Actigraphy-based assessment of circadian rhythmicity and sleep in patients with Usher syndrome type 2a: A case-control study.

This study aimed to improve our understanding of sleep problems as a comorbidity of hereditary deaf-blindness due to Usher syndrome type 2a. Fifteen patients with Usher syndrome type 2a with a conclusive genetic diagnosis and 15 unaffected controls participated in comprehensive sleep and activity assessments for 2 weeks, using the MotionWatch 8 actigraph and consensus sleep diary. Various sleep parameters including sleep opportunity window, sleep latency, sleep efficiency, and self-reported sleep quality were analysed.

Do emergency Medicaid programs improve post-discharge health care access for trauma patients? A statewide mixed-methods study.

Background: Hospital presumptive eligibility (HPE) emergency Medicaid programs offset patient bills at hospitalization and can provide long-term Medicaid coverage. We characterized postdischarge outpatient health care utilization among HPE Medicaid trauma patients and identified patient access facilitators and barriers once newly insured. We hypothesized utilization would be increased among HPE trauma patients compared with other HPE patients, but that challenges in access to care would remain.

Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus that causes severe respiratory illness in humans. There are no licensed vaccines against MERS-CoV and only a few candidates in phase I clinical trials. Here, we develop MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Integrating cardiovascular risk assessment into mobile low-dose CT lung screenings in rural Appalachia: A comprehensive analysis of the relationship between lung cancer risk, coronary artery calcium burden, and cardiovascular risk reduction strategies.

Objective: Mobile low-dose computed tomography (LDCT) lung screenings are part of an outreach program in rural Appalachia to detect early lung cancer. Coronary artery calcium (CAC) scoring on LDCT can identify calcium deposits in coronary arteries and can prompt consideration of risk modification for prevention of cardiovascular disease (CVD) events. It is not known if Lung CT Screening Reporting & Data System (Lung-RADS) scoring correlates with CAC scores.

Computationally designed mRNA-launched protein nanoparticle vaccines.

Both protein nanoparticle and mRNA vaccines were clinically de-risked during the COVID-19 pandemic. These vaccine modalities have complementary strengths: antigen display on protein nanoparticles can enhance the magnitude, quality, and durability of antibody responses, while mRNA vaccines can be rapidly manufactured and elicit antigen-specific CD4 and CD8 T cells. Here we leverage a computationally designed icosahedral protein nanoparticle that was redesigned for optimal secretion from eukaryotic cells to develop an mRNA-launched nanoparticle vaccine for SARS-CoV-2.

RNA Sequencing Experimental Analysis Workflow Using Caenorhabditis elegans.

RNA sequencing is an approach to transcriptomic profiling that enables the detection of differentially expressed genes in response to genetic mutation or experimental treatment, among other uses. Here we describe a method for the use of a customizable, user-friendly bioinformatic pipeline to identify differentially expressed genes in RNA sequencing data obtained from C. elegans, with attention to the improvement in reproducibility and accuracy of results.

Quantifying abnormal alveolar microstructure in cystic fibrosis lung disease via hyperpolarized Xe diffusion MRI.

Rationale: Cystic Fibrosis (CF) progresses through recurrent infection and inflammation, causing permanent lung function loss and airway remodeling. CT scans reveal abnormally low-density lung parenchyma in CF, but its microstructural nature remains insufficiently explored due to clinical CT limitations. To this end, diffusion-weighted Xe MRI is a non-invasive and validated measure of lung microstructure.

Multi-omics analysis reveals drivers of loss of β-cell function after newly diagnosed autoimmune type 1 diabetes: An INNODIA multicenter study.

Aims: Heterogeneity in the rate of β-cell loss in newly diagnosed type 1 diabetes patients is poorly understood and creates a barrier to designing and interpreting disease-modifying clinical trials. Integrative analyses of baseline multi-omics data obtained after the diagnosis of type 1 diabetes may provide mechanistic insight into the diverse rates of disease progression after type 1 diabetes diagnosis.

Methods: We collected samples in a pan-European consortium that enabled the concerted analysis of five different omics modalities in data from 97 newly diagnosed patients.

Pulsed electric field effect on acrylamide reduction and quality attributes of continuous-style Lamoka potato chips.

Potato chips are a popular snack, well-liked because of their texture-flavor combination. Potato chips are made by frying slices of potato in vegetable oil to achieve a crispy texture. Frying potato slices initiates the Maillard reaction, resulting in chemical changes that enhance taste, color, and texture, but also undesired acrylamides, which are suspected carcinogens.

Biocatalytic Strategy for the Highly Stereoselective Synthesis of Fluorinated Cyclopropanes.

Fluorinated cyclopropanes are highly desired pharmacophores in drug discovery owing to the rigid nature of the cyclopropane ring and the beneficial effects of C-F bonds on the pharmacokinetic properties, cell permeability, and metabolic stability of drug molecules. Herein a biocatalytic strategy for the stereoselective synthesis of mono-fluorinated and gem-difluoro cyclopropanes is reported though the use of engineered myoglobin-based catalysts. In particular, this system allows for a broad range of gem-difluoro alkenes to be cyclopropanated in the presence of diazoacetonitrile with excellent diastereo and enantiocontrol (up to 99 : 1 d.

Long-term efficacy of a 2-year MRI treat-to-target strategy on disease activity and radiographic progression in patients with rheumatoid arthritis in clinical remission: 5-year follow-up of the IMAGINE-RA randomised trial.

Objective: To investigate whether a 2-year MRI treat-to-target strategy targeting the absence of osteitis combined with clinical remission, compared with a conventional treat-to-target strategy targeting clinical remission only (IMAGINE-rheumatoid arthritis (RA) trial) improves clinical and radiographic outcomes over 5 years in patients with RA in clinical remission.

Methods: IMAGINE-more was an observational extension study of the original 2-year IMAGINE-RA randomised trial (NCT01656278). Clinical examinations and radiographs (hands and feet) were obtained yearly.

Mental health, chronic and infectious conditions among pregnant persons in US state prisons and local jails 2016-2017.

Background: Pregnant individuals in incarcerated settings have unique healthcare needs. Rates of mental health, infectious diseases, and chronic disease are higher among nonpregnant incarcerated women compared with those who are not, but the prevalence of these conditions among pregnant people in custody has not been documented.

Objectives: The objective of this study is to describe the prevalence of metabolic, infectious, and mental health conditions in pregnant people to identify the medical needs of high-risk pregnancies in US state prisons and local jails.

Impact of Nicotine Replacement Therapy Sampling on Cessation-Related Processes.

Objectives: Smoking prevalence remains high among low-income smokers. Understanding processes (eg, withdrawal, craving, motivation) in early smoking cessation is crucially important for designing effective interventions for this population.

Methods: This is a secondary analysis of a novel, in-session sampling intervention (ie, In Vivo) as compared with standard care behavioral smoking cessation counseling (SC) among community-dwelling low-income smokers (n = 83).

Anti-TIGIT antibody improves PD-L1 blockade through myeloid and T cells.

Tiragolumab, an anti-TIGIT antibody with an active IgG1κ Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (ClinicalTrials.gov: NCT03563716 ) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone. However, there remains little consensus on the mechanism(s) of response with this combination.

Central Nervous System Antimicrobial Exposure and Proposed Dosing for Anthrax Meningitis.

Background: The high mortality of systemic anthrax is likely a consequence of the severe central nervous system inflammation that occurs in anthrax meningitis. Effective treatment of such infections requires, at a minimum, adequate cerebrospinal fluid (CSF) antimicrobial concentrations.

Methods: We reviewed English medical literature and regulatory documents to extract information on serum and CSF exposures for antimicrobials with in vitro activity against Bacillus anthracis.

Pharmacokinetics (PK) of Tiragolumab in First-in-Human Study in Patients with Mixed Solid Tumors (GO30103).

Tiragolumab is a first-in-class, fully human IgG1/kappa anti-TIGIT monoclonal antibody that blocks the binding of TIGIT to CD155 (the poliovirus receptor). We summarize the pharmacokinetics (PK) data from the phase 1a/1b GO30103 study of Q3W (every 3 weeks) sequential dosing of tiragolumab (2, 8, 30, 100, 400, 600, or 1200 mg) followed by atezolizumab (1200 mg), Q4W (every 4 weeks) sequential dosing (tiragolumab 840 mg followed by atezolizumab 1680 mg), and Q4W co-infusion (tiragolumab 840 mg plus atezolizumab 1680 mg). Serum samples were collected at multiple time points following tiragolumab and atezolizumab intravenous infusion in patients with solid tumors for PK and immunogenicity assessment.

Deletion of the Candida albicans TLO gene family using CRISPR-Cas9 mutagenesis allows characterisation of functional differences in α-, β- and γ- TLO gene function.

The Candida albicans genome contains between ten and fifteen distinct TLO genes that all encode a Med2 subunit of Mediator. In order to investigate the biological role of Med2/Tlo in C. albicans we deleted all fourteen TLO genes using CRISPR-Cas9 mutagenesis.

The speed and acceleration of the ball carrier and tackler into contact during front-on tackles in rugby league.

The aim was to use a combination of video analysis and microtechnology (10 Hz global positioning system [GPS]) to quantify and compare the speed and acceleration of ball-carriers and tacklers during the pre-contact phase (contact - 0.5s) of the tackle event during rugby league match-play. Data were collected from 44 professional male rugby league players from two Super League clubs across two competitive matches.

A Novel Metric "Exercise Cardiac Load" Proposed to Track and Predict the Deterioration of the Autonomic Nervous System in Division I Football Athletes.

Current metrics like baseline heart rate (HR) and HR recovery fail in predicting overtraining (OT), a syndrome manifesting from a deteriorating autonomic nervous system (ANS). Preventing OT requires tracking the influence of internal physiological loads induced by exercise training programs on the ANS. Therefore, this study evaluated the predictability of a novel, exercise cardiac load metric on the deterioration of the ANS.