2,901 results match your criteria Friedreich Ataxia


Hereditary spastic paraplegia type 11 (SPG11) is associated with obesity and hypothalamic damage.

J Neurol Sci 2020 Jun 20;416:116982. Epub 2020 Jun 20.

Department of Neurology, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126. Cidade Universitária "Zeferino Vaz"; Campinas, SP 13083-887, Brazil. Electronic address:

SPG11 mutations lead to heterogeneous neurological phenotypes, but metabolic abnormalities have not yet been explored in this disease. In this study, we investigate whether SPG11 pathogenic variants might affect metabolic regulation, leading to weight changes and if this could relate to hypothalamic damage. In this cross-sectional case-control study, we selected a group of individuals with confirmed SPG11 mutations (n = 20), paired with healthy controls - both groups underwent brain MRI, from which we performed manual hypothalamic segmentation - and patients with Friedreich Ataxia (FRDA), having collected weight and height data for BMI-comparison. Read More

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http://dx.doi.org/10.1016/j.jns.2020.116982DOI Listing

Feasibility and Acceptability of Lee Silverman Voice Treatment in Progressive Ataxias.

Cerebellum 2020 Jun 25. Epub 2020 Jun 25.

Sheffield Teaching Hospitals NHS Trust, University of Sheffield, Sheffield, S10 2TG, UK.

Communication difficulties have considerable impact on people with progressive ataxia, yet there are currently no evidence-based treatments. LSVT LOUD® focuses on the production of healthy vocal loudness whilst also improving breath support, vocal quality, loudness and articulation in participating patients. This study aimed to investigate whether Lee Silverman Voice Treatment (LSVT LOUD®) can improve communication effectiveness in these patients. Read More

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http://dx.doi.org/10.1007/s12311-020-01153-3DOI Listing

Mitochondrial damage and senescence phenotype of cells derived from a novel frataxin G127V point mutation mouse model of Friedreich's ataxia.

Dis Model Mech 2020 Jun 25. Epub 2020 Jun 25.

Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL 35294, USA

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by reduced expression of the mitochondrial protein frataxin (FXN). Most FRDA patients are homozygous for large expansions of GAA repeat sequences in intron 1 of , while a fraction of patients are compound heterozygotes with a missense or nonsense mutation in one allele and expanded GAAs in the other. A prevalent missense mutation among FRDA patients changes a glycine at position 130 to valine (G130V). Read More

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http://dx.doi.org/10.1242/dmm.045229DOI Listing

HMTase Inhibitors as a Potential Epigenetic-Based Therapeutic Approach for Friedreich's Ataxia.

Front Genet 2020 5;11:584. Epub 2020 Jun 5.

Ataxia Research Group, Division of Biosciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United Kingdom.

Friedreich's ataxia (FRDA) is a progressive neurodegenerative disorder caused by a homozygous GAA repeat expansion mutation in intron 1 of the frataxin gene (), which instigates reduced transcription. As a consequence, reduced levels of frataxin protein lead to mitochondrial iron accumulation, oxidative stress, and ultimately cell death; particularly in dorsal root ganglia (DRG) sensory neurons and the dentate nucleus of the cerebellum. In addition to neurological disability, FRDA is associated with cardiomyopathy, diabetes mellitus, and skeletal deformities. Read More

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http://dx.doi.org/10.3389/fgene.2020.00584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291394PMC

MR imaging and spectroscopy in degenerative ataxias: toward multimodal, multisite, multistage monitoring of neurodegeneration.

Curr Opin Neurol 2020 Jun 8. Epub 2020 Jun 8.

Department of Neurology.

Purpose Of Review: Degenerative ataxias are rare and currently untreatable movement disorders, primarily characterized by neurodegeneration in the cerebellum and brainstem. We highlight MRI studies with the most potential for utility in pending ataxia trials and underscore advances in disease characterization and diagnostics in the field.

Recent Findings: With availability of advanced MRI acquisition methods and specialized software dedicated to the analysis of MRI of the cerebellum, patterns of cerebellar atrophy in different degenerative ataxias are increasingly well defined. Read More

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http://dx.doi.org/10.1097/WCO.0000000000000834DOI Listing

Vestibular impact of Friedreich ataxia in early onset patients.

Cerebellum Ataxias 2020 28;7. Epub 2020 May 28.

Center for Balance Evaluation in Children (EFEE), Otolaryngology Department, Assistance Publique des Hôpitaux de Paris, Universitary Robert-Debré Hospital, F-75019 Paris, France.

Background: Friedreich ataxia (FRDA) is the most frequent form of inherited ataxias. Vestibular and auditory assessments are not commonly part of the check up for these patients despite hearing and balance complaints. Screening of vestibular and auditory function was performed in a large group of young patients with genetically confirmed FRDA. Read More

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http://dx.doi.org/10.1186/s40673-020-00115-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254732PMC

Cerebellar cognitive disorder parallels cerebellar motor symptoms in Friedreich ataxia.

Ann Clin Transl Neurol 2020 Jun 8;7(6):1050-1054. Epub 2020 Jun 8.

Department of Neurology, CUB Hôpital Erasme, Université libre de Bruxelles (ULB), Brussels, Belgium.

Dentate nuclei (DN) are involved in cerebellar modulation of motor and cognitive functions, whose impairment causes ataxia and cerebellar cognitive affective syndrome (CCAS). Friedreich ataxia (FRDA) disease progression relates to degeneration of the dentate nucleus and dentato-thalamic pathways, causing cerebellar ataxia. Volumetric MRI also shows mild loss in the cerebellar cortex, brainstem, and motor cortex. Read More

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http://dx.doi.org/10.1002/acn3.51079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317641PMC

Significance of NT-proBNP and High-sensitivity Troponin in Friedreich Ataxia.

J Clin Med 2020 May 28;9(6). Epub 2020 May 28.

Cardiology Department, AP-HP, Sorbonne Université, Pitié-Salpêtrière University Hospital, 75013 Paris, France.

Background: Friedreich's ataxia (FA) is a rare autosomal recessive mitochondrial disease resulting of a triplet repeat expansion guanine-adenine-adenine (GAA) in the frataxin (FXN) gene, exhibiting progressive cerebellar ataxia, diabetes and cardiomyopathy. We aimed to determine the relationship between cardiac biomarkers, serum N-terminal pro-brain natriuretic peptide (NT-proBNP), and serum cardiac high-sensitivity troponin (hsTnT) concentrations, and the extent of genetic abnormality and cardiac parameters.

Methods: Between 2013 and 2015, 85 consecutive genetically confirmed FA adult patients were prospectively evaluated by measuring plasma hsTnT and NT-proBNP concentrations, electrocardiogram, and echocardiography. Read More

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http://dx.doi.org/10.3390/jcm9061630DOI Listing

CRISPR-Cas9 Gene Editing of Hematopoietic Stem Cells from Patients with Friedreich's Ataxia.

Mol Ther Methods Clin Dev 2020 Jun 3;17:1026-1036. Epub 2020 May 3.

Division of Genetics, Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by expansion of GAA repeats in intron 1 of the frataxin () gene, leading to significant decreased expression of frataxin, a mitochondrial iron-binding protein. We previously reported that syngeneic hematopoietic stem and progenitor cell (HSPC) transplantation prevented neurodegeneration in the FRDA mouse model YG8R. We showed that the mechanism of rescue was mediated by the transfer of the functional frataxin from HSPC-derived microglia/macrophage cells to neurons/myocytes. Read More

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http://dx.doi.org/10.1016/j.omtm.2020.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240056PMC

Analysis of Putative Epigenetic Regulatory Elements in the Genomic Locus.

Int J Mol Sci 2020 May 12;21(10). Epub 2020 May 12.

Departamento Biología Molecular and Centro de Biología Molecular "Severo Ochoa" (UAM-CSIC), Universidad Autónoma de Madrid, 28049 Madrid, Spain.

Friedreich´s ataxia (FRDA) is an autosomal recessive disease caused by an abnormally expanded Guanine-Adenine-Adenine (GAA) repeat sequence within the first intron of the frataxin gene ). The molecular mechanisms associated with FRDA are still poorly understood and most studies on gene regulation have been focused on the region around the minimal promoter and the region in which triplet expansion occurs. Nevertheless, since there could be more epigenetic changes involved in the reduced levels of transcripts, the aim of this study was to obtain a more detailed view of the possible regulatory elements by analyzing data from ENCODE and Roadmap consortia databases. Read More

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http://dx.doi.org/10.3390/ijms21103410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279236PMC

Neurofilament light chain as a potential biomarker of disease status in Friedreich ataxia.

J Neurol 2020 May 8. Epub 2020 May 8.

Department of Pediatrics and Neurology, The Children's Hospital of Philadelphia; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Background: The present study evaluates serum neurofilament light chain (NfL) as a biomarker of disease features in Friedreich's ataxia (FRDA).

Methods: NfL levels from serum of 117 subjects (85 FRDA patients, 13 carriers, and 19 controls) were assayed and correlated with disease features such as smaller GAA repeat length (GAA1), age, sex, and level of neurological dysfunction.

Results: Mean serum NfL levels were higher in FRDA patients than in carriers or unaffected controls in two independent cohorts of subjects. Read More

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http://dx.doi.org/10.1007/s00415-020-09868-3DOI Listing

Primary proprioceptive neurons from human induced pluripotent stem cells: a cell model for afferent ataxias.

Sci Rep 2020 May 8;10(1):7752. Epub 2020 May 8.

Laboratory of Experimental Neurology, Université Libre de Bruxelles (ULB), 1070, Brussels, Belgium.

Human induced pluripotent stem cells (iPSCs) are used to generate models of human diseases that recapitulate the pathogenic process as it occurs in affected cells. Many differentiated cell types can currently be obtained from iPSCs, but no validated protocol is yet available to specifically generate primary proprioceptive neurons. Proprioceptors are affected in a number of genetic and acquired diseases, including Friedreich ataxia (FRDA). Read More

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http://dx.doi.org/10.1038/s41598-020-64831-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210273PMC

ExpansionHunter Denovo: a computational method for locating known and novel repeat expansions in short-read sequencing data.

Genome Biol 2020 Apr 28;21(1):102. Epub 2020 Apr 28.

Illumina Inc., 5200 Illumina Way, San Diego, CA, 92122, USA.

Repeat expansions are responsible for over 40 monogenic disorders, and undoubtedly more pathogenic repeat expansions remain to be discovered. Existing methods for detecting repeat expansions in short-read sequencing data require predefined repeat catalogs. Recent discoveries emphasize the need for methods that do not require pre-specified candidate repeats. Read More

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http://dx.doi.org/10.1186/s13059-020-02017-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187524PMC

Neurologic outcomes in Friedreich ataxia: Study of a single-site cohort.

Authors:
Massimo Pandolfo

Neurol Genet 2020 Jun 20;6(3):e415. Epub 2020 Mar 20.

Service of Neurology, Hôpital Erasme, and Laboratory of Experimental Neurology, Université Libre de Bruxelles (ULB), Brussels, Belgium.

Objective: To investigate the pattern of progression of neurologic impairment in Friedreich ataxia (FRDA) and identify patients with fast disease progression as detected by clinical rating scales.

Methods: Clinical, demographic, and genetic data were analyzed from 54 patients with FRDA included at the Brussels site of the European Friedreich's Ataxia Consortium for Translational Studies, with an average prospective follow-up of 4 years.

Results: Afferent ataxia predated other features of FRDA, followed by cerebellar ataxia and pyramidal weakness. Read More

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http://dx.doi.org/10.1212/NXG.0000000000000415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164967PMC

An Overview of the Current State and the Future of Ataxia Treatments.

Neurol Clin 2020 05 27;38(2):449-467. Epub 2020 Feb 27.

Division of Movement Disorders, Department of Neurology, Columbia University Medical Center, 650 West 168th Street, Room 305, New York, NY 10032, USA. Electronic address:

Cerebellar ataxia can be caused by a variety of disorders, including degenerative processes, autoimmune and paraneoplastic illness as well as by gene mutations inherited in autosomal dominant, autosomal recessive, or X-linked fashions. In this review, we highlight the treatments for cerebellar ataxia in a systematic way, to provide guidance for clinicians who treat patients with cerebellar ataxia. In addition, we review therapies currently under development for ataxia, which we feel is currently one of the most exciting fields in neurology. Read More

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http://dx.doi.org/10.1016/j.ncl.2020.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220524PMC

Frataxin-deficient cardiomyocytes present an altered thiol-redox state which targets actin and pyruvate dehydrogenase.

Redox Biol 2020 05 5;32:101520. Epub 2020 Apr 5.

Dept. Ciències Mèdiques Bàsiques, Fac. Medicina, IRBLLeida, Universitat de Lleida, Lleida, Spain. Electronic address:

Friedreich ataxia (FA) is a cardioneurodegenerative disease caused by deficient frataxin expression. This mitochondrial protein has been related to iron homeostasis, energy metabolism, and oxidative stress. Previously, we set up a cardiac cellular model of FA based on neonatal rat cardiac myocytes (NRVM) and lentivirus-mediated frataxin RNA interference. Read More

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http://dx.doi.org/10.1016/j.redox.2020.101520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152683PMC

Late-onset autosomal recessive cerebellar ataxia and neuropathy with a novel splicing mutation in the gene.

J Integr Neurosci 2020 Mar;19(1):125-129

Division of Neurology, Department of Internal Medicine, Jichi Medical University School of Medicine, Tochigi, 329-0498, Japan.

Autosomal recessive cerebellar ataxias comprise many types of diseases. The most frequent autosomal recessive cerebellar ataxias are Friedreich ataxia, but other types are relatively rare. We encountered a consanguineous family with two cases of late-onset cerebellar ataxia with neuropathy. Read More

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http://dx.doi.org/10.31083/j.jin.2020.01.1239DOI Listing

Calpain-Inhibitors Protect Frataxin-Deficient Dorsal Root Ganglia Neurons from Loss of Mitochondrial Na/Ca Exchanger, NCLX, and Apoptosis.

Neurochem Res 2020 Apr 6. Epub 2020 Apr 6.

Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, Lleida, Spain.

Calpains are calcium-dependent proteases activated in apoptotic cell death and neurodegeneration. Friedreich Ataxia is a neurodegenerative rare disease caused by frataxin deficiency, a mitochondrial protein. Dorsal root ganglion (DRG) sensory neurons are among the cellular types most affected in this disease. Read More

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http://dx.doi.org/10.1007/s11064-020-03020-3DOI Listing
April 2020
2.593 Impact Factor

A wearable video-oculography based evaluation of saccades and respective clinical correlates in patients with early onset ataxia.

J Neurosci Methods 2020 May 20;338:108697. Epub 2020 Mar 20.

Department of Neuroscience - Unit of Neurorehabilitation, IRCCS Bambino Gesù Children's Hospital, Rome - Via Torre Di Palidoro s.n.c. 00050, Palidoro, Rome, Italy.

Background: Friedreich Ataxia (FRDA) and other inherited chronic ataxias (CAs) are common causes of early onset ataxias (EOA), a group of conditions still lacking effective therapies and biomarkers. Ocular saccades are considered a reliable paradigm of motor control, useful to track the functioning of underlying neural networks and serving as potential markers for neurological diseases.

New Method: A non-invasive video-oculography device (EyeSeeCam) was used to test saccadic parameters (latency, amplitude, duration, velocity) and peak velocity/amplitude ratio ("main sequence") in pediatric patients with FRDA, CAs and healthy controls, providing correlations with standard clinical scores. Read More

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http://dx.doi.org/10.1016/j.jneumeth.2020.108697DOI Listing
May 2020
2.025 Impact Factor

The Assessment of Upper Limb Functionality in Friedreich Ataxia via Self-Feeding Activity.

IEEE Trans Neural Syst Rehabil Eng 2020 Apr 2;28(4):924-933. Epub 2020 Mar 2.

The objective assessment of motor impairment resulting from neurological disorders forms the basis for effective rehabilitation and therapeutic programs. Such assessments conducted through the engagement of suitable daily activities can serve as an effective surrogate measure for the assessment of independent living. This study considers an instrumented spoon in the assessment of upper-limb functionality through the self-feeding activity of a group of individuals clinically diagnosed with the debilitating condition, Friedreich ataxia (FRDA). Read More

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http://dx.doi.org/10.1109/TNSRE.2020.2977354DOI Listing

[Epigenetic regulation of clinical manifestations of Friedreich's disease].

Zh Nevrol Psikhiatr Im S S Korsakova 2020 ;120(1):20-26

Research Center of Neurology, Moscow, Russia.

Aim: To study a methylation profile of FXN gene and its influence on the clinical phenotype of Friedreich's desease (FD).

Material And Methods: The methylation pattern was analyzed in 17 patients with FD. Forty-five CpG-sites in the promoter region and the region of intron 1 of FXN: before the GAA-expansion (UP-GAA) and after the GAA-expansion (DOWN-GAA), were studied. Read More

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http://dx.doi.org/10.17116/jnevro202012001120DOI Listing

Rating scales for rare neurological diseases: What are we learning from Friedreich ataxia?

Authors:
Massimo Pandolfo

Neurol Genet 2019 Dec 25;5(6):e380. Epub 2019 Nov 25.

Department of Neurology (M.P.), Hôpital Erasme, Université Libre de Bruxelles; and Laboratory of Experimental Neurology (M.P.), Université Libre de Bruxelles, Brussels, Belgium.

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http://dx.doi.org/10.1212/NXG.0000000000000380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927356PMC
December 2019

Psychometric properties of the Friedreich Ataxia Rating Scale.

Neurol Genet 2019 Dec 29;5(6):371. Epub 2019 Oct 29.

Clinical Data Science GmbH (C.R.), Basel, Switzerland; Bruce Lefroy Centre for Genetic Health Research (L.A.C., M.B.D.), Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics (L.A.C., M.B.D.), University of Melbourne, Parkville, Victoria, Australia; Department of Neurology (S.H.S.), McKnight Brain Institute, Room, Gainesville, FL; University of Minnesota (K.B.); University of Chicago (C.M.G.); Ohio State University (J.C.H.); Divisions of Neurology and Clinical and Metabolic Genetics (G.Y.), Department of Paediatrics, the Hospital for Sick Children, University of Toronto, Ontario, Canada Hospital; University of Rochester (B.R.); University of Iowa (K.D.M.); Emory University (G.W.); University of South Florida (T.Z.); Friedreich's Ataxia Research Alliance (S.P.), Downingtown, PA; and Division of Neurology (D.R.L.), Children's Hospital of Philadelphia.

Objective: To investigate the psychometric properties of the Friedreich Ataxia Rating Scale neurologic examination (FARSn) and its subscores, as well as the influence of the modifications resulting in the now widely used modified FARS (mFARS) examination.

Methods: Based on cross-sectional FARS data from the FA-Clinical Outcome Measures cohort, we conducted correlation-based psychometric analyses to investigate the interplay of items and subscores within the FARSn/mFARS constructs.

Results: The results provide support for both the FARSn and the mFARS constructs, as well as individually for their upper limb and lower limb coordination components. Read More

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http://dx.doi.org/10.1212/NXG.0000000000000371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927357PMC
December 2019

Ocular Involvement in Friedreich Ataxia Patients and its Relationship with Neurological Disability, a Follow-up Study.

Diagnostics (Basel) 2020 Jan 29;10(2). Epub 2020 Jan 29.

Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, 28040 Madrid, Spain.

Background: This study compared functional and structural visual changes in Friedreich ataxia (FRDA) patients with healthy controls (HC) and correlated these changes with neurological disability.

Methods: Eight FRDA Spanish patients and eight HC were selected from 2014 to 2018. Best corrected visual acuity (BCVA), visual field (VF), optic coherence tomography (OCT), and neurological disability measured by "scale for the assessment and rating of ataxia" (SARA) were taken in a basal exploration and repeated after 6 months. Read More

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http://dx.doi.org/10.3390/diagnostics10020075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168917PMC
January 2020

Correlation of Visual Quality of Life With Clinical and Visual Status in Friedreich Ataxia.

J Neuroophthalmol 2020 Jun;40(2):213-217

Division of Neurology (PA, AL, DRL), Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; and Departments of Neurology (RN-K, LJB), Population Health and Ophthalmology, NYU School of Medicine, Sackler Institute of Graduate Biomedical Sciences, New York, New York.

Background: The primary objective was to determine the association of patient-reported vision-specific quality of life to disease status and visual function in patients with Friedreich's ataxia (FRDA).

Methods: Patients with FRDA were assessed with the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) along with measures of disease status (ataxia stage) and visual function (low- and high-contrast letter acuity scores). The relations of NEI-VFQ-25 scores to those for disease status and visual function were examined. Read More

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http://dx.doi.org/10.1097/WNO.0000000000000878DOI Listing

An Instrumented Measurement Scheme for the Assessment of Upper Limb Function in Individuals with Friedreich Ataxia.

Conf Proc IEEE Eng Med Biol Soc 2019 07;2019:317-320

Continuous and objective assessment is essential for accurate monitoring of the progression of neurodegenerative conditions such as Friedreich ataxia. However, current clinical assessments predominantly rely on the ability of the affected individual to complete specific clinical tests which may not capture the intricate kinematic details associated with ataxia Moreover, such testing often consists of a level of subjectivity of the assessing clinician. In this paper, we propose an objective measuring instrument, in the form of a spoon, equipped with the Internet-of-Things (IoT) based system and relevant machine learning techniques to quantitatively assess impairment levels while engaged in routine daily activity. Read More

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http://dx.doi.org/10.1109/EMBC.2019.8857107DOI Listing

Frataxin Structure and Function.

Subcell Biochem 2019 ;93:393-438

Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencia Exactas y Naturales, Instituto de Biociencias, Biotecnología y Biomedicina (iB3), Universidad de Buenos Aires, Intendente Güiraldes 2160-Ciudad Universitaria, 1428EGA, C.A.B.A, Argentina.

Mammalian frataxin is a small mitochondrial protein involved in iron sulfur cluster assembly. Frataxin deficiency causes the neurodegenerative disease Friedreich's Ataxia. Valuable knowledge has been gained on the structural dynamics of frataxin, metal-ion-protein interactions, as well as on the effect of mutations on protein conformation, stability and internal motions. Read More

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http://dx.doi.org/10.1007/978-3-030-28151-9_13DOI Listing
February 2020

Predictors of loss of ambulation in Friedreich's ataxia.

EClinicalMedicine 2020 Jan 8;18:100213. Epub 2020 Jan 8.

Children's Hospital of Philadelphia, Philadelphia, PA, United States.

Background: Friedreich's ataxia (FRDA) is a characterized by progressive loss of coordination and balance leading to loss of ambulation (LoA) in nearly all affected individuals. While transition to becoming fully wheelchair bound is a critical milestone in the disease course, it presents a particularly challenging prediction, mostly due to variability in inter- and intra-subject severity and progression. For these reasons, LoA or potential surrogates have been impractical as outcomes in clinical trials. Read More

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http://dx.doi.org/10.1016/j.eclinm.2019.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953645PMC
January 2020

Large-scale contractions of Friedreich's ataxia GAA repeats in yeast occur during DNA replication due to their triplex-forming ability.

Proc Natl Acad Sci U S A 2020 01 7;117(3):1628-1637. Epub 2020 Jan 7.

Department of Biology, Tufts University, Medford, MA 02155

Friedreich's ataxia (FRDA) is a human hereditary disease caused by the presence of expanded (GAA) repeats in the first intron of the gene [V. Campuzano , 271, 1423-1427 (1996)]. In somatic tissues of FRDA patients, (GAA) repeat tracts are highly unstable, with contractions more common than expansions [R. Read More

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http://dx.doi.org/10.1073/pnas.1913416117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983365PMC
January 2020

Multiple mechanisms underpin cerebral and cerebellar white matter deficits in Friedreich ataxia: The IMAGE-FRDA study.

Hum Brain Mapp 2020 May 6;41(7):1920-1933. Epub 2020 Jan 6.

School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, Victoria, Australia.

Friedreich ataxia is a progressive neurodegenerative disorder with reported abnormalities in cerebellar, brainstem, and cerebral white matter. White matter structure can be measured using in vivo neuroimaging indices sensitive to different white matter features. For the first time, we examined the relative sensitivity and relationship between multiple white matter indices in Friedreich ataxia to more richly characterize disease expression and infer possible mechanisms underlying the observed white matter abnormalities. Read More

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http://dx.doi.org/10.1002/hbm.24921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267947PMC

Health related quality of life in Friedreich Ataxia in a large heterogeneous cohort.

J Neurol Sci 2020 Mar 24;410:116642. Epub 2019 Dec 24.

Division of Neurology, Children's Hospital of Philadelphia, 502 Abramson Research Center, 3615 Civic Center Blvd, Philadelphia, PA 19104-4318, United States of America. Electronic address:

Introduction: This study assessed the Health Related Quality of Life (HRQOL) of individuals with Friedreich Ataxia (FRDA) through responses to HRQOL questionnaires.

Methods: The SF-36, a generic HRQOL instrument, and symptom specific scales examining vision, fatigue, pain and bladder function were administered to individuals with FRDA and analyzed by comparison with disease features. Multiple linear regression models were used to study independent effects of genetic severity and age. Read More

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http://dx.doi.org/10.1016/j.jns.2019.116642DOI Listing
March 2020
2.474 Impact Factor

Genetic Analysis of Hereditary Ataxias in Peru Identifies SCA10 Families with Incomplete Penetrance.

Cerebellum 2020 Apr;19(2):208-215

Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Relative frequency of hereditary ataxias remains unknown in many regions of Latin America. We described the relative frequency in spinocerebellar ataxias (SCA) due to (CAG)n and to (ATTCT)n expansions, as well as Friedreich ataxia (FRDA), among cases series of ataxic individuals from Peru. Among ataxic index cases from 104 families (38 of them with and 66 without autosomal dominant pattern of inheritance), we identified 22 SCA10, 8 SCA2, 3 SCA6, 2 SCA3, 2 SCA7, 1 SCA1, and 9 FRDA cases (or families). Read More

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http://dx.doi.org/10.1007/s12311-019-01098-2DOI Listing

Longitudinal Increases in Cerebral Brain Activation During Working Memory Performance in Friedreich Ataxia: 24-Month Data from IMAGE-FRDA.

Cerebellum 2020 Apr;19(2):182-191

School of Psychological Sciences and the Turner Institute for Brain and Mental Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.

Friedreich ataxia (FRDA) has been associated with functional abnormalities in cerebral and cerebellar networks, particularly in the ventral attention network. However, how functional alterations change with disease progression remains largely unknown. Longitudinal changes in brain activation, associated with working memory performance (N-back task), and grey matter volume were assessed over 24 months in 21 individuals with FRDA and 28 healthy controls using functional and structural magnetic resonance imaging, respectively. Read More

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http://dx.doi.org/10.1007/s12311-019-01094-6DOI Listing

Exenatide induces frataxin expression and improves mitochondrial function in Friedreich ataxia.

JCI Insight 2020 01 30;5(2). Epub 2020 Jan 30.

ULB Center for Diabetes Research and.

Friedreich ataxia is an autosomal recessive neurodegenerative disease associated with a high diabetes prevalence. No treatment is available to prevent or delay disease progression. Friedreich ataxia is caused by intronic GAA trinucleotide repeat expansions in the frataxin-encoding FXN gene that reduce frataxin expression, impair iron-sulfur cluster biogenesis, cause oxidative stress, and result in mitochondrial dysfunction and apoptosis. Read More

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http://dx.doi.org/10.1172/jci.insight.134221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098728PMC
January 2020

Nanoscopic X-ray imaging and quantification of the iron cellular architecture within single fibroblasts of Friedreich's ataxia patients.

J Synchrotron Radiat 2020 Jan 1;27(Pt 1):185-198. Epub 2020 Jan 1.

Department of Analytical Chemistry, Ghent University, Ghent, Belgium.

Friedreich's ataxia (FRDA) is a neurodegenerative disease characterized by an increase in intracytoplasmic iron concentration. Here the nanoscale iron distribution within single fibroblasts from FRDA patients was investigated using synchrotron-radiation-based nanoscopic X-ray fluorescence and X-ray in-line holography at the ID16A nano-imaging beamline of the ESRF. This unique probe was deployed to uncover the iron cellular two-dimensional architecture of freeze-dried FRDA fibroblasts. Read More

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http://dx.doi.org/10.1107/S1600577519015510DOI Listing
January 2020
2.736 Impact Factor

Age of onset determines intrinsic functional brain architecture in Friedreich ataxia.

Ann Clin Transl Neurol 2020 01 18;7(1):94-104. Epub 2019 Dec 18.

Laboratoire de Cartographie fonctionnelle du Cerveau, ULB Neuroscience Institute (UNI), Université libre de Bruxelles (ULB), Brussels, Belgium.

Objective: Friedreich ataxia (FRDA) is the commonest hereditary ataxia in Caucasians. Most patients are homozygous for expanded GAA triplet repeats in the first intron of the frataxin (FXN) gene, involved in mitochondrial iron metabolism. Here, we used magnetoencephalography (MEG) to characterize the main determinants of FRDA-related changes in intrinsic functional brain architecture. Read More

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http://dx.doi.org/10.1002/acn3.50966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952309PMC
January 2020

Electrophysiological evidence for limited progression of the proprioceptive impairment in Friedreich ataxia.

Clin Neurophysiol 2020 Feb 2;131(2):574-576. Epub 2019 Dec 2.

Laboratoire de Cartographie fonctionnelle du Cerveau, ULB-Neuroscience Institute (UNI), Université libre de Bruxelles (ULB), Brussels, Belgium; Department of Functional Neuroimaging, Service of Nuclear Medicine, CUB Hôpital Erasme, Université libre de Bruxelles, Brussels, Belgium.

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http://dx.doi.org/10.1016/j.clinph.2019.10.021DOI Listing
February 2020

Neurochemical profiles in hereditary ataxias: A meta-analysis of Magnetic Resonance Spectroscopy studies.

Neurosci Biobehav Rev 2020 01 12;108:854-865. Epub 2019 Dec 12.

RWTH Aachen University, Department of Neurology, Aachen, Germany; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Research Center Jülich GmbH and RWTH Aachen University, Aachen, Germany. Electronic address:

Magnetic resonance spectroscopy (MRS) is applied to investigate the neurochemical profiles of degenerative hereditary ataxias. This meta-analysis provides a quantitative review and reappraisal of MRS findings in spinocerebellar ataxias (SCA) and Friedreich ataxia (FA) available to date. From each study, changes in N-acetyl aspartate (NAA), choline-containing compounds (Cho) and myo-Inositol (mI) ratios to total creatine (Cr) were calculated for groups of patients (1499 patients in total: SCA1 = 223, SCA2 = 298, SCA3 = 711, SCA6 = 165, and FA = 102) relative to their own control group, mostly in cerebellum and pons. Read More

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http://dx.doi.org/10.1016/j.neubiorev.2019.12.019DOI Listing
January 2020

Iron Hack - A symposium/hackathon focused on porphyrias, Friedreich's ataxia, and other rare iron-related diseases.

F1000Res 2019 19;8:1135. Epub 2019 Jul 19.

Global and Planetary Health, College of Public Health, University of South Florida, USF Genomics Program, 3720 Spectrum Blvd, Tampa, FL, 33612, USA.

: Basic and clinical scientific research at the University of South Florida (USF) have intersected to support a multi-faceted approach around a common focus on rare iron-related diseases. We proposed a modified version of the National Center for Biotechnology Information's (NCBI) Hackathon-model to take full advantage of local expertise in building "Iron Hack", a rare disease-focused hackathon. As the collaborative, problem-solving nature of hackathons tends to attract participants of highly-diverse backgrounds, organizers facilitated a symposium on rare iron-related diseases, specifically porphyrias and Friedreich's ataxia, pitched at general audiences. Read More

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http://dx.doi.org/10.12688/f1000research.19140.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894363PMC

Friedreich's Ataxia: Case series and the Additive Value of Cardiovascular Magnetic Resonance.

J Neuromuscul Dis 2020 ;7(1):61-67

First Department of Paediatrics, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, Athens, Greece.

BackgroundFriedreich's ataxia (FA) is an autosomal-recessive neurodegenerative disease characterised by neurologic, cardiac and endocrine abnormalities. Currently, Friedreich cardiomyopathy (FA-CM) staging is based on early ECG findings, high sensitivity troponin (hsTNT) ≥14 ng/ml and echocardiographic left ventricular (LV) morphologic and functional evaluation. However, further parameters, accessible only by cardiovascular magnetic resonance (CMR), such as myocardial oedema, perfusion defects, replacement and/or diffuse myocardial fibrosis, may have a place in the staging of FA-CA. Read More

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http://dx.doi.org/10.3233/JND-180373DOI Listing
January 2020

Pediatric Neuromuscular Disorders.

Pediatr Clin North Am 2020 02;67(1):45-57

Seaview Orthopaedic & Medical Associates, 1200 Eagle Avenue, Ocean, NJ 07712, USA. Electronic address:

Neuromuscular disorders are pathologies that can severely affect the quality of life as well as longevity of patients. The most common disorders include cerebral palsy and myelodysplasia. The orthopedic manifestations of these disorders can be treated operatively or nonoperatively. Read More

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http://dx.doi.org/10.1016/j.pcl.2019.09.002DOI Listing
February 2020

Left ventricular structural and functional changes in Friedreich ataxia - Relationship with body size, sex, age and genetic severity.

PLoS One 2019 13;14(11):e0225147. Epub 2019 Nov 13.

Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.

Introduction: Although a concentric pattern of left ventricular (LV) geometry appears to be common in Friedreich ataxia (FRDA), there is no accepted method for diagnosing LV abnormalities in FRDA, sex and body size have often not been taken into consideration, and it has not been clear whether children and adults should be classified using the same criteria. The aim of this study was to better define the LV geometric changes in FRDA with respect to sex, body size and subject age, and to investigate the relationship of LV changes with genetic severity, as assessed by GAA repeat length within the shorter allele of the FXN gene (GAA1).

Methods: Echocardiography was performed in 216 subjects (68 children, 148 adults), measurements were made at end-diastole of LV internal diameter (LVEDID), septal wall thickness (SWT), LV length (LVEDL) and LV volume (LVEDV), and calculations were made of relative wall thickness (RWT), LV mass and LV ejection fraction (LVEF). Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225147PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853335PMC

Speech and Language Disorders in Friedreich Ataxia: Highlights on Phenomenology, Assessment, and Therapy.

Cerebellum 2020 Feb;19(1):126-130

Department of Neurosciences, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.

Speech and language disorders are prominent signs in Friedreich ataxia (FRDA), which significantly impact on patients' quality of life. Despite such relevance, several issues regarding phenomenology, assessment, and treatment are still unmet. In this short review, we thus analyzed the existing literature to summarize what is known about the features of speech and language disorders in FRDA, which methods are used for evaluation and rating, and what are the available therapeutic strategies and future direction of scientific research in this field, in order to highlight critical aspects for a better clinical approach to the problem. Read More

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http://dx.doi.org/10.1007/s12311-019-01084-8DOI Listing
February 2020

Evolutionarily conserved susceptibility of the mitochondrial respiratory chain to SDHI pesticides and its consequence on the impact of SDHIs on human cultured cells.

PLoS One 2019 7;14(11):e0224132. Epub 2019 Nov 7.

Université de Paris, NeuroDiderot, INSERM, Paris, France.

Succinate dehydrogenase (SDH) inhibitors (SDHIs) are used worldwide to limit the proliferation of molds on plants and plant products. However, as SDH, also known as respiratory chain (RC) complex II, is a universal component of mitochondria from living organisms, highly conserved through evolution, the specificity of these inhibitors toward fungi warrants investigation. We first establish that the human, honeybee, earthworm and fungal SDHs are all sensitive to the eight SDHIs tested, albeit with varying IC50 values, generally in the micromolar range. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224132PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837341PMC
March 2020
4 Reads
3.234 Impact Factor

Potential biomarker identification for Friedreich's ataxia using overlapping gene expression patterns in patient cells and mouse dorsal root ganglion.

PLoS One 2019 30;14(10):e0223209. Epub 2019 Oct 30.

Department of Molecular Biosciences, University of California, Davis, Davis, California, United States of America.

Friedreich's ataxia (FA) is a neurodegenerative disease with no approved therapy that is the result of frataxin deficiency. The identification of human FA blood biomarkers related to disease severity and neuro-pathomechanism could support clinical trials of drug efficacy. To try to identify human biomarkers of neuro-pathomechanistic relevance, we compared the overlapping gene expression changes of primary blood and skin cells of FA patients with changes in the Dorsal Root Ganglion (DRG) of the KIKO FA mouse model. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223209PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821053PMC

Cerebellum and cognition in Friedreich ataxia: a voxel-based morphometry and volumetric MRI study.

J Neurol 2020 Feb 22;267(2):350-358. Epub 2019 Oct 22.

Department of Neurosciences and Reproductive and Odontostomatological Sciences, University "Federico II", Naples, Italy.

Background: Recent studies have suggested the presence of a significant atrophy affecting the cerebellar cortex in Friedreich ataxia (FRDA) patients, an area of the brain long considered to be relatively spared by neurodegenerative phenomena. Cognitive deficits, which occur in FRDA patients, have been associated with cerebellar volume loss in other conditions. The aim of this study was to investigate the correlation between cerebellar volume and cognition in FRDA. Read More

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http://dx.doi.org/10.1007/s00415-019-09582-9DOI Listing
February 2020
3 Reads

Targeting NRF2 for the Treatment of Friedreich's Ataxia: A Comparison among Drugs.

Int J Mol Sci 2019 Oct 21;20(20). Epub 2019 Oct 21.

Unit of Muscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.

NRF2 (Nuclear factor Erythroid 2-related Factor 2) signaling is impaired in Friedreich's Ataxia (FRDA), an autosomal recessive disease characterized by progressive nervous system damage and degeneration of nerve fibers in the spinal cord and peripheral nerves. The loss of frataxin in patients results in iron sulfur cluster deficiency and iron accumulation in the mitochondria, making FRDA a fatal and debilitating condition. There are no currently approved therapies for the treatment of FRDA and molecules able to activate NRF2 have the potential to induce clinical benefits in patients. Read More

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http://dx.doi.org/10.3390/ijms20205211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829337PMC
October 2019
1 Read

[Diagnostic algorithm for autosomal recessive ataxia].

Zh Nevrol Psikhiatr Im S S Korsakova 2019 ;119(9):74-82

Research Center of Neurology, Moscow, Russia.

Aim: To develop a complex algorithm for autosomal recessive ataxia (ARA) diagnosis applicable for Russian patients with degenerative ataxias.

Material And Methods: 48 patients with of presumably degenerative ataxias were examined. Clinical evaluation was performed with the use of the SARA and ICARS scales (for ataxia) and MoCA (cognitive functions), and a set of laboratory tests was carried out, including electromyography, brain MRI, and DNA analysis of mutations responsible for Friedreich's disease and spinocerebellar ataxias (SCAs) types 1, 2, 3, 6 and 17. Read More

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http://dx.doi.org/10.17116/jnevro201911909174DOI Listing
February 2020

Induced pluripotent stem cells-derived neurons from patients with Friedreich ataxia exhibit differential sensitivity to resveratrol and nicotinamide.

Sci Rep 2019 10 10;9(1):14568. Epub 2019 Oct 10.

INSERM UMR 861, I-STEM, AFM, 91100, Corbeil-Essonnes, France.

Translation of pharmacological results from in vitro cell testing to clinical trials is challenging. One of the causes that may underlie these discrepant results is the lack of the phenotypic or species-specific relevance of the tested cells; today, this lack of relevance may be reduced by relying on cells differentiated from human pluripotent stem cells. To analyse the benefits provided by this approach, we chose to focus on Friedreich ataxia, a neurodegenerative condition for which the recent clinical testing of two compounds was not successful. Read More

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http://dx.doi.org/10.1038/s41598-019-49870-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787055PMC
October 2019
3 Reads
5.078 Impact Factor

SINEUP non-coding RNAs rescue defective frataxin expression and activity in a cellular model of Friedreich's Ataxia.

Nucleic Acids Res 2019 11;47(20):10728-10743

Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT), Genova, Italy.

Friedreich's ataxia (FRDA) is an untreatable disorder with neuro- and cardio-degenerative progression. This monogenic disease is caused by the hyper-expansion of naturally occurring GAA repeats in the first intron of the FXN gene, encoding for frataxin, a protein implicated in the biogenesis of iron-sulfur clusters. As the genetic defect interferes with FXN transcription, FRDA patients express a normal frataxin protein but at insufficient levels. Read More

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http://dx.doi.org/10.1093/nar/gkz798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6847766PMC
November 2019
1 Read