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.

Input: Consider Input: Context: Inflammatory risk factors in childhood, e.g. obesity, impact on carotid artery intima media thickness (CIMT), an early indicator of atherosclerosis. Little is known on potential infectious origins in childhood. We investigated the association between number of reported different childhood infectious diseases and CIMT in adolescence.', "288 SAPALDIA offspring (8-21years) underwent a clinical examination in 2010-2011: anthropometry, blood pressure, CIMT, blood draw (cardiovascular biomarkers, cotinine). Offspring and parents gave information on individuals' and family health, child's vaccination status, infectious diseases and other early life factors. Life-time prevalence of bronchitis, pneumonia, tonsillitis, otitis, mononucleosis, meningitis, appendicitis, and scarlet fever were investigated, separately, and as cumulative infectious disease score. Multilevel adjusted linear regression analysis on the association between subjects' CIMT average and infectious diseases score was performed, stratifying by sex.", 'Youth (mean age 14.8yrs; 53% female) reported on average 1.3 of the listed infectious diseases; 22% boys and 15% girls reported 3 infectious diseases (p=0.136). Two-thirds were vaccinated according to recommendations (boys 56%, girls 61.5%, p=0.567). Sex-stratified analyses yielded significantly increased CIMT in boys with 3 infectious diseases vs. none (0.046mm, 95%CI 0.024; 0.068). In girls, the effect was of same direction but statistically non-significant (0.011mm, 95%CI-0.015; 0.036).
Answer: The SAPALDIA Youth study complements current evidence on infectious origins of atherosclerosis in adults. The larger effects observed in boys may relate to a higher vulnerability of the vasculature and/or to infectious pathogens. Our data are suggestive of an early impact of childhood infectious diseases on vascular health.

Output: Are infectious diseases associated with carotid intima media thickness in adolescence?

Input: Consider Input: Context: To determine whether the number and location of positive surgical margins (PSMs) in radical prostatectomy (RP) surgical specimens affect biochemical recurrence (BCR) rates.', 'The locations of PSMs were recorded for 1308 consecutive men who underwent RP between October 2000 and December 2006. BCR was defined as three consecutive prostate-specific antigen (PSA) level rises with the peak level >or=0.15 ng/mL. Multivariate regression analyses were used to identify preoperative predictors of PSMs and BCR. The estimated 5-year risk of BCR was calculated using the Kaplan-Meier method.', 'In all, 128 (9.8%) men had one or more PSMs. The mean body mass index, mean preoperative serum PSA level, the distributions of clinical stage and biopsy Gleason scores, and the presence or absence of biopsy perineural invasion were significantly different between men with or with no PSMs. In multivariate analysis, baseline serum PSA level, Gleason score and perineural invasion were independent preoperative predictors of PSMs. The 5-year actuarial BCR rates were dependent on the site of the PSM (P = 0.035) and not the number of PSMs (P = 0.18). The rank order of estimated 5-year BCR rates according to the site of PSMs were base > anterior > posterolateral > apex approximately posterior.
Answer: About half of the men with PSMs in the RP surgical specimen in our prospective series did not develop BCR. The risk of BCR was dependent on the site and not the number of PSMs. Adjuvant therapy should be considered in cases with anterior and basilar PSMs due to the very high risk of BCR.

Output: Does site of positive surgical margins influence biochemical recurrence after radical prostatectomy?

Input: Consider Input: Context: Activation of Kupffer cells by gut-derived endotoxin plays a pivotal role in alcoholic liver injury. On the other hand, it was reported that acute ethanol administration reduced activation of Kupffer cells. We found that Kupffer cells isolated from rat treated only once with ethanol were sensitized to endotoxin 24 hrs later correlatively with CD14 expression. Moreover, it was shown that Kupffer cell activation by endotoxin via Toll-like receptor (TLR)-4 is involved in alcohol-induced liver injury and ethanol-induced oxidative stress is important in the regulation of transcription factor NFkappaB activation and cytokine production by Kupffer cells. Here, we show that IRAK, one of signaling molecules of TLR-4, regulates tolerance and sensitization to LPS and acute ethanol increases in IRAK expression through a mechanism dependent upon oxidant production.', 'Female C57BL/6 mice were given ethanol (5 g/kg) intragastrically, and LPS was injected 1 or 21 hrs later. Serum transaminase levels were measured. Moreover, some mice were treated with NADPH oxidase inhibitor diphenyleneiodonium sulfate (DPI, 1 mg/kg/day) or infected with adenovirus (1 x 10 plaque-forming units, intravenously) containing IkappaB superrepressor gene, which prevent NFkappaB activation of Kupffer cells, for three days. Kupffer cells were isolated from mice 1 hr and 21 hrs after ethanol treatment. After the addition of LPS, TNF-alpha in the media was measured using ELISA, Electrophoretic mobility shift assay (EMSA) was performed to analyze DNA binding activity of NFkappaB. Further, expression of Interleukin-1 receptor-associated kinase (IRAK) was evaluated by Western blotting.', 'LPS-induced increases in transaminases were blunted in mice treated with ethanol before 1 hr. However, ethanol treatment 21 hrs earlier augmented LPS-increased transaminases three-fold over controls. Pretreatment with nonabsorbable antibiotics blocked these effects of ethanol. LPS-induced TNF-alpha production by Kupffer cells isolated from mice 1 hr after ethanol was reduced to about 60% of values from control Kupffer cells, while LPS-induced TNF-alpha production by Kupffer cells isolated from mice treated with ethanol 21 hrs earlier increased 1.5-fold over control Kupffer cells. In Kupffer cells from mice 1 hr after ethanol treatment, expression of IRAK was decreased, and LPS-induced activation of NFkappaB was decreased correlatively. In contrast, ethanol treatment to mice increased expression of IRAK in Kupffer cells 21hrs later and LPS-induced activation of NFkappaB was elevated significantly. On the other hands, DPI treatment for three days prior to ethanol did not prevent decreases in IRAK expression due to ethanol treatment for 1 hr. However, DPI treatment blunted ethanol-induced increases in IRAK expression. Additionally, inhibition of NKkappaB activation with dominant-negative IkappaBalpha blunted ethanol-induced increase in IRAK expression. Contrary, inhibition of NKkappaB did not affect decrease of IRAK expression due to ethanol treatment for 1 hr.
Answer: Ethanol causes tolerance in the early phase after ethanol consumption, while sensitization was observed later. Both tolerance and sensitization were induced by gut-derived endotoxin. These findings indicate that ethanol-induced both tolerance and sensitization of Kupffer cells to endotoxin involve IRAK expression. Further, NADPH oxidase plays a pivotal role in the increase in IRAK expression due to ethanol via activation of NFkappaB signaling pathway. In conclusion, these data indicate that acute ethanol causes sensitization to endotoxin through mechanisms dependent upon oxidative stress.
Output: Is ethanol-induced sensitization to endotoxin in Kupffer cells dependent upon oxidative stress?