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.

[EX Q]: Context: Long-QT syndrome (LQTS), a cardiac arrhythmia disorder with variable phenotype, often results in devastating outcomes, including sudden cardiac death. Variable expression, independently from the primary disease-causing mutation, can partly be explained by genetic modifiers. This study investigates variants in a known LQTS-causative gene, AKAP9, for potential LQTS-type 1-modifying effects.', "Members of a South African LQTS-type 1 founder population (181 noncarriers and 168 mutation carriers) carrying the identical-by-descent KCNQ1 p.Ala341Val (A341V) mutation were evaluated for modifying effects of AKAP9 variants on heart rate-corrected QT interval (QTc), cardiac events, and disease severity. Tag single nucleotide polymorphisms in AKAP9 rs11772585, rs7808587, rs2282972, and rs2961024 (order, 5'-3'positive strand) were genotyped. Associations between phenotypic traits and alleles, genotypes, and haplotypes were statistically assessed, adjusting for the degree of relatedness and confounding variables. The rs2961024 GG genotype, always represented by CGCG haplotype homozygotes, revealed an age-dependent heart rate-corrected QT interval increase (1% per additional 10 years) irrespective of A341V mutation status (P=0.006). The rs11772585 T allele, found uniquely in the TACT haplotype, more than doubled (218%) the risk of cardiac events (P=0.002) in the presence of A341V; additionally, it increased disease severity (P=0.025). The rs7808587 GG genotype was associated with a 74% increase in cardiac event risk (P=0.046), whereas the rs2282972 T allele, predominantly represented by the CATT haplotype, decreased risk by 53% (P=0.001).
Answer: AKAP9 has been identified as an LQTS-type 1-modifying gene. Variants investigated altered heart rate-corrected QT interval irrespective of mutation status, as well as cardiac event risk, and disease severity, in mutation carriers.
[EX A]: Is aKAP9 a genetic modifier of congenital long-QT syndrome type 1?

[EX Q]: Context: In patients with moderate-to-severe psoriasis, health-related quality of life (HRQOL) has been shown to improve in parallel with improvement in disease severity.', 'To evaluate the role of pruritus (itch) in mediating the relationship between improvements in disease severity and HRQOL.', 'Data from a phase 2 clinical trial, in which 142 patients with moderate-to-severe plaque psoriasis received ixekizumab or placebo, were used for this posthoc analysis. Relationships between improvement in Psoriasis Area and Severity Index (PASI), Itch Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI), as well as in individual DLQI domains (symptoms and feelings, treatment, work and school, daily activities, leisure, and personal relationships) from baseline to week 16 were determined. Multiple hierarchical linear regressions and Sobel tests were conducted to evaluate the results.', 'Improvement in PASI was highly correlated with pruritus improvement and improvements in DLQI total and domain scores at week 16 (P<001). Multiple hierarchical linear regression analyses showed a statistically significant (P<001) association between improvement in pruritus and improvement in DLQI total score and each of the six DLQI domain scores after adjusting for improvement in PASI. Sobel tests indicated that pruritus had a significant mediation effect (P<005) on the association of PASI improvement with improvement in DLQI total score and all domains except the personal relationships score.
Answer: Pruritus appears to be an important mediator of the association between improvements in disease severity and HRQOL in patients with moderate-to-severe psoriasis.
[EX A]: Is itching a significant problem and a mediator between disease severity and quality of life for patients with psoriasis : results from a randomized controlled trial?

[EX Q]: Context: Time to achieve target temperature varies substantially for patients who undergo targeted temperature management (TTM) after cardiac arrest. The association between arrival at target temperature and neurologic outcome is poorly understood. We hypothesized that shorter time from initiation of cooling to target temperature ("induction") will be associated with worse neurologic outcome, reflecting more profound underlying brain injury and impaired thermoregulatory control.', 'This was a multicenter retrospective study analyzing data from the Penn Alliance for Therapeutic Hypothermia (PATH) Registry. We examined the association between time from arrest to return of spontaneous circulation (ROSC) ("downtime"), ROSC to initiation of TTM ("pre-induction") and "induction" with cerebral performance category (CPC).', 'A total of 321 patients were analyzed, of whom 30.8% (99/321) had a good neurologic outcome. Downtime for survivors with good outcome was 11 (IQR 6-27) min vs. 21 (IQR 10-36) min (p=0.002) for those with poor outcome. Pre-induction did not vary between good and poor outcomes (98 (IQR 36-230) min vs. 114 (IQR 34-260) (p=ns)). Induction time in the good outcome cohort was 237 (IQR 142-361) min compared to 180 (IQR 100-276) min (p=0.004). Patients were categorized by induction time (<120min, 120-300min, >300min). Using multivariable logistic regression adjusted for age, initial rhythm, and downtime, induction time >300min was associated with good neurologic outcome when compared to those with an induction time <120min.
Answer: In this multicenter cohort of post-arrest TTM patients, shorter induction time was associated with poor neurologic outcome.
[EX A]:
Is shorter time to target temperature associated with poor neurologic outcome in post-arrest patients treated with targeted temperature management?