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: Individuals with Williams syndrome, a neurogenetic condition caused by deletion of a set of genes at chromosomal location 7q11.23, exhibit a remarkable suite of traits including hypersociality with high, nonselective friendliness and low social anxiety, expressive language relatively well-developed but under-developed social-communication skills overall, and reduced visual-spatial abilities. Deletions and duplications of the Williams-syndrome region have also been associated with autism, and with schizophrenia, two disorders centrally involving social cognition. Several lines of evidence have linked the gene GTF2I (General Transcription Factor IIi) with the social phenotypes of Williams syndrome, but a role for this gene in sociality within healthy populations has yet to be investigated.', 'We genotyped a large set of healthy individuals for two single-nucleotide polymorphisms in the GTF2I gene that have recently been significantly associated with autism, and thus apparently exhibit functional effects on autism-related social phenotypes. GTF2I genotypes for these SNPs showed highly significant association with low social anxiety combined with reduced social-communication abilities, which represents a metric of the Williams-syndrome cognitive profile as described from previous studies.
Answer: These findings implicate the GTF2I gene in the neurogenetic basis of social communication and social anxiety, both in Williams syndrome and among individuals in healthy populations.

Output: Are cognitive-behavioral phenotypes of Williams syndrome associated with genetic variation in the GTF2I gene , in a healthy population?


Input: Consider Input: Context: Most solid human tumors exist in an acidic microenvironment, due in part to inefficient vasculature and a higher intrinsic rate of glycolysis. This leads to a tumor-selective pH gradient, which can be exploited therapeutically with antitumor agents such as the camptothecins (CPTs). Previous work in this laboratory has shown that camptothecin activity is enhanced 40- to 60-fold in monolayer cell culture by reducing the extracellular pH to 6.8. Three-dimensional histoculture has been shown to be a technique that allows human tumor tissue to grow in an in vivo-like way with maintenance of tissue histology and function and drug sensitivity for long periods of time.', 'In the current study, we utilized these features of histoculture to study new analogues of camptothecin that have superior pharmacological properties.', 'We evaluated six CPT analogues in histocultures of human brain, neuroblastoma, breast, colon, and prostate tumors. Fragments were exposed to 10,11-methylenedioxy-CPT (MDC), 7-chloromethyl-MDC, SN-38, topotecan (TPT), 9-amino-CPT, 10-amino-CPT, paclitaxel, 5-fluorouracil, 4-hydroperoxycyclophosphamide and doxorubicin, and antitumor activity was assessed. For in vivo tumor outgrowth studies, fragments were treated in parallel, implanted into nude mice, and monitored for development of tumors. RESULTS. Against 15 of 16 tumor xenografts and all primary tumor samples tested, all compounds were cytotoxic at pH 7.4 (IC(50) range 13-921 microM). MDC, SN-38, TPT, and 9-amino-CPT achieved an average 5-fold increase in activity (range 3-14) at pH 6.8, while 7-chloromethyl-MDC was enhanced 8-fold (range 6-14). The most potentiated analogue was 10-amino-CPT at 27-fold (range 17-49). In contrast, the other agents were active against one or more tumor types but were not enhanced by acidic pH. Importantly, the toxicity of MDC in histoculture of D54 glioma xenografts strongly correlated with the outgrowth of treated fragments subsequently implanted in vivo.
Answer: Evaluation of anticancer drug activity in native-state histoculture supports the concept that pH modulation may be an important approach to improve the selectivity and antitumor effectiveness of camptothecin-based chemotherapy.

Output: Is the activity of camptothecin analogues enhanced in histocultures of human tumors and human tumor xenografts by modulation of extracellular pH?


Input: Consider Input: Context: Hostility may predict coronary heart disease morbidity and mortality, as well as the metabolic syndrome. We tested to see if high levels of the attitudinal and emotional aspects of hostility lead to progression of carotid atherosclerosis in women and if the metabolic syndrome is a mediator of the association.', 'Two hundred nine healthy women were followed during the perimenopausal and postmenopausal periods. Carotid artery ultrasound scans measured intima-media thickness (IMT) an average 7.4 (SD = 0.9, range 4.2-10.8) and 10.5 years (SD = 1.1, range = 6.9-13.0) after baseline. Hostility was measured at baseline and at the first carotid scan with Spielberger Trait Anger (being angry frequently) and Anger In (suppressing angry feelings) scales, and the Cook-Medley Hostility Inventory (hostile, cynical attitudes toward others). Metabolic syndrome was measured at the study entry and through the second carotid scan.', 'Baseline Trait Anger scores predicted an increase in IMT across 3 years (p < .05) and predicted the risk for developing the metabolic syndrome (p < .05). The risk for developing the metabolic syndrome, in turn, predicted an increase in IMT across 3 years (p < .05). Anger suppression and cynical attitudes were not associated with progression of carotid atherosclerosis.
Answer: Anger predicts progression of carotid atherosclerosis, and the metabolic syndrome may mediate this association. Women who experience angry feelings frequently may benefit from interventions aimed at reducing anger and reducing the metabolic syndrome components early in the natural history of atherosclerosis.


Output: Do trait anger and the metabolic syndrome predict progression of carotid atherosclerosis in healthy middle-aged women?