Global profiling of alternative splicing in non-small cell lung cancer reveals novel histological and population differences.

Lung cancer is one of the most frequently diagnosed cancers in the US. African-American (AA) men are more likely to develop lung cancer with higher incidence and mortality rates than European-American (EA) men. Herein, we report high-confidence alternative splicing (AS) events from high-throughput, high-depth total RNA sequencing of lung tumors and non-tumor adjacent tissues (NATs) in two independent cohorts of patients with adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC).

Silacrown ethers as ion transport modifiers and preliminary observations of cardiovascular cell line response.

Crown ethers have been shown to have physiological effects ascribed to their ionophoric properties. However, high levels of toxicity precluded interest in their evaluation as therapeutic agents. We prepared new silacrown analogs of crown ethers.

Common and uncommon risky drinking patterns in young adulthood uncovered by person-specific computational modeling.

Objective: Alcohol use offers social benefits for young adults, but also carries risk of significant negative consequences. Better understanding of processes driving alcohol use for those who experience negative consequences can prevent these harms. These at-risk young adults likely have drinking patterns in common and patterns unique to each individual.

Immune Checkpoint Blockade Delays Cancer Development and Extends Survival in DNA Polymerase Mutator Syndromes.

Mutations in the exonuclease domains of the replicative nuclear DNA polymerases POLD1 and POLE are associated with increased cancer incidence, elevated tumor mutation burden (TMB), and enhanced response to immune checkpoint blockade (ICB). Although ICB is approved for treatment of several cancers, not all tumors with elevated TMB respond, highlighting the need for a better understanding of how TMB affects tumor biology and subsequently immunotherapy response. To address this, we generated mice with germline and conditional mutations in the exonuclease domains of Pold1 and Pole.

Public Health.

Background: Characterizing changes in cognitive function during the last years of life is vital for providing appropriate care, supporting quality of life, and planning for future demands on our medical and social resources. The aim of this project was to construct a cognitive function trajectory file spanning the last five years of life to better understand common patterns of cognitive aging.

Method: The analytic cohort included 2019 Medicare decedents, aged 50 or older at death, with five years of continuous enrollment before death (n = 1,952,408).

Public Health.

Background: Dramatically varying estimates of survival time following an initial diagnosis of Alzheimer's disease and other dementias have been reported across different studies. The prevalence of dementia increases with age while survival time decreases with increasing age at diagnosis. This study aimed to investigate how survival time after a diagnosis of dementia varies by sex, race/ethnicity, and age at time of diagnosis.

Public Health.

Background: Clinicians have observed various patterns of decline in cognitive function at the end of life. In a period of dynamic evolution in dementia care technology and delivery, tracking trends in cognitive function during last years of life provides a perspective on the need of patients and their caregivers and on demands on healthcare system. This work aims to characterize the functional decline in cognition during the last five years of life.

Public Health.

Background: Most older adults prefer aging in place; however, patients with dementia and advanced illness often need institutional care, even if only for a brief period of time. In the context of the aging US population and the increasing number of individuals living with dementia, understanding place of care trajectory patterns is important for patient-centered care planning and health policy decisions. The purpose of this study was to characterize place of care trajectories during the last three years of life among Medicare beneficiaries diagnosed with dementia.

Public Health.

Background: This work focuses on methodological aspects in assessing the association between group-based aging trajectories and sociodemographic and clinical factors. The group-based trajectories are derived from the latent class analysis of longitudinal variables of clinical interest. Each individual would be assigned a class membership with the highest posterior probability (modal assignment) and each class represents a particular pattern in the trajectory of the longitudinal variables.

Public Health.

Background: Individuals with dementia often have one or more chronic conditions, and the disease burden and care experience may differ based on the plurality of chronic conditions. We aim to describe the individual characteristics, health care use, and place of death for individuals with dementia and multiple comorbidities.

Method: A retrospective cohort of individuals who died in 2019 with dementia, and were continuously enrolled in Medicare for at least three years.

Examining the use of interoceptive exposure exercises in people with and without a history of chronic physical health problems.

Interoceptive exposure (IE) exercises are underused, especially in people with chronic physical health problems. Secondary data analyses were conducted to examine the use of and acute responses to IE exercises in individuals with and without a history of chronic physical health problem(s). Participants ( = 413; Mage = 38.

Development of a Population Pharmacokinetic Gabapentin Model Leveraging Therapeutic Drug Monitoring Concentrations.

Gabapentin has variable pharmacokinetics (PK), which contributes to difficulty in dosing and increased risk of adverse events. The objective of this study was to leverage gabapentin concentrations from therapeutic drug monitoring (TDM) to develop a population PK (popPK) model and characterize significant covariates that impact gabapentin PK. Data were retrospectively collected from 82 hospitalized adult patients with TDM gabapentin concentrations.

Genetic Variant Analyses Identify Novel Candidate Autism Risk Genes from a Highly Consanguineous Cohort of 104 Families from Oman.

Deficits in social communication, restricted interests, and repetitive behaviours are hallmarks of autism spectrum disorder (ASD). Despite high genetic heritability, the majority of clinically diagnosed ASD cases have unknown genetic origins. We performed genome sequencing on mothers, fathers, and affected individuals from 104 families with ASD in Oman, a Middle Eastern country underrepresented in international genetic studies.

Synergistic Anti-Cancer Effects of Curcumin and Thymoquinone Against Melanoma.

Combining anti-cancer agents in cancer therapies is becoming increasingly common because of their improved efficacy, reduced toxicity, and decreased risk of resistance development. Melanoma, a highly aggressive form of skin cancer characterized by limited treatment options due to chemoresistance, poses a considerable challenge for effective management. Here, we test the hypothesis that dietary supplements such as thymoquinone (TQ) and curcumin (CU) cooperatively modulate cancer-associated cellular mechanisms to inhibit melanoma progression.

A novel anxiety-associated SNP identified in () is associated with decreased protein binding to nicotinic acetylcholine receptors.

Introduction: Anxiety disorders are among the most common mental illnesses in the US. An estimated 31.1% of U.

Starch-rich plant foods 780,000 y ago: Evidence from Acheulian percussive stone tools.

In contrast to animal foods, wild plants often require long, multistep processing techniques that involve significant cognitive skills and advanced toolkits to perform. These costs are thought to have hindered how hominins used these foods and delayed their adoption into our diets. Through the analysis of starch grains preserved on basalt anvils and percussors, we demonstrate that a wide variety of plants were processed by Middle Pleistocene hominins at the site of Gesher Benot Ya'aqov in Israel, at least 780,000 y ago.

Efficient Method for Imaging Murine Lungs that Preserves Spatial Dynamics of Fungal Spores in the Airways.

Fungi infect humans when environmental spores are inhaled into the lungs. The lung is a heterogeneous organ. Conducting airways, including bronchi and bronchioles, branch until terminating in the alveolar airspace where gas exchange occurs.

Therapeutic Potential of Dexmedetomidine in Neuropsychiatric Disorders: From the Bench to the Clinic.

Neuropsychiatric disease encompasses a range of conditions resulting from various dysfunctions within the nervous system, manifesting in diverse neurological impairments. These disorders, including depression, schizophrenia, anxiety, and Alzheimer's disease, impose significant economic and psychological burdens on both individuals and society overall. Recent clinical and preclinical studies have highlighted the potential therapy of dexmedetomidine (Dex), a highly selective α2 adrenergic receptor agonist, not only as an effective sedation but also as a neuroprotective agent.

The community dynamic alterations mechanisms of traveling plastics in the Pearl River estuary with the salinity influence.

Most ocean plastics originate from terrestrial emissions, and the plastisphere on the plastics would alter during the traveling due to the significant differences in biological communities between freshwater and marine ecosystems. Microorganisms are influenced by the increasing salinity during traveling. To understand the contribution of plastic on the alteration in biological communities of plastisphere during traveling, this study investigated the alterations in microbial communities on plastics during the migration from freshwater to brackish water and saltwater.

Genomic signatures of adaptation in native lizards exposed to human-introduced fire ants.

Understanding the process of genetic adaptation in response to human-mediated ecological change will help elucidate the eco-evolutionary impacts of human activity. In the 1930s red imported fire ants (Solenopsis invicta) were accidently introduced to the Southeastern USA, where today they are both venomous predators and toxic prey to native eastern fence lizards (Sceloporus undulatus). Here, we investigate potential lizard adaptation to invasive fire ants by generating whole-genome sequences from 420 lizards across three populations: one with long exposure to fire ants, and two unexposed populations.