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: Women diagnosed with pregnancy-associated breast cancer postpartum have a worse prognosis, stage for stage, than other women with breast cancer. The time of breast involution is tumor promotional. The extracellular matrix protein tenascin-C is upregulated during involution in animal models and promotes breast cancer progression. It interacts with transforming growth factor (TGF), which also is involved in breast involution and breast cancer progression. Little is known about the expression of tenascin-C during human breast involution, nor its relationship to TGF. The purpose of this study was to investigate the expression of tenascin-C throughout lactation, as well as its relationship to TGF1 and TGF2.', 'Three milk samples from 25 lactating women (transitional, whole, and wean) were collected, separated into components (cells, fat, and skim), and the skim fraction analyzed for total protein, tenascin-C, TGF1, and TGF2. Tenascin-C, TGF1, and TGF2 were detectable in all milk samples.', 'Highest tenascin-C levels on average were found in whole milk, whereas highest mean TGF1 and TGF2 levels were in wean milk. Wean samples on average had higher levels of both TGF1 (26%) and TGF2 (>500%) than matched transitional milk samples. Tenascin-C levels in wean milk were associated with nursing length (p = 0.048). Combining all three milk collection time points, tenascin-C exhibited a weak inverse correlation with TGF1 and TGF2 (p < 0.1). The inverse correlation at the wean time point was stronger for TGF2 than -1 (-0.37 versus -0.25). Tenascin-C, a protein known to promote breast cancer progression, is expressed throughout lactation.\Question: Does expression of the Extracellular Matrix Protein Tenascin-C vary During Lactation?

SOLUTION: The inverse correlation with TGF2 in wean milk suggests a possible interaction during breast involution, which should be further investigated.

PROBLEM: Context: One anesthesiologist performance metric is the incidence of "prolonged" (15 min or longer after dressing complete) times to extubation. The authors used several methods to identify the performance outliers and assess whether targeting these outliers for reduction could improve operating room workflow.', "Time to extubation data were retrieved for 27,757 anesthetics and 81 faculty anesthesiologists. Provider-specific incidences of prolonged extubation were assessed by using unadjusted frequentist statistics and a Bayesian model adjusted for prone positioning, American Society of Anesthesiologist's base units, and case duration.", '20.31% of extubations were "prolonged," and 40% of anesthesiologists were identified as outliers using a frequentist approach, that is, incidence greater than upper 95% CI (20.71%). With an adjusted Bayesian model, only one anesthesiologist was deemed an outlier. If an average anesthesiologist performed all extubations, the incidence of prolonged extubations would change negligibly (to 20.67%). If the anesthesiologist with the highest incidence of prolonged extubations was replaced with an average anesthesiologist, the change was also negligible (20.01%). Variability among anesthesiologists in the incidence of prolonged extubations was significantly less than among other providers.\Question: Is prolonged Operative Time to Extubation a Useful Metric for Comparing the Performance of Individual Anesthesia Providers?

SOLUTION: Bayesian methodology with covariate adjustment is better suited to performance monitoring than an unadjusted, nonhierarchical frequentist approach because it is less likely to identify individuals spuriously as outliers. Targeting outliers in an effort to alter operating room activities is unlikely to have an operational impact (although monitoring may serve other purposes). If change is deemed necessary, it must be made by improving the average behavior of everyone and by focusing on anesthesia providers rather than on faculty.

PROBLEM: Context: In a recent clinical trial, patients with newly diagnosed glioblastoma multiforme benefited from chloroquine (CQ) in combination with conventional therapy (resection, temozolomide [TMZ], and radiation therapy). In the present study, the authors report the mechanism by which CQ enhances the therapeutic efficacy of TMZ to aid future studies aimed at improving this therapeutic regimen.', 'Using in vitro and in vivo experiments, the authors determined the mechanism by which CQ enhances TMZ cytotoxicity. They focused on the inhibition-of-autophagy mechanism of CQ by knockdown of the autophagy-associated proteins or treatment with autophagy inhibitors. This mechanism was tested using an in vivo model with subcutaneously implanted U87MG tumors from mice treated with CQ in combination with TMZ.', 'Knockdown of the autophagy-associated proteins (GRP78 and Beclin) or treatment with the autophagy inhibitor, 3-methyl adenine (3-MA), blocked autophagosome formation and reduced CQ cytotoxicity, suggesting that autophagosome accumulation precedes CQ-induced cell death. In contrast, blocking autophagosome formation with knockdown of GRP78 or treatment with 3-MA enhanced TMZ cytotoxicity, suggesting that the autophagy pathway protects from TMZ-induced cytotoxicity. CQ in combination with TMZ significantly increased the amounts of LC3B-II (a marker for autophagosome levels), CHOP/GADD-153, and cleaved PARP (a marker for apoptosis) over those with untreated or individual drug-treated glioma cells. These molecular mechanisms seemed to take place in vivo as well. Subcutaneously implanted U87MG tumors from mice treated with CQ in combination with TMZ displayed higher levels of CHOP/GADD-153 than did untreated or individual drug-treated tumors.\Question: Does chloroquine enhance temozolomide cytotoxicity in malignant gliomas by blocking autophagy?

SOLUTION:
Taken together, these results demonstrate that CQ blocks autophagy and triggers endoplasmic reticulum stress, thereby increasing the chemosensitivity of glioma cells to TMZ.