| 1. |
- Fresard, Laure, et al.
(author)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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In: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Journal article (peer-reviewed)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
- Feng, Hongliang, et al.
(author)
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Association between accelerometer-measured amplitude of rest-activity rhythm and future health risk : a prospective cohort study of the UK Biobank
- 2023
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In: The Lancet Healthy Longevity. - 2666-7568. ; 4:5, s. e200-e210
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Journal article (peer-reviewed)abstract
- BACKGROUND: The health effects of rest-activity rhythm are of major interest to public health, but its associations with health outcomes remain elusive. We aimed to examine the associations between accelerometer-measured rest-activity rhythm amplitude and health risks among the general UK population.METHODS: We did a prospective cohort analysis of UK Biobank participants aged 43-79 years with valid wrist-worn accelerometer data. Low rest-activity rhythm amplitude was defined as the first quintile of relative amplitude; all other quintiles were classified as high rest-activity rhythm amplitude. Outcomes of interest were defined using International Classification of Diseases 10th Revision codes and consisted of incident cancer and cardiovascular, infectious, respiratory, and digestive diseases, and all-cause and disease-specific (cardiovascular, cancer, and respiratory) mortality. Participants with a current diagnosis of any outcome of interest were excluded. We assessed the associations between decreased rest-activity rhythm amplitude and outcomes using Cox proportional hazards models.FINDINGS: Between June 1, 2013, and Dec 23, 2015, 103 682 participants with available raw accelerometer data were enrolled. 92 614 participants (52 219 [56·4%] women and 40 395 [42·6%] men) with a median age of 64 years (IQR 56-69) were recruited. Median follow-up was 6·4 years (IQR 5·8-6·9). Decreased rest-activity rhythm amplitude was significantly associated with increased incidence of cardiovascular diseases (adjusted hazard ratio 1·11 [95% CI 1·05-1·16]), cancer (1·08 [1·01-1·16]), infectious diseases (1·31 [1·22-1·41]), respiratory diseases (1·26 [1·19-1·34]), and digestive diseases (1·08 [1·03-1·14]), as well as all-cause mortality (1·54 [1·40-1·70]) and disease-specific mortality (1·73 [1·34-2·22] for cardiovascular diseases, 1·32 [1·13-1·55] for cancer, and 1·62 [1·25-2·09] for respiratory diseases). Most of these associations were not modified by age older than 65 years or sex. Among 16 accelerometer-measured rest-activity parameters, low rest-activity rhythm amplitude had the strongest or second- strongest associations with nine health outcomes.INTERPRETATION: Our results suggest that low rest-activity rhythm amplitude might contribute to major health outcomes and provide further evidence to promote risk-modifying strategies associated with rest-activity rhythm to improve health and longevity.
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| 3. |
- Huang, Hongyun, et al.
(author)
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Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)
- 2018
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In: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 27:2, s. 310-324
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Research review (peer-reviewed)abstract
- Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.
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