TASK DEFINITION: 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.
PROBLEM: Context: Anti-Mullerian hormone (AMH) may have a role in disordered folliculogenesis in polycystic ovary syndrome (PCOS). Though there have been several investigations into circulating AMH levels in patients with PCOS, no previous studies have compared AMH concentrations in the follicular fluid of unstimulated ovaries in women with PCOS with that of normally ovulating women.', 'Follicular fluid was aspirated from 4-8-mm follicles of unstimulated ovaries during routine laparoscopy or laparotomy from women with anovulatory PCOS (n = 11) and those with regular ovulatory cycles (n = 8). Follicular AMH was compared in the two groups. Serum samples were analysed for AMH and endocrine profile.', 'Follicular fluid AMH levels were significantly higher (P < 0.0001) in women with anovulatory PCOS (median: 466.2 ng/ml) compared with normal-ovulatory controls (median: 78.0 ng/ml). Mean follicular fluid AMH levels in PCOS patients were 60 times higher than in the serum. Moreover, there was a significant correlation between the follicular fluid and serum concentrations of AMH in the PCOS group (r = 0.86; P = 0.007) but not in controls.
Answer: Highly elevated AMH in follicular fluid from PCOS patients in contrast to age-matched normal controls suggests that increased circulating concentrations of AMH are partly due to the increased production of AMH by individual follicles and not simply attributable to the increased number of small antral follicles. This suggests an intrinsic abnormality in the ovarian follicles themselves in PCOS, which could contribute to disordered folliculogenesis.

SOLUTION: Is anti-Mullerian hormone increased in follicular fluid from unstimulated ovaries in women with polycystic ovary syndrome?

PROBLEM: Context: Prostate cancer (PCa) is a leading cause of cancer-related death in men, which emphasizes the need for novel therapeutic approaches. Targeting microRNA (miRNA) has been considered as a therapeutic strategy against cancers. Human miR-204-5p potentially targeting BCL2 has been reported to be downregulated in various cancers. We hypothesized that miR-204-5p overexpression induces cancer cell apoptosis by repressing BCL2 expression.', 'A vector harboring mature miR-204-5p was constructed and delivered into human PCa cells. The expression level of miR-204-5p was determined by miRNA quantitative polymerase chain reaction (QPCR). Luciferase reporter assays were performed to verify the function of mature miR-204-5p and its direct binding to BCL2 transcripts. The expression levels of BCL-2 messenger RNA (mRNA) and protein samples were measured by QPCR and Western blot, respectively. Cell viability was detected by WST-1 assays. Induction of apoptosis was determined by increased levels of cleavage caspase 3 and caspase 3/7 activity.', "The expression levels of miR-204-5p were downregulated in PCa cells compared with normal prostate epithelial cells. Transfection of pSM-204 resulted in up to 6.2-fold higher expression of miR-204-5p when compared with pSM control. The mRNA levels of several potential target genes of miR-204-5p were decreased in pSM-204-transfected PC3 and Rv1 cells. BCL2 mRNA and protein expression decreased in miR-204-5p-transfected cells, which led to cytochrome C release from mitochondria. It subsequently increased cleaved caspase 3 and caspase 3/7 activities and reduced cell viability. Cotransfection of a reporter vector harboring the BCL2 3'-untranslated region to compete with endogenous transcripts partially rescued miR-204-5p-induced apoptosis.
Answer: Human miR-204-5p targets BCL2 in PCa cells. Restoration of miR-204-5p in PCa could therefore be considered as a novel strategy by targeting antiapoptotic BCL2.

SOLUTION: Does tumor suppressor miRNA-204-5p promote apoptosis by targeting BCL2 in prostate cancer cells?

PROBLEM: Context: The current American Joint Committee on Cancer Seventh Edition (AJCC7) pathologic staging for esophageal adenocarcinoma (EAC) is derived from data assessing the outcomes of patients having undergone esophagectomy without neoadjuvant treatment and has unclear significance in patients who have received multimodality therapy. Lymph nodes with evidence of neoadjuvant treatment effect without residual cancer cells may be observed and are not traditionally considered in pathologic reports, but may have prognostic significance.', 'All patients who underwent esophagectomy after completing neoadjuvant therapy for EAC at our institution between 2006 and 2012 were reviewed. Slides of pathologic specimens were reexamined for locoregional treatment-response nodes lacking viable cancer cells but with evidence of acellular mucin pools, central fibrosis, necrosis, or calcifications suggesting prior tumor involvement. Kaplan-Meier survival functions were estimated, and Cox proportional hazards regression models were used to compare staging models.', 'Ninety patients (82 men) underwent esophagectomy after neoadjuvant therapy for EAC (mean age, 61.8 ± 8.9 years). All patients received preoperative chemotherapy, and 50 patients also underwent preoperative radiotherapy. Median Kaplan-Meier survival was 55.6 months, and 5-year survival was 35% (95% confidence interval, 19% to 62%). A total of 100 treatment-response nodes were found in 38 patients. For patients with limited nodal disease (62 ypN0-N1), the presence of treatment-response nodes was associated with significantly worse survival (p = 0.03) compared with patients lacking such nodes. Adjusting for patient age and AJCC7 pathologic stage showed the presence of treatment-response nodes significantly increased the risk of death (hazard ratio, 2.7; 95% confidence interval, 1.1 to 6.9; p = 0.04). When stage-adjusted survival was modeled, counting treatment-response nodes as positive nodes offered a better model fit than ignoring them.
Answer: Treatment-response lymph nodes detected from esophagectomy specimens in patients having undergone neoadjuvant chemotherapy or combined chemoradiation for EAC provide valuable prognostic information, particularly in patients with limited nodal disease. The current practice of considering lymph nodes lacking viable cancer cells, but with evidence of tumor necrosis, as pathologically negative likely results in understaging. Future efforts at revising the staging system for EAC should consider incorporating treatment-response lymph nodes in the analysis.

SOLUTION:
Is neoadjuvant treatment response in negative nodes an important prognosticator after esophagectomy?