TASK DEFINITION: Given a passage with a context and an answer, 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: Context: Serum elevations of interleukin-6 (IL-6) correlate with multiple organ dysfunction syndrome and mortality in critically injured trauma patients. Data from rodent models of controlled hemorrhage suggest that recombinant IL-6 (rIL-6) infusion protects tissue at risk for ischemia-reperfusion injury. Exogenous rIL-6 administered during shock appears to abrogate inflammation, providing a protective rather than a deleterious influence. In an examination of this paradox, the current study aimed to determine whether rIL-6 decreases inflammation in a clinically relevant large animal model of uncontrolled hemorrhagic shock, (UHS), and to investigate the mechanism of protection.', 'Swine were randomized to four groups (8 animals in each): (1) sacrifice, (2) sham (splenectomy followed by hemodilution and cooling to 33 degrees C), (3) rIL-6 infusion (sham plus UHS using grade 5 liver injury with packing and resuscitation plus blinded infusion of rIL-6 [10 mcg/kg]), and (4) placebo (UHS plus blinded vehicle). After 4 hours, blood was sampled, estimated blood loss determined, animals sacrificed, and lung harvested for RNA isolation. Quantitative reverse transcriptase-polymerase chain reaction was used to assess granulocyte colony-stimulating factor (G-CSF), IL-6, and tumor necrosis factor-alpha (TNFalpha) messenger ribonucleic acid (mRNA) levels. Serum levels of IL-6 and TNFalpha were measured by enzyme-linked immunoassay (ELISA).', 'As compared with placebo, IL-6 infusion in UHS did not increase estimated blood loss or white blood cell counts, nor decrease hematocrit or platelet levels. As compared with the sham condition, lung G-CSF mRNA production in UHS plus placebo increased eightfold (*p < 0.05). In contrast, rIL-6 infusion plus UHS blunted G-CSF mRNA levels, which were not significantly higher than sham levels (p = 0.1). Infusion of rIL-6 did not significantly affect endogenous production of either lung IL-6 or mRNA. As determined by ELISA, rIL-6 infusion did not increase final serum levels of IL-6 or TNFalpha over those of sham and placebo conditions.
Answer: Exogenous rIL-6 blunts lung mRNA levels of the proinflammatory cytokine G-CSF. The administration of rIL-6 does not increase the local expression of IL-6 nor TNFalpha mRNA in the lung. Additionally, rIL-6 infusion does not appear to cause systemic toxicity.

SOLUTION: Does interleukin-6 infusion blunt proinflammatory cytokine production without causing systematic toxicity in a swine model of uncontrolled hemorrhagic shock?

PROBLEM: Context: PA-MSHA, a genetically engineered Pseudomonas aeruginosa (PA) strain, is currently under investigation as a new anti-cancer drug. It can induce cell cycle arrest and apoptosis in different human cancer cells, including hormone receptor negative breast cancer cells. However, the underlying mechanism of tumor lethality mediated by PA-MSHA remains to be fully investigated.', 'The effect of PA-MSHA on human hormone receptor negative breast cancer cells was analyzed by morphological measurement, western blot, cell proliferation assay and mouse xenograft model.', 'PA-MSHA was found to induce endoplasmic reticulum (ER) stress in breast cancer cell lines through the IRE1 signaling pathway. Inhibiting autophagy potentiated the cytotoxic effect of PA-MSHA while treating breast cancer cell lines. In mouse xenograft model, PA-MSHA produced more pronounced tumor suppression in mice inoculated with IRE1 gene knockdown. MDA-MB-231HM cells.
Answer: These findings demonstrated inhibiting autophagy together with PA-MSHA might be a promising therapeutic strategy in treating hormone receptor negative breast cancer cells.

SOLUTION: Does inhibition of autophagy enhance the cytotoxic effect of PA-MSHA in breast cancer?

PROBLEM: Context: Non-response to cardiac resynchronization therapy (CRT) might be due to insufficient resynchronization as a result of a sub-optimal left ventricular lead positon (LV-LP).', 'To evaluate the impact of different LV-LPs on mortality and symptomatic improvement in a large cohort of patients treated with CRT.', "We performed a nationwide cohort study on consecutive patients receiving a CRT device from 1997 to 2012 registered in the Danish pacemaker and ICD register. The LV-LP was defined clockwise in a left anterior oblique (LAO) view and categorized as anterior (≤2 o'clock), lateral (2 to 4 o'clock) or posterior (>4 o'clock), and as basal, mid-ventricular, or apical in a right anterior oblique (RAO) view. Outcomes were all cause mortality and clinical response (improvement in NYHA class). Adjusted hazard ratio (aHR) and odds ratio (aOR) with 95% confidence intervals (CI) were calculated using Cox and logistic regression analysis.", 'A total of 2594 patients were included. A lateral LV-LP, (aHR 0.77, 95% CI 0.64-0.92, p=0.004), and a posterior LV-LP, (aHR 0.71 95% CI 0.53-0.97, p=0.029) were associated with lower mortality as compared to an anterior LV-LP. A lateral LV-PV was associated with higher clinical response rate as compared to an anterior LV-LP (aOR 1.37, 1.03-1.83, p=0.032). No statistically significant associations were observed between LV-LP in the RAO view and mortality or clinical response.
Answer: An anterior left ventricular lead position is associated with increased all-cause mortality and lower clinical response rate in patients treated with CRT and should be avoided.

SOLUTION:
Is an anterior left ventricular lead position associated with increased mortality and non-response in cardiac resynchronization therapy?