Evidence map›Paper›PMID 39437787›Full record

ArticleCell genomics2024

Mechanism-free repurposing of drugs for C9orf72-related ALS/FTD using large-scale genomic data.

Sara Saez-Atienzar, Cleide Dos Santos Souza, Ruth Chia, Selina N Beal, Ileana Lorenzini, Ruili Huang, Jennifer Levy, Camelia Burciu, Jinhui Ding, J Raphael Gibbs and 97 more

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Article in Cell genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Genetic analysis of neurodegenerative diseases.The Journal of clinical investigation · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

107 authors.

Sara Saez-AtienzarNeuromuscular Diseases Research Section, National Institute on Aging, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Department of Neurology, Ohio State University, Columbus, OH 43210, USA. Electronic address: sara.saezatienzar@osumc.edu.
Cleide Dos Santos SouzaSheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK.
Ruth ChiaNeuromuscular Diseases Research Section, National Institute on Aging, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Selina N BealSheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK.
Ileana LorenziniDepartment of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
Ruili HuangDivision of Pre-clinical Innovation, National Center for Advancing Translational Sciences (NCATS), NIH, Rockville, MD 20850, USA.
Jennifer LevyDepartment of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
Camelia BurciuDepartment of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
Jinhui DingComputational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.
J Raphael GibbsComputational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.
Ashley JonesMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Ramita DewanNeuromuscular Diseases Research Section, National Institute on Aging, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Viviana PensatoUnit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Silvia PeverelliDepartment of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan, Italy.
Lucia CorradoDepartment of Health Sciences, University of Eastern Piedmont, Novara, Italy.
Joke J F A van VugtDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Wouter van RheenenDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Ceren TuncaNeurodegeneration Research Laboratory (NDAL), Research Center for Translational Medicine (KUTTAM), Koç University School of Medicine, Istanbul, Turkey.
Elif BayraktarNeurodegeneration Research Laboratory (NDAL), Research Center for Translational Medicine (KUTTAM), Koç University School of Medicine, Istanbul, Turkey.
Menghang XiaDivision of Pre-clinical Innovation, National Center for Advancing Translational Sciences (NCATS), NIH, Rockville, MD 20850, USA.
International ALS Genomics Consortium
ITALSGEN Consortium
SLAGEN Consortium
Project MinE ALS Sequencing Consortium
Alfredo IacoangeliMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK; Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre and Dementia Unit, South London and Maudsley NHS Foundation Trust and King's College London, London, UK.
Aleksey ShatunovMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Cinzia TilocaDepartment of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan, Italy.
Nicola TicozziDepartment of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy.
Federico VerdeDepartment of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy.
Letizia MazziniAmyotrophic Lateral Sclerosis Center, Department of Neurology "Maggiore della Carità" University Hospital, Novara, Italy.
Kevin KennaDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Ahmad Al KhleifatMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Sarah Opie-MartinMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Flavia RaggiDepartment of Neurosciences, University of Padova, Padova, Italy.
Massimiliano FilostoNeMO-Brescia Clinical Center for Neuromuscular Diseases, University of Brescia, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Stefano Cotti PiccinelliNeMO-Brescia Clinical Center for Neuromuscular Diseases, University of Brescia, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Alessandro PadovaniDepartment of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Stella GagliardiGenomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, Italy.
Maurizio InghilleriDepartment of Human Neurosciences, Rare Neuromuscular Diseases Centre, Sapienza University, 00185 Rome, Italy; IRCCS Neuromed, Pozzilli, Italy.
Alessandra FerliniUnit of Medical Genetics, Department of Medical Science, University of Ferrara, Ferrara, Italy.
Rosario Vasta"Rita Levi Montalcini" Department of Neuroscience, Amyotrophic Lateral Sclerosis Center, University of Turin, Turin, Italy.
Andrea Calvo"Rita Levi Montalcini" Department of Neuroscience, Amyotrophic Lateral Sclerosis Center, University of Turin, Turin, Italy; Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy.
Cristina Moglia"Rita Levi Montalcini" Department of Neuroscience, Amyotrophic Lateral Sclerosis Center, University of Turin, Turin, Italy; Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy.
Antonio Canosa"Rita Levi Montalcini" Department of Neuroscience, Amyotrophic Lateral Sclerosis Center, University of Turin, Turin, Italy; Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy; Institute of Cognitive Sciences and Technologies, C.N.R., Rome, Italy.
Umberto Manera"Rita Levi Montalcini" Department of Neuroscience, Amyotrophic Lateral Sclerosis Center, University of Turin, Turin, Italy; Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy.
Maurizio Grassano"Rita Levi Montalcini" Department of Neuroscience, Amyotrophic Lateral Sclerosis Center, University of Turin, Turin, Italy.
Jessica MandrioliDepartment of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; Department of Neurosciences, Azienda Ospedaliero Universitaria di Modena, Modena, Italy.
Gabriele Mora"Rita Levi Montalcini" Department of Neuroscience, Amyotrophic Lateral Sclerosis Center, University of Turin, Turin, Italy.
Christian LunettaDepartment of Neurorehabilitation, Istituti Clinici Scientifici Maugeri IRCCS, Institute of Milan, Milan, Italy; NEMO Clinical Center Milano, Fondazione Serena Onlus, Milan, Italy.
Raffaella TanelOperative Unit of Neurology, S. Chiara Hospital, Trento, Italy.
Francesca TrojsiDepartment of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli," Naples, Italy.
Patrizio CardinaliNeurology Unit, AST Fermo, Marche, Italy.
Salvatore Gallone"Rita Levi Montalcini" Department of Neuroscience, Amyotrophic Lateral Sclerosis Center, University of Turin, Turin, Italy.
Maura Brunetti"Rita Levi Montalcini" Department of Neuroscience, Amyotrophic Lateral Sclerosis Center, University of Turin, Turin, Italy.
Daniela GalimbertiNeurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy; Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Milan, Italy.
Maria SerpenteNeurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Chiara FenoglioNeurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy; Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Milan, Italy.
Elio ScarpiniNeurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Giacomo P ComiDepartment of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy; Neurology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Stefania CortiDepartment of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy; Neurology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Roberto Del BoDepartment of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy; Neurology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Mauro CeroniGenomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, Italy; Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.
Giuseppe Lauria Pinter3rd Neurology Unit, Motor Neuron Diseases Center, Fondazione IRCCS Istituto Neurologico "Carlo Besta," Milan, Italy; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Franco TaroniUnit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Eleonora Dalla Bella3rd Neurology Unit, Motor Neuron Diseases Center, Fondazione IRCCS Istituto Neurologico "Carlo Besta," Milan, Italy.
Enrica Bersano3rd Neurology Unit, Motor Neuron Diseases Center, Fondazione IRCCS Istituto Neurologico "Carlo Besta," Milan, Italy; "L. Sacco" Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milan, Italy.
Charles J CurtisSocial Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London, London, UK; NIHR BioResource Centre Maudsley, NIHR Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust (SLaM), London, UK.
Sang Hyuck LeeSocial Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London, London, UK; NIHR BioResource Centre Maudsley, NIHR Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust (SLaM), London, UK.
Raymond ChungSocial Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London, London, UK; NIHR BioResource Centre Maudsley, NIHR Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust (SLaM), London, UK.
Hamel PatelDepartment of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK; NIHR BioResource Centre Maudsley, NIHR Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust (SLaM), London, UK.
Karen E MorrisonSchool of Medicine, Dentistry, and Biomedical Sciences, Faculty of Medicine Health and Life Sciences, Queen's University, Belfast, UK.
Johnathan Cooper-KnockSheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, and the NIHR Sheffield Biomedical Research Centre, Sheffield, UK.
Pamela J ShawSheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, and the NIHR Sheffield Biomedical Research Centre, Sheffield, UK.
Gerome BreenSocial Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London, London, UK; NIHR BioResource Centre Maudsley, NIHR Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust (SLaM), London, UK.
Richard J B DobsonDepartment of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London, London SE5 8AF, UK; NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK; Health Data Research UK London, University College London, London, UK; Institute of Health Informatics, University College London, London, UK; NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust, London, UK.
Clifton L DalgardDepartment of Anatomy, Physiology, & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
American Genome Center
Sonja W ScholzNeurodegenerative Diseases Research Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, USA; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD 21287, USA.
Ammar Al-ChalabiMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK; Department of Clinical Neuroscience, King's College Hospital, London SE5 9RS, UK.
Leonard H van den BergDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Russell McLaughlinComplex Trait Genomics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
Orla HardimanAcademic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; Department of Neurology, Beaumont Hospital, Dublin, Ireland.
Cristina CeredaGenomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, Italy.
Gianni SorarùDepartment of Neurosciences, University of Padova, Padova, Italy.
Sandra D'AlfonsoDepartment of Health Sciences, University of Eastern Piedmont, Novara, Italy.
Siddharthan ChandranEuan MacDonald Centre for Motor Neurone Disease Research, Edinburgh, UK; UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK.
Suvankar PalEuan MacDonald Centre for Motor Neurone Disease Research, Edinburgh, UK; Centre for Neuroregeneration and Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.
Antonia RattiDepartment of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan, Italy; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy.
Cinzia GelleraUnit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Kory JohnsonBioinformatics Section, Information Technology Program (ITP), Division of Intramural Research (DIR), National Institute of Neurological Disorders & Stroke, NIH, Bethesda, MD 20892, USA.
Tara Doucet-O'HareNeuro-oncology Branch, Center for Cancer Research, National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA.
Nicholas PasternackTranslational Neuroscience Center, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, USA.
Tongguang WangTranslational Neuroscience Center, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, USA.
Avindra NathTranslational Neuroscience Center, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, USA.
Gabriele SicilianoDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Vincenzo SilaniDepartment of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy.
Ayşe Nazlı BaşakNeurodegeneration Research Laboratory (NDAL), Research Center for Translational Medicine (KUTTAM), Koç University School of Medicine, Istanbul, Turkey.
Jan H VeldinkDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
William CamuALS Center, CHU Gui de Chauliac, University of Montpellier, Montpellier, France.
Jonathan D GlassDepartment of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
John E LandersDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA, USA.
Adriano Chiò"Rita Levi Montalcini" Department of Neuroscience, Amyotrophic Lateral Sclerosis Center, University of Turin, Turin, Italy; Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy; Institute of Cognitive Sciences and Technologies, C.N.R., Rome, Italy.
Rita SattlerDepartment of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
Christopher E ShawUnited Kingdom Dementia Research Institute, Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK; Centre for Brain Research, University of Auckland, Auckland, New Zealand.
Laura FerraiuoloSheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK.
Isabella FoghUnited Kingdom Dementia Research Institute, Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Bryan J TraynorNeuromuscular Diseases Research Section, National Institute on Aging, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD 21287, USA; Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK; National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, USA; RNA Therapeutics Laboratory, National Center for Advancing Translational Sciences (NCATS), NIH, Rockville, MD 20850, USA. Electronic address: traynorb@mail.nih.gov.

Funding

Genome wide SNP analysis in Amyotrophic Lateral SclerosisZIAAG000933 · NIA · NATIONAL INSTITUTE ON AGING · PI TRAYNOR, BRYAN · 2009 to 2025
$9.8M
Genetic etiology of Fronto-Temporal Dementia, a dementia related to Alzheimers diseaseZIAAG000934 · NIA · NATIONAL INSTITUTE ON AGING · PI TRAYNOR, BRYAN · 2009 to 2025
$5.2M
Ataxin-2 complex proteins in neurodegeneration.R35NS127253 · NINDS · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Stefan M. PULST · 2022 to 2026
$4.6M
Intramural NIH HHS ZIA AG000933Intramural NIH HHS ZIA AG000934NINDS NIH HHS R35 NS127253
6 · The paper itself

Abstract

Repeat expansions in the C9orf72 gene are the most common genetic cause of (ALS) and frontotemporal dementia (FTD). Like other genetic forms of neurodegeneration, pinpointing the precise mechanism(s) by which this mutation leads to neuronal death remains elusive, and this lack of knowledge hampers the development of therapy for C9orf72-related disease. We used an agnostic approach based on genomic data (n = 41,273 ALS and healthy samples, and n = 1,516 C9orf72 carriers) to overcome these bottlenecks. Our drug-repurposing screen, based on gene- and expression-pattern matching and information about the genetic variants influencing onset age among C9orf72 carriers, identified acamprosate, a γ-aminobutyric acid analog, as a potentially repurposable treatment for patients carrying C9orf72 repeat expansions. We validated its neuroprotective effect in cell models and showed comparable efficacy to riluzole, the current standard of care. Our work highlights the potential value of genomics in repurposing drugs in situations where the underlying pathomechanisms are inherently complex. VIDEO ABSTRACT.

Indexed as

Amyotrophic Lateral SclerosisC9orf72 ProteinDrug RepositioningFrontotemporal DementiaDNA Repeat ExpansionFemaleGenomicsHumansMaleNeuroprotective AgentsRiluzoleC9orf72 ProteinC9orf72 protein, humanNeuroprotective AgentsRiluzoleacamprosateage at onsetamyotrophic lateral sclerosisC9orf72drug repurposingfrontotemporal dementiatranslation

Identifiers

PMID39437787
PMCPMC11605688

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