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.

Ex Input:
Genetic variability in hepatic uptake was recently shown to influence the disposition and cholesterol-lowering effects of statins. Ezetimibe, an inhibitor of the intestinal cholesterol uptake protein Niemann-Pick C 1 like 1, is another drug for which genetic polymorphisms of hepatic organic anion transporting polypeptides (OATPs) are expected to be of clinical relevance because ezetimibe undergoes intensive enterohepatic circulation for which hepatic uptake transporters may be rate-limiting determinants.', 'Using OATP1B3-, OATP2B1-, and OATP1B1-transfected HEK cells, including the OATP1B1 variants OATP1B1*1b and OATP1B1*5, we measured the uptake of ezetimibe and its glucuronide and we analyzed the competition with the common OATP-substrate bromosulfophthalein. Disposition and sterol-lowering effects of 20-mg ezetimibe were measured in 35 healthy participants genotyped for OATP1B1, ABCB1, ABCC2, and UGT1A1.', 'Ezetimibe glucuronide inhibited bromosulfophthalein uptake in all OATP-transfected cells (50% inhibitory concentration (IC50): 0.14-0.26 mumol/l) whereas ezetimibe was 30-100 times less potent. Only the glucuronide was accumulated significantly in cells expressing OATP1B1 and OATP2B1. Its uptake in cells expressing OATP1B1*1b and *5 was reduced. In-vivo studies showed there was a gene-dose-dependent decrease in the area under the curve of ezetimibe in participants with the OATP1B1*1b protein (*1a/*1a, N=12, 112+/-66 ngxh/ml vs. *1a/*1b, N=8, 88+/-39 ngxh/ml vs. *1b/*1b, N=5, 55+/-18 ngxh/ml; Jonkheere-Terpstra, P=0.041) and a tendency for increased glucuronide exposure (704+/-296 vs. 878+/-369 vs. 1059+/-363 ngxh/ml; P=0.092). Fecal ezetimibe excretion was significantly decreased whereas renal glucuronide excretion was increased in carriers of *1b/*1b. Fecal excretion was also diminished in carriers of OATP1B1*5 and *15. The sterol-lowering effect of ezetimibe was not influenced by OATP1B1 polymorphisms.

Ex Output:
Is disposition of ezetimibe influenced by polymorphisms of the hepatic uptake carrier OATP1B1?


Ex Input:
Ductal carcinoma in situ with microinvasion (DCISM) is a rare diagnosis with a good prognosis. Although nodal metastases are uncommon, sentinel lymph node biopsy (SLNB) remains standard care. Volume of disease in invasive breast cancer is associated with SLNB positivity, and, thus we hypothesized that in a large cohort of patients with DCISM, multiple foci of microinvasion might be associated with a higher risk of positive SLNB.', 'Records from a prospective institutional database were reviewed to identify patients with DCISM who underwent SLNB between June 1997 and December 2010. Pathology reports were reviewed for number of microinvasive foci and categorized as 1 focus or ≥2 foci. Demographic, pathologic, treatment, and outcome data were obtained and analyzed.', 'Of 414 patients, 235 (57 %) had 1 focus of microinvasion and 179 (43 %) had ≥2 foci. SLNB macrometastases were found in 1.4 %, and micrometastases were found in 6.3 %; neither were significantly different between patients with 1 focus versus ≥2 foci (p = 1.0). Patients with positive SLNB or ≥2 foci of microinvasion were more likely to receive chemotherapy. At median 4.9 years (range 0-16.2 years) follow-up, 18 patients, all in the SLNB negative group, had recurred for an overall 5-year recurrence-free proportion of 95.9 %.

Ex Output:
Is extent of microinvasion in ductal carcinoma in situ associated with sentinel lymph node metastases?


Ex Input:
MicroRNAs (miRNAs) play important roles in chondrogenic differentiation of mesenchymal stem cells (MSCs). However, the regulation of miR-30a during such process has not yet been well understood. The aim of the study was to investigate the effects of miR-30a on chondrogenic differentiation of MSCs and explore the underlying mechanisms.', 'MSCs were isolated from rat bone marrow, and their immunophenotypes and multilineage differentiation potentials were identified. MiR-30a mimics or inhibitor were transfected into rat MSCs and SW1353 cells, respectively, and then the effects of miR-30a on chondrogenic differentiation were detected. The predicted target gene Delta-like 4 (DLL4, a ligand of the Notch signaling family) was verified by luciferase reporter assay, quantitative real time PCR and western blot.', "MiR-30a was significantly up-regulated during chondrogenic differentiation of rat MSCs. Additionally, transfection of miR-30a mimics remarkably promoted the differentiation of rat MSCs into chondrocytes as evidence by the notably increased mRNA and protein expression levels of chondrogenic markers Collagen II and aggrecan as well as the enhanced alcian blue staining intensity, whereas inhibition of miR-30a obviously suppressed such process. Furthermore, during chondrogenesis, DLL4 expression was found to significantly decrease at both mRNA and protein levels, which was negatively regulated by miR-30a through directly targeting the 3'UTR of DLL4.

Ex Output:

Does microRNA-30a promote chondrogenic differentiation of mesenchymal stem cells through inhibiting Delta-like 4 expression?