RON

Introduction: Immune checkpoint inhibitors (ICIs) represent the standard therapy for metastatic melanoma. However, a few patients do not respond to ICIs and reliable predictive biomarkers are needed. Methods: This pilot study investigates the association between mRNA levels of programmed cell death-1 (PD-1) ligand 1 (PD-L1), interferon-gamma (IFN-γ), and transforming growth factor-β (TGF-β) in circulating extracellular vesicles (EVs) and survival in 30 patients with metastatic melanoma treated with first line anti-PD-1 antibodies...

Real-world water wave fields exhibit significant nonlinear and nonisospectral characteristics, making it challenging to predict their evolution by relying solely on numerical simulation or exact solutions using integrable system theory. Hence, this paper introduces a fast and adaptive method of modal identification and prediction in nonisospectral water wave fields using the reduced-order nonlinear solution (RONS) scheme. Specifically, we discuss the coarse graining and mode extraction of wave field snapshots from the data-driven and physics-driven perspectives and utilize the RONS method for principle modal prediction of nonisospectral water wave fields...

BACKGROUND: Coronary microvascular dysfunction (CMD) is a prevalent condition among patients with cardiovascular risk factors, leading to a reduced quality of life and an increased risk of major adverse cardiovascular events. Novel invasive techniques have emerged to more accurately diagnose CMD. However, CMD's natural history remains poorly understood due to limited data. To address this knowledge gap, the Coronary Microvascular Disease Registry (CMDR) was established with the primary aim of standardizing comprehensive coronary functional testing and understanding of CMD...

Consensus-based recommendations are needed to better guide paediatric otolaryngologists in providing standardised care to children with sleep-disordered breathing (SDB). Here we present a unique case of vallecular cyst found during SDB workup in a patient in their middle childhood (6-12 years old). While the patient underwent successful cyst resection, he was noted to have a suspected recurrence 6 months later. Immediately prior to revision excision, repeat awake flexible fibre-optic laryngoscopy revealed complete resolution of the suspected recurrence...

BACKGROUND: Lipoprotein(a) (Lp[a]) is a causal genetic risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited long-term follow-up data from large U.S. population cohorts. OBJECTIVES: This study examined the relationship of Lp(a) with ASCVD outcomes in a large, pooled, multi-ethnic U.S. METHODS: The study included data on Lp(a) and ASCVD outcomes from 5 U.S. PROSPECTIVE STUDIES: MESA (Multi-Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults), JHS (Jackson Heart Study), FHS-OS (Framingham Heart Study-Offspring), and ARIC (Atherosclerosis Risk In Communities)...

This study assesses the agreement of Artificial Intelligence-Quantitative Computed Tomography (AI-QCT) with qualitative approaches to atherosclerotic disease burden codified in the multisociety 2022 CAD-RADS 2.0 Expert Consensus. 105 patients who underwent cardiac computed tomography angiography (CCTA) for chest pain were evaluated by a blinded core laboratory through FDA-cleared software (Cleerly, Denver, CO) that performs AI-QCT through artificial intelligence, analyzing factors such as % stenosis, plaque volume, and plaque composition...

BACKGROUND AND OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disorder that primarily affects the joints in children. Notably, it is known to co-occur with uveitis. Adalimumab, a monoclonal anti-TNF antibody, is effective in treating both conditions. A deeper understanding of the pharmacokinetics (PK) of adalimumab in JIA is crucial to advance in more personalized treatment approaches. The objective of this study is to evaluate the population PK profile of adalimumab in JIA and to explain causes for its variability...

Background: Headache is a debilitating complication following an aneurysmal subarachnoid hemorrhage (aSAH). Despite its impact on morbidity and quality of life, limited evidence characterizes the effectiveness of opioids. Objective: The aim of this study was to evaluate opioid associated reduction in pain scores in patients with aSAH-associated headache. Methods: This is a retrospective study of adult patients with an aSAH, Hunt and Hess grades I - III, admitted to a neurosciences intensive care unit. Descriptive and inferential statistics were used to characterize headache treatment strategies and opioid associated reduction in pain scores...

The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation of the vaccination campaign against the virus. Consequently, immunity against smallpox and related orthopoxviruses like Monkeypox virus gradually declines, highlighting the need for efficient countermeasures not only for the prevention, but also for the treatment of already exposed individuals. We have recently developed human-like monoclonal antibodies (mAbs) from vaccinia virus-immunized non-human primates. Two mAbs, MV33 and EV42, targeting the two infectious forms of the virus, were selected for in vivo evaluation, based on their in vitro neutralization potency...

Reliable population estimates are important for making informed management decisions about wildlife species. Standardized survey protocols have been developed for monitoring population trends of the wood turtle (Glyptemys insculpta), a semi-aquatic freshwater turtle species of conservation concern throughout its distribution in east-central North America. The protocols use repeated active search surveys of defined areas, allowing for estimation of survey-specific detection probability (p) and site-specific abundance...

Unicellular organisms are known to exert tight control over their cell size. In the case of diatoms, abundant eukaryotic microalgae, two opposing notions are widely accepted. On the one hand, the rigid silica cell wall that forms inside the parental cell is thought to enforce geometrical reduction of the cell size. On the other hand, numerous exceptions cast doubt on the generality of this model. Here, we monitored clonal cultures of the diatom Stephanopyxis turris for up to 2 yr, recording the sizes of thousands of cells, in order to follow the distribution of cell sizes in the population...

BACKGROUND: Although clinical guidelines prioritize the treatment of depression and anxiety in young persons, there is accumulating evidence that the presence of symptoms of borderline personality disorder (BPD) is associated with the limited effectiveness of these standard treatments. These findings stress the need for interventions addressing early-stage BPD in young people with presenting symptoms of anxiety and depressive disorders. The aim of this study is to investigate the (cost-)effectiveness of an early intervention programme for BPD (MBT-early) compared to first-choice psychological treatment for depression and anxiety according to Dutch treatment guidelines (CBT), in adolescents with either depression, anxiety, or both, in combination with early-stage BPD...

BACKGROUND: Listeriosis is rare after hematopoietic stem cell transplantation (HCT). Little is known about listeriosis in this population. OBJECTIVES: To describe listeriosis following HCT and assess risk factors for listeriosis. STUDY DESIGN: In this retrospective international case control study, we described 41 listeriosis episodes during 2000-2021 in HCT recipients (111 transplant centers; 30 countries) and assessed risk factors for listeriosis by comparing to matched controls...

BACKGROUND: Screening of high-risk patients is advocated to achieve early detection and treatment of clinical atrial fibrillation (AF). The Dutch-GERAF study will address two major issues. Firstly, the effectiveness and feasibility of an opportunistic screening strategy for clinical AF will be assessed in frail older patients and, secondly, observational data will be gathered regarding the efficacy and safety of oral anticoagulation (OAC). METHODS: This is a multicentre study on opportunistic screening of geriatric patients for clinical AF using a smartphone photoplethysmography (PPG) application...

Influenza remains a public health threat, partly due to suboptimal effectiveness of vaccines. One factor impacting vaccine effectiveness is strain mismatch, occurring when vaccines no longer match circulating strains due to antigenic drift or the incorporation of inadvertent (eg, egg-adaptive) mutations during vaccine manufacturing. In this review, we summarize the evidence for antigenic drift of circulating viruses and/or egg-adaptive mutations occurring in vaccine strains during the 2011-2020 influenza seasons...

The aim of our study was to investigate whether theories of congruence are better tested using polynomial regression analysis, rather than expressing discrepancy between implicit and explicit measures as continuous or categorical difference scores. This paper also aims to make knowledge more accessible by providing a step-by-step explanation of both methods, illustrating differences between them, and making materials openly available for other researchers. In this paper, implicit and explicit measures of self-esteem are used as predictors for depressive symptoms, anxiety, and aggression in a general population sample ( N = 135)...

Structured RNA lies at the heart of many central biological processes, from gene expression to catalysis. While advances in deep learning enable the prediction of accurate protein structural models, RNA structure prediction is not possible at present due to a lack of abundant high-quality reference data. Furthermore, available sequence data are generally not associated with organismal phenotypes that could inform RNA function. We created GARNET (Gtdb Acquired RNa with Environmental Temperatures), a new database for RNA structural and functional analysis anchored to the Genome Taxonomy Database (GTDB)...

BACKGROUND AND OBJECTIVES: Hexokinase 1 (encoded by HK1 ) catalyzes the first step of glycolysis, the adenosine triphosphate-dependent phosphorylation of glucose to glucose-6-phosphate. Monoallelic HK1 variants causing a neurodevelopmental disorder (NDD) have been reported in 12 individuals. METHODS: We investigated clinical phenotypes, brain MRIs, and the CSF of 15 previously unpublished individuals with monoallelic HK1 variants and an NDD phenotype. RESULTS: All individuals had recurrent variants likely causing gain-of-function, representing mutational hot spots...

BACKGROUND: Pediatric urolithiasis is relatively uncommon and is generally associated with predisposing anatomic or metabolic abnormalities. In the adult population, emergency department (ED) admissions have been associated with an increase in ambient temperature. The same association has not been evaluated in the pediatric population. OBJECTIVES: To analyze trends in ED admissions due to renal colic in a pediatric population (≤ 18 years old) and to assess the possible effect of climate on ED admissions...

Using immunotherapy to fight cancer, and specifically, the use of engineered T-cells expressing a chimeric receptor against an antigen found on malignant cells (chimeric antigen receptor, CAR-T cells) constitutes a significant breakthrough in the treatment of the disease. In recent years, several CAR-T therapies have been approved in Europe and the USA, and some are already approved and funded through the national health basket in Israel, for the indications of diffuse large B-cell lymphoma, mantle cell lymphoma and B-cell acute lymphoblastic leukemia, after the failure of at least two lines of treatment...