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.

[Q]: Context: A functional vacuolar adenosine triphosphatase (v-ATPase) complex regulates canonical Wnt/β-catenin signaling. The goal of this study was to identify the distribution of the v-ATPase in human and murine models of pancreatic intraepithelial neoplasms (PanINs) and assess its role in Wnt/β-catenin signaling.', 'We evaluated the immunolabeling pattern of the v-ATPase in human PanIN specimens and murine PanIN-1 and PanIN-2 lesions obtained from Ptf1a(Cre/+); LSL-Kras(G12D) mice. Wnt/β-catenin signaling was interrogated in primary PanIN cells by examining the phosphorylated levels of its surface coreceptor, low-density lipoprotein receptor-related protein-6 (LRP6), and its intracellular effector, nonphosphorylated β-catenin. The response of primary PanIN cells to epidermal growth factor (EGF) was assessed in the absence and presence of the v-ATPase inhibitor, concanamycin.', 'In advanced (PanIN-2), but not early (PanIN-1), lesions, the v-ATPase assumed a polarized phenotype. Blocking the v-ATPase disrupted Wnt/β-catenin signaling in primary PanIN cells despite significantly higher levels of the total and activated Wnt cell surface coreceptor, LRP6. Vacuolar adenosine triphosphatase blockade significantly decreased the total and activated levels of EGF receptor, a determinant of PanIN progression. The activation of EGF receptor and its intracellular mediator, p44/42 mitogen-activated protein kinase, was also reduced by v-ATPase blockade. This led to diminished proliferation in response to EGF ligand.
Answer: The v-ATPase regulates Wnt/β-catenin and EGF receptor signaling in PanINs.
[A]: Does polarization of the vacuolar adenosine triphosphatase delineate a transition to high-grade pancreatic intraepithelial neoplasm lesions?


[Q]: Context: A computerized physician order entry (CPOE) system with embedded clinical decision support can reduce medication errors in hospitals, but might increase the time taken to generate orders.', 'We aimed to quantify the effects of temporal (month, day of week, hour of shift) and other factors (grade of doctor, prior experience with the system, alert characteristics, and shift type) on the time taken to generate a prescription order.', 'A large university teaching hospital using a locally developed CPOE system with an extensive audit database.', 'We retrospectively analyzed prescription orders from the audit database between August 2011 and July 2012.', 'The geometric mean time taken to generate a prescription order within the CPOE system was 11.75\u2005s (95% CI 11.72 to 11.78). Time to prescribe was most affected by the display of high-level (24.59\u2005s (24.43 to 24.76); p<0.001) or previously unseen (18.87\u2005s (18.78 to 18.96); p<0.001) alerts. Prescribers took significantly less time at weekends (11.29\u2005s (11.23 to 11.35)) than on weekdays (11.88\u2005s (11.84 to 11.91); p<0.001), in the first (11.25\u2005s (11.16 to 11.34); p<0.001) and final (11.56\u2005s (11.47 to 11.66); p<0.001) hour of their shifts, and after the first month of using the system.
Answer: The display of alerts, prescribing experience, system familiarity, and environment all affect the time taken to generate a prescription order. Our study reinforces the need for appropriate alerts to be presented to individuals at an appropriate place in the workflow, in order to improve prescribing efficiency.
[A]: Do temporal and other factors that influence the time doctors take to prescribe using an electronic prescribing system?


[Q]: Context: Various pathways involved in the pathogenesis of sJIA have been identified through gene expression profiling in peripheral blood mononuclear cells (PBMC), but not in neutrophils. Since neutrophils are important in tissue damage during inflammation, and are elevated as part of the acute phase response, we hypothesised that neutrophil pathways could also be important in the pathogenesis of sJIA. We therefore studied the gene profile in both PBMC and neutrophils of sJIA patients treated with tocilizumab.', 'We studied the transcriptomes of peripheral blood mononuclear cells (PBMC) and neutrophils from eight paired samples obtained from 4 sJIA patients taken before and after treatment, selected on the basis that they achieved ACR90 responses within 12 weeks of therapy initiation with tocilizumab. RNA was extracted and gene expression profiling was performed using Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform. A longitudinal analysis using paired t-test (p\u2009<\u20090.05 and FC\u2009≥\u20091.5) was applied to identify differentially expressed genes (DEGs) between the two time points followed by ingenuity pathway analysis. Gene Set Enrichment Analysis (GSEA) and quantitative real-time PCR were then performed to verify the microarray results.', 'Gene ontology analysis in neutrophils revealed that response to tocilizumab significantly altered genes regulating mitochondrial dysfunction and oxidative stress (p\u2009=\u20094.6E-05). This was independently verified with GSEA, by identifying a set of oxidative genes whose expression correlated with response to tocilizumab. In PBMC, treatment of sJIA with tocilizumab appeared to affect genes in Oncostatin M signalling and B cell pathways.
Answer: For the first time we demonstrate that neutrophils from sJIA patients responding to tocilizumab showed significantly different changes in gene expression. These data could highlight the importance of mitochondrial genes that modulate oxidative stress in the pathogenesis of sJIA.
[A]:
Are mitochondrial and oxidative stress genes differentially expressed in neutrophils of sJIA patients treated with tocilizumab : a pilot microarray study?