{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:45:15Z","timestamp":1790815515166,"version":"4.1.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,11]]},"DOI":"10.7759\/cureus.85814","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T05:53:47Z","timestamp":1749707627000},"source":"Crossref","is-referenced-by-count":6,"title":["Potential of Nerve Growth Factor (NGF)- and Brain-Derived Neurotrophic Factor (BDNF)-Targeted Gene Therapy for Alzheimer\u2019s Disease: A Narrative Review"],"prefix":"10.7759","author":[{"given":"Prakhya Chowdary","family":"Koya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saieesha Chowdary","family":"Kolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varun","family":"Madala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh Babu","family":"Sayana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00062","article-title":"The brain NGF metabolic pathway in health and in Alzheimer\u2019s pathology","volume":"13","author":"Cuello AC","year":"2019","unstructured":"Cuello AC, Pentz R, Hall H. The brain NGF metabolic pathway in health and in Alzheimer\u2019s pathology. Front Neurosci. 2019, 13:62. 10.3389\/fnins.2019.00062","journal-title":"Front Neurosci"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27061816","article-title":"Role of cholinergic signaling in Alzheimer's disease","volume":"27","author":"Chen ZR","year":"2022","unstructured":"Chen ZR, Huang JB, Yang SL, Hong FF. Role of cholinergic signaling in Alzheimer's disease. Molecules. 2022, 27:10.3390\/molecules27061816","journal-title":"Molecules"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/s0079-6123(03)46028-7","article-title":"Nerve growth factor: from animal models of cholinergic neuronal degeneration to gene therapy in Alzheimer\u2019s disease","volume":"146","author":"Tuszynski MH","year":"2004","unstructured":"Tuszynski MH, Blesch A. Nerve growth factor: from animal models of cholinergic neuronal degeneration to gene therapy in Alzheimer\u2019s disease. Prog Brain Res. 2004, 146:439-49. 10.1016\/s0079-6123(03)46028-7","journal-title":"Prog Brain Res"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e318068d6d2","article-title":"Nerve growth factor gene therapy in Alzheimer disease","volume":"21","author":"Tuszynski MH","year":"2007","unstructured":"Tuszynski MH. Nerve growth factor gene therapy in Alzheimer disease. Alzheimer Dis Assoc Disord. 2007, 21:179-89. 10.1097\/WAD.0b013e318068d6d2","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15471","article-title":"Basal forebrain cholinergic system in the dementias: vulnerability, resilience, and resistance","volume":"158","author":"Geula C","year":"2021","unstructured":"Geula C, Dunlop SR, Ayala I, Kawles AS, Flanagan ME, Gefen T, Mesulam MM. Basal forebrain cholinergic system in the dementias: vulnerability, resilience, and resistance. J Neurochem. 2021, 158:1394-411. 10.1111\/jnc.15471","journal-title":"J Neurochem"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1376764","article-title":"The role of the nucleus basalis of Meynert in neuromodulation therapy: a systematic review from the perspective of neural network oscillations","volume":"16","author":"Jiao L","year":"2024","unstructured":"Jiao L, Kang H, Geng Y, Liu X, Wang M, Shu K. The role of the nucleus basalis of Meynert in neuromodulation therapy: a systematic review from the perspective of neural network oscillations. Front Aging Neurosci. 2024, 16:1376764. 10.3389\/fnagi.2024.1376764","journal-title":"Front Aging Neurosci"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.01.004","article-title":"GDNF, NGF and BDNF as therapeutic options for neurodegeneration","volume":"138","author":"Allen SJ","year":"2013","unstructured":"Allen SJ, Watson JJ, Shoemark DK, Barua NU, Patel NK. GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther. 2013, 138:155-75. 10.1016\/j.pharmthera.2013.01.004","journal-title":"Pharmacol Ther"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00363","article-title":"Brain-derived neurotrophic factor: a key molecule for memory in the healthy and the pathological brain","volume":"13","author":"Miranda M","year":"2019","unstructured":"Miranda M, Morici JF, Zanoni MB, Bekinschtein P. Brain-derived neurotrophic factor: a key molecule for memory in the healthy and the pathological brain. Front Cell Neurosci. 2019, 13:363. 10.3389\/fncel.2019.00363","journal-title":"Front Cell Neurosci"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.0233","article-title":"Adeno-associated viral vector (serotype 2)-nerve growth factor for patients with Alzheimer disease a randomized clinical trial","volume":"75","author":"Rafii MS","year":"2018","unstructured":"Rafii MS, Tuszynski MH, Thomas RG, et al.. Adeno-associated viral vector (serotype 2)-nerve growth factor for patients with Alzheimer disease a randomized clinical trial. JAMA Neurol. 2018, 75:834-41. 10.1001\/jamaneurol.2018.0233","journal-title":"JAMA Neurol"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2013.09.004","article-title":"A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer's disease","volume":"10","author":"Rafii MS","year":"2014","unstructured":"Rafii MS, Baumann TL, Bakay RA, et al.. A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer's disease. Alzheimers Dement. 2014, 10:571-81. 10.1016\/j.jalz.2013.09.004","journal-title":"Alzheimers Dement"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.1807","article-title":"Nerve growth factor gene therapy activation of neuronal responses in Alzheimer disease","volume":"72","author":"Tuszynski MH","year":"2015","unstructured":"Tuszynski MH, Yang JH, Barba D, et al.. Nerve growth factor gene therapy activation of neuronal responses in Alzheimer disease. JAMA Neurol. 2015, 72:1139-47. 10.1001\/jamaneurol.2015.1807","journal-title":"JAMA Neurol"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26094271","article-title":"From synaptic plasticity to neurodegeneration: BDNF as a transformative target in medicine","volume":"26","author":"Toader C","year":"2025","unstructured":"Toader C, Serban M, Munteanu O, Covache-Busuioc RA, Enyedi M, Ciurea AV, Tataru CP. From synaptic plasticity to neurodegeneration: BDNF as a transformative target in medicine. Int J Mol Sci. 2025, 26:10.3390\/ijms26094271","journal-title":"Int J Mol Sci"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22830","article-title":"Sendai virus vector-mediated brain-derived neurotrophic factor expression ameliorates memory deficits and synaptic degeneration in a transgenic mouse model of Alzheimer's disease","volume":"90","author":"Iwasaki Y","year":"2012","unstructured":"Iwasaki Y, Negishi T, Inoue M, Tashiro T, Tabira T, Kimura N. Sendai virus vector-mediated brain-derived neurotrophic factor expression ameliorates memory deficits and synaptic degeneration in a transgenic mouse model of Alzheimer's disease. J Neurosci Res. 2012, 90:981-9. 10.1002\/jnr.22830","journal-title":"J Neurosci Res"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1012851108","article-title":"CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer's disease","volume":"107","author":"Caccamo A","year":"2010","unstructured":"Caccamo A, Maldonado MA, Bokov AF, Majumder S, Oddo S. CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2010, 107:22687-92. 10.1073\/pnas.1012851108","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2025.101649","article-title":"Hippocampus-targeted BDNF gene therapy to rescue cognitive impairments of Alzheimer\u2019s disease in multiple mouse models","author":"Tang S","year":"2025","unstructured":"Tang S, Luo W, Wu S, et al.. Hippocampus-targeted BDNF gene therapy to rescue cognitive impairments of Alzheimer\u2019s disease in multiple mouse models. Genes Dis. 2025, 101649. 10.1016\/j.gendis.2025.101649","journal-title":"Genes Dis"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.3389\/FNINS.2019.00038","article-title":"Innovative therapy for Alzheimer\u2019s disease-with focus on biodelivery of NGF","volume":"13","author":"Mitra S","year":"2019","unstructured":"Mitra S, Behbahani H, Eriksdotter M. Innovative therapy for Alzheimer\u2019s disease-with focus on biodelivery of NGF. Front Neurosci. 2019, 13:434303. 10.3389\/FNINS.2019.00038","journal-title":"Front Neurosci"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1080\/02648725.2018.1523521","article-title":"Current viral-mediated gene transfer research for treatment of Alzheimer's disease","volume":"35","author":"Sasmita AO","year":"2019","unstructured":"Sasmita AO. Current viral-mediated gene transfer research for treatment of Alzheimer's disease. Biotechnol Genet Eng Rev. 2019, 35:26-45. 10.1080\/02648725.2018.1523521","journal-title":"Biotechnol Genet Eng Rev"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00038","article-title":"Innovative therapy for Alzheimer\u2019s disease-with focus on biodelivery of NGF","volume":"13","author":"Mitra S","year":"2019","unstructured":"Mitra S, Behbahani H, Eriksdotter M. Innovative therapy for Alzheimer\u2019s disease-with focus on biodelivery of NGF. Front Neurosci. 2019, 13:38. 10.3389\/fnins.2019.00038","journal-title":"Front Neurosci"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2015.09.008","article-title":"Neural stem cells rescue cognitive and motor dysfunction in a transgenic model of dementia with lewy bodies through a BDNF-dependent mechanism","volume":"5","author":"Goldberg NR","year":"2015","unstructured":"Goldberg NR, Caesar J, Park A, et al.. Neural stem cells rescue cognitive and motor dysfunction in a transgenic model of dementia with lewy bodies through a BDNF-dependent mechanism. Stem Cell Reports. 2015, 5:791-804. 10.1016\/j.stemcr.2015.09.008","journal-title":"Stem Cell Reports"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2019.367","article-title":"Postmortem analysis in a clinical trial of AAV2-NGF gene therapy for alzheimer\u2019s disease identifies a need for improved vector delivery","volume":"31","author":"Castle MJ","year":"2020","unstructured":"Castle MJ, Baltan\u00e1s FC, Kovacs I, Nagahara AH, Barba D, Tuszynski MH. Postmortem analysis in a clinical trial of AAV2-NGF gene therapy for alzheimer\u2019s disease identifies a need for improved vector delivery. Hum Gene Ther. 2020, 31:415-22. 10.1089\/hum.2019.367","journal-title":"Hum Gene Ther"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/64.4.263","article-title":"The role of nerve growth factor receptors in cholinergic basal forebrain degeneration in prodromal Alzheimer disease","volume":"64","author":"Counts SE","year":"2005","unstructured":"Counts SE, Mufson EJ. The role of nerve growth factor receptors in cholinergic basal forebrain degeneration in prodromal Alzheimer disease. J Neuropathol Exp Neurol. 2005, 64:263-72. 10.1093\/jnen\/64.4.263","journal-title":"J Neuropathol Exp Neurol"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro.1994.5.3.179","article-title":"Nerve growth factor and Alzheimer's disease","volume":"5","author":"Scott SA","year":"1994","unstructured":"Scott SA, Crutcher KA. Nerve growth factor and Alzheimer's disease. Rev Neurosci. 1994, 5:179-211. 10.1515\/revneuro.1994.5.3.179","journal-title":"Rev Neurosci"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2006.09.001","article-title":"Nerve growth factor in treatment and pathogenesis of Alzheimer's disease","volume":"80","author":"Williams BJ","year":"2006","unstructured":"Williams BJ, Eriksdotter-Jonhagen M, Granholm AC. Nerve growth factor in treatment and pathogenesis of Alzheimer's disease. Prog Neurobiol. 2006, 80:114-28. 10.1016\/j.pneurobio.2006.09.001","journal-title":"Prog Neurobiol"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3390\/cells11010016","article-title":"The nerve growth factor metabolic pathway dysregulation as cause of Alzheimer\u2019s cholinergic atrophy","volume":"11","author":"Do Carmo S","year":"2021","unstructured":"Do Carmo S, Kannel B, Cuello AC. The nerve growth factor metabolic pathway dysregulation as cause of Alzheimer\u2019s cholinergic atrophy. Cells. 2021, 11:10.3390\/cells11010016","journal-title":"Cells"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00446","article-title":"Exploring the pathogenesis of Alzheimer disease in basal forebrain cholinergic neurons: converging insights from alternative hypotheses","volume":"13","author":"Chen XQ","year":"2019","unstructured":"Chen XQ, Mobley WC. Exploring the pathogenesis of Alzheimer disease in basal forebrain cholinergic neurons: converging insights from alternative hypotheses. Front Neurosci. 2019, 13:446. 10.3389\/fnins.2019.00446","journal-title":"Front Neurosci"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00533","article-title":"Nerve growth factor pathobiology during the progression of Alzheimer\u2019s disease","volume":"13","author":"Mufson EJ","year":"2019","unstructured":"Mufson EJ, Counts SE, Ginsberg SD, et al.. Nerve growth factor pathobiology during the progression of Alzheimer\u2019s disease. Front Neurosci. 2019, 13:533. 10.3389\/fnins.2019.00533","journal-title":"Front Neurosci"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2022.11.007","article-title":"MSC based gene delivery methods and strategies improve the therapeutic efficacy of neurological diseases","volume":"23","author":"Zhou H","year":"2023","unstructured":"Zhou H, He Y, Xiong W, et al.. MSC based gene delivery methods and strategies improve the therapeutic efficacy of neurological diseases. Bioact Mater. 2023, 23:409-37. 10.1016\/j.bioactmat.2022.11.007","journal-title":"Bioact Mater"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12312","article-title":"Lenti-GDNF gene therapy protects against Alzheimer's disease-like neuropathology in 3xTg-AD mice and MC65 cells","volume":"20","author":"Revilla S","year":"2014","unstructured":"Revilla S, Ursulet S, \u00c1lvarez-L\u00f3pez MJ, et al.. Lenti-GDNF gene therapy protects against Alzheimer's disease-like neuropathology in 3xTg-AD mice and MC65 cells. CNS Neurosci Ther. 2014, 20:961-72. 10.1111\/cns.12312","journal-title":"CNS Neurosci Ther"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2010.01038.x","article-title":"Gene therapy in Alzheimer's disease - potential for disease modification","volume":"14","author":"Nilsson P","year":"2010","unstructured":"Nilsson P, Iwata N, Muramatsu S, Tjernberg LO, Winblad B, Saido TC. Gene therapy in Alzheimer's disease - potential for disease modification. J Cell Mol Med. 2010, 14:741-57. 10.1111\/j.1582-4934.2010.01038.x","journal-title":"J Cell Mol Med"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.735928","article-title":"Nerve growth factor-based therapy in Alzheimer\u2019s disease and age-related macular degeneration","volume":"15","author":"Amadoro G","year":"2021","unstructured":"Amadoro G, Latina V, Balzamino BO, Squitti R, Varano M, Calissano P, Micera A. Nerve growth factor-based therapy in Alzheimer\u2019s disease and age-related macular degeneration. Front Neurosci. 2021, 15:735928. 10.3389\/fnins.2021.735928","journal-title":"Front Neurosci"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.3233\/jad-2008-15210","article-title":"Towards non invasive nerve growth factor therapies for Alzheimer's disease","volume":"15","author":"Cattaneo A","year":"2008","unstructured":"Cattaneo A, Capsoni S, Paoletti F. Towards non invasive nerve growth factor therapies for Alzheimer's disease. J Alzheimers Dis. 2008, 15:255-83. 10.3233\/jad-2008-15210","journal-title":"J Alzheimers Dis"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy132","article-title":"The cholinergic system in the pathophysiology and treatment of Alzheimer's disease","volume":"141","author":"Hampel H","year":"2018","unstructured":"Hampel H, Mesulam MM, Cuello AC, et al.. The cholinergic system in the pathophysiology and treatment of Alzheimer's disease. Brain. 2018, 141:1917-33. 10.1093\/brain\/awy132","journal-title":"Brain"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10051143","article-title":"Brain-derived neurotropic factor in neurodegenerative disorders","volume":"10","author":"Ibrahim AM","year":"2022","unstructured":"Ibrahim AM, Chauhan L, Bhardwaj A, et al.. Brain-derived neurotropic factor in neurodegenerative disorders. Biomedicines. 2022, 10:10.3390\/biomedicines10051143","journal-title":"Biomedicines"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2025.1518868","article-title":"Neurotrophic factor alpha 1 gene therapy in Alzheimer's disease: scope and advancements","volume":"18","author":"Shaikh A","year":"2025","unstructured":"Shaikh A, Ahmad F, Teoh SL, Kumar J, Yahaya MF. Neurotrophic factor alpha 1 gene therapy in Alzheimer's disease: scope and advancements. Front Mol Neurosci. 2025, 18:1518868. 10.3389\/fnmol.2025.1518868","journal-title":"Front Mol Neurosci"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-025-03227-4","article-title":"Electrophysiology-based screening identifies neuronal HtrA serine peptidase 2 (HTRA2) as a synaptic plasticity regulator participating in tauopathy","volume":"15","author":"Zheng N","year":"2025","unstructured":"Zheng N, Li K, Cao J, et al.. Electrophysiology-based screening identifies neuronal HtrA serine peptidase 2 (HTRA2) as a synaptic plasticity regulator participating in tauopathy. Transl Psychiatry. 2025, 15:5. 10.1038\/s41398-025-03227-4","journal-title":"Transl Psychiatry"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.3390\/jnt6020010","article-title":"Nanotheranostics revolutionizing gene therapy: emerging applications in gene delivery enhancement","volume":"6","author":"Guzm\u00e1n-Sastoque P","year":"2025","unstructured":"Guzm\u00e1n-Sastoque P, Rodr\u00edguez CF, Monsalve MC, et al.. Nanotheranostics revolutionizing gene therapy: emerging applications in gene delivery enhancement. J Nanotheranostics. 2025, 6:10. 10.3390\/jnt6020010","journal-title":"J Nanotheranostics"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13113098","article-title":"Novel therapeutic strategies in Alzheimer\u2019s disease: pitfalls and challenges of anti-amyloid therapies and beyond","volume":"13","author":"Tondo G","year":"2024","unstructured":"Tondo G, De Marchi F, Bonardi F, et al.. Novel therapeutic strategies in Alzheimer\u2019s disease: pitfalls and challenges of anti-amyloid therapies and beyond. J Clin Med. 2024, 13:10.3390\/jcm13113098","journal-title":"J Clin Med"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.4236\/OALIB.1112714","article-title":"BDNF gene therapy: a potential solution for neurodegenerative diseases","volume":"12","author":"Katkar T","year":"2025","unstructured":"Katkar T. BDNF gene therapy: a potential solution for neurodegenerative diseases. OALibJ. 2025, 12:1-16. 10.4236\/OALIB.1112714","journal-title":"OALibJ"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.3389\/fgeed.2022.899209","article-title":"Gene therapy: the next-generation therapeutics and their delivery approaches for neurological disorders","volume":"4","author":"Paul A","year":"2022","unstructured":"Paul A, Collins MG, Lee HY. Gene therapy: the next-generation therapeutics and their delivery approaches for neurological disorders. Front Genome Ed. 2022, 4:899209. 10.3389\/fgeed.2022.899209","journal-title":"Front Genome Ed"}],"container-title":["Cureus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cureus.com\/articles\/374686-potential-of-nerve-growth-factor-ngf--and-brain-derived-neurotrophic-factor-bdnf-targeted-gene-therapy-for-alzheimers-disease-a-narrative-review","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T05:53:48Z","timestamp":1749707628000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cureus.com\/articles\/374686-potential-of-nerve-growth-factor-ngf--and-brain-derived-neurotrophic-factor-bdnf-targeted-gene-therapy-for-alzheimers-disease-a-narrative-review"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,11]]},"references-count":39,"URL":"https:\/\/doi.org\/10.7759\/cureus.85814","relation":{},"ISSN":["2168-8184"],"issn-type":[{"value":"2168-8184","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6,11]]}}}