Single cell and spatial analysis of immune-hot and immune-cold tumours identifies fibroblast subtypes associated with distinct immunological niches and positive immunotherapy response.

Cancer-associated Fibroblasts (CAFs) have emerged as critical regulators of anti-tumour immunity, with both beneficial and detrimental properties that remain poorly characterised. To investigate this, we performed single-cell and spatial transcriptomic analysis, comparing head & neck squamous cell carcinoma (HNSCC) subgroups, which although heterogenous, can be considered broadly immune-hot and immune-cold (human papillomavirus [HPV]+ve and HPV-ve tumours respectively). This identified six fibroblast subpopulations, including two with immunomodulatory gene expression profiles (IL-11 + inflammatory [i]CAF and CCL19 + fibroblastic reticular cell [FRC]-like).

Effects of tenofovir disoproxil fumarate on intrahepatic viral burden and liver immune microenvironment in patients with chronic hepatitis B.

Background: The impact of nucleos(t)ide analogues on intrahepatic viral burden and immune microenvironment in patients with chronic hepatitis B (CHB) is not clear.

Objective: We aimed to characterise the effects of tenofovir disoproxil fumarate (TDF) on intrahepatic viral burden and the liver immune microenvironment in patients with CHB.

Design: Core liver biopsies were collected at baseline and year 3 from patients with CHB with minimally raised serum alanine aminotransferase in a double-blind placebo-controlled trial (NCT01522625).

Leveraging immuno-fluorescence data to reduce pathologist annotation requirements in lung tumor segmentation using deep learning.

The main bottleneck in training a robust tumor segmentation algorithm for non-small cell lung cancer (NSCLC) on H&E is generating sufficient ground truth annotations. Various approaches for generating tumor labels to train a tumor segmentation model was explored. A large dataset of low-cost low-accuracy panCK-based annotations was used to pre-train the model and determine the minimum required size of the expensive but highly accurate pathologist annotations dataset.

Selective depletion of HBV-infected hepatocytes by class A capsid assembly modulators requires high levels of intrahepatic HBV core protein.

Capsid assembly mediated by hepatitis B virus (HBV) core protein (HBc) is an essential part of the HBV replication cycle, which is the target for different classes of capsid assembly modulators (CAMs). While both CAM-A ("aberrant") and CAM-E ("empty") disrupt nucleocapsid assembly and reduce extracellular HBV DNA, CAM-As can also reduce extracellular HBV surface antigen (HBsAg) by triggering apoptosis of HBV-infected cells in preclinical mouse models. However, there have not been substantial HBsAg declines in chronic hepatitis B (CHB) patients treated with CAM-As to date.

The Role of Social Media in the Experiences of COVID-19 Among Long-Hauler Women: Qualitative Study.

Background: The extant literature suggests that women are more vulnerable to COVID-19 infection and at higher risk for developing long COVID. Due to pandemic mitigation recommendations, social media was relied upon for various aspects of daily life, likely with differences of usage between genders.

Objective: This study aimed to explore the role and functions of social media in the lives of long-hauler women.

Repurposing mebendazole against triple-negative breast cancer CNS metastasis.

Purpose: Triple-negative breast cancer (TNBC) often metastasizes to the central nervous system (CNS) and has the highest propensity among breast cancer subtypes to develop leptomeningeal disease (LMD). LMD is a spread of cancer into leptomeningeal space that speeds up the disease progression and severely aggravates the prognosis. LMD has limited treatment options.

Electrolyte Dependence of Li Transport Mechanisms in Small Molecule Solvents from Classical Molecular Dynamics.

As demands on Li-ion battery performance increase, the need for electrolytes with high ionic conductivity and a high Li transference number () becomes crucial to boost power density. Unfortunately, in liquid electrolytes is typically <0.5 due to Li migrating via a vehicular mechanism, whereby Li diffuses along with its solvation shell, making its diffusivity slower than the counteranion.

Impact of enacted stigma on mental health, substance use, and HIV-related behaviors among sexual minority men in Zambia.

Sexual minority men (SMM) in Zambia face significant challenges including stigma, discrimination, and mental health issues, which further impact their HIV-related risk behaviors. This study aimed to investigate the associations between enacted stigma, substance abuse, HIV-related behaviors, and mental health (i.e.

Measurement Instruments Assessing Multi-Faceted Stigma Regarding Sexual and Gender Minorities: A Systematic Review of Psychometric Properties.

Stigma against sexual and gender minorities (SGM) populations has serious negative health effects for SGM populations. Despite the growing need for accurate stigma measurement in SGM, there are insufficient valid measurement instruments. Moreover, the lack of consistency in construct usage makes comparisons across studies particularly challenging.

Stigmatizing clinical setting erodes physician-patient interaction quality for sexual minority men through perceived HIV stigma and HIV infection concerns in Zambia.

This study investigated whether perceived HIV stigma and HIV infection concerns among healthcare providers (HCPs) mediate the association between stigmatizing clinical setting and their interaction quality with sexual minority men (SMM) patients in Zambia. In 2021, a cross-sectional survey was conducted with 91 HCPs offering HIV-related services to SMM in Zambia. Path analysis was conducted to examine the potential mediation effect of "perceived HIV stigma" and "HIV infection concern" among HCPs in the association between "stigmatizing clinical setting" and their "interaction quality with SMM".

Repurposing mebendazole against triple-negative breast cancer leptomeningeal disease.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype that often metastasizes to the brain. Leptomeningeal disease (LMD), a devastating brain metastasis common in TNBC, has limited treatment options. We sought to test whether the common anti-helminthic drug mebendazole (MBZ) may be effective against murine TNBC LMD.

Physician-Patient Interaction Quality Mediates the Association Between HIV-Related Stigma and HIV-Prevention Behaviors Among Sexual Minority Men in Zambia.

HIV-related stigma is a major challenge to HIV prevention for sexual minority men (SMM) in Zambia, but little is known about the underlying mechanisms. This study aimed to investigate whether physician-patient interaction quality mediates the relationship between HIV-related stigma and HIV-prevention behaviors among SMM. Data were collected using a cross-sectional survey from 194 SMM (aged: mean = 24.

Substance use, psychiatric symptoms, personal mastery, and social support among COVID-19 long haulers: A compensatory model.

Background: Substance use has become a critical health concern during the COVID-19 pandemic, and emerging attention has been paid to people with the persistent symptoms of COVID-19 (COVID-19 long haulers) due to their high vulnerability. However, scant research has investigated their substance use and relevant psychosocial factors. The current study was to (1) examine substance use behaviors (i.

Efficient Removal of Uranyl Ions Using PAMAM Dendrimer: Simulation and Experiment.

In this work, using atomistic molecular dynamics (MD) simulations and polymer-assisted ultrafiltration experiments, we explore the adsorption and removal of uranyl ions from aqueous solutions using poly(amidoamine) (PAMAM) dendrimers. The effects of uranyl ion concentration and the pH of the solution were examined for PAMAM dendrimers of generations 3, 4, and 5. Our simulation results show that PAMAM has a high adsorption capacity for the uranyl ions.

Intrahepatic quantification of HBV antigens in chronic hepatitis B reveals heterogeneity and treatment-mediated reductions in HBV core-positive cells.

Background & Aims: Patterns of liver HBV antigen expression have been described but not quantified at single-cell resolution. We applied quantitative techniques to liver biopsies from individuals with chronic hepatitis B and evaluated sampling heterogeneity, effects of disease stage, and nucleos(t)ide (NUC) treatment, and correlations between liver and peripheral viral biomarkers.

Methods: Hepatocytes positive for HBV core and HBsAg were quantified using a novel four-plex immunofluorescence assay and image analysis.

Artificial Intelligence-Based Chatbots for Promoting Health Behavioral Changes: Systematic Review.

Background: Artificial intelligence (AI)-based chatbots can offer personalized, engaging, and on-demand health promotion interventions.

Objective: The aim of this systematic review was to evaluate the feasibility, efficacy, and intervention characteristics of AI chatbots for promoting health behavior change.

Methods: A comprehensive search was conducted in 7 bibliographic databases (PubMed, IEEE Xplore, ACM Digital Library, PsycINFO, Web of Science, Embase, and JMIR publications) for empirical articles published from 1980 to 2022 that evaluated the feasibility or efficacy of AI chatbots for behavior change.

Interaortocaval Lymph Node Metastasis in Gall Bladder Cancer: Is It Regional Node or Metastatic Disease?

Background And Objectives: Interaortocaval or para-aortic lymph node (IACLN) metastasis in gall bladder cancer (GBC) is usually a contraindication to curative resection with a prognosis similar to liver or peritoneal metastases. However, few authors have reported survival similar to regional lymph node (RLN) positive disease after curative resection in these patients. This study aims to analyse the role of curative surgery in such cases.

Mapping the hepatic immune landscape identifies monocytic macrophages as key drivers of steatohepatitis and cholangiopathy progression.

Background And Aims: The progression of chronic liver diseases towards liver cirrhosis is accompanied by drastic tissue changes. This study combines elaborate transcriptomic and histological methods aiming at spatially resolving the hepatic immune microenvironment in NAFLD (including NASH, primary sclerosing cholangitis, primary biliary cholangitis, and severe alcoholic hepatitis).

Approach And Results: Human liver samples were subjected to RNA-sequencing (n=225) and imaging cytometry (n=99) across 3 independent patient cohorts.

A rare case of peritoneal metastases from oropharyngeal squamous cell carcinoma in a young male after completion of chemoradiotherapy.

Distant metastases are frequent in head and neck squamous cell carcinomas (HNSCC), but they are limited to some organs like lungs, bone, mediastinum, liver and brain. Peritoneal metastases (PMs) from HNSCC are extremely rare. A 28-year-old chronic smoker and alcoholic was diagnosed with squamous cell carcinoma of oropharynx.

Substance use, psychiatric symptoms, personal mastery, and social support among COVID-19 long haulers: A compensatory model.

Background: Substance use has become a critical health concern during the COVID-19 pandemic, and emerging attention has been paid to people with the persistent symptoms of COVID-19 (COVID-19 long haulers) due to their high vulnerability. However, scant research has investigated their substance use and relevant psychosocial factors. The current study was to (1) examine substance use behaviors (i.

Resilience resources and coping strategies of COVID-19 female long haulers: A qualitative study.

Background: Female long haulers deal with persistent post-acute COVID-19 symptoms that have serious health implications. This study aimed to identify resilience resources at multiple socio-ecological levels for female long haulers and describe how resilience resources affect their responses to long COVID.

Methods: Purposive sampling was adopted to recruit participants through social media from April to June 2021 followed by 15 semi-structured interviews.

Molecular Rectifiers with a Very High Rectification Ratio Enabled by Oxidative Damage in Double-Stranded DNA.

In this work, we report a novel strategy to construct highly efficient molecular diodes using oxidatively damaged DNA molecules. Being exposed to several endogenous and exogenous events, DNA suffers from constant oxidative damage, leading to the oxidation of guanine to 8-oxoguanine (8oxoG). Here, we study the charge migration properties of native and oxidatively damaged DNA using a multiscale multiconfigurational methodology comprising molecular dynamics, density functional theory, and kinetic Monte Carlo simulations.

Emerging Trends in Stroke Epidemiology in Indian Women Over the Last Decade.

Background And Objective: Temporal trends in clinico-epidemiological parameters of stroke among Indian women have not been studied. We aimed to study the changes in these parameters over the last decade.

Material And Methods: 417 strokes (ischemic/hemorrhagic) were prospectively recruited in two timelines.

Multi-parametric analysis of human livers reveals variation in intrahepatic inflammation across phases of chronic hepatitis B infection.

Background & Aims: Chronic HBV is clinically categorized into 4 phases by a combination of serum HBV DNA levels, HBeAg status and alanine aminotransferase (ALT): immunotolerant (IT), immune-active (IA), inactive carrier (IC) and HBeAg-negative hepatitis (ENEG). Immune and virological measurements in the blood have proven useful but are insufficient to explain the interrelation between the immune system and the virus since immune dynamics differ in the blood and liver. Furthermore, the inflammatory response in the liver and parenchymal cells cannot be fully captured in blood.