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.

Ex Input:
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?

Ex Output:
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.


Ex Input:
Context: We sought to assess whether mechanical unloading has beneficial effects on cardiomyocytes from doxorubicin-induced cardiomyopathy in rats.', 'Mechanical unloading by a left ventricular assist device (LVAD) improves the cardiac function of terminal heart failure in humans. However, previous animal studies have failed to demonstrate beneficial effects of mechanical unloading in the myocardium.', 'The effects of mechanical unloading by heterotopic abdominal heart transplantation were evaluated in the myocardium from doxorubicin-treated rats by analyzing the intracellular free calcium level ([Ca(2+)](i)) and the levels of intracellular Ca(2+)-regulatory proteins.', 'In doxorubicin-treated rats, the duration of cell shortening and [Ca(2+)](i) transients in cardiomyocytes was prolonged (432 +/- 28.2% of control in 50% relaxation time; 184 +/- 10.5% of control in [Ca(2+)](i) 50% decay time). Such prolonged time courses significantly recovered after mechanical unloading (114 +/- 10.4% of control in 50% relaxation time; 114 +/- 5.8% of control in 50% decay time). These effects were accompanied by an increase in sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) protein levels (0.97 +/- 0.05 in unloaded hearts vs. 0.41+/- 0.09 in non-unloaded hearts). The levels of other intracellular Ca(2+)-regulatory proteins (phospholamban and ryanodine receptor) were not altered after mechanical unloading in doxorubicin-treated hearts. These parameters in unloaded hearts without doxorubicin treatment were similar to normal hearts.\Question: Does mechanical unloading improve intracellular Ca2+ regulation in rats with doxorubicin-induced cardiomyopathy?

Ex Output:
Mechanical unloading increases functional sarcoplasmic reticulum Ca(2+) ATPase and improves [Ca(2+)](i) handling and contractility in rats with doxorubicin-induced cardiomyopathy. These beneficial effects of mechanical unloading were not observed in normal hearts.


Ex Input:
Context: To facilitate indefinite proliferation, stem cells and most cancer cells require the activity of telomerase, which counteracts the successive shortening of telomeres caused by incomplete DNA replication at the very end of each chromosome. Human telomerase activity is often determined by the expression level of telomerase reverse transcriptase (TERT), the catalytic subunit of the ribonucleoprotein complex. The low expression level of TERT and the lack of adequate antibodies have made it difficult to study telomerase-related processes in human cells.', 'To overcome the low CRISPR-Cas9 editing efficiency at the TERT locus, we develop a two-step "pop-in/pop-out" strategy to enrich cells that underwent homologous recombination (HR). Using this technique, we fuse an N-terminal FLAG-SNAP-tag to TERT, which allows us to reliably detect TERT in western blots, immunopurify it for biochemical analysis, and determine its subcellular localization by fluorescence microscopy. TERT co-localizes detectably with only 5-7 % of the telomeres at a time in S-phase HeLa cells; no nucleolar localization is detected. Furthermore, we extend this approach to perform single base-pair modifications in the TERT promoter; reverting a recurrent cancer-associated TERT promoter mutation in a urothelial cancer cell line results in decreased telomerase activity, indicating the mutation is causal for telomerase reactivation.\Question: Does a novel two-step genome editing strategy with CRISPR-Cas9 provide new insights into telomerase action and TERT gene expression?

Ex Output:

We develop a two-step CRISPR-Cas9 genome editing strategy to introduce precise modifications at the endogenous TERT locus in human cell lines. This method provides a useful tool for studying telomerase biology, and suggests a general approach to edit loci with low targeting efficiency and to purify and visualize low abundance proteins.