In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.

Context: Transport across the blood-brain barrier (BBB) is an important mediator of beta-amyloid (Aβ) accumulation in the brain and a contributing factor in the pathogenesis of Alzheimer's disease (AD). One of the receptors responsible for the transport of Aβ in the BBB is the low density lipoprotein receptor-related protein 1 (LRP1). LRP1 is susceptible to proteolytic shedding at the cell surface, which prevents endocytic transport of ligands. Previously, we reported a strong inverse correlation between LRP1 shedding in the brain and Aβ transit across the BBB. Several proteases contribute to the ectodomain shedding of LRP1 including the α-secretase, a desintegrin and metalloproteinase domain containing protein 10 (ADAM10).", 'The role of ADAM10 in the shedding of LRP1 and Aβ BBB clearance was assessed through pharmacological inhibition of ADAM10 in an in vitro model of the BBB and through the use of ADAM10 endothelial specific knock-out mice. In addition, an acute treatment paradigm with an ADAM10 inhibitor was also tested in an AD mouse model to assess the effect of ADAM10 inhibition on LRP1 shedding and Aβbrain accumulation.', 'In the current studies, inhibition of ADAM10 reduced LRP1 shedding in brain endothelial cultures and increased Aβ42 transit across an in vitro model of the BBB. Similarly, transgenic ADAM10 endothelial knockout mice displayed lower LRP1 shedding in the brain and significantly enhanced Aβ clearance across the BBB compared to wild-type animals. Acute treatment with the ADAM10-selective inhibitor GI254023X in an AD mouse model substantially reduced brain LRP1 shedding and increased Aβ40 levels in the plasma, indicating enhanced Aβ transit from the brain to the periphery. Furthermore, both soluble and insoluble Aβ40 and Aβ42 brain levels were decreased following GI254023X treatment, but these effects lacked statistical significance.\Question: Does inhibition of ADAM10 promote the clearance of Aβ across the BBB by reducing LRP1 ectodomain shedding?
These studies demonstrate a role for ADAM10 in the ectodomain shedding of LRP1 in the brain and the clearance of Aβ across the BBB, which may provide a novel strategy for attenuating Aβ accumulation in the AD brain.

Context: B-type natriuretic peptide (BNP) correlates with cardiac filling pressures and outcomes in patients with heart failure. In heart transplant recipients, we hypothesize that a within-individual change in BNP over time would be more helpful than absolute BNP in detecting International Society of Heart and Lung Transplantation (ISHLT) grade 2R or greater rejection.', 'N-terminal pro-BNP (NT-proBNP) levels were measured in 146 consecutive transplant recipients undergoing routine endomyocardial biopsies. In the cross-sectional analysis, multiple observations per individual were accounted for using generalized estimation equations.', "A cross-sectional analysis demonstrated a weak association between NT-proBNP levels and rejection, with an odds ratio (OR) of 1.01 for every 100-pg/mL increase in NT-proBNP (p = 0.02). However, with a doubling of an individual's NT-proBNP level, the OR for significant rejection was 2.9 (95% confidence interval [CI] 1.2-7.0), the OR with a 5-fold increase was 9.1 (95% CI, 2.7-31.5), and the OR with a 10-fold increase was 27.7 (95% CI, 5.9-129). A 10-fold increase in NT-proBNP offered a negative predictive value of 95% for the diagnosis of rejection. The relationship between within-individual increases in NT-proBNP and rejection persisted after adjusting for a fall in ejection fraction and a rise pulmonary capillary wedge pressure, and was a stronger predictor than changes in these parameters.\Question: Does the change in B-type natriuretic peptide levels over time predict significant rejection in cardiac transplant recipients?
There is a strong, graded relationship between the within-individual increase in NT-proBNP and the odds of significant rejection independent of hemodynamic parameters. These results suggest that the change in NT-proBNP rather than absolute BNP levels may offer a non-invasive approach to detect rejection.

Context: Bracing is a common treatment for patients with adolescent idiopathic scoliosis (AIS) and is recommended for most skeletally immature patients with a curve of 25-45° in order to prevent or delay curve progression. The aim of this study was to determine at which body habitus orthotic management for AIS becomes less effective. We hypothesize that overweight children are more likely to fail brace treatment.', 'This was a retrospective cohort study involving consecutive patients with AIS treated with a thoracolumbosacral orthosis at a large pediatric tertiary care center. Patients were divided into three groups based on BMI: (1) high-BMI group (BMI >85th percentile); (2) low-BMI group (BMI <20th percentile); (3) mid-BMI group (BMI 20th-85th percentile). Successful orthotic treatment was defined as an increase in the primary curve of <5°, prevention of progression past 45°, and avoidance of surgery.', 'The study cohort comprised 182 patients with a mean age of 12.5\xa0years at brace prescription and a mean follow-up of 2\xa0years. Compared to the mid-BMI group, high- and low-BMI patients were significantly more likely to fail orthotic management. The association between high-BMI and orthotic failure disappeared when compliance and in-brace correction were taken into account, but the association between low-BMI and each poor outcome remained significant.\Question: 's it just the big kids : both high and low BMI impact bracing success for adolescent idiopathic scoliosis?

Based on our results, children on either end of the BMI spectrum are more likely to fail brace treatment for scoliosis than their mid-BMI counterparts. In high-BMI patients, this appears to be in large part attributable to an inadequacy of in-brace curve correction as well as to poorer brace compliance, while a low BMI appears to be an independent risk factor for brace failure.