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: Hepatocyte nuclear factor 4α (HNF4α) is a liver enriched transcription factor and is indispensable for liver development. However, the role of HNF4α in hepatocellular carcinoma (HCC) progression remains to be elucidated. We report that reduced HNF4α expression correlated well with the aggressive clinicopathological characteristics of HCC and predicted poor prognosis of patients. HNF4α levels were even lower in metastatic HCCs, and ectopic HNF4α expression suppressed the metastasis of hepatoma cells both in vitro and in vivo. Forced HNF4α expression attenuated the expression and nuclear translocation of RelA (p65) and impaired NF-κB activation through an IKK-independent mechanism. Blockage of RelA robustly attenuated the suppressive effect of HNF4α on hepatoma cell metastasis. MicroRNA (miR)-7 and miR-124 were transcriptionally up-regulated by HNF4α, which repressed RelA expression by way of interaction with RelA-3' untranslated region (UTR). In addition, nuclear factor kappa B (NF-κB) up-regulated the expression of miR-21 in hepatoma cells, resulting in decreased HNF4α levels through down-regulating HNF4α-3'UTR activity.

SOLUTION: Does hepatocyte nuclear factor 4α-nuclear factor-κB feedback circuit modulate liver cancer progression?

PROBLEM: Polo-like kinase 1 (PLK1) controls the main cell-cycle checkpoints, suggesting utility of its inhibition for cancer treatment, including of highly proliferative pediatric cancer. This preclinical study explored the selective PLK1 inhibitor volasertib (BI 6727) alone and combined with chemotherapy in pediatric malignancies.', 'Inhibition of proliferation was explored in vitro using dimethylthiazol carboxymethoxyphenyl sulfophenyl tetrazolium (MTS) assay. Mice bearing human xenografts were treated with weekly intravenous injections of volasertib.', 'Volasertib inhibited proliferation in all 40 cell lines tested, with a mean half-maximal growth inhibitory concentration of 313 nmol/l (range: 4-5000 nmol/l). Volasertib was highly active against RMS-1 alveolar rhabdomyosarcoma xenografts, resulting in 100% tumor regression. Activity was associated with complete and prolonged G2/M arrest and subsequent apoptotic cell death. Volasertib showed synergistic activity with vincristine but antagonistic effects with etoposide.

SOLUTION: Does polo-like Kinase Inhibitor Volasertib exhibit Antitumor Activity and Synergy with Vincristine in Pediatric Malignancies?

PROBLEM: Despite recent advancements in post-cardiac arrest resuscitation, the optimal measurement of postarrest outcome remains unclear. We hypothesized that Cerebral Performance Category score can predict the long-term outcome of postarrest survivors who received targeted temperature management during their postarrest hospital care.', 'Retrospective chart review.', 'Two academic medical centers from May 2005 to December 2012.', 'The medical records of 2,417 out-of-hospital and in-hospital patients post cardiac arrest were reviewed to identify 140 of 582 survivors who received targeted temperature management.', 'None.', 'The Cerebral Performance Category scores at hospital discharge were determined by three independent abstractors. The 1-month, 6-month, and 12-month survival of these patients was determined by reviewing hospital records and querying the Social Security Death Index and by follow-up telephone calls. The association of unadjusted long-term survival and adjusted survival with Cerebral Performance Category was calculated. Of the 2,417 patients who were identified to have undergone cardiac arrest, 24.1% (582/2,417) were successfully resuscitated, of whom 24.1% (140/582) received postarrest targeted temperature management. Overall, 42.9% of patients (60/140) were discharged with Cerebral Performance Category 1, 27.1% (38/140) with Cerebral Performance Category 2, 18.6% (26/140) with Cerebral Performance Category 3, and 11.4% (16/140) with Cerebral Performance Category 4. Cerebral Performance Category 1 survivors had the highest long-term survival followed by Cerebral Performance Categories 2 and 3, with Cerebral Performance Category 4 having the lowest long-term survival (p < 0.001, log-rank test). We found that Cerebral Performance Category 3 (hazard ratio = 3.62, p < 0.05) and Cerebral Performance Category 4 (hazard ratio = 12.73, p < 0.001) remained associated with worse survival after adjusting for age, gender, race, shockable rhythm, time to targeted temperature management initiation, total duration of resuscitation, withdrawal of care, and location of arrest.

SOLUTION:
Does cerebral performance category at hospital discharge predict long-term survival of cardiac arrest survivors receiving targeted temperature management*?