Deciphering the interplay between SETD2 mediated H3K36me3 and RNA N6-methyladenosine in clear cell renal cell carcinoma (ccRCC).

RNA N6-methyladenosine (m6A) plays diverse roles in RNA metabolism and its deregulation contributes to tumor initiation and progression. Clear cell renal cell carcinoma (ccRCC) is characterized by near ubiquitous loss of followed by mutations in epigenetic regulators , , and . Mutations in , a histone H3 lysine 36 trimethylase (H3K36me3), are associated with reduced survival, greater metastatic propensity, and metabolic reprogramming.

Fentanyl and Fentanyl Analog Screening Using ASAP-MS With LiveID Confirmation.

Rationale: Fentanyl and fentanyl analogs continue to pose a serious threat to the public health. The vast number of fentanyl analogs emerging on the black-market call for optimized analytical methods for the detection, analysis, and characterization of these extremely dangerous drugs.

Methods: Atmospheric pressure solids analysis probe (ASAP) mass spectrometry was used for the rapid analysis of 250 synthetic opioid standards, including 211 fentanyl analogs, 32 non-fentanyl related opioids, and 8 fentanyl precursors.

In this current wildfire crisis, acknowledge widespread suffering.

With climate change causing more extreme weather events globally, climate scientists have argued that societies have three options: mitigation, adaptation or suffering. In recent years, devastating wildfires have caused significant suffering, yet the extent of this suffering has not been defined. To encapsulate this suffering, we determined impacts and effects of extreme wildfires through two systematic literature reviews.

Incorporating Perineorrhaphy into the LeFort Colpocleisis: A Modified Surgical Approach.

Introduction And Hypothesis: Perineorrhaphy with levator myorrhaphy is considered a standard part of colpocleisis. Typically, this is done through a separate incision after colpocleisis is completed. We present a video to demonstrate a modified approach to LeFort colpocleisis incorporating perineorrhaphy into the procedure.

What role does wealth play in the racial health gap in the United States? Examining differences among African Americans, Latinos, and non-Hispanic Whites.

Wealth resources has received little attention when studying how socioeconomic status shapes health outcomes. In the United States (USA), there is a growing body of evidence acknowledging a widening racial/ethnic wealth gap. However, little is known about wealth's role in shaping health inequity.

Furin-Mediated Modification Is Required for Epithelial Sodium Channel-Activating Activity of Soluble (Pro)Renin Receptor in Cultured Collecting Duct Cells.

(Pro)renin receptor (PRR) contains overlapping cleavage site for site-1 protease (S1P) and furin for generation of soluble PRR (sPRR). Although S1P-mediated cleavage mediates the release of sPRR, the functional implication of furin-mediated cleavage is unclear. Here we tested whether furin-mediated cleavage was required for the activity of sPRR in activating ENaC in cultured M-1 cells.

Increasing cellular NAD protects hepatocytes against palmitate-induced lipotoxicity by preventing PARP-1 inhibition and the mTORC1-p300 pathway activation.

Hepatic lipotoxicity, resulting from excessive lipid accumulation in hepatocytes, plays a central role in the pathogenesis of various metabolic liver diseases. Despite recent progress, the precise mechanisms remain incompletely understood. Employing excessive exposure to palmitate in hepatocytes as our primary experimental model and mice studies, we aimed to uncover the mechanisms behind hepatic lipotoxicity, thereby developing potential treatments.

Tau oligomers impair memory and synaptic plasticity through the cellular prion protein.

Deposition of abnormally phosphorylated tau aggregates is a central event leading to neuronal dysfunction and death in Alzheimer's disease (AD) and other tauopathies. Among tau aggregates, oligomers (TauOs) are considered the most toxic. AD brains show significant increase in TauOs compared to healthy controls, their concentration correlating with the severity of cognitive deficits and disease progression.

Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer's disease.

Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directly observed. The residual approach has been widely applied to estimate CR, where the degree of resilience is estimated through a linear model's residuals.

Effect of SARS-CoV2 Infection on Endovascular Thrombectomy Outcomes - Data from the Florida Stroke Registry.

Background And Purpose: Endovascular thrombectomy outcomes are impacted by changes in stroke systems of care. During the pandemic, SARS-CoV2 positive status had major implications on hospital arrival and treatment models of non-COVID related hospital admissions. Using the Florida Stroke Registry, we compared the rates of in-hospital death and discharge outcomes of patients treated with endovascular thrombectomy who tested positive for SARS-CoV2 infection during their hospitalization.

In vitro comparative analysis of metabolic capabilities and inhibitory profiles of selected CYP2D6 alleles on tramadol metabolism.

Tramadol, the 41st most prescribed drug in the United States in 2021 is a prodrug activated by CYP2D6, which is highly polymorphic. Previous studies showed enzyme-inhibitor affinity varied between different CYP2D6 allelic variants with dextromethorphan and atomoxetine metabolism. However, no study has compared tramadol metabolism in different CYP2D6 alleles with different CYP2D6 inhibitors.

Investigation of Genomic and Transcriptomic Risk Factors of Clopidogrel Response in African Americans.

Clopidogrel, an anti-platelet drug, is used to prevent thrombosis after percutaneous coronary intervention. Clopidogrel resistance results in recurring ischemic events, with African Americans (AA) suffering disproportionately. The aim of this study was to discover novel biomarkers of clopidogrel resistance in African Americans using genome and transcriptome data.

Association between change in alcohol use reported during routine healthcare screening and change in subsequent hospitalization: A retrospective cohort study.

Background And Aims: Primary care systems often screen for unhealthy alcohol use with brief self-report tools such as the 3-item Alcohol Use Disorders Identification Test for consumption (AUDIT-C). There is little research examining whether change in alcohol use measured on the AUDIT-C captures meaningful change in outcomes affected by alcohol use. This study aimed to measure the association between change in AUDIT-C and change in all-cause hospitalization risk, measured in the year after each AUDIT-C.

Chromosome-level assembly of basil genome unveils the genetic variation driving Genovese and Thai aroma types.

Basil, Ocimum basilicum L., is a widely cultivated aromatic herb, prized for its culinary and medicinal uses, predominantly owing to its unique aroma, primarily determined by eugenol for Genovese cultivars or methyl chavicol for Thai cultivars. To date, a comprehensive basil reference genome has been lacking, with only a fragmented draft available.

A multi-cohort study of longitudinal and cross-sectional Alzheimer's disease biomarkers in cognitively unimpaired older adults.

Introduction: The generalizability of neuroimaging and cognitive biomarkers in their sensitivity to detect preclinical Alzheimer's disease (AD) and power to predict progression in large, multisite cohorts remains unclear.

Method: Longitudinal demographics, T1-weighted magnetic resonance imaging (MRI), and cognitive scores of 3036 cognitively unimpaired (CU) older adults (amyloid beta [Aβ]-negative/positive [A-/A+]: 1270/1558) were included. Cross-sectional and longitudinal cognition and medial temporal lobe (MTL) structural measures were extracted.

Alcohol use and HIV suppression after completion of financial incentives for alcohol abstinence and isoniazid adherence: a randomized controlled trial.

Background: In a recent randomized trial, six months of financial incentives contingent for recent alcohol abstinence led to lower levels of hazardous drinking, while incentives for recent isoniazid (INH) ingestion had no impact on INH adherence, during TB preventive therapy among persons with HIV (PWH). Whether the short-term incentives influence long-term alcohol use and HIV viral suppression post-intervention is unknown.

Methods: We analyzed twelve-month HIV viral suppression and alcohol use in the Drinkers' Intervention to Prevent Tuberculosis study, a randomized controlled trial among PWH with latent TB and unhealthy alcohol use in south-western Uganda.

Safety, reactogenicity, and immunogenicity of Ad26.COV2.S co-administered with a quadrivalent standard-dose or high-dose seasonal influenza vaccine: a non-inferiority randomised controlled trial.

Background: Vaccine co-administration can increase vaccination coverage. We assessed the safety, reactogenicity, and immunogenicity of concomitant administration of Ad26.COV2.

Neurocognitive Markers during Maximum Alcohol Use in Late Adolescence as Predictors of Change in Later Drinking Behaviors.

Background: The influence of alcohol use on later neurocognitive functioning is well researched, yet few studies have investigated whether neurocognition post-drinking initiation in adolescence predicts changes in later alcohol use.

Objective: Investigate neurocognitive task performance during maximum alcohol use in late adolescence as predictors of drinking behaviors 3-7 years later.

Methods: Analyses () were conducted on a longitudinal dataset involving adolescents (12-13 years-old) who were followed for 16 years.

Survival disparities among Alzheimer's disease patients in Hawaii.

Background: Survival after an Alzheimer's disease (AD) diagnosis is vital for patients, their families, caregivers, and healthcare providers. Hawaii, known for its diverse ethnic population, exhibits significant racial health disparities.

Objective: This study examined racial/ethnic and socioeconomic disparities in AD survival in Hawaii and developed machine learning models to predict overall survival using Hawaii Medicare data.

Insights into the flexibility of the domain-linking loop in actinobacterial coproheme decarboxylase through structures and molecular dynamics simulations.

Prokaryotic heme biosynthesis in Gram-positive bacteria follows the coproporphyrin-dependent heme biosynthesis pathway. The last step in this pathway is catalyzed by the enzyme coproheme decarboxylase, which oxidatively transforms two propionate groups into vinyl groups yielding heme b. The catalytic reaction cycle of coproheme decarboxylases exhibits four different states: the apo-form, the substrate (coproheme)-bound form, a transient three-propionate intermediate form (monovinyl, monopropionate deuteroheme; MMD), and the product (heme b)-bound form.

Cardio-renal effect of dapagliflozin and dapagliflozin- saxagliptin combination on CD34 + ve hematopoietic stem cells (HSCs) and podocyte specific markers in type 2 diabetes (T2DM) subjects: a randomized trial.

Introduction: Effects of Dapagliflozin (Dapa) and Dapagliflozin-Saxagliptin combination (Combo) was examined on peripheral blood derived CD34 + Hematopoetic Stem Cells (HSCs) as a cellular CVD biomarker. Both Dapa (a sodium-glucose co-transporter 2 or SGLT2, receptor inhibitor) and Saxagliptin (a Di-peptydl-peptidase-4 or DPP4 enzyme inhibitor) are commonly used type 2 diabetes mellitus or T2DM medications, however the benefit of using the combination has not been evaluated for cardio-renal risk assessment, in a real-life practice setting, compared to a placebo.

Hypothesis: We hypothesized that Dapa will improve the outcomes when compared to placebo and the Combo maybe even more beneficial.

Changes in the treatment and outcomes of different severities of neonatal hypoxic ischemic encephalopathy in California: a retrospective cohort study.

Objective: Evaluate the changes in management and outcomes of Californian infants with hypoxic ischemic encephalopathy (HIE).

Study Design: Infants with HIE were identified from a California administrative birth cohort using ICD codes and divided into two epochs, Epoch 1 (2010-2015) and Epoch 2 (2016-2019). Risk ratios (RR) for induced hypothermia (IH) in each epoch and their outcomes were calculated using log-linear regression.

Obsessive-compulsive symptoms in individuals with a history of eating disorders.

Background: OCD symptoms are well documented in anorexia nervosa (AN) and to a lesser extent in bulimia nervosa (BN), yet remain virtually unstudied in binge-eating disorder (BED).

Methods: In this cross-sectional observational study, 5927 participants with lifetime eating disorders (EDs) (i.e.

Fluid flow impacts endothelial-monocyte interactions in a model of vascular inflammatory fibrosis.

The aberrant vascular response associated with tendon injury results in circulating immune cell infiltration and a chronic inflammatory feedback loop leading to poor healing outcomes. Studying this dysregulated tendon repair response in human pathophysiology has been historically challenging due to the reliance on animal models. To address this, our group developed the human tendon-on-a-chip (hToC) to model cellular interactions in the injured tendon microenvironment; however, this model lacked the key element of physiological flow in the vascular compartment.