Discovery of Methylated DNA Biomarkers for Potential Non-Endoscopic Detection of Barrett's Esophagus and Esophageal Adenocarcinoma.

Background And Aims: We sought to develop a minimally-invasive, robust, accessible nonendoscopic strategy to diagnose Barrett's esophagus (BE), esophageal adenocarcinoma (EAC), and its immediate precursor lesion, high-grade dysplasia (HGD) based on methylated DNA biomarkers applied to a retrievable sponge-capsule device in a cohort representative of the BE population (i.e., mostly short-segment, non-dysplastic BE, NDBE).

The Roles of Ninjurin1 and Estrogen in Modulating AOM/DSS-Induced Colitis-Associated Colorectal Cancer in Male Mice.

Purpose: Ninjury-induced protein 1 (Ninj1) is associated with inflammation and tumor progression and shows increased expression in various cancers. This study aimed to investigate the role of Ninj1 in colitis-associated colorectal cancer (CRC) by focusing on its interaction with 17β-estradiol (E2).

Materials And Methods: Using an azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse model of colitis-associated CRC, wild-type (WT) and Ninj1 knockout (KO) male mice were treated with or without E2.

Hierarchical gradients of multiple timescales in the mammalian forebrain.

Many anatomical and physiological features of cortical circuits, ranging from the biophysical properties of synapses to the connectivity patterns among different neuron types, exhibit consistent variation along the hierarchical axis from sensory to association areas. Notably, the temporal correlation of neural activity at rest, known as the intrinsic timescale, increases systematically along this hierarchy in both primates and rodents, analogous to the increasing scale and complexity of spatial receptive fields. However, how the timescales for task-related activity vary across brain regions and whether their hierarchical organization appears consistently across different mammalian species remain unexplored.

Optimal Long-term Antiplatelet Regimen for Patients with High Ischaemic and Bleeding Risks After Percutaneous Coronary Intervention.

Aim To assess an optimal long-term antiplatelet strategy in patients at both high ischaemic and bleeding risks after percutaneous coronary intervention (PCI). Methods and results Patients both at high ischaemic and bleeding risks were eligible for inclusion. We excluded patients with any ischaemic and major bleeding complications during the mandatory period of dual antiplatelet therapy (DAPT).

Exploring NNMT: from metabolic pathways to therapeutic targets.

Cellular metabolism-related epigenetic modulation plays a pivotal role in the maintenance of cellular homeostasis. Nicotinamide N-methyltransferase (NNMT) serves as a crucial link between cellular metabolism and epigenetics by catalyzing nicotinamide methylation using the universal methyl donor S-adenosyl-L-methionine. This direct connection bridges the methylation-mediated one-carbon metabolism with nicotinamide adenine dinucleotide levels.

Safety and Efficacy of Pivot-Balloon for Severe Tricuspid Regurgitation: The First-in-Man Experiences.

Background And Objectives: Among various emerging catheter-based treatments for severe tricuspid regurgitation (TR), the spacer device can reduce the regurgitation orifice without manipulating the valve leaflet. However, its clinical application has been hampered by traumatic anchoring to the myocardium and the coaxial alignment of the balloon resulting in insufficient TR reduction. This study aimed to evaluate the early-stage safety, technical feasibility, and preliminary efficacy of the novel atraumatic vertical spacer in patients with isolated severe TR.

Fecal Microbiome Composition Correlates with Pathologic Complete Response in Patients with Operable Esophageal Cancer Treated with Combined Chemoradiotherapy and Immunotherapy.

: Preclinical and clinical data indicate that chemoradiotherapy (CRT) in combination with checkpoint inhibitors may prime an anti-tumor immunological response in esophageal cancer. However, responses to neoadjuvant therapy can vary widely and the key biomarkers to determine response remain poorly understood. The fecal microbiome is a novel and potentially modifiable biomarker of immunotherapy response, and both fecal and tumor microbes have been found to associate with outcomes in esophageal cancer.

Ninjurin1 deficiency differentially mitigates colorectal cancer induced by azoxymethane and dextran sulfate sodium in male and female mice.

This study investigated the role of Ninjurin1 (Ninj1), encoding a small transmembrane protein, in colitis-associated colon tumorigenesis in relation to sex hormones. Male and female wild-type (WT) and Ninj1 knockout (KO) mice were treated with azoxymethane (AOM) and dextran sulfate sodium (DSS), with or without testosterone propionate (TP). At week 2 (acute colitis stage), Ninj1 KO exhibited an alleviation in the colitis symptoms in both male and female mice.

Deep learning-based analysis of EGFR mutation prevalence in lung adenocarcinoma H&E whole slide images.

EGFR mutations are a major prognostic factor in lung adenocarcinoma. However, current detection methods require sufficient samples and are costly. Deep learning is promising for mutation prediction in histopathological image analysis but has limitations in that it does not sufficiently reflect tumor heterogeneity and lacks interpretability.

Neurodevelopmental imprints of sociomarkers in adolescent brain connectomes.

Neural consequences of social disparities are not yet rigorously investigated. How socioeconomic conditions influence children's connectome development remains unknown. This paper endeavors to gauge how precisely the connectome structure of the brain can predict an individual's social environment, thereby inversely assessing how social influences are engraved in the neural development of the Adolescent brain.

Mitochondria Activity and CXCR4 Collaboratively Promote the Differentiation of CD11c B Cells Induced by TLR9 in Lupus.

Lupus is characterized by the autoantibodies against nuclear Ags, underscoring the importance of identifying the B cell subsets driving autoimmunity. Our research focused on the mitochondrial activity and CXCR4 expression in CD11c B cells from lupus patients after stimulation with a TLR9 agonist, CpG-oligodeoxyribonucleotide (ODN). We also evaluated the response of CD11c B cells in ODN-injected mice.

An inducible sphingosine kinase 1 in hepatic stellate cells potentiates liver fibrosis.

Hepatic stellate cells (HSCs) play a role in hepatic fibrosis and sphingosine kinase (SphK) is involved in biological processes. As studies on the regulatory mechanisms and functions of SphK in HSCs during liver fibrosis are currently limited, this study aimed to elucidate the regulatory mechanism and connected pathways of SphK upon HSC activation. The expression of SphK1 was higher in HSCs than in hepatocytes, and upregulated in activated primary HSCs.

Hierarchical gradients of multiple timescales in the mammalian forebrain.

Many anatomical and physiological features of cortical circuits, ranging from the biophysical properties of synapses to the connectivity patterns among different neuron types, exhibit consistent variation along the hierarchical axis from sensory to association areas. Notably, the scale of temporal correlation of neural activity at rest, known as the intrinsic timescale, increases systematically along this hierarchy in both primates and rodents, analogous to the growing scale and complexity of spatial receptive fields. However, how the timescales for task-related activity vary across brain regions and whether their hierarchical organization appears consistently across different mammalian species remain unexplored.

EUS-guided hydrogel injection to separate pancreatic head carcinoma from duodenum for enhanced radiotherapy: Multi-site feasibility study.

The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum. In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas.

Patterns and sources of spatial inequity in freight crashes: An application of decomposition analysis.

Despite considerable increases in road freight traffic and associated crashes over the past decade, our understanding of their spatial distribution remains limited. This is concerning because freight vehicle crashes often lead to fatal and severe injuries. This study focuses on Seoul, South Korea and contributes to the literature by investigating the patterns and sources of spatial inequity in freight crashes.

Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses.

Gastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity of dual programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy responses for these tumors. We report a phase Ib trial that evaluated neoadjuvant nivolumab (Arm A, n = 16) or nivolumab-relatlimab (Arm B, n = 16) in combination with chemoradiotherapy in 32 patients with resectable stage II/stage III gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses.

Factors associated with different types of freight crashes: A macro-level analysis.

Introduction: Despite evidence showing higher fatality rates in freight-related crashes, there has been limited exploration of their spatial distribution and factors associated with such distribution. This gap in the literature primarily stems from the focus of existing studies on micro-level factors predicting the frequency or severity of injuries in freight crashes. The present study delves into the factors contributing to freight crashes at the neighborhood level, particularly focusing on different types of freight crashes: collisions involving a freight vehicle and a passenger vehicle, crashes between freight vehicles, and freight vehicle-non-motorized crashes.