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Myocardial infarction in ANCA-associated vasculitis : A population-based cohort study

Objectives To determine the incidence rate (IR) and predictors of myocardial infarction (MI) in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) as well as to estimate the IR ratio (IRR) of MI in AAV versus the background population. Methods 325 patients diagnosed with AAV 1997-2016 in Skåne, Sweden were included. Data were collected from the time of AAV dia

Chemical reaction mechanism between trimethylgallium and oxygen for β-gallium oxide growth: Thermodynamic and experimental studies

The metalorganic chemical vapor deposition (MOCVD) dynamics of beta-gallium oxide (β-Ga2O3) growth using trimethylgallium (TMGa) and oxygen as precursors were investigated through both theoretical thermodynamic analysis and experimental validation in a horizontal low-pressure hot-wall reactor. Thermodynamic analysis revealed that high-purity β-Ga2O3 can be grown through the complete combustion of

Scalable Vertical In-Ga-As Nanowire MOSFET With 67 mV/dec at 126μm Gate Width

Heterogeneous integration of III-V narrow bandgap transistors on silicon technology is desirable for high frequency circuit implementations. Such high-speed transistors must, however, scale to large gate widths to be suitable for general circuit design. Averaging among many variable channels is a key challenge for nanowire devices. A simplified, but high-speed compatible, nanowire device process w

Terahertz frequency-domain 4 × 4 Mueller matrix ellipsometer instrument designed for high-frequency magnetic resonance measurements

We report a Mueller matrix ellipsometer design using dual continuously rotating anisotropic meta wave plates, which determines the full set of Mueller matrix elements in the terahertz spectral range. The instrument operates in the frequency domain and employs a frequency tunable, solid state synthesizer based, continuous wave terahertz source with sub-MHz bandwidth. The implemented source permits

Willingness to Undergo Joint Surgery Following a First-Line Intervention for Osteoarthritis : Data From the Better Management of People With Osteoarthritis Register

Objective: To assess the proportion of participants reconsidering their willingness to undergo surgery after 3 and 12 months. Secondary aims were to analyze and compare the characteristics of individuals willing and unwilling to undergo joint surgery for osteoarthritis (OA) before a first-line intervention, and to study the association between pain intensity, walking difficulties, self-efficacy, a

Transcription Factor Programming of Human Pluripotent Stem Cells to Functionally Mature Astrocytes for Monocultures and Cocultures with Neurons

Astrocytes are essential cells for normal brain functionality and have recently emerged as key players in many neurological diseases. However, the limited availability of human primary astrocytes for cell culture studies hinders our understanding of their physiology and precise role in disease development and progression. Here, we describe a detailed step-by-step protocol to rapidly and efficientl

CRISPR/Cas9 Genome Engineering in Human Pluripotent Stem Cells for Modeling of Neurological Disorders

Recent advances in genome editing have brought new hopes for personalized and precision medicine but have also dramatically facilitated disease modeling studies. Combined with reprogramming approaches, stem cells and differentiation toward neural lineages, genome engineering holds great potential for regenerative approaches and to model neurological disorders. The use of patient-specific induced p

Utilization of healthcare and prescription medicines after non-pharmacological interventions for depression - A 3-year register follow-up of an RCT in primary care

Depression is a common, recurrent disorder. There is a need for readily available treatments with few negative side effects, that demands little resources and that are effective both in the short- and long term. Our aim was to investigate the long-term effectiveness of two different interventions; physical exercise and internet-based cognitive behavioural therapy (internet-CBT), compared to usual

Single-cell transcriptomics captures features of human midbrain development and dopamine neuron diversity in brain organoids

Three-dimensional brain organoids have emerged as a valuable model system for studies of human brain development and pathology. Here we establish a midbrain organoid culture system to study the developmental trajectory from pluripotent stem cells to mature dopamine neurons. Using single cell RNA sequencing, we identify the presence of three molecularly distinct subtypes of human dopamine neurons w

Importance of patellofemoral and tibiofemoral cartilage lesions on trajectory of self-reported outcomes in patients at high risk of knee OA : 4–6 years follow-up of patients undergoing meniscal surgery

Objective: We evaluated whether patient-reported outcome trajectories (i.e., changes over time) differed by intraoperative compartmental cartilage lesion pattern over 4–6 years following arthroscopic meniscal surgery. Methods: In this ancillary study of the Knee Arthroscopy Cohort Southern Denmark cohort, we intraoperatively categorized cartilage lesions as isolated patellofemoral, isolated tibiof

High PGD2 receptor 2 levels are associated with poor prognosis in colorectal cancer patients and induce VEGF expression in colon cancer cells and migration in a zebrafish xenograft model

Background: Despite intense research, the prognosis for patients with advanced colorectal cancer (CRC) remains poor. The prostaglandin D2 receptors DP1 and DP2 are explored here as potential therapeutic targets for advanced CRC. Methods: A CRC cohort was analysed to determine whether DP1 and DP2 receptor expression correlates with patient survival. Four colon cancer cell lines and a zebrafish meta

Copeptin as a marker of atherosclerosis and arteriosclerosis

Background and aims: The precursor peptide of vasopressin, copeptin, has previously been linked to increased risk of developing diabetes mellitus, coronary artery disease and cardiovascular mortality. Whether elevated copeptin is associated with markers of atherosclerosis and arteriosclerosis in the general population is not known. Methods: In this population-based, cross-sectional study, coronary

Decreased PGC1beta expression results in disrupted human erythroid differentiation, impaired hemoglobinization and cell cycle exit

Production of red blood cells relies on proper mitochondrial function, both for their increased energy demands during differentiation and for proper heme and iron homeostasis. Mutations in genes regulating mitochondrial function have been reported in patients with anemia, yet their pathophysiological role often remains unclear. PGC1β is a critical coactivator of mitochondrial biogenesis, with incr

FRET-Based Screening Identifies p38 MAPK and PKC Inhibition as Targets for Prevention of Seeded α-Synuclein Aggregation

Aggregation of α-synuclein is associated with neurodegeneration and a hallmark pathology in synucleinopathies. These aggregates are thought to function as prion-like particles where the conformation of misfolded α-synuclein determines the traits of the induced pathology, similar to prion diseases. Still, little is known about the molecular targets facilitating the conformation-specific biological

In-Depth Analysis of Disease Manifestations in Antineutrophil Cytoplasmic Antibody–Associated Vasculitides Identifies Distinct Clinical Phenotypes

Objective: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are heterogeneous disorders. The aim of this study was to identify and characterize subgroups of patients based on sex, ANCA, age at diagnosis, and organ involvement. Methods: In total, 1,167 patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were retrospectively recruited to the s

Molecular mechanism of α-synuclein aggregation on lipid membranes revealed

The central hallmark of Parkinson's disease pathology is the aggregation of the α-synuclein protein, which, in its healthy form, is associated with lipid membranes. Purified monomeric α-synuclein is relatively stable in vitro, but its aggregation can be triggered by the presence of lipid vesicles. Despite this central importance of lipids in the context of α-synuclein aggregation, their detailed m

Diagnosing Monogenic Stroke at Younger Age

BACKGROUND: An increasing number of monogenic conditions underlying stroke are being identified. We explored the possibilities of increasing the diagnostic yield of monogenic stroke in a population under 56 years of age. METHODS: Fifty probands ≤55 years at their first stroke episode were characterized clinically and investigated by whole genome sequencing. Probands had one or more of: (1) one or

Subclassification of obesity for precision prediction of cardiometabolic diseases

Obesity and cardiometabolic disease often, but not always, coincide. Distinguishing subpopulations within which cardiometabolic risk diverges from the risk expected for a given body mass index (BMI) may facilitate precision prevention of cardiometabolic diseases. Accordingly, we performed unsupervised clustering in four European population-based cohorts (N ≈ 173,000). We detected five discordant p