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Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study

ObjectiveMepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real-life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) were observed. We undertook this study to assess the

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and m

Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate suc

The contribution of population age-sex structure to the excess mortality estimates of 2020–2021 in Denmark, Finland, Iceland, Norway, and Sweden

The Nordic countries offer an ideal case study of the COVID-19 pandemic due to their comparability, high data quality, and variable mitigations. We investigated the age- and sex-specific mortality patterns during 2020–2021 for the five Nordic countries and analysed the total age- and sex-adjusted excess deaths, ratios of actual to expected death rates, and age-standardized excess death estimates.

Circulating Metabolites Associated with Albuminuria in a Hispanic/Latino Population

Background. Albuminuria is associated with metabolic abnormalities, but these relationships are not well understood. We studied the association of metabolites with albuminuria in Hispanics/Latinos, a population with high risk for metabolic disease. Methods. We used data from 3,736 participants from the Hispanic Community Health Study/Study of Latinos, of which 16% had diabetes and 9% had an increa

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (6

Atomic Hydrogen Annealing of Graphene on InAs Surfaces and Nanowires : Interface and Morphology Control for Optoelectronics and Quantum Technologies

Folding two-dimensional graphene around one-dimensional III-V nanowires yields a new class of hybrid nanomaterials combining their excellent complementary properties. However, important for high-quality electrical and optical performance, needed in many applications, are well-controlled oxide-free interfaces and a tight folding morphology. To improve the interface chemistry between the graphene an

Autumn fueling behavior in passerines in relation to migratory distance and daylength

Songbirds have evolved diverse strategies to cope with seasonality, including long-, medium-, and short-distance migration. There is some evidence that birds with a longer migration distance deposit fuel faster. However, most studies focus on long-distance migrants. Comparisons between species with different migration distances are necessary to broaden our understanding of fueling capacity in migr

Generation of two compound heterozygous HGSNAT-mutated lines from healthy induced pluripotent stem cells using CRISPR/Cas9 to model Sanfilippo C syndrome

Sanfilippo C syndrome (Mucopolysaccharidosis IIIC) is a rare lysosomal storage disorder caused by mutations in the HGSNAT gene. It is characterized by a progressive and severe neurodegeneration, for which there is no treatment available. Here, we report the generation of two HGSNAT-mutated cell lines from a healthy human induced pluripotent stem cell (hiPSC) line using CRISPR/Cas9 editing. These n

Timing rather than movement decisions explains age-related differences in wind support for a migratory bird

Migratory birds must make complex decisions to use wind to their advantage during flight and increasing flight performance is particularly important while crossing ecological barriers. Age-related differences in how birds deal with wind have suggested experience improves necessary skills in gaining positive wind support. However, differences in wind support between age groups over ecological barri

Baseline Prostate-specific Antigen Level in Midlife and Aggressive Prostate Cancer in Black Men

Background: Prostate-specific antigen (PSA) measurement in midlife predicts long-term prostate cancer (PCa) mortality among white men. Objective: To determine whether baseline PSA level during midlife predicts risk of aggressive PCa in black men. Design, setting, and participants: Nested case-control study among black men in the Southern Community Cohort Study recruited between 2002 and 2009. A pr

Secondary prevention and lifestyle indices after stroke in a long-term perspective

OBJECTIVES: To describe the long-term perspective regarding prevalence of risk factors, secondary stroke prevention, and lifestyle indices after stroke.METHODS: From a population-based one-year cohort (n = 416), we performed an observational study of 145 survivors at 16 months and 10 years after stroke (age 27-97 years) regarding secondary prevention including reaching acceptable treatment goals;

B cells treated with CTB-p210 acquire a regulatory phenotype in vitro and reduce atherosclerosis in apolipoprotein E deficient mice

Objective: Intranasal immunization with a fusion protein of the ApoB100-derived peptide p210 and the cholera toxin B subunit (CTB-p210) has previously been shown to induce mucosal tolerance and reduce atherosclerosis development, but the exact mode of action remains to be elucidated. Recent studies have indicated an important role for B cells in mucosal tolerance, in particular by induction of reg

Identification and characterization of potent and selective aquaporin-3 and aquaporin-7 inhibitors

The aquaglyceroporins are a subfamily of aquaporins that conduct both water and glycerol. Aquaporin-3 (AQP3) has an important physiological function in renal water reabsorption, and AQP3-mediated hydrogen peroxide (H2O2) permeability can enhance cytokine signaling in several cell types. The related aquaglyceroporin AQP7 is required for dendritic cell chemokine responses and antigen uptake. Selecti

Complement C3 and incident hospitalization due to chronic kidney disease : a population-based cohort study

BACKGROUND: Circulating C3 has been associated with diabetes and hypertension, which are the leading causes of chronic kidney disease (CKD). C3 activation is considered to contribute to several renal diseases. Here we examined whether elevated C3 concentration is associated with hospitalization due to CKD in the general population, and whether this relationship is mediated by factors such as diabe

Current state of Lobaria pulmonaria in southernmost Sweden.

Sites of Lobaria pulmonaria reported from the nemoral zone of the Swedish provinces Skåne and Blekinge since 1990 were revisited. At each locality, the habitat ecology and lichen viability were investigated. A substantial decline was noted, particularly in Skåne, as L. pulmonaria was found at only 24 sites, 22 of which were forests and two were wooded meadows. The commonest habitats for L. pulmona

Investigating Critical Friendship: Peeling Back the Layers

This self-study documents two teacher educators’ professionalinquiry into the notions of critical friendship. Specifically, we asked:How does our interactive inquiry on the topic of critical friendshiplead us to new understandings of critical friends? Three theoreticalperspectives framed this study – More Knowledgeable Others,Thought Collective, and reflection. Data sources included (a) artifactsfThis self-study documents two teacher educators’ professional inquiry into the notions of critical friendship. Specifically, we asked: How does our interactive inquiry on the topic of critical friendship lead us to new understandings of critical friends? Three theoretical perspectives framed this study – More Knowledgeable Others, Thought Collective, and reflection. Data sources included (a) artif

In Vitro Functional Characterization of Human Neurons and Astrocytes Using Calcium Imaging and Electrophysiology

Recent progress in stem cell biology and epigenetic reprogramming has opened up previously unimaginable possibilities to study and develop regenerative approaches for neurological disorders. Human neurons and glial cells can be generated by differentiation of embryonic and neural stem cells and from somatic cells through reprogramming to pluripotency (followed by differentiation) as well as by dir

Irregularity and lack of p waves in short tachycardia episodes predict atrial fibrillation and ischemic stroke

Background: Atrial fibrillation (AF) is defined as an irregular supraventricular tachycardia (SVT) without p waves, with duration >30 seconds. Whether AF characteristics during short SVT episodes predict AF and stroke is not known. Objective: The purpose of this study was to determine whether irregularity and lack of p waves, alone or in combination, during short SVT episodes increase the risk of

High Level of Fasting Plasma Proenkephalin-A Predicts Deterioration of Kidney Function and Incidence of CKD

High levels of proenkephalin-A (pro-ENK) have been associated with decreased eGFR in an acute setting. Here, we examined whether pro-ENK levels predict CKD and decline of renal function in a prospective cohort of 2568 participants without CKD (eGFR>60 ml/min per 1.73 m2) at baseline. During a mean follow-up of 16.6 years, 31.7% of participants developed CKD. Participants with baseline pro-ENK leve