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Background: Current systemic therapies for metastatic pancreatic ductal adenocarcinoma are associated with poor outcomes with a 5-year overall survival rate under 5%. We aimed to assess the safety and antitumour activity of mitazalimab, a human CD40 agonistic IgG1 antibody, with modified FOLFIRINOX (mFOLFIRINOX; fluorouracil, leucovorin, oxaliplatin, and irinotecan), in chemotherapy-naive patients

Personal Protective Equipment (PPE) noncompliance has been addressed through various lenses. In current literature, there is a greater focus on improving training and safety culture. Improving PPE design to persuade PPE compliance is less explored, especially in sectors beyond healthcare. This study investigates the reasons behind PPE noncompliance across construction, maritime, and chimney sweepi

Sphingosine-1-phosphate receptors (S1PRs) are promising therapeutic targets in cardiovascular disease, including ischemic stroke. However, important spatiotemporal information for alterations of S1PR expression is lacking. Here, we investigated the role of S1PR3 in ischemic stroke in rodent models and patient samples. We show that S1PR3 is acutely upregulated in perilesional reactive astrocytes af

Thermally sprayed Al2O3 coatings containing graphene nano platelets (GNP) have been shown to exhibit improved wear resistance. To understand the positive influence of GNP on wear properties, scanning transmission X-ray microscopy (STXM) analyses were performed to determine the structural and chemical changes that occur on the GNP and alumina matrix after wear tests. STXM results acquired at the C

Accessible housing for the aging population is important, but large-scale reliable information on accessibility problems in ordinary housing is lacking. This study aimed to describe the prevalence of environmental barriers and analyze potential accessibility problems in the Swedish housing stock and to evaluate the validity and representativeness of housing data collected in a citizen science proj

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10−8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing to

Background: Polygenic prediction studies in continental Africans are scarce. Africa’s genetic and environmental diversity pose a challenge that limits the generalizability of polygenic risk scores (PRS) for body mass index (BMI) within the continent. Studies to understand the factors that affect PRS variability within Africa are required. Methods: Using the first multi-ancestry genome-wide associa

Background: Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited. Methods: We included 259,884 men from eight European cohorts, with 11,760 incident PCa’s and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases wit

High-order harmonic generation (HHG) provides scalable sources of coherent extreme ultraviolet radiation with pulse duration down to the attosecond time scale. Efficient HHG requires the constructive interplay between microscopic and macroscopic effects in the generation volume, which can be achieved over a large range of experimental parameters from the driving field properties to those of the ge

Cancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties. Thus, increasing CSC numbers via small molecule-mediated cellular reprogramming appears to be a valid alternative tool. Using the S

Background: Elevated levels of cardiac troponin T has been observed in patients seeking care at the emergency department (ED) presenting with chest pain but without myocardial infarction (MI). The clinical importance of this observation remains, however, still unclear. Our main aim was to study the role of cardiac troponin T in patients admitted to the emergency department with acute dyspnea, a gr

Understanding the trade-off between energy expenditure of carrying large fuel loads and the risk of fuel depletion is imperative to understand the evolution of flight strategies during long-distance animal migration. Global flyways regularly involve sea crossings that may impose flight prolongations on migrating land-birds and thereby reduce their energy reserves and survival prospects. We studied

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment inter

Materials with heterogeneous microstructures have been reported to have an attractive combination of strength and ductility. This is attributed to synergistic strengthening effects from the difference in strength of fine- and coarse-grained regions. Understanding the interaction of the regions is crucial for further optimization of the microstructures. In this work, we fabricated nickel of harmoni

Hydropower is a renewable, reliable, and highly predictable source of energy. It has been used for centuries. The tariff of energy generation is divided into two parts: fixed charges and variable charges. Fixed charges are based on the availability of machinery (i.e., plant availability factor) and variable charges are based on the actual energy generation. The energy generation targets are decide

We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic re

Background and aims: Obesity and type 2 diabetes are significant risk factors for atherosclerotic cardiovascular disease (CVD) worldwide, but the underlying pathophysiological links are poorly understood. Neurotensin (NT), a 13-amino-acid hormone peptide, facilitates intestinal fat absorption and contributes to obesity in mice fed a high-fat diet. Elevated levels of pro-NT (a stable NT precursor p

α-Synuclein is a small neuronal protein enriched at presynaptic termini. It is hypothesized to play a role in neurotransmitter release and synaptic vesicle cycling, while the formation of α-synuclein amyloid fibrils is associated with several neurodegenerative diseases, most notably Parkinson’s Disease. The molecular mechanisms of both the physiological and pathological functions of α-synuclein re