • 2683721, 19357639
    • Bossi A, Lehner B. Tissue specificity and the human protein interaction network. Mol Syst Biol 2009, 5:260. 2683721, 19357639.
    • (2009) Mol Syst Biol , vol.5 , pp. 260
    • Bossi, A.1    Lehner, B.2
  • 43
    • 78249263183 scopus 로고    scopus 로고
    • Tissue-Specific Protein Expression in Human Cells, Tissues and Organs
    • Gry M, Oksvold P, Ponten F, Uhlen M. Tissue-Specific Protein Expression in Human Cells, Tissues and Organs. J Proteomics Bioinform 2010, 3:286-293.
    • (2010) J Proteomics Bioinform , vol.3 , pp. 286-293
    • Gry, M.1    Oksvold, P.2    Ponten, F.3    Uhlen, M.4
  • 44
    • 20644444103 scopus 로고    scopus 로고
    • Neutrophil beta2 integrins: moderators of life or death decisions
    • 10.1016/j.it.2005.05.002, 15922663
    • Mayadas T, Cullere X. Neutrophil beta2 integrins: moderators of life or death decisions. Trends Immunol 2005, 26:388-395. 10.1016/j.it.2005.05.002, 15922663.
    • (2005) Trends Immunol , vol.26 , pp. 388-395
    • Mayadas, T.1    Cullere, X.2
  • 45
    • 34548656855 scopus 로고    scopus 로고
    • Signaling Pathways Downstream of Pattern-Recognition Receptors and Their Cross Talk
    • 10.1146/annurev.biochem.76.060605.122847, 17328678
    • Lee MS, Kim Y-J. Signaling Pathways Downstream of Pattern-Recognition Receptors and Their Cross Talk. Annu Rev Biochem 2007, 76:447-480. 10.1146/annurev.biochem.76.060605.122847, 17328678.
    • (2007) Annu Rev Biochem , vol.76 , pp. 447-480
    • Lee, M.S.1    Kim, Y.-J.2
  • 46
    • 66449088641 scopus 로고    scopus 로고
    • Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses
    • 10.1128/CMR.00046-08, 2668232, 19366914
    • Mogensen TH. Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses. Clinical Microbiology Reviews 2009, 22:240-273. 10.1128/CMR.00046-08, 2668232, 19366914.
    • (2009) Clinical Microbiology Reviews , vol.22 , pp. 240-273
    • Mogensen, T.H.1
  • 47
    • 71449101597 scopus 로고    scopus 로고
    • The immunology of ankylosing spondylitis and rheumatoid arthritis: a tale of similarities and dissimilarities
    • Inman RD, El-Gabalawy HS. The immunology of ankylosing spondylitis and rheumatoid arthritis: a tale of similarities and dissimilarities. Clin Exp Rheumatol 2009, 27(Suppl. 55):S26-S32.
    • (2009) Clin Exp Rheumatol , vol.27 , Issue.SUPPL. 55
    • Inman, R.D.1    El-Gabalawy, H.S.2
  • 48
    • 33645315510 scopus 로고    scopus 로고
    • Charting protein complexes, signaling pathways, and networks in the immune system
    • 10.1111/j.0105-2896.2006.00369.x, 16623772
    • Bauch A, Superti-Furga G. Charting protein complexes, signaling pathways, and networks in the immune system. Immunological Reviews 2006, 210(1):187-207. 10.1111/j.0105-2896.2006.00369.x, 16623772.
    • (2006) Immunological Reviews , vol.210 , Issue.1 , pp. 187-207
    • Bauch, A.1    Superti-Furga, G.2
  • 49
    • 33748500241 scopus 로고    scopus 로고
    • Spondyloarthropathy: disease at the crossroads of immunity
    • 10.1016/j.berh.2006.06.010, 16980217
    • FitzGerald O, McInnes I. Spondyloarthropathy: disease at the crossroads of immunity. Best Pract Res Clin Rheumatol 2006, 20(5):949-967. 10.1016/j.berh.2006.06.010, 16980217.
    • (2006) Best Pract Res Clin Rheumatol , vol.20 , Issue.5 , pp. 949-967
    • FitzGerald, O.1    McInnes, I.2
  • 50
    • 70349568508 scopus 로고    scopus 로고
    • Bone Loss in the Spondyloarthropathies: Role of Osteoclast, RANKL, RANK and OPG in the Spondyloarthropathies
    • 10.1007/978-1-4419-0298-6_6, 19731622
    • Anandarajah A, Schwarz E. Bone Loss in the Spondyloarthropathies: Role of Osteoclast, RANKL, RANK and OPG in the Spondyloarthropathies. Adv Exp Med Biol 2009, 649:85-99. 10.1007/978-1-4419-0298-6_6, 19731622.
    • (2009) Adv Exp Med Biol , vol.649 , pp. 85-99
    • Anandarajah, A.1    Schwarz, E.2
  • 51
    • 33846972636 scopus 로고    scopus 로고
    • Eating bone or adding it: the Wnt pathway decides
    • 10.1038/nm0207-133, 17290270
    • Goldring S, Goldring M. Eating bone or adding it: the Wnt pathway decides. Nat Med 2007, 13:133-134. 10.1038/nm0207-133, 17290270.
    • (2007) Nat Med , vol.13 , pp. 133-134
    • Goldring, S.1    Goldring, M.2
  • 52
    • 67651154370 scopus 로고    scopus 로고
    • Progress in spondylarthritis. Mechanisms of new bone formation in spondyloarthritis
    • 10.1186/ar2642, 3459482, 22634718
    • Lories R, Luyten F, de Vlam K. Progress in spondylarthritis. Mechanisms of new bone formation in spondyloarthritis. Arthritis Research & Therapy 2009, 11(2):221. 10.1186/ar2642, 3459482, 22634718.
    • (2009) Arthritis Research & Therapy , vol.11 , Issue.2 , pp. 221
    • Lories, R.1    Luyten, F.2    de Vlam, K.3
  • 54
    • 46649094432 scopus 로고    scopus 로고
    • Cross-generation and cross-laboratory predictions of Affymetrix microarrays by rank-based methods
    • 10.1016/j.jbi.2007.11.005, 18234562
    • Liu H-C, Chen C-Y, Liu Y-T, Chu C-B, Liang D-C, Shih L-Y, Lin C-J. Cross-generation and cross-laboratory predictions of Affymetrix microarrays by rank-based methods. Journal of Biomedical Informatics 2008, 41(4):570-579. 10.1016/j.jbi.2007.11.005, 18234562.
    • (2008) Journal of Biomedical Informatics , vol.41 , Issue.4 , pp. 570-579
    • Liu, H.-C.1    Chen, C.-Y.2    Liu, Y.-T.3    Chu, C.-B.4    Liang, D.-C.5    Shih, L.-Y.6    Lin, C.-J.7
  • 57
    • 0033982936 scopus 로고    scopus 로고
    • KEGG: Kyoto Encyclopedia of Genes and Genomes
    • 10.1093/nar/28.1.27, 102409, 10592173
    • Kanehisa M, Goto S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res 2000, 28(1):27-30. 10.1093/nar/28.1.27, 102409, 10592173.
    • (2000) Nucleic Acids Res , vol.28 , Issue.1 , pp. 27-30
    • Kanehisa, M.1    Goto, S.2
  • 58
    • 0000488788 scopus 로고
    • Network structure and minimum degree
    • Seidman SB. Network structure and minimum degree. Social Networks 1983, 5:269-287.
    • (1983) Social Networks , vol.5 , pp. 269-287
    • Seidman, S.B.1
  • 59
    • 0033028596 scopus 로고    scopus 로고
    • Systematic determination of genetic network architecture
    • 10.1038/10343, 10391217
    • Tavazoie S, Hughes JD, Campbell MJ, Cho RJ, Church GM. Systematic determination of genetic network architecture. Nat Genet 1999, 22(3):281-285. 10.1038/10343, 10391217.
    • (1999) Nat Genet , vol.22 , Issue.3 , pp. 281-285
    • Tavazoie, S.1    Hughes, J.D.2    Campbell, M.J.3    Cho, R.J.4    Church, G.M.5


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