Impact of Endorectal Coil Use on Extraprostatic Extension Detection in Prostate MRI: A Retrospective Monocentric Study.

Rationale And Objectives: Accurate preoperative mpMRI-based detection of extraprostatic extension (EPE) in prostate cancer (PCa) is critical for surgical planning and patient outcomes. This study aims to evaluate the impact of endorectal coil (ERC) use on the diagnostic performance of mpMRI in detecting EPE.

Materials And Methods: This retrospective study with prospectively collected data included participants who underwent mpMRI and subsequent radical prostatectomy for PCa between 2007 and 2024.

Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets.

Autoimmune neurology is a rapidly expanding field driven by the discovery of neuroglial autoantibodies and encompassing a myriad of conditions affecting every level of the nervous system. Traditionally, autoantibodies targeting intracellular antigens are considered markers of T cell-mediated cytotoxicity, while those targeting extracellular antigens are viewed as pathogenic drivers of disease. However, recent advances highlight complex interactions between these immune mechanisms, suggesting a continuum of immunopathogenesis.

A community-based intervention (the Omama Project) improves neurodevelopment in impoverished 2-year-old Roma children: a quasi-experimental observational study.

Unlabelled: High rates of childhood neurodisability are reported among the Roma, Europe's largest ethnic minority community. Interventions targeting early child development (ECD) during the first 2 years of life can improve neurodevelopmental outcomes in vulnerable children; however, evidence from Roma preschoolers is scarce. In a quasi-experimental observational study, we compared neurodevelopmental outcomes at age 2 years, measured on the INTERGROWTH-21st Project Neurodevelopmental Assessment (INTER-NDA), between Roma children receiving a community-based ECD intervention (RI, n = 98), and age- and sex-matched Roma and non-Roma children (RC, n = 99 and NRC, n = 54, respectively) who did not receive the intervention in Eastern Slovakia.

AI-assisted detection for chest X-rays (AID-CXR): a multi-reader multi-case study protocol.

Introduction: A chest X-ray (CXR) is the most common imaging investigation performed worldwide. Advances in machine learning and computer vision technologies have led to the development of several artificial intelligence (AI) tools to detect abnormalities on CXRs, which may expand diagnostic support to a wider field of health professionals. There is a paucity of evidence on the impact of AI algorithms in assisting healthcare professionals (other than radiologists) who regularly review CXR images in their daily practice.

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.

Deciphering the nature and statistical optimization of antimicrobial metabolites of two endophytic bacilli.

In this study, Allium sativum, garlic, was selected to isolate endophytic bacteria and to evaluate the antimicrobial, antiviral, antioxidant, and cytotoxic activities of their produced metabolites followed by identification of the biosynthetic gene cluster of the antimicrobial metabolites using Oxford Nanopore Technology (ONT). Two bacterial isolates, C6 and C11, were found to have a broad-spectrum antagonistic effect against four standard microbial strains and were molecularly identified using 16 S ribosomal RNA sequence analysis and deposited in a local culture collection as B. velezensis CCASU-C6, and B.

Defining proteoform-specific interactions for drug targeting in a native cell signalling environment.

Understanding the dynamics of membrane protein-ligand interactions within a native lipid bilayer is a major goal for drug discovery. Typically, cell-based assays are used, however, they are often blind to the effects of protein modifications. In this study, using the archetypal G protein-coupled receptor rhodopsin, we found that the receptor and its effectors can be released directly from retina rod disc membranes using infrared irradiation in a mass spectrometer.

Evaluation of a novel malaria anti-sporozoite vaccine candidate, R21 in Matrix-M adjuvant, in the UK and Burkina Faso: two phase 1, first-in-human trials.

Background: Malaria remains a substantial public health burden among young children in sub-Saharan Africa and a highly efficacious vaccine eliciting a durable immune response would be a useful tool for controlling malaria. R21 is a malaria vaccine comprising nanoparticles, formed from a circumsporozoite protein and hepatitis B surface antigen (HBsAg) fusion protein, without any unfused HBsAg, and is administered with the saponin-based Matrix-M adjuvant. This study aimed to assess the safety and immunogenicity of the malaria vaccine candidate, R21, administered with or without adjuvant Matrix-M in adults naïve to malaria infection and in healthy adults from malaria endemic areas.

R21 in Matrix-M adjuvant in UK malaria-naive adult men and non-pregnant women aged 18-45 years: an open-label, partially blinded, phase 1-2a controlled human malaria infection study.

Background: R21 is a novel malaria vaccine, composed of a fusion protein of the malaria circumsporozoite protein and hepatitis B surface antigen. Following favourable safety and immunogenicity in a phase 1 study, we aimed to assess the efficacy of R21 administered with Matrix-M (R21/MM) against clinical malaria in adults from the UK who were malaria naive in a controlled human malaria infection study.

Methods: In this open-label, partially blinded, phase 1-2A controlled human malaria infection study undertaken in Oxford, Southampton, and London, UK, we tested five novel vaccination regimens of R21/MM.

Singlet fission in carotenoid dimers - the role of the exchange and dipolar interactions.

A theory of singlet fission in carotenoid dimers is presented which aims to explain the mechanism behind the creation of two uncorrelated triplets. Following the excitation of a carotenoid chain "bright" B+u state, there is ultrafast internal conversion to the intrachain "dark" 1B-u triplet-pair state. This strongly exchange-coupled state evolves into a pair of triplets on separate chains and spin-decoheres to form a pair of single, unentangled triplets, corresponding to complete singlet fission.

Myocardial Abnormalities Across the AHA/ACC Stages of Heart Failure in Patients With Diabetes.

Background: Cardiac magnetic resonance imaging (CMR) could serve as a robust tool for comprehensive evaluation of early changes across heart failure (HF) stages classified by the American Heart Association/American College of Cardiology guideline in diabetes mellitus (DM).

Objectives: The authors aimed to explore phenotypic imaging features characterizing DM participants at different HF stages by CMR.

Methods: DM participants with preserved ejection fraction who underwent CMR examination between January 2020 and December 2021 were evaluated.

A multimodal neural signature of face processing in autism within the fusiform gyrus.

Atypical face processing is commonly reported in autism. Its neural correlates have been explored extensively across single neuroimaging modalities within key regions of the face processing network, such as the fusiform gyrus (FFG). Nonetheless, it is poorly understood how variation in brain anatomy and function jointly impacts face processing and social functioning.

The mitochondrial genome of H. Lév. & Vaniot, an endemic sedge in Korea.

H. Lév. & Vaniot is an endemic species in Korea and is included in the clade of section in the recent classification system.

Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas.

Interaction between genetic risk score and dietary carbohydrate intake on high- density lipoprotein cholesterol levels: Findings from the Study of Obesity, Nutrition, Genes and Social factors (SONGS).

Background & Aims: Cardiometabolic traits are complex interrelated traits that result from a combination of genetic and lifestyle factors. This study aimed to assess the interaction between genetic variants and dietary macronutrient intake on cardiometabolic traits [body mass index, waist circumference, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, triacylglycerol, systolic blood pressure, diastolic blood pressure, fasting serum glucose, fasting serum insulin, and glycated haemoglobin].

Methods: This cross-sectional study consisted of 468 urban young adults aged 20 ± 1 years, and it was conducted as part of the Study of Obesity, Nutrition, Genes and Social factors (SONGS) project, a sub-study of the Young Lives study.

A multilevel framework for recruitment and retention in implementation trials: An illustrative example.

Background: Implementation and hybrid effectiveness-implementation trials aspire to speed the translation of science into practice by generating crucial evidence for improving the uptake of effective health interventions. By design, they pose unique recruitment and retention challenges due to their aims, units of analysis, and sampling plans, which typically require many clinical sites (i.e.

Are Current Patient-Reported Outcome Measures Fit for Purpose to Evaluate Unicompartmental Knee Arthroplasty?

The optimal procedure for isolated end-stage medial compartment knee osteoarthritis (OA) remains uncertain, with debate persisting between unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA). The aim of this narrative review is to evaluate current outcome measures in knee arthroplasty (KA) and explore how evolving patient populations and technological advancements may necessitate the use of different patient-reported outcome measures (PROMs) for evaluating UKA. While UKA offers potential advantages over TKA in early pain relief and functional outcomes, most randomised control trials using traditional PROMs have failed to show definitive superiority.

Effects of Automated Versus Conventional Ventilation on Quality of Oxygenation-A Substudy of a Randomized Crossover Clinical Trial.

: Attaining adequate oxygenation in critically ill patients undergoing invasive ventilation necessitates intense monitoring through pulse oximetry (SpO) and frequent manual adjustments of ventilator settings like the fraction of inspired oxygen (FiO) and the level of positive end-expiratory pressure (PEEP). Our aim was to compare the quality of oxygenation with the use of automated ventilation provided by INTELLiVENT-Adaptive Support Ventilation (ASV) vs. ventilation that is not automated, i.

The false evidence rate: An approach to frequentist error rate control conditioning on the observed value.

A value is conventionally interpreted either as a) the probability by chance of obtaining more extreme results than those observed or b) a tool for declaring significance at a prespecified level. Both approaches carry difficulties: b) does not allow users to make inferences based on the data in hand, and is not rigorously followed by researchers in practice, while (a) is not meaningful as an error rate. Although values retain an important role, these shortcomings are likely to have contributed significantly to the scientific reproducibility crisis.

Dysregulation of the NLRP3 Inflammasome and Promotion of Disease by IL-1β in a Murine Model of Sandhoff Disease.

Sandhoff disease (SD) is a progressive neurodegenerative lysosomal storage disorder characterized by GM2 ganglioside accumulation as a result of mutations in the gene, which encodes the β-subunit of the enzyme β-hexosaminidase. Lysosomal storage of GM2 triggers inflammation in the CNS and periphery. The NLRP3 inflammasome is an important coordinator of pro-inflammatory responses, and we have investigated its regulation in murine SD.

Predicting cognitive decline from neuropsychiatric symptoms and Alzheimer's disease biomarkers: A machine learning approach to a population-based data.

Background: The aim of this study was to examine the potential added value of including neuropsychiatric symptoms (NPS) in machine learning (ML) models, along with demographic features and Alzheimer's disease (AD) biomarkers, to predict decline or non-decline in global and domain-specific cognitive scores among community-dwelling older adults.

Objective: To evaluate the impact of adding NPS to AD biomarkers on ML model accuracy in predicting cognitive decline among older adults.

Methods: The study was conducted in the setting of the Mayo Clinic Study of Aging, including participants aged ≥ 50 years with information on demographics (i.

Evaluation of efficiency and effectiveness of different recruitment strategies for the FINGER-NL multidomain lifestyle intervention trial via the Dutch Brain Research Registry.

Introduction: Recruitment of participants for intervention studies is challenging. We evaluated the effectiveness and efficiency of a participant recruitment campaign through an online registry for the FINGER-NL study, a multi-domain lifestyle intervention trial targeting cognitively healthy individuals aged 60-79 with dementia prevention potential. Additionally, we explored which recruitment strategy successfully reached individuals from underrepresented groups in research.