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: Impaired neurodevelopmental outcome represents a major morbidity for survivors of infant heart surgery for congenital heart defects. Previous studies in these neonates have reported preoperative microcephaly, periventricular leukomalacia, and other findings. The hypothesis of this study is that preoperative cerebral blood flow is substantially diminished and might relate to preoperative neurologic conditions.', 'Preoperative brain magnetic resonance imaging was performed. Cerebral blood flow measurements in infants with congenital heart defects were obtained by using a novel noninvasive magnetic resonance imaging technique, pulsed arterial spin-label perfusion magnetic resonance imaging. Cerebral blood flow was measured before the operation under standard ventilation and repeated after increased carbon dioxide.', 'A total of 25 term infants were studied. The average age at the time of the operation was 4.4 +/- 4.6 days. Congenital heart defects varied widely. Microcephaly occurred in 24% (6/25). Baseline cerebral blood flow was 19.7 +/- 9.2 mL . 100 g -1 . min -1 (8.0-42.2 mL . 100 g -1 . min -1 ). Five patients had cerebral blood flow measurements of less than 10 mL . 100 g -1 . min -1 . Mean hypercarbic cerebral blood flow increased to 40.1 +/- 20.3 mL . 100 g -1 . min -1 (11.4-94.0 mL . 100 g -1 . min -1 , P < .001). Pairwise analyses found that low hemoglobin levels were associated with higher baseline cerebral blood flow values ( P = .04). Periventricular leukomalacia occurred in 28% (7/25) and was associated with decreased baseline cerebral blood flow values ( P = .05) and a smaller change in cerebral blood flow with hypercarbia ( P = .003).
Answer: Structural brain abnormalities are common in these neonates before surgical intervention. Preoperative cerebral blood flow for this cohort was low and drastically reduced in some patients. Low cerebral blood flow values were associated with periventricular leukomalacia. Carbon dioxide reactivity was preserved but might be compromised by some aspects of the cardiac anatomy. The full spectrum of cerebral blood flow measurements with this technique in congenital heart defects and their long-term significance require continued investigation.

Output: Is preoperative cerebral blood flow diminished in neonates with severe congenital heart defects?


Input: Consider Input: Context: A complex network of putative molecular interactions underlies the architecture and function of cell-matrix adhesions. Most of these interactions are implicated from coimmunoprecipitation studies using expressed components, but few have been demonstrated or characterized functionally in living cells.', 'We introduce fluorescence fluctuation methods to determine, at high spatial and temporal resolution, "when" and "where" molecular complexes form and their stoichiometry in nascent adhesions (NAs). We focus on integrin-associated molecules implicated in integrin activation and in the integrin-actin linkage in NAs and show that these molecules form integrin-containing complexes hierarchically within the adhesion itself. Integrin and kindlin reside in a molecular complex as soon as adhesions are visible; talin, although also present early, associates with the integrin-kindlin complex only after NAs have formed and in response to myosin II activity. Furthermore, talin and vinculin association precedes the formation of the integrin-talin complex. Finally, α-actinin enters NAs periodically and in clusters that transiently associate with integrins. The absolute number and stoichiometry of these molecules varies among the molecules studied and changes as adhesions mature.
Answer: These observations suggest a working model for NA assembly whereby transient α-actinin-integrin complexes help nucleate NAs within the lamellipodium. Subsequently, integrin complexes containing kindlin, but not talin, emerge. Once NAs have formed, myosin II activity promotes talin association with the integrin-kindlin complex in a stoichiometry consistent with each talin molecule linking two integrin-kindlin complexes.

Output: Do integrin-associated complexes form hierarchically with variable stoichiometry in nascent adhesions?


Input: Consider Input: Context: Chemoresistance is a main obstacle to effective esophageal cancer (EC) therapy. We hypothesize that altered expression of microRNAs (miRNAs) play a role in EC cancer progression and resistance to 5-fluorouracil (5-FU) based chemotherapeutic strategies.', 'Four pairs of esophageal adenocarcinoma (EAC) cell lines and corresponding 5-FU resistant variants were established. The expression levels of miRNAs previously shown to be involved in the general regulation of stem cell pathways were analyzed by qRT-PCR. The effects of selected miRNAs on proliferation, apoptosis, and chemosensitivity were evaluated both in vitro and in vivo. We identified a particular miRNA and analyzed its putative target genes in 14 pairs of human EC tumor specimens with surrounding normal tissue by qRT-PCR as well as Wnt pathway associated genes by immunohistochemistry in another 45 EAC tumor samples.', 'MiR-221 was overexpressed in 5-FU resistant EC cell lines as well as in human EAC tissue. DKK2 was identified as a target gene for miR-221. Knockdown of miR-221 in 5-FU resistant cells resulted in reduced cell proliferation, increased apoptosis, restored chemosensitivity, and led to inactivation of the Wnt/β-catenin pathway mediated by alteration in DKK2 expression. Moreover, miR-221 reduction resulted in alteration of EMT-associated genes such as E-cadherin and vimentin as well as significantly slower xenograft tumor growth in nude mice. RT profiler analysis identified a substantial dysregulation of 4 Wnt/β-catenin signaling and chemoresistance target genes as a result of miR-221 modulation: CDH1, CD44, MYC, and ABCG2.
Answer: MiR-221 controls 5-FU resistance of EC partly via modulation of Wnt/β-catenin-EMT pathways by direct targeting of DKK2 expression. MiR-221 may serve as a prognostic marker and therapeutic target for patients with 5-FU resistant EAC.


Output: Does miR-221 mediate Chemoresistance of Esophageal Adenocarcinoma by Direct Targeting of DKK2 Expression?