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.

Q: Context: Previous follow-up studies indicate that increased visual cortical, ventral cingulate and subcortical responses of depressed individuals to sad facial stimuli, but not happy stimuli could represent reversible markers of disease severity. We hypothesized that greater responses in these areas to sad stimuli, but not happy stimuli, would predict better subsequent clinical outcome. We also explored areas that would predict a poor outcome.', 'Twelve melancholically depressed individuals in the early stages of antidepressant treatment in a secondary care setting participated in two experiments comparing responses to varying intensities of sad and happy facial stimuli, respectively, using event related functional MRI. They repeated the experiments after a mean delay of 12 weeks of treatment.', 'There was a variation in response to treatment. Greater right visual cortex and right subgenual cingulate (R-BA25) responses to sad stimuli, but not happy stimuli, in the early stages of treatment were associated with a good clinical outcome. Greater ventrolateral prefrontal cortex responses to either stimulus type were associated with a relatively poor outcome.\Question: Do subgenual cingulate and visual cortex responses to sad faces predict clinical outcome during antidepressant treatment for depression?

A: The sample size was modest and patients were taking a variety of antidepressants.
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Q: 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?

A: 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.
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Q: Context: Cigarette smoking is correlated with other risk factors for gout such as adiposity and alcohol intake. The goal of this study was to study the direction and magnitude of association between cigarette smoking and risk for gout.', 'We analysed 54-year follow-up data (1948-2002) for 2279 men and 2785 women who were gout-free at their first assessment as a part of the Framingham Heart Study. Using Cox proportional hazards models we estimated the association between cigarette smoking and incident gout among men and women separately after adjusting for age, BMI, alcohol intake, hypertension, kidney disease and diabetes.', 'There were 399 incident cases (249 men and 150 women) of gout over 151 058 person-years of observation. Incidence rates of gout per 1000 person-years for smokers and non-smokers were 2.13 (95% CI 1.79, 2.53) and 3.04 (95% CI 2.70, 3.42), respectively. In multivariable Cox models, cigarette smoking was associated with gout with a hazard ratio of 0.76 (95% CI 0.59, 0.98) overall, 0.68 (95% CI 0.49, 0.93) among men and 0.92 (95% CI 0.60, 1.41) among women. Lower risk for smokers was evident among all obesity categories, but not among women. Sensitivity analysis suggested that the magnitude of the true odds ratio might be lower than our calculations.\Question: Is cigarette smoking associated with a reduction in the risk of incident gout : results from the Framingham Heart Study original cohort?

A:
Cigarette smoking is associated with lower incidence of gout and this is not explained by differences in the prevalence of risk factors. The mechanistic underpinnings of this epidemiological finding merits further study.
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