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.
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Question: Context: The clinical value of oesophageal histology in non-complicated gastro-oesophageal reflux disease (GORD) is controversial. Our aim was to explore the role of histology in preoperative diagnosis and postoperative follow-up in GORD.', 'From 40 patients 2 histopathologists graded and scored 191 oesophageal biopsies in a blinded manner to evaluate inter- and intraobserver variation pre- and postoperatively. Correlation between preoperative histology and objective clinical findings (endoscopy, esophageal 24-hour pH monitoring, and manometry) was calculated as well.', 'Pathologist I interpreted 16 (50%) preoperative biopsies as normal, 5 (16%) with mild, 4 (12.5%) moderate, and 7 (21.9%) severe reflux changes. Pathologist II interpreted 11 (35.5%) preoperative biopsies as normal, 11 (35.5%) with mild, 6 (19.4%) moderate, and 3 (9.7%) severe reflux changes. In preoperative biopsies, interobserver variation was 33.8% and intraobserver variation 9.7%. A positive correlation was detectable between preoperative endoscopic and morphologic findings; no correlation existed between either acid reflux or LES pressure and oesophageal morphology. Normal pH monitoring and fundic wrap were noted postoperatively in all cases. In postoperative histology no significant differences according to pathologist I existed when compared with preoperative changes: 22 normal (69%), 7 mild (22%), 1 moderate (3.1%), and 2 severe (6.3%). Compared to preoperative analysis, pathologist II interpreted 24 (77%, p = 0.001) of the postoperative findings as normal, 1 (3%, p = 0.003) as mild, 4 (12.9%, n.s.) as moderate, and 2 (6.5% n.s.) as severe reflux changes. In postoperative biopsies interobserver variation was 21.1% and intraobserver variation 5.6%.
Answer: The role of oesophageal histology in preoperative diagnosis and postoperative follow-up of GORD may be considered limited.

Answer: Is oesophageal histology in gastro-oesophageal reflux disease of minor pre- and postoperative diagnostic value?


Question: Context: Cigarette smoke disrupts the protective barrier established by the airway epithelium through direct damage to the epithelial cells, leading to cell death. Since the morphology of the airway epithelium of smokers does not typically demonstrate necrosis, the most likely mechanism for epithelial cell death in response to cigarette smoke is apoptosis. We hypothesized that cigarette smoke directly up-regulates expression of apoptotic genes, which could play a role in airway epithelial apoptosis.', 'Microarray analysis of airway epithelium obtained by bronchoscopy on matched cohorts of 13 phenotypically normal smokers and 9 non-smokers was used to identify specific genes modulated by smoking that were associated with apoptosis. Among the up-regulated apoptotic genes was pirin (3.1-fold, p < 0.002), an iron-binding nuclear protein and transcription cofactor. In vitro studies using human bronchial cells exposed to cigarette smoke extract (CSE) and an adenovirus vector encoding the pirin cDNA (AdPirin) were performed to test the direct effect of cigarette smoke on pirin expression and the effect of pirin expression on apoptosis.', 'Quantitative TaqMan RT-PCR confirmed a 2-fold increase in pirin expression in the airway epithelium of smokers compared to non-smokers (p < 0.02). CSE applied to primary human bronchial epithelial cell cultures demonstrated that pirin mRNA levels increase in a time-and concentration-dependent manner (p < 0.03, all conditions compared to controls). Overexpression of pirin, using the vector AdPirin, in human bronchial epithelial cells was associated with an increase in the number of apoptotic cells assessed by both TUNEL assay (5-fold, p < 0.01) and ELISA for cytoplasmic nucleosomes (19.3-fold, p < 0.01) compared to control adenovirus vector.
Answer: These observations suggest that up-regulation of pirin may represent one mechanism by which cigarette smoke induces apoptosis in the airway epithelium, an observation that has implications for the pathogenesis of cigarette smoke-induced diseases.

Answer: Is upregulation of pirin expression by chronic cigarette smoking associated with bronchial epithelial cell apoptosis?


Question: Context: LIM homeobox transcription factor 1, alpha (LMX1A) and neuregulin 1 (NRG1) are susceptibility genes for schizophrenia that have been implicated in the dopaminergic pathway and have been associated with altered cognitive functioning. We hypothesized that single nucleotide polymorphisms (SNPs) in LMX1A and NRG1 would be associated with cognitive functioning in bipolar disorder.', 'In total, four SNPs were directly genotyped. Regression models with five aggregated cognitive domains and intelligence quotient (IQ) score were run using risk variants of LMX1A (rs11809911, rs4657412, rs6668493) and NRG1 (rs35753505) as predictors. Models were performed in a clinical sample of patients with bipolar disorder (n = 114) and healthy controls (n = 104).', 'The risk variants of the rs11809911 SNP in LMX1A were negatively associated with IQ score and memory/learning, whereas the risk variants of rs35753505 in NRG1 were positively associated with IQ score (adjusted R(2) = 0.17, Q = 0.006) and memory/learning (adjusted R(2) = 0.24, Q = 0.001). The risk variants of the rs35753505 SNP in NRG1 were positively associated with language (adjusted R(2) = 0.11, Q = 0.006), visuospatial functions (adjusted R(2) = 0.23, Q = 0.001), and attention/speed (adjusted R(2) = 0.25, Q = 0.001). Results could not be replicated in controls.
Answer: The risk variants of the rs35753505 SNP were associated with increased performance in several cognitive domains and IQ, whereas the risk variants of the rs11809911 SNP in LMX1A was associated with reduced IQ and memory/learning.

Answer:
Are polymorphisms of dopamine pathway genes NRG1 and LMX1A associated with cognitive performance in bipolar disorder?