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Background: Pressure overload of the heart occurs in patients with hypertension or valvular stenosis and induces cardiac fibrosis because of excessive production of extracellular matrix by activated cardiac fibroblasts. This initially provides essential mechanical support to the heart, but eventually compromises function. Osteopontin is associated with fibrosis; however, the underlying signaling m
Progress in the definition of the roles of various costimulators and cytokines in determining the type and height of immune responses has made it important to explore genetically altered tumor cells expressing such molecules for therapeutic immunizations. We have studied the effect of therapeutic subcutaneous (s.c.) immunizations on the growth of preexisting intracerebral brain tumor isografts in
Background: Diffuse large B-cell lymphoma (DLBCL) exhibits immunological heterogeneity that influences outcomes of immunochemotherapy, with CD8+ T cells playing a critical role in patient prognosis. Methods: We integrated single-cell and bulk transcriptome data to establish a CD8⁺ T cell–associated prognostic signature. Single-cell RNA sequencing data from 29 samples (28 individuals), including DL
Background: Studies on long-term exposure to air pollution at high levels suggest an association with increased risk of metabolic syndrome (MetS). We aimed to study this relationship at very low levels, less well-studied, yet of public health importance. Methods: The Swedish CArdioPulmonary bioImage Study (SCAPIS) consists of randomly selected subjects aged 50–64 years from six large cities in Swe
Cytolysin A (ClyA) is a pore-forming protein from a strongly silenced gene in non-pathogenic Escherichia coli, including typical commensal isolates in the intestinal microbiome of healthy mammalian hosts. Upon overproduction, ClyA-expressing bacteria display a cytolytic phenotype. However, it remains unclear whether sublytic amounts of native ClyA play a role in commensal E. coli-host interactions
The detailed pathways of photoactivity on ultrafast time scales are a topic of contemporary interest. Using a tabletop apparatus based on a laser plasma X-ray source and an array of cryogenic microcalorimeter X-ray detectors, we measured a transient X-ray absorption spectrum during the ferrioxalate photoreduction reaction. With these high-efficiency detectors, we observe the Fe K edge move to lowe
Since 1955, a form of diabetes in lean, young (BMI <18·5 kg/m2, age <30 years) individuals with a history suggestive of undernutrition from before birth and throughout childhood has been described in the literature. In 1985, WHO formally classified it as malnutrition-related diabetes, but subsequently removed the classification in 1999 over a disagreement as to whether undernutrition was a suffici
We present a new suite of edge ('Engineering Dwarfs at Galaxy formation's Edge') cosmological zoom simulations. The suite includes 15 radiation-hydrodynamical dwarf galaxies covering the ultrafaint to the dwarf irregular regime () to enable comparisons with observed scaling relations. Each object in the suite is evolved at high resolution () and includes stellar radiation, winds, and supernova fee
BACKGROUND: Dapagliflozin improved cardiometabolic outcomes following myocardial infarction in patients without prior type-2 diabetes (T2DM) in the DAPA-MI (dapagliflozin in patients with myocardial infarction) trial. The effect of glycemic status and body mass index (BMI) post–myocardial infarction requires elucidation. METHODS: Participants with T2DM diagnosis, without baseline hemoglobin A1c, o
Determining the prevalence of atmospheres on terrestrial planets is a core objective in exoplanetary science. While M dwarf systems offer a promising opportunity, conclusive observations of terrestrial atmospheres have remained elusive, with many yielding flat transmission spectra. We observe four transits of the hot terrestrial planet TOI-1685 b using James Webb Space Telescope (JWST)’s Near Infr
BACKGROUND: Fever is associated with brain injury after cardiac arrest. It is unknown whether fever management with a feedback-controlled device impacts patient-centered outcomes in cardiac arrest patients. This trial aims to investigate fever management with or without a temperature control device after out-of-hospital cardiac arrest. METHODS: The TEMP-CARE trial is part of the 2 × 2 × 2 factoria
BACKGROUND: HYPO-RT-PC is a phase 3 trial comparing ultra-hypofractionated and conventionally fractionated radiotherapy in intermediate-to-high-risk localised prostate cancer. This 10-year update reports long-term efficacy and toxicity outcomes.METHODS: In this open-label, randomised, phase 3, non-inferiority trial done in ten centres in Sweden and two in Denmark, we recruited men aged 75 years or
Background: Ambulatory oxygen therapy can be used to treat exertional hypoxaemia during daily life activities in people with fibrotic interstitial lung disease (ILD). However, evidence for its efficacy is scarce. This trial aimed to compare the effects of ambulatory oxygen with ambulatory air on physical activity in daily life over 6 months in people with fibrotic ILD and isolated exertional hypox
Background: Postoperative lymph node irradiation can affect shoulder morbidity in breast cancer patients, yet widely accepted dose-volume constraints for the shoulder joint are lacking. The SENOMAC trial randomized patients with breast cancer and 1–2 sentinel lymph node (SLN) macrometastases to axillary lymph node dissection (ALND) or SLN biopsy only. We aimed to analyze the association between th
Introduction: Synovial fibroblasts (S-Fib) are recognized as key drivers of joint inflammation in adult arthritis. Moreover, data are limited on the processes driving monocyte activation in oligoarticular juvenile idiopathic arthritis (oJIA). Therefore, we aimed to explore if S-Fib from patients with oJIA induce monocyte activation. Methods: S-Fib were isolated from the synovial fluid (SF) of n =
Extracellular matrix (ECM) is a dynamic 3-dimensional network of macromolecules that provides structural support for the cells and tissues. Accumulated knowledge clearly demonstrated over the last decade that ECM plays key regulatory roles since it orchestrates cell signaling, functions, properties and morphology. Extracellularly secreted as well as cell-bound factors are among the major members o
Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopi
Genetic studies promise to provide insight into the molecular mechanisms underlying type 2 diabetes (T2D). Variants associated with T2D are often located in tissue-specific enhancer clusters or super-enhancers. So far, such domains have been defined through clustering of enhancers in linear genome maps rather than in three-dimensional (3D) space. Furthermore, their target genes are often unknown.
The plasma proteins alpha1-microglobulin (alpha1-m) and bikunin are synthesized in the liver as a common precursor which is cleaved just before secretion. Half of plasma alpha1-m is covalently linked to fibronectin and alpha1-inhibitor-3, and more than 95% of bikunin is part of pre-alpha-inhibitor, inter-alpha-inhibitor and related large molecules. Both alpha1-m and bikunin have been shown to be i
