TASK DEFINITION: Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: To investigate the mechanisms of anti-atherosclerotic action of ezetimibe in rat vascular smooth muscle cells (VSMCs) in vitro.', 'VSMCs of SD rats were cultured in the presence of Chol:MβCD (10 μg/mL) for 72 h, and intracellular lipid droplets and cholesterol levels were evaluated using Oil Red O staining, HPLC and Enzymatic Fluorescence Assay, respectively. The expression of caveolin-1, sterol response element-binding protein-1 (SREBP-1) and ERK1/2 were analyzed using Western blot assays. Translocation of SREBP-1 and ERK1/2 was detected with immunofluorescence.', 'Treatment with Chol:MβCD dramatically increased the cellular levels of total cholesterol (TC), cholesterol ester (CE) and free cholesterol (FC) in VSMCs, which led to the formation of foam cells. Furthermore, Chol:MβCD treatment significantly decreased the expression of caveolin-1, and stimulated the expression and nuclear translocation of SREBP-1 in VSMCs. Co-treatment with ezetimibe (3 μmol/L) significantly decreased the cellular levels of TC, CE and FC, which was accompanied by elevation of caveolin-1 expression, and by a reduction of SREBP-1 expression and nuclear translocation. Co-treatment with ezetimibe dose-dependently decreased the expression of phosphor-ERK1/2 (p-ERK1/2) in VSMCs. The ERK1/2 inhibitor PD98059 (50 μmol/L) altered the cholesterol level and the expression of p-ERK1/2, SREBP-1 and caveolin-1 in the same manner as ezetimibe did.

SOLUTION: Does ezetimibe suppress cholesterol accumulation in lipid-loaded vascular smooth muscle cells in vitro via MAPK signaling?

PROBLEM: There is insufficient knowledge of infectious risk in patients after splenectomy; minimal data exists specifically for trauma patients. This study evaluated patient knowledge and practices regarding infection risk after traumatic splenectomy. Our hypothesis was that patients with poor knowledge regarding their asplenic state would be less likely to pursue medical care in the event of an illness than those with good knowledge.', 'Non-randomized, cohort study of all posttraumatic splenectomy patients < or =11 years after injury in 2 rural trauma centers. Patients received a validated questionnaire; weighted responses determined knowledge about infection risks and appropriate follow-up actions.', 'Fifty-four percent of patients responded to the questionnaire. Overall, 47% of responders were identified as having adequate knowledge regarding infectious risk, and only 28% would pursue appropriate medical care. Of patients with adequate knowledge, 42% were more likely to pursue appropriate care versus 15% of patients with inadequate knowledge (p = 0.06). Patients with adequate knowledge were more likely to receive an annual influenza vaccine (p = 0.03) and contact their provider with fewer symptoms (p = 0.03). Logistic regression revealed significant interactions between knowledge and presence of comorbidities (p = 0.04). Focusing on patients with poor knowledge and absence of comorbidities, none would engage in appropriate action in the event of illness (p < 0.01). A longer time since injury, >3 years, was associated with a diminished likelihood of appropriate action (p = 0.03). The relationship between knowledge and action was not accounted for by other potential confounders.

SOLUTION: Do time lapse and comorbidities influence patient knowledge and pursuit of medical care after traumatic splenectomy?

PROBLEM: Genetic and molecular signatures have been incorporated into cancer prognosis prediction and treatment decisions with good success over the past decade. Clinically, these signatures are usually used in early-stage cancers to evaluate whether they require adjuvant therapy following surgical resection. A molecular signature that is prognostic across more clinical contexts would be a useful addition to current signatures.', 'We defined a signature for the ubiquitous tissue factor, E2F4, based on its shared target genes in multiple tissues. These target genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) experiments using a probabilistic method. We then computationally calculated the regulatory activity score (RAS) of E2F4 in cancer tissues, and examined how E2F4 RAS correlates with patient survival.', "Genes in our E2F4 signature were 21-fold more likely to be correlated with breast cancer patient survival time compared to randomly selected genes. Using eight independent breast cancer datasets containing over 1,900 unique samples, we stratified patients into low and high E2F4 RAS groups. E2F4 activity stratification was highly predictive of patient outcome, and our results remained robust even when controlling for many factors including patient age, tumor size, grade, estrogen receptor (ER) status, lymph node (LN) status, whether the patient received adjuvant therapy, and the patient's other prognostic indices such as Adjuvant! and the Nottingham Prognostic Index scores. Furthermore, the fractions of samples with positive E2F4 RAS vary in different intrinsic breast cancer subtypes, consistent with the different survival profiles of these subtypes.

SOLUTION:
Does e2F4 regulatory program predict patient survival prognosis in breast cancer?