Risk-Benefit Analysis of Novel Treatments for Patients with Generalized Myasthenia Gravis.

Introduction: This study used network meta-analysis (NMA) to inform and compare the number needed to treat (NNT), number needed to harm (NNH), and cost per improved outcome (CPIO) associated with more recently approved treatments for anti-acetylcholine receptor antibody-positive (anti-AChR Ab+) generalized myasthenia gravis (gMG).

Methods: Clinical trials of neonatal Fc receptor (FcRn) inhibitors, efgartigimod intravenous (IV) and rozanolixizumab, and complement inhibitors, ravulizumab and zilucoplan, versus placebo (with background conventional treatment) were included in the primary NMA to compare efficacy and safety outcomes. The outputs from the NMAs were used to estimate NNT and NNH of each treatment versus placebo.

The spleen assumes a major role in blood glucose regulation in type 1 diabetes patients treated with BCG.

The Bacillus Calmette-Guérin (BCG) vaccine, which has been used for > 100 years to prevent tuberculosis, is well-established for bladder cancer treatment, and under study for neurological and autoimmune diseases. In patients with type 1 diabetes (T1D), BCG vaccinations have been shown in randomized clinical trials to gradually lower blood sugar to near normal levels. This effect appears to be driven by a BCG-induced shift in lymphoid cells' glucose metabolism from oxidative phosphorylation to aerobic glycolysis.

Psychometric properties of MG-ADL items and MG-ADL score: An assessment of distributional characteristics, validity and factor structure in two large datasets.

Background: The Myasthenia Gravis-Activities of Daily Living scale (MG-ADL) is an 8-item outcome measure to assess symptoms and functional limitations in myasthenia gravis (MG) patients. The MG-ADL score is an equally weighted level sum score that is used as primary outcome measures in clinical trials, in clinical practice, and as an end-point in health economic evaluation. This data analysis aims to obtain detailed knowledge of measurement properties of MG-ADL items and the MG-ADL score.

Late in the US pandemic, multi-dose BCG vaccines protect against COVID-19 and infectious diseases.

The Bacillus Calmette-Guérin vaccine has many off-target benefits, including protection from diverse infectious diseases. As SARS-CoV-2 evolved, COVID-19 disease became more transmissible and less lethal. In this Phase III double-blinded, placebo-controlled trial conducted late in the pandemic, we tested at-risk US adults with type 1 diabetes if multi-dose BCG protected against COVID-19 and other infectious disease, co-primary outcomes.

Morphology, behavior, and phylogenomics of Oxytoxum lohmannii, Dinoflagellata.

Dinoflagellates are an abundant and diverse group of protists representing a wealth of unique biology and ecology. While many dinoflagellates are photosynthetic or mixotrophic, many taxa are heterotrophs, often with complex feeding strategies. Compared to their photosynthetic counterparts, heterotrophic dinoflagellates remain understudied, as they are difficult to culture.

Trends and Disparities in the Utilization of Thymectomy for Myasthenia Gravis in the United States.

Background And Objectives: In 2016, a randomized controlled trial demonstrated the clinical efficacy of trans-sternal thymectomy for patients with non-thymomatous myasthenia gravis (MG). Whether large-scale changes occurred in clinical practice after this trial is unknown.

Methods: We performed a retrospective longitudinal cross-sectional analysis using National Inpatient Sample (NIS) data from 2012 to 2019.

Does Surgical Removal of the Thymus Have Deleterious Consequences?

The role of immunosenescence, particularly the natural process of thymic involution during aging, is increasingly acknowledged as a factor contributing to the development of autoimmune diseases and cancer. Recently, a concern has been raised about deleterious consequences of the surgical removal of thymic tissue, including for patients who undergo thymectomy for myasthenia gravis (MG) or resection of a thymoma. This review adopts a multidisciplinary approach to scrutinize the evidence concerning the long-term risks of cancer and autoimmunity postthymectomy.

Effect of Lower Extremity Nerve Decompression in Patients With Painful Diabetic Peripheral Neuropathy: The Diabetic Neuropathy Nerve Decompression Randomized, Observation Group and Placebo Surgery-Controlled Clinical Trial.

Objective: To evaluate the effect of nerve decompression on pain in patients with lower extremity painful diabetic peripheral neuropathy (DPN).

Background: Currently, no treatment provides lasting relief for patients with DPN. The benefits of nerve decompression remain inconclusive.

ColabFit exchange: Open-access datasets for data-driven interatomic potentials.

Data-driven interatomic potentials (IPs) trained on large collections of first principles calculations are rapidly becoming essential tools in the fields of computational materials science and chemistry for performing atomic-scale simulations. Despite this, apart from a few notable exceptions, there is a distinct lack of well-organized, public datasets in common formats available for use with IP development. This deficiency precludes the research community from implementing widespread benchmarking, which is essential for gaining insight into model performance and transferability, and also limits the development of more general, or even universal, IPs.

Serum metabolomics of treatment response in myasthenia gravis.

Objective: High-dose prednisone use, lasting several months or longer, is the primary initial therapy for myasthenia gravis (MG). Upwards of a third of patients do not respond to treatment. Currently no biomarkers can predict clinical responsiveness to corticosteroid treatment.

An observation-based, reduced-form model for oxidation in the remote marine troposphere.

The hydroxyl radical (OH) fuels atmospheric chemical cycling as the main sink for methane and a driver of the formation and loss of many air pollutants, but direct OH observations are sparse. We develop and evaluate an observation-based proxy for short-term, spatial variations in OH (Proxy) in the remote marine troposphere using comprehensive measurements from the NASA Atmospheric Tomography (ATom) airborne campaign. Proxy is a reduced form of the OH steady-state equation representing the dominant OH production and loss pathways in the remote marine troposphere, according to box model simulations of OH constrained with ATom observations.

Attitudes and Beliefs Toward Thymectomy in the Myasthenia Gravis Patient Registry.

Objectives: To evaluate patient attitudes and beliefs toward thymectomy for myasthenia gravis (MG).

Methods: The Myasthenia Gravis Foundation of America administered a questionnaire to the MG Patient Registry, an ongoing longitudinal survey of adult MG patients. Questions assessed reasons for or against thymectomy and how hypothetical scenarios would have affected their decision.

Quality of Life in Digital Device Users Who are Treated with Systane Hydration PF.

Purpose: To understand the impact of Systane Hydration PF on dryness symptoms and quality of life in digital device users and to determine if participants prefer either the unit-dose or multi-dose dispensing system of Systane Hydration PF.

Materials And Methods: This 2-week, three visit study recruited regular digital device users. Participants were required to score ≤80 on the Impact of Dry Eye on Everyday Life (IDEEL) Quality of Life (QoL) Work domain and between 13 and 32 on the Ocular Surface Disease Index (OSDI) questionnaire.

Metabolic and bariatric surgery for obesity in Prader Willi syndrome: systematic review and meta-analysis.

Obesity is the leading cause of morbidity and mortality in patients with Prader-Willi Syndrome (PWS). Our objective was to compare changes in body mass index (BMI) after metabolic and bariatric surgery (MBS) for the treatment of obesity (BMI ≥35 kg/m) in PWS. A systematic review of MBS in PWS was performed using PubMed, Embase, and Cochrane Central, identifying 254 citations.

Phase 2 trial in acetylcholine receptor antibody-positive myasthenia gravis of transition from intravenous to subcutaneous immunoglobulin: The MGSCIg study.

Background And Purpose: Data on maintenance therapy with subcutaneous immunoglobulin (SCIg) in myasthenia gravis (MG) are limited. We report on transitioning acetylcholine receptor (AChR) antibody-positive (Ab+) MG patients on stable intravenous immunoglobulin (IVIg) regimens as part of routine clinical care to SCIg 1:1.2.

Reproductive and developmental toxicology studies of iminosugar UV-4.

UV-4 (N-(9-methoxynonyl)-1-deoxynojirimycin) is a host-targeted antiviral agent, which targets mammalian proteins (endoplasmic reticulum glucosidases) rather than virally encoded proteins. This mechanism confers both broad-spectrum activity and low potential for generation of viral drug resistance mutations. Reproductive and developmental studies of UV-4 evaluated effects on fertility and early embryonic development in rats, embryo-fetal development in rats and rabbits, and pre- and postnatal development including maternal function in rats.

Multiple BCG vaccinations for the prevention of COVID-19 and other infectious diseases in type 1 diabetes.

There is a need for safe and effective platform vaccines to protect against coronavirus disease 2019 (COVID-19) and other infectious diseases. In this randomized, double-blinded, placebo-controlled phase 2/3 trial, we evaluate the safety and efficacy of a multi-dose Bacillus Calmette-Guérin (BCG) vaccine for the prevention of COVID-19 and other infectious disease in a COVID-19-unvaccinated, at-risk-community-based cohort. The at-risk population is made of up of adults with type 1 diabetes.

Evaluating the Impact of Chemical Complexity and Horizontal Resolution on Tropospheric Ozone Over the Conterminous US With a Global Variable Resolution Chemistry Model.

A new configuration of the Community Earth System Model (CESM)/Community Atmosphere Model with full chemistry (CAM-chem) supporting the capability of horizontal mesh refinement through the use of the spectral element (SE) dynamical core is developed and called CESM/CAM-chem-SE. Horizontal mesh refinement in CESM/CAM-chem-SE is unique and novel in that pollutants such as ozone are accurately represented at human exposure relevant scales while also directly including global feedbacks. CESM/CAM-chem-SE with mesh refinement down to ∼14 km over the conterminous US (CONUS) is the beginning of the Multi-Scale Infrastructure for Chemistry and Aerosols (MUSICAv0).

Investigational New Drug Enabling Nonclinical Safety Assessment of the Iminosugar UV-4, a Broad-Spectrum Host-Targeted Antiviral Agent.

The iminosugar UV-4 is a broad-spectrum antiviral drug candidate with activity and against multiple, diverse viruses. The toxicological profile of UV-4, dosed as the hydrochloride salt, was evaluated in single-dose and repeat-dose oral toxicity studies in mice, rats, dogs, and non-human primates (NHP). No moribundity or deaths were associated with the drug up to the maximum tolerated dose.

Investigational New Drug Enabling Nonclinical Safety Pharmacology Assessment of the Iminosugar UV-4, a Broad-Spectrum Host-Targeted Antiviral Agent.

UV-4 (N-(9-methoxynonyl)-1-deoxynojirimycin) is a broad-spectrum antiviral drug candidate with demonstrated activity in vitro and in vivo against multiple, diverse viruses. Nonclinical safety pharmacology studies were conducted to support the filing of an Investigational New Drug (IND) application. Preliminary in vitro pharmacology testing evaluating potential for binding to "off-target" receptors and enzymes indicated no significant liability for advanced development of UV-4.

Ozone chemistry in western U.S. wildfire plumes.

Wildfires are a substantial but poorly quantified source of tropospheric ozone (O). Here, to investigate the highly variable O chemistry in wildfire plumes, we exploit the in situ chemical characterization of western wildfires during the FIREX-AQ flight campaign and show that O production can be predicted as a function of experimentally constrained OH exposure, volatile organic compound (VOC) reactivity, and the fate of peroxy radicals. The O chemistry exhibits rapid transition in chemical regimes.

Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study.

Objective: To determine whether rituximab is safe and potentially beneficial, warranting further investigation in an efficacy trial for acetylcholine receptor antibody-positive generalized MG (AChR-Ab+ gMG).

Methods: The B-Cell Targeted Treatment in MG (BeatMG) study was a randomized, double-blind, placebo-controlled, multicenter phase-2 trial that utilized a futility design. Individuals 21-90 years of age, with AChR-Ab+ gMG (MG Foundation of America Class II-IV) and receiving prednisone ≥15 mg/day were eligible.