TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: The caudal-type homeodomain transcriptional factor CDX2, a member of the caudal-related homeobox gene family, plays a crucial role in the regulation of cell proliferation and differentiation in the gut. Recent studies have reported that expression of CDX2 was an independent marker of outcome in patients with resected adenocarcinoma of ampulla of Vater, gastric cancer, and colon cancer. The clinicopathological significance of CDX2 expression has hitherto remained unclear in biliary tract carcinoma (BTC). The aim of this study was to determine whether CDX2 expression in BTC indicates clinical outcome.', 'The expression of CDX2 was investigated immunohistochemically in surgically resected specimens from 164 patients with BTC, including 74 intrahepatic cholangiocarcinomas, 49 extrahepatic cholangiocarcinomas, and 41 gallbladder carcinomas. The correlation between expression of CDX2 and clinicopathological factors, including overall survival, tumor location, tumor stage, and degree of tumor differentiation, was examined in patients with BTC.', 'In total, 27 of the 164 (16.46%) patients with BTC expressed CDX2. The frequency of CDX2 expression was much higher in the extrahepatic cholangiocarcinomas (22.45%) and gallbladder carcinomas (29.27%) than in the intrahepatic cholangiocarcinomas (5.41%), the difference being statistically significant (P = 0.002). Factors influencing survival on univariate analysis were tumor stage (P < 0.00001), degree of tumor differentiation (P = 0.0002), and CDX2 expression (P = 0.01). On multivariate analysis using the Cox proportional hazard model, CDX2 expression and tumor stage were independent prognostic factors in patients with BTC.\Question: Is expression of the caudal-type homeodomain transcription factor CDX2 related to clinical outcome in biliary tract carcinoma?

SOLUTION: Expression of CDX2 was an independent indicator of outcome in patients with BTC in addition to tumor stage and tumor differentiation. The mechanism by which CDX2 expression influences behavior of biliary tract carcinoma needs further investigation.

PROBLEM: Context: Reduction-oxidation (redox) signaling, the translation of an oxidative intracellular environment into a cellular response, is mediated by the reversible oxidation of specific cysteine thiols. The latter can result in disulfide formation between protein hetero- or homodimers that alter protein function until the local cellular redox environment has returned to the basal state. We have previously shown that this mechanism promotes the nuclear localization and activity of the Forkhead Box O4 (FOXO4) transcription factor.', 'In this study, we sought to investigate whether redox signaling differentially controls the human FOXO3 and FOXO4 paralogs.', 'We present evidence that FOXO3 and FOXO4 have acquired paralog-specific cysteines throughout vertebrate evolution. Using a proteome-wide screen, we identified previously unknown redox-dependent FOXO3 interaction partners. The nuclear import receptors Importin-7 (IPO7) and Importin-8 (IPO8) form a disulfide-dependent heterodimer with FOXO3, which is required for its reactive oxygen species-induced nuclear translocation. FOXO4 does not interact with IPO7 or IPO8.\Question: Does evolutionary acquisition of cysteines determine FOXO paralog-specific redox signaling?

SOLUTION: IPO7 and IPO8 control the nuclear import of FOXO3, but not FOXO4, in a redox-sensitive and disulfide-dependent manner. Our findings suggest that evolutionary acquisition of cysteines has contributed to regulatory divergence of FOXO paralogs, and that phylogenetic analysis can aid in the identification of cysteines involved in redox signaling.

PROBLEM: Context: In patients undergoing total knee replacement (TKR), most blood loss occurs post-operatively, and the return of unwashed filtered shed blood (USB) from post-operative drainage may represent an alternative to allogeneic blood transfusion (ABT). We evaluated the impact of USB return on the cellular immune response (CIR) after TKR.', 'Forty TKR patients, intended to receive post-operative USB, entered the study. Blood samples were obtained before and 6 h, 24 h, 72 h and 7 days after surgery, and from USB, after it had been passed through a 40-microm filter. Full blood cell counts, lymphocyte subsets and immunoglobulins (IgA, IgG, IgM) were measured in all samples. A set of clinical data was collected from each patient.', 'Twenty-four of the 25 patients received a mean of 1.2 USB units and did not need additional ABT (USB group). Twelve of the 15 remaining patients who received neither USB nor ABT served as a control group for the post-operative CIR study. All patients showed a post-operative decrease in T-cell and natural killer (NK) cell counts, but not B-cell counts, and there were no significant differences between the groups with regard to CIR parameters, post-operative infection or hospital stay.\Question: Does post-operative unwashed shed blood transfusion modify the cellular immune response to surgery for total knee replacement?

SOLUTION:
Post-operative salvage and return of USB after TKR does not seem to increase the post-operative infection rate or hospital stay, and does not modify CIR induced by surgery. These findings add to the clinical experience that post-operative USB return, as a source of autologous blood, is safe, and questions the beneficial effect of blood washing.