Longitudinal analysis of the gut microbiota during anti-PD-1 therapy reveals stable microbial features of response in melanoma patients.

Immune checkpoint inhibitors (ICIs) improve outcomes in advanced melanoma, but many patients are refractory or experience relapse. The gut microbiota modulates antitumor responses. However, inconsistent baseline predictors point to heterogeneity in responses and inadequacy of cross-sectional data.

Using Phosphatidylethanol as an Adjunct to Self-Reported Alcohol Use Improves Identification of Liver Fibrosis Risk.

Introduction: Accurate assessment of alcohol use informs prevention and management of liver disease. We examined whether phosphatidylethanol (PEth, an alcohol metabolite) blood concentrations are associated with liver fibrosis risk independently of self-reported alcohol use, among persons with and without HIV.

Methods: We pooled individual-level data from 12 studies from the United States, Russia, Uganda, and South Africa with PEth, Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), and fibrosis-4 (FIB-4) measurements.

Characterising impaired awareness of hypoglycaemia and associated risks through HypoA-Q: findings from a T1D Exchange cohort.

Aims/hypothesis: We aimed to: (1) externally validate the five-item Hypoglycaemia Awareness Questionnaire (HypoA-Q) impaired awareness subscale (HypoA-Q IA); (2) examine how impaired awareness of hypoglycaemia (IAH) relates to the risk of severe hypoglycaemia and level 2 hypoglycaemia; and (3) identify factors associated with IAH.

Methods: Nationwide survey of T1D Exchange registrants was conducted to collect data on demographics, 6 month severe-hypoglycaemia history, hypoglycaemia awareness status (via HypoA-Q IA, the Gold instrument and the Clarke instrument) and continuous glucose monitor (CGM) measures. The Clarke hypoglycaemia awareness factor (Clarke-HAF) was calculated to exclude severe-hypoglycaemia history items.

Identification and characterization of thiamine analogs with antiplasmodial activity.

Thiamine is metabolized into thiamine pyrophosphate (TPP), an essential enzyme cofactor. Previous work has shown that oxythiamine, a thiamine analog, is metabolized by thiamine pyrophosphokinase (TPK) into oxythiamine pyrophosphate within the malaria parasite and then inhibits TPP-dependent enzymes, killing the parasite and . To identify a more potent antiplasmodial thiamine analog, 11 commercially available compounds were tested against and .

Focal granule cell bilamination of the dentate gyrus-its prevalence across the human age spectrum and review of the literature.

The prevalence of focal granule cell bilamination (FGCB) in the hippocampal dentate gyrus varies from 0% to 44%, depending on age and study population. FGCB is commonly thought to be a specific feature of temporal lobe epilepsy (TLE) but its prevalence in cases without TLE is unclear. Using formalin-fixed, paraffin-embedded hippocampal sections, this retrospective postmortem study evaluated the prevalence of FGCB and other granule cell pathologies in infants (1-12 months of age, n = 16), children (4-10 years, n = 6), and adults (28-91 years, n = 15) with no known history of epilepsy or seizures.

A robust deep learning approach for identification of RNA 5-methyluridine sites.

RNA 5-methyluridine (m5U) sites play a significant role in understanding RNA modifications, which influence numerous biological processes such as gene expression and cellular functioning. Consequently, the identification of m5U sites can play a vital role in the integrity, structure, and function of RNA molecules. Therefore, this study introduces GRUpred-m5U, a novel deep learning-based framework based on a gated recurrent unit in mature RNA and full transcript RNA datasets.

The VEGFA-Induced MAPK-AKT/PTEN/TGFβ Signal Pathway Enhances Progression and MDR in Gastric Cancer.

Background/objectives: Gastric cancer (GC) is a globally frequent cancer, in particular leading in mortality caused by digestive tract cancers in China. Vascular endothelial growth factor A (VEGFA) is excessively expressed in cancers including GC; its involvement in GC development, particularly in multidrug resistance (MDR), and the signal route it affects in GC remain unknown. To explore the roles VEGFA plays during progression and MDR formation in GC, we studied its function in a VEGFA-deleted GC cell platform.

Anticancer Activity of Vitamin D, Lumisterol and Selected Derivatives against Human Malignant Melanoma Cell Lines.

Despite the recent development of improved methods of treating melanoma such as targeted therapy, immunotherapy or combined treatment, the number of new cases worldwide is increasing. It is well known that active metabolites of vitamin D and lumisterol (L) exert photoprotective and antiproliferative effects on the skin, while UV radiation is a major environmental risk factor for melanoma. Thus, many natural metabolites and synthetic analogs of steroidal and secosteroidal molecules have been tested on various cancer cells and in animal models.

Drinking firsts at home and with parental knowledge: Racial/ethnic differences in associations with later alcohol outcomes among underage youth.

Background: Prior research has shown that early alcohol experiences, such as age of initiation and speed of progression between drinking milestones, vary across racial/ethnic groups. To inform culturally tailored prevention efforts, this longitudinal study examined racial/ethnic differences in the associations of drinking firsts at home and with parental knowledge with alcohol use outcomes among underage youth.

Methods: The study included baseline and five follow-up surveys, collected every 6 months, from California adolescents (ages 12-16 years at baseline).

Differential effects of myosin activators on myocardial contractile function in nonfailing and failing human hearts.

The second-generation myosin activator danicamtiv (DN) has shown improved function compared with the first-generation myosin activator omecamtiv mecarbil (OM) in nonfailing myocardium by enhancing cardiac force generation but attenuating slowed relaxation. However, whether the functional improvement with DN compared with OM persists in remodeled failing myocardium remains unknown. Therefore, this study aimed to investigate the differential contractile responses to myosin activators in nonfailing and failing myocardium.

A (sub)field guide to quality control in hippocampal subfield segmentation on high-resolution T-weighted MRI.

Inquiries into properties of brain structure and function have progressed due to developments in magnetic resonance imaging (MRI). To sustain progress in investigating and quantifying neuroanatomical details in vivo, the reliability and validity of brain measurements are paramount. Quality control (QC) is a set of procedures for mitigating errors and ensuring the validity and reliability of brain measurements.

Factor V Leiden (R506Q), Prothrombin G20210A, and MTHFR C677T Variants and Thrombophilia in Qatar Biobank Participants: A Case Control Study.

Thrombophilia, a predisposition to develop blood clots, is very common and can have serious sequelae. This study aimed to determine the prevalence of three thrombophilia-related genetic variants-factor V Leiden (FVL), prothrombin (F2) G20210A, and MTHFR C677T-in the Qatari population and their associations with self-reported thrombosis. We analysed samples from 408 Qatari participants [304 controls and 104 with self-reported thrombosis (deep vein thrombosis, pulmonary embolus, or ischaemic stroke)] from the Qatar Biobank.

Enhancing causal inference in population-based neuroimaging data in children and adolescents.

Recent years have seen the increasing availability of large, population-based, longitudinal neuroimaging datasets, providing unprecedented capacity to examine brain-behavior relationships in the neurodevelopmental context. However, the ability of these datasets to deliver causal insights into brain-behavior relationships relies on the application of purpose-built analysis methods to counter the biases that otherwise preclude causal inference from observational data. Here we introduce these approaches (i.

Disease Activity in Pregnant and Postpartum Women With Multiple Sclerosis Receiving Ocrelizumab or Other Disease-Modifying Therapies.

Background And Objectives: Women with multiple sclerosis (MS) are at risk of disease reactivation in the early postpartum period. Ocrelizumab (OCR) is an anti-CD20 therapy highly effective at reducing MS disease activity. Data remain limited regarding use of disease-modifying therapies (DMTs), including OCR, and disease activity during peripregnancy periods.

Feasibility, acceptability, and preliminary efficacy of a self-directed online psychosocial intervention for women with metastatic breast cancer: Finding My Way-Advanced.

Purpose: Few digital interventions target patients with advanced cancer. Hence, we feasibility-tested Finding My Way-Advanced (FMW-A), a self-guided program for women with metastatic breast cancer.

Methods: A single-site randomised controlled pilot trial was conducted.

Slow dissociation kinetics of fentanyls and nitazenes correlates with reduced sensitivity to naloxone reversal at the μ-opioid receptor.

Background And Purpose: Fentanyls and nitazenes are μ-opioid receptor agonists responsible for a large number of opioid overdose deaths. Here, we determined the potency, dissociation kinetics and antagonism by naloxone at the μ receptor of several fentanyl and nitazene analogues, compared to morphine and DAMGO.

Experimental Approach: In vitro assays of G protein activation and signalling and arrestin recruitment were performed.

A Multi-Responsive Hydrogel Combined With Mild Heat Stimulation Promotes Diabetic Wound Healing by Regulating Inflammatory and Enhancing Angiogenesis.

The repair of diabetic wound still encounters huge challenges, such as disordered inflammatory regulation and impaired neovascularization. Here, a pH/ROS/glucose responsive and photothermal hydrogel is developed for diabetic wound healing. The hydrogel is formed through cross-linkage between phenylboronic acid-modified carboxymethyl chitosan (CMCS-PBA) and oxide dextran (OXD), utilizing Schiff base and phenylboronate ester bonds.

Diversity, functional classification and genotyping of SHV β-lactamases in .

Interpreting the phenotypes of alleles in genomes is complex. Whilst all strains are expected to carry a chromosomal copy conferring resistance to ampicillin, they may also carry mutations in chromosomal alleles or additional plasmid-borne alleles that have extended-spectrum β-lactamase (ESBL) activity and/or β-lactamase inhibitor (BLI) resistance activity. In addition, the role of individual mutations/a changes is not completely documented or understood.