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Dena Dubal, MD, PhD

Title(s)Associate Professor, Neurology
SchoolSchool of Medicine
Address675 Nelson Rising Lane
San Francisco CA 94158
Phone415-502-7237
ORCID ORCID Icon0000-0001-7504-4372 Additional info
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    Other Positions
    Title(s)UCSF Weill Institute for Neurosciences


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    The goal of our research is to investigate mechanisms of longevity, resilience and neurodegenerative disease. Broadly we investigate how aging pathways can confer resilience to a brain and counter neurodegenerative diseases like Alzheimer’s. Using genetic mouse models, cell culture methods, and study of human populations using cutting-edge techniques, we study whether longevity-derived mechanisms can pave a path toward development of urgently needed therapies in aging and disease.

    To this end, we are unraveling mechanisms that underlie female longevity, studying sex chromosomal contributions to neurodegenerative disease, and investigating the longevity hormone klotho in the normal and diseased brain.

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    Klotho and Neurodegenerative Disease
    NIH/NINDS R01NS092918Apr 1, 2016 - Mar 31, 2021
    Role: Principal Investigator
    Collagen VI: Novel Mechanisms and Functions in Alzheimer's Disease
    NIH/NIA K08AG034531Sep 1, 2009 - Sep 30, 2011
    Role: Principal Investigator

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Sexual dimorphism of physical activity on cognitive aging: Role of immune functioning. Brain Behav Immun. 2020 May 06. Casaletto KB, Lindbergh C, Memel M, Staffaroni A, Elahi F, Weiner-Light S, You M, Fonseca C, Karydas A, Jacobs E, Dubal DB, Yaffe K, Kramer JH. PMID: 32387511.
      View in: PubMed   Mentions:    Fields:    
    2. Longevity Gene KLOTHO and Alzheimer Disease-A Better Fate for Individuals Who Carry APOE e4. JAMA Neurol. 2020 Apr 13. Dubal DB, Yokoyama JS. PMID: 32282012.
      View in: PubMed   Mentions:    Fields:    
    3. Best of JAMA Neurology 2019: Research That Drives Practice. JAMA Neurol. 2020 Jan 06. Kamel H, Dubal DB. PMID: 31904807.
      View in: PubMed   Mentions:    Fields:    
    4. Pathways to brain resilience. Nat Med. 2019 07; 25(7):1027. Dubal DB. PMID: 31270494.
      View in: PubMed   Mentions:    Fields:    Translation:Humans
    5. Neural-Derived Extracellular Vesicles in Clinical Trials: Message in a Bottle. JAMA Neurol. 2019 04 01; 76(4):402-404. Dubal DB, Pleasure SJ. PMID: 30640380.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansCells
    6. KLOTHO heterozygosity attenuates APOE4-related amyloid burden in preclinical AD. Neurology. 2019 Apr 16; 92(16):e1878-e1889. Erickson CM, Schultz SA, Oh JM, Darst BF, Ma Y, Norton D, Betthauser T, Gallagher CL, Carlsson CM, Bendlin BB, Asthana S, Hermann BP, Sager MA, Blennow K, Zetterberg H, Engelman CD, Christian BT, Johnson SC, Dubal DB, Okonkwo OC. PMID: 30867273.
      View in: PubMed   Mentions: 1     Fields:    Translation:Humans
    7. Cognitive aging is not created equally: differentiating unique cognitive phenotypes in "normal" adults. Neurobiol Aging. 2019 05; 77:13-19. Casaletto KB, Elahi FM, Staffaroni AM, Walters S, Contreras WR, Wolf A, Dubal D, Miller B, Yaffe K, Kramer JH. PMID: 30772736.
      View in: PubMed   Mentions: 1     Fields:    Translation:Humans
    8. Female XX sex chromosomes increase survival and extend lifespan in aging mice. Aging Cell. 2019 02; 18(1):e12871. Davis EJ, Lobach I, Dubal DB. PMID: 30560587.
      View in: PubMed   Mentions:    Fields:    Translation:AnimalsCells
    9. Ovarian Cycle Stages Modulate Alzheimer-Related Cognitive and Brain Network Alterations in Female Mice. eNeuro. 2018 Nov-Dec; 5(6). Broestl L, Worden K, Moreno AJ, Davis EJ, Wang D, Garay B, Singh T, Verret L, Palop JJ, Dubal DB. PMID: 30627643.
      View in: PubMed   Mentions:    Fields:    Translation:HumansAnimals
    10. QOL-47. ApoE4 AS A GENETIC PREDICTOR FOR NEUROCOGNITIVE OUTCOMES IN PEDIATRIC BRAIN TUMOR SURVIVORS. Neuro-Oncology. 2018 Jun 22; 20(suppl_2):i167-i167. Cassie Kline, Erin Felton, Lennox Byer, Schuyler Stoller, Joseph Torkildson, Karen Gauvain, David Samuel, Elizabeth Tong, John Liu, Heather Fullerton, Dena Dubal, Sabine Mueller. .
      View in: Publisher Site   Mentions:
    11. The Way of Tau: Secretion and Synaptic Dysfunction. Trends Mol Med. 2018 07; 24(7):595-597. Dubal DB. PMID: 29807705.
      View in: PubMed   Mentions: 2     Fields:    Translation:HumansAnimalsCells
    12. Cord blood klotho levels are inversely associated with leptin in healthy Latino neonates at risk for obesity. J Pediatr Endocrinol Metab. 2018 Apr 25; 31(5):515-520. Wojcicki JM, Prather AA, Epel E, Wang D, Dubal DB. PMID: 29648999.
      View in: PubMed   Mentions: 1     Fields:    Translation:Humans
    13. Apolipoprotein E e4 and Risk Factors for Alzheimer Disease-Let's Talk About Sex. JAMA Neurol. 2017 10 01; 74(10):1167-1168. Dubal DB, Rogine C. PMID: 28846761.
      View in: PubMed   Mentions: 1     Fields:    Translation:Humans
    14. Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and a-Synuclein Transgenic Mice. Cell Rep. 2017 08 08; 20(6):1360-1371. Leon J, Moreno AJ, Garay BI, Chalkley RJ, Burlingame AL, Wang D, Dubal DB. PMID: 28793260.
      View in: PubMed   Mentions: 10     Fields:    Translation:AnimalsCells
    15. BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention. Neurology. 2017 May 30; 88(22):2098-2106. Boots EA, Schultz SA, Clark LR, Racine AM, Darst BF, Koscik RL, Carlsson CM, Gallagher CL, Hogan KJ, Bendlin BB, Asthana S, Sager MA, Hermann BP, Christian BT, Dubal DB, Engelman CD, Johnson SC, Okonkwo OC. PMID: 28468845.
      View in: PubMed   Mentions: 6     Fields:    Translation:Humans
    16. Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging. Brain Imaging Behav. 2017 04; 11(2):391-400. Yokoyama JS, Marx G, Brown JA, Bonham LW, Wang D, Coppola G, Seeley WW, Rosen HJ, Miller BL, Kramer JH, Dubal DB. PMID: 27714549.
      View in: PubMed   Mentions: 5     Fields:    Translation:Humans
    17. Sex biology contributions to vulnerability to Alzheimer's disease: A think tank convened by the Women's Alzheimer's Research Initiative. Alzheimers Dement. 2016 11; 12(11):1186-1196. Snyder HM, Asthana S, Bain L, Brinton R, Craft S, Dubal DB, Espeland MA, Gatz M, Mielke MM, Raber J, Rapp PR, Yaffe K, Carrillo MC. PMID: 27692800.
      View in: PubMed   Mentions: 25     Fields:    Translation:Humans
    18. LONGEVITY GENE KLOTHO ALTERS APOE4-RELATED CORTICAL THINNING: FINDINGS FROM THE WISCONSIN REGISTRY FOR ALZHEIMER’S PREVENTION. Alzheimer's & Dementia. 2016 Jul 1; 12(7):p56. Stephanie A. Schultz, Elizabeth A. Boots, Jennifer M. Oh, Burcu F. Darst, Rebecca L. Koscik, Catherine L. Gallagher, Cynthia M. Carlsson, Howard A. Rowley, Barbara B. Bendlin, Sanjay Asthana, Mark A. Sager, Kirk J. Hogan, Bruce P. Hermann, Corinne D. Engelman, Sterling C. Johnson, Dena B. Dubal, Ozioma C. Okonkwo. .
      View in: Publisher Site   Mentions:
    19. LONGEVITY GENE KLOTHO ALTERS APOE4-RELATED CORTICAL THINNING: FINDINGS FROM THE WISCONSIN REGISTRY FOR ALZHEIMER’S PREVENTION. Alzheimer's & Dementia. 2016 Jul 1; 12(7):p377-p378. Stephanie A. Schultz, Elizabeth A. Boots, Jennifer M. Oh, Burcu F. Darst, Rebecca L. Koscik, Catherine L. Gallagher, Cynthia M. Carlsson, Howard A. Rowley, Barbara B. Bendlin, Sanjay Asthana, Mark A. Sager, Kirk J. Hogan, Bruce P. Hermann, Corinne D. Engelman, Sterling C. Johnson, Dena B. Dubal, Ozioma C. Okonkwo. .
      View in: Publisher Site   Mentions:
    20. Network dysfunction in a-synuclein transgenic mice and human Lewy body dementia. Ann Clin Transl Neurol. 2015 11; 2(11):1012-28. Morris M, Sanchez PE, Verret L, Beagle AJ, Guo W, Dubal D, Ranasinghe KG, Koyama A, Ho K, Yu GQ, Vossel KA, Mucke L. PMID: 26732627.
      View in: PubMed   Mentions: 4     Fields:    
    21. Longevity factor klotho and chronic psychological stress. Transl Psychiatry. 2015 Jun 16; 5:e585. Prather AA, Epel ES, Arenander J, Broestl L, Garay BI, Wang D, Dubal DB. PMID: 26080320.
      View in: PubMed   Mentions: 10     Fields:    Translation:Humans
    22. Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice. J Neurosci. 2015 Feb 11; 35(6):2358-71. Dubal DB, Zhu L, Sanchez PE, Worden K, Broestl L, Johnson E, Ho K, Yu GQ, Kim D, Betourne A, Kuro-O M, Masliah E, Abraham CR, Mucke L. PMID: 25673831.
      View in: PubMed   Mentions: 32     Fields:    Translation:HumansAnimalsCells
    23. Variation in longevity gene KLOTHO is associated with greater cortical volumes. Ann Clin Transl Neurol. 2015 Mar; 2(3):215-30. Yokoyama JS, Sturm VE, Bonham LW, Klein E, Arfanakis K, Yu L, Coppola G, Kramer JH, Bennett DA, Miller BL, Dubal DB. PMID: 25815349.
      View in: PubMed   Mentions: 19     Fields:    
    24. Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory. Nat Neurosci. 2015 Mar; 18(3):423-34. Orr AG, Hsiao EC, Wang MM, Ho K, Kim DH, Wang X, Guo W, Kang J, Yu GQ, Adame A, Devidze N, Dubal DB, Masliah E, Conklin BR, Mucke L. PMID: 25622143.
      View in: PubMed   Mentions: 42     Fields:    Translation:HumansAnimalsCells
    25. Life extension factor klotho enhances cognition. Cell Rep. 2014 May 22; 7(4):1065-76. Dubal DB, Yokoyama JS, Zhu L, Broestl L, Worden K, Wang D, Sturm VE, Kim D, Klein E, Yu GQ, Ho K, Eilertson KE, Yu L, Kuro-o M, De Jager PL, Coppola G, Small GW, Bennett DA, Kramer JH, Abraham CR, Miller BL, Mucke L. PMID: 24813892.
      View in: PubMed   Mentions: 58     Fields:    Translation:HumansAnimalsCells
    26. Reversible suppression of electrocerebral activity. Neurohospitalist. 2013 Oct; 3(4):229-30. Broestl L, Cornes S, Dubal DB. PMID: 24198906.
      View in: PubMed   Mentions:
    27. Sex and gonadal hormones in mouse models of Alzheimer's disease: what is relevant to the human condition? Biol Sex Differ. 2012 Nov 05; 3(1):24. Dubal DB, Broestl L, Worden K. PMID: 23126652.
      View in: PubMed   Mentions: 9     Fields:    
    28. Human P301L-mutant tau expression in mouse entorhinal-hippocampal network causes tau aggregation and presynaptic pathology but no cognitive deficits. PLoS One. 2012; 7(9):e45881. Harris JA, Koyama A, Maeda S, Ho K, Devidze N, Dubal DB, Yu GQ, Masliah E, Mucke L. PMID: 23029293.
      View in: PubMed   Mentions: 39     Fields:    Translation:HumansAnimalsCells
    29. T-cell lymphoproliferative disorder following mycophenolate treatment for myasthenia gravis. Muscle Nerve. 2009 Jun; 39(6):849-50. Dubal DB, Mueller S, Ruben BS, Engstrom JW, Josephson SA. PMID: 19358236.
      View in: PubMed   Mentions:    Fields:    Translation:HumansCells
    30. Collagen VI protects neurons against Abeta toxicity. Nat Neurosci. 2009 Feb; 12(2):119-21. Cheng JS, Dubal DB, Kim DH, Legleiter J, Cheng IH, Yu GQ, Tesseur I, Wyss-Coray T, Bonaldo P, Mucke L. PMID: 19122666.
      View in: PubMed   Mentions: 40     Fields:    Translation:HumansAnimalsCells
    31. P1-465: Role of collagen VI in Alzheimer's disease: Potential mechanisms of protection. Alzheimer's & Dementia. 2008 Jul 1; 4(4):t356. Dena B. Dubal, Jason Cheng, Justin Legleiter, Sarah Wilkins, Paolo Bonaldo, Gui-Qiu Yu, Lennart Mucke. .
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    32. A case of paraneoplastic myelopathy associated with the neuromyelitis optica antibody. Nat Clin Pract Neurol. 2008 May; 4(5):284-8. Mueller S, Dubal DB, Josephson SA. PMID: 18317500.
      View in: PubMed   Mentions: 9     Fields:    Translation:Humans
    33. Differential modulation of estrogen receptors (ERs) in ischemic brain injury: a role for ERalpha in estradiol-mediated protection against delayed cell death. Endocrinology. 2006 Jun; 147(6):3076-84. Dubal DB, Rau SW, Shughrue PJ, Zhu H, Yu J, Cashion AB, Suzuki S, Gerhold LM, Bottner MB, Dubal SB, Merchanthaler I, Kindy MS, Wise PM. PMID: 16527848.
      View in: PubMed   Mentions: 69     Fields:    Translation:AnimalsCells
    34. Stroke injury in rats causes an increase in activin A gene expression which is unaffected by oestradiol treatment. J Neuroendocrinol. 2006 Feb; 18(2):97-103. Böttner M, Dubal DB, Rau SW, Suzuki S, Wise PM. PMID: 16420278.
      View in: PubMed   Mentions: 4     Fields:    Translation:AnimalsCells
    35. Are estrogens protective or risk factors in brain injury and neurodegeneration? Reevaluation after the Women's health initiative. Endocr Rev. 2005 May; 26(3):308-12. Wise PM, Dubal DB, Rau SW, Brown CM, Suzuki S. PMID: 15851820.
      View in: PubMed   Mentions: 45     Fields:    Translation:HumansAnimals
    36. Mechanisms of sex-based neuropathologies. Principles of Sex-based Differences in Physiology. 2004 Jan 1; 34:281-294. Phyllis M. Wise, Dena B. Dubal, Shane W. Rau, Adrienne B. Cashion. .
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    37. Activin gene expression increases after stroke injury: Modulation by estradiol. Experimental and Clinical Endocrinology & Diabetes. 2004 Jan 1; 112(S 1). M Böttner, DB Dubal, SW Rau, PM Wise. .
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    38. Are Estrogens Protective or Risk Factors in the Brain? Insights Derived From Animal Models. Endocrine Aspects of Successful Aging: Genes, Hormones and Lifestyles. 2004 Jan 1; 165-173. Phyllis M. Wise, Dena B. Dubal. .
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    39. Estradiol attenuates programmed cell death after stroke-like injury. J Neurosci. 2003 Dec 10; 23(36):11420-6. Rau SW, Dubal DB, Böttner M, Gerhold LM, Wise PM. PMID: 14673006.
      View in: PubMed   Mentions: 46     Fields:    Translation:Animals
    40. Estradiol differentially regulates c-Fos after focal cerebral ischemia. J Neurosci. 2003 Nov 19; 23(33):10487-94. Rau SW, Dubal DB, Böttner M, Wise PM. PMID: 14627632.
      View in: PubMed   Mentions: 10     Fields:    Translation:Animals
    41. Ms Jones: reflections on aging, illness, and medicine. Fam Med. 2003 Mar; 35(3):165-6. Dubal D. PMID: 12670107.
      View in: PubMed   Mentions:    Fields:    Translation:Humans
    42. Estrogen and neuroprotection: from clinical observations to molecular mechanisms. Dialogues Clin Neurosci. 2002 Jun; 4(2):149-61. Dubal DB, Wise PM. PMID: 22034440.
      View in: PubMed   Mentions: 8     Fields:    
    43. Neuroendocrine modulation and repercussions of female reproductive aging. Recent Prog Horm Res. 2002; 57:235-56. Wise PM, Smith MJ, Dubal DB, Wilson ME, Rau SW, Cashion AB, Böttner M, Rosewell KL. PMID: 12017546.
      View in: PubMed   Mentions: 37     Fields:    Translation:HumansAnimals
    44. Estradiol is a protective factor in the adult and aging brain: understanding of mechanisms derived from in vivo and in vitro studies. Brain Res Brain Res Rev. 2001 Nov; 37(1-3):313-9. Wise PM, Dubal DB, Wilson ME, Rau SW, Böttner M, Rosewell KL. PMID: 11744096.
      View in: PubMed   Mentions: 53     Fields:    Translation:AnimalsCells
    45. In Vitro and In Vivo Approaches to the Study of the Neuroprotective Actions of Estradiol. Neuroplasticity, Development, and Steroid Hormone Action. 2001 Jul 30. Phyllis Wise, Melinda Wilson, Dena Dubal, Shane Rau. .
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    46. Minireview: neuroprotective effects of estrogen-new insights into mechanisms of action. Endocrinology. 2001 Mar; 142(3):969-73. Wise PM, Dubal DB, Wilson ME, Rau SW, Böttner M. PMID: 11181507.
      View in: PubMed   Mentions: 44     Fields:    Translation:HumansAnimals
    47. Estrogen receptor a, not ß, is a critical link in estradiol-mediated protection against brain injury. Proceedings of the National Academy of Sciences. 2001 Feb 13; 98(4):1952-1957. Dena B. Dubal, Hong Zhu, Jin Yu, Shane W. Rau, Paul J. Shughrue, Istvan Merchenthaler, Mark S. Kindy, Phyllis M. Wise. .
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    48. Estrogen receptor alpha, not beta, is a critical link in estradiol-mediated protection against brain injury. Proc Natl Acad Sci U S A. 2001 Feb 13; 98(4):1952-7. Dubal DB, Zhu H, Yu J, Rau SW, Shughrue PJ, Merchenthaler I, Kindy MS, Wise PM. PMID: 11172057.
      View in: PubMed   Mentions: 171     Fields:    Translation:Animals
    49. Estrogens: trophic and protective factors in the adult brain. Front Neuroendocrinol. 2001 Jan; 22(1):33-66. Wise PM, Dubal DB, Wilson ME, Rau SW, Liu Y. PMID: 11141318.
      View in: PubMed   Mentions: 50     Fields:    Translation:HumansAnimalsCells
    50. Neuroprotective effects of estradiol in middle-aged female rats. Endocrinology. 2001 Jan; 142(1):43-8. Dubal DB, Wise PM. PMID: 11145565.
      View in: PubMed   Mentions: 59     Fields:    Translation:HumansAnimals
    51. Neuroprotective Effects of Estradiol in Middle-Aged Female Rats 1. Endocrinology. 2001 Jan 1; 142(1):43-48. Dena B. Dubal, Phyllis M. Wise. .
      View in: Publisher Site   Mentions:
    52. Estradiol protects against ischemic brain injury in middle-aged rats. Biol Reprod. 2000 Oct; 63(4):982-5. Wise PM, Dubal DB. PMID: 10993817.
      View in: PubMed   Mentions: 25     Fields:    Translation:Animals
    53. Estradiol protects against injury-induced cell death in cortical explant cultures: a role for estrogen receptors. Brain Res. 2000 Aug 11; 873(2):235-42. Wilson ME, Dubal DB, Wise PM. PMID: 10930549.
      View in: PubMed   Mentions: 33     Fields:    Translation:Animals
    54. Estradiol is a neuroprotective factor in in vivo and in vitro models of brain injury. J Neurocytol. 2000 May-Jun; 29(5-6):401-10. Wise PM, Dubal DB, Wilson ME, Rau SW. PMID: 11424956.
      View in: PubMed   Mentions: 13     Fields:    Translation:Animals
    55. Neuroprotective actions of estradiol in the adult and aging brain: Potential mechanisms of action. Neurobiology of Aging. 2000 May 1; 21:212-213. Phyllis M. Wise, Dena Dubal, Melinda E. Wilson, Shane W. Rau. .
      View in: Publisher Site   Mentions:
    56. Estradiol: a protective and trophic factor in the brain. J Alzheimers Dis. 1999 Nov; 1(4-5):265-74. Dubal DB, Wilson ME, Wise PM. PMID: 12214124.
      View in: PubMed   Mentions: 6     Fields:    
    57. Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors. J Neurosci. 1999 Aug 01; 19(15):6385-93. Dubal DB, Shughrue PJ, Wilson ME, Merchenthaler I, Wise PM. PMID: 10414967.
      View in: PubMed   Mentions: 116     Fields:    Translation:Animals
    58. Neuroendocrine influences and repercussions of the menopause. Endocr Rev. 1999 Jun; 20(3):243-8. Wise PM, Smith MJ, Dubal DB, Wilson ME, Krajnak KM, Rosewell KL. PMID: 10368769.
      View in: PubMed   Mentions: 10     Fields:    Translation:Humans
    59. Estradiol protects against ischemic injury. J Cereb Blood Flow Metab. 1998 Nov; 18(11):1253-8. Dubal DB, Kashon ML, Pettigrew LC, Ren JM, Finklestein SP, Rau SW, Wise PM. PMID: 9809515.
      View in: PubMed   Mentions: 129     Fields:    Translation:HumansAnimals
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