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GLPG1972/S201086 is a disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS-5) inhibitor in development as an osteoarthritis disease-modifying therapy. We report the safety, tolerability, pharmacokinetics, and pharmacodynamics (turnover of plasma/serum ARGS-aggrecan neoepitope fragments [ARGS]) of GLPG1972 in 3 randomized, double-blind, placebo-controlled phase 1 trials. Study A, a

Fibrogenic processes instigate fatal chronic diseases leading to organ failure and death. Underlying biological processes involve induced massive deposition of extracellular matrix (ECM) by aberrant fibroblasts. We subjected diseased primary human lung fibroblasts to an advanced three-dimensional phenotypic high-content assay and screened a repurposing drug library of small molecules for inhibitin

In order to understand species’ sensitivity to habitat change, we must correctly determine if a species is associated with a habitat or not, and if it is associated, its degree of specialization for that habitat. However, definitions of species’ habitat association and specialization are often static, categorical classifications that coarsely define species as either habitat specialists or general

Both disturbed sleep and lack of exercise can disrupt metabolism in pregnancy. Accelerometery was used to objectively assess movement during waking (physical activity) and movement during sleeping (sleep disturbance) periods and evaluated relationships with continuous blood glucose variation during pregnancy. Data was analysed prospectively. 15-women without pre-existing diabetes mellitus wore con

The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear) and from deceased controls without knee OA.Synovial fluid samples were analyzed using state-of-the-art

OBJECTIVES: Acute type A aortic dissection (ATAAD) is a rare but severe condition, routinely treated with emergent cardiac surgery. Many surgeons have the notion that patients with ATAAD tend to come in clusters, but no studies have examined these observations. This investigation was undertaken to study the potential association between the lunar cycle and the incidence of ATAAD. METHODS: We colle

Continued professional development (CPD), tailored to teachers’ needs and expectations, is required for updated skills and knowledge. In this study, twenty-five teachers working with first and second grade students participated in an 11-week programme focusing on enhancing classroom communication. The participating teachers were randomly assigned to either a direct intervention track (intervention

OBJECTIVES: To evaluate incidence of self-reported falls and associated factors in a ten-year perspective after stroke.METHODS: From a population-based cohort of first-ever stroke patients (n = 416) included in the Lund Stroke Register between March 1, 2001, and February 28, 2002, we performed a follow up of all 145 survivors ten years after stroke. We collected data on age, gender, main stroke ty

Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes coding for ribosomal proteins. Among these genes, the ribosomal protein S19 (RPS19) gene is the most frequently mutated. Previously, a mouse model deficient in RPS19 was developed by our laboratory, which recapitulates the hematopoietic disease phenotype by manifesting pathologic f

Background: Presently, persons with diabetes are classified as having type 1 (T1D) or type 2 diabetes (T2D) based on clinical diagnosis. However, adult patients exhibit diverse clinical representations and this makes treatment approaches challenging to personalize. A recent Scandinavian study proposed a novel classification of adult diabetes into five clusters based on disease pathophysiology and

Purpose: Vocabulary relates to overall language proficiency and is important for academic success. Word definition (WD) tasks can be used to assess vocabulary depth and definition skills. We investigate monolingual and bilingual children's performances on a WD task, and how bilingualism, level of parental education, school characteristics (proportion of students with Swedish as second language and

Type 1 diabetes is a chronic autoimmune disease requiring insulin treatment for survival. Prolonged duration of type 1 diabetes is associated with increased risk of microvascular complications. Although chronic hyperglycemia and diabetes duration have been considered as the major risk factors for vascular complications, this is not universally seen among all patients. Persons with long-term type 1

Human malignant hematopoietic stem and progenitor cells (HSPCs) reside in bone marrow (BM) niches, which remain challenging to explore due to limited in vivo accessibility and constraints with humanized animal models. Several in vitro systems have been established to culture patient-derived HSPCs in specific microenvironments, but they do not fully recapitulate the complex features of native bone

Preeclampsia (PE) is a pregnancy syndrome characterized by hypertension and organ damage manifesting after 20 gestational weeks. The etiology is of multifactorial origin, where placental stress causes increased levels of placenta-derived extracellular vesicles (STBEVs) in the maternal circulation, shown to cause inflammation, endothelial activation, vasoconstriction, and anti-angiogenic activity.

The clinical translation of induced pluripotent stem cells (iPSCs) holds great potential for personalized therapeutics. However, one of the main obstacles is that the current workflow to generate iPSCs is expensive, time-consuming, and requires standardization. A simplified and cost-effective microfluidic approach is presented for reprogramming fibroblasts into iPSCs and their subsequent different

The two-dimensional electron gas (2DEG) that forms on a semiconductor surface can be used to explore a variety of phenomena in quantum physics and plays an important role in nanoscale electronics, such as transistors. Controlling its formation is, thus, relevant. Using angle-resolved photoemission spectroscopy (ARPES) and accumulating the signal over many nanocrystals, we find that on clean InAs n

X-ray time-resolved tomography is one of the most popular X-raytechniques to probe dynamics in three dimensions (3D). Recent developments in time-resolved tomography opened the possibility of recordingkilohertz-rate 3D movies. However, tomography requires rotating thesample with respect to the X-ray beam, which prevents characterization of faster structural dynamics. Here, we present megahertz (MH

BACKGROUND: Bronchodilator responsiveness (BDR) in asthma involves both the central and peripheral airways but is primarily relieved with beta-2-agonists and evaluated by spirometry. To date, antimuscarinics can be added as a reliever medication in more severe asthma. We hypothesize that combining both short-acting beta-2 agonist (SABA) and short-acting muscarinic antagonist (SAMA) could also impr