TASK DEFINITION: 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.
PROBLEM: Context: The CARD14 gene encodes a protein that enhances nuclear factor (NF)-B activation and the upregulation of proinflammatory pathway genes. CARD14 is upregulated in psoriatic vs. normal skin, and rare and common CARD14 variants have been associated with the risk of developing psoriasis. Our hypothesis was that CARD14 variants could also influence the response to antitumour necrosis factor (anti-TNF) therapies among patients with psoriasis.', 'To determine whether CARD14 gene variants were linked to a significant positive anti-TNF response in patients with psoriasis.', 'DNA from 116 patients with psoriasis was subjected to next-generation sequencing of the CARD14 gene. All of the patients were nonresponders or had contraindications to conventional systemic treatments.', 'A reduction of at least 75% in Psoriasis Area and Severity Index (PASI 75) at week 24 was considered a positive response to treatment. In total 116 patients (79 responders and 37 nonresponders) were next-generation sequenced, and we identified five nucleotide variants that would result in missense amino acid changes. These variants were determined in all of the patients, and allele and genotype frequencies were compared between the two groups. We found a significantly higher frequency of rs11652075 CC (p.Arg820Trp) among the group with a positive response (P = 0.01, odds ratio 3.71, 95% confidence interval 1.30-10.51). Furthermore, among responders, six patients were heterozygous carriers of the rare p.Glu422Lys variant, and two patients were heterozygous for p.Arg682Trp (P = 0.04).\Question: Do common and rare CARD14 gene variants affect the antitumour necrosis factor response among patients with psoriasis?

SOLUTION: The common CARD14 p.Arg820Trp variant might have a significant effect on the response to anti-TNF therapies among patients with psoriasis. In addition, rare CARD14 missense variants could also predispose to a better response.

PROBLEM: Context: Ag-dependent activation of IgE-bearing mast cells is a critical first step in immediate hypersensitivity and other allergic responses. Recent studies have revealed Ag-independent effects of monoclonal mouse IgE molecules on mast cell survival and activation. However, no studies have been performed on the effects of polyclonal IgE molecules. Here, we tested whether polyclonal mouse and human IgE molecules affect survival and cytokine production in mast cells.', 'Mast cells were cultured in the presence of polyclonal mouse and human IgE molecules, and cell survival and cytokine production were analyzed.', 'Polyclonal mouse IgE molecules in sera from mice with atopic dermatitis-like allergic skin inflammation, enhanced survival and cytokine production in mast cell cultures. Similar to the effects of monoclonal IgE, the polyclonal IgE effects were mediated by the high-affinity IgE receptor, FcepsilonRI. Human polyclonal IgE molecules present in sera from atopic dermatitis patients were also capable of activating mast cells, and inducing IL-8 production in human cord blood-derived mast cells.\Question: Does polyclonal IgE induce mast cell survival and cytokine production?

SOLUTION: These results imply that polyclonal IgE in atopic dermatitis and other atopic conditions might modulate mast cell number and function, thus amplifying the allergic response.

PROBLEM: Context: To examine the association between social relationships measured by the Social Network Scale and coronary artery disease (CAD) risk and mortality among a sample of women with suspected CAD.', 'Five hundred three women (mean age, 59 years) with suspected CAD warranting clinical investigation completed a diagnostic protocol including psychosocial testing, CAD risk factor assessment, and quantitative coronary angiography. Patients were subsequently followed for a mean of 2.3 years to track all-cause mortality.', 'Women reporting higher social network scores showed a consistent pattern of reduced coronary artery disease risk, including lower blood glucose levels (r = -0.11; p = .03), lower smoking rates (odds ratio [OR] = 0.81; 95% confidence interval [CI] = 0.71-0.93; p = .002), lower waist-hip ratios (r = -0.18; p < .01), and lower rates of hypertension (OR = 0.90; 95% CI = 0.81-0.99; p = .04) and diabetes (OR = 0.83; 95% CI = 0.73-0.94; p = .004). Based on quantitative angiogram findings, high social network scorers also had less severe CAD (mean angiogram stenosis value, 40.8 vs. 27.2 for low and high scoring social network groups, respectively; p < .001). Finally, mortality rates over follow-up showed a dose-response pattern in relation to quartile scorers on the Social Network Index, with low scorers showing more than twice the death rate of high scorers (relative risk = 2.4; p = .03).\Question: Are social networks associated with lower mortality rates among women with suspected coronary disease : the National Heart , Lung , and Blood Institute-Sponsored Women 's Ischemia Syndrome Evaluation study?

SOLUTION:
Among a cohort of women with suspected CAD, smaller social circles were associated with increased CAD risk factors and mortality, an effect that appeared to be explained largely by income level. The findings extend previous studies of social network effects on health by highlighting risk among women with suspected CAD, and suggest mechanisms for further study.