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.

Ex Input:
Context: Biological evidence reported in the literature supports the role of CELSR1 as being essential for valvular function in murine lymphatics. Yet thus far, there have been no variants in CELSR1 associated with lymphatic dysfunction in humans.', 'In this report, a rare early inactivating mutation in CELSR1 is found to be causal for non-syndromic, lower extremity lymphedema in a family across three generations. Near-infrared fluorescence lymphatic imaging shows that instead of being propelled within the lumen of well-defined lymphatic vessels, lymph moved in regions of both legs in an unusual fashion and within sheet-like structures.
Answer: CELSRI may be responsible for primary, non-syndromic lymphedema in humans.

Ex Output:
Is a novel mutation in CELSR1 associated with hereditary lymphedema?


Ex Input:
Context: Chronic inflammation is hypothesized to influence prostate cancer development, although a definitive link has not been established.', 'Prostate cancer cases (N = 191) detected on a for-cause (clinically indicated) or end-of-study (protocol directed) biopsy, and frequency-matched controls (N = 209), defined as negative for cancer on an end-of-study biopsy, were sampled from the placebo arm of the Prostate Cancer Prevention Trial. Inflammation prevalence and extent in benign areas of biopsy cores were visually assessed using digital images of hematoxylin and eosin-stained sections. Logistic regression was used to estimate associations.', 'Of note, 86.2% of cases and 78.2% of controls had at least one biopsy core (of three assessed) with inflammation in benign areas, most of which was chronic. Men who had at least one biopsy core with inflammation had 1.78 [95% confidence interval (CI), 1.04-3.06] times the odds of prostate cancer compared with men who had zero cores with inflammation. The association was stronger for high-grade disease (Gleason sum 7-10, N = 94; OR, 2.24; 95% CI, 1.06-4.71). These patterns were present when restricting to cases and controls in whom intraprostatic inflammation was the least likely to have influenced biopsy recommendation because their prostate-specific antigen (PSA) was low (<2 ng/mL at biopsy).
Answer: Inflammation, most of which was chronic, was common in benign prostate tissue, and was positively associated with prostate cancer, especially high grade. The association did not seem to be due to detection bias.

Ex Output:
Is chronic inflammation in benign prostate tissue associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial?


Ex Input:
Context: We examined hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and nuclear factor-kappaB in acquired cystic disease of the kidney associated with renal cell carcinoma to elucidate the roles of these factors in cyst formation and subsequent tumor transformation.', 'Immunohistochemical expression of hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and phosphorylated nuclear factor-kappaB (active form) were examined in 20 normal kidney samples obtained from nephrectomy for localized renal cell carcinoma and 25 kidneys with acquired cystic disease associated renal cell carcinoma from 23 patients on dialysis.', 'Only faint or weak immunostaining for hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and phosphorylated nuclear factor-kappaB was observed in normal kidney tissues. In nontumor areas of the kidneys with acquired cystic disease expressions of these 3 proteins was up-regulated in tubular and cyst epithelial cells. Acquired cysts were classified into 3 types according to cyst epithelium morphology, namely flat, cuboidal and hyperplastic. Hyperplastic cysts were the predominant cysts expressing hypoxia-inducible protein 2 and hypoxia-inducible factor-1alpha. Although up-regulation of hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and phosphorylated nuclear factor-kappaB was observed in renal cell carcinoma, positive hypoxia-inducible protein 2 immunostaining was detected predominantly in papillary renal cell carcinoma, while positive hypoxia-inducible factor-1alpha and phosphorylated nuclear factor-kappaB immunostaining was prominent in clear cell renal cell carcinoma.
Answer: Hypoxia-inducible protein 2, hypoxia-inducible factor-1alpha and phosphorylated nuclear factor-kappaB may be involved in a continuous process of the evolution of phenotypic expression from a simple cyst to epithelial hyperplasia and eventually to tumor.

Ex Output:

Is over expression of hypoxia-inducible protein 2 , hypoxia-inducible factor-1alpha and nuclear factor kappaB putatively involved in acquired renal cyst formation and subsequent tumor transformation in patients with end stage renal failure?