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.

Example Input: Context: Animal experiment studies have revealed a positive association between intake of citrus fruits and bone health. Nomilin, a limonoid present in citrus fruits, is reported to have many biological activities in mammalian systems, but the mechanism of nomilin on bone metabolism regulation is currently unclear.', 'To reveal the mechanism of nomilin on osteoclastic differentiation of mouse primary bone marrow-derived macrophages (BMMs) and the mouse RAW 264.7 macrophage cell line into osteoclasts.', 'Controlled laboratory study. Effects of nomilin on osteoclastic differentiation were studied in in vitro cell cultures.', 'Cell viability of RAW 264.7 cells and BMMs was measured with the Cell Counting Kit. TRAP-positive multinucleated cells were counted as osteoclast cell numbers. The number and area of resorption pits were measured as bone-resorbing activity. Osteoclast-specific genes expression was evaluated by quantitative real-time PCR; and proteins expression was evaluated by western blot.', 'Nomilin significantly decreased TRAP-positive multinucleated cell numbers compared with the control, and exhibited no cytotoxicity. Nomilin decreased bone resorption activity. Nomilin downregulated osteoclast-specific genes, NFATc1 and TRAP mRNA levels. Furthermore, nomilin suppressed MAPK signaling pathways.
Answer: This study demonstrates clearly that nomilin has inhibitory effects on osteoclastic differentiation in vitro. These findings indicate that nomilin-containing herbal preparations have potential utility for the prevention of bone metabolic diseases.
Example Output: Does citrus limonoid nomilin inhibit osteoclastogenesis in vitro by suppression of NFATc1 and MAPK signaling pathways?

Example Input: Context: Preoperative anemia may affect postoperative mortality and morbidity following elective cranial operations.', 'The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was used to identify elective cranial neurosurgical cases (2006-2012). Morbidity was defined as wound infection, systemic infection, cardiac, respiratory, renal, neurologic, and thromboembolic events, and unplanned returns to the operating room. For 30-day postoperative mortality and morbidity, adjusted odds ratios (ORs) were estimated with multivariable logistic regression.', 'Of 8015 patients who underwent elective cranial neurosurgery, 1710 patients (21.4%) were anemic. Anemic patients had an increased 30-day mortality of 4.1% versus 1.3% in non-anemic patients (P < 0.001) and an increased 30-day morbidity rate of 25.9% versus 14.14% in non-anemic patients (P < 0.001). The 30-day morbidity rates for all patients undergoing cranial procedures were stratified by diagnosis: 26.5% aneurysm, 24.7% sellar tumor, 19.7% extra-axial tumor, 14.8% intra-axial tumor, 14.4% arteriovenous malformation, and 5.6% pain. Following multivariable regression, the 30-day mortality in anemic patients was threefold higher than in non-anemic patients (4.1% vs 1.3%; OR = 2.77; 95% CI: 1.65-4.66). The odds of postoperative morbidity in anemic patients were significantly higher than in non-anemic patients (OR = 1.29; 95% CI: 1.03-1.61). There was a significant difference in postoperative morbidity event odds with a hematocrit level above (OR = 1.07; 95% CI: 0.78-1.48) and below (OR = 2.30; 95% CI: 1.55-3.42) 33% [hemoglobin (Hgb) 11 g/dl].
Answer: Preoperative anemia in elective cranial neurosurgery was independently associated with an increased risk of 30-day postoperative mortality and morbidity when compared to non-anemic patients. A hematocrit level below 33% (Hgb 11 g/dl) was associated with a significant increase in postoperative morbidity.
Example Output: Does preoperative anemia increase postoperative morbidity in elective cranial neurosurgery?

Example Input: Context: Dysplastic nodules (DN) may be divided into high-grade and low-grade, and the former has been known as a precancerous or borderline lesion. Recently many morphological characteristics concerning these types of DN have been reported. In the present study we attempted to evaluate the scirrhous change in DN as an indicative feature of high-grade DN, based on the morphological and cell-kinetic analyses using immunohistochemical stains for Ki-67.', "We reviewed 35 livers with DN and selected 15 DN with scirrhous change. We stained DN-bearing sections of each case with hematoxylin and eosin, trichrome, reticulin and Perls' stain. We tried to subclassify and characterize the scirrhous change according to the fibrosis pattern. We also stained with Ki-67 immunohistochemically to assess the proliferative activity of DN with scirrhous change.", 'We found two types of scirrhous change, that is, pericellular and stellate. The pericellular type was related to the Mallory body-forming cholestatic degeneration, whereas the stellate type was associated with extensive portal fibrosis probably induced by ischemic damage. Among DN with scirrhous change, high-grade DN comprised five nodules (33%) and there were 10 (67%) low-grade nodules. There was no significant relationship between the presence or the types of scirrhous change and the grade of DN. The significant differences of Ki-67 labeling indices between types of scirrhous change were not shown in this study. We also could not find the differences between Ki-67 labeling indices of scirrhous DN (high and low grades) and those of surrounding regenerative nodules.
Answer: This evidence indicated that the scirrhous change in DN was not a specific feature of high-grade DN. We also found that scirrhous DN have two morphological varieties that may represent biologically different processes, that is, pericellular scirrhous type and stellate scirrhous type.
Example Output:
Do scirrhous changes in dysplastic nodules indicate high-grade status?