Soluble biomarkers for Neuromyelitis Optica Spectrum Disorders: a mini review.

The Neuromyelitis Optica Spectrum Disorders (NMOSD) constitute a spectrum of rare autoimmune diseases of the central nervous system characterized by episodes of transverse myelitis, optic neuritis, and other demyelinating attacks. Previously thought to be a subtype of multiple sclerosis, NMOSD is now known to be a distinct disease with unique pathophysiology, clinical course, and treatment options. Although there have been significant recent advances in the diagnosis and treatment of NMOSD, the field still lacks clinically validated biomarkers that can be used to stratify disease severity, monitor disease activity, and inform treatment decisions.

A case of immunotherapy-responsive autoimmune hemichorea.

Introduction: Subacute adult-acquired hemichorea is a striking presentation with a broad differential, including ischemic, metabolic, and inflammatory causes.

Case: We encountered a 74-year-old woman with rapid onset of hemichorea and associated encephalopathy. Following a thorough workup without identification of clear imaging or laboratory abnormalities, we empirically treated with IVIg.

Dissemination and implementation of clinical practice guidelines: a longitudinal, mixed-methods evaluation of the Canadian Task Force on Preventive Health Care's knowledge translation efforts.

Background: The Canadian Task Force on Preventive Health Care (task force) develops evidence-based preventive health care guidelines and knowledge translation (KT) tools to facilitate guideline dissemination and implementation. We aimed to determine practitioners' awareness of task force guidelines and KT tools and explore barriers and facilitators to their use.

Methods: The task force's KT team completed annual evaluations using surveys and interviews with primary care providers in Canada from 2014 to 2020, to assess practitioners' awareness and determinants of use of task force guidelines and tools.

The impact of vaccination status on importation of COVID-19 among international travellers.

Governments worldwide are looking for ways to safely enable international travel while mitigating the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated coronavirus disease 2019 (COVID-19). However, few data describe the impact of vaccination on importation of COVID-19. We took advantage of the sequential introduction of two government policies in Canada to evaluate the real-world evidence of vaccine effectiveness among 30,361 international travellers arriving by air in Alberta, Canada.

Population surveillance approach to detect and respond to new clusters of COVID-19.

Background: To maintain control of the coronavirus disease 2019 (COVID-19) epidemic as lockdowns are lifted, it will be crucial to enhance alternative public health measures. For surveillance, it will be necessary to detect a high proportion of any new cases quickly so that they can be isolated, and people who have been exposed to them traced and quarantined. Here we introduce a mathematical approach that can be used to determine how many samples need to be collected per unit area and unit time to detect new clusters of COVID-19 cases at a stage early enough to control an outbreak.

COVID-19 infection among international travellers: a prospective analysis.

Objectives: This report estimates the risk of COVID-19 importation and secondary transmission associated with a modified quarantine programme in Canada.

Design And Participants: Prospective analysis of international asymptomatic travellers entering Alberta, Canada.

Interventions: All participants were required to receive a PCR COVID-19 test on arrival.

Comprehensive identification of somatic nucleotide variants in human brain tissue.

Background: Post-zygotic mutations incurred during DNA replication, DNA repair, and other cellular processes lead to somatic mosaicism. Somatic mosaicism is an established cause of various diseases, including cancers. However, detecting mosaic variants in DNA from non-cancerous somatic tissues poses significant challenges, particularly if the variants only are present in a small fraction of cells.

MIPP-Seq: ultra-sensitive rapid detection and validation of low-frequency mosaic mutations.

Background: Mosaic mutations contribute to numerous human disorders. As such, the identification and precise quantification of mosaic mutations is essential for a wide range of research applications, clinical diagnoses, and early detection of cancers. Currently, the low-throughput nature of single allele assays (e.

The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing.

We characterize the landscape of somatic mutations-mutations occurring after fertilization-in the human brain using ultra-deep (~250×) whole-genome sequencing of prefrontal cortex from 59 donors with autism spectrum disorder (ASD) and 15 control donors. We observe a mean of 26 somatic single-nucleotide variants per brain present in ≥4% of cells, with enrichment of mutations in coding and putative regulatory regions. Our analysis reveals that the first cell division after fertilization produces ~3.

Large mosaic copy number variations confer autism risk.

Although germline de novo copy number variants (CNVs) are known causes of autism spectrum disorder (ASD), the contribution of mosaic (early-developmental) copy number variants (mCNVs) has not been explored. In this study, we assessed the contribution of mCNVs to ASD by ascertaining mCNVs in genotype array intensity data from 12,077 probands with ASD and 5,500 unaffected siblings. We detected 46 mCNVs in probands and 19 mCNVs in siblings, affecting 2.

Developing trustworthy recommendations as part of an urgent response (1-2 weeks): a GRADE concept paper.

Objectives: The aim of this study is to propose an approach for developing trustworthy recommendations as part of urgent responses (1-2 week) in the clinical, public health, and health systems fields.

Study Design And Setting: We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the Grading of Recommendations Assessment, Development and Evaluation Rapid Guidelines project group, and obtained feedback from the larger Grading of Recommendations Assessment, Development and Evaluation working group.

Results: A request for developing recommendations within 2 week is the usual trigger for an urgent response.

Accurate detection of mosaic variants in sequencing data without matched controls.

Detection of mosaic mutations that arise in normal development is challenging, as such mutations are typically present in only a minute fraction of cells and there is no clear matched control for removing germline variants and systematic artifacts. We present MosaicForecast, a machine-learning method that leverages read-based phasing and read-level features to accurately detect mosaic single-nucleotide variants and indels, achieving a multifold increase in specificity compared with existing algorithms. Using single-cell sequencing and targeted sequencing, we validated 80-90% of the mosaic single-nucleotide variants and 60-80% of indels detected in human brain whole-genome sequencing data.

Linked-read analysis identifies mutations in single-cell DNA-sequencing data.

Whole-genome sequencing of DNA from single cells has the potential to reshape our understanding of mutational heterogeneity in normal and diseased tissues. However, a major difficulty is distinguishing amplification artifacts from biologically derived somatic mutations. Here, we describe linked-read analysis (LiRA), a method that accurately identifies somatic single-nucleotide variants (sSNVs) by using read-level phasing with nearby germline heterozygous polymorphisms, thereby enabling the characterization of mutational signatures and estimation of somatic mutation rates in single cells.

Risk of sexual transmission of human immunodeficiency virus with antiretroviral therapy, suppressed viral load and condom use: a systematic review.

Background: The Public Health Agency of Canada reviewed sexual transmission of HIV between serodiscordant partners to support examination of the criminal justice system response to HIV nondisclosure by the Department of Justice of Canada. We sought to determine HIV transmission risk when an HIV-positive partner takes antiretroviral therapy, has a suppressed viral load or uses condoms.

Methods: We conducted an overview and systematic review update by searching MEDLINE and other databases (Jan.

Somatic Mutation in Pediatric Neurological Diseases.

Genetic variation contributes significantly to brain function and dysfunction, and studying the genetic factors responsible for neurological phenotypes is tremendously valuable for understanding brain development, physiology, and pathophysiology, as well as for advancements in disease diagnostics and therapeutics. Many genetic determinants of neurobiology are inherited from parents through the germline and are present in all cells of an individual, but others, known as somatic or mosaic mutations, may be acquired post-conception and are therefore present in only a subset of an individual’s cells. While the relationship between somatic mutation and cancer is clear, recent studies have also established a role for somatic mutations in several non-malignant neurological diseases of childhood, including cerebral cortical malformations and epilepsy disorders, autism spectrum disorder, and other neuropsychiatric diseases.

Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies: The PRISMA-DTA Statement.

Importance: Systematic reviews of diagnostic test accuracy synthesize data from primary diagnostic studies that have evaluated the accuracy of 1 or more index tests against a reference standard, provide estimates of test performance, allow comparisons of the accuracy of different tests, and facilitate the identification of sources of variability in test accuracy.

Objective: To develop the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagnostic test accuracy guideline as a stand-alone extension of the PRISMA statement. Modifications to the PRISMA statement reflect the specific requirements for reporting of systematic reviews and meta-analyses of diagnostic test accuracy studies and the abstracts for these reviews.

Aging and neurodegeneration are associated with increased mutations in single human neurons.

It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of 15 normal individuals (aged 4 months to 82 years), as well as 9 individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease.

2009-2010 Influenza A(H1N1)-related critical illness among Aboriginal and non-Aboriginal Canadians.

Background: Preliminary studies suggested that Aboriginal Canadians had disproportionately higher rates of infection, hospitalization, and critical illness due to pandemic Influenza A(H1N1)pdm09.

Methods: We used a prospective cohort study of critically ill patients with laboratory confirmed or probable H1N1 infection in Canada between April 16 2009 and April 12 2010. Baseline characteristics, medical interventions, clinical course and outcomes were compared between Aboriginal and non-Aboriginal patients.

Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor as the cause of microcephaly-micromelia syndrome.

While next-generation sequencing has accelerated the discovery of human disease genes, progress has been largely limited to the "low hanging fruit" of mutations with obvious exonic coding or canonical splice site impact. In contrast, the lack of high-throughput, unbiased approaches for functional assessment of most noncoding variants has bottlenecked gene discovery. We report the integration of transcriptome sequencing (RNA-seq), which surveys all mRNAs to reveal functional impacts of variants at the transcription level, into the gene discovery framework for a unique human disease, microcephaly-micromelia syndrome (MMS).