Duvelisib is a novel NFAT inhibitor that mitigates adalimumab-induced immunogenicity.

Introduction: TNFα inhibitor (TNFi) immunogenicity in rheumatoid arthritis (RA) is a major obstacle to its therapeutic effectiveness. Although methotrexate (MTX) can mitigate TNFi immunogenicity, its adverse effects necessitate alternative strategies. Targeting nuclear factor of activated T cells (NFAT) transcription factors may protect against biologic immunogenicity.

The Role of Sex and Gender in Acute Kidney Injury - Consensus Statements from the 33 Acute Disease Quality Initiative.

Sex differences exist in acute kidney injury (AKI), and the role that sex and gender play along the AKI care continuum remains unclear. The 33 Acute Disease Quality Initiative meeting evaluated available data on the role of sex and gender in AKI and identified knowledge gaps. Data from experimental models, pathophysiology, epidemiology, clinical care, gender, social determinants of health, education, and advocacy were reviewed.

Pharmacogenetics: Opportunities for the Research Program and Other Large Data Sets to Advance the Field.

Pharmacogenetic variation is common and an established driver of response for many drugs. There has been tremendous progress in pharmacogenetics knowledge over the last 30 years and in clinical implementation of that knowledge over the last 15 years. But there have also been many examples where translation has stalled because of the lack of available data sets for discovery or validation research.

Use of Potentially Nephrotoxic Drugs in Type 2 Diabetes Patients on SGLT2i: A Trajectories Analysis.

Purpose: To characterize trajectories of nephrotoxic potential (NxP) drug use among older adults with Type 2 Diabetes (T2D) treated with SGLT2is and identify associated patient characteristics.

Methods: Using 2012-2019 Medicare data, we selected patients with T2D who filled at least one prescription for SGLT2is. Index date was the date of the first SGLT2i prescription filled.

Exploring the association between sleep quality, internet addiction, and related factors among adolescents in Dakshinkali Municipality, Nepal.

Background: Poor sleep quality and internet addiction are significant issues affecting adolescents globally, and Nepal is no exception. Several studies have independently assessed the prevalence and associated factors of poor sleep quality and internet addiction among Nepali adolescents and youth, but the relationship between sleep-related attributes and internet addiction remains unexplored. This study aimed to explore the prevalence and contributing factors of poor sleep quality and internet addiction along with the relationship between sleep quality-related attributes and internet addiction.

Phase I trial of ATR inhibitor elimusertib with FOLFIRI in advanced or metastatic gastrointestinal malignancies (ETCTN 10406).

Background: ATR is an apical DDR kinase activated at damaged replication forks. Elimusertib is an oral ATR inhibitor and potentiates irinotecan in human colorectal cancer models.

Methods: To establish dose and tolerability of elimusertib with FOLFIRI, a Bayesian Optimal Interval trial design was pursued.

How Should Clinicians Discuss Deprescribing with Caregivers of Older Adults Living with Dementia? A Qualitative Study.

Background: Preventive medications are potential targets for deprescribing in older adults with dementia as goals of care change from preventive to palliative. Yet, prescribers lack communication guidance to address deprescribing.

Objective: Using bisphosphonates as a case example, we sought to characterize and compare communication preferences of prescribers and family/informal caregivers regarding deprescribing.

Engineering vaginal film platform for mucoadhesion and sustained drug release for HIV-1 prevention.

User adherence contributes to the effectiveness of topical pre-exposure prophylactic products designed to protect against human immunodeficiency virus type 1 (HIV-1) infection. Long-acting approaches that do not require daily or coitally-dependent use could potentially improve user adherence. This study aims to develop a long-acting vaginal film to deliver an integrase inhibitor, MK-2048, for prevention of HIV-1 infection.

Targeting TRPC channels for control of arthritis-induced bone erosion.

Arthritis leads to bone erosion due to an imbalance between osteoclast and osteoblast function. Our prior investigations revealed that the Ca-selective ion channel, Orai1, is critical for osteoclast maturation. Here, we show that the small-molecule ELP-004 preferentially inhibits transient receptor potential canonical (TRPC) channels.

A Cross-Biomeasure Study to Optimize Antiretroviral Adherence Estimation.

Background: Incomplete adherence to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) reduces effectiveness. Adherence biomeasures (i.e.

The role of multi-modality imaging for the assessment of left atrium and left atrial appendage. A clinical consensus statement of the European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).

Structural, architectural, contractile or electrophysiological alterations may occur in the left atrium (LA). The concept of LA cardiopathy is supported by accumulating scientific evidence demonstrating that LA remodeling has become a cornerstone diagnostic and prognostic marker. The structure and the function of LA and left atrial appendage (LAA) which is an integral part of the LA, are key elements for a better understanding of multiple clinical conditions, most notably atrial fibrillation (AF), cardioembolism, heart failure and mitral valve diseases.

Acceptability of a dapivirine levonorgestrel vaginal ring in two Phase 1 trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019): Implications for multipurpose prevention technology development.

End-user feedback early in product development is important for optimizing multipurpose prevention technologies for HIV and pregnancy prevention. We evaluated the acceptability of the 90-day dapivirine levonorgestrel ring (DPV-LNG ring) used for 14 days compared to a dapivirine-only ring (DVR-200mg) in MTN-030/IPM 041 (n = 23), and when used for 90 days cyclically or continuously in MTN-044/IPM 053/CCN019 (n = 25). We enrolled healthy, non-pregnant, HIV-negative women aged 18-45 in Pittsburgh, PA and Birmingham, AL (MTN-030 only).

Impact of sleep quality on academic achievements of undergraduate medical students: a cross-sectional study from Saudi Arabia.

Background: Sleep is an active process that affects human health and quality of life. Sleep is essential for learning and memory consolidation. Good sleep is required for good academic performance.

MicroRNA biomarkers and host response pathways in severe pulmonary hemorrhagic syndrome due to leptospirosis: A multi-omics study.

Background: Severe pulmonary hemorrhagic syndrome (SPHS) remains a fatal complication of leptospirosis with poorly understood mechanisms and an urgent need for effective biomarkers.

Methods: A nested case-control analysis was conducted using blood specimens from two previous Thai leptospirosis cohorts. Candidate microRNAs were initially discovered through a global profiling of 798 serum microRNAs in five SPHS and seven non-SPHS patients, and then validated using real-time polymerase chain reactions in 168 patients.

Mesenchymal stromal cells promote the formation of lung cancer organoids via Kindlin-2.

Background: Patient-derived lung cancer organoids (PD-LCOs) demonstrate exceptional potential in preclinical testing and serve as a promising model for the multimodal management of lung cancer. However, certain lung cancer cells derived from patients exhibit limited capacity to generate organoids due to inter-tumor or intra-tumor variability. To overcome this limitation, we have created an in vitro system that employs mesenchymal stromal cells (MSCs) or fibroblasts to serve as a supportive scaffold for lung cancer cells that do not form organoids.

Advancing Delirium Treatment Trials in Older Adults: Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS).

Objectives: To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults.

Design: A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs).

Identifying and treating metabolic dysfunction-associated steatotic liver disease among at-risk Veterans.

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD), an increasing public health concern, remains challenging to diagnose and risk-stratify. We assessed the 1) prevalence of MASLD risk factors among Veterans in Veterans Health Administration (VA) care, 2) factors associated with MASLD diagnosis; and 3) associations between MASLD diagnosis and receipt of care.

Methods: Veterans with MASLD risk factors, including obesity, pre-diabetes, diabetes, or dyslipidemia, were identified using International Classification of Diseases-10 codes and followed in 2019-2022.

Quality by Design (QbD)-Driven Development and Optimization of Tacrolimus-Loaded Microemulsion for the Treatment of Skin Inflammation.

Skin inflammation represents a hallmark of many skin conditions, from psoriasis to eczema. Here, we present a novel microemulsion formulation for delivering a low dose of potent immunosuppressant, tacrolimus, to the skin for local inflammation control. The efficacy of topically delivered tacrolimus in controlling skin inflammation can be enhanced by packaging it into microemulsions.

Cardiovascular Safety of Anti-CGRP Monoclonal Antibodies in Older Adults or Adults With Disability With Migraine.

Importance: Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP mAbs) offer effective migraine-specific preventive treatment. However, concerns exist about their potential cardiovascular risks due to CGRP blockade.

Objective: To compare the incidence of cardiovascular disease (CVD) between Medicare beneficiaries with migraine who initiated anti-CGRP-mAbs vs onabotulinumtoxinA in the US.