Physical activity may protect myelin via modulation of high-density lipoprotein.

Introduction: Physical activity is associated with greater myelin content in older individuals with cerebral small vessel disease (CSVD), a condition marked by demyelination. However, potential mechanisms underlying this relationship remain understudied.

Methods: We assessed cross-sectionally whether serum high-density lipoprotein (HDL), low-density lipoprotein, and triglycerides moderated the association between physical activity and in vivo myelin in older individuals with CSVD and mild cognitive impairment.

Fingolimod and risk of skin cancer among individuals with multiple sclerosis: a population-based cohort study protocol.

Introduction: Long-term population-based safety studies, applying advanced causal inference techniques, including an active comparator with new-user design, are needed to investigate skin cancer outcomes among individuals with multiple sclerosis (MS) treated with fingolimod. This study aims to describe a protocol for investigating the relationship between fingolimod use and the incidence of skin cancer among individuals with MS.

Methods And Analysis: We will use population-based administrative health data from two Canadian provinces (British Columbia and Alberta) to conduct an observational cohort 'trial emulation' study with an active comparator and new-user design.

The Role of Machine Learning in the Detection of Cardiac Fibrosis in Electrocardiograms: Scoping Review.

Background: Cardiovascular disease remains the leading cause of mortality worldwide. Cardiac fibrosis impacts the underlying pathophysiology of many cardiovascular diseases by altering structural integrity and impairing electrical conduction. Identifying cardiac fibrosis is essential for the prognosis and management of cardiovascular disease; however, current diagnostic methods face challenges due to invasiveness, cost, and inaccessibility.

The Canadian Prospective Cohort Study to understand progression in multiple sclerosis: baseline characteristics.

Background: Disease progression is observed across the spectrum of people with multiple sclerosis (MS) and identification of effective treatment strategies to halt progression remains one of the greatest unmet clinical needs.

Objectives: The Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) was designed to evaluate a wide range of factors associated with the onset and rate of clinical disease progression in MS and to describe the interplay between these factors.

Design: A prospective cohort study.

Physical reserve and its underpinning functional neural networks moderate the relationship between white matter hyperintensity and postural balance in older adults with subcortical ischemic vascular cognitive impairment.

White matter hyperintensities (WMH) are markers of subcortical ischemic vascular cognitive impairment (SIVCI) associated with impaired postural balance. Physical reserve (PR) is a recently established construct that reflects one's capacity to maintain physical function despite brain pathology. This cross-sectional study aims to map functional networks associated with PR, and examining the relationship between PR, WMH, and postural balance.

SSiT: Saliency-Guided Self-Supervised Image Transformer for Diabetic Retinopathy Grading.

Self-supervised Learning (SSL) has been widely applied to learn image representations through exploiting unlabeled images. However, it has not been fully explored in the medical image analysis field. In this work, Saliency-guided Self-Supervised image Transformer (SSiT) is proposed for Diabetic Retinopathy (DR) grading from fundus images.

Bivalent non-human gal-α1-3-gal glycan epitopes in the Fc region of a monoclonal antibody model can be recognized by anti-Gal-α1-3-Gal IgE antibodies.

Monoclonal antibody (mAb) production using non-human cells can introduce non-human glycan epitopes including terminal galactosyl-α1-3-galactose (α1-3-Gal) moieties. Cetuximab is a commercial mAb associated with causing anaphylaxis in some patients due to the binding of endogenous anti-α1-3-Gal IgE to the Fab (containing bi-α1-3-galactosylated glycans) but not to the Fc region (containing mono-α1-3-galactosylated glycans). Despite being low in abundance in typical commercial mAbs, the inherent sensitivity of cell culture conditions on glycosylation profiles, and the development of novel glycoengineering strategies, novel antibody-based modalities, and biosimilars by various manufacturers with varying procedures, necessitates a better understanding of the structural requirements for anti-α1-3-Gal IgE binding to the Fc region.

Resistance Training Maintains White Matter and Physical Function in Older Women with Cerebral Small Vessel Disease: An Exploratory Analysis of a Randomized Controlled Trial.

Background: As the aging population grows, there is an increasing need to develop accessible interventions against risk factors for cognitive impairment and dementia, such as cerebral small vessel disease (CSVD). The progression of white matter hyperintensities (WMHs), a key hallmark of CSVD, can be slowed by resistance training (RT). We hypothesize RT preserves white matter integrity and that this preservation is associated with improved cognitive and physical function.

Tissue-Engineered Disease Modeling of Lymphangioleiomyomatosis Exposes a Therapeutic Vulnerability to HDAC Inhibition.

Lymphangioleiomyomatosis (LAM) is a rare disease involving cystic lung destruction by invasive LAM cells. These cells harbor loss-of-function mutations in TSC2, conferring hyperactive mTORC1 signaling. Here, tissue engineering tools are employed to model LAM and identify new therapeutic candidates.

Accounting for uncertainty in training data to improve machine learning performance in predicting new disease activity in early multiple sclerosis.

Introduction: Machine learning (ML) has great potential for using health data to predict clinical outcomes in individual patients. Missing data are a common challenge in training ML algorithms, such as when subjects withdraw from a clinical study, leaving some samples with missing outcome labels. In this study, we have compared three ML models to determine whether accounting for label uncertainty can improve a model's predictions.

Identifying the Key Components in ResNet-50 for Diabetic Retinopathy Grading from Fundus Images: A Systematic Investigation.

Although deep learning-based diabetic retinopathy (DR) classification methods typically benefit from well-designed architectures of convolutional neural networks, the training setting also has a non-negligible impact on prediction performance. The training setting includes various interdependent components, such as an objective function, a data sampling strategy, and a data augmentation approach. To identify the key components in a standard deep learning framework (ResNet-50) for DR grading, we systematically analyze the impact of several major components.

Employment status, productivity loss, and associated factors among people with multiple sclerosis.

Background: Multiple Sclerosis (MS) affects people in their most productive years of life. Consequently, MS can substantially affect employment and work-related outcomes.

Objectives: This study characterizes productivity loss and employment status of people with multiple sclerosis (pwMS) and investigates associated factors.

Aerobic exercise improves executive functions in females, but not males, without the BDNF Val66Met polymorphism.

Background: Aerobic exercise promotes cognitive function in older adults; however, variability exists in the degree of benefit. The brain-derived neurotropic factor (BDNF) Val66Met polymorphism and biological sex are biological factors that have been proposed as important modifiers of exercise efficacy. Therefore, we assessed whether the effect of aerobic exercise on executive functions was dependent on the BDNFval66met genotype and biological sex.

Bivalent vaccines effectively protect mice against influenza A and respiratory syncytial viruses.

Influenza and Respiratory Syncytial virus (RSV) infections together contribute significantly to the burden of acute lower respiratory tract infections. Despite the disease burden, no approved RSV vaccine is available. While approved vaccines are available for influenza, seasonal vaccination is required to maintain protection.

Myelin heterogeneity for assessing normal appearing white matter myelin damage in multiple sclerosis.

Background And Purpose: Conventional MRI measures of multiple sclerosis (MS) disease severity, such as lesion volume and brain atrophy, do not provide information about microstructural tissue changes, which may be driving physical and cognitive progression. Myelin damage in normal-appearing white matter (NAWM) is likely an important contributor to MS disability. Myelin water fraction (MWF) provides quantitative measurements of myelin.

Specific location of galactosylation in an afucosylated antiviral monoclonal antibody affects its FcγRIIIA binding affinity.

Monoclonal antibodies (mAbs) comprise an essential type of biologic therapeutics and are used to treat diseases because of their anti-cancer and anti-inflammatory properties, and their ability to protect against respiratory infections. Its production involves post-translational glycosylation, a biosynthetic process that conjugates glycans to proteins, which plays crucial roles in mAb bioactivities including effector functions and pharmacokinetics. These glycans are heterogeneous and have diverse chemical structures whose composition is sensitive to manufacturing conditions, rendering the understanding of how specific glycan structures affect mAb bioactivity challenging.

Weight for It: Resistance Training Mitigates White Matter Hyperintensity-Related Disruption to Functional Networks in Older Females.

Background: White matter hyperintensities (WMH) are associated with impaired cognition and increased falls risk. Resistance training (RT) is a promising intervention to reduce WMH progression, improve executive functions, and reduce falls. However, the underlying neurobiological process by which RT improves executive functions and falls risk remain unclear.

Selective reversed-phase high-performance liquid chromatography method for the determination of intact SARS-CoV-2 spike protein.

Protein-based vaccines are playing an increasingly important role in the COVID-19 pandemic. As late-stage clinical data are finalized and released, the number of protein-based vaccines expected to enter the market will increase significantly. Most protein-based COVID-19 vaccines are based on the SARS-CoV-2 spike protein (S-protein), which plays a major role in viral attachment to human cells and infection.

Myelin Content and Gait Impairment in Older Adults with Cerebral Small Vessel Disease and Mild Cognitive Impairment.

We investigated whether myelin is associated with gait parameters in older adults with cerebral small vessel disease (cSVD). Cross-sectional data from sixty-four participants with cSVD and mild cognitive impairment were analyzed. Myelin was assessed via MRI multi-echo gradient and spin echo T relaxation sequence, indexed as myelin water fraction (MWF).

Unusual β1-4-galactosidase activity of an α1-6-mannosidase from Xanthomonas manihotis in the processing of branched hybrid and complex glycans.

Mannosidases are a diverse group of glycoside hydrolases that play crucial roles in mannose trimming of oligomannose glycans, glycoconjugates, and glycoproteins involved in numerous cellular processes, such as glycan biosynthesis and metabolism, structure regulation, cellular recognition, and cell-pathogen interactions. Exomannosidases and endomannosidases cleave specific glycosidic bonds of mannoside linkages in glycans and can be used in enzyme-based methods for sequencing of isomeric glycan structures. α1-6-mannosidase from Xanthomonas manihotis is known as a highly specific exoglycosidase that removes unbranched α1-6 linked mannose residues from oligosaccharides.

Myelin water imaging in relapsing multiple sclerosis treated with ocrelizumab and interferon beta-1a.

Background: Myelin water imaging is a magnetic resonance imaging (MRI) technique that quantifies myelin damage and repair in multiple sclerosis (MS) via the myelin water fraction (MWF).

Objective: In this substudy of a phase 3 therapeutic trial, OPERA II, MWF was assessed in relapsing MS participants assigned to interferon beta-1a (IFNb-1a) or ocrelizumab (OCR) during a two-year double-blind period (DBP) followed by a two-year open label extension (OLE) with ocrelizumab treatment.

Methods: MWF in normal appearing white matter (NAWM), including both whole brain NAWM and 5 white matter structures, and chronic lesions, was assessed in 29 OCR and 26 IFNb-1a treated participants at weeks 0, 24, 48 and 96 (DBP), and weeks 144 and 192 (OLE), and in white matter for 23 healthy control participants at weeks 0, 48 and 96.