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: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of growth factors that have been implicated in skin patho-physiology. Although endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) appear to be involved in mitogenesis and chemotaxis in epidermal keratinocytes, the activation of eNOS and VEGF production induced by HB-EGF and its signaling mechanism remains undefined.', 'We examined possible signal transduction pathways by which HB-EGF leads to eNOS activation and VEGF production in human epidermal keratinocyte cell line (HaCaT cells).', 'The phosphorylation of epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK; p42/p44 MAPK), Akt and eNOS were examined by Western blotting analysis. VEGF production was determined by enzyme-linked immunosorbent assay. Various inhibitors were utilized to investigate the signaling mechanisms of eNOS activation and VEGF production.', 'HB-EGF-induced phosphorylation of EGFR with maximum phosphorylation at 1h. HB-EGF-induced phosphorylation of p42/p44 MAPK in a few minutes. It activated Akt with maximum phosphorylation at 1h and eNOS with maximum phosphorylation at 3h. The HB-EGF-induced eNOS activation was significantly blocked by the p42/p44 MAPK inhibitor U0126 and the phosphatidylinositol 3-kinase (P13K) inhibitor LY294002. HB-EGF increased VEGF production. The HB-EGF-induced VEGF production was blocked by U0126 and LY294002. Finally, the HB-EGF-induced activation of Akt and eNOS was suppressed by VEGF competitive antagonist, CBO-P11.
Answer: These results demonstrate that HB-EGF-induced eNOS activation depends on p42/p44 MAPK, PI3K/Akt pathways and endogenous VEGF in HaCaT cells.

Output: Do hB-EGF-induced VEGF production and eNOS activation depend on both PI3 kinase and MAP kinase in HaCaT cells?

Input: Consider Input: Context: Associations between multidrug resistance and the Mycobacterium tuberculosis Beijing genotype have been described mainly in populations with poor tuberculosis (TB) control such as prisons and inner cities, and may reflect shared risk factors rather than a biological association.', 'To study the association between genotype and drug resistance among TB patients in a population with adequate TB control.', 'Three rural districts in Vietnam. The study was performed at the Pham Ngoc Thach Tuberculosis and Lung Disease Hospital, Ho Chi Minh City, and the Tien Giang Provincial Tuberculosis and Lung Disease Hospital, My Tho, Vietnam.', 'Pretreatment sputum specimens were collected for culture, drug susceptibility testing and spoligotyping of all sputum smear-positive pulmonary TB patients consecutively diagnosed over a 3-year period.', 'Beijing genotype infections were observed in 614 of 1744 (35%) patients. Beijing strains were more common among female (adjusted odds ratio [aOR] 1.4, P = 0.005), young (aOR 2.8, P < 0.001) and previously treated patients (aOR 2.4, P < 0.001). The Beijing genotype was associated with any resistance (aOR 3.7, P < 0.001) and multidrug resistance (aOR 6.8, P < 0.001) among new patients, and with any resistance (aOR 2.7, P = 0.005) but not with multidrug resistance (aOR 1.4, P = 0.545) among previously treated patients.
Answer: In Vietnam, Beijing genotype is associated with young age and in new patients with multidrug resistance despite adequate TB control, suggesting a biological association. This potentially undermines the effectiveness of TB control in countries where Beijing genotype infections are common.

Output: Is the Beijing genotype associated with young age and multidrug-resistant tuberculosis in rural Vietnam?

Input: Consider Input: Context: Understanding the dynamics of the gut-brain axis has clinical implications for physical and mental health conditions, including obesity and anxiety. As such disorders have early life antecedents, it is of value to determine if associations between the gut microbiome and behavior are present in early life in humans.', 'We used next generation pyrosequencing to examine associations between the community structure of the gut microbiome and maternal ratings of child temperament in 77 children at 18-27months of age. It was hypothesized that children would differ in their gut microbial structure, as indicated by measures of alpha and beta diversity, based on their temperamental characteristics.', 'Among both boys and girls, greater Surgency/Extraversion was associated greater phylogenetic diversity. In addition, among boys only, subscales loading on this composite scale were associated with differences in phylogenetic diversity, the Shannon Diversity index (SDI), beta diversity, and differences in abundances of Dialister, Rikenellaceae, Ruminococcaceae, and Parabacteroides. In girls only, higher Effortful Control was associated with a lower SDI score and differences in both beta diversity and Rikenellaceae were observed in relation to Fear. Some differences in dietary patterns were observed in relation to temperament, but these did not account for the observed differences in the microbiome.
Answer: Differences in gut microbiome composition, including alpha diversity, beta diversity, and abundances of specific bacterial species, were observed in association with temperament in toddlers. This study was cross-sectional and observational and, therefore, does not permit determination of the causal direction of effects. However, if bidirectional brain-gut relationships are present in humans in early life, this may represent an opportunity for intervention relevant to physical as well as mental health disorders.
Output: Is gut microbiome composition associated with temperament during early childhood?