Given a passage, 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.

Ex Input:
The potential for a compound to cause hepatotoxicity and nephrotoxicity is a matter of extreme interest for human health risk assessment. To assess liver and kidney toxicity, repeated-dose toxicity (RDT) studies are conducted mainly on rodents. However, these tests are expensive, time-consuming and require large numbers of animals. For early toxicity screening, in silico models can be applied, reducing the costs, time and animals used. Among in silico approaches, structure-activity relationship (SAR) methods, based on the identification of chemical substructures (structural alerts, SAs) related to a particular activity (toxicity), are widely employed.', 'We identified and evaluated some SAs related to liver and kidney toxicity, using RDT data on rats taken from the hazard evaluation support system (HESS) database. We considered only SAs that gave the best percentages of true positives (TP).

Ex Output:
Does identification of structural alert for liver and kidney toxicity using repeated dose toxicity data?

Ex Input:
We investigated whether a computed tomography (CT)-based score could predict a large infarct ( 80 mL) on early diffusion-weighted magnetic resonance imaging (DWI).', 'Acute stroke patients considered for endovascular therapy within 8 hours of the onset of symptoms were included. The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was determined on noncontrast CT and computed tomography angiography source images (CTA-SI). Limited collateral flow was defined as less than 50% collateral filling on CTA-SI.', 'Fifty-six patients were analyzed. National Institutes of Health Stroke Scale score was 20 (15-24) in the large infarct group and 16 (11-20) in the small infarct group (P = .049). ASPECTS on noncontrast CT and CTA-SI was 5 (3-8) and 3 (2-6) in the large infarct group and 9 (8-10) and 8 (7-9) in the small infarct group (both P < .001), respectively. Limited collateral flow was frequent in the large infarct group than in the small infarct group (92% vs. 11%, P < .001). Multivariate analysis found that CTA-SI ASPECTS less than or equal to 5 (odds ratio [OR], 40.55; 95% confidence interval [CI], 1.10-1493.44; P = .044) and limited collateral flow (OR, 114.64; 95% CI, 1.93-6812.79; P = .023) were associated with a large infarct. Absence of ASPECTS less than or equal to 5 and limited collateral flow on CTA-SI predicted absence of a large infarct with a sensitivity of .89, specificity of 1.00, positive predictive value of 1.00, and negative predictive value of .71.

Ex Output:
Do collateral flow and brain changes on computed tomography angiography predict infarct volume on early diffusion-weighted imaging?

Ex Input:
Members of the Ewing sarcoma family of tumors (ESFT) contain tumor-associated translocations that give rise to oncogenic transcription factors, most commonly EWS/FLI1. EWS/FLI1 plays a dominant role in tumor progression by modulating the expression of hundreds of target genes. Here, the impact of EWS/FLI1 inhibition, by RNAi-mediated knockdown, on cellular signaling was investigated using mass spectrometry-based phosphoproteomics to quantify global changes in phosphorylation. This unbiased approach identified hundreds of unique phosphopeptides enriched in processes such as regulation of cell cycle and cytoskeleton organization. In particular, phosphotyrosine profiling revealed a large upregulation of STAT3 phosphorylation upon EWS/FLI1 knockdown. However, single-cell analysis demonstrated that this was not a cell-autonomous effect of EWS/FLI1 deficiency, but rather a signaling effect occurring in cells in which knockdown does not occur. Conditioned media from knockdown cells were sufficient to induce STAT3 phosphorylation in control cells, verifying the presence of a soluble factor that can activate STAT3. Cytokine analysis and ligand/receptor inhibition experiments determined that this activation occurred, in part, through an IL6-dependent mechanism. Taken together, the data support a model in which EWS/FLI1 deficiency results in the secretion of soluble factors, such as IL6, which activate STAT signaling in bystander cells that maintain EWS/FLI1 expression. Furthermore, these soluble factors were shown to protect against apoptosis.

Ex Output:
Does phosphoproteomic profiling reveal IL6-mediated paracrine signaling within the Ewing sarcoma family of tumors?