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Preheart failure comorbidities and impact on prognosis in heart failure patients : a nationwide study

Background: Data regarding the impact of preheart failure (HF) comorbidities on the prognosis of HF are scarce, especially in the younger HF patients. Objectives: To investigate pre-existing comorbidities in HF patients versus matched controls and to assess their impact on mortality. Methods: We included all first-time in-hospital and outpatient diagnoses of HF from 1995 to 2017, and comorbidities

Incidence of Ischemic Stroke in Individuals with and without Aortic Valve Stenosis : A Danish Retrospective Cohort Study

Background and Purpose - Aortic valve stenosis may lead to atrial and ventricular remodeling, predisposes to atrial fibrillation, and may also be an independent risk factor of ischemic stroke. However, information on stroke rates among persons with aortic valve stenosis are sparse. We aimed to determine the incidence rates and relative risks of ischemic stroke in individuals with diagnosed aortic

Two-Step Acoustophoresis Separation of Live Tumor Cells from Whole Blood

There is an unmet clinical need to extract living circulating tumor cells (CTCs) for functional studies and in vitro expansion to enable drug testing and predict responses to therapy in metastatic cancer. Here, we present a novel two-step acoustophoresis (A2) method for isolation of unfixed, viable cancer cells from red blood cell (RBC) lysed whole blood. The A2 method uses an initial acoustofluid

Inferring causal pathways between metabolic processes and liver fat accumulation: an IMI DIRECT study

Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) often co-occur. Defining causal pathways underlying this relationship may help optimize the prevention and treatment of both diseases. Thus, we assessed the strength and magnitude of the putative causal pathways linking dysglycemia and fatty liver, using a combination of causal inference methods.Measures of glycemia, insulin dynam

Simultaneous determination of folate and methotrexate metabolites in serum by LC-MS/MS during high-dose methotrexate therapy

High-dose methotrexate (HDMTX) is a central component in the treatment of acute lymphoblastic leukemia, osteosarcoma, and some lymphomas and brain tumors. MTX is given at lethal doses and then is followed by rescue treatment with folinic acid (FA). Despite FA rescue, many patients suffer severe toxicity. The pharmacokinetics of FA rescue have not been sufficiently studied. However, optimization of

Resonant X-ray photo-oxidation of light-harvesting iron (II/III) N-heterocyclic carbene complexes

Two photoactive iron N-heterocyclic carbene complexes [FeII(btz)2(bpy)]2+ and [FeIII(btz)3]3+, where btz is 3,3’-dimethyl-1,1’-bis(p-tolyl)-4,4’-bis(1,2,3-triazol-5-ylidene) and bpy is 2,2’-bipyridine, have been investigated by Resonant Photoelectron Spectroscopy (RPES). Tuning the incident X-ray photon energy to match core-valence excitations provides a site specific probe of the electronic struc

Clonal competition within complex evolutionary hierarchies shapes AML over time

Clonal heterogeneity and evolution has major implications for disease progression and relapse in acute myeloid leukemia (AML). To model clonal dynamics in vivo, we serially transplanted 23 AML cases to immunodeficient mice and followed clonal composition for up to 15 months by whole-exome sequencing of 84 xenografts across two generations. We demonstrate vast changes in clonality that both progres

A new genetic tool to improve immune-compromised mouse models : Derivation and CRISPR/Cas9-mediated targeting of NRG embryonic stem cell lines

Development of human hematopoietic stem cells and differentiation of embryonic stem (ES) cells/induced pluripotent stem (iPS) cells to hematopoietic stem cells are poorly understood. NOD (Non-obese diabetic)-derived mouse strains, such as NSG (NOD-Scid-il2Rg) or NRG (NOD-Rag1-il2Rg), are the best available models for studying the function of fetal and adult human hematopoietic cells as well as ES/

Differential impedance spectra analysis reveals optimal actuation frequency in bulk mode acoustophoresis

This work reports a method to select the optimal working frequency in transversal bulk resonator acoustophoretic devices by electrical impedance measurements. The impedance spectra of acoustophoretic devices are rich in spurious resonance peaks originating from different resonance modes in the system not directly related to the channel resonance, why direct measurement of the piezoelectric transdu

Screening for comorbid autoimmune disease should be considered in children with ANA positive juvenile idiopathic arthritis – results from the south-Swedish juvenile idiopathic arthritis cohort

Background: There is no consensus or clinical guidelines for screening routines of autoimmune disease in individuals with juvenile idiopathic arthritis (JIA), since results are conflicting whether the risk for such conditions is increased or not among individuals with JIA. The aim of this study was to investigate if the frequency of comorbid autoimmune conditions is increased after JIA diagnosis i

Differential Cytotoxicity and Inflammatory Responses to Particulate Matter Components in Airway Structural Cells

Particulate matter (PM) is a major component of ambient air pollution. PM exposure is linked to numerous adverse health effects, including chronic lung diseases. Air quality guidelines designed to regulate levels of ambient PM are currently based on the mass concentration of different particle sizes, independent of their origin and chemical composition. The objective of this study was to assess th

Arterial Stiffness and Markers of Atrial Myopathy

Background: Arterial stiffness, measured using carotid-femoral pulse wave velocity (c-f PWV) and heart rate-corrected augmentation index (Aix75), is associated with cardiovascular disease, and in some studies incident atrial fibrillation (AF). In this cross-sectional study, we aimed to investigate whether arterial stiffness is associated with markers of atrial myopathy, which refers to structural

Performance of a point-of-care ultrasound platform for artificial intelligence-enabled assessment of pulmonary B-lines

Background: The incorporation of artificial intelligence (AI) into point-of-care ultrasound (POCUS) platforms has rapidly increased. The number of B-lines present on lung ultrasound (LUS) serve as a useful tool for the assessment of pulmonary congestion. Interpretation, however, requires experience and therefore AI automation has been pursued. This study aimed to test the agreement between the AI

Serine phosphorylation mimics of Aβ form distinct, non-cross-seeding fibril morphs

The self-assembly of amyloid-β peptide (Aβ) into fibrils and oligomers is linked to Alzheimer's disease (AD). Fibrillar aggregates in AD patient's brains contain several post-translational modifications, including phosphorylation at positions 8 and 26. These play a key role in modifying the aggregation propensity of Aβ, yet how they affect the mechanism of aggregation is only poorly understood. He

Screening performance and characteristics of breast cancer detected in the Mammography Screening with Artificial Intelligence trial (MASAI) : a randomised, controlled, parallel-group, non-inferiority, single-blinded, screening accuracy study

Background: Emerging evidence suggests that artificial intelligence (AI) can increase cancer detection in mammography screening while reducing screen-reading workload, but further understanding of the clinical impact is needed. Methods: In this randomised, controlled, parallel-group, non-inferiority, single-blinded, screening-accuracy study, done within the Swedish national screening programme, wo

Epigenetic biomarkers predict macrovascular events in individuals with type 2 diabetes

Prediction of incident macrovascular events (iMEs) in individuals with type 2 diabetes (T2D) remains suboptimal. We aim to discover blood-based epigenetic biomarkers predicting iMEs in 752 newly diagnosed individuals with T2D, among whom 102 developed iMEs during follow-up. 461 DNA methylation sites, e.g., near ARID3A, GATA5, HDAC4, IRS2, and TMEM51, associate with iMEs. Using cross-validation, a

A genome-wide association study of imaging-defined atherosclerosis

Imaging-defined atherosclerosis represents an intermediate phenotype of atherosclerotic cardiovascular disease (ASCVD). Genome-wide association studies (GWAS) on directly measured coronary plaques using coronary computed tomography angiography (CCTA) are scarce. In the so far largest population-based cohort with CCTA data, we performed a GWAS on coronary plaque burden as determined by the segment

Atrial Fibrillation, Venous Thromboembolism, and Risk of Pulmonary Hypertension : A Swedish Nationwide Register Study

BACKGROUND: Atrial fibrillation (AF) is suggested to be associated with venous thromboembolism (VTE) and might thereby play a role in the development of chronic thromboembolic pulmonary hypertension (PH). By elevating left-sided filling pressure and promoting atrial myopathy, AF may also play a role in the development of postcapillary PH. We aimed to investigate the association between AF, with or

Mitochondrial proteome landscape unveils key insights into melanoma severity and treatment strategies

BACKGROUND: Melanoma, the deadliest form of skin cancer, exhibits resistance to conventional therapies, particularly in advanced and metastatic stages. Mitochondrial pathways, including oxidative phosphorylation and mitochondrial translation, have emerged as critical drivers of melanoma progression and therapy resistance. This study investigates the mitochondrial proteome in melanoma to uncover no