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:
Complex regional pain syndrome (CRPS) is a painful condition with approximately 50,000 annual new cases in the United States. It is a major cause of work-related disability, chronic pain after limb fractures, and persistent pain after extremity surgery. Additionally, CRPS patients often experience cognitive changes, anxiety, and depression. The supraspinal mechanisms linked to these CRPS-related comorbidities remain poorly understood.', 'The authors used a previously characterized mouse model of tibia fracture/cast immobilization showing the principal stigmata of CRPS (n = 8 to 20 per group) observed in humans. The central hypothesis was that fracture/cast mice manifest changes in measures of thigmotaxis (indicative of anxiety) and working memory reflected in neuroplastic changes in amygdala, perirhinal cortex, and hippocampus.', 'The authors demonstrate that nociceptive sensitization in these mice is accompanied by altered thigmotactic behaviors in the zero maze but not open field assay, and working memory dysfunction in novel object recognition and social memory but not in novel location recognition. Furthermore, the authors found evidence of structural changes and synaptic plasticity including changes in dendritic architecture and decreased levels of synaptophysin and brain-derived neurotrophic factor in specific brain regions.

Ex Output:
Do brain neuroplastic changes accompany anxiety and memory deficits in a model of complex regional pain syndrome?


Ex Input:
Activation of the transcription factor NF-κB and expression of pro-inflammatory mediators have been considered as major events of acute pancreatitis (AP). Karyopherin alpha 2 (KPNA2), a member of the importin α family, reportedly modulates p65 subcellular localization.', 'This study aimed to investigate the expression and possible functions of KPNA2 in the AP cell and animal model, focusing on its association with NF-κB activation.', 'An AP cell model was established with the cerulein-stimulated AR42J and isolated rat pancreatic acinar cells. The AP rat model was induced by the intraperitoneal injection of cerulein. The secretion of TNF-α, IL-6, and LDH was detected by ELISA kits and the production of NO using nitric oxide kit. Expression of KPNA2 was measured by RT-PCR and Western blot. Expression levels of IKKα, phosphorylation of p65, and total p65 were detected by Western blot. Co-localization of KPNA2 with p65 was observed by immunofluorescence assay. To determine the biological functions of KPNA2 in cerulein-induced inflammatory response, RNA interference was employed to knockdown KPNA2 expression in AR42J and isolated pancreatic acini cells.', 'Cerulein stimulated KPNA2 expression and IL-6, TNF-α, NO, and LDH production in rat pancreatic acinar cells. Cerulein triggered the phosphorylation and nuclear translocation of NF-κB p65 subunit, indicating the NF-κB activation. The co-localization and nuclear accumulation of KPNA2 and p65 were detected in cerulein-treated cells. Knocking down KPNA2 hindered cerulein-induced nuclear transportation of p65 and alleviated the subsequent inflammatory response in rat pancreatic acinar cells. Additionally, KPNA2 expression was significantly up-regulated in cerulein-induced AP rat model.

Ex Output:
Does karyopherin Alpha 2 promote the Inflammatory Response in Rat Pancreatic Acinar Cells Via Facilitating NF-κB Activation?


Ex Input:
We sought to investigate the effect of cardiac medication on long-term mortality in patients with peripheral arterial disease (PAD).', 'Peripheral arterial disease is associated with increased cardiovascular morbidity and mortality. Treatment guidelines recommend aggressive management of risk factors and lifestyle modifications. However, the potential benefit of cardiac medication in patients with PAD remains ill defined.', 'In this prospective observational cohort study, 2,420 consecutive patients (age, 64 +/- 11 years, 72% men) with PAD (ankle-brachial index < or =0.90) were screened for clinical risk factors and cardiac medication. Follow-up end point was death from any cause. Propensity scores for statins, beta-blockers, aspirin, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, diuretics, nitrates, coumarins, and digoxin were calculated. Cox regression models were used to analyze the relation between cardiac medication and long-term mortality.', 'Medical history included diabetes mellitus in 436 patients (18%), hypercholesterolemia in 581 (24%), smoking in 837 (35%), hypertension in 1,162 (48%), coronary artery disease in 1,065 (44%), and a history of heart failure in 214 (9%). Mean ankle-brachial index was 0.58 (+/-0.18). During a median follow-up of eight years, 1,067 patients (44%) died. After adjustment for risk factors and propensity scores, statins (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.36 to 0.58), beta-blockers (HR 0.68, 95% CI 0.58 to 0.80), aspirins (HR 0.72, 95% CI 0.61 to 0.84), and ACE inhibitors (HR 0.80, 95% CI 0.69 to 0.94) were significantly associated with a reduced risk of long-term mortality.

Ex Output:

Is cardioprotective medication associated with improved survival in patients with peripheral arterial disease?