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: To test the hypothesis that pharmacological plasminogen activator inhibitor (PAI)-1 inhibition protects against renin-angiotensin-aldosterone system-induced cardiovascular injury, the effect of a novel orally active small-molecule PAI-1 inhibitor, PAI-039, was examined in a mouse model of angiotensin (Ang) II-induced vascular remodeling and cardiac fibrosis.', 'Uninephrectomized male C57BL/6J mice were randomized to vehicle subcutaneus, Ang II (1 mug/h) subcutaneous, vehicle+PAI-039 (1 mg/g chow), or Ang II+PAI-039 during high-salt intake for 8 weeks. Ang II caused significant medial, adventitial, and aortic wall thickening compared with vehicle. PAI-039 attenuated Ang II-induced aortic remodeling without altering the pressor response to Ang II. Ang II increased heart/body weight ratio and cardiac fibrosis. PAI-039 did not attenuate the effect of Ang II on cardiac hypertrophy and increased fibrosis. The effect of PAI-039 on Ang II/salt-induced aortic remodeling and cardiac fibrosis was comparable to the effect of genetic PAI-1 deficiency. Ang II increased aortic mRNA expression of PAI-1, collagen I, collagen III, fibronectin, osteopontin, monocyte chemoattractant protein-1, and F4/80; PAI-039 significantly decreased the Ang II-induced increase in aortic osteopontin expression at 8 weeks.
Answer: This study demonstrates that pharmacological inhibition of PAI-1 protects against Ang II-induced aortic remodeling. Future studies are needed to determine whether the interactive effect of Ang II/salt and reduced PAI-1 activity on cardiac fibrosis is species-specific. In this study, the effect of pharmacological PAI-1 inhibition in a mouse model of Ang II-induced vascular remodeling and cardiac fibrosis was examined. PAI-1 inhibition significantly attenuated Ang II-induced aortic medial and wall thickening, but not cardiac hypertrophy, and enhanced Ang II/salt-induced cardiac fibrosis.
[A]: Does pharmacological inhibition and genetic deficiency of plasminogen activator inhibitor-1 attenuate angiotensin II/salt-induced aortic remodeling?


[Q]: Context: Rhinovirus (RV) infection in asthma induces varying degrees of airway inflammation (e.g. neutrophils), but the underlying mechanisms remain unclear.', 'The major goal was to determine the role of genetic variation [e.g. single nucleotide polymorphisms (SNPs)] of Toll-interacting protein (Tollip) in airway epithelial responses to RV in a type 2 cytokine milieu.', 'DNA from blood of asthmatic and normal subjects was genotyped for Tollip SNP rs5743899 AA, AG and GG genotypes. Human tracheobronchial epithelial (HTBE) cells from donors without lung disease were cultured to determine pro-inflammatory and antiviral responses to IL-13 and RV16. Tollip knockout and wild-type mice were challenged with house dust mite (HDM) and infected with RV1B to determine lung inflammation and antiviral response.', 'Asthmatic subjects carrying the AG or GG genotype (AG/GG) compared with the AA genotype demonstrated greater airflow limitation. HTBE cells with AG/GG expressed less Tollip. Upon IL-13 and RV16 treatment, cells with AG/GG (vs. AA) produced more IL-8 and expressed less antiviral genes, which was coupled with increased NF-κB activity and decreased expression of LC3, a hallmark of the autophagic pathway. Tollip co-localized and interacted with LC3. Inhibition of autophagy decreased antiviral genes in IL-13- and RV16-treated cells. Upon HDM and RV1B, Tollip knockout (vs. wild-type) mice demonstrated higher levels of lung neutrophilic inflammation and viral load, but lower levels of antiviral gene expression.
Answer: Our data suggest that Tollip SNP rs5743899 may predict varying airway response to RV infection in asthma.
[A]: Does tollip SNP rs5743899 modulate human airway epithelial responses to rhinovirus infection?


[Q]: Context: Currently, there is no standardised screening for prostate cancer in Europe. Assessment of risk is opportunistically undertaken in consultation with the GP or urologist. Evaluation of the prostate gland consists of a prostate-specific antigen (PSA) serum level and a digital rectal examination (DRE) of the gland. DRE is an essential part of the assessment that can independently predict prostate cancer in the setting of a normal PSA level.', 'To evaluate the clinical usefulness of the DRE in general practice and urology clinics, and to ascertain its positive predictive value and sensitivity.', 'A retrospective analysis study of a cohort of Irish men who underwent TRUS guided biopsy of the prostate in a single Irish tertiary referral centre, despite a normal PSA level. Patients were identified from a Rapid Access Prostate Clinic patient database. Pathological biopsy results were correlated with clinical DRE findings.', 'Patient demographics, PSA levels, and DRE findings from a prospectively established database and hospital data systems from May 2009 to October 2013 were analysed.', 'Of 103 men referred over a 53-month period with a normal age-adjusted PSA level, 67% were referred on the basis of an abnormal DRE alone. Thirty-five per cent of males with a normal PSA had prostate cancer. DRE alone had a sensitivity and specificity of 81% and 40% respectively in diagnosing prostate cancer, with a positive predictive value of 42%. Seventy-six per cent of these men had high-grade disease.
Answer: DRE is a key part of the assessment for prostate cancer. It can independently identify patients at risk of prostate cancer, with a substantial proportion of these having clinically significant disease requiring treatment. This study reinforces the importance of DRE in the primary care setting in the assessment for prostate cancer. An abnormal DRE, even in the setting of a normal PSA level, necessitates referral.
[A]:
Is digital rectal examination in primary care important for early detection of prostate cancer : a retrospective cohort analysis study?