Treatment With Avacopan in Patients With Respiratory Tract Manifestations of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Objective: The ADVOCATE trial demonstrated that treatment of active granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) with avacopan was noninferior in achieving remission at week 26 and superior for sustained remission at week 52 compared with a prednisone taper. This analysis of ADVOCATE evaluated the efficacy and safety of avacopan in patients with ear, nose, throat (ENT), or lung manifestations.

Methods: This post hoc analysis included patients enrolled in ADVOCATE with ENT or lung manifestations at baseline.

Enhanced Transcriptional Activation in Developing Mouse Photoreceptors.

Purpose: Retinal development in the mouse continues past birth and provides a widely used model system in which photoreceptor formation can be observed and manipulated. This experimental paradigm provides opportunities for both gain-of-function and loss-of-function studies, which can be accomplished through in vivo or ex vivo plasmid delivery and electroporation. However, the cis-regulatory elements used to implement this approach have not been fully evaluated or optimized for the unique transcriptional environment of photoreceptors.

COVID-19 Pandemic and Racial and Ethnic Disparities in Long-Term Nursing Home Stay or Death Following Hospital Discharge.

Importance: Long-term nursing home stay or death (long-term NH stay or death), defined as new long-term residence in a nursing home or death following hospital discharge, is an important patient-centered outcome.

Objective: To examine whether the COVID-19 pandemic was associated with changes in long-term NH stay or death among older adults with sepsis, and whether these changes were greater in individuals from racial and ethnic minoritized groups.

Design, Setting, And Participants: This cross-sectional study used patient-level data from the Medicare Provider Analysis and Review File, the Master Beneficiary Summary File, and the Minimum Data Set.

Prophylactic Use of Cardiac Medications and Survival in Duchenne Muscular Dystrophy.

Introduction/aims: Prophylactic treatment of left ventricular dysfunction (LVD) in Duchenne muscular dystrophy (DMD) delays onset of LVD, but there is limited data showing impact on survival. Our aim was to describe survival among treated and untreated individuals with DMD.

Methods: Retrospective, population-based surveillance data from the Muscular Dystrophy Surveillance, Tracking and Research Network (MD STARnet) were used.

Symptomatic Improvement in Adults and Adolescents With Eosinophilic Esophagitis Requires Higher Systemic Dupilumab Exposure Than Histologic Response.

Introduction: We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications.

Methods: Results for the phase 3 LIBERTY EoE TREET study coprimary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses.

Results: A steep initial relationship then plateau was observed between higher dupilumab steady-state trough concentrations and decreased eosinophilic infiltration at week 24, whereas a graded exposure-response relationship was observed for symptomatic improvement at week 24.

Gender Differences in Barriers in Career Development Among a Cohort of Dental Researchers. A Cross-Sectional Study.

Background: This cross-sectional study investigated gender differences in barriers to career development among dental researchers and between academic and non-academic women.

Methods: An anonymous 34-item survey assessing barriers to career development and workplace obstacles (14 items), along with demographic/occupation characteristics (22 items), was distributed among dental researchers at the Women In Science Network meetings at 2024 AADOCR/IADR General Session (QR code) and through AADOCR/IADR discussion board (online platform). Differences in barriers and workplace obstacles were analyzed between women and men with chi-square tests; comparisons were repeated among women working within versus outside academia.

Nutraceuticals and Headache 2024: Riboflavin, Coenzyme Q10, Feverfew, Magnesium, Melatonin, and Butterbur.

Nutraceuticals are not regulated by the US Food and Drug Administration, so a careful literature review is essential to make clinical decisions. Riboflavin or vitamin B2 can be recommended for migraine prevention in adults, but pediatric use is not proven. Adverse events are minimal.

Remote Food Security Research Project: Applying an Indigenist Research Lens.

This paper aimed to reflect on how Rigney's model of Indigenist research informed the research design of a project which explored community-led solutions to improve food security in remote Aboriginal and Torres Strait Islander communities. The project was conducted in partnership with two Aboriginal Community Controlled Health Organisations (ACCHOs); Apunipima Cape York Health Council (Apunipima) and Central Australian Aboriginal Congress (Congress), communities in Central Australia and Cape York, Queensland and researchers from the University of Queensland, Monash University, Dalhousie University and Menzies School of Health Research. On reflection the principles of Indigenist research were evident providing a means of resistance to oppression through Indigenous stakeholders being in control of research to address social determinants, in this case food security.

The impact of imprecise case definitions in electronic health record research: a melanoma case-study from the Million Veteran Program.

Cases for a disease can be defined broadly using diagnostic codes, or narrowly using gold-standard confirmation that often is not available in large administrative datasets. These different definitions can have significant impacts on the results and conclusions of studies. We conducted this study to assess how using melanoma phecodes versus histologic confirmation for invasive or in situ melanoma impacts the results of a genome-wide association study (GWAS) using the Million Veteran Program.

Bulk thermally conductive polyethylene as a thermal interface material.

As the demand for high-power-density microelectronics rises, overheating becomes the bottleneck that limits device performance. In particular, the heterogeneous integration architecture can magnify the importance of heat dissipation and necessitate electrical insulation between critical junctions to prevent dielectric breakdown. Consequently, there is an urgent need for thermal interface materials (TIMs) with high thermal conductivity and electrical insulation to address this challenge.

Clinical use of measurable residual disease in adult ALL: recommendations from a panel of U.S. experts.

Measurable residual disease (MRD) is a powerful predictor of clinical outcomes in acute lymphoblastic leukemia (ALL). In addition to its clear prognostic importance, MRD information is increasingly used in clinical decision algorithms to guide therapeutic interventions. While it is well-established that achievement of MRD-negative remission is an important endpoint of ALL therapy, the prognostic and therapeutic implications of MRD in an individual patient are influenced by both disease-related factors (e.

Different PD-L1 Assays Reveal Distinct Immunobiology and Clinical Outcomes in Urothelial Cancer.

Testing for PD-L1 expression by immunohistochemistry (IHC) is used to predict immune checkpoint blockade (ICB) benefit but has performed inconsistently in urothelial cancer (UC) clinical trials. Different approaches are used for PD-L1 IHC. We analyzed paired PD-L1 IHC data on UC samples using the SP142 and 22C3 assays from the phase 3 IMvigor130 trial and found discordant findings summarized by four phenotypes: PD-L1 positive by both assays (PD-L1 double positive; PD-L1DP), PD-L1 positive by the SP142 assay only (SP142 single positive; SP142SP), PD-L1 positive by the 22C3 assay only (22C3 single positive; 22C3SP), and PD-L1 negative by both assays double negative (PD-L1 double negative; PD-L1DN).

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).

The Role of WDR77 in Cancer: More Than a PRMT5 Interactor.

WD repeat domain 77 protein (WDR77), a WD-40 domain-containing protein, is a crucial regulator of cellular pathways in cancer progression. While much of the past research on WDR77 has focused on its interaction with PRMT5 in histone methylation, WDR77's regulatory functions extend beyond this pathway, influencing diverse mechanisms such as mRNA translation, chromatin assembly, cell cycle regulation, and apoptosis. WDR77 is a key regulator of cell cycle progression, regulating the transition from the G1 phase.

Direct and Indirect Protein Interactions Link FUS Aggregation to Histone Post-Translational Modification Dysregulation and Growth Suppression in an ALS/FTD Yeast Model.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are incurable neurodegenerative disorders sharing pathological and genetic features, including mutations in the gene. FUS is an RNA-binding protein that mislocalizes to the cytoplasm and aggregates in ALS/FTD. In a yeast model, FUS proteinopathy is connected to changes in the epigenome, including reductions in the levels of H3S10ph, H3K14ac, and H3K56ac.

Stakeholders' Roles in Evolutionizing Education: An Evolutionary-Based Toolkit Surrounding Elementary Education.

There is a rapidly growing body of research in the field of evolutionary educational psychology that examines children's evolved motivational and educational inclinations as they relate to modern learning and schooling. It is generally agreed that schools are inherently mismatched with how children of our species evolved to learn, thereby contributing to difficulty learning and associated adverse schooling outcomes. Many researchers argue that, by making small changes to schools that help to better align instructional methods and childhood as a whole with our species' evolved learning mechanisms, we can lessen the negative impacts from evolutionary mismatch and create better outcomes for modern students.

Virtually Connected: Do Shared Novel Activities in Virtual Reality Enhance Self-Expansion and Relationship Quality?

According to self-expansion theory, sharing novel experiences with a romantic partner can help prevent boredom and maintain relationship quality. However, in today's globalized modern world, partners spend less time together and are more likely to live apart than in previous generations, limiting opportunities for shared novel experiences. In two in-lab experiments, we tested whether shared novel activities in virtual reality (VR) could facilitate self-expansion, reduce boredom, and enhance relationship quality.

University STEM Students' Perceived Challenges During the COVID-19 Pandemic.

University students faced unprecedented challenges and stressors during the COVID-19 pandemic. STEM students experienced unique challenges because many had traditional lectures and hands-on learning in laboratories or field settings. This qualitative study aimed to explore STEM university students' experiences and difficulties perceived during the pandemic.

HDNLS: Hybrid Deep-Learning and Non-Linear Least Squares-Based Method for Fast Multi-Component T1ρ Mapping in the Knee Joint.

Non-linear least squares (NLS) methods are commonly used for quantitative magnetic resonance imaging (MRI), especially for multi-exponential T1ρ mapping, which provides precise parameter estimation for different relaxation models in tissues, such as mono-exponential (ME), bi-exponential (BE), and stretched-exponential (SE) models. However, NLS may suffer from problems like sensitivity to initial guesses, slow convergence speed, and high computational cost. While deep learning (DL)-based T1ρ fitting methods offer faster alternatives, they often face challenges such as noise sensitivity and reliance on NLS-generated reference data for training.

Risk factors affecting polygenic score performance across diverse cohorts.

Apart from ancestry, personal or environmental covariates may contribute to differences in polygenic score (PGS) performance. We analyzed the effects of covariate stratification and interaction on body mass index (BMI) PGS (PGS) across four cohorts of European (N = 491,111) and African (N = 21,612) ancestry. Stratifying on binary covariates and quintiles for continuous covariates, 18/62 covariates had significant and replicable R differences among strata.

PARP inhibitors differentially regulate immune responses in distinct genetic backgrounds of high-grade serous tubo-ovarian carcinoma models.

Immune checkpoint inhibitors (ICIs) have revolutionized treatment for several tumor indications without demonstrated benefit for ovarian cancer patients. To improve the therapeutic ratio of ICIs in ovarian cancer patients, several different clinical trials are testing combinations with poly (ADP-ribose) polymerase (PARP) inhibitors. Comparing the immunomodulatory effects of clinically advanced PARP inhibitors may help to identify the best partner to combine with ICIs.

High-Performance TiCT-MXene/Mycelium Hybrid Membrane for Efficient Lead Remediation: Design and Mechanistic Insights.

This study presents a hybrid microfiltration technology designed for high-performance lead (Pb(II)) remediation, especially from aqueous solutions with high Pb(II) concentrations, by utilizing two-dimensional (2D) TiCT-MXene layers deposited on dry mycelium membranes. The hybrid TiCT-MXene/mycelium (MyMX) membranes were fabricated via a single-step electrochemical deposition (ECD) technique, which enabled a uniform coating of 2D TiCT-MXene onto individual hyphal fibers of a prefabricated mycelium membrane. Optimized ECD parameters for high Pb(II) uptake were identified using scanning electron microscopy and energy-dispersive X-ray spectroscopy.