Undifferentiated chest pain is a major driver of emergency department (ED) overcrowding and contributes to morbidity and mortality. Early risk stratification for major adverse cardiac events (MACE) allows for early discharge and ED decongestion. We developed a multimodal machine learning model integrating EHR data, laboratory results, demographic and comorbidity features and chest x-ray impressions to predict 30-day MACE in patients presenting to the ED with chest pain. Using 49,348 ED encounters from two healthcare systems, our model achieved a high area under the curve (AUC) of 82.0% at the development site and 74.6% at the external validation site. Predictions occurred within 6 h of ED arrival and demonstrated consistently high negative predictive values across time, supporting safe early-rule out. This model demonstrates the potential of integrating AI modeling to enhance early MACE risk stratification and improve ED overcrowding and efficiency.
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.
Background: Ethical and professional pharmacy practice is fundamental to supporting patient safety and trust. Despite advances in Good Pharmacy Practice (GPP), evidence from developing systems indicates gaps in ethical performance. This study aimed to assess the ethical dimensions of community pharmacists' practice in Jordan from the public's perspective, focusing on counseling quality, privacy, autonomy, and fairness. Methods: A cross-sectional survey was conducted among 710 community pharmacy clients across Jordan using a validated questionnaire measured five ethical domains and an attitude scale. Composite scores for patient satisfaction, ethical conduct, and pharmacist attitude were calculated. Descriptive statistics and logistic regression were used to identify demographic predictors. Results: Participants were predominantly female (57.9%) and from central Jordan (69.6%). Mean domain scores were: history-taking (51.3 ± 34.3), counseling (60.3 ± 29.6), privacy (67.8 ± 26.1), autonomy (60.2 ± 36.6), and justice (86.5 ± 24.0). Counseling was strongest for medication use and timing but weakest for safety aspects-adverse effects (41.4%), storage (40.1%), and drug interactions (31.7%). Justice and professionalism received the highest perception scores, while privacy and autonomy received moderate ratings. Gender (female) and south region predicted higher satisfaction and ethical perception (p < 0.05). Conclusion: Community pharmacists in Jordan were perceived as demonstrating strong fairness and professionalism, but gaps remain in safety-oriented counseling and privacy assurance. These findings highlight areas where communication practices, privacy infrastructure, and ethics-oriented training may warrant further attention. Strengthening these areas could contribute to supporting patient trust and the ethical quality of community pharmacy services.
Emerging studies suggest that antibiotics can disrupt the gut microbiome and alter vaccine-induced immune responses. However, the specific consequences of early-life exposure on neonatal immune development remain poorly understood. Here, we examined how two antibiotics frequently used in perinatal care, broad-spectrum ampicillin (AMP) and the extended-spectrum combination amoxicillin/clavulanate (AMOX/CLAV), administered during gestation and lactation, influence neonatal gut microbiome composition, fecal metabolome profiles, and responses to the 20-valent pneumococcal conjugate vaccine (PCV20). Maternal treatment with AMOX/CLAV, but not AMP, significantly reduced PCV-specific IgG titers at 4 and 6 weeks post-prime immunization compared to untreated controls. Exclusive exposure to AMOX/CLAV also impaired neutrophil-mediated opsonophagocytic killing, indicating reduced antibody functionality. These effects were transient, with immune parameters normalizing by 8 weeks post-prime immunization. Metabolomic and microbiome profiling revealed that maternal AMP and AMOX/CLAV differentially perturbed specific metabolite classes, including bile acids, N-acyl lipids, and indole derivatives. Key commensal taxa, including Bacteroidales and Coriobacteriales were also impacted within the gut microbiota. Together, these findings reveal a previously underappreciated maternal-offspring route of antibiotic influence that is transiently associated with neonatal vaccine responsiveness and microbiome and metabolome alterations. These results highlight maternal antibiotic exposure as a possible modifiable factor shaping early-life immunity.
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.
This study presents a centrifuge modeling investigation of the seismic performance of shallow, rocking-dominated foundations supported by soil-cement columns intended to limit detrimental settlement and rotation, while preserving the beneficial energy dissipation afforded by a rocking foundation. The footings investigated in this study are modeled after shallow foundations supporting a two-span highway bridge, which served as the archetypal bridge in previous centrifuge studies. While earlier studies proved that rocking foundations in sand exhibit good re-centering while dissipating energy, this study aims to broaden the use cases for the rocking foundation concept for heavily loaded foundations in dry sand that may be prone to excessive settlement by incorporating ground improvement in the form of soil-cement columns with different configurations. A baseline case was developed for a rocking footing without ground improvement by subjecting the soil-foundation system to shaking at a level that caused excessive settlement (more than 5% of its length in this study) and permanent rotation. Foundation performance in the baseline case and rocking footings with ground improvement was assessed based on settlement accumulation rate with increasing cumulative rotation demand, and a correlation diagram relating re-centering and energy dissipation. Test results demonstrate that footings without ground improvement dissipate the most energy but experience excessive settlement. In contrast, paired soil-cement columns at either end of the footing's length preserved adequate energy dissipation and re-centering, while minimizing settlement to an acceptable limit.
This study aims to advance the use of a lightweight recycled backfill formed from shredded waste tires with large particle sizes, referred to as Type B tire derived aggregate (TDA), for geotechnical seismic isolation (GSI). A shake table was used to perform dynamic testing of single-degree-of-freedom (SDOF) superstructures on a shallow footing embedded in layers of Type B TDA with different thicknesses across a broad set of base excitations. Results indicate nonlinearity in the moment-rocking response and the hysteretic damping of TDA confirmed its effectiveness as a low-modulus seismic isolation layer. TDA exhibited excellent re-centering behavior, outperforming soil-based seismic protection systems for the conditions studied. While TDA thickness had little direct effect on the moment-rocking response, specimen mass strongly influenced stability and hysteresis. Residual settlements remained small and independent of layer thickness, with larger settlements occurring only when the predominant period of input motions matched the rocking system's natural period. While more energy dissipation occurred through rocking compared to shearing, greater shear displacements were observed for more heavily loaded footings on thicker TDA layers. Residual shear displacements were negligible for all cases. System identification analyses revealed that TDA led to a period lengthening of 2.15 compared to a fixed-base condition. Although TDA amplifies ground motion as expected, the layer thickness plays complex effects due to multiple modes and the TDA first-mode shearing mechanism remained approximately constant even when the specimen was subjected to high-amplitude ground motions.
Research on the Tokamak à Configuration Variable addresses a wide range of key questions relevant to ITER and future fusion power plants. Over the past two years, highly productive experimental campaigns have led to major advances across several areas: the ITER baseline scenario; pedestal properties in low-collisionality, peeling-limited conditions; and the development of high- βN, non-inductive regimes. Alternative high-confinement scenarios have likewise received significant attention, with remarkable progress in quasi-continuous exhaust operation, X-point radiator plasmas, and negative triangularity configurations. Substantial achievements were also made in the mitigation or benign termination of runaway electron beams, in elucidating fast-ion loss mechanisms, and in improving exhaust behaviour in both conventional and alternative divertor geometries. These experimental results have been strongly supported by advances in modelling and their direct application to the experiment, ranging from gyrokinetic simulations of core and pedestal turbulence to fluid-based studies of scrape-off layer and divertor physics in diverse geometries. Plasma control has taken on an increasingly important role, with model-based and data-driven approaches now closely intertwined with physics studies. This article provides a overview of these recent activities, together with a brief outlook on forthcoming upgrades and next steps.
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.
