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: To investigate the expression and clinical significance of programmed cell death 4 (PDCD4), a novel metabolism-associated gene, during polycystic ovary syndrome (PCOS) pathogenesis.', 'Case-control study.', 'University hospital.', 'A total of 77 PCOS patients and 67 healthy women as matched controls.', 'PDCD4 expression in peripheral blood mononuclear cells analyzed by quantitative real-time polymerase chain reaction, and apoptosis of granulosa cells (GCs) detected by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and small-interfering RNA.', 'PDCD4 expression, body mass index (BMI), insulin 0, insulin 120, glucose 120, homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for β-cell function (HOMA-β), triglycerides, high-density lipoprotein (HDL), and GC apoptosis.', 'The PCOS patients had higher PDCD4 expression, but BMI was similar as matched with the obese group, which positively correlated with BMI, insulin 0, insulin 120, glucose 120, HOMA-IR, HOMA-β, triglycerides and negatively correlated with HDL (P<.05). After metformin treatment, PDCD4 expression was distinctly down-regulated for the obese women with PCOS with insulin resistance. Compared with the healthy controls, the apoptosis percentage of GCs was higher in the PCOS group and was decreased by knocking down PDCD4. Furthermore, expression of proapotosis factor Bax and the Bax/Bcl-2 ratio were lower, whereas the expression of antiapoptosis factor Bcl-2 was increased. In a multivariate logistic regression analysis, the level of PDCD4 expression independently related to the odds of PCOS risk after controlling for estradiol and insulin 120 (odds ratio 1.318).
Answer: Our study suggests for the first time that higher PDCD4 expression might play an important role in PCOS pathogenesis by affecting obesity, insulin resistance, lipid metabolism disorders, and GC apoptosis.
Example Output: Is higher PDCD4 expression associated with obesity , insulin resistance , lipid metabolism disorders , and granulosa cell apoptosis in polycystic ovary syndrome?

Example Input: 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.
Example Output: Is oesophageal histology in gastro-oesophageal reflux disease of minor pre- and postoperative diagnostic value?

Example Input: Context: Histamine is a biogenic amine that has been shown to contribute to several pathological conditions, such as allergic conditions, experimental encephalomyelitis, and malaria. In humans, as well as in murine models of malaria, increased plasma levels of histamine are associated with severity of infection. We reported recently that histamine plays a critical role in the pathogenesis of experimental cerebral malaria (CM) in mice infected with Plasmodium berghei ANKA. Histamine exerts its biological effects through four different receptors designated H1R, H2R, H3R, and H4R.', 'In the present work, we explored the role of histamine signaling via the histamine H3 receptor (H3R) in the pathogenesis of murine CM. We observed that the lack of H3R expression (H3R(-/-) mice) accelerates the onset of CM and this was correlated with enhanced brain pathology and earlier and more pronounced loss of blood brain barrier integrity than in wild type mice. Additionally tele-methylhistamine, the major histamine metabolite in the brain, that was initially present at a higher level in the brain of H3R(-/-) mice was depleted more quickly post-infection in H3R(-/-) mice as compared to wild-type counterparts.
Answer: Our data suggest that histamine regulation through the H3R in the brain suppresses the development of CM. Thus modulating histamine signaling in the central nervous system, in combination with standard therapies, may represent a novel strategy to reduce the risk of progression to cerebral malaria.
Example Output:
Does histamine H ( 3 ) receptor-mediated signaling protect mice from cerebral malaria?