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: Lieber-DeCarli diet has been used to induce obesity and non-alcoholic steatohepatitis (NASH). As scarce anatomical and clinical-related information on this diet model exists and being exercise an advised strategy to counteract metabolic diseases, we aimed to analyze the preventive (voluntary physical activity - VPA) and therapeutic (endurance training - ET) effect of exercise on clinical/anatomical features of rats fed with Lieber-DeCarli diet.', 'In the beginning of the protocol, Sprague-Dawley rats were divided into standard-diet sedentary (SS, n = 20), standard-diet VPA (SVPA, n = 10), high-fat diet sedentary (HS, n = 20) and high-fat diet VPA (HVPA, n = 10) groups. After 9-weeks, half (n = 10) of SS and HS groups were engaged in an ET program (8 wks/5 d/wk/60 min/day). At this time, a blood sample was collected for biochemical analysis. At the end of protocol (17-weeks) anatomic measures were assessed. Heart, liver, femur and visceral fat were weighted and blood was collected again. Liver section was used for histopathological examination.', 'At 17-weeks, high-fat diet increased visceral adiposity (HS vs. SS), which was counteracted by both exercises. However, ET was the only intervention able to diminished obesity-related measures and the histological features of NASH. Moreover, blood analysis at 9 weeks showed that high-fat diet increased ALT, AST, cholesterol and HDL while VLDL and TG levels were decreased (HS vs. SS). Notably, although these parameters were counteracted after 9-weeks of VPA, they were transitory and not observed after 17-weeks.

SOLUTION: Does physical exercise antagonize clinical and anatomical features characterizing Lieber-DeCarli diet-induced obesity and related metabolic disorders?

PROBLEM: Human insulin is commonly used to treat hyperglycemia in patients with diabetes, but its potential link with female breast cancer is under debate. This study investigated whether human insulin use might be associated with breast cancer risk in Taiwanese women with type 2 diabetes.', 'The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 482,033 women with type 2 diabetes were followed up for breast cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, cumulative dose and cumulative duration of insulin) were calculated and the adjusted hazard ratios were estimated by Cox regression. The potential risk modification by concomitant treatment with metformin, statin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) was also evaluated.', 'There were 59,798 ever-users and 422,235 never-users of human insulin, with respective numbers of incident breast cancer of 559 (0.93 %) and 4,711 (1.12 %), and respective incidence of 207.9 and 215.1 per 100,000 person-years. The overall adjusted hazard ratio (95 % confidence interval) did not show a significant association with insulin [1.033 (0.936-1.139)]. However, patients in the third tertiles of dose-response parameters might show a significantly higher risk of breast cancer while compared to never-users: 1.185 (1.026-1.368), 1.260 (1.096-1.450) and 1.257 (1.094-1.446) for ≥67 months for time since starting insulin, ≥39,000 units for cumulative dose of insulin, and ≥21.8 months for cumulative duration of insulin, respectively. Additional analyses suggested that the breast cancer risk associated with human insulin use might be beneficially modified by concomitant use of metformin, statin and ACEI/ARB.

SOLUTION: Does prolonged use of human insulin increase breast cancer risk in Taiwanese women with type 2 diabetes?

PROBLEM: Chikungunya virus causes chronic infection with manifestations of joint pain. Human synovial fibroblasts get infected with CHIKV and could lead to pro-inflammatory responses. MicroRNAs have potentials to regulate the gene expression of various anti-viral and pro-inflammatory genes. The study aims to investigate the role of miR-146a in modulation of inflammatory responses of human synovial fibroblasts by Chikungunya virus.', 'To study the role of miR-146a in CHIKV pathogenesis in human synovial cells and underlying inflammatory manifestations, we performed CHIKV infection in primary human synovial fibroblasts. Western blotting, real-time PCR, luciferase reporter assay, overexpression and knockdown of cellular miR-146a strategies have been employed to validate the role of miR-146a in regulation of pro-inflammatory NF-κB pathway.', 'CHIKV infection induced the expression of cellular miR-146a, which resulted into down-regulation of TRAF6, IRAK1, IRAK2 and increased replication of CHIKV in human synovial fibroblasts. Exogenous expression of miR-146a in human synovial fibroblasts led to decreased expression of TRAF6, IRAK1, IRAK2 and decreased replication of CHIKV. Inhibition of cellular miR-146a by anti-miR-146a restored the expression levels of TRAF6, IRAK1 and IRAK2. Downregulation of TRAF6, IRAK1 and IRAK2 led to downstream decreased NF-κB activation through negative feedback loop.

SOLUTION:
Does chikungunya virus exploit miR-146a to regulate NF-κB pathway in human synovial fibroblasts?