University of California, San Francisco

Toward Tumor-Conditional Release of Histone Deacetylase Inhibitors from Nongenotoxic Drug Conjugates

Abstract Inhibition of histone deacetylase (HDAC) metalloenzymes with hydroxamic acid-based inhibitors is compromised by generally poor metalloenzyme selectivity and the potential for genotoxicity arising from isocyanate metabolites. Here, we applied our previously described plat...

Synthesis, Evaluation, and Context for Applications of SF5-Containing [1.1.1]Bicyclopentane and [ 2 ]Staffane “Hybrid Bioisosteres”

Abstract Bioisosteric replacements are conventionally applied as single-variable changes to a parent molecule during drug discovery campaigns. Herein, we evaluate hybrid bioisosteric replacements as strategic combinations of multiple substitutions that counterbalance the physicoc...

Dissipative Quantum Algorithms for Excited-State Quantum Chemistry

Abstract Electronic excited states are central to a vast array of physical and chemical phenomena, yet accurate and efficient methods for preparing them on quantum devices remain challenging and are comparatively underexplored. We introduce a general dissipative algorithm for sel...

Health disparities learning in a Project-Based Quality Improvement Curriculum

Abstract Background Health disparities remain a persistent challenge in medicine, exacerbated by inequitable practices within healthcare systems and among professionals. Quality improvement (QI) methods are well-suited for discovering and addressing disparities, and many medical...

Formation of Tobacco-Specific Nitrosamines from the Atmospheric Aging of Nicotine in E-Cigarette Aerosols

Abstract The atmospheric aging of nicotine-containing e-cigarette aerosols in the presence of nitrogen dioxide (NO2) and ozone (O3) may significantly alter their chemical composition and toxicological properties. However, the chemical transformation of nicotine within the complex...

Frontline healthcare worker barriers impacting tuberculosis service demand and access in high burden settings: a scoping review

Background: Extensive literature exists on health-seeking behaviour and barriers related to the uptake of tuberculosis (TB)-related services in high TB burden settings. However, prior reviews have focused on patient- and health facility/systems-level barriers to TB-related care....

Structure based discovery of antipsychotic-like TAAR1 agonists

Abstract Schizophrenia is a severe mental illness whose current treatments primarily target dopamine and serotonin receptors. These drugs often cause side effects and vary in effectiveness across patients. The trace amine-associated receptor 1 (TAAR1), which modulates monoamine s...

Establishment, Implementation, and Sustainability of Digital Dentistry in Dental Schools

ABSTRACT Digital dentistry technology and its workflows offer important benefits, including advancements in patient care and diagnostic capabilities. Dental schools have been adopting and integrating these advanced technologies into their educational and patient care practices. T...

A noncontiguous code for RNA-guided DNA recognition at the origin of CRISPR-Cas

CRISPR-Cas provides RNA-mediated adaptive immunity, but how its first RNA-guided effector arose is unclear. In this study, we report the discovery of Viral Interference Programmable Repeat (VIPR) systems consisting of a Vipr protein ancestral to the earliest CRISPR-Cas effectors...

Adult Mixed Epithelial and Stromal Tumor of the Kidney Harbors Recurrent Whole Chromosome 12 Gain

Mixed epithelial and stromal tumor (MEST), including adult cystic nephroma (CN), is an uncommon benign renal neoplasm that mostly occurs in middle-aged women. To date, a comprehensive molecular genetic investigation of MEST and/or adult CN has not been performed. Fourteen archiva...

Adipocytes as a Mechanistic Link Between Incretin-Based Therapies and Hair Loss

The physiological effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RAs extend beyond glucose metabolism and body weight regulation. Accumulating clinical evidence has highlighted an association betwee...

Rheumatology Informatics System for Effectiveness (RISE) Registry Participation Associated with Significant Gains in Quality Measure Performance: An Interrupted Time Series Analysis

OBJECTIVE: To examine the association between participation in a qualified clinical data registry and quality measure performance. METHODS: We included practices that joined the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry b...

At the Edge of Stability: the Unexpected Isolation of an f-Element Triphenylphosphine Complex

Abstract While PPh3 is a dominant ligand in transition-metal chemistry, it is completely absent in rare-earth and actinide structural chemistry. The open coordination site and high Lewis acidity of (CpSiMe3)3U are leveraged to generate the first structurally characterized PPh3 co...

Pancreatic Cancer Screening and Early Detection: Where Are We Now?

Screening for pancreatic cancer with imaging techniques in high-risk individuals—including patients with a genetic predisposition, a family history, or precursor lesions—is critical for improving early detection and survival outcomes, and multimodal strategies that integrate AI-e...

VIPR RNA-guided DNA recognition by noncontiguous geometric triplex formation

Viral interference programmable repeat (VIPR) systems use a noncontiguous code for RNA-guided transcriptional silencing. How the Vipr protein and a VIPR RNA (vrRNA) comprising alternating GGY and NN segments achieve precise DNA targeting is unknown. Here, we present 21 cryo–elect...

Dry Eye Disease Therapies at a Crossroads—A Call for Reform

This Viewpoint discusses current approval pathways for dry eye disease medications and the need to advance the standard of evidence for these medications.

Tuning the Activation Barrier for Oxygen Exchange on Mixed Conducting Oxide with Fine Control of Transition Metal Impurities

Abstract The energy barrier for oxygen exchange at the surface of mixed conducting oxides is a multifactor term that remains difficult to predict with existing models. Here, we describe an experimental approach to fine-tune this barrier on Pr0.1Ce0.9O2-δ used as a model mixed con...

High-grade astrocytoma with piloid features: a clinical and genomic analysis of prognostic factors using a large cohort

BACKGROUND: High-grade astrocytoma with piloid features (HGAP) is a recently defined tumor type that is not well-understood. Prognostic factors of clinical outcomes are not well-established. METHODS: Methylation profiling was performed on tumor samples, many at the National Cance...

Intramedullary Fixation for Epibasilar Thumb Metacarpal Fractures: A Case Series

Intramedullary (IM) fixation has gained popularity in the fixation of hand and finger fractures, given the ability to start early postoperative range of motion and relatively minimally invasive insertion. This article describes the surgical technique and clinical outcomes of intr...

The Ischemia–Plaque Paradox: A Mechanistic Framework for Chronic Coronary Syndromes

Percutaneous coronary intervention relieves angina in chronic coronary syndromes, yet contemporary randomized trials have not shown that relieving ischemia reduces death or myocardial infarction when added to optimal medical therapy. This discordance requires a mechanistic reeval...