PlantRNA, a database for tRNAs of photosynthetic eukaryotes.

International audiencePlantRNA database (http://plantrna.ibmp.cnrs.fr/) compiles transfer RNA (tRNA) gene sequences retrieved from fully annotated plant nuclear, plastidial and mitochondrial genomes. The set of annotated tRNA gene sequences has been manually curated for maximum quality and confidence. The novelty of this database resides in the inclusion of biological information relevant to the function of all the tRNAs entered in the library. This includes 5'- and 3'-flanking sequences, A and B box sequences, region of transcription initiation and poly(T) transcription termination stretches, tRNA intron sequences, aminoacyl-tRNA synthetases and enzymes responsible for tRNA maturation and modification. Finally, data on mitochondrial import of nuclear-encoded tRNAs as well as the bibliome for the respective tRNAs and tRNA-binding proteins are also included. The current annotation concerns complete genomes from 11 organisms: five flowering plants (Arabidopsis thaliana, Oryza sativa, Populus trichocarpa, Medicago truncatula and Brachypodium distachyon), a moss (Physcomitrella patens), two green algae (Chlamydomonas reinhardtii and Ostreococcus tauri), one glaucophyte (Cyanophora paradoxa), one brown alga (Ectocarpus siliculosus) and a pennate diatom (Phaeodactylum tricornutum). The database will be regularly updated and implemented with new plant genome annotations so as to provide extensive information on tRNA biology to the research community

Innovative multidimensional gait evaluation using IMU in multiple sclerosis: introducing the semiogram

BackgroundQuantifying gait using inertial measurement units has gained increasing interest in recent years. Highly degraded gaits, especially in neurological impaired patients, challenge gait detection algorithms and require specific segmentation and analysis tools. Thus, the outcomes of these devices must be rigorously tested for both robustness and relevancy in order to recommend their routine use. In this study, we propose a multidimensional score to quantify and visualize gait, which can be used in neurological routine follow-up. We assessed the reliability and clinical coherence of this method in a group of severely disabled patients with progressive multiple sclerosis (pMS), who display highly degraded gait patterns, as well as in an age-matched healthy subjects (HS) group.MethodsTwenty-two participants with pMS and nineteen HS were included in this 18-month longitudinal follow-up study. During the follow-up period, all participants completed a 10-meter walk test with a U-turn and back, twice at M0, M6, M12, and M18. Average speed and seven clinical criteria (sturdiness, springiness, steadiness, stability, smoothness, synchronization, and symmetry) were evaluated using 17 gait parameters selected from the literature. The variation of these parameters from HS values was combined to generate a multidimensional visual tool, referred to as a semiogram.ResultsFor both cohorts, all criteria showed moderate to very high test–retest reliability for intra-session measurements. Inter-session quantification was also moderate to highly reliable for all criteria except smoothness, which was not reliable for HS participants. All partial scores, except for the stability score, differed between the two populations. All partial scores were correlated with an objective but not subjective quantification of gait severity in the pMS population. A deficit in the pyramidal tract was associated with altered scores in all criteria, whereas deficits in cerebellar, sensitive, bulbar, and cognitive deficits were associated with decreased scores in only a subset of gait criteria.ConclusionsThe proposed multidimensional gait quantification represents an innovative approach to monitoring gait disorders. It provides a reliable and informative biomarker for assessing the severity of gait impairments in individuals with pMS. Additionally, it holds the potential for discriminating between various underlying causes of gait alterations in pMS

Data_Sheet_1_Innovative multidimensional gait evaluation using IMU in multiple sclerosis: introducing the semiogram.PDF

BackgroundQuantifying gait using inertial measurement units has gained increasing interest in recent years. Highly degraded gaits, especially in neurological impaired patients, challenge gait detection algorithms and require specific segmentation and analysis tools. Thus, the outcomes of these devices must be rigorously tested for both robustness and relevancy in order to recommend their routine use. In this study, we propose a multidimensional score to quantify and visualize gait, which can be used in neurological routine follow-up. We assessed the reliability and clinical coherence of this method in a group of severely disabled patients with progressive multiple sclerosis (pMS), who display highly degraded gait patterns, as well as in an age-matched healthy subjects (HS) group.MethodsTwenty-two participants with pMS and nineteen HS were included in this 18-month longitudinal follow-up study. During the follow-up period, all participants completed a 10-meter walk test with a U-turn and back, twice at M0, M6, M12, and M18. Average speed and seven clinical criteria (sturdiness, springiness, steadiness, stability, smoothness, synchronization, and symmetry) were evaluated using 17 gait parameters selected from the literature. The variation of these parameters from HS values was combined to generate a multidimensional visual tool, referred to as a semiogram.ResultsFor both cohorts, all criteria showed moderate to very high test–retest reliability for intra-session measurements. Inter-session quantification was also moderate to highly reliable for all criteria except smoothness, which was not reliable for HS participants. All partial scores, except for the stability score, differed between the two populations. All partial scores were correlated with an objective but not subjective quantification of gait severity in the pMS population. A deficit in the pyramidal tract was associated with altered scores in all criteria, whereas deficits in cerebellar, sensitive, bulbar, and cognitive deficits were associated with decreased scores in only a subset of gait criteria.ConclusionsThe proposed multidimensional gait quantification represents an innovative approach to monitoring gait disorders. It provides a reliable and informative biomarker for assessing the severity of gait impairments in individuals with pMS. Additionally, it holds the potential for discriminating between various underlying causes of gait alterations in pMS.</p

Severe phenotype in patients with large deletions of NF1

International audienceComplete deletion of the NF1 gene is identified in 5–10% of patients with neurofibromatosis type 1 (NF1). Several studies have previously described particularly severe forms of the disease in NF1 patients with deletion of the NF1 locus, but comprehensive descriptions of large cohorts are still missing to fully characterize this contiguous gene syndrome. NF1-deleted patients were enrolled and phenotypically characterized with a standardized questionnaire between 2005 and 2020 from a large French NF1 cohort. Statistical analyses for main NF1-associated symptoms were performed versus an NF1 reference population. A deletion of the NF1 gene was detected in 4% (139/3479) of molecularly confirmed NF1 index cases. The median age of the group at clinical investigations was 21 years old. A comprehensive clinical assessment showed that 93% (116/126) of NF1-deleted patients fulfilled the NIH criteria for NF1. More than half had café-au-lait spots, skinfold freckling, Lisch nodules, neurofibromas, neurological abnormalities, and cognitive impairment or learning disabilities. Comparison with previously described “classic” NF1 cohorts showed a significantly higher proportion of symptomatic spinal neurofibromas, dysmorphism, learning disabilities, malignancies, and skeletal and cardiovascular abnormalities in the NF1-deleted group. We described the largest NF1-deleted cohort to date and clarified the more severe phenotype observed in these patients

Implementation of a centralized pharmacovigilance system in academic pan‐European clinical trials : experience from EU‐Response and conect4children consortia

Setting-up a high quality, compliant and efficient pharmacovigilance (PV) system in multi-country clinical trials can be more challenging for academic sponsors than for companies. To ensure the safety of all participants in academic studies and that the PV system fulfils all regulations, we set up a centralized PV system that allows sponsors to delegate work on PV. This initiative was put in practice by our Inserm-ANRS MIE PV department in two distinct multinational European consortia with 19 participating countries: conect4children (c4c) for paediatrics research and EU-Response for Covid-19 platform trials. The centralized PV system consists of some key procedures to harmonize the complex safety processes, creation of a local safety officer (LSO) network and centralization of all safety activities. The key procedures described the safety management plan for each trial and how tasks were shared and delegated between all stakeholders. Processing of serious adverse events (SAEs) in a unique database guaranteed the full control of the safety data and continuous evaluation of the risk-benefit ratio. The LSO network participated in efficient regulatory compliance across multiple countries. In total, there were 1312 SAEs in EU-Response and 83 SAEs in c4c in the four trials. We present here the lessons learnt from our experience in four clinical trials. We managed heterogeneous European local requirements and implemented efficient communication with all trial teams. Our approach builds capacity for PV that can be used by multiple academic sponsors