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2018 Fiscal Year Annual Research Report

Establishment of an intercontinental cohort database for ABCA4-associated retinal disorder, aiming for clinical trial of treatment

Research Project

Project/Area Number 16H06269
Research Institution独立行政法人国立病院機構(東京医療センター臨床研究センター)

Principal Investigator

藤波 芳  独立行政法人国立病院機構(東京医療センター臨床研究センター), 視覚研究部 視覚生理学研究室, 室長 (60646206)

Project Period (FY) 2016-04-01 – 2019-03-31
Keywords眼遺伝学
Outline of Annual Research Achievements

本研究の目的は、東京医療センター(NISO)、英国UCL、米国NIH、STGD国際共同プロジェクト(ProgSTAR)の連携の下、3大陸を跨いだABCA4関連網膜症国際コホート・共有データベースの作成である。本研究は1)臨床診断・患者リクルート、2)遺伝子検索、3)国際データベース・コホート作成、4)変異インパクトスコア算出、5)遺伝子型・表現型関連解析、(6)コホート間変異頻度比較、(7)治療法考案、の七段階で遂行された。

平成31年度までに、NISOでは155症例、英国UCLからは190症例、米国NEI/NIH、ProgStar studiesからは193症例が登録され、計518症例がデータベースに登録された。網羅的遺伝子検索により同定された高頻度ABCA4変異は、本邦ではc.1760+2T>G(変異頻度:16.7%)、p.Arg2149Ter(6.0%)、英国では、p.Gly1961Glu (10.4%)、c.5461-10T>C(6.8%)、米国では、p.Gly1961Glu(13.6%)、p.Gly863Ala (7.0%)であった。253のミスセンス変異に対して、インパクトスコアが算出された。91変異はnative conformationの消失(36.0%)が予測されたのに対して、68変異(26.9%)はstabilizing effectが示唆された。ヌル変異の有無による遺伝子型分類、変異インパクトスコアは、発症年齢、電気生理学的表現型分類と関連・相関を示した。コホート間の変異頻度比較では、各コホート間における優位な頻度差異を認めた。治療考案は、薬物治療、遺伝子治療、再生細胞移植等について行われ、視サイクル制御薬を用いた治療治験をはじめ、複数の治療治験がデータベースの情報をもとに遂行されるに至った。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

  • Research Products

    (54 results)

All 2019 2018 Other

All Int'l Joint Research (5 results) Journal Article (20 results) (of which Int'l Joint Research: 12 results,  Peer Reviewed: 17 results,  Open Access: 7 results) Presentation (26 results) (of which Int'l Joint Research: 26 results,  Invited: 8 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] UCL Institute of Ophthalmology/Moorfields Eye Hospital/Manchester Royal Eye Hospital(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      UCL Institute of Ophthalmology/Moorfields Eye Hospital/Manchester Royal Eye Hospital
    • # of Other Institutions
      3
  • [Int'l Joint Research] National Eye Institute/Columbia University/Johns Hopkins University(英国)

    • Country Name
      UNITED KINGDOM
    • Counterpart Institution
      National Eye Institute/Columbia University/Johns Hopkins University
    • # of Other Institutions
      5
  • [Int'l Joint Research] Universite de Paris 06(フランス)

    • Country Name
      FRANCE
    • Counterpart Institution
      Universite de Paris 06
  • [Int'l Joint Research] Eberhard-Karls University Hospital(ドイツ)

    • Country Name
      GERMANY
    • Counterpart Institution
      Eberhard-Karls University Hospital
  • [Int'l Joint Research] Peiking union medical college hospital/Third Military Medical University/Henan Eye Hospital(中国)

    • Country Name
      CHINA
    • Counterpart Institution
      Peiking union medical college hospital/Third Military Medical University/Henan Eye Hospital
    • # of Other Institutions
      1
  • [Journal Article] Clinical findings of end-stage retinitis pigmentosa with a homozygous PDE6A variant (p.R653X)2019

    • Author(s)
      Mizobuchi Kei、Katagiri Satoshi、Hayashi Takaaki、Yoshitake Kazutoshi、Fujinami Kaoru、Kuniyoshi Kazuki、Mishima Reimi、Tsunoda Kazushige、Iwata Takeshi、Nakano Tadashi
    • Journal Title

      American Journal of Ophthalmology Case Reports

      Volume: 13 Pages: 110~115

    • DOI

      https://doi.org/10.1016/j.ajoc.2018.12.019

    • Peer Reviewed
  • [Journal Article] High-Resolution Retinal Imaging Reveals Preserved Cone Photoreceptor Density and Choroidal Thickness in Female Carriers of Choroideremia2019

    • Author(s)
      Suzuki Kai、Gocho Kiyoko、Akeo Keiichiro、Kikuchi Sachiko、Kubota Daiki、Katagiri Satoshi、Fujinami Kaoru、Tsunoda Kazushige、Iwata Takeshi、Yamaki Kunihiko、Igarashi Tsutomu、Nakano Tadashi、Takahashi Hiroshi、Hayashi Takaaki、Kameya Shuhei
    • Journal Title

      Ophthalmic Surgery, Lasers and Imaging Retina

      Volume: 50 Pages: 76~85

    • DOI

      https://doi.org/10.3928/23258160-20190129-03

    • Peer Reviewed
  • [Journal Article] Cross-Sectional and Longitudinal Assessment of the Ellipsoid Zone in Childhood-Onset Stargardt Disease2019

    • Author(s)
      Tanna Preena、Georgiou Michalis、Strauss Rupert W.、Ali Naser、Kumaran Neruban、Kalitzeos Angelos、Fujinami Kaoru、Michaelides Michel
    • Journal Title

      Translational Vision Science & Technology

      Volume: 8 Pages: 1~1

    • DOI

      https://doi.org/10.1167/tvst.8.2.1

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Three cases of acute-onset bilateral photophobia2019

    • Author(s)
      Ueno Shinji、Inooka Daiki、Meinert Monika、Ito Yasuki、Tsunoda Kazushige、Fujinami Kaoru、Iwata Takeshi、Ohde Hisao、Terasaki Hiroko
    • Journal Title

      Japanese Journal of Ophthalmology

      Volume: 63 Pages: 172~180

    • DOI

      https://doi.org/10.1007/s10384-018-00649-0

    • Peer Reviewed
  • [Journal Article] Novel mutations in the RS1 gene in Japanese patients with X-linked congenital retinoschisis2019

    • Author(s)
      Kondo Hiroyuki、Oku Kazuma、Katagiri Satoshi、et al.
    • Journal Title

      Human Genome Variation

      Volume: 6 Pages: -

    • DOI

      https://doi.org/10.1038/s41439-018-0034-6

    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of Causative Genes in Inherited Retinal Disorders from Spectral-Domain Optical Coherence Tomography Utilizing Deep Learning Techniques2019

    • Author(s)
      Fujinami-Yokokawa Yu、Pontikos Nikolas、Yang Lizhu、Tsunoda Kazushige、Yoshitake Kazutoshi、Iwata Takeshi、Miyata Hiroaki、Fujinami Kaoru、Japan Eye Genetics Consortium on behalf of
    • Journal Title

      Journal of Ophthalmology

      Volume: 2019 Pages: 1~7

    • DOI

      https://doi.org/10.1155/2019/1691064

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Missense variants in the X-linked gene PRPS1 cause retinal degeneration in females2018

    • Author(s)
      Fiorentino Alessia、Fujinami Kaoru、Arno Gavin, et al.
    • Journal Title

      Human Mutation

      Volume: 39 Pages: 80~91

    • DOI

      https://doi.org/10.1002/humu.23349

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Case of cone dystrophy with normal fundus appearance associated with biallelic POC1B variants2018

    • Author(s)
      Kominami Azusa、Ueno Shinji、Kominami Taro、Nakanishi Ayami、Ito Yasuki、Fujinami Kaoru、Tsunoda Kazushige、Hayashi Takaaki、Kikuchi Sachiko、Kameya Shuhei、Iwata Takeshi、Terasaki Hiroko
    • Journal Title

      Ophthalmic Genetics

      Volume: 39 Pages: 255~262

    • DOI

      https://doi.org/10.1080/13816810.2017.1408846

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Early Patterns of Macular Degeneration in ABCA4 -Associated Retinopathy2018

    • Author(s)
      Khan Kamron N.、Kasilian Melissa、Mahroo Omar A.R.、Tanna Preena、Kalitzeos Angelos、Robson Anthony G.、Tsunoda Kazushige、Iwata Takeshi、Moore Anthony T.、Fujinami Kaoru、Michaelides Michel
    • Journal Title

      Ophthalmology

      Volume: 125 Pages: 735~746

    • DOI

      https://doi.org/10.1016/j.ophtha.2017.11.020

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Visual Acuity Change Over 24 Months and Its Association With Foveal Phenotype and Genotype in Individuals With Stargardt Disease2018

    • Author(s)
      Kong Xiangrong、Fujinami Kaoru、Strauss Rupert W.、Munoz Beatriz、West Sheila K.、Cideciyan Artur V.、Michaelides Michel、Ahmed Mohamed、Ervin Ann-Margret、Sch?nbach Etienne、Cheetham Janet K.、Scholl Hendrik P. N.、for the ProgStar Study Group
    • Journal Title

      JAMA Ophthalmology

      Volume: 136 Pages: 920~920

    • DOI

      https://doi.org/10.1001/jamaophthalmol.2018.2198

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A Cross-Sectional and Longitudinal Study of Retinal Sensitivity in RPE65-Associated Leber Congenital Amaurosis2018

    • Author(s)
      Kumaran Neruban、Rubin Gary S.、Kalitzeos Angelos、Fujinami Kaoru、Bainbridge James W. B.、Weleber Richard G.、Michaelides Michel
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 59 Pages: 3330~3330

    • DOI

      https://doi.org/10.1167/iovs.18-23873

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 黄斑ジストロフィの分子病態2018

    • Author(s)
      藤波 芳、藤波(横川)優、Lizhu Yang、Xiao Liu、Gavin Arno
    • Journal Title

      眼科

      Volume: 60(4) Pages: 309-321

    • Int'l Joint Research
  • [Journal Article] 第65回日本臨床視覚電気生理学会.POC1B関連網膜症における表現型スペクトラム:眼底正常な錐体ジストロフィ2018

    • Author(s)
      藤波 芳
    • Journal Title

      日本眼科学会雑誌

      Volume: 122(3) Pages: 251

  • [Journal Article] Clinical and Genetic Characteristics of East Asian Patients with Occult Macular Dystrophy:East Asia Inherited Retinal Disease Consortium (EAIRDc).2018

    • Author(s)
      藤波 芳
    • Journal Title

      日本眼科学会雑誌

      Volume: 122(4) Pages: 330-331

    • Int'l Joint Research
  • [Journal Article] ISCEV extended protocol for the dark-adapted red flash ERG2018

    • Author(s)
      Thompson Dorothy A.、Fujinami Kaoru、Perlman Ido、Hamilton Ruth、Robson Anthony G.
    • Journal Title

      Documenta Ophthalmologica

      Volume: 136 Pages: 191~197

    • DOI

      https://doi.org/10.1007/s10633-018-9644-z

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Retinal findings in a patient with mutations in ABCC6 and ABCA42018

    • Author(s)
      Mahroo Omar A.、Fujinami Kaoru、Moore Anthony T.、Webster Andrew R.
    • Journal Title

      Eye

      Volume: 32 Pages: 1542~1543

    • DOI

      https://doi.org/10.1038/s41433-018-0106-3

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinical Features of Japanese Patients With Anti-α-enolase Antibody?Positive Autoimmune Retinopathy: Novel Subtype of Multiple Drusen2018

    • Author(s)
      Ando Ryo、Saito Wataru、Kanda Atsuhiro、Kase Satoru、Fujinami Kaoru、Sugahara Michitaka、Nakamura Yosuke、Eguchi Shuichiro、Mori Shohei、Noda Kousuke、Shinoda Kei、Ishida Susumu
    • Journal Title

      American Journal of Ophthalmology

      Volume: 196 Pages: 181~196

    • DOI

      https://doi.org/10.1016/j.ajo.2018.08.044

    • Peer Reviewed
  • [Journal Article] Macular dysfunction in patients with macula-on rhegmatogenous retinal detachments2018

    • Author(s)
      Akiyama Kunihiko、Fujinami Kaoru、Watanabe Ken、Noda Toru、Miyake Yozo、Tsunoda Kazushige
    • Journal Title

      British Journal of Ophthalmology

      Volume: 103 Pages: 404~409

    • DOI

      https://doi.org/10.1136/bjophthalmol-2018-312153

    • Peer Reviewed
  • [Journal Article] Detailed genetic characteristics of an international large cohort of patients with Stargardt disease: ProgStar study report 82018

    • Author(s)
      Fujinami Kaoru、Strauss Rupert W、Chiang John (Pei-Wen)、et al.
    • Journal Title

      British Journal of Ophthalmology

      Volume: 103 Pages: 390~397

    • DOI

      https://doi.org/10.1136/bjophthalmol-2018-312064

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] VALIDITY AND EFFICACY OF INTERNAL LIMITING MEMBRANE PEELING DURING INITIAL VITRECTOMY FOR RHEGMATOGENOUS RETINAL DETACHMENT2018

    • Author(s)
      Akiyama Kunihiko、Fujinami Kaoru、Watanabe Ken、Fukui Masaki、Tsunoda Kazushige、Noda Toru
    • Journal Title

      Retinal Cases & Brief Reports

      Volume: - Pages: 1~1

    • DOI

      https://doi.org/10.1097/ICB.0000000000000758

    • Peer Reviewed
  • [Presentation] clinical and Genetic Characteristics of East Asian Patients with Occult Macular Dystrophy (Miyake’s disease); EAOMD Report No.1.2018

    • Author(s)
      Fujinami K, Yang L, Joo K, Tsunoda K, Kawamura Y, Fujinami (Yokokawa) Y, Arno G, Kurihara T, Tsubota K, Zou X, Li H, Park KH, Iwata T, Miyake Y, Woo SJ, Sui R
    • Organizer
      The Association for Research in Vision and Ophthalmology (ARVO) 2018 Conference.
    • Int'l Joint Research
  • [Presentation] Multimodal Imaging of East Asian Patients with Occult Macular Dystrophy (Miyake’s disease) EAOMD Report No. 3.2018

    • Author(s)
      Joo K, Yang L, Tsunoda K, Kondo M, Fujinami (Yokokawa) Y, Arno G, Kurihara T, Tsubota K, Iwata T, Zou X, Li H, Miyake Y, Park KH, Fujinami K, Sui R, Woo SJ.
    • Organizer
      The Association for Research in Vision and Ophthalmology (ARVO) 2018 Conference.
    • Int'l Joint Research
  • [Presentation] Genotype Phenotype Association in East Asian Patients with Occult Macular Dystrophy (Miyake’s disease); EAOMD Report No.4.2018

    • Author(s)
      Fujinami (Yokokawa) Y, Yang L, Joo K, Tsunoda K, Kondo M, Arno G, Liu X, Tsubota K, Iwata T, Zou X, Li H, Park KH, Miyake Y, Woo SJ, Sui R, Fujinami K.
    • Organizer
      The Association for Research in Vision and Ophthalmology (ARVO) 2018 Conference.
    • Int'l Joint Research
  • [Presentation] Clinical and Genetic Characteristics of East Asian Patients with Stargardt disease; EAStar Report No.1.2018

    • Author(s)
      Fujinami K, Liu X, Joo K, Tsunoda K, Hayashi T, Shinoda K, Mizota A, Kondo M, Kuniyoshi K, Fujinami (Yokokawa) Y, Yang L, Arno G, Kurihara T, Tsubota K, Miyake Y, Li Y, Park KH, Ma DJ, Yu HG, Lei B, Iwata T, Woo SJ, Li S.
    • Organizer
      The 56th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV)
    • Int'l Joint Research
  • [Presentation] Distribution of generalized functional phenotype of East Asian Patients with Stargardt Disease (STGD1): EAStar studies report 2.2018

    • Author(s)
      Liu X, Yang L, Joo K, Tsunoda K, Hayashi T, Shinoda K, Mizota A, Kondo M, Kuniyoshi K, Fujinami (Yokokawa) Y, Arno G, Kurihara T, Tsubota K, Miyake Y, Li Y, Park KH, Ma DJ, Yu HG, Lei B, Iwata T, Woo SJ, Li S, Fujinami K.
    • Organizer
      The 56th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV)
    • Int'l Joint Research
  • [Presentation] Full-field Electroretinograms Features of East Asian Patients with Occult Macular Dystrophy (Miyake’s disease); EAOMD Report No.2.1.2018

    • Author(s)
      Yang L, Joo K, Tsunoda K, Mineo K, Fujinami (Yokokawa) Y, Arno G, Kurihara T, Tsubota K, Iwata T, Zou X, Li H, Park KH, Miyake Y, Woo SJ, Sui R, Fujinami K.
    • Organizer
      The 56th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV)
    • Int'l Joint Research
  • [Presentation] Genotype Phenotype Association in East Asian Patients with Occult Macular Dystrophy (Miyake’s disease); EAOMD Report No.4.2018

    • Author(s)
      Fujinami (Yokokawa) Y, Yang L, Joo K, Tsunoda K, Kondo M, Arno G, Liu X, Kuriahra T, Tsubota K, Zou X, Li H, Park KH, Miyake Y, Iwata T, Woo SJ, Sui R, Fujinami K.
    • Organizer
      The 56th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV)
    • Int'l Joint Research
  • [Presentation] Influence of internal limiting membrane peeling on macular function in patients treated for macula-on rhegmatogenous retinal detachment2018

    • Author(s)
      Akiyama K, Fujinami K, Watanabe K, Noda T, Miyake Y, Tsunoda K.
    • Organizer
      The 56th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV)
    • Int'l Joint Research
  • [Presentation] Integrity of Outer Retinal Layers after Internal Limiting Membrane Peeling during Vitrectomy for Macula-on Retinal Detachment2018

    • Author(s)
      Akiyama K, Watanabe K, Fujinami K, Tsunoda K, Noda T.
    • Organizer
      EURETINA Congress
    • Int'l Joint Research
  • [Presentation] East Asia Inherited Retinal Disease Consortium.2018

    • Author(s)
      Fujinami K.
    • Organizer
      Ophthalmic genetics seminar 2018
    • Int'l Joint Research / Invited
  • [Presentation] Nationwide and international collaborative studies of inherited retinal disease: an approach from diagnosis to treatment.2018

    • Author(s)
      Fujinami K.
    • Organizer
      National teaching course 2018
    • Int'l Joint Research / Invited
  • [Presentation] Stargardt disease.2018

    • Author(s)
      Fujinami K.
    • Organizer
      36th World Ophthalmology Congress 2018
    • Int'l Joint Research / Invited
  • [Presentation] Nationwide and international collaborative studies in Inherited retinal disorder.2018

    • Author(s)
      Fujinami K.
    • Organizer
      France-Japan Collaborative Genomic Research Meeting 2018
    • Int'l Joint Research / Invited
  • [Presentation] Autosomal Dominant Occult Macular Dystrophy (Miyake's disease): nationwide and international collaborative studies.2018

    • Author(s)
      Fujinami K.
    • Organizer
      Germany-Japan Collaborative Research Congress 2018
    • Int'l Joint Research / Invited
  • [Presentation] Nationwide and International studies of Inherited Retinal Disorders: Japan Eye Genetics Consortium and East Asia Inherited Retinal Disease.2018

    • Author(s)
      Fujinami K.
    • Organizer
      The 120th Annual Meeting of the Korean Ophthalmology Society
    • Int'l Joint Research / Invited
  • [Presentation] Laboratory of Visual Physiology, National Institute of Sensory Organs: history and science.2018

    • Author(s)
      Fujinami K.
    • Organizer
      1st East Asia Inherited Retinal Disease Society Seminar and Courses
    • Int'l Joint Research / Invited
  • [Presentation] Paediatric Stargardt Disease2018

    • Author(s)
      Fujinami K.
    • Organizer
      1st East Asia Inherited Retinal Disease Society Seminar and Courses
    • Int'l Joint Research / Invited
  • [Presentation] 中心窩剥離のない網膜剥離に対する内境界膜剥離が中心窩網膜の層構造に与える影響2018

    • Author(s)
      秋山邦彦、渡辺健、福井正樹、藤波芳、角田和繁、野田徹
    • Organizer
      第72回日本臨床眼科学会
    • Int'l Joint Research
  • [Presentation] 遺伝性網膜疾患におけるABCA4遺伝子多型の集団遺伝学的解析2018

    • Author(s)
      中伊津美、藤波優、Gavin Arno、Nikolas Pontikos、Michel Michaelides、Andrew R. Webster、藤波芳、大橋順
    • Organizer
      第72回日本人類学会大会
    • Int'l Joint Research
  • [Presentation] 抗α-enolase抗体陽性自己免疫性網膜症の網膜電図所見2018

    • Author(s)
      安藤亮、齋藤航、神田敦宏、加瀬諭、藤波芳、菅原道孝、中村洋介、江口秀一郎、野田航介、篠田啓、石田晋
    • Organizer
      第75回日本臨床視覚電気生理学会
    • Int'l Joint Research
  • [Presentation] DRAM2関連網膜症の臨床像とその長期経過2018

    • Author(s)
      國吉一樹,亀谷修平,林孝彰,櫻本宏之,久保田大紀,片桐 聡,藤波 芳,角田和繁,岩田岳,日下俊次
    • Organizer
      第75回日本臨床視覚電気生理学会
    • Int'l Joint Research
  • [Presentation] 黄斑変性を伴った脊髄小脳変性症(SCA1)の一例2018

    • Author(s)
      廣瀬文音、藤波芳、野田徹、片桐聡、林孝彰、松浦知和、永井紀博、岩田岳、角田和繁
    • Organizer
      第75回日本臨床視覚電気生理学会
    • Int'l Joint Research
  • [Presentation] Inherited retinal disease: an approach from diagnosis to treatment.2018

    • Author(s)
      藤波芳
    • Organizer
      2017年度 大学共同利用機関法人 情報・システム研究機構 国立遺伝学研究所 研究会
    • Int'l Joint Research
  • [Presentation] 遺伝性網膜疾患の診断から治療へのアプローチ2018

    • Author(s)
      藤波芳
    • Organizer
      大阪府網膜色素変性症協会 第15回定期総会医療講演会
    • Int'l Joint Research
  • [Presentation] 遺伝性網膜疾患:診断から治療への考え方2018

    • Author(s)
      藤波芳
    • Organizer
      東京都網膜色素変性症協会医療講演会
    • Int'l Joint Research
  • [Presentation] ABCA4遺伝子関連疾患2018

    • Author(s)
      藤波芳
    • Organizer
      第72回日本臨床眼科学会
    • Int'l Joint Research
  • [Book] 診療で役立つ! 近視進行予防のサイエンス2019

    • Author(s)
      坪田 一男
    • Total Pages
      192
    • Publisher
      金原出版
    • ISBN
      9784307351713
  • [Remarks] USA UK Japan Trilateral Collaborative Research

    • URL

      http://www.fujinamik.com/progect

  • [Remarks] NISO Global Stargardt Disease Database

    • URL

      https://niso.kankakuki.go.jp/stgkarte/

URL: 

Published: 2019-12-27  

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