UC San Diego

Purpose of Review: Concurrent HIV and hepatitis B virus (HBV) affect an estimated 4-5 million people worldwide and remain a major driver of liver-related morbidity and mortality, even among individuals receiving tenofovir-containing antiretroviral therapy (ART). Both viruses establish long-lived reservoirs that are not eliminated by current antiviral therapies. This review summarizes current mechanistic and clinical frameworks for understanding concurrent HIV and HBV, highlights the interplay between their viral reservoirs, and discusses the implications of these interactions for cure strategies. Recent Findings: The liver functions as a multicellular reservoir. HBV persists within hepatocytes as nuclear covalently closed circular DNA (cccDNA) and integrated viral sequences. HIV persists as integrated provirus in tissue-resident CD4⁺ T cells and liver macrophages, with evidence supporting viral transfer or cell-to-cell spread involving stellate cells and hepatocytes. Concurrent HIV and HBV accelerate fibrosis and immune dysfunction through shared pathogenic pathways, including epigenetic silencing, cytokine- and checkpoint-mediated T-cell exhaustion, metabolic stress, and inflammation driven by the gut-liver axis. HBV-associated liver injury promotes recruitment of HIV target cells, while HIV-associated immune dysregulation impairs HBV control. Despite these interlinked biological mechanisms, individuals living with HIV and HBV are frequently excluded from clinical trials, slowing therapeutic progress and exacerbating health inequities. Summary: Concurrent HIV and HBV represent a synergistic disease model that demands integrated therapeutic approaches and inclusive research frameworks. Priority needs include robust tissue-based reservoir measurements, validated biomarkers that distinguish latent from transcriptionally active viral states, combination strategies incorporating antiviral, antifibrotic, and immunomodulatory agents, and community-engaged clinical trial designs that are inclusive of individuals living with HIV and HBV and safe in the context of HBV. Advancing these areas will be essential to achieving durable remission-and ultimately functional cure-for both viruses.

Regulation of adipogenesis has classically been viewed through the lens of transcription initiation driven by lineage defining transcription factors. In this study, we uncover transcription elongation as a critical and previously underappreciated regulatory layer controlling adipocyte cell fate. We demonstrate that the elongation factors Spt4 and Spt6 are indispensable for adipogenic differentiation, as their depletion severely impairs adipogenic gene induction and perilipin expression. Spt4 and Spt6 directly regulate the genes coding for core adipogenic transcription factors, including Cebpa, Pparg, Krox20, and Stat3, by promoting RNA polymerase II (Pol II) progression through their gene bodies. In the absence of these factors, Pol II becomes stalled at the transcriptional start sites of these adipogenic genes. These data support a post transcription initiation requirement for Spt4 and Spt6 in productive elongation rather than promoter loading. Our findings identify transcription elongation control as a key determinant of adipogenic fate.

Purpose of ReviewTailoring treatment strategies to the biological features of invasive disease and the individual needs and preference of each patient has transformed the way we manage breast cancer. This article calls for a similar shift in the management paradigm of ductal carcinoma in situ (DCIS) from a uniform treatment model toward a risk-stratified stepwise approach that aligns with the heterogeneous nature of the disease to avoid overtreatment.Recent FindingsMost DCIS lesions are hormone receptor positive, and only a subset have a risk for progression to invasive cancer. Early results from observational and clinical studies indicate that active surveillance is a safe and feasible alternative to upfront surgical treatment for low-risk DCIS. Ongoing clinical trials like RECAST will further inform and refine strategies for optimal management of this condition.SummaryThe integration of risk-adapted management strategies, endocrine risk-reducing interventions, and advanced imaging modalities into active surveillance protocols hold significant potential to reduce overtreatment and personalize care for patients with DCIS. Early data from clinical trials support the notion that providing a period of active surveillance is safe and offers a critical assessment window during which DCIS treatment can be individualized. Strengthening the evidence base to support the adoption of active surveillance as an initial approach in the management of DCIS is an important clinical priority.

Amable Liñán, the founder of the Spanish school of fluid mechanics, passed away in Madrid on November 8, 2025. A leading theoretician in combustion and fluid mechanics, he made exemplary use of perturbation methods to simplify the analysis of complex fluid-flow problems. The present manuscript reviews his contributions to combustion science and non-reactive fluid mechanics. Two representative examples of his purely fluid-mechanical work are discussed in detail to illustrate how the disparate time and length scales that characterize many fluid-flow problems can be exploited to simplify their description.

This paper presents 3D numerical simulations of GRS bridge abutments under different conditions of bridge surcharge stress, with the goal of better understanding 3D deformation behavior and evaluating the internal stability for 3D loading conditions. Backfill soil was modeled using a nonlinear elastoplastic model with the Duncan–Chang hyperbolic stress–strain relationship and the Mohr–Coulomb failure criterion. A corresponding 2D model representative of that typically used in the routine analysis and design of GRS bridge abutments was also developed for comparison. Results show that the facing displacements, bridge seat settlements, and maximum reinforcement tensile forces obtained from the 2D simulations are close to those of the longitudinal centerline section in the 3D simulations. These findings suggest that 2D simulations can reasonably predict the deformations and reinforcement tensile forces in the abutment despite the simplified plane strain assumption. Parametric analyses further reveal that facing displacements increase with abutment width but stabilize for larger widths, while abutment width has a negligible influence on bridge seat settlements. Increasing abutment height results in greater facing displacements, bridge seat settlements, and reinforcement tensile forces due to increased stress levels within the abutment structure.

Cancer-associated fibroblasts (CAFs) are key regulators of the tumor microenvironment (TME), shaping immune surveillance, stromal architecture, metastatic progression, and therapeutic resistance across solid tumors. Although traditionally classified into heterogeneous subtypes, emerging evidence indicates that CAF phenotypes are not fixed lineages, but dynamic stress-adaptive states continuously reshaped by hypoxia, oxidative stress, nutrient deprivation, metabolic pressure, and therapy-induced injury. These pressures reprogram CAFs transcriptional, metabolic, and secretory programs, enabling CAFs to amplify tumor-promoting signals that reinforce immunosuppression, extracellular matrix (ECM) remodeling, metastatic niche formation, and treatment resistance. Viewing CAF biology through this stress-adaptation framework provides a mechanistic explanation for the limited success of indiscriminate stromal depletion strategies and highlights the need for more selective, context-aware therapeutic intervention. In this review, we examine how microenvironmental and therapeutic stress rewires CAF identity and function across tumor progression, integrating insights from single-cell, spatial, and translational evidence. We further discuss emerging strategies aimed at disrupting stress-adaptive CAF programs, including modulation of inflammatory signaling, stromal mechanotransduction, metabolic dependencies, and senescence-associated secretory phenotypes. Reframing CAFs as dynamic stress-responsive hubs rather than static stromal subtypes may provide a conceptual foundation for next-generation stromal-targeted therapies designed to overcome immunosuppression and therapeutic resistance.

This study explores how learners leverage the spatial and kinesthetic affordances of an immersive, fully 3D coding environment in virtual reality (VR). A workshop was conducted in which high school students engaged in creative coding activities using a new node-based VR coding platform. Their code histories were recorded in video format through screen casting from their headsets. Audio-free videos were subsequently annotated to characterize users’ interactions with nodes and UI elements during code construction, execution, and debugging. At a minimum, creating a computer program using this platform requires loading appropriate nodes and making connections with wires between event and data ports. However, it was found that users engaged with elements of their code in much more complex ways, treating them at times as though they were tangible objects. Learners moved and rearranged nodes, hovered objects in space, fidgeted, and virtually touched, gestured, or traced over nodes and wires. These actions served to enact relational features and computational concepts underlying their code in support of planning, prediction, modeling, and other cognitive processes important for computer science (CS) learning. Preliminary outcomes suggesting growth in CS abilities. Guidelines for VR platform design are discussed.

Building from the work of von Bell et al. (2022), we study the Ehrhart theory of order polytopes arising from a special class of distributive lattices, known as generalized snake posets. We present arithmetic properties satisfied by the Ehrhart polynomials of order polytopes of generalized snake posets along with a computation of their Gorenstein index. Then we give a combinatorial description of the chain polynomial of generalized snake posets as a direction to obtain the h ⁎ -polynomial of their associated order polytopes. Additionally, we present explicit formulae for the h ⁎ -polynomial of the order polytopes of the two extremal examples of generalized snake posets, namely the ladder and regular snake poset. We then provide a recursive formula for the h ⁎ -polynomial of any generalized snake posets and show that the h ⁎ -vectors are entry-wise bounded by the h ⁎ -vectors of the two extremal cases.