Progress and challenges in the elimination of hepatitis C among people who inject drugs in Germany: results of a pilot study for a national monitoring system, 10 years after the first data collection.

Background: People who inject drugs (PWID) are at high risk of blood-borne infections, and injection drug use contributes significantly to hepatitis C virus (HCV) transmission. The WHO has therefore set targets of reducing HCV incidence and prevalence among PWID and increasing treatment coverage to eliminate HCV by 2030. The DRUCK study (2011-2014) found high HCV prevalence and low treatment coverage among PWID in Germany.

Global versus local matrix remodeling drives rotational versus invasive collective migration of epithelial cells.

The coordinated movement of cell collectives is essential for normal epithelial tissue development, maintenance, and cancer progression. Here, we report on a minimal 3D extracellular matrix (ECM) system wherein both invasive collective migration (ICM) and rotational collective migration (RCM) arise spontaneously from individually seeded epithelial cells of mammary and hepatic origin, regardless of whether they express adherens junctions, and lead to ductal-like and acinar-like structures, respectively. Quantitative microscopy and cellular Potts modeling reveal that initial differences in cell protrusion dynamics and matrix-remodeling localization generate RCM and ICM behavior in confining 3D ECM.

Optimization of Potent and Selective Cyclohexyl Acid ERAP1 Inhibitors Using Structure- and Property-Based Drug Design.

Endoplasmic reticulum aminopeptidase 1 (ERAP1) cleaves the -terminal amino acids of peptides, which can then bind onto major histocompatibility class I (MHC-I) molecules for presentation onto the cell surface, driving the activation of adaptive immune responses. In cancer, overtrimming of mature antigenic peptides can reduce cytotoxic T-cell responses, and ERAP1 can generate self-antigenic peptides which contribute to autoimmune cellular responses. Therefore, modulation of ERAP1 activity has potential therapeutic indications for cancer immunotherapy and in autoimmune disease.

Project ECHO Diabetes Trial Improves Outcomes for Medically Underserved People.

Objective: The Project Extension for Community Healthcare Outcomes (ECHO) model is used in 180 countries to address chronic disease care through a provider empowerment, tele-education approach. Few studies have rigorously evaluated the impact of the program on patient outcomes using randomized designs.

Research Design And Methods: Implementation of an ECHO Diabetes program was evaluated using a stepped-wedge design with recruitment of 20 federally qualified health centers (FQHCs) across California and Florida with randomized, phased-in intervention entry.

Patient-Clinician Communication Interventions Across Multiple Primary Care Sites: A Cluster Randomized Clinical Trial.

Importance: Despite various attempts to improve patient-clinician communication, there has been limited head-to-head comparison of these efforts.

Objective: To assess whether clinician coaching (mobile application or in-person) is more effective than reminder posters in examination rooms and whether mobile app use is noninferior to in-person coaching.

Design, Setting, And Participants: A cluster randomized clinical trial with 3 arms.

Blood IL-1α and IL-6 predict specific breast cancer-induced increases in hippocampal pro-inflammatory cytokines in mice.

Neuroinflammation is a key factor in cognitive and behavioral changes seen in patients with non-CNS cancers, and cytokine levels in the blood are often used as a proxy for brain inflammation. However, this approach has yielded inconsistent results, and a common inflammatory signature remains elusive. To explore whether a blood-to-brain inflammatory signature exists across breast cancer types, we assessed cytokine and glial protein responses in the hippocampus, prefrontal cortex (PFC), and their relationship to serum cytokines in mice bearing three different mammary cancers (n = 40).

Molecular interactions between male and female schistosomes - a role for remote communication?

Persistent physical interaction between male and female schistosome adult worms has long been shown to be crucial for their development and sexual maturation, particularly for the female. Although not fully understood, worm pairing promotes local molecular communication between sexes, driving gonad and vitellaria differentiation. In this opinion article we (i) summarise evidence concerning molecular interactions underlying the physical pairing, and (ii) propose a new paradigm whereby remote male-female molecular communication may play an overlooked role in parasite sexual maturation.

Photosynthetic responses to temperature across the tropics: a meta-analytic approach.

Background And Aims: Tropical forests exchange more carbon dioxide (CO2) with the atmosphere than any other terrestrial biome. Yet, uncertainty in the projected carbon balance over the next century is roughly three-times greater for the tropics than other ecosystems. Our limited knowledge of tropical plant physiological responses, including photosynthetic, to climate change is a substantial source of uncertainty in our ability to forecast the global terrestrial carbon sink.

Digital Technologies Tracking Active and Passive Data Collection in Depressive Disorders: Lessons Learned From a Case Series.

In this case series, we present several examples from participants (2 patients and 1 healthy control) of a 12-week pilot feasibility study to create a digital phenotype of depression (unipolar or bipolar) through active and passive data collection from a smartphone and a wearable device combined with routine clinical care for mood disorders. The selected cases represent real clinical examples that highlight the intrinsic challenges that should be expected when conducting similar studies, including appropriate health data privacy protection, clinical standardization, and interindividual differences in levels of engagement and acceptability of active and passive data collection (ie, self-reported, behavioral, cognitive, and physiological data), particularly with patient-generated data in mobile apps, digital proficiency habituation, and consistent use of wearable devices. In the context of the rapidly growing use of digital technologies in psychiatry, anticipating challenges for the integration of personal mobile devices and smartphone mental health apps as aides to track specific aspects of depressive disorders is critical for a clinically meaningful digital transformation of mood disorders care.

Robust self-supervised denoising of voltage imaging data using CellMincer.

Voltage imaging is a powerful technique for studying neuronal activity, but its effectiveness is often constrained by low signal-to-noise ratios (SNR). Traditional denoising methods, such as matrix factorization, impose rigid assumptions about noise and signal structures, while existing deep learning approaches fail to fully capture the rapid dynamics and complex dependencies inherent in voltage imaging data. Here, we introduce CellMincer, a novel self-supervised deep learning method specifically developed for denoising voltage imaging datasets.

Yatakemycin biosynthesis requires two deoxyribonucleases for toxin self-resistance.

The highly active natural product yatakemycin (YTM) from sp. TP-A0356 is a potent DNA damaging agent with antimicrobial and antitumor properties. The YTM biosynthesis gene cluster () contains several toxin self-resistance genes.

Non-adherence to immunosuppressive medications in kidney transplant recipients- a systematic scoping review.

Background: Rejection and graft failure remain common in kidney transplant recipients. Non-adherence to immunosuppressive medications is considered a major contributary factor to reduced long-term graft survival, particularly in younger people. Improvements in clinical practice based on adherence studies has been minimal.

Determining Targets for Antiretroviral Drug Concentrations: A Causal Framework Illustrated With Pediatric Efavirenz Data From the CHAPAS-3 Trial.

Background: Determining a therapeutic window for maintaining antiretroviral drug concentrations within an appropriate range is required for identifying effective dosing regimens. The limits of this window are typically calculated using predictive models. We propose that target concentrations should instead be calculated based on counterfactual probabilities of relevant outcomes and describe a counterfactual framework for this.

Divergent changes in complement pathway gene expression in schizophrenia and bipolar disorder: Links to inflammation and neurogenesis in the subependymal zone.

Deficits in neurogenesis markers in the subependymal zone (SEZ) are associated with elevated inflammation in schizophrenia and bipolar disorder. However, the extent to which complement factors are also changed in the SEZ of these major psychiatric disorders and their impact on neurogenesis remains poorly understood. We extracted RNA from the SEZ of 93 brains, including controls (n = 32), schizophrenia (n = 32), and bipolar disorder (n = 29) cases.

Dementia Risk and Social Determinants of Health Among Adults Racialized as Black: A Community-Based System Dynamics Perspective.

Background: The aging population in the USA is projected to increase significantly, with a corresponding rise in dementia cases, particularly among racial minorities. This study examines the key drivers of racial disparities in dementia risk among older Black adults in the St. Louis area, a region characterized by entrenched structural racism.

Deep learning-based classifier for carcinoma of unknown primary using methylation quantitative trait loci.

Cancer of unknown primary (CUP) constitutes between 2% and 5% of human malignancies and is among the most common causes of cancer death in the United States. Brain metastases are often the first clinical presentation of CUP; despite extensive pathological and imaging studies, 20%-45% of CUP are never assigned a primary site. DNA methylation array profiling is a reliable method for tumor classification but tumor-type-specific classifier development requires many reference samples.

HEAL-D Online: Exploring the potential for the spread and adoption of a virtual culturally tailored diabetes self-management programme for adults of African and Caribbean heritage.

Background: People of African and Caribbean heritage in the UK have a higher prevalence of Type 2 Diabetes (T2D) and poorer health outcomes than white Europeans. Healthy Eating and Active Lifestyles for Diabetes Online (HEAL-D Online) is a co-designed, culturally tailored T2D self-management programme for black African and Caribbean adults, which, due to online delivery, is well positioned for spread. This qualitative evaluation uses the Exploration-Preparation-Implementation-Sustainment (EPIS) framework to explore factors affecting scale-up from delivery and commissioning perspectives.

Viral sequence determines HLA-E-restricted T cell recognition of hepatitis B surface antigen.

The non-polymorphic HLA-E molecule offers opportunities for new universal immunotherapeutic approaches to chronic infectious diseases. Chronic Hepatitis B virus (HBV) infection is driven in part by T cell dysfunction due to elevated levels of the HBV envelope (Env) protein hepatitis B surface antigen (HBsAg). Here we report the characterization of three genotypic variants of an HLA-E-binding HBsAg peptide, Env identified through bioinformatic predictions and verified by biochemical and cellular assays.

Partisan language in a polarized world: In-group language provides reputational benefits to speakers while polarizing audiences.

We examine the impact of partisan language (i.e., language that describes events in a manner that supports a political agenda), both with regard to peoples' perceptions of the speakers who use it and their evaluations of the events it is used to describe.

Arousal threshold modifies the effect of CPAP on executive function among individuals with obstructive sleep apnea.

Unlabelled: Arousal Threshold Modifies the Effect of CPAP on Executive Function Among Individuals with Obstructive Sleep Apnea.

Background: Obstructive Sleep Apnea (OSA) is associated with neurocognitive dysfunction. However, randomized trials evaluating the effects of continuous positive airway pressure (CPAP) on neurocognition in those without dementia do not show a benefit.

The Impact of Intimate Partner Violence on Gay Men's Personal and Working Lives.

Research into intimate partner violence (IPV) has focused on the experience of female victims resulting from dominant theoretical frameworks and societal biases casting females as victims and males as abusers. While emergent studies suggest that gay male victims experience a higher prevalence rate and more severe consequences from IPV than heterosexuals victims (male or female), few studies have explored the impact of IPV on gay male victims personal and working lives. We conducted a qualitative case study analysis using an Interpretive Phenomenological Analysis by interviewing four gay males with experience of IPV.

IL-1 receptor antagonist anakinra downregulates inflammatory cytokines during renal normothermic machine perfusion: Preliminary results.

Background: The interleukin 1 (IL-1) cytokine group plays a key role in sterile inflammation and may be an important target for transplant-related renal injury. This study examined the effects of anakinra, a non-specific IL-1 receptor antagonist, administered during normothermic machine perfusion (NMP) of porcine kidneys.

Method: Paired porcine kidneys (n = 5 pairs) underwent 15 min of warm ischemia plus 2 h of static cold storage in ice.

Predicting individual patient and hospital-level discharge using machine learning.

Background: Accurately predicting hospital discharge events could help improve patient flow and the efficiency of healthcare delivery. However, using machine learning and diverse electronic health record (EHR) data for this task remains incompletely explored.

Methods: We used EHR data from February-2017 to January-2020 from Oxfordshire, UK to predict hospital discharges in the next 24 h.