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.

Input: Consider Input: This longitudinal study had three aims: 1) determine the extent to which boys at high average risk and low average risk for substance use disorder differ on a construct of neurobehavioral disinhibition, 2) evaluate the capacity of neurobehavioral disinhibition to predict substance use frequency at age 16, and 3) demonstrate the utility of neurobehavioral disinhibition in predicting substance use disorder.', 'The authors derived an index of neurobehavioral disinhibition from measures of affect, behavior, and cognition. The neurobehavioral disinhibition score was used to discriminate youth at high and low average risk for substance use disorder and to predict substance use frequency after 4-6 years and substance use disorder after 7-9 years.', 'The neurobehavioral disorder score significantly discriminated boys at high average risk from those at low average risk at ages 10-12. Neurobehavioral disinhibition at age 16, in conjunction with substance use frequency and risk status group, predicted substance use disorder at age 19 with 85% accuracy and accounted for 50% of the variance in Drug Use Screening Inventory overall problem density score. Neurobehavioral disinhibition was a stronger predictor of substance use disorder (odds ratio=6.83) than substance consumption frequency (odds ratio=3.19).

Output: Does neurobehavioral disinhibition in childhood predict early age at onset of substance use disorder?


Input: Consider Input: The scope of this work was to study synergism between human papillomavirus (HPV) infection and tobacco in vitro, both known to be independent risk factors for oral cancer.', 'HPV-positive and HPV-negative oral keratinocytes and oral HPV-negative fibroblasts were exposed to smokeless tobacco extract (STE) prepared from the Scandinavian (STE1) and US-type (STE2) snuff. Cell cycle profiles were determined with flow cytometry, and HPV E6/E7 mRNA expression in HPV-positive cells was assayed using RT-qPCR.', 'The exposure of HPV-positive keratinocytes with STE2 increased the number of aneuploid cells from 27% to 80% of which 44% were in S-phase, while none of the diploid cells were in S-phase. The changes after STE1 exposure were less than seen after STE2: from 27% to 31% of which 34% were in S-phase. STE had no effect on HPV16 E6/E7 expression in HPV-positive keratinocytes. In oral spontaneously transformed, HPV-negative keratinocytes, the number of aneuploid cells at G2-M stage increased after STE1 and STE2 exposure from 3% to 9% and 7%, respectively. In HPV-negative oral fibroblasts, the number of cells at G2-M phase increased from 11% to 21% after STE1 and 29% after STE2 exposure.

Output: Does smokeless tobacco increase aneuploidy in oral HPV16 E6/E7-transformed keratinocytes in vitro?


Input: Consider Input: Mdm4 negatively regulates the p53 tumor suppressor. Mdm4 loss in mice leads to an embryonic lethal phenotype that is p53-dependent. Biochemical studies indicate that Mdm4 also binds p73, a member of the p53 family, with higher affinity than p53. In this study, the significance of the Mdm4 and p73 interaction in vivo during embryogenesis and tumorigenesis was examined. The data revealed that p73 loss did not rescue either the early Mdm4-deficient embryonic lethality or the runted phenotype of Mdm4(Δ2/Δ2) p53(+/-) embryos. Furthermore, studies in the developing central nervous system wherein both genes have prominent roles indicated that loss of p73 also did not rescue the Mdm4-null brain phenotype as did p53 loss. This p53 dependency occurred despite evidence for p73-specific transcriptional activity. In tumor studies, the combination of Mdm4 overexpression and p73 loss did not alter survival of mice or the tumor spectrum as compared with Mdm4 overexpression alone. In summary, these data demonstrate that the Mdm4-p73 axis cannot override the dominant role of p53 in development and tumorigenesis.


Output: Does p53 Activity dominate That of p73 upon Mdm4 Loss in Development and Tumorigenesis?