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: The clinical value of oesophageal histology in non-complicated gastro-oesophageal reflux disease (GORD) is controversial. Our aim was to explore the role of histology in preoperative diagnosis and postoperative follow-up in GORD.', 'From 40 patients 2 histopathologists graded and scored 191 oesophageal biopsies in a blinded manner to evaluate inter- and intraobserver variation pre- and postoperatively. Correlation between preoperative histology and objective clinical findings (endoscopy, esophageal 24-hour pH monitoring, and manometry) was calculated as well.', 'Pathologist I interpreted 16 (50%) preoperative biopsies as normal, 5 (16%) with mild, 4 (12.5%) moderate, and 7 (21.9%) severe reflux changes. Pathologist II interpreted 11 (35.5%) preoperative biopsies as normal, 11 (35.5%) with mild, 6 (19.4%) moderate, and 3 (9.7%) severe reflux changes. In preoperative biopsies, interobserver variation was 33.8% and intraobserver variation 9.7%. A positive correlation was detectable between preoperative endoscopic and morphologic findings; no correlation existed between either acid reflux or LES pressure and oesophageal morphology. Normal pH monitoring and fundic wrap were noted postoperatively in all cases. In postoperative histology no significant differences according to pathologist I existed when compared with preoperative changes: 22 normal (69%), 7 mild (22%), 1 moderate (3.1%), and 2 severe (6.3%). Compared to preoperative analysis, pathologist II interpreted 24 (77%, p = 0.001) of the postoperative findings as normal, 1 (3%, p = 0.003) as mild, 4 (12.9%, n.s.) as moderate, and 2 (6.5% n.s.) as severe reflux changes. In postoperative biopsies interobserver variation was 21.1% and intraobserver variation 5.6%.
Answer: The role of oesophageal histology in preoperative diagnosis and postoperative follow-up of GORD may be considered limited.

SOLUTION: Is oesophageal histology in gastro-oesophageal reflux disease of minor pre- and postoperative diagnostic value?

PROBLEM: Context: We utilized whole-genome mapping of promoters that are activated by DNA hypomethylation in hepatocellular carcinoma (HCC) clinical samples to shortlist novel targets for anticancer therapeutics. We provide a proof of principle of this approach by testing six genes short-listed in our screen for their essential role in cancer growth and invasiveness.', 'We used siRNA- or shRNA-mediated depletion to determine whether inhibition of these genes would reduce human tumor xenograft growth in mice as well as cell viability, anchorage-independent growth, invasive capacities, and state of activity of nodal signaling pathways in liver, breast, and bladder cancer cell lines.', 'Depletion of EXOSC4, RNMT, SENP6, WBSCR22, RASAL2, and NENF effectively and specifically inhibits cancer cell growth and cell invasive capacities in different types of cancer, but, remarkably, there is no effect on normal cell growth, suggesting a ubiquitous causal role for these genes in driving cancer growth and metastasis. Depletion of RASAL2 and NENF in vitro reduces their growth as explants in vivo in mice. RASAL2 and NENF depletion interferes with AKT, WNT, and MAPK signaling pathways as well as regulation of epigenetic proteins that were previously demonstrated to drive cancer growth and metastasis.
Answer: Our results prove that genes that are hypomethylated and induced in tumors are candidate targets for anticancer therapeutics in multiple cancer cell types. Because these genes are particularly activated in cancer, they constitute a group of targets for specific pharmacologic inhibitors of cancer and cancer metastasis. Clin Cancer Res; 20(12); 3118-32. ©2014 AACR.

SOLUTION: Does genome-wide study of hypomethylated and induced genes in patients with liver cancer unravel novel anticancer targets?

PROBLEM: Context: Therapeutic angiogenesis is a promising strategy for treating ischemia. Our previous work showed that endogenous endothelial tissue factor (TF) expression induces intracrine signaling and switches-on angiogenesis in microvascular endothelial cells (mECs). We have hypothesized that activated mECs could exert a further paracrine regulation through the release of TF-rich microvascular endothelial microparticles (mEMPs) and induce neovascularization of ischemic tissues.', 'Here, we describe for the first time that activated mECs are able to induce reparative neovascularization in ischemic zones by releasing TF-rich microparticles. We show in vitro and in vivo that mEMPs released by both wild-type and TF-upregulated-mECs induce angiogenesis and collateral vessel formation, whereas TF-poor mEMPs derived from TF-silenced mECs are not able to trigger angiogenesis. Isolated TF-bearing mEMPs delivered to nonperfused adductor muscles in a murine hindlimb ischemia model enhance collateral flow and capillary formation evidenced by MRI. TF-bearing mEMPs increase angiogenesis operating via paracrine regulation of neighboring endothelial cells, signaling through the β1-integrin pathway Rac1-ERK1/2-ETS1 and triggering CCL2 (chemokine [C-C motif] ligand 2) production to form new and competent mature neovessels.
Answer: These findings demonstrate that TF-rich mEMPs released by microvascular endothelial cells can overcome the consequences of arterial occlusion and tissue ischemia by promoting postischemic neovascularization and tissue reperfusion.

SOLUTION:
Do angiogenic microvascular endothelial cells release microparticles rich in tissue factor that promotes postischemic collateral vessel formation?