Pharmacologic Management of Heart Failure with Preserved Ejection Fraction (HFpEF) in Older Adults.

There are several pharmacologic agents that have been touted as guideline-directed medical therapy for heart failure with preserved ejection fraction (HFpEF). However, it is important to recognize that older adults with HFpEF also contend with an increased risk for adverse effects from medications due to age-related changes in pharmacokinetics and pharmacodynamics of medications, as well as the concurrence of geriatric conditions such as polypharmacy and frailty. With this review, we discuss the underlying evidence for the benefits of various treatments in HFpEF and incorporate key considerations for older adults, a subpopulation that may be at higher risk for adverse drug events.

Light buckets and laser beams: mechanisms and applications of photobiomodulation (PBM) therapy.

Photobiomodulation (PBM) therapy, a non-thermal light therapy using nonionizing light sources, has shown therapeutic potential across diverse biological processes, including aging and age-associated diseases. In 2023, scientists from the National Institute on Aging (NIA) Intramural and Extramural programs convened a workshop on the topic of PBM to discuss various proposed mechanisms of PBM action, including the stimulation of mitochondrial cytochrome C oxidase, modulation of cell membrane transporters and receptors, and the activation of transforming growth factor-β1. They also reviewed potential therapeutic applications of PBM across a range of conditions, including cardiovascular disease, retinal disease, Parkinson's disease, and cognitive impairment.

Evaluation of UV-A and UV-B transmission through the windows of gas, hybrid, and electric vehicles.

UV-A exposure is a major risk factor for melanoma, nonmelanoma skin cancer, photoaging, and exacerbation of photodermatoses. Since people spend considerable time in cars daily, inadequate UV-A attenuation by car windows can significantly contribute to the onset or exacerbation of these skin diseases. Given recent market trends in the automobile industry and known impact of car windows on cumulative lifelong UV damage to the skin, there is a need to comparatively evaluate UV transmission across windows in electric vehicles (EV), hybrid vehicles (HV), and gas vehicles (GV) as well as variability based on year of manufacture and mileage to inform car manufacturers and consumers of the potential for UV exposure to the skin based on vehicle.

Ritlecitinib, a JAK3 /TEC inhibitor, modulates the markers of celiac autoimmunity in alopecia areata and vitiligo patients.

Background: Celiac disease (CeD) has shown an association with autoimmune disorders including vitiligo and alopecia areata (AA). Ritlecitinib, a JAK3 and TEC kinase family inhibitor, has been approved for treatment of patients with AA and is in late-stage development for vitiligo. Ritlecitinib inhibits cytotoxic T cells, NK cells, and B cells which play a role in the pathogenesis of CeD.

Reciprocal relationships between adolescent mental health difficulties and alcohol consumption.

The directionality of the relationship between adolescent alcohol consumption and mental health difficulties remains poorly understood. This study investigates the longitudinal relationship between alcohol use frequency, internalizing and externalizing symptoms from the ages of 11 to 17. We conducted a random-intercept cross-lagged panel model across three timepoints (ages: 11yrs, 14yrs, 17yrs; 50.

Comparison of the amyloid plaque proteome in Down syndrome, early-onset Alzheimer's disease, and late-onset Alzheimer's disease.

Down syndrome (DS) is strongly associated with Alzheimer's disease (AD) due to APP overexpression, exhibiting Amyloid-β (Aβ) and Tau pathology similar to early-onset (EOAD) and late-onset AD (LOAD). We evaluated the Aβ plaque proteome of DS, EOAD, and LOAD using unbiased localized proteomics on post-mortem paraffin-embedded tissues from four cohorts (n = 20/group): DS (59.8 ± 4.

Land use and cover changes and sand fly (Diptera: Psychodidae) assemblages in an emerging focus of leishmaniasis.

Land use and cover changes lead to fragmentation of the natural habitats of sand flies and modify the epidemiological profile of leishmaniasis. This process contributes to the infestation of adjacent rural settlements by vector sand fly species with different degrees of adaptation, promoting leishmaniasis outbreaks. This study aimed to assess land use and cover changes over a 12-year period and investigate the diversity and abundance of sand fly assemblages in the rural area of Codó, Maranhão State, Brazil.

Lineage-dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and independent immunotherapeutic targets.

Background: Neuroblastoma is a heterogeneous disease with adrenergic (ADRN)- and therapy resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype and propose pan-neuroblastoma and cell state specific targetable cell-surface proteins.

Methods: We characterized cell lines, patient-derived xenografts, and patient samples as ADRN-dominant or MES-dominant to define subtype-specific and pan-neuroblastoma gene sets.

Quantitative Pupillometry Predicts Neurologic Deterioration in Patients with Large Middle Cerebral Artery Stroke.

Objective: This study assesses whether longitudinal quantitative pupillometry predicts neurological deterioration after large middle cerebral artery (MCA) stroke and determines how early changes are detectable.

Methods: This prospective, single-center observational cohort study included patients with large MCA stroke admitted to Boston Medical Center's intensive care unit (2019-2024). Associations between time-to-neurologic deterioration and quantitative pupillometry, including Neurological Pupil Index (NPi), were assessed using Cox proportional hazards models with time-dependent covariates adjusted for age, sex, and Alberta Stroke Program Early CT Score.

Factors influencing evidence-based cardiovascular disease prevention programming in rural African American communities: a community-engaged concept mapping study.

Background: African Americans experience cardiovascular disease (CVD) disparities, and the burden is greatest in the rural south. Although evidence-based CVD prevention and management programs have been tailored to this context, implementation has been limited and not sustained long-term. To understand how to implement and sustain evidence-based CVD programs at scale, we must explore the perspectives of organizations serving rural African American communities and situate findings within foundational Implementation Science frameworks.

Meta-analyses of mouse and human prostate single-cell transcriptomes reveal widespread epithelial plasticity in tissue regression, regeneration, and cancer.

Background: Despite extensive analysis, the dynamic changes in prostate epithelial cell states during tissue homeostasis as well as tumor initiation and progression have been poorly characterized. However, recent advances in single-cell RNA-sequencing (scRNA-seq) technology have greatly facilitated studies of cell states and plasticity in tissue maintenance and cancer, including in the prostate.

Methods: We have performed meta-analyses of new and previously published scRNA-seq datasets for mouse and human prostate tissues to identify and compare cell populations across datasets in a uniform manner.

Enriched phenotypes in rare variant carriers suggest pathogenic mechanisms in rare disease patients.

Background: The mechanistic pathways that give rise to the extreme symptoms exhibited by rare disease patients are complex, heterogeneous, and difficult to discern. Understanding these mechanisms is critical for developing treatments that address the underlying causes of diseases rather than merely the presenting symptoms. Moreover, the same dysfunctional series of interrelated symptoms implicated in rare recessive diseases may also lead to milder and potentially preventable symptoms in carriers in the general population.

Enhancing prehospital decision-making: exploring user needs and design considerations for clinical decision support systems.

Background: In prehospital emergency care, providers face significant challenges in making informed decisions due to factors such as limited cognitive support, high-stress environments, and lack of experience with certain patient conditions. Effective Clinical Decision Support Systems (CDSS) have great potential to alleviate these challenges. However, such systems have not yet been widely adopted in real-world practice and have been found to cause workflow disruptions and usability issues.

Safety and Efficacy of Deutetrabenazine at High versus Lower Daily Dosages in the ARC-HD Study to Treat Chorea in Huntington Disease.

Background: Huntington disease (HD) is a progressive neurodegenerative disease that causes psychiatric and neurological symptoms, including involuntary and irregular muscle movements (chorea). Chorea can disrupt activities of daily living, pose safety issues, and may lead to social withdrawal. The vesicular monoamine transporter 2 inhibitors tetrabenazine, deutetrabenazine, and valbenazine are approved treatments that can reduce chorea.

The Impact of COVID-19 on the Division of Household Labor Among Women Physicians and Advanced Practice Providers.

Background: COVID-19 increased the burden of childcare on parents, leaving women vulnerable to increased disparities in the division of domestic labor. Women healthcare workers may be at heightened risk of worsening gender parity in the workplace as a result.

Objective: To examine the impact of the COVID-19 pandemic on gender parity in the division of household responsibilities among women healthcare workers.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

Explainable deep learning and virtual evolution identifies antimicrobial peptides with activity against multidrug-resistant human pathogens.

Artificial intelligence (AI) is a promising approach to identify new antimicrobial compounds in diverse microbial species. Here we developed an AI-based, explainable deep learning model, EvoGradient, that predicts the potency of antimicrobial peptides (AMPs) and virtually modifies peptide sequences to produce more potent AMPs, akin to in silico directed evolution. We applied this model to peptides encoded in low-abundance human oral bacteria, resulting in the virtual evolution of 32 peptides into potent AMPs.

Acoustic features of instrumental movie soundtracks elicit distinct and mostly non-overlapping extra-musical meanings in the mind of the listener.

Music can evoke powerful emotions in listeners. However, the role that instrumental music (music without any vocal part) plays in conveying extra-musical meaning, above and beyond emotions, is still a debated question. We conducted a study wherein participants (N = 121) listened to twenty 15-second-long excerpts of polyphonic instrumental soundtrack music and reported (i) perceived emotions (e.

Epicardial adipose tissue, cardiac damage, and mortality in patients undergoing TAVR for aortic stenosis.

Computed tomography (CT)-derived Epicardial Adipose Tissue (EAT) is linked to cardiovascular disease outcomes. However, its role in patients undergoing Transcatheter Aortic Valve Replacement (TAVR) and the interplay with aortic stenosis (AS) cardiac damage (CD) remains unexplored. We aim to investigate the relationship between EAT characteristics, AS CD, and all-cause mortality.

Challenges and opportunities for digital twins in precision medicine from a complex systems perspective.

Digital twins (DTs) in precision medicine are increasingly viable, propelled by extensive data collection and advancements in artificial intelligence (AI), alongside traditional biomedical methodologies. We argue that including mechanistic simulations that produce behavior based on explicitly defined biological hypotheses and multiscale mechanisms is beneficial. It enables the exploration of diverse therapeutic strategies and supports dynamic clinical decision-making through insights from network science, quantitative biology, and digital medicine.

Preoperative prediction of tumor budding and lymphovascular invasion in colon cancer using dual-energy CT: a prospective study with internal model validation.

Objective: This study evaluates the potential of dual-energy CT (DECT) for preoperative prediction of tumor budding (TB) and lymphovascular invasion (LVI) in colon cancer.

Methods: This prospective study enrolled 153 patients (mean age 61.33 years ± 0.