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: The proportion of dendritic cell subpopulations in the skin is important for the severity of atopic dermatitis because topical treatment with tacrolimus leads to rapid depletion of inflammatory dendritic epidermal cells, whereas Langerhans cells (LCs) predominate in cured sites.', 'The effects of tacrolimus and TGF-beta1 on LC differentiation and the idea of tacrolimus skewing the differentiation of epidermal precursors to LCs were evaluated.', 'The presence of LC markers, MHC, and costimulatory molecules and stimulatory capacity toward T cells of monocyte-derived LCs were analyzed. Skin samples of patients with atopic dermatitis were assessed by means of immunofluorescence microscopy before and after tacrolimus treatment. TGF-beta production of skin cells was analyzed.', 'Tacrolimus and TGF-beta1 act synergistically on the generation of LCs and the expression of CD40, CD80, CD86, CD83, and MHC II; stabilize TGF-beta receptor II expression; and decrease the stimulatory capacity of LCs toward T cells. In vivo the number of epidermal LCs in tacrolimus-treated skin increased.
Answer: The synergism between TGF-beta1 and tacrolimus leads to the generation of LCs, reduced expression of costimulatory and MHC II molecules, and reduced stimulatory activity. Shifting the balance of the dendritic cell population to LCs might be of major importance for the therapeutic effect of tacrolimus.
Example Output: Do tacrolimus and TGF-beta act synergistically on the generation of Langerhans cells?

Example Input: Context: Recent changes in the NHS have led to a considerably increased workload for histopathologists prompting the publication of guidelines from the Royal College of Pathologists regarding specimen analysis. In most hospitals, cholecystectomy specimens are routinely sent for histology regardless of whether or not there is any visible macroscopic abnormality suggestive of malignancy. Our aim was to assess whether it would be safe to adopt a policy of processing only suspicious gallbladders without compromising patient management and outcome.', 'A retrospective analysis of all cholecystectomies performed between 1995 and 1999 was conducted using computerised histopathology records and patient notes. The histopathology department has a standardised procedure for the evaluation of cholecystectomy specimens and all gallbladders had been processed in this manner.', '1308 patients had undergone cholecystectomy (mean 262/year). All specimens had been sent for histology: 1249 of the specimens showed chronic cholecystitis, 38 acute cholecystitis or empyema and 16 were removed as part of another procedure. In five gallbladders there was evidence of primary carcinoma. In all cases the gallbladder was opened at the time of surgery (as commented upon in the operation notes) and all showed macroscopic evidence suggestive of carcinoma. Pre-operative ultrasound scanning identified probable carcinoma in three of the five cases.
Answer: All cases of gallbladder carcinoma were diagnosed pre-operatively or intra-operatively and a histological diagnosis did not alter the management or outcome of any of these patients. Selective histopathology of the gallbladder is safe and may be a more measured approach saving histolopathology departments time and money.
Example Output:
Is a selective approach to histopathology of the gallbladder justifiable?