{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:09:44Z","timestamp":1794006584605,"version":"4.8.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":230,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020948","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020948","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016040","name":"Takeda","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016040","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Accumulation of pathological forms of \u03b1-synuclein is a hallmark of Parkinson\u2019s disease. MEDI1341 (also known as TAK-341) is a high-affinity, \u03b1-synuclein-specific, fully human monoclonal antibody that binds the C-terminal region of human \u03b1-synuclein. Pre-clinical studies of MEDI1341 demonstrated significant reductions in \u03b1-synuclein accumulation and propagation along axons. Two randomized, double-blind, placebo-controlled, Phase 1 studies administering MEDI1341 intravenously were conducted; a single ascending dose study (NCT03272165) of MEDI1341 (70, 210, 400, 1200, 2400 or 4500\u2005mg; n = 6 each) or placebo (n = 13 total) in healthy participants and a multiple ascending dose study (NCT04449484) of 4-weekly MEDI1341 (1200 or 2000\u2005mg; n = 9 each) or placebo (n = 7 total) in participants with Parkinson\u2019s disease. Both studies assessed the safety and tolerability of MEDI1341 versus placebo, with MEDI1341 pharmacokinetics, pharmacodynamics and immunogenicity as secondary objectives. Pharmacokinetic (MEDI1341 in serum and CSF) and pharmacodynamic (total \u03b1-synuclein in plasma, and free \u03b1-synuclein in CSF) concentrations were determined using validated electrochemiluminescence assays. Overall, 49 healthy participants (67.3% male; mean [standard deviation] age 43.4 [9.5] years) were included in the single ascending dose study and 25 participants with Parkinson\u2019s disease (72.0% male; mean [standard deviation] age 63.0 [9.0] years; 88% Hoehn and Yahr stage 2) were included in the multiple ascending dose study. Treatment-emergent adverse events were reported in 23 healthy participants (MEDI1341, n = 17; placebo, n = 6) and 10 participants with Parkinson\u2019s disease (MEDI1341, n = 9; placebo, n = 1). The most common treatment-related treatment-emergent adverse events were headache, fall and nausea. Dose proportional increases were observed for maximum concentration in serum and area under the curve (AUC) in both studies, with the exception of a supra-proportional increase in AUC0\u2013\u221e from 2400 to 4500\u2005mg (single ascending dose study). Median time to maximum concentration was 1\u2005h after intravenous administration and geometric mean terminal elimination half-life ranged from 16.6 to 24.3 days across both studies. Suppression of \u03b1-synuclein in CSF was greatest at the highest doses investigated: \u221253.6% median change from baseline on Day 15 [4500\u2005mg (healthy participants)] and \u221259.0% median change from baseline on Day 85 [2000\u2005mg (participants with Parkinson\u2019s disease)]. Across all doses and time points, individual participant CSF MEDI1341 concentrations were &amp;lt;1% of their respective serum concentrations. MEDI1341 had favourable safety, tolerability, pharmacokinetic and pharmacodynamic profiles in healthy participants and those with Parkinson\u2019s disease, supporting further clinical development. MEDI1341 is the first monoclonal antibody targeted against \u03b1-synuclein to demonstrate a &amp;gt; 50% reduction in CSF-free \u03b1-synuclein.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf304","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T11:20:27Z","timestamp":1755516027000},"source":"Crossref","is-referenced-by-count":11,"title":["Phase 1, randomized trials of MEDI1341: cerebrospinal fluid free \u03b1-synuclein lowered by &amp;gt;50%"],"prefix":"10.1093","volume":"7","author":[{"given":"Craig","family":"Shering","sequence":"first","affiliation":[{"name":"Neuroscience, BioPharmaceuticals R&D, AstraZeneca , Boston, MA 02210 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pomfret","sequence":"additional","affiliation":[{"name":"Neuroscience, BioPharmaceuticals R&D, AstraZeneca , Trumpington, Cambridge CB2 0AA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Kubiak","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca , Gaithersburg, MA 20878 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle J","family":"Pouliquen","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca , Trumpington, Cambridge CB2 0AA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Quantitative Clinical Pharmacology, Takeda Development Center Americas Inc. , Cambridge, MA 02142 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Simen","sequence":"additional","affiliation":[{"name":"Neuroscience Therapy Area Unit, Takeda Development Center Americas Inc. , Cambridge, MA 02142 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ratti","sequence":"additional","affiliation":[{"name":"Neuroscience Therapy Area Unit, Takeda Development Center Americas Inc. , Cambridge, MA 02142 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zubair","family":"Hussain","sequence":"additional","affiliation":[{"name":"Neuroscience, BioPharmaceuticals R&D, AstraZeneca , Trumpington, Cambridge CB2 0AA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Perkinton","sequence":"additional","affiliation":[{"name":"Neuroscience, BioPharmaceuticals R&D, AstraZeneca , Trumpington, Cambridge CB2 0AA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Tan","sequence":"additional","affiliation":[{"name":"Neuroscience, BioPharmaceuticals R&D, AstraZeneca , Trumpington, Cambridge CB2 0AA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten M","family":"Scott","sequence":"additional","affiliation":[{"name":"Neuroscience, BioPharmaceuticals R&D, AstraZeneca , Trumpington, Cambridge CB2 0AA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thor","family":"Ostenfeld","sequence":"additional","affiliation":[{"name":"Neuroscience, BioPharmaceuticals R&D, AstraZeneca , Trumpington, Cambridge CB2 0AA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Chessell","sequence":"additional","affiliation":[{"name":"Neuroscience, BioPharmaceuticals R&D, AstraZeneca , Trumpington, Cambridge CB2 0AA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"issue":"3","key":"2025091004162495200_fcaf304-B1","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/s41419-023-05672-9","article-title":"Alpha-synuclein in Parkinson's disease and other synucleinopathies: From overt neurodegeneration back to early synaptic dysfunction","volume":"14","author":"Calabresi","year":"2023","journal-title":"Cell Death Dis"},{"issue":"6","key":"2025091004162495200_fcaf304-B2","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/s41583-023-00697-7","article-title":"Multiple system atrophy: At the crossroads of cellular, molecular and genetic mechanisms","volume":"24","author":"Stefanova","year":"2023","journal-title":"Nat Rev Neurosci"},{"issue":"3","key":"2025091004162495200_fcaf304-B3","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/S1474-4422(12)70327-7","article-title":"The natural history of multiple system atrophy: A prospective European cohort study","volume":"12","author":"Wenning","year":"2013","journal-title":"Lancet Neurol"},{"issue":"6645","key":"2025091004162495200_fcaf304-B4","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"Alpha-synuclein in Lewy bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"issue":"3","key":"2025091004162495200_fcaf304-B5","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/ejn.14094","article-title":"The clinical heterogeneity of Parkinson's disease and its therapeutic implications","volume":"49","author":"Greenland","year":"2019","journal-title":"Eur J Neurosci"},{"key":"2025091004162495200_fcaf304-B6","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0079-6123(10)84017-8","article-title":"The challenge of non-motor symptoms in Parkinson's disease","volume":"184","author":"Chaudhuri","year":"2010","journal-title":"Prog Brain Res"},{"key":"2025091004162495200_fcaf304-B7","volume-title":"Parkinson\u2019s disease: Pathogenesis and clinical aspects","author":"Kouli","year":"2018"},{"issue":"5","key":"2025091004162495200_fcaf304-B8","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1002\/mds.28984","article-title":"\u03b1-Synuclein radiotracer development and in vivo imaging: Recent advancements and new perspectives","volume":"37","author":"Alzghool","year":"2022","journal-title":"Mov Disord"},{"issue":"5321","key":"2025091004162495200_fcaf304-B9","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","article-title":"Mutation in the alpha-synuclein gene identified in families with Parkinson's disease","volume":"276","author":"Polymeropoulos","year":"1997","journal-title":"Science"},{"issue":"12","key":"2025091004162495200_fcaf304-B10","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S1474-4422(19)30320-5","article-title":"Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: A meta-analysis of genome-wide association studies","volume":"18","author":"Nalls","year":"2019","journal-title":"Lancet Neurol"},{"issue":"9","key":"2025091004162495200_fcaf304-B11","doi-asserted-by":"crossref","first-page":"e7114","DOI":"10.1371\/journal.pone.0007114","article-title":"Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy","volume":"4","author":"Al-Chalabi","year":"2009","journal-title":"PLoS One"},{"issue":"5","key":"2025091004162495200_fcaf304-B12","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/ana.21685","article-title":"SNCA variants are associated with increased risk for multiple system atrophy","volume":"65","author":"Scholz","year":"2009","journal-title":"Ann Neurol"},{"issue":"2","key":"2025091004162495200_fcaf304-B13","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/S1474-4422(23)00405-2","article-title":"A biological definition of neuronal \u03b1-synuclein disease: Towards an integrated staging system for research","volume":"23","author":"Simuni","year":"2024","journal-title":"Lancet Neurol"},{"issue":"6","key":"2025091004162495200_fcaf304-B14","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1038\/s41591-023-02358-9","article-title":"Propagative \u03b1-synuclein seeds as serum biomarkers for synucleinopathies","volume":"29","author":"Okuzumi","year":"2023","journal-title":"Nat Med"},{"issue":"22","key":"2025091004162495200_fcaf304-B15","doi-asserted-by":"crossref","first-page":"8645","DOI":"10.3390\/ijms21228645","article-title":"The role of \u03b1-synuclein oligomers in Parkinson's disease","volume":"21","author":"Du","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"1","key":"2025091004162495200_fcaf304-B16","doi-asserted-by":"crossref","first-page":"5512","DOI":"10.1038\/s41467-022-33252-6","article-title":"Small soluble \u03b1-synuclein aggregates are the toxic species in Parkinson's disease","volume":"13","author":"Emin","year":"2022","journal-title":"Nat Commun"},{"issue":"10","key":"2025091004162495200_fcaf304-B17","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1093\/brain\/awaa238","article-title":"Brain-first versus body-first Parkinson's disease: A multimodal imaging case-control study","volume":"143","author":"Horsager","year":"2020","journal-title":"Brain"},{"issue":"5","key":"2025091004162495200_fcaf304-B18","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/nm1746","article-title":"Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation","volume":"14","author":"Li","year":"2008","journal-title":"Nat Med"},{"issue":"2","key":"2025091004162495200_fcaf304-B19","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson's disease","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol Aging"},{"issue":"39","key":"2025091004162495200_fcaf304-B20","doi-asserted-by":"crossref","first-page":"13454","DOI":"10.1523\/JNEUROSCI.1292-12.2012","article-title":"Antibody-aided clearance of extracellular \u03b1-synuclein prevents cell-to-cell aggregate transmission","volume":"32","author":"Bae","year":"2012","journal-title":"J Neurosci"},{"issue":"28","key":"2025091004162495200_fcaf304-B21","doi-asserted-by":"crossref","first-page":"9441","DOI":"10.1523\/JNEUROSCI.5314-13.2014","article-title":"Reducing C-terminal-truncated alpha-synuclein by immunotherapy attenuates neurodegeneration and propagation in Parkinson's disease-like models","volume":"34","author":"Games","year":"2014","journal-title":"J Neurosci"},{"issue":"4","key":"2025091004162495200_fcaf304-B22","doi-asserted-by":"crossref","first-page":"e19338","DOI":"10.1371\/journal.pone.0019338","article-title":"Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease","volume":"6","author":"Masliah","year":"2011","journal-title":"PLoS One"},{"key":"2025091004162495200_fcaf304-B23","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3389\/fnmol.2019.00299","article-title":"Targeting alpha-synuclein as a therapy for Parkinson's disease","volume":"12","author":"Fields","year":"2019","journal-title":"Front Mol Neurosci"},{"key":"2025091004162495200_fcaf304-B24","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.parkreldis.2020.01.010","article-title":"MSA: From basic mechanisms to experimental therapeutics","volume":"73","author":"Heras-Garvin","year":"2020","journal-title":"Parkinsonism Relat Disord"},{"key":"2025091004162495200_fcaf304-B25","doi-asserted-by":"crossref","first-page":"705407","DOI":"10.3389\/fneur.2021.705407","article-title":"A phase II study to evaluate the safety and efficacy of prasinezumab in early Parkinson's disease (PASADENA): Rationale, design, and baseline data","volume":"12","author":"Pagano","year":"2021","journal-title":"Front Neurol"},{"issue":"4","key":"2025091004162495200_fcaf304-B26","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/s41591-024-02886-y","article-title":"Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson's disease","volume":"30","author":"Pagano","year":"2024","journal-title":"Nat Med"},{"issue":"5","key":"2025091004162495200_fcaf304-B27","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1056\/NEJMoa2202867","article-title":"Trial of prasinezumab in early-stage Parkinson's disease","volume":"387","author":"Pagano","year":"2022","journal-title":"N Engl J Med"},{"issue":"5","key":"2025091004162495200_fcaf304-B28","doi-asserted-by":"crossref","first-page":"e209137","DOI":"10.1212\/WNL.0000000000209137","article-title":"Cinpanemab in early Parkinson disease: Evaluation of biomarker results from the phase 2 SPARK clinical trial","volume":"102","author":"Hutchison","year":"2024","journal-title":"Neurology"},{"issue":"5","key":"2025091004162495200_fcaf304-B29","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1056\/NEJMoa2203395","article-title":"Trial of cinpanemab in early Parkinson's disease","volume":"387","author":"Lang","year":"2022","journal-title":"N Engl J Med"},{"issue":"1","key":"2025091004162495200_fcaf304-B30","doi-asserted-by":"crossref","first-page":"14342","DOI":"10.1038\/s41598-023-41382-0","article-title":"Analysis of clinical failure of anti-tau and anti-synuclein antibodies in neurodegeneration using a quantitative systems pharmacology model","volume":"13","author":"Geerts","year":"2023","journal-title":"Sci Rep"},{"key":"2025091004162495200_fcaf304-B31","doi-asserted-by":"crossref","first-page":"104582","DOI":"10.1016\/j.nbd.2019.104582","article-title":"Preclinical development of a high affinity \u03b1-synuclein antibody, MEDI1341, that can enter the brain, sequester extracellular \u03b1-synuclein and attenuate \u03b1-synuclein spreading in vivo","volume":"132","author":"Schofield","year":"2019","journal-title":"Neurobiol Dis"},{"issue":"7825","key":"2025091004162495200_fcaf304-B32","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/s41586-020-2317-6","article-title":"Structures of \u03b1-synuclein filaments from multiple system atrophy","volume":"585","author":"Schweighauser","year":"2020","journal-title":"Nature"},{"issue":"8","key":"2025091004162495200_fcaf304-B33","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1002\/mds.27738","article-title":"Randomized phase I clinical trial of anti-\u03b1-synuclein antibody BIIB054","volume":"34","author":"Brys","year":"2019","journal-title":"Mov Disord"},{"issue":"10","key":"2025091004162495200_fcaf304-B34","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1001\/jamaneurol.2018.1487","article-title":"Safety and tolerability of multiple ascending doses of PRX002\/RG7935, an anti-\u03b1-synuclein monoclonal antibody, in patients with Parkinson disease: A randomized clinical trial","volume":"75","author":"Jankovic","year":"2018","journal-title":"JAMA Neurol"},{"key":"2025091004162495200_fcaf304-B35","doi-asserted-by":"crossref","first-page":"105543","DOI":"10.1016\/j.nbd.2021.105543","article-title":"ABBV-0805, a novel antibody selective for soluble aggregated \u03b1-synuclein, prolongs lifespan and prevents buildup of \u03b1-synuclein pathology in mouse models of Parkinson's disease","volume":"161","author":"Nordstr\u00f6m","year":"2021","journal-title":"Neurobiol Dis"},{"key":"2025091004162495200_fcaf304-B36"},{"key":"2025091004162495200_fcaf304-B37","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1002\/mds.29784","article-title":"Randomized phase I trial of the \u03b1-synuclein antibody lu AF82422","volume":"39","author":"Buur","year":"2024","journal-title":"Mov Disord"},{"issue":"1","key":"2025091004162495200_fcaf304-B38","doi-asserted-by":"crossref","first-page":"1994690","DOI":"10.1080\/19420862.2021.1994690","article-title":"Nonclinical safety evaluation, pharmacokinetics, and target engagement of lu AF82422, a monoclonal IgG1 antibody against alpha-synuclein in development for treatment of synucleinopathies","volume":"13","author":"Fjord-Larsen","year":"2021","journal-title":"MAbs"},{"issue":"10","key":"2025091004162495200_fcaf304-B39","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.3390\/biom11101419","article-title":"Structural and functional insights into \u03b1-synuclein fibril polymorphism","volume":"11","author":"Mehra","year":"2021","journal-title":"Biomolecules"},{"issue":"4","key":"2025091004162495200_fcaf304-B40","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1038\/s41596-022-00787-3","article-title":"Seed amplification assay for the detection of pathologic alpha-synuclein aggregates in cerebrospinal fluid","volume":"18","author":"Concha-Marambio","year":"2023","journal-title":"Nat Protoc"},{"issue":"2","key":"2025091004162495200_fcaf304-B41","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/mds.26878","article-title":"First-in-human assessment of PRX002, an anti-\u03b1-synuclein monoclonal antibody, in healthy volunteers","volume":"32","author":"Schenk","year":"2017","journal-title":"Mov Disord"},{"issue":"4","key":"2025091004162495200_fcaf304-B42","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1590\/2176-9451.19.4.027-029.ebo","article-title":"How sample size influences research outcomes","volume":"19","author":"Faber","year":"2014","journal-title":"Dental Press J Orthod"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcaf304\/64084860\/fcaf304.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/5\/fcaf304\/64084860\/fcaf304.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/5\/fcaf304\/64084860\/fcaf304.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T08:16:42Z","timestamp":1757492202000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcaf304\/8238147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":42,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcaf304","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2025]]},"article-number":"fcaf304"}}