Clinical Characteristics of Virologically Confirmed Respiratory Syncytial Virus in English Primary Care: Protocol for an Observational Study of Acute Respiratory Infection.

Background: There are gaps in our understanding of the clinical characteristics and disease burden of the respiratory syncytial virus (RSV) among community-dwelling adults. This is in part due to a lack of routine testing at the point of care. More data would enhance our assessment of the need for an RSV vaccination program for adults in the United Kingdom.

Hybrid strains of enterotoxigenic/Shiga toxin-producing , United Kingdom, 2014-2023.

Diarrhoeagenic (DEC) pathotypes are defined by genes located on mobile genetic elements, and more than one definitive pathogenicity gene may be present in the same strain. In August 2022, UK Health Security Agency (UKHSA) surveillance systems detected an outbreak of hybrid Shiga toxin-producing /enterotoxigenic (STEC-ETEC) serotype O101:H33 harbouring both Shiga toxin () and heat-stable toxin (). These hybrid strains of DEC are a public health concern, as they are often associated with enhanced pathogenicity.

Cerebral Microbleeds and Amyloid Pathology Estimates From the Amyloid Biomarker Study.

Importance: Baseline cerebral microbleeds (CMBs) and APOE ε4 allele copy number are important risk factors for amyloid-related imaging abnormalities in patients with Alzheimer disease (AD) receiving therapies to lower amyloid-β plaque levels.

Objective: To provide prevalence estimates of any, no more than 4, or fewer than 2 CMBs in association with amyloid status, APOE ε4 copy number, and age.

Design, Setting, And Participants: This cross-sectional study used data included in the Amyloid Biomarker Study data pooling initiative (January 1, 2012, to the present [data collection is ongoing]).

Dual Biological Role and Clinical Impact of De Novo Chromatin Activation in Chronic Lymphocytic Leukemia.

Previous studies have reported that chronic lymphocytic leukemia (CLL) shows a de novo chromatin activation pattern as compared to normal B cells. Here, we explored whether the level of chromatin activation is related to the clinical behavior of CLL. We identified that in some regulatory regions, increased de novo chromatin activation is linked to clinical progression whereas, in other regions, it is associated with an indolent course.

Evaluating the impact of CRBN mutations on response to immunomodulatory drugs and novel CRBN-binding agents in myeloma.

Immunomodulatory drug (IMiD) resistance is a key clinical challenge in myeloma treatment. Previous data suggests almost one third of myeloma patients acquire mutations in the key IMiD effector cereblon by the time they are pomalidomide refractory. Some events, including stop codons/frameshift mutations and copy loss, having clearly explicable effects on cereblon function.

Depressive Symptoms and Amyloid Pathology.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

Clinical Phenotype and Prognosis of Asymptomatic Patients With Transthyretin Cardiac Amyloid Infiltration.

Importance: Patients with transthyretin (ATTR) cardiac amyloid infiltration are increasingly diagnosed at earlier disease stages with no heart failure (HF) symptoms and a wide range of cardiac amyloid infiltration.

Objective: To characterize the clinical phenotype and natural history of asymptomatic patients with ATTR cardiac amyloid infiltration.

Design, Setting, And Participants: This cohort study analyzed data of all patients at 12 international centers for amyloidosis from January 1, 2008, through December 31, 2023.

On face value: a ghost driver field study investigating interactions between pedestrians and a driverless vehicle with anthropomorphic displays.

In a novel, on-road study, using a 'Ghost Driver' to emulate an automated vehicle (AV), we captured over 10 hours of video (n = 520) and 64 survey responses documenting the behaviour and attitudes of pedestrians in response to the AV. Three prototype external human-machine interfaces (eHMIs) described the AV's behaviour, awareness and intention using elements of anthropomorphism: High (human face), Low (car motif), Abstract (partial representation of human features that lacked precise visual reference); these were evaluated against a (no eHMI) baseline. Despite many pedestrians reporting that they still relied on vehicular cues to negotiate their crossing, there was a desire/expectation expressed for explicit communication with future AVs.

Improving Therapeutic Adherence and Reducing Therapeutic Inertia in the Management of People with Cardiometabolic Diseases: A Call-to-Action from the Middle East.

Hypertension, dyslipidemia, and type 2 diabetes are highly prevalent and poorly controlled cardiometabolic diseases in the Middle East. Therapeutic non-adherence and therapeutic inertia are major contributors to this suboptimal disease control. Regardless of the cardiometabolic disease, evidence-based solutions may be used to improve therapeutic non-adherence and overcome inertia, and thereby help to alleviate the heavy burden of cardiovascular disease in the Middle East.

Preventing inappropriate signals pre- and post-ligand perception by a toggle switch mechanism of ERECTA.

Dynamic control of signaling events requires swift regulation of receptors at an active state. By focusing on the Arabidopsis ERECTA (ER) receptor kinase, which perceives peptide ligands to control multiple developmental processes, we report a mechanism preventing inappropriate receptor activity. The ER C-terminal tail (ER_CT) functions as an autoinhibitory domain: Its removal confers higher kinase activity and hyperactivity during inflorescence and stomatal development.

A double dissociation between semantic and spatial cognition in visual to default network pathways.

Processing pathways between sensory and default mode network (DMN) regions support recognition, navigation, and memory but their organisation is not well understood. We show that functional subdivisions of visual cortex and DMN sit at opposing ends of parallel streams of information processing that support visually mediated semantic and spatial cognition, providing convergent evidence from univariate and multivariate task responses, intrinsic functional and structural connectivity. Participants learned virtual environments consisting of buildings populated with objects, drawn from either a single semantic category or multiple categories.

SMAD4 and KRAS Status Shape Cancer Cell-Stromal Crosstalk and Therapeutic Response in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) contains an extensive stroma that modulates response to therapy, contributing to the dismal prognosis associated with this cancer. Evidence suggests that PDAC stromal composition is shaped by mutations within malignant cells, but most previous work has focused on pre-clinical models driven by KrasG12D and mutant Trp53. Elucidation of the contribution of additional known oncogenic drivers, including KrasG12V mutation and Smad4 loss, is needed to increase understanding of malignant cell-stroma crosstalk in PDAC.

Impact of Scanner Manufacturer, Endorectal Coil Use, and Clinical Variables on Deep Learning-assisted Prostate Cancer Classification Using Multiparametric MRI.

Purpose To assess the impact of scanner manufacturer and scan protocol on the performance of deep learning models to classify prostate cancer (PCa) aggressiveness on biparametric MRI (bpMRI). Materials and Methods In this retrospective study, 5,478 cases from ProstateNet, a PCa bpMRI dataset with examinations from 13 centers, were used to develop five deep learning (DL) models to predict PCa aggressiveness with minimal lesion information and test how using data from different subgroups-scanner manufacturers and endorectal coil (ERC) use (Siemens, Philips, GE with and without ERC and the full dataset)-impacts model performance. Performance was assessed using the area under the receiver operating characteristic curve (AUC).

Multisensory integration operates on correlated input from unimodal transient channels.

Audiovisual information reaches the brain via both sustained and transient input channels, representing signals' intensity over time or changes thereof, respectively. To date, it is unclear to what extent transient and sustained input channels contribute to the combined percept obtained through multisensory integration. Based on the results of two novel psychophysical experiments, here we demonstrate the importance of the transient (instead of the sustained) channel for the integration of audiovisual signals.

On the generalization of accommodation to head-related transfer functions.

To date, there is strong evidence indicating that humans with normal hearing can adapt to non-individual head-related transfer functions (HRTFs). However, less attention has been given to studying the generalization of this adaptation to untrained conditions. This study investigated how adaptation to one set of HRTFs can generalize to another set of HRTFs.

From human to superhuman: the impact of the microbiome on physiology.

The complex microbial community residing in the human gut has long been understood to regulate gastrointestinal physiology and to participate in digestive diseases, but its extraintestinal actions and influences are increasingly recognized. This article discusses bidirectional interactions between the gut microbiome and athletic performance, metabolism, longevity and the ability of the gut-brain axis to influence cognitive function and mental health.

Marek's disease virus-encoded microRNA-M6-5p facilitates viral latent infection by targeting histone demethylase KDM2B.

Marek's disease virus (MDV), a highly contagious and oncogenic avian alphaherpesvirus, establishes a latent infection primarily in CD4 T cells. Latent infections are necessary for both persistent lifelong MDV infection and viral tumorigenesis. MicroRNAs (miRNAs) play critical roles as post-transcriptional regulators of viral infections.

Molecular detection of parasites and host preference in wild-caught Culicoides biting midges (Diptera: Ceratopogonidae) in Chiang Mai and Nakhon Si Thammarat Provinces, Thailand.

Culicoides biting midges (Diptera: Ceratopogonidae) have been reported as potential vectors for haemoparasites. Information about host-vector-parasite specificity is required to confirm their status. Here, molecular detection of haemosporidians, Leishmania, trypanosomatids, and filarial nematodes in biting midges was conducted to understand their potential role as vectors, and their host preference was determined.

Methods for detecting, building, and improving tryptophan mannosylation in glycoprotein structures.

Tryptophan mannosylation, the covalent addition of an α-ᴅ-mannose sugar to a tryptophan side chain, is a post-translational modification (PTM) that can affect protein stability, folding, and interactions. Compared to other forms of protein glycosylation, it is relatively uncommon but is affected by conformational anomalies and modeling errors similar to those seen in N- and O-glycans in the Protein Data Bank (PDB). In this work, we report methods for detecting, building, and improving mannose structures linked to tryptophans.

Lacrimal Sac CLL: A Review of Clinical Features, Investigations, and Management.

Purpose: This study reviews all reported cases of lacrimal gland chronic lymphocytic leukemia (CLL) to identify patterns in clinical presentation, diagnosis, and management to aid in early recognition and treatment of this uncommon occurrence.

Methods: A comprehensive search of medical literature databases was performed to identify studies reporting lacrimal sac involvement in CLL from 1970 to 2024. Data were extracted regarding demographics, symptoms, diagnostic methods, treatment, and outcomes.

Evaluating Process and Outcomes of Public Involvement in Applied Health and Social Care Research: A Rapid Systematic Review.

Objective: Public Involvement (PI) in applied health and social care research has grown exponentially in the UK. This review aims to synthesise published UK evidence that evaluates the process and/or outcome(s) of PI in applied health and social care research to identify key contextual factors, effective strategies, outcomes and public partner experiences underpinning meaningful PI in research.

Methods: Following a pre-registered protocol, we systematically searched four databases and two key journals for studies conducted within the UK between January 2006 and July 2024.

An outbreak of Shiga toxin-producing serotype O103:H2 associated with unpasteurized soft cheese, England and Wales, 2022.

In July 2022, a genetically linked and geographically dispersed cluster of 12 cases of Shiga toxin-producing (STEC) O103:H2 was detected by the UK Health Security Agency using whole genome sequencing. Review of food history questionnaires identified cheese (particularly an unpasteurized brie-style cheese) and mixed salad leaves as potential vehicles. A case-control study was conducted to investigate exposure to these products.

Mineral Stress Drives Loss of Heterochromatin: An Early Harbinger of Vascular Inflammaging and Calcification.

Background: Vascular calcification is a detrimental aging pathology markedly accelerated in patients with chronic kidney disease. Prelamin A is a biomarker of vascular smooth muscle cell aging that accelerates calcification however the mechanisms remain undefined.

Methods: Vascular smooth muscle cells were transduced with prelamin A using an adenoviral vector and epigenetic modifications were monitored using immunofluorescence and targeted polymerase chain reaction array.