Fault Detection and Classification in Transmission Line Using Wavelet Transform and ANN

In recent years, there is an increased interest in fault classification algorithms. The reason, behind this interest is the escalating power demand and multiple interconnections of utilities in grid. This paper presents an application of wavelet transforms to detect the faults and further to perform classification by supervised learning paradigm. Different architectures of ANN are tested with the statistical attributes of a wavelet transform of a voltage signal as input features and binary digits as outputs. The proposed supervised learning module is tested on a transmission network. It is observed the Layer Recurrent Neural Network (LRNN) architecture performs satisfactorily when it is compared with the simulation results. The transmission network is simulated on Matlab. The performance indices Mean Square Error (MSE), Mean Absolute Error (MAE), Root Mean Square Error (RMSE) and Sum Square Error (SSE) are used to determine the efficacy of the neural network

Inflammation, fibrosis and skeletal muscle regeneration in LGMDR9 are orchestrated by macrophages

Aims: Variable degrees of inflammation, necrosis, regeneration and fibrofatty replacement are part of the pathological spectrum of the dystrophic process in alpha dystroglycanopathy LGMDR9 (FKRP-related, OMIM #607155), one of the most prevailing types of LGMDs worldwide. Inflammatory processes and their complex interplay with vascular, myogenic and mesenchymal cells may have a major impact on disease development. The purpose of our study is to describe the specific immune morphological features in muscle tissue of patients with LGMDR9 to enable a better understanding of the phenotype of muscle damage leading to disease progression. Methods: We have analysed skeletal muscle biopsies of 17 patients genetically confirmed as having LGMDR9 by histopathological and molecular techniques. Results: We identified CD206+ MHC class II+ and STAT6+ immune-repressed macrophages dominating the endomysial infiltrate in areas of myofibre regeneration and fibrosis. Additionally, PDGFRβ+ pericytes were located around MHC class II+ activated capillaries residing in close proximity to areas of fibrosis and regenerating fibres. Expression of VEGF was found on many regenerating neonatal myosin+ fibres, myofibres and CD206+ macrophages also co-expressed VEGF. Conclusion: Our results show characteristic immune inflammatory features in LGMDR9 and more specifically shed light on the predominant role of macrophages and their function in vascular organisation, fibrosis and myogenesis. Understanding disease-specific immune phenomena potentially inform about possibilities for anti-fibrotic and anti-inflammatory therapeutic strategies, which may complement Ribitol replacement and gene therapies for LGMDR9 that may be available in the future

Identification of Candidate Protein Markers in Skeletal Muscle of Laminin-211-Deficient CMD Type 1A-Patients

Laminin-211 deficiency leads to the most common form of congenital muscular dystrophy in childhood, MDC1A. The clinical picture is characterized by severe muscle weakness, brain abnormalities and delayed motor milestones defining MDC1A as one of the most severe forms of congenital muscular diseases. Although the molecular genetic basis of this neurological disease is well-known and molecular studies of mouse muscle and human cultured muscle cells allowed first insights into the underlying pathophysiology, the definition of marker proteins in human vulnerable tissue such as skeletal muscle is still lacking. To systematically address this need, we analyzed the proteomic signature of laminin-211-deficient vastus muscle derived from four patients and identified 86 proteins (35 were increased and 51 decreased) as skeletal muscle markers and verified paradigmatic findings in a total of two further MDC1A muscle biopsies. Functions of proteins suggests fibrosis but also hints at altered synaptic transmission and accords with central nervous system alterations as part of the clinical spectrum of MDC1A. In addition, a profound mitochondrial vulnerability of the laminin-211-deficient muscle is indicated and also altered abundances of other proteins support the concept that metabolic alterations could be novel mechanisms that underline MDC1A and might constitute therapeutic targets. Intersection of our data with the proteomic signature of murine laminin-211-deficient gastrocnemius and diaphragm allowed the definition of nine common vulnerable proteins representing potential tissue markers

A de novo CSDE1 variant causing neurodevelopmental delay, intellectual disability, neurologic and psychiatric symptoms in a child of consanguineous parents.

Funder: National Human Genome Research Institute; Id: http://dx.doi.org/10.13039/100000051Funder: Broad Institute; Id: http://dx.doi.org/10.13039/100013114Funder: Horizon 2020; Id: http://dx.doi.org/10.13039/100010661Funder: Muscular Dystrophy Canada; Id: http://dx.doi.org/10.13039/501100000223Funder: Evelyn Trust; Id: http://dx.doi.org/10.13039/501100004282Funder: European Regional Development Fund; Id: http://dx.doi.org/10.13039/501100008530CSDE1 encodes the cytoplasmic cold shock domain-containing protein E1 (CSDE1), which is highly conserved across species and functions as an RNA-binding protein involved in translationally coupled mRNA turnover. CSDE1 displays a bidirectional role: promoting and repressing the translation of RNAs but also increasing and decreasing the abundance of RNAs. Preclinical studies highlighted an involvement of CSDE1 in different forms of cancer. Moreover, CSDE1 is highly expressed in human embryonic stem cells and plays a role in neuronal migration and differentiation. A genome-wide association study suggested CSDE1 as a potential autism-spectrum disorder risk gene. A multicenter next generation sequencing approach unraveled likely causative heterozygous variants in CSDE1 in 18 patients, identifying a new autism spectrum disorder-related syndrome consisting of autism, intellectual disability, and neurodevelopmental delay. Since then, no further patients with CSDE1 variants have been reported in the literature. Here, we report a 9.5-year-old girl from a consanguineous family of Turkish origin suffering from profound delayed speech and motor development, moderate intellectual disability, neurologic and psychiatric symptoms as well as hypoplasia of corpus callosum and mildly reduced brain volume on brain magnetic resonance imaging associated with a recurrent de novo mutation in CSDE1 (c.367C > T; p.R123*) expanding the phenotypical spectrum associated with pathogenic CSDE1 variants

Diagnostic utility of small fiber analysis in skin biopsies from children with chronic pain

Introduction Small fiber neuropathies (SFN) are associated with a reduction in quality of life. In adults, epidermal nerve fiber density (END) analysis is recommended for the diagnosis of SFN. In children, END assessment is not often performed. We analyzed small nerve fiber innervation to elucidate the potential diagnostic role of skin biopsies in young patients with pain. Methods Epidermal nerve fiber density and sudomotor neurite density (SND) were assessed in skin biopsies from 26 patients aged 7 to 20 years (15 female patients) with unexplained chronic pain. The results were compared with clinical data. Results Epidermal nerve fiber density was abnormal in 50% and borderline in 35% of patients. An underlying medical condition was found in 42% of patients, including metabolic, autoimmune, and genetic disorders. Discussion Reduction of epidermal nerve fibers can be associated with treatable conditions. Therefore, the analysis of END in children with pain may help to uncover a possible cause and guide potential treatment options

High-sensitive cardiac troponin I (hs-cTnI) concentrations in newborns diagnosed with spinal muscular atrophy

BackgroundSpinal muscular atrophy (SMA) is a genetic neurodegenerative disease leading to muscular weakness and premature death. Three therapeutic options are currently available including gene replacement therapy (GRT), which is potentially cardiotoxic. High-sensitive cardiac troponin I (hs-cTnI) is widely used to monitor potential cardiac contraindications or side effects of GRT, but reference data in healthy newborns are limited and lacking in neonates with SMA. The aim of this study is to determine the range of pre-therapeutic hs-cTnI concentrations in neonates with SMA and to provide guidance for the assessment of these values.MethodsHs-cTnI levels, genetic and clinical data of 30 newborns (age range 2–26 days) with SMA were retrospectively collected from 6 German neuromuscular centers. In addition, hs-cTnI levels were measured in 16 neonates without SMA.ResultsThe median hs-cTnI concentration in neonates with SMA was 39.5 ng/L (range: 4–1205). In 16 newborns with SMA, hs-cTnI levels were above the test-specific upper reference limit (URL). Exploratory statistical analysis revealed no relevant correlation between hs-cTnI levels and gender, gestational age, mode of delivery, SMN2 copy number, symptoms of SMA or abnormal cardiac findings.DiscussionOur results suggest higher hs-cTnI plasma levels in newborns with and without SMA compared to assay-specific reference values generated in adults. Given the wide range of hs-cTnI values in neonates with SMA, hs-cTnI levels must be determined before treatment in each patient and post-treatment elevations should be interpreted in the context of the course rather than as individual values

Homozygous WASHC4 variant in two sisters causes a syndromic phenotype defined by dysmorphisms, intellectual disability, profound developmental disorder, and skeletal muscle involvement.

Funder: European Regional Development Fund; Id: http://dx.doi.org/10.13039/501100008530Recessive variants in WASHC4 are linked to intellectual disability complicated by poor language skills, short stature, and dysmorphic features. The protein encoded by WASHC4 is part of the Wiskott-Aldrich syndrome protein and SCAR homolog family, co-localizes with actin in cells, and promotes Arp2/3-dependent actin polymerization in vitro. Functional studies in a zebrafish model suggested that WASHC4 knockdown may also affect skeletal muscles by perturbing protein clearance. However, skeletal muscle involvement has not been reported so far in patients, and precise biochemical studies allowing a deeper understanding of the molecular etiology of the disease are still lacking. Here, we report two siblings with a homozygous WASHC4 variant expanding the clinical spectrum of the disease and provide a phenotypical comparison with cases reported in the literature. Proteomic profiling of fibroblasts of the WASHC4-deficient patient revealed dysregulation of proteins relevant for the maintenance of the neuromuscular axis. Immunostaining on a muscle biopsy derived from the same patient confirmed dysregulation of proteins relevant for proper muscle function, thus highlighting an affliction of muscle cells upon loss of functional WASHC4. The results of histological and coherent anti-Stokes Raman scattering microscopic studies support the concept of a functional role of the WASHC4 protein in humans by altering protein processing and clearance. The proteomic analysis confirmed key molecular players in vitro and highlighted, for the first time, the involvement of skeletal muscle in patients. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland

Expanding the clinical and molecular spectrum of ATP6V1A related metabolic cutis laxa.

Several inborn errors of metabolism show cutis laxa as a highly recognizable feature. One group of these metabolic cutis laxa conditions is autosomal recessive cutis laxa type 2 caused by defects in v-ATPase components or the mitochondrial proline cycle. Besides cutis laxa, muscular hypotonia and cardiac abnormalities are hallmarks of autosomal recessive cutis laxa type 2D (ARCL2D) due to pathogenic variants in ATP6V1A encoding subunit A of the v-ATPase. Here, we report on three affected individuals from two families with ARCL2D in whom we performed whole exome and Sanger sequencing. We performed functional studies in fibroblasts from one individual, summarized all known probands' clinical, molecular, and biochemical features and compared them, also to other metabolic forms of cutis laxa. We identified novel missense and the first nonsense variant strongly affecting ATP6V1A expression. All six ARCL2D affected individuals show equally severe cutis laxa and dysmorphism at birth. While for one no information was available, two died in infancy and three are now adolescents with mild or absent intellectual disability. Muscular weakness, ptosis, contractures, and elevated muscle enzymes indicated a persistent myopathy. In cellular studies, a fragmented Golgi compartment, a delayed Brefeldin A-induced retrograde transport and glycosylation abnormalities were present in fibroblasts from two individuals. This is the second and confirmatory report on pathogenic variants in ATP6V1A as the cause of this extremely rare condition and the first to describe a nonsense allele. Our data highlight the tremendous clinical variability of ATP6V1A related phenotypes even within the same family