Spatial-Structural Mechanisms of Racialized Disparities in Overdose Mortality: A Spatiotemporal Analysis.

Efforts to understand and respond to the opioid crisis have focused on overdose fatalities. Overdose mortality rates (ratios of overdoses resulting in death) are rarely examined though they are important indicators of harm reduction effectiveness. Factors that vary across urban communities likely determine which community members are receiving the resources needed to reduce fatal overdose risk.

DNA methylation clocks struggle to distinguish inflammaging from healthy aging, but feature rectification improves coherence and enhances detection of inflammaging.

Biological age estimation from DNA methylation and determination of relevant biomarkers is an active research problem which has predominantly been tackled with black-box penalized regression. Machine learning is used to select a small subset of features from hundreds of thousands of CpG probes and to increase generalizability typically lacking with ordinary least-squares regression. Here, we show that such feature selection lacks biological interpretability and relevance in the clocks of the first and next generations and clarify the logic by which these clocks systematically exclude biomarkers of aging and age-related disease.

5-HT agonism as a neurotherapeutic for sarcopenia: preclinical proof of concept.

Sarcopenia, the pathological age-related loss of muscle mass and strength, contributes to physical decline, frailty, and diminished healthspan. The impact of sarcopenia is expected to rise as the aging population grows, and treatments remain limited. Therefore, novel approaches for enhancing physical function and strength in older adults are desperately needed.

Estimating correlations in low-reliability settings with constrained hierarchical models.

It is popular to study individual differences in cognition with experimental tasks, and the main goal of such approaches is to analyze the pattern of correlations across a battery of tasks and measures. One difficulty is that experimental tasks are often low in reliability as effects are small relative to trial-by-trial variability. Consequently, it remains difficult to accurately estimate correlations.

Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

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.

Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.

Role of stereotactic radiosurgery for intracranial epidermoid tumors: a systematic review to assess its safety, efficacy, and complication profile.

Background: Even a gross total resection of a benign epidermoid tumor (ET) carries a high risk of recurrence. The management strategy mostly involves redo surgical excision but at a significant cost of morbidity and mortality. The role of adjuvant radiation therapies in this scenario is still undefined.

Generating allogeneic CAR-NKT cells for off-the-shelf cancer immunotherapy with genetically engineered HSP cells and feeder-free differentiation culture.

The clinical potential of current chimeric antigen receptor-engineered T (CAR-T) cell therapy is hampered by its autologous nature that poses considerable challenges in manufacturing, costs and patient selection. This spurs demand for off-the-shelf therapies. Here we introduce an ex vivo feeder-free culture method to differentiate gene-engineered hematopoietic stem and progenitor (HSP) cells into allogeneic invariant natural killer T (NKT) cells and their CAR-armed derivatives (CAR-NKT cells).

Dynamical constraints on neural population activity.

The manner in which neural activity unfolds over time is thought to be central to sensory, motor and cognitive functions in the brain. Network models have long posited that the brain's computations involve time courses of activity that are shaped by the underlying network. A prediction from this view is that the activity time courses should be difficult to violate.

Comparison of failure rates between full-barium and striped barium distal shunt catheters: a matched case-control study.

Purpose: We hypothesize that distal shunt catheters fully impregnated with barium are more prone to failure compared to distal catheters with only a barium stripe. We sought to evaluate this distinction using a matched case-control study.

Methods: Patient records over an 8-year period were queried for distal shunt revisions for fracture or disconnection (cases).

Cost burden of productivity loss due to sickness presenteeism among nurses in South Korea: A cross-sectional study.

Aim: This study aimed to estimate the annual cost burden of productivity loss due to sickness presenteeism among hospital nurses in South Korea.

Background: Despite nurses being potentially more vulnerable to presenteeism, few studies have analyzed nurses' productivity losses due to sickness presenteeism.

Methods: This cross-sectional study employed an online survey in January 2023 with 607 nurses working in general/tertiary hospitals in South Korea.

The Role of Social Deficits in the Link Between Social Gambling Motives and Problem Gambling.

In comparison to other motives for gambling, social motives (e.g., gambling for social interaction) are often suggested to be the least problematic and, in some cases, even a protective factor for problem gambling.

mtSTAT3 suppresses rheumatoid arthritis by regulating Th17 and synovial fibroblast inflammatory cell death with IL-17-mediated autophagy dysfunction.

Th17 cells are activated by STAT3 factors in the nucleus, and these factors are correlated with the pathologic progression of rheumatoid arthritis (RA). Recent studies have demonstrated the presence of STAT3 in mitochondria, but its function is unclear. We investigated the novel role of mitochondrial STAT3 (mitoSTAT3) in Th17 cells and fibroblast-like synoviocytes (FLSs) and analyzed the correlation of mitoSTAT3 with RA.

Survey and perspective on verification, validation, and uncertainty quantification of digital twins for precision medicine.

Digital twins in precision medicine provide tailored health recommendations by simulating patient-specific trajectories and interventions. We examine the critical role of Verification, Validation, and Uncertainty Quantification (VVUQ) for digital twins in ensuring safety and efficacy, with examples in cardiology and oncology. We highlight challenges and opportunities for developing personalized trial methodologies, validation metrics, and standardizing VVUQ processes.

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.