clonevdjseq: A workflow and bioinformatics management system for sequencing, archiving, and analysis of VDJ sequences from clonal libraries.

Background: Advances in next-generation sequencing technologies have facilitated extensive analysis of B cell and T cell receptor (BCR/TCR, respectively) sequences from monoclonal hybridoma libraries, single B cells, and single T cells, generating vast amounts of important data pertaining to antigen recognition. However, existing workflows and bioinformatics tools often lack the flexibility and scalability needed to handle large clonal level datasets effectively. An initial system and hybridoma dependent version of this code was distributed as part of the NeuroMabSeq publication, but clonevdjseq aims to be a technical addendum for broader system compatibility and enhanced modeling.

Resonance broadening effects of weak turbulence on Earth's radiation belt electrons.

The quasilinear diffusion theory is generalized to include the resonance broadening effect of weak turbulence on relativistic electrons in Earth's radiation belts. In contrast with quasilinear resonant diffusion, in which cases the resonant condition should be rigorously satisfied, the second-order theory demonstrates that the wave-driven scattering of relativistic electrons could be broadened into an area of velocity space adjacent to the resonant region. It is shown that a finite departure time, resulted from the second-order wave-particle interaction, is the key factor controlling the occurrence and effectiveness of such a resonance broadening.

Histone Deacetylase Inhibitor Largazole Deactivates A Subset of Superenchancers and Causes Mitotic Chromosome Mis-alignment by Suppressing SP1 and BRD4.

Histone deacetylase inhibitors have been investigated as potential therapeutic agents for cancer and other diseases. HDIs are known to promote histone acetylation, resulting in an open chromatin conformation and generally increased gene expression. In previous work, we reported that a subset of genes, particularly those regulated by superenhancers, can be suppressed by the HDAC inhibitor largazole.

Mediator kinase inhibition suppresses hyperactive interferon signaling in Down syndrome.

Hyperactive interferon (IFN) signaling is a hallmark of Down syndrome (DS), a condition caused by Trisomy 21 (T21); strategies that normalize IFN signaling could benefit this population. Mediator-associated kinases CDK8 and CDK19 drive inflammatory responses through incompletely understood mechanisms. Using sibling-matched cell lines with/without T21, we investigated Mediator kinase function in the context of hyperactive IFN in DS over a 75 min to 24 hr timeframe.

Comparative genomic analysis identifies potential adaptive variation in .

is associated with respiratory disease in wild and domestic Caprinae globally, with wide variation in disease outcomes within and between host species. To gain insight into phylogenetic structure and mechanisms of pathogenicity for this bacterial species, we compared genomes for 99 samples from 6 countries (Australia, Bosnia and Herzegovina, Brazil, China, France and USA) and 4 host species (domestic sheep, domestic goats, bighorn sheep and caribou). Core genome sequences of assemblies from domestic sheep and goats fell into two well-supported phylogenetic clades that are divergent enough to be considered different bacterial species, consistent with each of these two clades having an evolutionary origin in separate host species.

Diroximel Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: NEDA-3 After Re-Baselining in the Phase 3 EVOLVE-MS-1 Study.

Introduction: Diroximel fumarate (DRF) and dimethyl fumarate (DMF) are orally administered fumarate disease-modifying therapies (DMTs) for multiple sclerosis (MS). The safety, tolerability, and exploratory efficacy of DRF were evaluated in the phase 3 EVOLVE-MS-1 study. No Evidence of Disease Activity (NEDA-3) is a composite efficacy endpoint used in clinical trials for MS defined as no relapse, no 24-week confirmed disability progression (CDP), no new/newly enlarging T2 lesions, and no new gadolinium-enhancing lesions.

Thalamic atrophy and dysconnectivity are associated with cognitive impairment in a multi-center, clinical routine, real-word study of people with relapsing-remitting multiple sclerosis.

Background: Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient.

Objective: To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting.

Creativity training needs assessment for homeland security enterprise: a case for creative thinking.

Creativity, specifically creative problem solving, is often excluded from Homeland Security Enterprise efforts to train and develop their workforces. To determine if this lack of training was a key knowledge gap in the communities, we drew on organisational creativity literature. Using the personnel databases O*NET and Careers in the Military Database, we conducted a training needs assessment by identifying relevant job tasks, knowledge, skills, and abilities (KSA) that align with the creative process.

Transcription dosage compensation does not occur in Down syndrome.

Background: The increase in DNA copy number in Down syndrome (DS; caused by trisomy 21) has led to the DNA dosage hypothesis, which posits that the level of gene expression is proportional to the gene's DNA copy number. Yet many reports have suggested that a proportion of chromosome 21 genes are dosage compensated back towards typical expression levels (1.0×).

High-volume hybridoma sequencing on the NeuroMabSeq platform enables efficient generation of recombinant monoclonal antibodies and scFvs for neuroscience research.

The Neuroscience Monoclonal Antibody Sequencing Initiative (NeuroMabSeq) is a concerted effort to determine and make publicly available hybridoma-derived sequences of monoclonal antibodies (mAbs) valuable to neuroscience research. Over 30 years of research and development efforts including those at the UC Davis/NIH NeuroMab Facility have resulted in the generation of a large collection of mouse mAbs validated for neuroscience research. To enhance dissemination and increase the utility of this valuable resource, we applied a high-throughput DNA sequencing approach to determine immunoglobulin heavy and light chain variable domain sequences from source hybridoma cells.

Long wavelength-sensing cones of zebrafish retina exhibit multiple layers of transcriptional heterogeneity.

Introduction: Understanding how photoreceptor genes are regulated is important for investigating retinal development and disease. While much is known about gene regulation in cones, the mechanism by which tandemly-replicated opsins, such as human long wavelength-sensitive and middle wavelength-sensitive opsins, are differentially regulated remains elusive. In this study, we aimed to further our understanding of transcriptional heterogeneity in cones that express tandemly-replicated opsins and the regulation of such differential expression using zebrafish, which express the tandemly-replicated opsins and .

Mediator kinase inhibition suppresses hyperactive interferon signaling in Down syndrome.

Hyperactive interferon (IFN) signaling is a hallmark of Down syndrome (DS), a condition caused by trisomy 21 (T21); strategies that normalize IFN signaling could benefit this population. Mediator-associated kinases CDK8 and CDK19 drive inflammatory responses through incompletely understood mechanisms. Using sibling-matched cell lines with/without T21, we investigated Mediator kinase function in the context of hyperactive IFN in DS over a 75min - 24h timeframe.

NeuroMabSeq: high volume acquisition, processing, and curation of hybridoma sequences and their use in generating recombinant monoclonal antibodies and scFvs for neuroscience research.

The Neuroscience Monoclonal Antibody Sequencing Initiative (NeuroMabSeq) is a concerted effort to determine and make publicly available hybridoma-derived sequences of monoclonal antibodies (mAbs) valuable to neuroscience research. Over 30 years of research and development efforts including those at the UC Davis/NIH NeuroMab Facility have resulted in the generation of a large collection of mouse mAbs validated for neuroscience research. To enhance dissemination and increase the utility of this valuable resource, we applied a high-throughput DNA sequencing approach to determine immunoglobulin heavy and light chain variable domain sequences from source hybridoma cells.

Transcription dosage compensation does not occur in Down syndrome.

Background: Trisomy 21, also known as Down syndrome, describes the genetic condition of having an extra copy of chromosome 21. The increase in DNA copy number has led to the "DNA dosage hypothesis", which claims that the level of gene transcription is proportional to the gene's DNA copy number. Yet many reports have suggested that a proportion of chromosome 21 genes are dosage compensated back towards typical expression levels (1.

Arbaclofen extended-release tablets for spasticity in multiple sclerosis: open-label extension study.

Baclofen, a racemic γ-aminobutyric acid B receptor agonist, is commonly used for the management of multiple sclerosis-related spasticity but is associated with frequent dosing and poor tolerability. Arbaclofen, the active R-enantiomer of baclofen, exhibits 100- to 1000-fold greater specificity for the γ-aminobutyric acid B receptor compared with the S-enantiomer and ∼5-fold greater potency compared with racemic baclofen. Arbaclofen extended-release tablets allow a dosing interval of 12 h and have shown a favourable safety and efficacy profile in early clinical development.

Does point-of-care ultrasonography improve diagnostic accuracy in emergency department patients with undifferentiated hypotension? An international randomized controlled trial from the SHOC-ED investigators.

Purpose: Point-of-care ultrasonography (POCUS) is an established tool in the management of hypotensive patients in the emergency department (ED). We compared the diagnostic accuracy of a POCUS protocol versus standard assessment without POCUS in patients with undifferentiated hypotension.

Methods: This was an international, multicenter randomized controlled trial included three EDs in North America and three in South Africa from September 2012 to December 2016.

Arbaclofen extended-release tablets for spasticity in multiple sclerosis: randomized, controlled clinical trial.

Baclofen, a racemic GABA-B (GABA) receptor agonist, is commonly used for the management of multiple sclerosis-related spasticity but is associated with frequent dosing and poor tolerability. Arbaclofen, the active R-enantiomer of baclofen, exhibits 100- to 1000-fold greater specificity for the GABA receptor compared with the S-enantiomer and ∼5-fold greater potency compared with racemic baclofen. Arbaclofen extended-release tablets have a dosing interval of 12 hours and have shown a favourable safety and efficacy profile in early-phase clinical development.

Satisfaction with alemtuzumab in relapsing multiple sclerosis patients: Results from the real-world PRO-ACT study.

Background: Patient-reported outcomes are increasingly used in the management of patients with multiple sclerosis to understand the patient's perspective of disease and treatment. These measures provide insights into important factors including treatment satisfaction, physical and psychological function, and quality of life.

Objective: To present results from the real-world PRO-ACT study in patients with multiple sclerosis who switched to alemtuzumab from another disease-modifying therapy.

Non-diabetic fetal macrosomia: outcomes of elective delivery versus expectant management.

Background: Macrosomia in the absence of diabetes can be associated with increased neonatal and maternal morbidity. Management is usually undertaken on a case-by-case basis.

Aims: In order to inform local practice, this study aimed to evaluate the outcomes of the management of non-diabetic macrosomia in an Irish tertiary center.

A retrospective cohort study of pregnancy outcomes during the pandemic period of the SARS-CoV-2 omicron variant: A single center's experience.

Our retrospective review revealed that antenatal infection with the Omicron variant is associated with minimal symptoms in vaccinated patients, minimal medical intervention, and good obstetric outcomes.

Protocol variations in run-on transcription dataset preparation produce detectable signatures in sequencing libraries.

Background: A variety of protocols exist for producing whole genome run-on transcription datasets. However, little is known about how differences between these protocols affect the signal within the resulting libraries.

Results: Using run-on transcription datasets generated from the same biological system, we show that a variety of GRO- and PRO-seq preparation methods leave identifiable signatures within each library.

Efficacy and Safety Outcomes with Diroximel Fumarate After Switching from Prior Therapies or Continuing on DRF: Results from the Phase 3 EVOLVE-MS-1 Study.

Introduction: Diroximel fumarate (DRF) is an oral fumarate for relapsing multiple sclerosis (MS) with the same active metabolite as dimethyl fumarate (DMF). DRF has a safety/efficacy profile similar to DMF but with improved gastrointestinal (GI) tolerability and low (< 1%) treatment discontinuation due to GI adverse events (AEs). Efficacy and safety outcomes in patients who switched to DRF from other disease-modifying therapies (DMTs) have not been evaluated.

Delayed extubation in spine surgery is associated with increased postoperative complications and hospital episode-based resource utilization.

Study Objective: To elucidate the association between delayed extubation, postoperative complications, and episode-based resource utilization.

Design: Retrospective Propensity-Matched Cohort Study.

Setting: Single Large Academic Medical Center.