Symbolic Melodic Similarity: State of the Art and Future Challenges

Fostered by the introduction of the Music Information Retrieval Evaluation eXchange (MIREX) competition, the number of systems which calculate Symbolic Melodic Similarity has recently increased considerably. In order to understand the state of the art, we provide a comparative analysis of existing algorithms. The analysis is based on eight criteria that help characterising the systems, and highlighting strengths and weaknesses. We also propose a taxonomy which classifies algorithms based on their approach. Both taxonomy and criteria are fruitfully exploited for providing input for new forthcoming research in the area

Herpes Simplex virus type 2 myeloradiculitis with a pure motor presentationin a liver transplant recipient

In this case report, we describe the first PCR-confirmed case of HSV2 myeloradiculitis with a purely motor presentation, occurring in a 68-year-old liver transplant recipient. The patient reported ascending weakness with no sensory nor sphincteric symptoms, thereby resembling acute demyelinating inflammatory neuropathy, or Guillain-Barr\ue9 syndrome. HSV2 was detected in cerebrospinal fluid by PCR, and the patient was successfully treated with intravenous Acyclovir

Diaphragm and Lung Transplantation

Mutual interactions between the diaphragm and lung transplantation (LTx) are known to exist. Before LTx, many factors can exert notable impact on the diaphragmatic function, such as the underlying respiratory disease, the comorbidities, and the chronic treatments of the patient. In the post-LTx setting, even the surgical procedure itself can cause a stressful trauma to the diaphragm, potentially leading to morphological and functional alterations. Conversely, the diaphragm can significantly influence various aspects of the LTx process, ranging from graft-to-chest cavity size matching to the long-term postoperative respiratory performance of the recipient. Despite this, there are still no standard criteria for evaluating, defining, and managing diaphragmatic dysfunction in the context of LTx to date. This deficiency hampers the accurate assessment of those factors which affect the diaphragm and its reciprocal influence on LTx outcomes. The objective of this narrative review is to delve into the complex role the diaphragm plays in the different stages of LTx and into the modifications of this muscle following surgery

Nusinersen treatment and cerebrospinal fluid neurofilaments : An explorative study on Spinal Muscular Atrophy type 3 patients

The antisense oligonucleotide Nusinersen has been recently licensed to treat spinal muscular atrophy (SMA). Since SMA type 3 is characterized by variable phenotype and milder progression, biomarkers of early treatment response are urgently needed. We investigated the cerebrospinal fluid (CSF) concentration of neurofilaments in SMA type 3 patients treated with Nusinersen as a potential biomarker of treatment efficacy. The concentration of phosphorylated neurofilaments heavy chain (pNfH) and light chain (NfL) in the CSF of SMA type 3 patients was evaluated before and after six months since the first Nusinersen administration, performed with commercially available enzyme-linked immunosorbent assay (ELISA) kits. Clinical evaluation of SMA patients was performed with standardized motor function scales. Baseline neurofilament levels in patients were comparable to controls, but significantly decreased after six months of treatment, while motor functions were only marginally ameliorated. No significant correlation was observed between the change in motor functions and that of neurofilaments over time. The reduction of neurofilament levels suggests a possible early biochemical effect of treatment on axonal degeneration, which may precede changes in motor performance. Our study mandates further investigations to assess neurofilaments as a marker of treatment response

NGS-Based Genetic Analysis in a Cohort of Italian Patients with Suspected Inherited Myopathies and/or HyperCKemia

Introduction/Aims HyperCKemia is considered a hallmark of neuromuscular diseases. It can be either isolated or associated with cramps, myalgia, weakness, myoglobinuria, or rhabdomyolysis, suggesting a metabolic myopathy. The aim of this work was to investigate possible genetic causes in order to help diagnose patients with recurrent hyperCKemia or clinical suspicion of inherited metabolic myopathy. Methods A cohort of 139 patients (90 adults and 49 children) was analyzed using a custom panel containing 54 genes associated with hyperCKemia. Results A definite genetic diagnosis was obtained in 15.1% of cases, while candidate variants or variants of uncertain significance were found in a further 39.5%. Similar percentages were obtained in patients with infantile or adult onset, with some different causative genes. RYR1 was the gene most frequently identified, either with single or compound heterozygous variants, while ETFDH variants were the most common cause for recessive cases. In one patient, mRNA analysis allowed identifying a large LPIN1 deletion missed by DNA sequencing, leading to a certain diagnosis. Conclusion These data confirm the high genetic heterogeneity of hyperCKemia and metabolic myopathies. The reduced diagnostic yield suggests the existence of additional genes associated with this condition but also allows speculation that a significant number of cases presenting with hyperCKemia or muscle symptoms are due to extrinsic, not genetic, factors

Supporting people with type 2 diabetes in effective use of their medicine through mobile health technology integrated with clinical care (SuMMiT-D Feasibility): a randomised feasibility trial protocol

INTRODUCTION: Type 2 diabetes is common, affecting over 400 million people worldwide. Risk of serious complications can be reduced through use of effective treatments and active self-management. However, people are often concerned about starting new medicines and face difficulties in taking them regularly. Use of brief messages to provide education and support self-management, delivered through mobile phone-based text messages, can be an effective tool for some long-term conditions. We have developed messages aiming to support patients' self-management of type 2 diabetes in the use of medications and other aspects of self-management, underpinned by theory and evidence. The aim of this trial is to determine the feasibility of a large-scale clinical trial to test the effectiveness and cost-effectiveness of the intervention, compared with usual care. METHODS AND ANALYSIS: The feasibility trial will be a multicentre individually randomised, controlled trial in primary care recruiting adults (≥35 years) with type 2 diabetes in England. Consenting participants will be randomised to receive short text messages three times a week with messages designed to produce change in medication adherence or non-health-related messages for 6 months. The aims are to test recruitment methods, retention to the study, the feasibility of data collection and the mobile phone and web-based processes of a proposed definitive trial and to refine the text messaging intervention. The primary outcome is the rate of recruitment to randomisation of participants to the trial. Data, including patient reported measures, will be collected online at baseline and the end of the 6-month follow-up period. With 200 participants (100 in each group), this trial is powered to estimate 80% follow-up within 95% CIs of 73.8% to 85.3%. The analysis will follow a prespecified plan. ETHICS AND DISSEMINATION: Ethics approval was obtained from the West of Scotland Research Ethics Committee 05. The results will be disseminated through conference presentations, peer-reviewed journals and will be published on the trial website: www.summit-d.org (SuMMiT-D (SUpport through Mobile Messaging and digital health Technology for Diabetes)). TRIAL REGISTRATION NUMBER: ISRCTN13404264

Central nervous system involvement in common variable immunodeficiency: A case of acute unilateral optic neuritis in a 26 -year-old Italian Patient

Common Variable Immunodeficiency (CVID) is a group of heterogeneous primary immunodeficiencies sharing defective B lymphocytes maturation and dysregulated immune response and resulting in impaired immunoglobulin production. Clinical picture encompasses increased susceptibility to infections, hematologic malignancies, inflammatory, and autoimmune diseases. Neurological manifestations are uncommon and optic neuritis has been previously reported only in one case with bilateral involvement. We hereby report a case of a 26-year-old man affected by CVID undergoing regular immunoglobulin supplementation, who presented with acute unilateral demyelinating optic neuritis and lymphocytic pleocytosis in the cerebrospinal fluid. A variety of infectious, inflammatory, and neoplastic conditions were excluded and a diagnosis of clinically isolated optic neuritis was made. The patient was treated with a short course of intravenous steroids with complete recovery. Overall, this case expands our current knowledge about clinical spectrum of complications in CVID and highlights the need for further research about this complex disease

Supporting people with type 2 diabetes in effective use of their medicine through mobile health technology integrated with clinical care (SuMMiT-D pilot) : results of a feasibility randomised trial

Funding Information: This publication presents independent research funded by the National Institute for Health and Care Research (NIHR) under its Programme Grants for Applied Research programme (RP-PG-1214–20003). AF and RR are supported by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre. DPF is supported by the NIHR Manchester Biomedical Research Centre (IS-BRC-1215–20007). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. This research was funded in whole, or in part, by the National Institute for Health and Care Research (NIHR) under its Programme Grants for Applied Research programme (RP-PG-1214–20003). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The SuMMiT-D research team acknowledges the support of the Primary Care Clinical Trials Unit and the National Institute for Health and Care Research Clinical Research Network (NIHR CRN). The authors would like to thank the Thames Valley and South Midlands, West Midlands, South West Peninsula and the Greater Manchester Clinical Research Networks and the participating general practices for help with recruitment. The funder had no role in the design, execution, analyses, interpretation of the data, or decision to submit results for this study.Peer reviewe

Givinostat for Becker muscular dystrophy: a randomized, placebo-controlled, double-blind study

Objective: No treatments are approved for Becker muscular dystrophy (BMD). This study investigated the efficacy and safety of givinostat, a histone deacetylase pan-inhibitor, in adults with BMD. Methods: Males aged 18-65 years with a diagnosis of BMD confirmed by genetic testing were randomized 2:1 to 12 months treatment with givinostat or placebo. The primary objective was to demonstrate statistical superiority of givinostat over placebo for mean change from baseline in total fibrosis after 12 months. Secondary efficacy endpoints included other histological parameters, magnetic resonance imaging and spectroscopy (MRI and MRS) measures, and functional evaluations. Results: Of 51 patients enrolled, 44 completed treatment. At baseline, there was greater disease involvement in the placebo group than givinostat, based on total fibrosis (mean 30.8 vs. 22.8%) and functional endpoints. Mean total fibrosis did not change from baseline in either group, and the two groups did not differ at Month 12 (least squares mean [LSM] difference 1.04%; p = 0.8282). Secondary histology parameters, MRS, and functional evaluations were consistent with the primary. MRI fat fraction in whole thigh and quadriceps did not change from baseline in the givinostat group, but values increased with placebo, with LSM givinostat-placebo differences at Month 12 of -1.35% (p = 0.0149) and -1.96% (p = 0.0022), respectively. Adverse events, most mild or moderate, were reported by 88.2% and 52.9% patients receiving givinostat and placebo. Conclusion: The study failed to achieve the primary endpoint. However, there was a potential signal from the MRI assessments suggesting givinostat could prevent (or slow down) BMD disease progression.</p