ACQUIRED MUTATIONS IN PATIENTS WITH RELAPSED/REFRACTORY CLL WHO PROGRESSED IN THE ALPINE STUDY.

Some CLL patients who develop progressive disease (PD) during treatment with covalent Bruton tyrosine kinase inhibitors (cBTKi) acquire pathway resistance mutations in BTK or PLCG2. Here, we report gene mutation data from paired baseline and PD peripheral blood samples from 52 patients (zanubrutinib, n=24; ibrutinib, n=28) who, at an early median follow-up time of 25.7 months, progressed on zanubrutinib or ibrutinib treatment in the ALPINE trial (NCT03734016).

Long-Term Family Needs After a Traumatic Brain Injury: A VA TBI Model Systems Study.

Objective: To describe the self-reported needs of family caregivers of service members and veterans (SMVs) with traumatic brain injury (TBI) at 10 to 15 years post-injury and to identify unique predictors of unmet family needs.

Setting: Five Department of Veterans Affairs Polytrauma Rehabilitation Centers.

Participants: A total of 209 family caregivers of SMVs with TBI from the VA TBI Model Systems national database who completed a 10- or 15-year follow-up assessment.

Interplay between the cyclophilin homology domain of RANBP2 and MX2 regulates HIV-1 capsid dependencies on nucleoporins.

Unlabelled: Interlinked interactions between the viral capsid (CA), nucleoporins (Nups), and the antiviral protein myxovirus resistance 2 (MX2/MXB) influence human immunodeficiency virus 1 (HIV-1) nuclear entry and the outcome of infection. Although RANBP2/NUP358 has been repeatedly identified as a critical player in HIV-1 nuclear import and MX2 activity, the mechanism by which RANBP2 facilitates HIV-1 infection is not well understood. To explore the interactions between MX2, the viral CA, and RANBP2, we utilized CRISPR-Cas9 to generate cell lines expressing RANBP2 from its endogenous locus but lacking the C-terminal cyclophilin (Cyp) homology domain and found that both HIV-1 and HIV-2 infections were reduced significantly in RANBP2 cells.

[Health Literacy and Metabolic Control in Individuals Diagnosed with Type 2 Diabetes Mellitus: A Cluster Randomized Clinical Trial].

Unlabelled: People with type 2 diabetes mellitus (DM2) experience difficulties in self-management. One of the variables involved is the low level of health literacy (HL) which corresponds to the degree to which people access, understand, evaluate and use information to engage with health demands in different contexts, in order to promote and maintain good health.

Hypothesis: People diagnosed with diabetes mellitus who participate in an intervention to increase their level of health literacy improve their metabolic compensation measured in HBA1c.

Increased robustness and adaptation to simultaneous temperature and elevated extracellular potassium in the pyloric rhythm of the crab, .

Animals must deal with numerous perturbations, oftentimes concurrently. In this study, we examine the effects of two perturbations, high extracellular potassium and elevated temperature, on the resilience of the pyloric rhythm of the crab, . At control temperatures (11°C), high potassium saline (2.

Biological and Social Predictors of HIV-1 RNA Viral Suppression in ART Treated PWLH in Sub-Saharan Africa.

HIV remains a significant health issue, especially in sub-Saharan Africa. There are 39 million people living with HIV (PLWH) globally. Treatment with ART improves patient outcomes by suppressing the HIV RNA viral load.

Serious Bacterial Infections and Hepatitis C Virus Among People Who Inject Drugs: A Syndemic or Intertwined Epidemics?

Limited research has examined the possible synergistic interrelationships between serious bacterial infections (SBIs) of the heart (i.e., endocarditis), bone, spine, brain, or joints (e.

Papillary Muscles of the Left Ventricle: Integrating Electrical and Mechanical Dynamics.

Background: Papillary muscles are structures integrated into the mitral valve apparatus, having both electrical and mechanical roles. The importance of the papillary muscles (PM) is mainly related to cardiac arrhythmias and mitral regurgitation. The aim of this review is to offer an overview of the anatomy and physiology of the papillary muscles, along with their involvement in cardiovascular pathologies, including arrhythmia development in various conditions and their contribution to secondary mitral regurgitation.

Aptamer-Conjugated Multi-Quantum Dot-Embedded Silica Nanoparticles for Lateral Flow Immunoassay.

Lateral flow immunoassays (LFIAs) are widely used for their low cost, simplicity, and rapid results; however, enhancing their reliability requires the meticulous selection of ligands and nanoparticles (NPs). SiO@QD@SiO (QD) nanoparticles, which consist of quantum dots (QDs) embedded in a silica (SiO) core and surrounded by an outer SiO shell, exhibit significantly higher fluorescence intensity (FI) compared to single QDs. In this study, we prepared QD@PEG@Aptamer, an aptamer conjugated with QD using succinimidyl-[(N-maleimidopropionamido)-hexaethyleneglycol]ester, which is 130 times brighter than single QDs, for detecting carbohydrate antigen (CA) 19-9 through LFIA.

Extend Plastron Longevity on Superhydrophobic Surface Using Gas Soluble and Gas Permeable Polydimethylsiloxane (PDMS).

The gas (or plastron) trapped between micro/nano-scale surface textures, such as that on superhydrophobic surfaces, is crucial for many engineering applications, including drag reduction, heat and mass transfer enhancement, anti-biofouling, anti-icing, and self-cleaning. However, the longevity of the plastron is significantly affected by gas diffusion, a process where gas molecules slowly diffuse into the ambient liquid. In this work, we demonstrated that plastron longevity could be extended using a gas-soluble and gas-permeable polydimethylsiloxane (PDMS) surface.

Tuning Wetting Properties Through Surface Geometry in the Cassie-Baxter State.

Superhydrophobic coatings are beneficial for applications like self-cleaning, anti-corrosion, and drag reduction. In this study, we investigated the impact of surface geometry on the static, dynamic, and sliding contact angles in the Cassie-Baxter state. We used fluoro-silane-treated silicon micro-post patterns fabricated via lithography as model surfaces.

Potential mechanisms of non-coding RNA regulation in Alzheimer's disease.

Alzheimer's disease, a progressively degenerative neurological disorder, is the most common cause of dementia in the elderly. While its precise etiology remains unclear, researchers have identified diverse pathological characteristics and molecular pathways associated with its progression. Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.

Dynamic Importance of Genomic and Clinical Risk for Coronary Artery Disease Over the Life Course.

Background: Earlier identification of high coronary artery disease (CAD) risk individuals may enable more effective prevention strategies. However, existing 10-year risk frameworks are ineffective at earlier identification. We sought to understand how the variable importance of genomic and clinical factors across life stages may significantly improve lifelong CAD event prediction.

Biogeographic Insights Into the Late Miocene Diversification of the Giant Deep-Ocean Amphipod .

Mechanisms driving the spatial and temporal patterns of species distribution in the Earth's largest habitat, the deep ocean, remain largely enigmatic. The late Miocene to the Pliocene (~23-2.58 Ma) is a period that was marked by significant geological, climatic, and oceanographic changes.

Effects of vitamin D supplementation on cardiac biomarkers: Results from the STURDY trial.

Objectives: In observational studies, older adults with low serum vitamin D levels are at higher risk of cardiovascular disease (CVD), but randomized trials have failed to demonstrate reduction in CVD risk from vitamin D supplementation, possibly because the doses of vitamin D supplements tested were too low. Our objective was to determine if higher doses of vitamin D supplementation reduce high-sensitivity cardiac troponin (hs-cTnI) and N-terminal pro-b-type natriuretic peptide (NT-proBNP), markers of subclinical CVD.

Methods: The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a double-blind, randomized, response-adaptive trial that tested the effects of 4 doses of vitamin D3 supplementation (200, 1000, 2000, 4000 IU/day) on fall risk among older adults with low serum 25-hydroxyvitamin D concentrations (10-29 ng/mL).

Coronavirus Disease 2019 (COVID-19) Real World Data Infrastructure: A Big-Data Resource for Study of the Impact of COVID-19 in Patient Populations With Immunocompromising Conditions.

Background: We developed a United States-based real-world data resource to better understand the continued impact of the coronavirus disease 2019 (COVID-19) pandemic on immunocompromised patients, who are typically underrepresented in prospective studies and clinical trials.

Methods: The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing de-identified HealthVerity medical and pharmacy claims data from 1 December 2018 to 31 December 2023, with severe acute respiratory syndrome coronavirus 2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and, for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and End Results registry data.

Results: The CRWDi contains 4 cohorts: patients with cancer; patients with rheumatic diseases receiving pharmacotherapy; noncancer solid organ and hematopoietic stem cell transplant recipients; and people from the general population including adults and pediatric patients.

Synthetic data in generalizable, learning-based neuroimaging.

Synthetic data have emerged as an attractive option for developing machine-learning methods in human neuroimaging, particularly in magnetic resonance imaging (MRI)-a modality where image contrast depends enormously on acquisition hardware and parameters. This retrospective paper reviews a family of recently proposed methods, based on synthetic data, for generalizable machine learning in brain MRI analysis. Central to this framework is the concept of domain randomization, which involves training neural networks on a vastly diverse array of synthetically generated images with random contrast properties.

Population Pharmacokinetics of Pegcetacoplan in Patients with Geographic Atrophy or Neovascular Age-related Macular Degeneration.

Objective: To develop a population pharmacokinetic (PK) model to characterize serum pegcetacoplan concentration-time data after intravitreal administration in patients with geographic atrophy (GA) or neovascular age-related macular degeneration (nAMD).

Design: Pharmacokinetic modeling.

Participants: Two hundred sixty-one patients with GA or nAMD enrolled in 4 clinical studies of pegcetacoplan.

Machine learning for antimicrobial peptide identification and design.

Artificial intelligence (AI) and machine learning (ML) models are being deployed in many domains of society and have recently reached the field of drug discovery. Given the increasing prevalence of antimicrobial resistance, as well as the challenges intrinsic to antibiotic development, there is an urgent need to accelerate the design of new antimicrobial therapies. Antimicrobial peptides (AMPs) are therapeutic agents for treating bacterial infections, but their translation into the clinic has been slow owing to toxicity, poor stability, limited cellular penetration and high cost, among other issues.

Integrated SegFlow, µSIA, and UPLC for Online Sialic Acid Quantitation of Glycoproteins Directly from Bioreactors.

This study emphasizes the critical importance of closely monitoring and controlling the sialic acid content in therapeutic glycoproteins, including EPO, interferon-γ, Orencia, Enbrel, and others, as the level of sialylation directly impacts their pharmacokinetics (PK), immunogenicity, potency, and overall clinical performance due to its influence on protein clearance via hepatic asialoglycoprotein receptors (ASGPR). The ASGPR recognizes and binds to glycoproteins exposed to terminal galactose or N-acetylgalactosamine residues, leading to receptor-mediated endocytosis. Recent studies have demonstrated that sialylation of O-linked glycan plays a role in protecting against macrophage galactose lectin (MGL)-mediated clearance.

Impaired Visuospatial Processing in Cerebral Visual Impairment Revealed by Performance on a Conjunction Visual Search Task.

Cerebral visual impairment (CVI) is a brain-based visual disorder associated with injury and/or maldevelopment of central visual pathways. Visuospatial processing impairments are a cardinal feature of the complex clinical profile of individuals with CVI. Here, we assessed visuospatial processing abilities using a classic conjunction search task.

Incremental Cost-Effectiveness Ratios (ICERs) and Revised Metformin Cost-Effectiveness Conclusions in the Diabetes Prevention Program/ Diabetes Prevention Program Outcomes Study.

Based on previously published US Diabetes Prevention Program (DPP) cost-effectiveness analyses (CEAs), metformin continues to be promoted as "cost-effective." We reviewed a 10-year CEA to assess this. Treatment alternatives included placebo, branded metformin and individual lifestyle modification.

Age- and sex-specific care cascades to detect gaps in the care of children with tuberculosis in Bangladesh: a cohort study.

Background: Programmatic interventions to increase the detection of children with tuberculosis (TB) are rarely evaluated to understand age- and sex-specific completion rates. We applied modified TB screening and treatment cascade frameworks to assess indicators of effective implementation by age and sex of a TB screening program for children (zero to 14 years) in Bangladesh.

Methods: We implemented an intensified screening program for paediatric TB detection in 119 health care facilities (2018-21).

Reinforcement Learning is Impaired in the Sub-acute Post-stroke Period.

Background: In humans, most spontaneous recovery from motor impairment after stroke occurs in the first 3 months. Studies in animal models show higher responsiveness to training over a similar time-period. Both phenomena are often attributed to a milieu of heightened plasticity, which may share some mechanistic overlap with plasticity associated with normal motor learning.