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instruction:
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.
question:
Context: To determine the prevalence of fathers' attendance at pretest cancer genetic counseling sessions with mothers undergoing BRCA1/2 genetic testing for hereditary breast/ovarian cancer (HBOC) risk, and to identify psychosocial and other correlates of fathers' attendance.", 'One hundred and twenty-one fathers of minor-age children who were spouses/partners of women (mothers) undergoing such counseling and testing were recruited, completed a behavioral self-report survey, and provided data about their sociodemographic backgrounds, father-child cancer communication histories, parenting relationship quality, and information-seeking and perceived knowledge.', 'A total of 27.3% of fathers attended pretest cancer genetic counseling with mothers. Compared to fathers who did not attend pretest cancer genetic counseling, those who did had stronger parenting alliances with mothers, were more likely to have sought out information about BRCA1/2 testing, and felt more informed about testing. In an adjusted logistic regression model of session attendance, the strength of the parenting alliance was associated with a 6% increase in the likelihood of attending genetic counseling (odds ratio [OR]=1.06, 95% confidence interval [CI]=1.01, 1.12, p<.05) and greater perceived knowledge about BRCA1/2 testing was associated with a four-fold increase in the likelihood of session attendance (OR=4.03, CI=1.77, 9.37, p<.001).
Answer: One in three fathers attend pretest cancer genetic counseling with mothers undergoing BRCA1/2 testing; those who do have closer parenting relationships and are more informed about BRCA1/2 testing.
answer:
Does prevalence and correlate of mothers and fathers attending pretest cancer genetic counseling together?
question:
Context: Patients with chronic heart failure (CHF) have multiple abnormalities of autonomic regulation that have been associated to their high mortality rate. Heart rate recovery immediately after exercise is an index of parasympathetic activity, but its prognostic role in CHF patients has not been determined yet.', 'Ninety-two stable CHF patients (83M/9F, mean age: 51+/-12 years) performed an incremental symptom-limited cardiopulmonary exercise testing. Measurements included peak O2 uptake (VO2p), ventilatory response to exercise (VE/VCO2 slope), the first-degree slope of VO2 for the 1st minute of recovery (VO2/t-slope), heart rate recovery [(HRR1, bpm): HR difference from peak to 1 min after exercise] and chronotropic response to exercise [%chronotropic reserve (CR, %)=(peak HR-resting HR/220-age-resting HR)x100]. Left ventricular ejection fraction (LVEF, %) was also measured by radionuclide ventriculography.', 'Fatal events occurred in 24 patients (26%) during 21+/-6 months of follow-up. HRR1 was lower in non-survivors (11.4+/-6.4 vs. 20.4+/-8.1; p<0.001). All cause-mortality rate was 65% in patients with HRR1<or=12 bpm versus 11% in patients with HRR1>12 bpm (log-rank: 32.6; p<0.001). By multivariate survival analysis, HRR1 resulted as an independent predictor of mortality (chi2=19.2; odds ratio: 0.87; p<0.001) after adjustment for LVEF, VO2p, VE/VCO2 slope, CR and VO2/t-slope. In a subgroup of patients with intermediate exercise capacity (VO2p: 10-18, ml/kg/min), HRR1 was a strong predictor of mortality (chi2: 14.3; odds ratio: 0.8; p<0.001).
Answer: Early heart rate recovery is an independent prognostic risk indicator in CHF patients and could be used in CHF risk stratification.
answer:
Does early heart rate recovery after exercise predict mortality in patients with chronic heart failure?
question:
Context: Microalbuminuria and impaired endothelium-dependent vasodilation are both predictors for cardiac events in patients with type 2 diabetes. The aim of the study was to evaluate whether microalbuminuria correlated with coronary endothelium-dependent vasodilation.', 'We evaluated 84 patients (47 men, mean age 50.5 +/- 5.9 years) with type 2 diabetes for 9.4 +/- 3.4 years, without angiographic coronary stenosis and without major cardiovascular risk factors or other confounding factors, for endothelium investigation. Quantitative coronary angiography was used to assess coronary artery response to cold pressor testing, used to assess endothelium-dependent vasodilation, and to isosorbide dinitrate (endothelium-independent vasodilation).', 'Endothelium-dependent vasodilation differed in the patients with and without microalbuminuria (changes in coronary artery diameter during cold pressor testing: -15.0 +/- 1.9% vs. -10.2 +/- 1.3%, respectively, P < 0.05) and correlated with urinary albumin excretion rate (r = -0.39, P = 0.003), diastolic blood pressure (r = 0.29, P < 0.01), and left ventricular mass index (r = -0.24, P < 0.05). Independent predictors for endothelium-dependent vasodilation were urinary albumin excretion rate (beta -0.04 [95% CI -0.07 to -0.01], P < 0.005) and left ventricular mass index (-0.26 [-0.49 to -0.05], P < 0.05). Endothelium-independent vasodilation was similar in both groups.
Answer: Type 2 diabetic patients with microalbuminuria have a more severely impaired coronary endothelium-dependent vasodilation than those with normoalbuminuria. These data suggest a common pathophysiological process for both coronary vasomotor abnormalities and microalbuminuria.
answer:
| Is impaired coronary endothelium-dependent vasodilation associated with microalbuminuria in patients with type 2 diabetes and angiographically normal coronary arteries?
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Teacher: 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.
Teacher: Now, understand the problem? If you are still confused, see the following example:
Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
Solution: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Reason: The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
Now, solve this instance: Context: Erythromycin has been found to be a gastrointestinal prokinetic agent of hypertonic liquids, while acute hyperglycemia has been associated with delayed gastric emptying in diabetic patients.', 'To investigate whether hyperglycemia, per se, reduces gastric motility during erythromycin-induced acceleration on gastric emptying of hypertonic liquids in diabetic patients.', 'In 12 type-I diabetic patients following a hypertonic radiolabeled liquid meal, gastric emptying was measured scintigraphically during normoglycemia (5-8.9 mmol/l glucose) or hyperglycemia induced by intravenous (16-19 mmol/l) glucose infusion. The tests were performed on 4 separate days in random order after administering either placebo or 200 mg i.v. erythromycin.', 'In the hyperglycemic state compared to normoglycemia, the gastric emptying of the hypertonic liquid was reduced after placebo or erythromycin administration. The lag-phase duration (17.8+/-5.5 and 7.8+/-4.5 vs. 10.8+/-3.4 and 3.7+/-2.5 min, respectively, p<0.001), the overall gastric emptying time of the half meal (52.8+/-13 and 24.9+/-5.5 vs. 42.5+/-10.5 min and 16.6+/-6 min, respectively, p<0.001) and the retained percentage of liquid meal in the stomach at 60 and 100 min postprandially (p<0.001) were significantly increased.
Answer: The erythromycin-induced acceleration on gastric emptying of hypertonic liquids in diabetic patients is related to the plasma glucose level. The induced hyperglycemia reduces the erythromycin-induced acceleration of liquid-phase gastric emptying, decreasing the overall gastric emptying rate. In spite of the inhibitory effect of induced hyperglycemia on the gastric emptying of hypertonic liquids, erythromycin is still able to accelerate the emptying rate and could prove to be a useful prokinetic agent under hyperglycemic conditions.
Student: | Does induced-hyperglycemia attenuate erythromycin-induced acceleration of hypertonic liquid-phase gastric emptying in type-I diabetic patients? | task845_pubmedqa_question_generation |
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TASK DEFINITION: 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.
PROBLEM: Context: To develop a method for quick identification of sun-dried and sulfur-fumigated Cimicifugae Rhizoma by Fourier transform infrared spectroscopy (FTIR).', 'The alcoholic and aqueous extracts of sun-dried and sulfur-fumigated Cimicifugae Rhizoma were analyzed and compared by FTIR combined with second derivative infrared spectroscopy.', 'FTIR spectra showed that there were some differences in the positions of infrared absorption peaks and the relative intensities in the alcoholic and aqueous extracts of sun-dried and sulfur-fumigated Cimicifugae Rhizoma, and the second derivative IR spectra clearly enhanced the spectral resolution of their differences. FTIR spectra showed that the new absorption peaks of Cimicifugae Rhizoma appeared and a part of original absorption peaks disappeared after sulfur-fumigation in aqueous extracts, while a lot of new absorption peaks appeared and the intensities of almost all absorption peaks significantly decreased after sulfur-fumigation in alcoholic extracts. Second derivative IR spectra showed that both sun-dried and sulfur-fumigated Cimicifugae Rhizoma extracted by water differed significantly from each other ranging from about 3 950 to 3 940 cm(-1), 3 850 to 3 800 cm(-1), 1 800 to 1 750 cm(-1), as well as from 1 400 to 1 350 cm(-1); Differences also existed between sun-dried and sulfur-fumigated Cimicifugae Rhizoma extracted by ethanol ranging from about 3 980 to 3 960 cm(-1), 3 850 to 3 800 cm(-1), and 1 500 to 1 460 cm(-1).
Answer: The FTIR method combined with the second derivative IR spectrum can be used to analyze and distinguish sun-dried and sulfur-fumigated Cimicifugae Rhizoma quickly and accurately. The developed method provides an efficient approach for the quality control of Chinese herbal medicines with its simplicity and strong specificity.
SOLUTION: Do [ Quick identification and discrimination of sun-dried and sulfur-fumigated cimicifugae rhizoma by Fourier transform infrared spectroscopy ]?
PROBLEM: Context: Tumor necrosis factor-alpha (TNF-alpha) is a major pro-inflammatory cytokine. Recently, the G-308A polymorphism of the TNF-alpha gene has been associated with modified gene expression and increased TNF-alpha production in the -308A allele. We evaluated its influence on the incidence and clinical course of membranous glomerulonephritis.', 'We studied 53 patients with biopsy-proven primary membranous glomerulonephritis followed up for 5.7 +/- 4.9 years. 100 volunteers were analyzed as controls. According to the slope of the curve of reciprocal serum creatinine against time, group A (slow progressors, n = 35) and group B (fast progressors, n = 18) were defined. TNF-alpha G-308A polymorphism was determined by polymerase chain reaction amplification.', 'The frequency of the A-allele (associated with higher TNF-alpha levels) was significantly higher in patients than control subjects (patients: G-allele: 0.66, A-allele: 0.34; controls: G-allele 0.85, A-allele 0.15, p < 0.001). Similarly, the genotype distribution differed significantly between our study and control populations (patients: GG-genotype: 41.5%, GA: 49.1%, AA 9.4%; controls: GG: 71%, GA: 27%, AA 2%, p = 0.001). Age, renal function, proteinuria and blood pressure were similar at the time of renal biopsy between patients with different genotypes (NS). There was also a tendency towards an overpresentation of the A-allele in group B indicating a possible impact on the progression of membranous nephropathy, but a significance was not reached. Furthermore, no impact on renal survival in the Kaplan- Meier analysis was detected (NS).
Answer: Our results suggest that TNF-alpha gene G-308A polymorphism is a risk factor for the development of membranous glomerulonephritis.
SOLUTION: Is tumor necrosis factor-alpha gene G-308A polymorphism a risk factor for the development of membranous glomerulonephritis?
PROBLEM: Context: Diabetes mellitus (DM) is frequently associated with peripheral and central complications and has recently emerged as a risk factor for cognitive impairment and dementia. Kynurenic acid (KYNA), a unique tryptophan derivative, displays pleiotropic effects including blockade of ionotropic glutamate and α7 nicotinic receptors. Here, the influence of experimental diabetes on KYNA synthesis was studied in rat brain.', 'DM was induced by i.p. administration of streptozotocin (STZ). Five weeks later, KYNA content and the activity of semi-purified kynurenine aminotransferases (KATs) were measured in frontal cortex, hippocampus and striatum of diabetic and insulin-treated rats, using HPLC-based methods.', 'Hippocampal but not cortical or striatal KYNA concentration was considerably increased during DM, either untreated or treated with insulin (220% and 170% of CTR, respectively). The activity of kynurenine aminotransferase I (KAT I) was not affected by DM in all of the studied structures. KAT II activity was moderately increased in cortex (145% of CTR) and hippocampus (126% of CTR), but not in striatum of diabetic animals. Insulin treatment normalized cortical but not hippocampal KAT II activity.
Answer: A novel factor potentially implicated in diabetic hippocampal dysfunction has been identified. Observed increase of KYNA level may stem from the activation of endogenous neuroprotection, however, it may also have negative impact on cognition.
SOLUTION: | Does experimental diabetes mellitus type 1 increase hippocampal content of kynurenic acid in rats?
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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.
[EX Q]: 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.
[EX A]: Do integrin-associated complexes form hierarchically with variable stoichiometry in nascent adhesions?
[EX Q]: Context: Obstetric cholestasis is a cholestatic disease usually commencing in the third trimester of pregnancy and characterized by pruritus, elevation of liver enzymes, and increase in bile acids. The objective of this study was to compare the first trimester serum indicators of obstetric cholestasis with normal pregnancies.', 'Thirty-five patients diagnosed with obstetric cholestasis in a three-year period with first trimester biochemical assessment available were included in the study. Seventy patients with concordant pregnancy weeks, matched-age normal pregnancies were included as the control group. Pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) levels were analyzed.', 'No difference was observed between the two groups in terms of age and week of pregnancy. While the mean PAPP-A level was 0.76 ± 0.31 multiples of the medians (MoM) in the obstetric cholestasis group, it was determined to be 1.5 ± 0.84 in the control group (p = 0.0001). Among the two groups, the hCG levels were found to be higher in the obstetric cholestasis group (1.2 ± 0.79 MoM vs. 0.98 ± 0.53, p = 0.041).
Answer: In this study, the first trimester PAPP-A levels in the obstetric cholestasis cases were found to be significantly lower than the control group. Low PAPP-A levels should be a warning for obstetric cholestasis.
[EX A]: Are pregnancy-associated plasma protein a levels decreased in obstetric cholestasis?
[EX Q]: Context: Metabolic Syndrome (MetS) is associated with elevated risk for developing diabetes and cardiovascular disease. A key component of MetS is the development of insulin resistance (IR). The homeostatic model assessment (HOMA) model can determine IR by using insulin or C-peptide concentrations; however, the efficiency of insulin and C-peptide to determine MetS has not been compared. The aim of the study was to compare the efficiency of C-peptide and insulin to determine MetS in Mexicans.', "Anthropometrics, glucose, insulin, C-peptide, triglycerides, and high-density lipoproteins were determined in 156 nonpregnant females and 114 males. Subjects were separated into normal or positive for MetS. IR was determined by the HOMA2 calculator using insulin or C-peptide. Correlations were calculated using the Spearman correlation coefficient (ρ). Differences between correlations were determined by calculating Steiger's Z. The sensitivity was determined by the area under receiver operating characteristics curve (AUC) analysis.", 'Independent of the MetS definition [Adult Treatment Panel III (ATP III), International Diabetes Federation (IDF), or World Health Organization (WHO)], C-peptide and insulin were significantly higher in MetS subjects (P\u2009<\u20090.05). C-peptide and insulin correlated with all components of MetS; however, for waist circumference, waist-to-hip ratio, and fasting plasma glucose, C-peptide correlated better than insulin (P\u2009<\u20090.05). Moreover, C-peptide (AUC\u2009=\u20090.72-0.78) was a better marker than insulin (AUC\u2009=\u20090.62-0.72) for MetS (P\u2009<\u20090.05). Finally, HOMA2-IR calculated with C-peptide (AUC\u2009=\u20090.80-0.84) was more accurate than HOMA2-IR calculated with insulin (AUC\u2009=\u20090.68-0.75, P\u2009<\u20090.05) at determining MetS.
Answer: C-peptide is a strong indicator of MetS. Since C-peptide has recently emerged as a biomolecule with significant importance for inflammatory diseases, monitoring C-peptide levels will aid clinicians in preventing MetS.
[EX A]: | Does c-Peptide be a Sensitive Indicator for the Diagnosis of Metabolic Syndrome in Subjects from Central Mexico?
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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.
Q: Context: Interferon (IFN)-γ is a major cytokine produced by immune cells that plays diverse roles in modulating both the immune system and bone metabolism, but its role in autogenous bone grafting remains unknown. Here, we present that local IFN-γ administration improved the efficacy of autogenous bone graft treatment in an experimental rat model.', 'An autogenous bone graft model was prepared with critically sized rat calvariae defects. Four weeks (w) after bone graft implantation, rats were treated locally with IFN-γ or were not treated. The effect of IFN-γ on bone formation was evaluated for up to 8w with micro-computed tomography, quantitative histomorphometry, and Von Kossa staining. Osteoclastogenesis was assessed by tartrate-resistant acid phosphatase staining. Immunohistochemistry staining or quantitative polymerase chain reactions were used to estimate the expression of osteoclast differentiation factor and inflammatory cytokines including tumor necrosis factor (TNF)-α, a well-known stimulant of osteoclastogenesis and an inhibitor of osteoblast activity, in defects.', 'Newly formed bone gradually replaced the autogenous bone grafts within 4w, although severe bone resorption with osteoclastogenesis and TNF-α expression occurred after 6w in the absence of IFN-γ administration. IFN-γ administration markedly attenuated bone loss, osteoclastogenesis, and TNF-α expression, while it enhanced bone formation at 8w.
Answer: Local IFN-γ administration promoted bone formation in autogenous bone grafts possibly via regulating osteoclastogenesis and TNF-α expression. The data provide insights into the potential roles of IFN-γ in autogenous bone grafting.
A: Does interferon-γ enhance the efficacy of autogenous bone grafts by inhibiting postoperative bone resorption in rat calvarial defects?
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Q: Context: Chronic HIV/HCV co-infection carries increased risk of cirrhosis, hepatocellular carcinoma, and death. Due to anti-inflammatory properties, HMG co-A inhibitors (statins) may be useful adjunctive therapy to reduce liver disease progression.', 'Clinical information was extracted from the Veterans Affairs HIV and HCV Clinical Case Registries (1999 - 2010). HIV-related variables included combination anti-retroviral therapy (cART) era of diagnosis, CD4 cell count, and percent time with undetectable HIV viral load. Metabolic variables included diabetes, low-HDL, and hypertension. Statin use was measured as percent time with active prescription (time-updated throughout the follow-up period). Cox proportional hazards analysis was used to determine risk factors for cirrhosis (ICD-9 or APRI>2) overall and in groups stratified by alanine aminotransferase (ALT) level above and below 40\u200aIU/L.', 'The cohort included 5985\u200aHIV/HCV co-infected veterans. The majority was black race, and the mean age at index date was 45 years. Statin use was significantly protective of cirrhosis for patients with ALT ≤40\u200aIU/L; for every 30% increase in time on statin, there was a 32% decreased risk of developing cirrhosis (HR 0.68, 95% CI 0.47 -0.98). Diabetes and low-HDL were significantly associated with cirrhosis in patients with ALT > 40\u200aIU/L (HR 1.15, p\u200a<\u200a0.04 and HR 1.3, p\u200a<\u200a0.0001).
Answer: Statin drug use is beneficial in mitigating the risk of liver disease progression for HIV/HCV co-infected patients without advanced liver disease. Low-HDL and diabetes in co-infected patients with abnormal ALT have greater risk of cirrhosis development.
A: Do statin drugs decrease progression to cirrhosis in HIV/HCV co-infected individuals?
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Q: Context: The aim of this study was to evaluate the value and accuracy of multiplanar reconstruction (MPR) of three-dimensional (3D) transthoracic echocardiographic data sets in assessing mitral valve pathology in patients with surgical mitral valve prolapse (MVP).', 'Sixty-four patients with surgical MVP and preoperative two-dimensional (2D) and 3D transthoracic echocardiography were analyzed. The descriptions obtained by 3D MPR and 2D were compared in the context of the surgical findings.', 'Two-dimensional echocardiography correctly identified the prolapsing leaflets in 32 of 64 patients and 3D MPR in 46 of 64 patients (P=.016). Among the 27 patients with complex pathology (ie, more than isolated middle scallop of the posterior leaflet prolapse), 3D MPR identified 20 correctly, as opposed to 6 with 2D imaging (P<.001).
Answer: Interpretation of 3D transthoracic echocardiographic images with MPR improved the accuracy of the description of the MVP compared with 2D interpretation. This added value of 3D MPR was most important in extensive and/or commissural prolapse.
A: | Does multiplanar reconstruction of three-dimensional transthoracic echocardiography improve the presurgical assessment of mitral prolapse?
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Detailed Instructions: 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.
Q: Context: Infarct heterogeneity has been shown to be independently associated with adverse outcomes in previous smaller studies. However, it is unknown whether infarct characterization is an independent predictor of all-cause mortality in patients with advanced ischemic cardiomyopathy, after adjusting for clinical risk factors, severity of ischemic mitral regurgitation, incomplete revascularization, and device therapy.', 'A total of 362 patients with ischemic cardiomyopathy (left ventricular dysfunction with >70% stenosis in ≥1 epicardial coronary artery) underwent delayed hyperenhancement-magnetic resonance imaging and coronary angiography between 2002 and 2006. Total myocardial scar and peri-infarct (PI) area were measured using various threshold techniques. Multivariate survival analysis (primary end point of all-cause mortality) was conducted. One hundred fifty-seven deaths occurred during a mean 5.4-year follow-up (mean left ventricular ejection fraction, 23±9%; mean end-systolic volume index, 113±48 mL; mean total myocardial scar %, 25.5±16.0%; mean PI%, 5.7±2.9%). PI% (β=2.07; P<0.001) was an independent predictor of survival, independent of age, end-systolic volume, sex, mitral regurgitation, diabetes mellitus, dyslipidemia, coronary artery disease severity, implantable cardioverter defibrillator, and incomplete revascularization. PI% using 2 to 3 SD technique yielded the highest incremental prognostic power (χ(2) score 149).
Answer: In advanced ischemic cardiomyopathy, PI% is a powerful independent and incremental predictor of all-cause mortality. Infarct heterogeneity offers substantial further risk stratification when compared with quantification of total myocardial scar % alone even after adjusting for clinical risk factors, end-systolic volume index, mitral regurgitation, incomplete revascularization, and implantable cardioverter defibrillator implantation.
A: | Is infarct characterization and quantification by delayed enhancement cardiac magnetic resonance imaging a powerful independent and incremental predictor of mortality in patients with advanced ischemic cardiomyopathy? | task845_pubmedqa_question_generation |
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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.
[Q]: Context: To clarify the social issues and problems associated with burn care in Japan, based on a cost analysis of acute burn care.', 'A retrospective review was undertaken of 71 patients admitted with burns at Nippon Medical School between January 1 and December 31, 1997. A cost analysis was performed for three major burn patients with a burn surface area (BSA) of 70% to 80% and three minor burn patients with a BSA of 20% to 30%. A questionnaire was administered to both burn patients and medical providers in all 127 emergency centers to help improve long-term quality of life (QOL).', '80% of burn patients were under age 70. In the major burn cases, the amount of reimbursement according to the government-regulated fee schedule was much less than the cost of treatment. The ratio of the cost of both medication and materials to total cost of treatment was higher for patients with major burns. Patients responding to the survey acknowledged being generally happy despite suffering from psychological and financial problems. A total of 413 medical providers from 63 institutions responded to the survey regarding improving long-term QOL.
Answer: Acute burn care is a costly service. The goal of burn care should shift from saving lives to allowing for a productive return to society. Quality improvement, outcome measurement, and technology assessment combined with health economics research for burn care should be carried out in Japan.
[A]: Do the cost of burn care and implications for efficient care?
[Q]: Context: High visceral adipose tissue (VAT) and high liver fat (LF) are associated with the metabolic syndrome and diabetes. We studied changes in these two fat depots during weight loss and analyzed whether VAT and LF at baseline predict the response to lifestyle intervention.', 'One hundred twelve subjects (48 men and 64 women; age, 46 +/- 11 years; BMI, 29.2 +/- 4.4 kg/m(2)) were studied after a follow up-time of 264 +/- 60 (SD) days. Insulin sensitivity was estimated from the oral glucose tolerance test. Body fat depots were quantified using magnetic resonance imaging and spectroscopy.', 'Cross-sectionally high VAT (r = -0.22, p = 0.02) and high LF (r = -0.36, p < 0.0001) were independently associated with low insulin sensitivity. With intervention, BMI (-3.0%), VAT (-12.0%), and LF (-33.0%) were reduced (all p < 0.001). Insulin sensitivity was improved (+17%, p < 0.01). The changes in BMI (r = -0.41), VAT (r = -0.28), and LF (r = -0.39) were associated with the increase in insulin sensitivity (all p < 0.01). High VAT (r = -0.28, p = 0.01) and high LF (r = -0.38, p < 0.01) at baseline were associated with a lesser increase in insulin sensitivity.
Answer: Baseline values and changes in BMI, VAT, and LF are related to changes in insulin sensitivity during lifestyle intervention. Subjects with high VAT and LF have a lower chance of profiting from lifestyle intervention and may require intensified lifestyle prevention strategies or even pharmacological approaches to improve insulin sensitivity.
[A]: Are high visceral fat mass and high liver fat associated with resistance to lifestyle intervention?
[Q]: Context: Filaggrin (FLG) is a major protein component of the stratum corneum (SC) layer, and FLG loss-of-function mutations are a predisposing factor for atopic dermatitis (AD). Previous cohort studies of children from northern and western Europe have reported FLG loss-of-function mutation frequencies of 15.1-20.9% and 5.8-13.0% in AD and non-AD groups, respectively.', 'To elucidate the association between AD prevalence of FLG loss-of-function mutation carriers and climate conditions, we determined the AD prevalence and FLG loss-of-function mutation frequencies in a cohort of children from Ishigaki Island. Ishigaki Island has a subtropical climate with high humidity (monthly average, 60.8-78.7%) and high temperature (monthly average, 18.5-29.4°C) throughout the year.', 'We diagnosed AD prevalence and analyzed eight FLG loss-of-function mutations in the Japanese population against a cohort of 721 children from the Kyushu University Ishigaki Atopic Dermatitis Study (KIDS) cohort. Parents gave consent for the mutation analysis during their medical examinations from 2001 to 2006.', 'Average AD prevalence was 7.3% per year, and a total of 127 children (17.6%) were diagnosed with AD at least once between 2001 and 2006. The average total serum IgE level differed significantly between the AD and non-AD groups (199.0 and 69.0IU/ml, respectively). Although five kinds of FLG loss-of-function mutations isolated in previous Japanese FLG mutation studies were identified, the FLG loss-of-function mutation frequency in children of the KIDS cohort was not significantly different between the AD and non-AD groups (7.9% and 6.1%, respectively; P=0.174).
Answer: The FLG loss-of-function mutation frequency was not significantly different between the AD and non-AD groups in a cohort of children from Ishigaki Island, which has a subtropical climate, suggesting that FLG loss-of-function mutations are not always a predisposing factor for AD prevalence.
[A]: | Are filaggrin loss-of-function mutations a predisposing factor for atopic dermatitis in an Ishigaki Island under subtropical climate?
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Detailed Instructions: 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.
Problem:Context: Sympathetic nervous system hyperactivity promotes vascular disorders by its catabolic effects and by increasing arterial blood pressure. Levodopa-derived dopamine modulates sympathetic overactivity and is known to reduce blood pressure, but its effects on glucose and lipid metabolism have not been studied in large series of patients.', 'We retrospectively examined 483 consecutive parkinsonian patients, admitted to a single institute between 1970 and 1987, before statins were available. We compared risk factors for vascular disease in the 305 who were on levodopa with the 178 who had never received the drug.', 'On admission levodopa-treated patients had significantly lower plasma levels of triglycerides, total cholesterol and lipids, and lower frequency of diabetes and hypertension than untreated patients. Mean body mass index, resting blood pressure, fasting plasma glucose, and smoking did not differ between the groups. A year after enrollment 160 patients were re-hospitalized; of these 63 had started levodopa during first hospitalization. In these new levodopa users total cholesterol, triglycerides and lipids had reduced to levels comparable with those of longer-term levodopa users.
Answer: Levodopa use in parkinsonian patients is associated with reduced vascular risk factors. In causal terms this finding might be attributed to the inhibitory action of levodopa-derived dopamine on the sympathetic nervous system.
Solution: | Does sympathetic modulation by levodopa reduce vascular risk factors in Parkinson disease? | task845_pubmedqa_question_generation |
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Definition: 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: Context: Prolonged P wave duration is a marker of delayed inter-atrial conduction which may predict cardiovascular disease (CVD). Type 2 diabetes is a risk factor for all atherosclerotic manifestations including stroke. We evaluated the prognostic significance of prolonged P wave duration among middle-aged Finnish type 2 diabetes patients with and without prevalent non-major macrovascular disease (PNMMVD) with respect to total and stroke mortality.', 'We followed up for 18 years 739 type 2 diabetic patients without previous major CVD event at baseline. Participants were stratified according to P wave duration (<114 or ≥ 114 ms) and PNMMVD (i.e. coronary heart disease defined as ischaemic ECG changes and typical symptoms of angina pectoris, or claudication; yes or no). The Cox proportional hazards model was used to estimate the joint association between P wave duration, PNMMVD and the mortality risk.', 'During the follow-up, 509 patients died, and 59 of them died from stroke. Those who had prolonged P wave duration had 2.45 (95% confidence interval: 1.11-5.37) increased stroke mortality among PNMMVD patients. In patients without PNMMVD, there was no relationship between P wave duration and stroke mortality.
Answer: As an easily measurable factor P wave duration merits further studies with higher number of patients to evaluate its importance in the estimation of stroke risk in type 2 diabetic patients with PNMMVD.
Output: | Does prolonged P wave duration predict stroke mortality among type 2 diabetic patients with prevalent non-major macrovascular disease? | task845_pubmedqa_question_generation |
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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.
Example: Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
Example solution: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Example explanation: The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
Problem: Context: The establishment of accurate equations for glomerular filtration rate (GFR) estimations is still far from the realization. Factors such as age, diabetes, stage of CKD, pregnancy, muscle mass and ethic nation are associated with less reliance upon commonly utilized estimation equations. We aimed to compare the routine use of 24-hour creatinine clearance (CrCl) and GFR estimates calculated by Crockoft-Gault (CG) and modification of diet in renal disease (MDRD) formulas in patients with different levels of renal dysfunction in subgroups, based on Body Mass Index (BMI) and serum albumin (Alb) levels.', 'Two hundred and seventy-nine non diabetic patients (172 men and 107 women), aged 54±23 years, with BMI 27.3±4.4 were enrolled in the study. All patients presented creatinine 1.8±1.2 (mg/dL) and Alb 3.5±1.3g/dL. The comparison of CrCl versus CG had bias 3.1 while the comparison of CrCl versus MDRD had a bias of 6.6.', 'Univariate analysis showed that age, sex and BMI were not significant biases related to the CG, MDRD and CrCl. Indeed, the bias related to the CG was significantly lower than that related to MDRD in patients with either low or high serum albumin. Interestingly, the bias associated with CG was 1.3 in non-diabetic patients with Alb ≤3.5 mg /dL suggesting that CG equation could be used interchangeable to CrCl in these patients.
Answer: CG gave a better prediction of measured CrCl than MDRD in Mediterranean, non-diabetic, non-hospitalized patients although misclassification of patients with regard to renal impairment stage was not present.
| Solution: Does comparison of creatinine clearance estimate in subgroups based on Body Mass Index and albumin? | task845_pubmedqa_question_generation |
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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.
One example is below.
Q: Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
A: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Rationale: The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
Q: Context: Adipose tissue is responsible for releasing various adipokines that have been related to insulin resistance. Understanding the relationship of these adipokines to insulin resistance may foster the development of new treatments for diabetes.', 'The primary objective of this study was to determine whether an association between retinol-binding protein 4 (RBP4) and insulin resistance exists in nonobese individuals without a family history or diagnosis of diabetes. The secondary objective was to determine by a dual energy x-ray absorptiometry scan which adipose tissue depot most closely relates to RBP4 levels.', 'Cross-sectional analysis of 92 study participants ranging in age from 20 to 83 yr was performed. The range of body mass index (BMI) was from 18 to 30 kg/m(2). Exclusion criteria were a BMI greater than 30 kg/m(2), family history of diabetes, or a diagnosis of diabetes. Insulin sensitivity was determined by a hyperinsulinemic euglycemic clamp. Body fat was measured by dual energy x-ray absorptiometry scan.', 'RBP4 values were lower in females (35.8 +/- 1.7 microg/ml) compared with males (39.9 +/- 1.4 microg/ml; P = 0.06). RBP4 levels were found to correlate negatively with insulin sensitivity (r = -0.32; P = 0.002) and positively with age (r = 0.38; P < 0.001). RBP4 levels did not correlate with BMI (r = -0.13; P = 0.22), trunk fat (r = 0.16; P = 0.22), or percent body fat (r = 0.07; P = 0.65). However, RBP4 levels did correlate with percent trunk fat (r = 0.36; P = 0.001).
Answer: These findings indicate a relationship between RBP4, insulin sensitivity, and percent trunk fat in individuals who may not have features of insulin resistance.
A: | Is retinol-binding protein 4 associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes? | task845_pubmedqa_question_generation |
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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.
[Q]: Context: Parenteral control of gastric acid hypersecretion in conditions such as Zollinger-Ellison syndrome (ZES) or idiopathic gastric acid hypersecretion is necessary perioperatively or when oral medications cannot be taken for other reasons (e.g., during chemotherapy, acute upper gastrointestinal bleeding, or in intensive care unit settings).', 'We evaluated the efficacy and safety of 15-minute infusions of the proton pump inhibitor pantoprazole (80-120 mg every 8-12 hours) in controlling acid output for up to 7 days. Effective control was defined as acid output >10 milliequivalents per hour (mEq/h) (<5 mEq/h in patients with prior acid-reducing surgery) for 24 hours.', 'The 21 patients enrolled had a mean age of 51.9 years (range, 29-75) and a mean disease duration of 8.1 years (range, <0.5-21); 13 were male, 7 had multiple endocrine neoplasia syndrome type I, 4 had undergone acid-reducing surgery, 2 had received chemotherapy, and 13 had undergone gastrinoma resections without cure. Basal acid output (mean +/- SD) was 40.2 +/- 27.9 mEq/h (range, 11.2-117.9). In all patients, acid output was controlled within the first hour (mean onset of effective control, 41 minutes) after an initial 80-mg intravenous pantoprazole dose. Pantoprazole, 80 mg every 12 hours, was effective in 17 of 21 patients (81%) for up to 7 days. Four patients required upward dose titration, 2 required 120 mg pantoprazole every 12 hours, and 2 required 80 mg every 8 hours. At study end, acid output remained controlled for 6 hours beyond the next expected dose in 71% of patients (n = 15); mean acid output increased to 4.0 mEq/h (range, 0-9.7). No serious or unexpected adverse events were observed.
Answer: Intravenous pantoprazole, 160-240 mg/day administered in divided doses by 15-minute infusion, rapidly and effectively controlled acid output within 1 hour and maintained control for up to 7 days in all ZES patients.
[A]: Does intravenous pantoprazole rapidly control gastric acid hypersecretion in patients with Zollinger-Ellison syndrome?
[Q]: Context: The single nucleotide polymorphism rs10494366 in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene is associated with QTc prolongation, through an effect on the intracellular Ca levels. As sulfonylurea stimulate insulin secretion by an increased influx of Ca, we hypothesized that this polymorphism is associated with the glucose-lowering effect and mortality risk in sulfonylurea users.', 'Associations between the NOS1AP polymorphism, prescribed doses, and mortality rates in sulfonylurea, metformin, and insulin users were assessed in the Rotterdam Study, a population-based cohort study of 7983 elderly people.', 'We identified 619 participants who were prescribed oral antidiabetic drugs during follow-up. In glibenclamide users carrying the TG genotype, the prescribed doses were higher compared with the glibenclamide users carrying the TT genotype [0.38 defined daily dose units, 95% confidence interval (CI) 0.14-0.63]. Glibenclamide users with the TG or GG genotype had an increased mortality risk compared with glibenclamide users with the TT genotype [hazard ratio (HR) 2.80, 95% CI: 1.09-7.22]. Tolbutamide users with the TG or GG genotype (HR: 0.30, 95% CI: 0.14-0.63) and glimepiride users with the TG or GG genotype (HR: 0.18, 95% CI: 0.04-0.74) had a decreased mortality risk compared with tolbutamide and glimepiride users with the TT genotype.
Answer: In participants with the TG or GG genotype at rs10494366 in the NOS1AP gene, glibenclamide is less effective in reducing glucose levels and mortality rates were higher compared with glibenclamide users with the TT genotype. In tolbutamide and glimepiride users, the TG and GG genotype were associated with a reduced mortality rate.
[A]: Is common variation in the NOS1AP gene associated with reduced glucose-lowering effect and with increased mortality in users of sulfonylurea?
[Q]: Context: Peroxisome proliferator-activated receptor alpha (PPARα) is a key regulator of hepatic fat oxidation that serves as an energy source during starvation. Vanin-1 has been described as a putative PPARα target gene in liver, but its function in hepatic lipid metabolism is unknown.', 'We investigated the regulation of vanin-1, and total vanin activity, by PPARα in mice and humans. Furthermore, the function of vanin-1 in the development of hepatic steatosis in response to starvation was examined in Vnn1 deficient mice, and in rats treated with an inhibitor of vanin activity.', 'Liver microarray analyses reveals that Vnn1 is the most prominently regulated gene after modulation of PPARα activity. In addition, activation of mouse PPARα regulates hepatic- and plasma vanin activity. In humans, consistent with regulation by PPARα, plasma vanin activity increases in all subjects after prolonged fasting, as well as after treatment with the PPARα agonist fenofibrate. In mice, absence of vanin-1 exacerbates the fasting-induced increase in hepatic triglyceride levels. Similarly, inhibition of vanin activity in rats induces accumulation of hepatic triglycerides upon fasting. Microarray analysis reveal that the absence of vanin-1 associates with gene sets involved in liver steatosis, and reduces pathways involved in oxidative stress and inflammation.
Answer: We show that hepatic vanin-1 is under extremely sensitive regulation by PPARα and that plasma vanin activity could serve as a readout of changes in PPARα activity in human subjects. In addition, our data propose a role for vanin-1 in regulation of hepatic TG levels during fasting.
[A]: | Does pPAR-alpha dependent regulation of vanin-1 mediate hepatic lipid metabolism?
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Instructions: 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: Context: The purpose of this study was to determine whether periodontal disease is associated with endothelial dysfunction and systemic inflammation. Epidemiological studies suggest that severe periodontal disease is associated with increased cardiovascular disease risk, but the mechanisms remain unknown.', 'We assessed flow-mediated dilation and nitroglycerin-mediated dilation of the brachial artery using vascular ultrasound in 26 subjects with advanced periodontal disease and 29 control subjects. The groups were matched for age and sex, and patients with hypercholesterolemia, diabetes mellitus, hypertension, and history of cigarette smoking were excluded. We also examined serum levels of C-reactive protein using an established high-sensitivity method. Subjects with advanced periodontal disease had lower flow-mediated dilation compared with control patients (7.8+/-4.6% versus 11.7+/-5.3%, P=0.005). Nitroglycerin-mediated dilation was equivalent in the two groups. Subjects with advanced periodontitis exhibited higher serum levels of high-sensitivity C-reactive protein compared with healthy controls patients (2.3+/-2.3 versus 1.0+/-1.0 mg/L, P=0.03).
Answer: Subjects with advanced periodontal disease exhibit endothelial dysfunction and evidence of systemic inflammation, possibly placing them at increased risk for cardiovascular disease.
Output: | Is periodontal disease associated with brachial artery endothelial dysfunction and systemic inflammation? | task845_pubmedqa_question_generation |
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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.
One example is below.
Q: Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
A: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Rationale: The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
Q: Context: To examine the lipid profile in Chinese type 2 diabetic patients and their relationship with anthropometric parameters, glycaemic control and cardiovascular mortality.', 'A consecutive cohort of 562 newly referred patients with type 2 diabetes to a hospital-based diabetes centre were examined in 1996. Subjects treated with lipid lowering drugs at the time of referral were excluded. A total of 517 subjects were followed up over a mean (+/-SD) period of 4.6 +/- 0.9 years. Glycated haemoglobin (HbA1c), fasting insulin and lipid profile and anthropometric parameters were documented at the time of recruitment. Cardiovascular mortality, mainly due to coronary heart disease and stroke, was ascertained using death registry and review of hospital case notes in 2001.', 'Of the 517 subjects (mean age of 54.0 +/- 14.0 years), 42.6% were men. In this cohort, 63.3% of subjects were either overweight (BMI > or = 23 kg/m2) or obese (BMI > or = 25 kg/m2) using Asian criteria. The mean (+/-SD) total cholesterol (TC), LDL-Cholesterol (LDL-C), HDL-Cholesterol (HDL-C) and geometric mean (x// antilog SD) of triglycerides (TG) were 5.6 +/- 1.3 mmol/L, 3.6 +/- 1.1 mmol/L, 1.3 +/- 0.3 mmol/L and 1.46x//1.90 mmol/L respectively. TC and LDL-C correlated positively with HbA1c, HDL-C negatively with BMI and WC (waist circumference), while TG positively with HbA1c, BMI, WC and HOMA (insulin resistance estimated using the homeostasis model assessment). During the 4.6 years follow-up period, there were 61 deaths giving a total mortality rate of 11.4%, of which 15 (25%) were because of cardiovascular events. Apart from age and disease duration, logarithm of TG was significantly associated with increased risk of cardiovascular mortality (p = 0.049, relative risk = 2.97, 95% CI 1.00-8.77).
Answer: Chinese type 2 diabetic patients had a lower prevalence of obesity, lower TG and higher HDL-C than Caucasian patients. Despite the low incidence of cardiovascular death, TG, which was closely associated with obesity indexes, was significantly associated with cardiovascular death in these patients.
A: | Does triglyceride predict cardiovascular mortality and its relationship with glycaemia and obesity in Chinese type 2 diabetic patients? | task845_pubmedqa_question_generation |
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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.
[EX Q]: Context: Obstetric cholestasis is a cholestatic disease usually commencing in the third trimester of pregnancy and characterized by pruritus, elevation of liver enzymes, and increase in bile acids. The objective of this study was to compare the first trimester serum indicators of obstetric cholestasis with normal pregnancies.', 'Thirty-five patients diagnosed with obstetric cholestasis in a three-year period with first trimester biochemical assessment available were included in the study. Seventy patients with concordant pregnancy weeks, matched-age normal pregnancies were included as the control group. Pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) levels were analyzed.', 'No difference was observed between the two groups in terms of age and week of pregnancy. While the mean PAPP-A level was 0.76 ± 0.31 multiples of the medians (MoM) in the obstetric cholestasis group, it was determined to be 1.5 ± 0.84 in the control group (p = 0.0001). Among the two groups, the hCG levels were found to be higher in the obstetric cholestasis group (1.2 ± 0.79 MoM vs. 0.98 ± 0.53, p = 0.041).
Answer: In this study, the first trimester PAPP-A levels in the obstetric cholestasis cases were found to be significantly lower than the control group. Low PAPP-A levels should be a warning for obstetric cholestasis.
[EX A]: Are pregnancy-associated plasma protein a levels decreased in obstetric cholestasis?
[EX Q]: Context: Barrett esophagus (BE) is considered precursor condition of esophageal adenocarcinoma. Its incidence and prevalence are increasing in general population. Studies reported that metabolic syndrome (MS) or diabetes mellitus (DM) is related to increased risk of BE. Current study was to assess and better understand the relationship between MS /DM and BE.', "Electronic search was conducted in the database Pubmed/Medline (-December, 2015), Embase (-December, 2015), Cochrane Library (-December, 2015), and Web of Knowledge (-December, 2015). Studies included were assessed with summary odds ratios (ORs) with 95% confidence intervals (CIs) and compared exposure group with control group. The heterogeneity was examined by the funnel plot and the Egger's test. Subgroup analyses and sensitive analyses were performed for the detection of possible heterogeneity and impact on stability of analysis results.", "Twelve publications met the criteria and included 355,311 subjects were analyzed. The pooled results showed MS was closely associated with increased risk of BE (OR\u200a=\u200a1.23; 95%CI 1.03-1.47; P\u200a=\u200a0.024), and yet DM did not significantly increase the risk of BE (OR\u200a=\u200a1.07; 95%CI 0.82-1.38; P\u200a=\u200a0.627). Substantial heterogeneities were detected. No significant publication bias was detected by Egger's test (P\u200a=\u200a0.23).
Answer: Based on the results of current meta-analysis, MS is associated with increased risk of BE. Further long-term follow-up prospective study needs to verify the current results, and definite pathophysiological mechanism needs to be further investigated and clearly elucidated.
[EX A]: Is metabolic syndrome associated with increased risk of Barrett esophagus : A meta-analysis?
[EX Q]: Context: To maximize the benefit of carotid endarterectomy (CEA) in stroke prevention its complication rate must be minimized. The purpose of this study was to report the outcomes of a large series of CEA carried out under regional anaesthesia with selective shunting, with particular emphasis on identifying predictors for perioperative stroke and mortality.', 'Between 1987 and 2003 the data for 1665 consecutive regional anaesthetic CEA carried out in 1495 patients were collected prospectively; awake neurological testing facilitated selective shunting. Preoperative data, intraoperative events and postoperative in-hospital complications were recorded and analysed.', 'There were 38 non-fatal strokes (2.3%) and 10 deaths (0.6%), giving a combined stroke and mortality rate of 2.9%. Only patients who needed shunting were found to have significantly higher rate of postoperative stroke and mortality (7.0 vs 1.9%, P < 0.001). Patient characteristics, comorbidities, indication for operation (P = 0.34) and the degree of stenosis of the contralateral carotid artery (P = 0.65) were not found to be predictive of perioperative stroke or mortality, although the latter two were found to be predictive of the need for shunting (P < 0.001 and P = 0.002).
Answer: Regional anaesthetic CEA is a safe and effective technique with excellent morbidity and mortality rates. The technique can be undertaken safely regardless of the indication for endarterectomy or the status of the contralateral carotid artery. Patients who developed intraoperative neurological changes requiring shunting are identified as high risk for perioperative stroke or mortality and should therefore be carefully monitored postoperatively.
[EX A]: | Does intraoperative neurological changes in 1665 regional anaesthetic carotid endarterectomies predict postoperative stroke?
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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: Mast cells have been associated with obliterative bronchiolitis (OB) in human pulmonary allografts, although their role in the development of OB remains unknown.', 'In this study, we evaluated the role of mast cells in pulmonary allograft rejection using an orthotopic rat pulmonary allograft model that utilizes chronic aspiration of gastric fluid to reliably obtain OB. Pulmonary allograft recipients (n = 35) received chronic aspiration of gastric fluid with (n = 10) and without (n = 16) treatment with a mast cell membrane stabilizer, cromolyn sodium, or chronic aspiration with normal saline (n = 9) as a control.', 'The acute graft injury associated with long ischemic time in the model (6 hours total ischemic time; typical acute graft injury rate ~30%) was apparently blocked by cromolyn, because peri-operative mortality associated with the acute graft injury was not observed in any of the animals receiving cromolyn (p = 0.045). Further, the rats receiving cromolyn developed significantly fewer OB lesions than those treated with gastric fluid alone (p < 0.001), with a mean reduction of 46% of the airways affected.
Answer: These findings provide impetus for further studies aimed at elucidating the effects of cromolyn and the role of mast cells in pulmonary allotransplantation.
Output: Does cromolyn ameliorate acute and chronic injury in a rat lung transplant model?
Input: Consider Input: Context: The etiology of reduced left ventricular (LV) ejection fraction after exercise, without obstructive coronary artery disease or other established causes, is unclear. The aims of this study were to determine whether patients undergoing treadmill stress echocardiography with this abnormal LV contractile response to exercise (LVCRE) without established causes have resting LV long-axis dysfunction or microvascular dysfunction and to determine associations with this abnormal LVCRE.', 'Of 5,275 consecutive patients undergoing treadmill stress echocardiography, 1,134 underwent cardiac computed tomography angiography or invasive angiography. Having excluded patients with obstructive coronary artery disease, hypertensive response, submaximal heart rate response, resting LV ejection fraction < 50%, and valvular disease, 110 with "abnormal LVCRE" and 212 with "normal LVCRE" were analyzed. Resting mitral annular velocities were measured to assess LV long-axis function. Myocardial blush grade and corrected Thrombolysis In Myocardial Infarction frame count were determined angiographically to assess microvascular function.', "Comparing normal LVCRE with abnormal LVCRE, age (mean, 59.7 ± 11.1 vs 61.4 ± 10.0 years), hypertension (53% vs 55%), diabetes (16% vs 20%), and body mass index (mean, 29.1 ± 5.4 vs 29.5 ± 6.4 kg/m(2)) were similar (P > .05). Abnormal LVCRE had reduced resting LV long-axis function with lower septal (mean, 6.1 ± 1.9 vs 7.7 ± 2.2 cm/sec) and lateral (mean, 8.1 ± 2.9 vs 10.4 ± 3.0 cm/sec) e' velocities (P < .001) and larger resting left atrial volumes (mean, 37.3 ± 10.1 vs 31.1 ± 7.2 mL/m(2), P < .001). On multivariate analysis, female gender (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.15-1.99; P < .001), exaggerated chronotropic response (OR, 1.49; 95% CI, 1.09-2.05; P < .001), resting left atrial volume (OR, 2.38; 95% CI, 1.63-3.47; P < .001), and resting lateral e' velocity (OR, 1.70; 95% CI, 1.22-2.49; P = .003) were associated with abnormal LVCRE, but not myocardial blush grade or corrected Thrombolysis In Myocardial Infarction frame count.
Answer: An abnormal LVCRE in the absence of established causes is associated with resting LV long-axis dysfunction and is usually seen in women.
Output: Is abnormal left ventricular contractile response to exercise in the absence of obstructive coronary artery disease associated with resting left ventricular long-axis dysfunction?
Input: Consider Input: Context: Few prospective studies have examined personality and depression in older adults. The authors investigated whether the Five-Factor Model of personality traits-Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness-and trait combinations (styles) are related to incident major or minor depression.', 'Prospective data were gathered on a community sample of 512 older adults with disability and a history of significant health care utilization who were enrolled in a Medicare Demonstration Project.', 'Depression and personality traits and styles were assessed at baseline; depression was assessed again at approximately 12 and 22 months.', 'Participants who developed incident major depression were compared with those free of depression at all three assessments. Similar analyses were done for minor depression.', 'High Neuroticism and low Conscientiousness were risk factors for both major and minor depression. Combinations of high Neuroticism with low or high Extraversion or high Openness conferred risk for major depression. Other novel findings for major depression revealed new trait combinations of low Conscientiousness with low or high Extraversion, high Openness, or low Agreeableness. Three trait combinations, all involving low Conscientiousness, predicted risk for minor depression: high Neuroticism, high Agreeableness, and low Openness.
Answer: The present findings highlight the importance of examining combinations of personality traits or personality styles when identifying those who are most at-risk for geriatric depression. Since other personality domains may modify the risk related to high Neuroticism and low Conscientiousness, the prevention, diagnosis, and treatment of depression could be greatly improved by assessing older patients not only on all five domains of personality but in terms of their combinations.
| Output: Are the personality domains and styles of the five-factor model related to incident depression in Medicare recipients aged 65 to 100?
| task845_pubmedqa_question_generation |
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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.
Q: 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.
A: Is preoperative cerebral blood flow diminished in neonates with severe congenital heart defects?
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Q: Context: Diabetic cardiomyopathy (DCM) is associated with suppressed autophagy and augmented apoptosis in the heart although the interplay between the two remains elusive. The ability of mammalian sterile 20-like kinase 1 to regulate both autophagy and apoptosis prompted us to investigate it as a possible candidate in the progression of DCM.', 'Wild-type, Mst1 (also known as Stk4) transgenic and Mst1-knockout mice were challenged with streptozotocin to induce experimental diabetes. In addition, cultured neonatal mouse cardiomyocytes were subjected to simulated diabetes to probe mechanisms.', 'Mst1 knockout alleviated while Mst1 overexpression aggravated cardiac dysfunction in diabetes. Diabetic Mst1 transgenic mice exhibited decreased LC3 expression and enhanced protein aggregation. In contrast, typical autophagosomes were observed in diabetic Mst1-knockout mice with increased LC3 expression and reduced protein aggregation. Mst1 downregulation promoted autophagic flux as demonstrated by increased LC3-II and decreased p62 expression in the presence of bafilomycin A1. Furthermore, Mst1 overexpression increased, while Mst1 knockout decreased, cardiomyocyte apoptosis both in vivo and in vitro. Co-immunoprecipitation assays showed that Mst1 overexpression promoted Beclin1 binding to B cell lymphoma 2 (Bcl-2) and induced dissociation of Bcl-2 from Bax in diabetic mice. Conversely, Mst1 knockout disrupted the Beclin1-Bcl-2 complex and enhanced the interaction between Bcl-2 and Bax.
Answer: Mst1 knockout restores autophagy and protects against apoptosis in cardiomyocytes, en route to the rescue against DCM.
A: Does mST1 coordinately regulate autophagy and apoptosis in diabetic cardiomyopathy in mice?
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Q: Context: The goal of this investigation was to examine the effect of immunity to nerve growth factor (NGF) on alterations in sensory nerves from the urinary bladder in the dorsal root ganglia (DRG) and their projections to the L6/S1 spinal cord following urethral obstruction in the rat.', 'Female Wistar rats were immunized to murine 2.5S NGF, then obstructed by partial urethral ligation for 6 weeks. Retrograde axonal tracing with FluoroGold and WGA-HRP was used to measure areas of bladder DRG cells and afferent projections in the sacral spinal cord. Multiunit activity on bladder nerves allowed recording of micturition reflexes. Immunohistochemical staining for growth associated protein (GAP)-43 in the sacral parasympathetic nucleus (SPN) was used to assess potential growth or activity of axons in the spinal cord. Voiding frequencies were then measured in awake obstructed and NGF immune-obstructed rats.', 'Immunity to NGF prevented obstruction-induced hypertrophy of DRG neurons, reduced retrograde axonal labeling of sacral afferent projections, eliminated enhancement of a spinal micturition reflex and abolished the increased GAP-43 expression in the SPN. Immunity to NGF prevented the urinary frequency that accompanies obstruction.
Answer: Our results demonstrate that obstruction of the bladder elicits structural and functional plasticity in afferents as a result of ongoing neurotrophic interactions. Neurotrophic interactions offer a potential mechanism whereby symptoms and bladder hyperactivity develop with obstruction associated with benign prostatic hyperplasia.
A: | Does immunity to nerve growth factor prevent afferent plasticity following urinary bladder hypertrophy?
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| task845_pubmedqa_question_generation |
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Teacher: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.
Teacher: Now, understand the problem? Solve this instance: Context: Factors that influence energy metabolism and substrate oxidation, such as thyroid hormones (THs), may be important regulators of body weight.', 'We investigated associations of THs cross-sectionally with obesity, energy expenditure, and substrate oxidation and prospectively with weight change.', 'Euthyroid, nondiabetic, healthy, adult Pima Indians (n = 89; 47 M, 42 F) were studied. Percentage body fat (%BF) was measured by using dual-energy X-ray absorptiometry; sleeping metabolic rate (SMR), respiratory quotient, and substrate oxidation rates were measured in a respiratory chamber. Thyroid-stimulating hormone (TSH), free thyroxine (T(4)), free triiodothyronine (T(3)), and leptin concentrations were measured in fasting plasma samples.', 'TSH, but neither free T(3) nor free T(4), was associated with %BF and leptin concentrations (r = 0.27 and 0.29, respectively; both: P <or= 0.01). In multiple regression analyses adjusted for age, sex, fat mass, and fat-free mass, free T(3) was a positive predictor of SMR (P = 0.02). After adjustment for age, sex, %BF, and energy balance, free T(3) was a negative predictor of 24-h respiratory quotient (P < 0.05) and a positive predictor of 24-h lipid oxidation rate (P = 0.006). Prospectively, after an average follow-up of 4 +/- 2 y, the mean increase in weight was 3 +/- 9 kg. Baseline T(3) concentrations were associated with absolute and annual percentage of changes in weight (r = -0.27, P = 0.02, and r = -0.28, P = 0.009, for the age- and sex-adjusted associations, respectively).
Answer: In euthyroid Pima Indians, lower free T(3) but not free T(4) concentrations were an independent predictor of SMR and lipid oxidation and a predictor of weight gain. This finding indicates that control of T(4)-to-T(3) conversion may play a role in body weight regulation.
Student: | Do plasma concentrations of free triiodothyronine predict weight change in euthyroid persons? | task845_pubmedqa_question_generation |
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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.
Context: Normal glucose metabolism depends on pancreatic secretion of insulin and glucagon. The bihormonal hypothesis states that while lack of insulin leads to glucose underutilisation, glucagon excess is the principal factor in diabetic glucose overproduction. A recent study reported that streptozotocin-treated glucagon receptor knockout mice have normal glucose tolerance. We investigated the impact of acute disruption of glucagon secretin or action in a mouse model of severe diabetes by three different approaches: (1) alpha cell elimination; (2) glucagon immunoneutralisation; and (3) glucagon receptor antagonism, in order to evaluate the effect of these on glucose tolerance.', 'Severe diabetes was induced in transgenic and wild-type mice by streptozotocin. Glucose metabolism was investigated using OGTT in transgenic mice with the human diphtheria toxin receptor expressed in proglucagon producing cells allowing for diphtheria toxin (DT)-induced alpha cell ablation and in mice treated with either a specific high affinity glucagon antibody or a specific glucagon receptor antagonist.', 'Near-total alpha cell elimination was induced in transgenic mice upon DT administration and resulted in a massive decrease in pancreatic glucagon content. Oral glucose tolerance in diabetic mice was neither affected by glucagon immunoneutralisation, glucagon receptor antagonism, nor alpha cell removal, but did not deteriorate further compared with mice with intact alpha cell mass.
Answer: Disruption of glucagon action/secretion did not improve glucose tolerance in diabetic mice. Near-total alpha cell elimination may have prevented further deterioration. Our findings support insulin lack as the major factor underlying hyperglycaemia in beta cell-deficient diabetes.
Does acute disruption of glucagon secretion or action improve glucose tolerance in an insulin-deficient mouse model of diabetes?
Context: Progenitor cells isolated from cardiac explant-derived cells improve cardiac function after myocardial infarction (MI). To fully realize the therapeutic potential of these cells, it is essential to develop a safe and efficient delivery method. Therefore, the objective of this study was to determine the efficacy of our newly developed approach to retrograde coronary vein (RCV) infusion of cardiac c-Kit(+) cells in a small-animal model of congestive heart failure (CHF).', 'Sprague-Dawley rats underwent experimental MI. After 21 days, cardiac explant-derived c-Kit(+) cells were delivered to both sham and CHF animals using RCV delivery. Vehicle-treated (serum-free medium) sham and CHF animals were used as controls. Cardiac function and heart tissues were evaluated 21 days post-transplantation.', 'RCV-delivered cells were retained in infarcted hearts for at least 21 days after transplantation. At 21 days post-RCV infusion, the majority of transplanted c-Kit(+)/GFP(+) cells were localized in the left ventricle. Compared with vehicle-treated CHF animals, RCV-treated rats showed a significant improvement in cardiac function. Furthermore, RCV-treated rats exhibited an increase in capillary density, a decrease in total heart collagen, and a reduction in both infarct size and cardiomyocyte hypertrophy when compared with vehicle-treated CHF rats.
Answer: Our study showed that the RCV infusion approach is an efficient technique for targeted cell delivery to the infarcted myocardium. Cardiac c-Kit(+) cells, delivered using RCV infusion ameliorated progression of heart failure, improved cardiac function and retarded myocardial remodeling in heart failure rats.
Does retrograde coronary vein infusion of cardiac explant-derived c-Kit+ cells improves function in ischemic heart failure?
Context: Sleep disturbance is the primary clinical morbidity of restless legs syndrome (RLS). To date, sleep disturbance in RLS has been measured in (1) clinical samples with polysomnography (PSG) or (2) population-based samples by self-report. The objective of this study was to analyze sleep by PSG in a population-based sample with symptoms of RLS.', 'Cross-sectional observational study.', 'Community-based.', '3433 older men and women.', 'None.', 'RLS was evaluated using an 8-item self-administered questionnaire based on NIH diagnostic criteria and required symptoms occurring > or = five times per month and associated with at least moderate distress. Health-related quality of life (HRQOL) was determined using the SF-36. Unattended, in-home PSG was performed. Data were assessed using general linear models with adjustment for demographic, health-related variables, and apnea-hypopnea index (AHI). Subjects with RLS had longer adjusted mean sleep latency (39.8 vs 26.4 min, P < 0.0001) and higher arousal index (20.1 vs 18.0, P = 0.0145) than those without RLS. Sleep latency increased progressively as the frequency of RLS symptoms increased from 5-15 days per month to 6-7 days per week. No differences in sleep stage percentages were observed between participants with and without RLS. Subjects with RLS also reported poorer HRQOL in all physical domains as well as in the Mental Health and Vitality domains.
Answer: These novel PSG data from a nonclinical, community-based sample of individuals with RLS document sleep disturbance in the home even in individuals with intermittent symptoms.
| Does polysomnographic and health-related quality of life correlate of restless legs syndrome in the Sleep Heart Health Study?
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Teacher: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.
Teacher: Now, understand the problem? Solve this instance: Context: Activin A and inhibin A have been found to be elevated in women without diabetes subsequently developing pre-eclampsia. The aim was to investigate whether activin A and inhibin A in serum were elevated in type I diabetic women after developing pre-eclampsia and, if so, were they clinically useful as predictors of pre-eclampsia.', 'In a prospective study, maternal serum was analyzed for activin A and inhibin A in 115 women with type 1 diabetes at 10, 14, 22, 28, and 33 weeks of gestation.', 'Fourteen women (12%) developed pre-eclampsia (26-37 weeks of gestation) and 101 did not. The two groups were comparable regarding age, body mass index, and diabetes duration. There was no difference between serum concentrations of activin A and inhibin A in women developing pre-eclampsia and women who did not at any gestational period.
Answer: Serum concentrations of activin A and inhibin A could not predict preeclampsia in type I diabetes.
Student: | Are serum levels of activin A and inhibin A related to the increased susceptibility to pre-eclampsia in type I diabetic pregnancies? | task845_pubmedqa_question_generation |
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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.
[Q]: Context: Adipose tissue is responsible for releasing various adipokines that have been related to insulin resistance. Understanding the relationship of these adipokines to insulin resistance may foster the development of new treatments for diabetes.', 'The primary objective of this study was to determine whether an association between retinol-binding protein 4 (RBP4) and insulin resistance exists in nonobese individuals without a family history or diagnosis of diabetes. The secondary objective was to determine by a dual energy x-ray absorptiometry scan which adipose tissue depot most closely relates to RBP4 levels.', 'Cross-sectional analysis of 92 study participants ranging in age from 20 to 83 yr was performed. The range of body mass index (BMI) was from 18 to 30 kg/m(2). Exclusion criteria were a BMI greater than 30 kg/m(2), family history of diabetes, or a diagnosis of diabetes. Insulin sensitivity was determined by a hyperinsulinemic euglycemic clamp. Body fat was measured by dual energy x-ray absorptiometry scan.', 'RBP4 values were lower in females (35.8 +/- 1.7 microg/ml) compared with males (39.9 +/- 1.4 microg/ml; P = 0.06). RBP4 levels were found to correlate negatively with insulin sensitivity (r = -0.32; P = 0.002) and positively with age (r = 0.38; P < 0.001). RBP4 levels did not correlate with BMI (r = -0.13; P = 0.22), trunk fat (r = 0.16; P = 0.22), or percent body fat (r = 0.07; P = 0.65). However, RBP4 levels did correlate with percent trunk fat (r = 0.36; P = 0.001).
Answer: These findings indicate a relationship between RBP4, insulin sensitivity, and percent trunk fat in individuals who may not have features of insulin resistance.
[A]: Is retinol-binding protein 4 associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes?
[Q]: Context: Serum ghrelin levels are elevated in uremic patients. However, no data are available on the relationship between metabolic syndrome and serum ghrelin levels in peritoneal dialysis (PD) patients.', 'Metabolic syndrome and its components were defined using diagnostic criteria recommended by the International Diabetes Federation. Fasting serum samples were taken from 30 PD patients. Serum ghrelin levels were measured by using a commercial enzyme-linked immunosorbent assay kit.', 'Of the 30 PD patients, 53.3% (16/30) had metabolic syndrome. Fasting serum ghrelin corrected inversely with metabolic syndrome among these PDs patients (p = 0.002). By odds ratio (OR) analysis of metabolic syndrome and metabolic syndrome diagnostic criteria, the predictors for metabolic syndrome are fasting glucose [OR: 39.00; 95% confidence interval (CI): 3.80 to 399.85; p < 0.001], triglycerides (OR: 37.50; 95% CI: 3.64 to 386.51; p < 0.001), and waist circumference (OR: 4.20; 95% CI: 1.95 to 9.03; p < 0.001). Univariate linear regression analysis showed that body weight (r = -0.461, p = 0.010), waist circumference (r = -0.390, p = 0.033), and body mass index (r = -0.438, p = 0.016) were negatively correlated with serum ghrelin, and serum high density lipoprotein [HDL (r = 0.626, p < 0.001)] was positively correlated with serum ghrelin. Multivariate forward stepwise linear regression analysis of the significant variables showed that HDL (R(2) change = 0.392; p < 0.001) was the independent predictor of serum ghrelin in PD patients and explained 39.2% of the variance.
Answer: These results indicate an inverse association between circulating fasting ghrelin and metabolic syndrome in PD patients. Serum HDL was associated with serum ghrelin among PD patients.
[A]: Is fasting serum ghrelin level associated with metabolic syndrome in peritoneal dialysis patients?
[Q]: Context: Donor-specific transfusion (DST) and a brief course of anti-CD154 monoclonal antibody (mAb) induces permanent islet and prolonged skin allograft survival in mice. Induction of skin allograft survival requires the presence of CD4 cells and deletion of alloreactive CD8 cells. The specific roles of CD4 and CD4CD25 cells and the mechanism(s) by which they act are not fully understood.', 'We used skin and islet allografts, a CD8 T cell receptor (TCR) transgenic model system, and in vivo depleting antibodies to analyze the role of CD4 cell subsets in regulating allograft survival in mice treated with DST and anti-CD154 mAb.', 'Deletion of CD4 or CD25 cells during costimulation blockade induced rapid rejection of skin but only minimally shortened islet allograft survival. Deletion of CD4 or CD25 cells had no effect upon survival of healed-in islet allografts, and CD25 cell deletion had no effect upon healed-in skin allograft survival. In the TCR transgenic model, DST plus anti-CD154 mAb treatment deleted alloreactive CD8 T cells, and anti-CD4 mAb treatment prevented that deletion. In contrast, injection of anti-CD25 mAb did not prevent alloreactive CD8 T cell deletion.
Answer: These data document that (1) both CD4CD25 and CD4CD25 cells are required for induction of skin allograft survival, (2) CD4CD25 T cells are not required for alloreactive CD8 T cell deletion, and (3) CD4CD25 regulatory cells are not critical for islet allograft tolerance. It appears that skin and islet transplantation tolerance are mediated by different CD4 cell subsets and different mechanisms.
[A]: | Is regulation of skin and islet allograft survival in mice treated with costimulation blockade mediated by different CD4+ cell subsets and different mechanisms?
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instruction:
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.
question:
Context: Loss-of-function mutations in the progranulin gene (PGRN) were identified in frontotemporal lobar degeneration (FTLD) with ubiquitin-immunoreactive neuronal inclusions (FTLD-U). We assessed whether PGRN also contributes to genetic risk for Alzheimer disease (AD) in an extended Belgian AD patient group (n = 779, onset age 74.7 +/- 8.7 years).', 'A mutation analysis of the PGRN coding region was performed. The effect of missense mutations was assessed using in silico predictions and protein modeling. Risk effects of common genetic variants were estimated by logistic regression analysis and gene-based haplotype association analysis.', 'We observed seven missense mutations in eight patients (1.3%). Convincing pathogenic evidence was obtained for two missense mutations, p.Cys139Arg and p.Pro451Leu, affecting PGRN protein folding and leading to loss of PGRN by degradation of the misfolded protein. In addition, we showed that PGRN haplotypes were associated with increased risk for AD.
Answer: Our data support a role for PGRN in patients with clinically diagnosed Alzheimer disease (AD). Further, we hypothesize that at least some PGRN missense mutations might lead to loss of functional protein. Whether the underlying pathology in our cases proves to be AD, frontotemporal lobar degeneration, or a combination of the two must await further investigations.
answer:
Does genetic variability in progranulin contribute to risk for clinically diagnosed Alzheimer disease?
question:
Context: We examined the effect of prior heating, by exercise and warm-water immersion, on core cooling rates in individuals rendered mildly hypothermic by immersion in cold water.', 'There were seven male subjects who were randomly assigned to one of three groups: 1) seated rest for 15 min (control); 2) cycling ergometry for 15 min at 70% Vo2 peak (active warming); or 3) immersion in a circulated bath at 40 degrees C to an esophageal temperature (Tes) similar to that at the end of exercise (passive warming). Subjects were then immersed in 7 degrees C water to a Tes of 34.5 degrees C.', 'Initial Tes cooling rates (initial approximately 6 min cooling) differed significantly among the treatment conditions (0.074 +/- 0.045, 0.129 +/- 0.076, and 0.348 +/- 0.117 degrees C x min(-1) for control, active, and passive warming conditions, respectively); however, secondary cooling rates (rates following initial approximately 6 min cooling to the end of immersion) were not different between treatments (average of 0.102 +/- 0.085 degrees C x min(-1)). Overall Tes cooling rates during the full immersion period differed significantly and were 0.067 +/- 0.047, 0.085 +/- 0.045, and 0.209 +/- 0.131 degrees C x min(-1) for control, active, and passive warming, respectively.
Answer: These results suggest that prior warming by both active and, to a greater extent, passive warming, may predispose a person to greater heat loss and to experience a larger decline in core temperature when subsequently exposed to cold water. Thus, functional time and possibly survival time could be reduced when cold water immersion is preceded by whole-body passive warming, and to a lesser degree by active warming.
answer:
Does warming by immersion or exercise affect initial cooling rate during subsequent cold water immersion?
question:
Context: To describe the novel use of a chorioretinal biopsy technique to confirm the microbiological diagnosis of endogenous Escherichia coli (E. coli) endophthalmitis, when other investigations have been proven nondiagnostic.', 'Case report of an 82-year-old white man with endogenous endophthalmitis without a clearly identifiable source of infection.', 'After systemic cultures and multiple aqueous and vitreous samples were unable to identify a causative organism, chorioretinal biopsy of a subretinal abscess was used to confirm the microbiological diagnosis. This ensured appropriate ophthalmic and systemic treatment of infection.
Answer: Endogenous E. coli endophthalmitis is a rare and aggressive condition usually seen in patients with insulin-dependent diabetes with concurrent urinary tract infection. This case demonstrates chorioretinal biopsy to be a viable and effective method of establishing a firm microbiological diagnosis in cases of culture-negative endophthalmitis.
answer:
| Do cHORIORETINAL BIOPSY FOR THE DIAGNOSIS OF ENDOGENOUS ENDOPHTHALMITIS DUE TO ESCHERICHIA COLI?
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Given the task definition and input, reply with output. 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.
Context: Obstructive sleep apnea (OSA) has been linked with erectile dysfunction (ED), but it is unknown whether this association is maintained in the presence of other risk factors for ED.', 'The aim of this study was to evaluate the relationship between ED/sexual dysfunction and polysomnographic measures of sleep apnea in patients with known risk factors for ED.', 'Prospective cross-sectional analysis of 401 male patients undergoing in-lab polysomnography for suspected OSA. Erectile (EF) and sexual function were assessed by the 15-item International Index of Erectile Function (IIEF-15) questionnaire.', 'Severity of OSA via apnea-hypopnea index (AHI) and mean/lowest nocturnal oxygen saturation (SaO(2)). The IIEF-15 including the sexual domains: EF, intercourse satisfaction, orgasmic function, sexual desire, and overall satisfaction.', 'OSA (AHI > 5/h) was diagnosed in 92% of patients. ED (EF subdomain < or = 25) was present in 69% of patients with, and 34% of patients without OSA (P < 0.001). Multivariate stepwise regression analyses including known risk factors for ED, such as age, obesity, coronary heart disease, peripheral occlusive disease, hypertension, diabetes, prostate surgery, and beta-blocker treatment, and measures of sleep apnea identified mean nocturnal SaO(2) as independently associated with ED (P = 0.002; mean [95% CI] normalized slope 0.126 [0.047; 0.205]). Age (P < 0.001), peripheral occlusive disease (P = 0.001), prostate surgery (P = 0.018), and hypertension (P = 0.021) were confirmed as risk factors for ED, but did not abolish the sleep apnea-associated risk. Similar results were obtained for sexual dysfunction. Logistic regression analysis using the diagnosis of ED (EF subdomain < or = 25) as binary dependent variable confirmed that mean nocturnal SaO(2) (P = 0.012), as well as age (P < 0.001) were independently associated with ED.
Answer: ED and overall sexual dysfunction were highly prevalent in patients with suspected OSA. Irrespective of known risk factors, mean nocturnal SaO(2) was an additional, independent correlate of these dysfunctions, suggesting that OSA-related intermittent nocturnal hypoxemia specifically contributes to their development.
| Is sleep apnea an independent correlate of erectile and sexual dysfunction? | task845_pubmedqa_question_generation |
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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.
Example input: Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
Example output: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Example explanation: The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
Q: Context: Impaired diabetes wound healing can often lead to serious complications and remains a major health concern due to the lack of effective therapeutic approaches. Compromised angiogenesis, disrupted growth factor and cytokine activity are all attributable to diabetic wound healing impairment. The skin-derived precursors (SKPs) have been shown to differentiate into vascular and nerve cells, both of which are crucial components for wound repair. Given their easy accessibility and multipotency, the SKPs were proposed as an ideal therapeutic candidate for diabetic wound healing. Since the efficacy of cell therapy is limited by poor cell survival, collagen sponge was employed for better SKPs delivery.', 'SKPs were isolated and transplanted directly to the wound areas of diabetic mice in the absence and presence of collagen sponge. The effects of SKPs and/or collagen sponge on diabetic wound healing were examined histologically as well as immunostaining of isolectin and α-SMA. Mechanisms via which the SKPs facilitate wound healing were then investigated by transplanting SKPs that have been pre-labelled with a fluorescence dye, Dil. Expression patterns of Dil and an SKP marker, nestin, was also examined.
Answer: Accelerated wound healing and enhanced local capillary regeneration could be observed 14 days after skin ablation from both SKPs and collagen sponge co-transplanted and collagen sponge only groups. Subsequent analyses further revealed superior pro-angiogenic effects from the SKP and collagen sponge co-delivered group, which are mainly attributable to in vivo transdifferentation and paracrine signalling of the SKPs.
A: | Does co-Transplantation of Skin-Derived Precursors and Collagen Sponge facilitate Diabetic Wound Healing by Promoting Local Vascular Regeneration? | task845_pubmedqa_question_generation |
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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: The ability to achieve significant donor engraftment without fully myeloablative conditioning has revolutionized allogeneic stem cell transplantation. These nonmyeloablative approaches may allow extension of this potentially curative modality to an increasing number of patients including those with non-malignant diseases. Although a number of regimens have been explored, the optimal means of conditioning has not been determined.', 'We previously demonstrated that rapamycin (RAPA) has the ability to promote T-cell tolerance even in the presence of costimulation. In the current study, we examine the ability of rapamycin or the calcineurin inhibitor cyclosporine A (CSA) to promote chimerism in a murine haploidentical bone marrow transplantation model. Mice were conditioned with 300 cGy and received either RAPA at 3 mg/kg/day IP, CSA at 20 mg/kg/day IP, or no immunosuppression starting on the day before the transplant and continued for 4 weeks.', 'There was no apparent toxicity, and animals maintained normal blood counts throughout. More importantly, long-term macrochimerism was observed only in the RAPA-treated group.
Answer: These results establish a simple, nontoxic, irradiation-based regimen that facilitates engraftment without ablation. This strategy may prove useful in nonmalignant disorders such as hemoglobinopathies in which moderate levels of donor chimerism could prove curative.
Output: Does low-dose radiation plus rapamycin promote long-term bone marrow chimerism?
Input: Consider Input: Context: The use of cultured keratinocyte (CK) allografts for burn wounds offers a potentially unlimited supply of skin. It is unknown, however, whether CK allografts induce rejection in vivo. This study investigated the induction of immune responsiveness to CK allografts as measured by mixed lymphocyte response and serum cytotoxic antibody.', 'Female CBA mice (n = 160) were randomized to four equal groups, each receiving a 3 cm2 flank graft of autologous CBA CK (Auto CK), allogeneic C57BL/6 CK (Allo CK), C57BL/6 full thickness skin (Allo FT), or Sham. Graft take was assessed by gross and histologic examinations. Unidirectional mixed lymphocyte response was measured with graft recipient and donor splenocytes by use of tritiated thymidine uptake. Stimulation indexes were calculated. Serum cytotoxic antibody was measured by coculturing graft recipient serum with donor splenocytes and rabbit complement and assessing resultant cell killing.', 'Overall graft take was 50% for Allo CK and 74% for Auto CK, Allo FT, but not Allo CK, were associated with significantly increased stimulation indexes compared with Auto CK and Sham (p < 0.01). Allo FT, but not Allo CK, resulted in elevated titers of alloantibody, reaching significant levels 10 days after grafting (p < 0.05).
Answer: CK allografts do not result in increased in vitro T cell responses or enhanced alloantibody formation, indicating that sensitization to major histocompatibility antigens by CK does not occur. These data suggest that CK allografts may provide a possible source of grafts for victims of large burn wounds.
Output: Do cultured keratinocyte allografts fail to induce sensitization in vivo?
Input: Consider Input: Context: Population studies have shown obesity and diabetes to be risk factors for atherosclerosis. We assessed changes in the common carotid arteries in rat models of obesity and diabetes without hypertension.', 'Twenty 30-week-old male spontaneously diabetic and obese model Otsuka Long-Evans Tokushima Fatty (OLETF) and 20 control Long-Evans Tokushima Otsuka (LETO) rats were used in the experiments. The animals were considered diabetic if the plasma glucose level peaked at >300 mg/dL and remained at >200 mg/dL for 120 minutes. Blood gas physiological parameters were continuously monitored under anesthesia, and the flow of the carotid artery was assessed with ultrasonography. All animals were sacrificed with an overdose of anesthesia at the end of the experiment. Sections of the middle portion of the internal carotid artery were cut and stained with hematoxylin and eosin to assess the overall morphology.', 'All OLETF rats were diabetic, and all LETO rats were non-diabetic. The physiological parameters did not differ significantly between the control and model rats, whereas the carotid artery wall thickness (19.3 ± 3.2 vs. 6.1 ± 4.5 μm) was significantly different between the two groups. The blood flow velocity in the common carotid artery determined using ultrasonography and color Doppler sonography was significantly increased during systole in the model rats compared with that observed in the control rats (203 ± 20.3 vs. 55.3 ± 21.4 cm/sec).
Answer: The OLETF rats were obese, and diabetes worsened the degree of carotid artery stenosis. These results indicate the possibility of new therapies for carotid artery stenosis in obese and diabetic patients.
| Output: Is carotid artery stenosis exacerbated in spontaneously obese model rats with diabetes?
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Detailed Instructions: 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.
Q: Context: The glycolysis-derived metabolite methylglyoxal has been linked to clinical microvascular complications, including diabetic nephropathy. We aimed to further investigate the hypothesis that methylglyoxal is involved in decline in renal function by assessing the associations between measures of renal function during a 6-year follow-up in 1481 people with screen-detected Type 2 diabetes, as part of the Danish arm of the ADDITION-Europe trial (ADDITION-DK).', 'Biobank serum samples collected at ADDITION-DK baseline (2001-2006) and follow-up (2009-2010) were used in the current analysis of methylglyoxal. We assessed cross-sectional baseline and longitudinal associations between methylglyoxal and urinary albumin-to-creatinine ratio (ACR) or estimated GFR (eGFR), and between methylglyoxal and categories of albuminuria or reduced eGFR.', 'Baseline methylglyoxal was positively associated with ACR at baseline (12% higher ACR per doubling in methylglyoxal levels), and change in methylglyoxal during 6 years of follow-up was inversely associated with change in eGFR (-1.6 ml/min/1.73 m
Answer: In a population of people with screen-detected Type 2 diabetes, we observed associations between methylglyoxal and markers of renal function: 6-year change in methylglyoxal was inversely associated with 6-year change in eGFR. Also, methylglyoxal at baseline was positively associated with ACR at baseline. Our study lends further support to a role for methylglyoxal in the pathogenesis of diabetic nephropathy.
A: | Is methylglyoxal associated with changes in kidney function among individuals with screen-detected Type 2 diabetes mellitus? | task845_pubmedqa_question_generation |
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Detailed Instructions: 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.
Q: Context: To investigate the impact of minimum tacrolimus (TAC) on new-onset diabetes mellitus (NODM) after liver transplantation (LT).', 'We retrospectively analyzed the data of 973 liver transplant recipients between March 1999 and September 2014 in West China Hospital Liver Transplantation Center. Following the exclusion of ineligible recipients, 528 recipients with a TAC-dominant regimen were included in our study. We calculated and determined the mean trough concentration of TAC (cTAC) in the year of diabetes diagnosis in NODM recipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value for predicting NODM 6 mo after LT was identified using a receptor operating characteristic curve. TAC-related complications after LT was evaluated by χ(2) test, and the overall and allograft survival was evaluated using the Kaplan-Meier method. Risk factors for NODM after LT were examined by univariate and multivariate Cox regression.', 'Of the 528 transplant recipients, 131 (24.8%) developed NODM after 6 mo after LT, and the cumulative incidence of NODM progressively increased. The mean cTAC of NODM group recipients was significantly higher than that of recipients in the non-NODM group (7.66 ± 3.41 ng/mL vs 4.47 ± 2.22 ng/mL, P < 0.05). Furthermore, NODM group recipients had lower 1-, 5-, 10-year overall survival rates (86.7%, 71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P < 0.05) and allograft survival rates (92.8%, 84.6%, and 75.7% vs 96.1%, 91%, and 86.1%, P < 0.05) than the others. The best cutoff of mean cTAC for predicting NODM was 5.89 ng/mL after 6 mo after LT. Multivariate analysis showed that old age at the time of LT (> 50 years), hypertension pre-LT, and high mean cTAC (≥ 5.89 ng/mL) after 6 mo after LT were independent risk factors for developing NODM. Concurrently, recipients with a low cTAC (< 5.89 ng/mL) were less likely to become obese (21.3% vs 30.2%, P < 0.05) or to develop dyslipidemia (27.5% vs 44.8%, P <0.05), chronic kidney dysfunction (14.6% vs 22.7%, P < 0.05), and moderate to severe infection (24.7% vs 33.1%, P < 0.05) after LT than recipients in the high mean cTAC group. However, the two groups showed no significant difference in the incidence of acute and chronic rejection, hypertension, cardiovascular events and new-onset malignancy.
Answer: A minimal TAC regimen can decrease the risk of long-term NODM after LT. Maintaining a cTAC value below 5.89 ng/mL after LT is safe and beneficial.
A: | Does minimizing tacrolimus decrease the risk of new-onset diabetes mellitus after liver transplantation? | task845_pubmedqa_question_generation |
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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.
Example Input: Context: High visceral adipose tissue (VAT) and high liver fat (LF) are associated with the metabolic syndrome and diabetes. We studied changes in these two fat depots during weight loss and analyzed whether VAT and LF at baseline predict the response to lifestyle intervention.', 'One hundred twelve subjects (48 men and 64 women; age, 46 +/- 11 years; BMI, 29.2 +/- 4.4 kg/m(2)) were studied after a follow up-time of 264 +/- 60 (SD) days. Insulin sensitivity was estimated from the oral glucose tolerance test. Body fat depots were quantified using magnetic resonance imaging and spectroscopy.', 'Cross-sectionally high VAT (r = -0.22, p = 0.02) and high LF (r = -0.36, p < 0.0001) were independently associated with low insulin sensitivity. With intervention, BMI (-3.0%), VAT (-12.0%), and LF (-33.0%) were reduced (all p < 0.001). Insulin sensitivity was improved (+17%, p < 0.01). The changes in BMI (r = -0.41), VAT (r = -0.28), and LF (r = -0.39) were associated with the increase in insulin sensitivity (all p < 0.01). High VAT (r = -0.28, p = 0.01) and high LF (r = -0.38, p < 0.01) at baseline were associated with a lesser increase in insulin sensitivity.
Answer: Baseline values and changes in BMI, VAT, and LF are related to changes in insulin sensitivity during lifestyle intervention. Subjects with high VAT and LF have a lower chance of profiting from lifestyle intervention and may require intensified lifestyle prevention strategies or even pharmacological approaches to improve insulin sensitivity.
Example Output: Are high visceral fat mass and high liver fat associated with resistance to lifestyle intervention?
Example Input: Context: Licorice has been used to treat many ailments including cardiovascular disorders in China for long time. Recent studies have shown that the cardiac actions of licorice have been attributed to its active component, glycyrretinic acid (GA). However, its mechanism remains poorly understood.', 'The effects of GA on the cardiac sodium currents (I(Na)), L-type calcium currents (I(Ca,L)) and hyperpolarization-activated inward currents (I(f)) were investigated.', 'Human isoforms of wild-type and DeltaKPQ-mutant type sodium channels were expressed in Xenopus oocytes, and the resulting currents (peak and late I(Na)) were recorded using a two-microelectrode voltage-clamp technique. A perforated patch clamp technique was employed to record I(Ca,L) and I(f) from isolated rabbit sinoatrial node pacemaker cells.', 'GA inhibited peak I(Na) (33% at 90 microM) and late I(Na) (72% at 90 microM), but caused no significant effects on I(Ca,L) and I(f).
Answer: GA blocked cardiac sodium currents, particularly late I(Na.) Our findings might help to understand the traditional use of licorice in the treatment of cardiovascular disorders, because reduction of sodium currents (particularly late I(Na)) would be expected to provide protection from Na(+)-induced Ca(2+) overload and cell damage.
Example Output: Does glycyrretinic acid block cardiac sodium channels expressed in Xenopus oocytes?
Example Input: Context: Fibroblast growth factors (FGFs) are crucial signaling molecules that direct the development of the vertebrate brain. FGF8 gene signaling in particular, may be important for the development of the hypothalamus-pituitary-adrenal (HPA)-axis. Indeed, newborn Fgf8 hypomorphic mice harbor a major reduction in the number of vasopressin (VP) neurons in the paraventricular nucleus (PVN), the central output component of the HPA-axis. Additionally, recent studies indicated that adult heterozygous ((+/neo)) Fgf8 hypomorphic mice exhibit more anxiety-like behaviors than wildtype (WT) mice. These studies led us to investigate whether Fgf8 hypomorphy abrogated VP and/or corticotropin-releasing hormone (CRH) neuronal development in the postnatal day (PN) 21 and adult mouse PVN. Furthermore, we studied whether Fgf8 hypomorphy disrupted HPA responsiveness in these mice.', 'Using immunohistochemistry, we examined the development of VP and CRH neurons located in the PVN of PN 21 and adult Fgf8 (+/neo) mice. Moreover, we used a restraint stress (RS) paradigm and measured corticosterone levels with enzyme immunoassays in order to assess HPA axis activation.', 'The number of VP neurons in the PVN did not differ between WT and Fgf8 (+/neo) mice on PN 21 and in adulthood. In contrast, CRH immunoreactivity was much higher in Fgf8 (+/neo) mice than in WT mice on PN 21, this difference was no longer shown in adult mice. RS caused a higher increase in corticosterone levels in adult Fgf8 (+/neo) mice than in WT mice after 15\xa0min, but no difference was seen after 45\xa0min.
Answer: First, Fgf8 hypomorphy did not eliminate VP and CRH neurons in the mouse PVN, but rather disrupted the postnatal timing of neuropeptide expression onset in PVN neurons. Second, Fgf8 hypomorphy may, in part, be an explanation for affective disorders involving hyperactivity of the HPA axis, such as anxiety.
Example Output: | Does fibroblast growth factor 8 regulate postnatal development of paraventricular nucleus neuroendocrine cells?
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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.
Example Input: Context: Molecular staging of sentinel lymph nodes (SLNs) may identify patients who are node-negative by standard microscopic staging but are at increased risk for regional nodal recurrence; such patients may benefit from completion lymph node dissection (CLND).', 'In a multicenter, randomized clinical trial, patients with tumor-negative SLNs by standard pathology (hematoxylin and eosin [H and E] serial sections and immunohistochemistry [IHC]) underwent reverse transcriptase polymerase chain reaction (PCR) analysis of SLNs for melanoma-specific mRNA. Microscopically negative/PCR+ patients were randomized to observation, CLND, or CLND with high-dose interferon (HDI). For this post-hoc analysis, clinicopathologic features and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were compared between PCR+ patients who underwent CLND vs observation. Microscopic and molecular node-negative (PCR-) patients were included for comparison.', 'A total of 556 patients were PCR+: 180 underwent observation, and 376 underwent CLND. An additional 908 PCR- patients were observed. Median follow-up was 72 months. Disease-free survival (DFS) was significantly better for PCR+ patients who underwent CLND compared with observation (p\xa0= 0.0218). No statistically significant differences in OS or distant disease-free survival (DDFS) were seen. Regional lymph node recurrence-free survival (LNRFS) was improved in PCR+ patients with CLND compared to observation (p\xa0=\xa00.0065). The PCR+ patients in the observation group had the worst DFS; those with CLND had similar DFS to that in the PCR- group (p\xa0= 0.9044).
Answer: Patients with microscopically negative/PCR+ SLN have an increased risk of nodal recurrence that was mitigated by CLND. Although CLND did not affect OS, these data suggest that molecular detection of melanoma-specific mRNA in the SLN predicts a greater risk of nodal recurrence and deserves further study.
Example Output: Does molecular Staging of Sentinel Lymph Nodes identify Melanoma Patients at Increased Risk of Nodal Recurrence?
Example Input: Context: High visceral adipose tissue (VAT) and high liver fat (LF) are associated with the metabolic syndrome and diabetes. We studied changes in these two fat depots during weight loss and analyzed whether VAT and LF at baseline predict the response to lifestyle intervention.', 'One hundred twelve subjects (48 men and 64 women; age, 46 +/- 11 years; BMI, 29.2 +/- 4.4 kg/m(2)) were studied after a follow up-time of 264 +/- 60 (SD) days. Insulin sensitivity was estimated from the oral glucose tolerance test. Body fat depots were quantified using magnetic resonance imaging and spectroscopy.', 'Cross-sectionally high VAT (r = -0.22, p = 0.02) and high LF (r = -0.36, p < 0.0001) were independently associated with low insulin sensitivity. With intervention, BMI (-3.0%), VAT (-12.0%), and LF (-33.0%) were reduced (all p < 0.001). Insulin sensitivity was improved (+17%, p < 0.01). The changes in BMI (r = -0.41), VAT (r = -0.28), and LF (r = -0.39) were associated with the increase in insulin sensitivity (all p < 0.01). High VAT (r = -0.28, p = 0.01) and high LF (r = -0.38, p < 0.01) at baseline were associated with a lesser increase in insulin sensitivity.
Answer: Baseline values and changes in BMI, VAT, and LF are related to changes in insulin sensitivity during lifestyle intervention. Subjects with high VAT and LF have a lower chance of profiting from lifestyle intervention and may require intensified lifestyle prevention strategies or even pharmacological approaches to improve insulin sensitivity.
Example Output: Are high visceral fat mass and high liver fat associated with resistance to lifestyle intervention?
Example Input: Context: High-risk neuroblastoma (Nb) is incurable using current treatment regimens in the majority of patients. Oncolytic virotherapy is a novel approach being tested for several types of adult cancers.', 'To compare the susceptibility of Nb tumor models to oncolytic adenovirus and HSV mutants and delineate the mechanisms of resistance or sensitivity.', 'Human Nb cell lines were used to determine susceptibility to adenovirus type 5 wild-type and HSV1 mutant (NV1066) infection, adenovirus receptor expression, support of NV1066 replication, and induction of apoptosis. Human xenograft tumors in immunodeficient mice were evaluated for histological effects and tumor response to intratumoral injection of an oncolytic HSV mutant.', 'All eight Nb cell lines tested in culture were relatively resistant to infection with wild type and attenuated adenoviruses. Cells expressed the cocksackie-adenovirus attachment receptor (CAR) but had low or absent expression of the internalization receptors (alphavbeta3, alphavbeta5 integrins). In contrast, all cells were uniformly sensitive to infection with the attenuated HSV mutant, NV1066. Productive virus replication and induction of apoptosis were observed in HSV-infected cells. CHLA-20 and LAN-5 xenograft tumors injected with a single dose of NV1066 showed a significant antitumor response, and the animals had a prolonged survival post infection in comparison to the PBS-treated control group. HSV injected tumors showed extensive areas of necrosis and morphologic evidence of apoptosis.
Answer: Nb tumor models are resistant to adenovirus mediated oncolysis but highly sensitive to HSV mediated oncolysis. Further studies of HSV virotherapy as a novel treatment for Nb are warranted.
Example Output: | Are oncolytic herpes simplex virus mutants more efficacious than wild-type adenovirus Type 5 for the treatment of high-risk neuroblastomas in preclinical models?
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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.
Ex Input:
Context: The etiology of reduced left ventricular (LV) ejection fraction after exercise, without obstructive coronary artery disease or other established causes, is unclear. The aims of this study were to determine whether patients undergoing treadmill stress echocardiography with this abnormal LV contractile response to exercise (LVCRE) without established causes have resting LV long-axis dysfunction or microvascular dysfunction and to determine associations with this abnormal LVCRE.', 'Of 5,275 consecutive patients undergoing treadmill stress echocardiography, 1,134 underwent cardiac computed tomography angiography or invasive angiography. Having excluded patients with obstructive coronary artery disease, hypertensive response, submaximal heart rate response, resting LV ejection fraction < 50%, and valvular disease, 110 with "abnormal LVCRE" and 212 with "normal LVCRE" were analyzed. Resting mitral annular velocities were measured to assess LV long-axis function. Myocardial blush grade and corrected Thrombolysis In Myocardial Infarction frame count were determined angiographically to assess microvascular function.', "Comparing normal LVCRE with abnormal LVCRE, age (mean, 59.7 ± 11.1 vs 61.4 ± 10.0 years), hypertension (53% vs 55%), diabetes (16% vs 20%), and body mass index (mean, 29.1 ± 5.4 vs 29.5 ± 6.4 kg/m(2)) were similar (P > .05). Abnormal LVCRE had reduced resting LV long-axis function with lower septal (mean, 6.1 ± 1.9 vs 7.7 ± 2.2 cm/sec) and lateral (mean, 8.1 ± 2.9 vs 10.4 ± 3.0 cm/sec) e' velocities (P < .001) and larger resting left atrial volumes (mean, 37.3 ± 10.1 vs 31.1 ± 7.2 mL/m(2), P < .001). On multivariate analysis, female gender (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.15-1.99; P < .001), exaggerated chronotropic response (OR, 1.49; 95% CI, 1.09-2.05; P < .001), resting left atrial volume (OR, 2.38; 95% CI, 1.63-3.47; P < .001), and resting lateral e' velocity (OR, 1.70; 95% CI, 1.22-2.49; P = .003) were associated with abnormal LVCRE, but not myocardial blush grade or corrected Thrombolysis In Myocardial Infarction frame count.
Answer: An abnormal LVCRE in the absence of established causes is associated with resting LV long-axis dysfunction and is usually seen in women.
Ex Output:
Is abnormal left ventricular contractile response to exercise in the absence of obstructive coronary artery disease associated with resting left ventricular long-axis dysfunction?
Ex Input:
Context: Compared with standard donors, kidneys recovered from donors after cardiac death (DCD) exhibit higher rates of delayed graft function (DGF), and DCD livers demonstrate higher rates of biliary ischemia, graft loss, and worse patient survival. Current practice limits the use of these organs based on time from donor extubation to asystole, but data to support this is incomplete. We hypothesized that donor postextubation parameters, including duration and severity of hemodynamic instability or hypoxia might be a better predictor of subsequent graft function.', 'We performed a retrospective examination of the New England Organ Bank DCD database, concentrating on donor factors including vital signs after withdrawal of support.', 'Prolonged, severe hypotension in the postextubation period was a better predictor of subsequent organ function that time from extubation to asystole. For DCD kidneys, this manifested as a trend toward increased DGF. For DCD livers, this manifested as increased rates of poor outcomes. Maximizing the predictive value of this test in the liver cohort suggested that greater than 15 min between the time when the donor systolic blood pressure drops below 50 mm Hg and flush correlates with increased rates of diffuse biliary ischemia, graft loss, or death. Donor age also correlated with worse outcome.
Answer: Time between profound instability and cold perfusion is a better predictor of outcome than time from extubation to asystole. If validated, this information could be used to predict DGF after DCD renal transplant and improve outcomes after DCD liver transplant.
Ex Output:
Do donor postextubation hypotension and age correlate with outcome after donation after cardiac death transplantation?
Ex Input:
Context: Systemic lupus erythematosus (SLE) is characterised by the presence of antibodies to double stranded DNA (dsDNA), which are involved in the pathogenesis of SLE. Previous studies showed that at least two thirds of patients develop a clinical relapse within six months after a significant rise in the anti-dsDNA level, and most relapses were prevented by the administration of corticosteroids at the time of the rise.', 'To determine whether mofetil mycophenolate (MMF) can prevent a clinical relapse without the side effects associated with corticosteroids.', '36 patients with SLE were examined monthly to determine whether a rise in anti-dsDNA level had occurred. A rise was defined as an increase of 25% of the level of the previous sample of at least 15 IU/ml within a four month period. After a rise patients were treated with MMF 2000 mg daily for six months. Patients were monitored monthly for the occurrence of a clinical relapse and to assess the serological activity and state of activation of CD4+, CD8+, and CD19+ lymphocyte subsets.', 'Anti-dsDNA rose in 10 patients. Treatment with MMF was started in all these patients, and after six months no clinical relapse had occurred. Side effects were minimal. Antibodies to dsDNA decreased during the treatment (p<0.001), associated with a decrease in the state of activation of CD19+ lymphocytes. No changes were found in the state of activation of CD4+ or CD8+ lymphocyte subsets.
Answer: Administration of MMF after a rise in antibodies to dsDNA is well tolerated, decreases anti-dsDNA and B cell activation, and seems to prevent the occurrence of a clinical relapse in patients with SLE.
Ex Output:
| Does mycophenolate mofetil prevent a clinical relapse in patients with systemic lupus erythematosus at risk?
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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.
[Q]: Context: To assess, in a retrospective cohort, urinary tract urothelial carcinoma (UT-UC) in patients with various stages of chronic kidney disease (CKD) and their clinicopathological features, as patients with end-stage renal disease (ESRD) have a higher incidence of UT-UC, but the relationship between early stages of CKD and characteristics of UT-UC are less well known.', 'The study included 267 patients with pathologically confirmed UT-UC from January 1994 to December 2006; all had a physical examination (blood pressure), and measurements of laboratory data (serum creatinine, serum haemoglobin) and pathological data. The glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease equation. Patients were divided into three groups by individual GFR (mL/min), i.e. >60 (no/mild CKD), 30-60 (CKD stage 3) and <30 (CKD stage 4/5).', 'The CKD stages included 81 (30.3%) patients with none/mild CKD, 121 (45.3%) with CKD stage 3 and 65 (24.3%) with CKD stage 4/5. There was a significant and parallel increase in the frequency of UT-UC as CKD severity increased from none/mild CKD to stage 3 (11% vs 55%), and from CKD stage 3 to 4/5 (55% vs 71%; P < 0.05). Pathologically, the frequency of high-grade and high T stage UT-UC in patients with CKD stage 3 (90% and 35%, respectively) and CKD stage 4/5 (91% and 29%, respectively) were significantly greater than in the group with none/mild CKD (P < 0.001). Advanced age and more distant metastasis were independent risk factors for patient survival.
Answer: The aggressiveness of UT-UC increased with the severity of CKD, and this might have important clinical consequences.
[A]: Does the aggressiveness of urinary tract urothelial carcinoma increase with the severity of chronic kidney disease?
[Q]: Context: TECPR2 was first described as a disease causing gene when the c.3416delT frameshift mutation was found in five Jewish Bukharian patients with similar features. It was suggested to constitute a new subtype of complex hereditary spastic paraparesis (SPG49).', 'We report here 3 additional patients from unrelated non-Bukharian families, harboring two novel mutations (c.1319delT, c.C566T) in this gene. Accumulating clinical data clarifies that in addition to intellectual disability and evolving spasticity the main disabling feature of this unique disorder is autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events.
Answer: We suggest that the disease should therefore be classified as a new subtype of hereditary sensory-autonomic neuropathy. The discovery of additional mutations in non-Bukharian patients implies that this disease might be more common than previously appreciated and should therefore be considered in undiagnosed cases of intellectual disability with autonomic features and respiratory symptoms regardless of demographic origin.
[A]: Do tECPR2 mutations cause a new subtype of familial dysautonomia like hereditary sensory autonomic neuropathy with intellectual disability?
[Q]: Context: Korean red ginseng (ginseng, Panax ginseng C.A. Meyer) has traditionally been used in the treatment of most ageing-related diseases, such as obesity, diabetes, and dyslipidemia, but the mechanism of the effects is unclear. The aim of this study was to determine the effects of ginseng on obesity in a mouse model of female obesity (obese female db/db mouse) and to investigate the mechanism of anti-obesity effects.', 'After female db/db (B6.Cg-m Lepr(db)/++/J) mice were treated with 5% (w/w) ginseng for 13 weeks, variables and parameters of obesity and disorders related to obesity were examined. Blood vessel density and the expression of genes involved in angiogenesis were also measured.', 'Mice treated with ginseng for 13 weeks had less body weight and lower adipose tissue mass compared to control, untreated mice. The size of adipocytes was smaller in visceral adipose tissues of ginseng-treated mice. Obesity-related complications, such as hepatic steatosis, hypertriglyceridemia, and hyperglycemia, were markedly improved in treated mice. Blood vessel density was lower in visceral adipose tissue sections from treated mice than those from control mice. Concomitantly, mRNA levels for VEGF-A and FGF-2 were lower in both visceral adipose tissue from treated mice and treated 3T3-L1 cells compared to those from untreated controls. Protein levels for VEGF were also lower in visceral adipose tissue from treated mice. In contrast, ginseng increased mRNA expression of genes responsible for energy expenditure and fatty acid β-oxidation in visceral adipose tissue during ginseng-induced weight reduction.
Answer: These results suggest that ginseng may effectively treat female obesity and related disorders in part by inhibition of angiogenesis.
[A]: | Does ginseng treatment reverse obesity and related disorders by inhibiting angiogenesis in female db/db mice?
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Instructions: 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: Context: Intestinal transport exhibits distinct diurnal rhythmicity. Understanding the mechanisms behind this may reveal new therapeutic strategies to modulate intestinal function in disease states such as diabetes and obesity, as well as short bowel syndrome. Although diurnal rhythms have been amply documented for several intestinal transporters, the complexity of transepithelial transport has precluded definitive attribution of rhythmicity in glucose uptake to a single transporter. To address this gap, we assessed temporal changes in glucose transport mediated by the Na(+)/glucose cotransporter SGLT1.', 'SGLT1 expression was assessed at 4 times during the day: ZT3, ZT9, ZT15, and ZT21 (ZT, Zeitgeber time; lights on at ZT0; n = 8/ time). SGLT1 activity, which is defined as glucose uptake sensitive to the specific SGLT1 inhibitor phloridzin, was measured in everted intestinal sleeves. Changes in Sglt1 expression were assessed by real-time polymerase chain reaction (PCR) and immunoblotting.', 'Glucose uptake was significantly higher at ZT15 in jejunum (P < 0.05 vs ZT3). Phloridzin significantly reduced glucose uptake and completely abolished its rhythmicity. Sglt1 mRNA levels were significantly greater at ZT9 and ZT15 in jejunum and ileum, respectively (P < 0.05 vs ZT3), whereas SGLT1 protein levels were significantly greater at ZT15 in jejunum (P < 0.05 vs ZT3).
Answer: Our results definitively link diurnal changes in intestinal glucose uptake capacity to changes in both SGLT1 mRNA and protein. These findings suggest that modulation of transporter expression would enhance intestinal function and provide an impetus to elucidate the mechanisms that underlie diurnal rhythmicity in transcription. Modulation of intestinal function would benefit the management of malnutrition as well as diabetes and obesity.
Output: | Is diurnal rhythmicity in glucose uptake mediated by temporal periodicity in the expression of the sodium-glucose cotransporter ( SGLT1 )? | task845_pubmedqa_question_generation |
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Detailed Instructions: 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.
Problem:Context: Re-stenosis after percutaneous coronary angioplasty (PTCA) is related to clinical and angiographic features.', 'To describe the clinical and angiographic characteristic of our patients with coronary cardiopathy subjected to PTCA and the predictor factors for re-stenosis.', 'We gathered the clinical and angiographic characteristics of all patients who underwent a successful PTCA of a native coronary artery. All patients had a clinical assessment one year after the procedure. Patients were classified in Group 1, if they did not have angina or coronary events after the angioplasty or Group 2, if they had angina or a coronary event after the procedure. Only Group 2 patients were subjected to a coronary angiogram.', 'We collected 383 PTCA procedures. Follow up information was obtained in 92.2%. Three hundred forty two patients (89.3%) were assessed one year the procedure. Nine patients (2.3%) died of a cardiovascular cause. Ninety patients (26.3%) were classified in Group 2. In 65 patients, angiographic re-stenosis was demonstrated (19%). Re-stenosis occurred in 36 and 13% of patients with an without Diabetes Mellitus, respectively (p <0.01). The other clinical predictor variables were a history of myocardial infarction (p =0.007), obesity (p =0.041) and hypercholesterolemia (p =0.050). None of the angiographic characteristics predicted restenosis. Stents were protective factors against restenosis (15.6% in stented lesions vs 25.4% in nonstented; p =0.01).
Answer: Re-stenosis after angioplasty occurred in 19% of our patients with angina or coronary events. The clinical variables associated with a higher risk of re-stenosis were diabetes (the main risk factor), previous myocardial infarction, obesity and hypercholesterolemia. Angiographic variables were not associated with re-stenosis. The use of stents decreases the incidence of re-stenosis in all groups).
Solution: | Do [ One year follow up of successful coronary angioplasty in non selected patients ]? | task845_pubmedqa_question_generation |
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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.
Example Input: Context: Women with a family history of breast cancer face considerable uncertainty about whether to pursue standard screening, intensive screening, or prophylactic surgery. Accurate and individualized risk-estimation approaches may help these women make more informed decisions. Although highly penetrant genetic variants have been associated with familial breast cancer (FBC) risk, many individuals do not carry these variants, and many carriers never develop breast cancer. Common risk variants have a relatively modest effect on risk and show limited potential for predicting FBC development. As an alternative, we hypothesized that additional genomic data types, such as gene-expression levels, which can reflect genetic and epigenetic variation, could contribute to classifying a person's risk status. Specifically, we aimed to identify common patterns in gene-expression levels across individuals who develop FBC.", 'We profiled peripheral blood mononuclear cells from women with a family history of breast cancer (with or without a germline BRCA1/2 variant) and from controls. We used the support vector machines algorithm to differentiate between patients who developed FBC and those who did not. Our study used two independent datasets, a training set of 124 women from Utah (USA) and an external validation (test) set from Ontario (Canada) of 73 women (197 total). We controlled for expression variation associated with clinical, demographic, and treatment variables as well as lymphocyte markers.', 'Our multigene biomarker provided accurate, individual-level estimates of FBC occurrence for the Utah cohort (AUC = 0.76 [0.67-84]) . Even at their lower confidence bounds, these accuracy estimates meet or exceed estimates from alternative approaches. Our Ontario cohort resulted in similarly high levels of accuracy (AUC = 0.73 [0.59-0.86]), thus providing external validation of our findings. Individuals deemed to have "high" risk by our model would have an estimated 2.4 times greater odds of developing familial breast cancer than individuals deemed to have "low" risk.
Answer: Together, these findings suggest that gene-expression levels in peripheral blood cells reflect genomic variation associated with breast cancer risk and that such data have potential to be used as a non-invasive biomarker for familial breast cancer risk.
Example Output: Do gene-expression patterns in peripheral blood classify familial breast cancer susceptibility?
Example Input: Context: Anemia is an established adverse risk factor in cardiovascular disease. However, the effect of preoperative anemia is not well defined in heart surgery. This study evaluates the effect of preoperative anemia on early clinical outcomes in patients undergoing cardiac surgery.', 'A retrospective, observational, cohort study of prospectively collected data was undertaken on 7,738 consecutive patients undergoing heart surgery between April 2003 and February 2009. Of these, 1,856 patients with preoperative anemia were compared to 5,882 patients without anemia (control group). According to the World Health Organization, anemia was defined as hemoglobin level\u2009<\u200913 g/dl for men and <12 g/dl for women. Selection bias not controlled by multivariable methods was assessed with propensity-adjustment method.', 'Overall mortality was 2.1%. Preoperative anemia was associated with tripling in the risk of death (4.6% vs 1.5%, p\u2009<\u20090.0001) and postoperative renal dysfunction (18.5% vs 6.5%, p\u2009<\u20090.0001). There was also a significant difference between the anemic and non-anemic group in the risk of postoperative stroke (1.9% vs 1.1%, p\u2009=\u20090.008), atrial fibrillation (36.7% vs 33%, p\u2009=\u20090.003) and length of hospital stay\u2009>\u20097 days (54% vs 36.7%, p\u2009<\u20090.0001). In propensity-adjusted, multivariable logistic regression, preoperative anemia was an independent predictor of mortality (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.02 to 2.03), postoperative renal dysfunction (OR 1.73, 95% CI 1.43 to 2.1) and length of hospital stay\u2009>\u20097 days (OR 1.3, 95% CI 1.15 to 1.47).
Answer: In patients undergoing heart surgery, preoperative anemia is associated with an increased risk of mortality and postoperative morbidity.
Example Output: Does preoperative anemia increase mortality and postoperative morbidity after cardiac surgery?
Example Input: Context: Impaired diabetes wound healing can often lead to serious complications and remains a major health concern due to the lack of effective therapeutic approaches. Compromised angiogenesis, disrupted growth factor and cytokine activity are all attributable to diabetic wound healing impairment. The skin-derived precursors (SKPs) have been shown to differentiate into vascular and nerve cells, both of which are crucial components for wound repair. Given their easy accessibility and multipotency, the SKPs were proposed as an ideal therapeutic candidate for diabetic wound healing. Since the efficacy of cell therapy is limited by poor cell survival, collagen sponge was employed for better SKPs delivery.', 'SKPs were isolated and transplanted directly to the wound areas of diabetic mice in the absence and presence of collagen sponge. The effects of SKPs and/or collagen sponge on diabetic wound healing were examined histologically as well as immunostaining of isolectin and α-SMA. Mechanisms via which the SKPs facilitate wound healing were then investigated by transplanting SKPs that have been pre-labelled with a fluorescence dye, Dil. Expression patterns of Dil and an SKP marker, nestin, was also examined.
Answer: Accelerated wound healing and enhanced local capillary regeneration could be observed 14 days after skin ablation from both SKPs and collagen sponge co-transplanted and collagen sponge only groups. Subsequent analyses further revealed superior pro-angiogenic effects from the SKP and collagen sponge co-delivered group, which are mainly attributable to in vivo transdifferentation and paracrine signalling of the SKPs.
Example Output: | Does co-Transplantation of Skin-Derived Precursors and Collagen Sponge facilitate Diabetic Wound Healing by Promoting Local Vascular Regeneration?
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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.
Context: In patients with moderate-to-severe psoriasis, health-related quality of life (HRQOL) has been shown to improve in parallel with improvement in disease severity.', 'To evaluate the role of pruritus (itch) in mediating the relationship between improvements in disease severity and HRQOL.', 'Data from a phase 2 clinical trial, in which 142 patients with moderate-to-severe plaque psoriasis received ixekizumab or placebo, were used for this posthoc analysis. Relationships between improvement in Psoriasis Area and Severity Index (PASI), Itch Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI), as well as in individual DLQI domains (symptoms and feelings, treatment, work and school, daily activities, leisure, and personal relationships) from baseline to week 16 were determined. Multiple hierarchical linear regressions and Sobel tests were conducted to evaluate the results.', 'Improvement in PASI was highly correlated with pruritus improvement and improvements in DLQI total and domain scores at week 16 (P\xa0<\xa00·01). Multiple hierarchical linear regression analyses showed a statistically significant (P\xa0<\xa00·01) association between improvement in pruritus and improvement in DLQI total score and each of the six DLQI domain scores after adjusting for improvement in PASI. Sobel tests indicated that pruritus had a significant mediation effect (P\xa0<\xa00·05) on the association of PASI improvement with improvement in DLQI total score and all domains except the personal relationships score.
Answer: Pruritus appears to be an important mediator of the association between improvements in disease severity and HRQOL in patients with moderate-to-severe psoriasis.
Is itching a significant problem and a mediator between disease severity and quality of life for patients with psoriasis : results from a randomized controlled trial?
Context: Elevated levels of B-type natriuretic peptide (BNP) are associated with adverse clinical outcomes in acute coronary syndrome (ACS), but several questions remain outstanding. Firstly, it has not yet been determined whether an additional BNP sample at 7 weeks post ACS would enhance risk prediction. Secondly, we assessed whether the prognostic potential of BNP in ACS could be explained by echocardiographic abnormalities such as left ventricular hypertrophy (LVH).', 'We measured bedside BNP levels in 443 consecutive patients presenting with ACS and at 7 weeks outpatient follow-up. Main outcome measure was either all-cause mortality, readmission with ACS, or congestive heart failure) at 10 months from presentation.', 'Of the 443 patients, 120 patients presented with ST-elevation myocardial infarction (27%). There were 90 cardiovascular (CV) events at 10 months. Adjusting for age, sex, hypertension, diabetes mellitus, smoking status, renal dysfunction, left ventricular ejection fraction, and echocardiographic LVH elevated near patient BNP levels (>80 pg/mL) were still associated with subsequent CV events when measured on admission (adjusted relative risk [RR] 2.63 [95% CI 1.34-5.19)] and also at 7 weeks post ACS (adjusted RR 4.12 [95% CI 1.58-10.72]). Patients with persistent BNP elevation at 7 weeks were also at an increased risk of CV events compared to those with an initial high BNP which then fell (unadjusted RR 4.04 [95% CI 1.24-13.15]).
Answer: In ACS, bedside BNP levels predict CV events at 10 months, independent of many echocardiographic abnormalities including LVH. Furthermore, our study suggests that an additional 7 weeks post ACS BNP enhances risk stratification over and above a one-off high BNP at baseline.
Does serial bedside B-type natriuretic peptide strongly predict prognosis in acute coronary syndrome independent of echocardiographic abnormalities?
Context: Although N(2)O has been widely used as an anaesthetic adjuvant its effect on electroencephalographic (EEG) activity is poorly understood because it is usually studied in the presence of additional anaesthetics, including inhaled anaesthetics. We examined the EEG effects of N(2)O in rats using a hyperbaric chamber that permitted N(2)O to be the sole anaesthetic.', 'Rats (n=10) were anaesthetized with isoflurane and EEG activity was recorded from skull screws. The rats were placed into a hyperbaric chamber and mechanically ventilated. Isoflurane was eliminated while the chamber was pressurized with N(2)O. The minimum alveolar concentration (MAC) was determined in five rats by adjusting the chamber pressure and N(2)O concentration, and applying a tetanic noxious stimulus to the tail via an electrical pass-through. EEG responses to noxious stimulation (20 electrical pulses at 40 V applied to the tail at 0.1, 1 and 3 Hz, and 50 Hz tetanic stimulation at 60 mA applied for 30 s) were determined at 1.5 and 2 atm N(2)O.', 'The N(2)O MAC was 1.7+/-0.1 atm. No consistent EEG activation occurred during electrical stimulation at either partial pressure of N(2)O, although spontaneous EEG activation often occurred. Blood pressure increased after the 3 and 50 Hz stimuli. Four other rats anaesthetized with isoflurane had EEG activation with the 3 and 50 Hz stimuli.
Answer: These data indicate that N(2)O at peri-MAC partial pressures prevents EEG activation resulting from noxious electrical stimulation. Unlike the situation with isoflurane, stimulus-evoked EEG activation did not occur at peri-MAC anaesthetic concentrations, suggesting that N(2)O potently blocked ascending nociceptive transmission.
| Does nitrous oxide depress electroencephalographic responses to repetitive noxious stimulation in the rat?
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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: Normal glucose metabolism depends on pancreatic secretion of insulin and glucagon. The bihormonal hypothesis states that while lack of insulin leads to glucose underutilisation, glucagon excess is the principal factor in diabetic glucose overproduction. A recent study reported that streptozotocin-treated glucagon receptor knockout mice have normal glucose tolerance. We investigated the impact of acute disruption of glucagon secretin or action in a mouse model of severe diabetes by three different approaches: (1) alpha cell elimination; (2) glucagon immunoneutralisation; and (3) glucagon receptor antagonism, in order to evaluate the effect of these on glucose tolerance.', 'Severe diabetes was induced in transgenic and wild-type mice by streptozotocin. Glucose metabolism was investigated using OGTT in transgenic mice with the human diphtheria toxin receptor expressed in proglucagon producing cells allowing for diphtheria toxin (DT)-induced alpha cell ablation and in mice treated with either a specific high affinity glucagon antibody or a specific glucagon receptor antagonist.', 'Near-total alpha cell elimination was induced in transgenic mice upon DT administration and resulted in a massive decrease in pancreatic glucagon content. Oral glucose tolerance in diabetic mice was neither affected by glucagon immunoneutralisation, glucagon receptor antagonism, nor alpha cell removal, but did not deteriorate further compared with mice with intact alpha cell mass.
Answer: Disruption of glucagon action/secretion did not improve glucose tolerance in diabetic mice. Near-total alpha cell elimination may have prevented further deterioration. Our findings support insulin lack as the major factor underlying hyperglycaemia in beta cell-deficient diabetes.
Output: Does acute disruption of glucagon secretion or action improve glucose tolerance in an insulin-deficient mouse model of diabetes?
Input: Consider Input: Context: Despite advances in the diagnosis and management of idiopathic noncirrhotic portal hypertension, its pathogenesis remains elusive. Insight may be gained from study of early-onset familial idiopathic noncirrhotic portal hypertension, in which Mendelian mutations may account for disease. We performed exome sequencing of eight subjects from six kindreds with onset of portal hypertension of indeterminate etiology during infancy or childhood. Three subjects from two consanguineous families shared the identical rare homozygous p.N46S mutation in DGUOK, a deoxyguanosine kinase required for mitochondrial DNA replication; haplotype sharing demonstrated that the mutation in the two families was inherited from a remote common ancestor. All three affected subjects had stable portal hypertension with noncirrhotic liver disease for 6-16 years of follow-up. This mutation impairs adenosine triphosphate binding and reduces catalytic activity. Loss-of-function mutations in DGUOK have previously been implicated in cirrhosis and liver failure but not in isolated portal hypertension. Interestingly, treatment of patients with human immunodeficiency viral infection with the nucleoside analogue didanosine is known to cause portal hypertension in a subset of patients and lowers deoxyguanosine kinase levels in vitro; the current findings implicate these effects on deoxyguanosine kinase in the causal mechanism.
Answer: Our findings provide new insight into the mechanisms mediating inherited and acquired noncirrhotic portal hypertension, expand the phenotypic spectrum of DGUOK deficiency, and provide a new genetic test for a specific cause of idiopathic noncirrhotic portal hypertension. (Hepatology 2016;63:1977-1986).
Output: Does recurrent recessive mutation in deoxyguanosine kinase cause idiopathic noncirrhotic portal hypertension?
Input: Consider Input: Context: The aim of this study was to evaluate the frequency of sympathetic versus parasympathetic neuropathy among type 1 and type 2 diabetic patients.', 'There were 43 patients with type 1 and 17 with type 2 diabetes who were investigated. Sympathetic nerve function was assessed by measurement of the vasoconstriction (VAC) index by laser Doppler perfusion imaging of a locally heated finger followed by indirect cooling. Parasympathetic nerve function was assessed by R-R interval variation during deep breathing as measured by the expiration/inspiration (E/I) ratio. Results were expressed as age-corrected z scores in SD; VAC index >1.64 SD and E/I ratio <-1.64 SD were considered abnormal.', 'VAC index was abnormal in 40% with type 1 and 41% with type 2 diabetes, whereas the E/I ratio was abnormal in 42% with type 1 and 65% with type 2 diabetes. There was a clear association between VAC index and E/I ratio among type 1 (rs=0.525; P=0.0002) but not among type 2 (rs=0.10) diabetic patients. Among type 2 diabetic patients, the degree of dysfunction was most severe regarding parasympathetic function (P=0.0167).
Answer: Sympathetic and parasympathetic neuropathy were frequent in both type 1 and type 2 diabetic patients. However, there was a difference between the two types of diabetes. Sympathetic and parasympathetic nerve functions correlated in type 1 but not in type 2 diabetic patients. The explanation for this discrepancy might be that parasympathetic nerve function was most severely affected among type 2 diabetic patients.
| Output: Are sympathetic and parasympathetic neuropathy frequent in both type 1 and type 2 diabetic patients?
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Teacher: 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.
Teacher: Now, understand the problem? If you are still confused, see the following example:
Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
Solution: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Reason: The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
Now, solve this instance: Context: To measure the serum highly sensitive C-reactive protein (hs-CRP) and adiponectin levels, assess insulin sensitivity index (SI) and acute insulin response (AIR) in normal control (NC) subjects, patients with impaired glucose tolerance (IGT) and newly diagnosed type 2 diabetes mellitus (DM), and further explore the possible correlation between hs-CRP and SI, AIR and adiponectin in IGT and newly diagnosed type 2 DM groups.', "Age and sex matched 28 normal subjects, 31 patients with IGT, and 31 patients with newly diagnosed type 2 DM were included in the study. SI and AIR were assessed by the reduced sample number of Bergman's minimal model method with intravenous glucose tolerance test in subjects of each group.", 'Compared with NC group, serum hs-CRP was significantly increased in IGT and type 2 DM groups (p < 0.001), although there was no significant difference between the latter groups. Hs-CRP was negatively correlated with high density lipoprotein cholesterol (HDL-C), SI and adiponectin levels (p < 0.05 to p < 0.001), and positively correlated with systolic blood pressure (SBP), fasting plasma glucose (FPG), BMI, waist-to-hip ratio (WHR), postprandial 2h plasma glucose (2hPG), fasting serum insulin (FINS) and postprandial serum insulin (PSI) in IGT and newly diagnosed type 2 DM groups (p < 0.05 to p < 0.001). In general multivariate regression, only adiponectin was the significantly independent determinant for serum hs-CRP (regression coefficient -1.380; 95% CI -2.062 to 0.698, p < 0.001); meanwhile, TG, SI, hs-CRP, FINS, 2hPG and WHR were significantly independent determinants for serum adiponectin concentration (p < 0.05 to p < 0.001).
Answer: Elevated serum hs-CRP may play a role in the development of insulin resistance syndrome and type 2 diabetes. This elevation is accompanied by the opposite changes of adiponectin.
Student: | Are serum CRP levels equally elevated in newly diagnosed type 2 diabetes and impaired glucose tolerance and related to adiponectin levels and insulin sensitivity? | task845_pubmedqa_question_generation |
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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.
One example: Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
Solution is here: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Explanation: The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
Now, solve this: Context: The aim of the present study was to determine the effect of moderate aerobic exercise on cardiac autonomic function in type 2 diabetic patients.', 'Heart rate variability of 20 patients with type 2 diabetes was assessed. Resting electrocardiogram for the heart rate variability analysis at spontaneous respiration was recorded for 5\xa0min in the supine position before and after 6\xa0months of supervised aerobic training given three times per week.', 'In time domain measures, the square root of the mean of the sum of the squares of differences between adjacent R-R intervals (RMSSD; 29.7 [26-34.5] vs 46.4 [29.8-52.2]\xa0ms, P\xa0=\xa00.023) and the percentage of consecutive RR intervals that differ by more than 50\xa0ms (pNN50; 10.7 [5.5-12.7] vs 26.1 [6.6-37.2]%, P\xa0=\xa00.025] were significantly increased after exercise. In frequency domain measures, low frequency (62.4 [59.1-79.2] vs 37 [31.3-43.3]\xa0nu, P\xa0=\xa00.003) and low frequency/high frequency (1.67 [1.44-3.8] vs 0.58 [0.46-0.59]%, P\xa0=\xa00.009) were significantly decreased, whereas high frequency (95 [67-149] vs 229 [98-427]\xa0ms(2), P\xa0=\xa00.006) and high frequency (37.6 [20.8-40.9] vs 63 [56.7-68.7]\xa0normalized units, P\xa0=\xa00.003) were significantly increased after exercise. In a Poincaré plot, standard deviation perpendicular to the line of the Poincaré plot (SD1; 21.3 [18.5-24.8]-33.1 [21.5-37.2]\xa0ms, P\xa0=\xa00.027) was significantly increased after exercise.
Answer: These data suggest that three times per week moderate intensity aerobic exercise for 6 months improves cardiac rhythm regulation as measured by heart rate variability in type 2 diabetic patients.
Solution: | Does mild-to-moderate intensity exercise improve cardiac autonomic drive in type 2 diabetes? | task845_pubmedqa_question_generation |
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instruction:
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.
question:
Context: Fatty acid synthase has been shown to be over expressed in a wide range of cancers and it has emerged as a therapeutic target. We examined whether fatty acid synthase could be a novel therapeutic target for renal cell carcinoma using the pharmacological fatty acid synthase inhibitor C75 (Cayman Chemical, Ann Arbor, Michigan).', 'The effects of C75 on cell viability and proliferation in human renal cancer 769P (ATCC(R)), Caki-1 and KU20-01 cells were examined by MTS assay and cell counts. Cell cycle distribution was analyzed by flow cytometry and cell invasiveness was assessed by wound healing and Matrigel(trade mark) invasion assays. Fatty acid synthase expression and the effects of C75 on intracellular signaling pathways were analyzed by Western blotting. The antitumor efficacy of C75 was examined using Caki-1 cell xenografts.', 'All renal cancer cell lines expressed detectable fatty acid synthase. C75 (10 mug/ml) significantly inhibited cell viability and growth by arresting the cell cycle at the G2/M phase and inducing apoptosis (p <0.01). The covered area in the wound and the number of cells invading through a Matrigel chamber were significantly smaller for cells treated with C75 than they were for control cells treated with vehicle (p <0.001). C75 suppressed Her2 and epidermal growth factor receptor expression as well as STAT3 phosphorylation, while increasing p53 and p21(Waf1/Cip1) expression. Intraperitoneal administration of C75 at doses of 20 mg/kg per week for 28 days significantly reduced the tumor volume of Caki-1 xenografts (p <0.05).
Answer: Pharmacological inhibition of fatty acid synthase could be an effective strategy for treating renal cell carcinoma.
answer:
Does pharmacological inhibitor of fatty acid synthase suppress growth and invasiveness of renal cancer cells?
question:
Context: Central core disease is a congenital myopathy, characterized by presence of central core-like areas in muscle fibers. Patients have mild or moderate weakness, hypotonia and motor developmental delay. The disease is caused by mutations in the human ryanodine receptor gene (RYR1), which encodes a calcium-release channel. Since the RYR1 gene is huge, containing 106 exons, mutation screening has been limited to three 'hot spots', with particular attention to the C-terminal region. Recent next-generation sequencing methods are now identifying multiple numbers of variants in patients, in which interpretation and phenotype prevision is difficult.", "In a Brazilian Caucasian family, clinical, histopathological and molecular analysis identified a new case of central core disease in a 48-year female. Sanger sequencing of the C-terminal region of the RYR1 gene identified two different missense mutations: c.14256 A >\u2009C polymorphism in exon 98 and c.14693 T >\u2009C in exon 102, which have already been described as pathogenic. Trans-position of the 2 mutations was confirmed because patient's daughter, mother and sister carried only the exon 98's mutation, a synonymous variant that was subsequently found in the frequency of 013-0,05 of alleles. Further next generation sequencing study of the whole RYR1 gene in the patient revealed the presence of additional 5 common silent polymorphisms in homozygosis and 8 polymorphisms in heterozygosis.
Answer: Considering that patient's relatives showed no pathologic phenotype, and the phenotype presented by the patient is within the range observed in other central core disease patients with the same mutation, it was concluded that the c.14256 A > C polymorphism alone is not responsible for disease, and the associated additional silent polymorphisms are not acting as modifiers of the primary pathogenic mutation in the affected patient. The case described above illustrates the present reality where new methods for wide genome screening are becoming more accessible and able to identify a great variety of mutations and polymorphisms of unknown function in patients and their families.
answer:
Do silent polymorphisms in the RYR1 gene modify the phenotype of the p.4898 I > T pathogenic mutation in central core disease : a case report?
question:
Context: To evaluate the current evidence of the relationship between myopia, together with its structural and refractive component, and diabetic retinopathy (DR) risk.', "A systematic search was performed up to April, 2015. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated employing random-effects models. Three models were used to assess the association between myopia and risk of DR: axial length (AL) (per millimetre increase) and DR; myopia (myopia versus non-myopia) and DR; refractive error (RE) (per D decrease) and DR. Publication bias of the literature was evaluated using Begg's funnel plots and Egger's test.", 'A total of 11 studies that met the predefined criteria were included in this meta-analysis. Overall, longer AL (per millimetre increase) was associa-ted with a significantly decreased risk of DR (combined OR, 0.75; 95% CI, 0.65-0.86; p\xa0<\xa00.001); myopic eyes (myopia versus non-myopia) showed a lower risk of DR (combined OR, 0.70; 95% CI, 0.58-0.85; p\xa0<\xa00.001). A greater degree of myopic RE (per D decrease) also revealed a significantly decreased risk of DR (combined OR, 0.89; 95% CI, 0.85-0.93; p\xa0<\xa00.001). The sensitivity analyses and cumulative meta-analysis showed similar results. No publication bias was detected in any of the three models.
Answer: This meta-analysis suggests that both myopic refraction and longer AL are associated with a lower risk of DR. Further studies are needed to determine exact mechanisms underpinning the protective effect of myopia against DR.
answer:
| Are myopia and/or longer axial length protective against diabetic retinopathy : a meta-analysis?
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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.
Ex Input:
Context: High visceral adipose tissue (VAT) and high liver fat (LF) are associated with the metabolic syndrome and diabetes. We studied changes in these two fat depots during weight loss and analyzed whether VAT and LF at baseline predict the response to lifestyle intervention.', 'One hundred twelve subjects (48 men and 64 women; age, 46 +/- 11 years; BMI, 29.2 +/- 4.4 kg/m(2)) were studied after a follow up-time of 264 +/- 60 (SD) days. Insulin sensitivity was estimated from the oral glucose tolerance test. Body fat depots were quantified using magnetic resonance imaging and spectroscopy.', 'Cross-sectionally high VAT (r = -0.22, p = 0.02) and high LF (r = -0.36, p < 0.0001) were independently associated with low insulin sensitivity. With intervention, BMI (-3.0%), VAT (-12.0%), and LF (-33.0%) were reduced (all p < 0.001). Insulin sensitivity was improved (+17%, p < 0.01). The changes in BMI (r = -0.41), VAT (r = -0.28), and LF (r = -0.39) were associated with the increase in insulin sensitivity (all p < 0.01). High VAT (r = -0.28, p = 0.01) and high LF (r = -0.38, p < 0.01) at baseline were associated with a lesser increase in insulin sensitivity.
Answer: Baseline values and changes in BMI, VAT, and LF are related to changes in insulin sensitivity during lifestyle intervention. Subjects with high VAT and LF have a lower chance of profiting from lifestyle intervention and may require intensified lifestyle prevention strategies or even pharmacological approaches to improve insulin sensitivity.
Ex Output:
Are high visceral fat mass and high liver fat associated with resistance to lifestyle intervention?
Ex Input:
Context: Increasing evidence points to the inflammatory character of atherosclerosis and several parameters of inflammation have been proposed as cerebrovascular risk markers. The objective of the research was to examine the connection of serum inflammatory parameters and ultrasound (US) characteristics of the structure and size of carotid plaque. We assumed that the number of leukocytes (Le) was an indicator of carotid plaque instability and an increased risk of stroke.', 'Serum inflammatory parameters: erythrocyte sedimentation rate in the first (ESR I) and second hour (ESR II), the number of Le, high sensitivity C-reactive protein (hsCRP) and fibrinogen were measured by standard methods. All the subjects (n = 75) were divided into 3 groups (symptomatic, asymptomatic and control). US evaluation of extracranial carotid arteries was performed in a duplex system. Plaques were classified into categories according to stenosis percentage (≥ 50%, < 50%) and pursuant to echomorphological characteristics (Gray-Weale classification). In the subjects with stroke an ischemic lesion was confirmed by computed tomography.', 'The average values of biochemical parameters in the symptomatic group were: ESR I 29.57 ± 29.87 cm, ESR II 51.60 ± 36.87 cm, the number of Le 10.10 ± 3.20 x 10⁹ U/L, hsCRP 8.15 ± 5.50 mg/L and fibrinogen 4.03 ± 0.70 g/L. The average values of all testing biochemical parameters in symptomatic patients were significantly higher than in the asymptomatic ones and the control group: for ESR I (p < 0.05) and ESR II (p < 0.05); for the number of Le (p < 0.001); for hsCRP (p < 0.001) and fibrinogen (p < 0.001). Category I of echomorphological characteristics in the symptomatic group was present in 66.7% of the cases and it was significantly higher than in the asymptomatic (40.0%; p < 0.05) and the control group (20.0%; p < 0.01). Univariate logistic regression analysis confirmed that all testing biochemical parameters are indicators of stroke risk. Multivariate logistic regression analysis confirmed a statistically significant correlation of the number of Le and stroke risk, while the increase in the value by a unit of measurement was associated with the growth of risk by 3.22 times (from 1.67 to 6.22).
Answer: The number of Le is associated with the phenomenon of carotid plaque instability and may be a useful additional marker of increased risk for developing acute cerebral infarction.
Ex Output:
Does leucocyte count indicate carotid plaque instability in stroke patients?
Ex Input:
Context: The current study examined the relation of anger, hostility, and severity of depressive symptoms, alone and in combination, to C-reactive protein (CRP) in healthy men and women.', 'A high sensitivity enzyme linked immuno sorbent assay (ELISA) was used to evaluate CRP levels in a multiethnic sample of 127 healthy, nonsmoking men and women. Fasting blood samples were collected the same day the assessments were done of anger and hostility using the Buss-Perry Aggression Questionnaire (BPAQ) and depressive symptomatology using the Beck Depression Inventory (BDI). A psychological risk factor (PRF) score representing a composite summary indicator of BDI and BPAQ-anger and -hostility was generated using principal component analysis. Log-transformed CRP values were examined using univariate and multivariate analyses adjusting for control variables of age, gender, body mass index (BMI), alcohol use, exercise frequency, ratio of total to high-density lipoprotein cholesterol, and family history of premature coronary heart disease (CHD).', 'Log-normalized CRP was correlated with BDI (r = 0.21, p =.02) and BPAQ anger (r = 0.20, p =.02), but not with BPAQ hostility. After adjustment for control variables, BDI (beta = 0.05, p =.011), BPAQ anger (beta = 0.05, p =.007), and the PRF composite score (beta = 0.27, p =.005), but not BPAQ hostility (beta = 0.03, p =.11), were significantly associated with log-normalized CRP.
Answer: Greater anger and severity of depressive symptoms, separately and in combination with hostility, were significantly associated with elevations in CRP in apparently healthy men and women. These associations were independent of potential confounding factors.
Ex Output:
| Is c-reactive protein associated with psychological risk factors of cardiovascular disease in apparently healthy adults?
| task845_pubmedqa_question_generation |
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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.
[EX Q]: Context: Reduction-oxidation (redox) signaling, the translation of an oxidative intracellular environment into a cellular response, is mediated by the reversible oxidation of specific cysteine thiols. The latter can result in disulfide formation between protein hetero- or homodimers that alter protein function until the local cellular redox environment has returned to the basal state. We have previously shown that this mechanism promotes the nuclear localization and activity of the Forkhead Box O4 (FOXO4) transcription factor.', 'In this study, we sought to investigate whether redox signaling differentially controls the human FOXO3 and FOXO4 paralogs.', 'We present evidence that FOXO3 and FOXO4 have acquired paralog-specific cysteines throughout vertebrate evolution. Using a proteome-wide screen, we identified previously unknown redox-dependent FOXO3 interaction partners. The nuclear import receptors Importin-7 (IPO7) and Importin-8 (IPO8) form a disulfide-dependent heterodimer with FOXO3, which is required for its reactive oxygen species-induced nuclear translocation. FOXO4 does not interact with IPO7 or IPO8.
Answer: IPO7 and IPO8 control the nuclear import of FOXO3, but not FOXO4, in a redox-sensitive and disulfide-dependent manner. Our findings suggest that evolutionary acquisition of cysteines has contributed to regulatory divergence of FOXO paralogs, and that phylogenetic analysis can aid in the identification of cysteines involved in redox signaling.
[EX A]: Does evolutionary acquisition of cysteines determine FOXO paralog-specific redox signaling?
[EX Q]: Context: To study the effect of Cleistocalyx nervosum extract (CE) on diethylnitrosamine (DEN) and phenobarbital (PB) induced oxidative stress in early stages of rat hepatocarcinogenesis.', 'Male Wistar rats were divided into 4 groups, with Group 1 as a negative control and Group 2 was a positive control receiving DEN injections once a week and PB in drinking water for 6 weeks. Two weeks before DEN initiation and PB treatment, Groups 3 and 4, were fed with 500 and 1000 mg/kg of CEs, respectively, for 8 weeks.', 'A number of GST-P-positive foci, preneoplastic lesions, in the liver were markedly increased in carcinogen administered rats, but was comparatively decreased in rats treated with 1000 mg/kg of CE. The CE reduced malondialdehyde in serum and in the livers of rats treated with DEN and PB. Moreover, CE significantly increased the activities of glutathione peroxidase and catalase in rat liver.
Answer: CE appeared to exert its chemopreventive effects by modulating antioxidant status during DEN and PB induced early stages of hepatocarcinogenesis in rats.
[EX A]: Does cleistocalyx nervosum extract ameliorate chemical-induced oxidative stress in early stages of rat hepatocarcinogenesis?
[EX Q]: Context: This study tested the premise that immunoreactivity representing the p75 neurotrophin receptor (p75(NTR)) appears in plasma of diabetic rats in association with the early stages of neuronal dysfunction or damage. We also examined whether treatment beneficial to neuropathy might reduce the p75(NTR) immunoreactivity.', 'Plasma proteins were fractionated by SDS-PAGE and immunoblots exposed to p75(NTR) antibody, using receptor protein from cultured PC12 cells as an external standard. Rats were made diabetic with streptozotocin for various periods and exsanguinated. Plasma glucose, HbA(1)c and plasma proteins were determined. We also studied plasma samples from diabetic mice lacking the gene coding for p75(NTR), as well as the effect of sciatic nerve crush on healthy male Wistar rats.', 'Plasma p75(NTR) immunoreactivity began to exceed normal levels at 8 weeks after induction of diabetes, and was significantly raised at 10 (p<0.05) and 12 weeks (p<0.001). Treatment between 8 and 12 weeks with insulin, fidarestat (an aldose reductase inhibitor), nerve growth factor and neurotrophin 3 all normalised the plasma p75(NTR) immunoreactivity. Plasma from p75(NTR) (-/-) mice contained no such immunoreactivity, though it was present in plasma from wild-type mice. Following nerve crush, p75(NTR) immunoreactivity appeared in plasma of non-diabetic mice, indicating that this can be a result of nerve trauma.
Answer: These observations suggest that plasma p75(NTR) immunoreactivity may serve as an early indicator of neuronal dysfunction or damage in diabetes. The time course of its appearance relates well to that of early neuropathy and its response to interventions that are neuroprotective suggests that it might mirror neurological status.
[EX A]: | Does the p75 neurotrophin receptor appear in plasma in diabetic rats-characterisation of a potential early test for neuropathy?
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Detailed Instructions: 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.
Q: Context: The goal of this study was to identify genetic determinants of plasma N-terminal proatrial natriuretic peptide (NT-proANP) in the general community by performing a large-scale genetic association study and to assess its functional significance in in vitro cell studies and on disease susceptibility.', 'Genotyping was performed across 16 000 genes in 893 randomly selected individuals, with replication in 891 subjects from the community. Plasma NT-proANP1-98 concentrations were determined using a radioimmunoassay. Thirty-three genome-wide significant single-nucleotide polymorphisms were identified in the MTHFR-CLCN6-NPPA-NPPB locus and were all replicated. To assess the significance, in vitro functional genomic studies and clinical outcomes for carriers of a single-nucleotide polymorphism rs5063 (V32M) located in NPPA that represented the most significant variation in this genetic locus were assessed. The rs5063 variant allozyme in transfected HEK293 cells was decreased to 55±8% of wild-type protein (P=0.01) as assessed by quantitative western blots. Carriers of rs5063 had lower NT-proANP levels (1427 versus 2291 pmol/L; P<0.001) and higher diastolic blood pressures (75 versus 73 mm Hg; P=0.009) and were at an increased risk of stroke when compared with wild-type subjects independent of age, sex, diabetes mellitus, hypertension, atrial fibrillation, and cholesterol levels (hazard ratio, 1.6; P=0.004).
Answer: This is the first large-scale genetic association study of circulating NT-proANP levels performed with replication and functional assessment that identified genetic variants in the MTHFR-CLCN6-NPPA-NPPB cluster to be significantly associated with NT-proANP levels. The clinical significance of this variation is related to lower NT-proANP levels, higher blood pressures, and an increased risk of stroke in the general community.
A: | Does circulating atrial natriuretic peptide genetic association study identify a novel gene cluster associated with stroke in whites? | task845_pubmedqa_question_generation |
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Q: 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.
Context: To determine if early pregnancy serum biomarkers in high-risk women who develop preeclampsia vary according to risk factor.', 'We performed a secondary analysis of the Maternal-Fetal Medicine Units Network randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in high-risk women. Serum biomarker levels at enrollment (before initiation of aspirin or placebo) were compared between women who did and did not develop preeclampsia, both for the group as a whole and within each of 4 high-risk groups (insulin-dependent diabetes, hypertension, multiple gestation, and previous preeclampsia) using a regression model adjusting for gestational age at collection and prepregnancy body mass index.', '1258 women were included (233 with insulin-dependent diabetes, 387 with chronic hypertension, 315 with a multiple gestation, 323 with previous preeclampsia). Multiple early pregnancy serum biomarkers differed between women who did and did not develop preeclampsia. Each high-risk group had a unique and largely nonoverlapping pattern of biomarker abnormality. Differences between those who did and did not develop preeclampsia were noted in vascular cell adhesion molecule in the diabetes group; human chorionic gonadotropin, soluble tumor necrosis factor receptor-2, tumor necrosis factor-alpha, selectin and angiogenin in the chronic hypertension group; interleukin-6, placental growth factor, soluble fms-like tyrosine kinase plus endoglin to placental growth factor ratio in the multiple gestation group; and angiogenin in the previous preeclampsia group.
Answer: Patterns of serum biomarkers vary by high-risk group. These data support the hypothesis that multiple pathogenic pathways lead to the disease recognized clinically as preeclampsia.
A: | Is preeclampsia in high risk women characterized by risk group-specific abnormalities in serum biomarkers? | task845_pubmedqa_question_generation |
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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.
Example input: Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
Example output: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Example explanation: The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
Q: Context: Morus alba, a medicinal plant in Asia, has been used traditionally to treat diabetes mellitus and hypoglycemia. However, the effects of M. alba extract (MAE) on atopic dermatitis have not been verified scientifically. We investigated the effects of MAE on atopic dermatitis through in vitro and in vivo experiments.', 'We evaluated the effects of MAE on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7, as well as thymus and activation-regulated chemokine (TARC/CCL17) in HaCaT cells. In an in vivo experiment, atopic dermatitis was induced by topical application of house dust mites for four weeks, and the protective effects of MAE were investigated by measuring the severity of the skin reaction on the back and ears, the plasma levels of immunoglobulin E (IgE) and histamine, and histopathological changes in the skin on the back and ears.', 'MAE suppressed the production of NO and PGE2 in RAW 264.7 cells, as well as TARC in HaCaT cells, in a dose-dependent manner. MAE treatment of NC/Nga mice reduced the severity of dermatitis and the plasma levels of IgE and histamine. MAE also reduced the histological manifestations of atopic dermatitis-like skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration in the skin on the back and ears.
Answer: Our results suggest that MAE has potent inhibitory effects on atopic dermatitis-like lesion and may be a beneficial natural resource for the treatment of atopic dermatitis.
A: | Does morus alba L. suppress the development of atopic dermatitis induced by the house dust mite in NC/Nga mice? | task845_pubmedqa_question_generation |
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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.
[Q]: Context: Perturbation of the endoplasmic reticulum (ER) homeostasis has emerged as one of the prominent features of obesity and diabetes. This occurs when the adaptive unfolded protein response (UPR) fails to restore ER function in key metabolic tissues. We previously reported increased inflammation and impaired heat shock response (HSR) in obese human subjects that were restored by physical exercise. Here, we investigated the status of ER stress chaperone; glucose-regulated protein 78 (GRP78) and its downstream UPR pathways in human obese, and their modulation by a supervised 3-month physical exercise.', "Subcutaneous adipose tissue (SAT) and blood samples were collected from non-diabetic adult human lean (n=40) and obese (n=40, at baseline and after 3months of physical exercise). Transcriptomic profiling was used as a primary screen to identify differentially expressed genes and it was carried out on SAT samples using the UPR RT(2) Profiler PCR Array. Conventional RT-PCR, immunohistochemistry, immunofluorescence, Western blot and ELISA were used to validate the transcriptomic data. Correlation analyses with the physical, clinical and biochemical outcomes were performed using Pearson's rank correlation coefficient.", 'Levels of GRP78 and its three downstream UPR arms; activating transcription factor-6 (ATF6), inositol-requiring enzyme-1α (IRE1α) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) were increased in obese subjects. More interestingly, higher levels of circulating GRP78 protein were found in obese compared to lean subjects which correlated negatively with maximum oxygen uptake (VO2 Max) but positively with high-sensitivity C-reactive protein (hsCRP) and obesity indicators such as BMI, percentage body fat (PBF) and waist circumference. GRP78 increased secretion in obese was further confirmed in vitro using 3T3-L1 preadipocyte cells under ER stress. Finally, we showed that physical exercise significantly attenuated the expression and release of GRP78 with a concomitant reduction in the phosphorylation of IRE1α and eukaryotic initiation factor-2α (eIF2α).
Answer: Our results suggest that physical exercise alleviates ER stress in human obese through attenuation of GRP78 signaling network.
[A]: Does physical exercise alleviate ER stress in obese humans through reduction in the expression and release of GRP78 chaperone?
[Q]: Context: The gap between the tendon stumps in chronic Achilles tendon rupture has reportedly been filled with interposed scar tissue. In the authors' clinical experience, this interposed tissue is often thick and resists tension, so they considered it was possible to use the interposed tissue for reconstruction of Achilles tendon rupture.", 'Scar tissue interposed between the tendon stumps has the capacity to form tendon-like repair tissue in patients with chronic Achilles tendon rupture.', 'Case series; Level of evidence, 4.', 'Six patients with chronic rupture of the Achilles tendon underwent tendon reconstruction with the use of interposed tissue between the stumps. The average time from the primary injury to surgery was 22 weeks (range, 9 to 30 weeks). Preoperative magnetic resonance imaging (MRI), histology of the interposed tissue, and clinical results were evaluated. The average postoperative follow-up period was 31 months (range, 24 to 43 months).', 'Preoperative T2-weighted MRI in all cases revealed that chronically ruptured Achilles tendons were thickened and fusiform-shaped with diffuse intratendinous high-signal alterations throughout. Longitudinal high-signal bands were seen throughout the tendon, except at the musculotendinous junction and insertion on the calcaneus. Histologically, scar tissue interposed between the tendon stumps consisted of dense collagen fibers, and degenerative changes were not seen. After surgery, no patient had difficulty in walking or stair climbing, and all were able to perform a single-limb toe raise. The mean preoperative and postoperative American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores were 88.2 and 98.3 points, respectively; the difference was statistically significant (P = .0277).
Answer: Interposed tissue between the tendon stumps is suitable for repair of chronic Achilles tendon rupture if preoperative MRI shows a thickened fusiform-shaped Achilles tendon with diffuse intratendinous high-signal alterations throughout.
[A]: Do reconstruction of chronic achilles tendon rupture with the use of interposed tissue between the stumps?
[Q]: Context: When given in conjunction with surgery for treating cancer, radiation therapy may result in impaired wound healing, which, in turn, could cause skin ulcers. In this study, bilayer and monolayer autologous skin substitutes were used to treat an irradiated wound.', 'A single dose of 30 Gy of linear electron beam radiation was applied to the hind limb of nude mice before creating the skin lesion (area of 78.6 mm). Monolayer tissue-engineered skin substitutes (MTESSs) were prepared by entrapping cultured keratinocytes in fibrin matrix, and bilayer tissue-engineered skin substitutes (BTESSs) were prepared by entrapping keratinocytes and fibroblasts in separate layers. Bilayer tissue-engineered skin substitute and MTESS were implanted to the wound area. Gross appearance and wound area were analyzed to evaluate wound healing efficiency. Skin regeneration and morphological appearance were observed via histological and electron microscopy. Protein expressions of transforming growth factor β1 (TGF-β1), platelet-derived growth factor BB (PDGF-BB), and vascular endothelial growth factor (VEGF) in skin regeneration were evaluated by immunohistochemistry (IHC).', 'Macroscopic observation revealed that at day 13, treatments with BTESS completely healed the irradiated wound, whereas wound sizes of 1.1 ± 0.05 and 6.8 ± 0.14 mm were measured in the MTESS-treated and untreated control groups, respectively. Hematoxylin-eosin (H&E) analysis showed formation of compact and organized epidermal and dermal layers in the BTESS-treated group, as compared with MTESS-treated and untreated control groups. Ultrastructural analysis indicates maturation of skin in BTESS-treated wound evidenced by formation of intermediate filament bundles in the dermal layer and low intercellular space in the epidermal layer. Expressions of TGF-β1, PDGF-BB, and VEGF were also higher in BTESS-treated wounds, compared with MTESS-treated wounds.
Answer: These results indicate that BTESS is the preferred treatment for irradiated wound ulcers.
[A]: | Does tissue-Engineered Skin Substitute enhance Wound Healing after Radiation Therapy?
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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: We utilized whole-genome mapping of promoters that are activated by DNA hypomethylation in hepatocellular carcinoma (HCC) clinical samples to shortlist novel targets for anticancer therapeutics. We provide a proof of principle of this approach by testing six genes short-listed in our screen for their essential role in cancer growth and invasiveness.', 'We used siRNA- or shRNA-mediated depletion to determine whether inhibition of these genes would reduce human tumor xenograft growth in mice as well as cell viability, anchorage-independent growth, invasive capacities, and state of activity of nodal signaling pathways in liver, breast, and bladder cancer cell lines.', 'Depletion of EXOSC4, RNMT, SENP6, WBSCR22, RASAL2, and NENF effectively and specifically inhibits cancer cell growth and cell invasive capacities in different types of cancer, but, remarkably, there is no effect on normal cell growth, suggesting a ubiquitous causal role for these genes in driving cancer growth and metastasis. Depletion of RASAL2 and NENF in vitro reduces their growth as explants in vivo in mice. RASAL2 and NENF depletion interferes with AKT, WNT, and MAPK signaling pathways as well as regulation of epigenetic proteins that were previously demonstrated to drive cancer growth and metastasis.
Answer: Our results prove that genes that are hypomethylated and induced in tumors are candidate targets for anticancer therapeutics in multiple cancer cell types. Because these genes are particularly activated in cancer, they constitute a group of targets for specific pharmacologic inhibitors of cancer and cancer metastasis. Clin Cancer Res; 20(12); 3118-32. ©2014 AACR.
Answer: Does genome-wide study of hypomethylated and induced genes in patients with liver cancer unravel novel anticancer targets?
Question: Context: 99mTc-HMPAO is a well-established isotope useful in the detection of regional cerebral blood flow. Diabetes gives rise to arterial atherosclerotic changes that can lead to significant end organ dysfunction, prominently affecting perfusion to the heart, kidneys, eyes and brain. In the current study, we investigated the role of 99mTc-HMPAO cerebral perfusion scans in detecting early vascular changes in the diabetic brain.', 'Cerebral perfusion studies were performed on both control and streptozotocin-(STZ) induced diabetic male Wistar rats. Rat brain imaging using a gamma camera was performed for each group 0.5, 2, 4, and 24 hours post 99mTc-HMPAO injection. Data processing for each cerebral perfusion scan was performed by drawing a region of interest (ROI) circumferentially around the brain (B). Background (BKG) due to signal from the soft tissue of each rat was subtracted. Brain 99mTc-HMPAO uptake minus background counts (net brain counts; NBC) were then compared between the two groups.', 'The NBC (mean +/- SD) for the STZ group were statistically significantly higher (p = 0.0004) than those of the control group at each of the time points studied.
Answer: 99mTc-HMPAO brain scan may be useful in the detection of early atherosclerotic changes in the diabetic rat brain.
Answer: Does perfusion scanning using 99mTc-HMPAO detect early cerebrovascular changes in the diabetic rat?
Question: Context: Volatile anesthetic postconditioning has been documented to provide neuroprotection in adult animals. Our aim was to investigate whether sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage (HIBD) rats, and whether the PI3K/Akt pathway and mitochondrial permeability transition pore (mPTP) opening participate in the effect.', 'Seven-day-old Sprague-Dawley rats were subjected to brain HI and randomly allocated to 10 groups (n=24 each group) and treated as follows: (1) Sham, without hypoxia-ischemia; (2) HI/Control, received cerebral hypoxia-ischemia; (3) HI+Atractyloside (Atr), (4) HI+Cyclosporin A (CsA), (5) HI+sevoflurane (Sev), (6) HI+Sev+ LY294002 (LY), (7) HI+Sev+ L-NAME (L-N), (8) HI+Sev+ SB216763 (SB), (9) HI+Sev+Atr, and (10) HI+Sev+CsA. Twelve rats in each group underwent behavioral testing and their brains were harvested for hippocampus neuron count and morphology study. Brains of the other 12 animals were harvested 24h after intervention to examine the expression of Akt, p-Akt, eNOS, p-eNOS, GSK-3β, p-GSK-3β by Western bolting and mPTP opening.', 'Sevoflurane postconditioning significantly improved the long-term cognitive performance of the rats, increased the number of surviving neurons in CA1 and CA3 hippocampal regions, and protected the histomorphology of the left hippocampus. These effects were abolished by inhibitors of PI3K/eNOS/GSK-3β. Although blocking mPTP opening simulated sevoflurane postconditioning-induced neuroprotection, it failed to enhance it.
Answer: Sevoflurane postconditioning exerts a neuroprotective effect against HIBD in neonatal rats via PI3K/Akt/eNOS and PI3K/Akt/GSK-3β pathways, and blockage of mPTP opening may be involved in attenuation of histomorphological injury.
Answer: | Does sevoflurane postconditioning improve long-term learning and memory of neonatal hypoxia-ischemia brain damage rats via the PI3K/Akt-mPTP pathway?
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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.
Example Input: Context: Surfactant protein (SP) D shares target cells with the proinflammatory cytokine TNF-alpha, an important autocrine stimulator of dendritic cells and macrophages in the airways.', 'We sought to study the mechanisms by which TNF-alpha and SP-D can affect cellular components of the pulmonary innate immune system.', 'Cytokine and SP-D protein and mRNA expression was assessed by means of ELISA, Western blotting, and real-time PCR, respectively, by using in vivo models of allergic airway sensitization. Macrophage and dendritic cell phenotypes were analyzed by means of FACS analysis. Maturation of bone marrow-derived dendritic cells was investigated in vitro.', 'TNF-alpha, elicited either by allergen exposure or pulmonary overexpression, induced SP-D, IL-13, and mononuclear cell influx in the lung. Recombinant IL-13 by itself was also capable of enhancing SP-D in vivo and in vitro, and the SP-D response to allergen challenge was impaired in IL-13-deficient mice. Allergen-induced increase of SP-D in the airways coincided with resolution of TNF-alpha release and cell influx. SP-D-deficient mice had constitutively high numbers of alveolar mononuclear cells expressing TNF-alpha, MHC class II, CD86, and CD11b, characteristics of proinflammatory, myeloid dendritic cells. Recombinant SP-D significantly suppressed all of these molecules in bone marrow-derived dendritic cell cultures.
Answer: TNF-alpha can contribute to enhanced SP-D production in the lung indirectly through inducing IL-13. SP-D, on the other hand, can antagonize the proinflammatory effects of TNF-alpha on macrophages and dendritic cells, at least partly, by inhibiting production of this cytokine.
Example Output: Does surfactant protein D inhibit TNF-alpha production by macrophages and dendritic cells in mice?
Example Input: Context: Barrett esophagus (BE) is considered precursor condition of esophageal adenocarcinoma. Its incidence and prevalence are increasing in general population. Studies reported that metabolic syndrome (MS) or diabetes mellitus (DM) is related to increased risk of BE. Current study was to assess and better understand the relationship between MS /DM and BE.', "Electronic search was conducted in the database Pubmed/Medline (-December, 2015), Embase (-December, 2015), Cochrane Library (-December, 2015), and Web of Knowledge (-December, 2015). Studies included were assessed with summary odds ratios (ORs) with 95% confidence intervals (CIs) and compared exposure group with control group. The heterogeneity was examined by the funnel plot and the Egger's test. Subgroup analyses and sensitive analyses were performed for the detection of possible heterogeneity and impact on stability of analysis results.", "Twelve publications met the criteria and included 355,311 subjects were analyzed. The pooled results showed MS was closely associated with increased risk of BE (OR\u200a=\u200a1.23; 95%CI 1.03-1.47; P\u200a=\u200a0.024), and yet DM did not significantly increase the risk of BE (OR\u200a=\u200a1.07; 95%CI 0.82-1.38; P\u200a=\u200a0.627). Substantial heterogeneities were detected. No significant publication bias was detected by Egger's test (P\u200a=\u200a0.23).
Answer: Based on the results of current meta-analysis, MS is associated with increased risk of BE. Further long-term follow-up prospective study needs to verify the current results, and definite pathophysiological mechanism needs to be further investigated and clearly elucidated.
Example Output: Is metabolic syndrome associated with increased risk of Barrett esophagus : A meta-analysis?
Example Input: Context: This study was aimed to evaluate the analgesic efficacy duration of analgesia, and side effects of two different doses of caudal neostigmine used with levobupivacaine in children.', "Sixty boys, between 5 months and 5 years, undergoing genitourinary surgery were allocated randomly to one of three groups (n =20 each). Group I patients received caudal 0.25% levobupivacaine (1 ml.kg(-1)) alone. Groups II and III patients received neostigmine (2 and 4 microg.kg(-1) respectively) together with levobupivacaine used in the same does as Group I. Pain scores were assessed using Children's and Infant's Postoperative Pain Scale (CHIPPS) at 15th (t(1)) min after arrival to postanesthetic care unit, and 1st (t(2)), 2nd (t(3)), 3rd (t(4)), 4th (t(5)), 8th (t(6)), 16th (t(7)), and 24th (t(8)) hour postoperatively. Duration of analgesia, amount of additional analgesic (paracetamol), score of motor blockade and complications were recorded for 24 h postoperatively, and compared between groups.", 'CHIPPS scores were higher during t(2), t(3), t(6), t(7), and t(8) periods, duration of analgesia was shorter, and total analgesic consumption was higher in Group I compare to neostigmine groups (P < 0.05). Duration of postoperative analgesia and total analgesic consumption were similar in Groups II and III (P > 0.05). Adverse effects were not different between three groups.
Answer: Caudal neostigmine in doses of 2 and 4 microg.kg(-1) with levobupivacaine extends the duration of analgesia without increasing the incidence of adverse effects, and 2 microg.kg(-1) seems to be the optimal dose, as higher dose has no further advantages.
Example Output: | Does two different doses of caudal neostigmine co-administered with levobupivacaine produce analgesia in children?
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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.
Ex Input:
Context: Islet cell transplantation can cure type 1 diabetes (T1D), but only a minority of recipients remains insulin-independent in the following years. We tested the hypothesis that allograft rejection and recurrent autoimmunity contribute to this progressive loss of islet allograft function.', 'Twenty-one T1D patients received cultured islet cell grafts prepared from multiple donors and transplanted under anti-thymocyte globulin (ATG) induction and tacrolimus plus mycophenolate mofetil (MMF) maintenance immunosuppression. Immunity against auto- and alloantigens was measured before and during one year after transplantation. Cellular auto- and alloreactivity was assessed by lymphocyte stimulation tests against autoantigens and cytotoxic T lymphocyte precursor assays, respectively. Humoral reactivity was measured by auto- and alloantibodies. Clinical outcome parameters--including time until insulin independence, insulin independence at one year, and C-peptide levels over one year--remained blinded until their correlation with immunological parameters. All patients showed significant improvement of metabolic control and 13 out of 21 became insulin-independent. Multivariate analyses showed that presence of cellular autoimmunity before and after transplantation is associated with delayed insulin-independence (p = 0.001 and p = 0.01, respectively) and lower circulating C-peptide levels during the first year after transplantation (p = 0.002 and p = 0.02, respectively). Seven out of eight patients without pre-existent T-cell autoreactivity became insulin-independent, versus none of the four patients reactive to both islet autoantigens GAD and IA-2 before transplantation. Autoantibody levels and cellular alloreactivity had no significant association with outcome.
Answer: In this cohort study, cellular islet-specific autoimmunity associates with clinical outcome of islet cell transplantation under ATG-tacrolimus-MMF immunosuppression. Tailored immunotherapy targeting cellular islet autoreactivity may be required. Monitoring cellular immune reactivity can be useful to identify factors influencing graft survival and to assess efficacy of immunosuppression.
Ex Output:
Does cellular islet autoimmunity associate with clinical outcome of islet cell transplantation?
Ex Input:
Context: SOX2 and SOX9 are commonly overexpressed in glioblastoma, and regulate the activity of glioma stem cells (GSCs). Their specific and overlapping roles in GSCs and glioma treatment remain unclear.', 'SOX2 and SOX9 levels were examined in human biopsies. Gain and loss of function determined the impact of altering SOX2 and SOX9 on cell proliferation, senescence, stem cell activity, tumorigenesis and chemoresistance.', 'SOX2 and SOX9 expression correlates positively in glioma cells and glioblastoma biopsies. High levels of SOX2 bypass cellular senescence and promote resistance to temozolomide. Mechanistic investigations revealed that SOX2 acts upstream of SOX9. mTOR genetic and pharmacologic (rapamycin) inhibition decreased SOX2 and SOX9 expression, and reversed chemoresistance.
Answer: Our findings reveal SOX2-SOX9 as an oncogenic axis that regulates stem cell properties and chemoresistance. We identify that rapamycin abrogate SOX protein expression and provide evidence that a combination of rapamycin and temozolomide inhibits tumor growth in cells with high SOX2/SOX9.
Ex Output:
Does mTOR inhibition decrease SOX2-SOX9 mediated glioma stem cell activity and temozolomide resistance?
Ex Input:
Context: Microvillus inclusion disease (MVID) is a genetic disorder affecting intestinal absorption. It is caused by mutations in MYO5B or syntaxin 3 (STX3) affecting apical membrane trafficking. Morphologically, MVID is characterised by a depletion of apical microvilli and the formation of microvillus inclusions inside the cells, suggesting a loss of polarity. To investigate this hypothesis, we examined the location of essential apical polarity determinants in five MVID patients.', 'We found that the polarity determinants Cdc42, Par6B, PKCζ/ι and the structural proteins ezrin and phospho-ezrin were lost from the apical membrane and accumulated either in the cytoplasm or on the basal side of enterocytes in patients, which suggests an inversion of cell polarity. Moreover, microvilli-like structures were observed at the basal side as per electron microscopy analysis. We next performed Myo5B depletion in three dimensional grown human Caco2 cells forming cysts and found a direct link between the loss of Myo5B and the mislocalisation of the same apical proteins; furthermore, we observed that a majority of cysts displayed an inverted polarity phenotype as seen in some patients. Finally, we found that this loss of polarity was specific for MVID: tissue samples of patients with Myo5B-independent absorption disorders showed normal polarity but we identified Cdc42 as a potentially essential biomarker for trichohepatoenteric syndrome.
Answer: Our findings indicate that the loss of Myo5B induces a strong loss of enterocyte polarity, potentially leading to polarity inversion.
Ex Output:
| Is the localisation of the apical Par/Cdc42 polarity module specifically affected in microvillus inclusion disease?
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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: Nonalcoholic steatohepatitis (NASH) is associated with dyslipidemia and cardiovascular disease (CVD).', 'To determine the relationship between resolution of NASH and dyslipidemia.', 'Individuals in the Pioglitazone vs. Vitamin E vs. Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial with paired liver biopsies and fasting lipid levels were included (N = 222). In the PIVENS trial individuals were randomised to pioglitazone 30 mg, vitamin E 800 IU or placebo for 96 weeks. Change in lipid levels at 96 weeks was compared between those with and without NASH resolution.', 'Dyslipidemia at baseline was frequent, with low high-density lipoprotein (HDL) (<40 mg/dL in men or <50 mg/dL in women) in 63%, hypertriglyceridaemia (≥150 mg/dL) in 46%, hypercholesterolaemia (≥200 mg/dL) in 47% and triglycerides (TG)/HDL >5.0 in 25%. Low-density lipoprotein (LD) ≥160 mg/dL was found in 16% and elevated non-HDL cholesterol (non-HDL-C) (≥130 mg/dL) in 73%. HDL increased with NASH resolution but decreased in those without resolution (2.9 mg/dL vs. -2.5 mg/dL, P < 0.001). NASH resolution was associated with significant decreases in TG and TG/HDL ratio compared to those without resolution (TG: -21.1 vs. -2.3 mg/dL, P = 0.03 and TG/HDL: -0.7 vs. 0.1, P = 0.003). Non-HDL-C, LDL and cholesterol decreased over 96 weeks in both groups, but there was no significant difference between groups. Treatment group did not impact lipids.
Answer: NASH resolution is associated with improvements in TG and HDL but not in other cardiovascular disease risk factors including LDL and non-HDL-C levels. Individuals with resolution of NASH may still be at increased risk of cardiovascular disease. ClinicalTrials.gov identifier: NCT00063622.
Output: Is nASH resolution associated with improvements in HDL and triglyceride levels but not improvement in LDL or non-HDL-C levels?
Input: Consider Input: Context: Although diabetic patients often have gastrointestinal complications, the gastric mucosal function in diabetes has not been well documented.', 'To investigate the effect of fasting on the gastric mucosa in C57BL/KsJ-db +/+ db (db/db) mice, genetically non-insulin-dependent diabetic animals.', 'Blood glucose levels, gastric mucosal morphology, and the amount of gastric mucin were examined before and after 18 h of fasting with free access to water in db/db mice and their non-diabetic littermates (db/m).', 'Although 18 h of fasting reduced the blood glucose levels of both db/db and db/m mice, fasting decreased the amount of gastric adherent mucin and caused haemorrhagic gastric lesions only in db/db mice. After fasting, oral administration of ethanol induced much more severe gastric damage in db/db than in db/m mice. The above fasting-induced gastric damage such as haemorrhagic lesions, loss of the mucin, and the increased sensitivity to ethanol worsened as the duration of diabetes became longer. Glucose ingestion in drinking water during the fasting counteracted the fall in blood glucose and prevented the decrease in the amount of gastric mucin and the formation of gastric mucosal lesions in db/db mice.
Answer: These findings indicate that fasting-induced glucose deficit causes gastric mucosal lesions and increases the susceptibility of gastric mucosa to noxious agents owing to the loss of mucus glycoprotein in db/db mice. Prolonged diabetes is likely to augment the severity of fasting-induced impairment of the gastric mucosal function.
Output: Does fasting induce impairment of gastric mucosal integrity in non-insulin-dependent diabetic ( db/db ) mice?
Input: Consider Input: Context: To investigate the effect of therapeutic hypothermia in the prognostic value of the pituitary-adrenal axis in comatose patients after cardiac arrest.', 'Prospective observational study in intensive care units (ICU) of a university and an affiliated regional hospital.', 'Twenty-nine consecutive patients, in coma after cardiac arrest, admitted to the ICU and treated by hypothermia.', 'On ICU-admission (T=1), at reaching the target of 32-33 degrees C during therapeutic hypothermia (T=2), at the end of hypothermia (T=3) and 48h later (T=4), plasma adrenocorticotrophic hormone (ACTH), serum cortisol, albumin and corticosteroid-binding globulin (CBG) were measured. A short 250 microg ACTH test was performed at each time-point, except at T=1. The free cortisol index (FCI) and free cortisol calculated by Coolens method were also evaluated.', 'The ICU mortality was 59%, including withdrawal of life-sustaining treatment in 45% because of negative somatosensory evoked potentials. ACTH and (free) cortisol levels (mean 13.1 pmol/L vs. 6.0 pmol/L and 1250 nmol/L vs. 596 nmol/L, respectively) were higher in non-survivors than in survivors. Levels decreased in time, but the relative difference between outcome groups was maintained until T=4. The cortisol response to ACTH was lower in non-survivors at T=3 (P=0.047) only.
Answer: In comatose patients resuscitated from cardiac arrest, the pituitary-adrenal axis is activated particularly in those dying in the ICU, irrespective of therapeutic hypothermia. Hence, activation of the axis may be a marker of fatal cerebral damage. There is no firm evidence for relative adrenal insufficiency associated with death and a transiently blunted cortisol response to ACTH in non-survivors may be attributed to higher baseline values.
| Output: Is the pituitary-adrenal axis activated more in non-survivors than in survivors of cardiac arrest , irrespective of therapeutic hypothermia?
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Q: 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.
Context: To evaluate amiodarone prophylaxis in diabetics and non-diabetics. Further to clarify whether the risk of developing atrial fibrillation is higher for diabetics than non-diabetic patients, and to evaluate whether the diabetic status has any influence on the length of in-hospital stay.', 'Subgroup analysis within a randomized, controlled, double-blinded trial.', 'At 30 days of follow-up atrial fibrillation was equally frequent among diabetics (22%) and non-diabetics (17%) (p =0.41). The length of in-hospital stay for diabetics was prolonged with 25% (9%; 45%). The prophylactic amiodarone was found equally efficient in diabetics and non-diabetics, as the relative risk ratios were 1.2 (0.4-5.4) and 2.0 (0.3-12.5), respectively.
Answer: Diabetics and non-diabetics had the same effect of the amiodarone prophylaxis regime. Atrial fibrillation developed equally among diabetics and non-diabetics, but the length of stay was prolonged for diabetics.
A: | Does amiodarone protect diabetics and non-diabetics undergoing coronary artery bypass grafting equally? | task845_pubmedqa_question_generation |
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Detailed Instructions: 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.
See one example below:
Problem: Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
Solution: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Explanation: The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
Problem: Context: Despite advances in the understanding of diabetic retinopathy, the nature and time course of molecular changes in the retina with diabetes are incompletely described. This study characterized the functional and molecular phenotype of the retina with increasing durations of diabetes.', 'Using the streptozotocin-induced rat model of diabetes, levels of retinal permeability, caspase activity, and gene expression were examined after 1 and 3 months of diabetes. Gene expression changes were identified by whole genome microarray and confirmed by qPCR in the same set of animals as used in the microarray analyses and subsequently validated in independent sets of animals. Increased levels of vascular permeability and caspase-3 activity were observed at 3 months of diabetes, but not 1 month. Significantly more and larger magnitude gene expression changes were observed after 3 months than after 1 month of diabetes. Quantitative PCR validation of selected genes related to inflammation, microvasculature and neuronal function confirmed gene expression changes in multiple independent sets of animals.
Answer: These changes in permeability, apoptosis, and gene expression provide further evidence of progressive retinal malfunction with increasing duration of diabetes. The specific gene expression changes confirmed in multiple sets of animals indicate that pro-inflammatory, anti-vascular barrier, and neurodegenerative changes occur in tandem with functional increases in apoptosis and vascular permeability. These responses are shared with the clinically documented inflammatory response in diabetic retinopathy suggesting that this model may be used to test anti-inflammatory therapeutics.
Solution: | Does whole genome assessment of the retinal response to diabetes reveal a progressive neurovascular inflammatory response? | task845_pubmedqa_question_generation |
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TASK DEFINITION: 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.
PROBLEM: Context: The aim of this study was to investigate the association of lipoprotein(a) [Lp(a)] with the severity of coronary heart disease (CHD) in Han Chinese people.', 'Six hundred and seventy-nine patients with angiographically defined CHD were enrolled in this cross-sectional study. Fasting lipids were measured, and the severity of CHD was quantitatively assessed for each patient according to the number of stenotic coronary branches and the Gensini scoring system.', 'The levels of Lp(a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and apolipoprotein (apo) B100 increased, while high-density lipoprotein cholesterol (HDL-C) and apoAI decreased significantly with the number of stenotic vessels. The levels of Lp(a) increased and HDL-C and apoAI decreased significantly with the Gensini scores. The logistic regression analyses showed that Lp(a) and HDL-C were independently associated with the number of stenotic coronary vessels after adjusting for age, weight, body mass index, sex, smoking, alcohol consumption, hypertension, diabetes, triglycerides, TC, LDL-C, VLDL-C, apoAI, and apoB100. However, only Lp(a) was independently associated with the Gensini scores after adjustment.
Answer: Our data indicate that Lp(a) might be a useful marker in predicting the severity of coronary heart disease.
SOLUTION: Are plasma lipoprotein ( a ) levels associated with the severity of coronaryheart disease in Han Chinese people?
PROBLEM: Context: To explore the role of SCF/c-Kit signaling in the invasion of bladder cancer T24 cells.', 'Western blotting was used to detect the expression of c-Kit and PI3K pathway activation stimulated by stem cell factor (SCF) in T24 cells. The invasiveness of T24 cells before and after SCF stimulation and Wortmannin (aspecific PI3K inhibitor) treatment was evaluated using Transwell invasion assay (direct and indirect counting methods).', 'T24 cells expressed c-Kit protein and showed obvious Akt phosphorylation after stimulation with SCF (1 ng/ml) for 24 h. Compared to the control group, SCF stimulation (1 ng/ml) caused a greater number of T24 cells to migrate through the polycarbonate film (P<0.01), and this effect was blocked by the application of Wortmannin before the stimulation.
Answer: SCF/c-Kit signaling promotes the invasiveness of T24 cells, and this effect is mediated by the PI3K pathway.
SOLUTION: Does [ SCF/c-Kit signaling promote invasion of T24 cells via PI3K pathway ]?
PROBLEM: Context: Sympathetic nervous system hyperactivity promotes vascular disorders by its catabolic effects and by increasing arterial blood pressure. Levodopa-derived dopamine modulates sympathetic overactivity and is known to reduce blood pressure, but its effects on glucose and lipid metabolism have not been studied in large series of patients.', 'We retrospectively examined 483 consecutive parkinsonian patients, admitted to a single institute between 1970 and 1987, before statins were available. We compared risk factors for vascular disease in the 305 who were on levodopa with the 178 who had never received the drug.', 'On admission levodopa-treated patients had significantly lower plasma levels of triglycerides, total cholesterol and lipids, and lower frequency of diabetes and hypertension than untreated patients. Mean body mass index, resting blood pressure, fasting plasma glucose, and smoking did not differ between the groups. A year after enrollment 160 patients were re-hospitalized; of these 63 had started levodopa during first hospitalization. In these new levodopa users total cholesterol, triglycerides and lipids had reduced to levels comparable with those of longer-term levodopa users.
Answer: Levodopa use in parkinsonian patients is associated with reduced vascular risk factors. In causal terms this finding might be attributed to the inhibitory action of levodopa-derived dopamine on the sympathetic nervous system.
SOLUTION: | Does sympathetic modulation by levodopa reduce vascular risk factors in Parkinson disease?
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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.
Context: Glutamic acid decarboxylase autoantibodies (GADA) are the most frequent beta-cell-specific autoantibodies in type 1 diabetes and in latent autoimmune diabetes in adults (LADA). The autoimmune attack on pancreatic islet cells is associated with a T helper 1 cell (T(h)1) response, mainly represented by IgG(1)-subclass in humans. It has been proposed that the presence of IgG(4) may be associated with a T(h)2 response. The aim of our study was to compare the GADA IgG-subclass distribution between adult patients with type 1 diabetes and LADA.', 'Patients with type 1 diabetes (n=45) and patients with LADA (n=60) were included. Radioimmunoprecipitation assay with IgG-subclass specific Sepharose (IgG(1), IgG(2), IgG(3) and IgG(4)) was used to precipitate the antibody/antigen-complex.', 'We only detected IgG(4)-subclass of GADA in subjects with LADA (26.7%; p<0.001). IgG(1) was the most common GADA-subclass in both groups, however IgG(1) as the solely expressed subclass was more common among type 1 diabetic patients (77.8%; p<0.05). The rank order of the frequencies of IgG-subclasses in type 1 diabetes was IgG(1)>IgG(3)>IgG(2)>IgG(4) and in LADA patients IgG(1)>IgG(4)>IgG(2)>IgG(3).
Answer: The difference in GADA IgG-subclasses could indicate a different immune response, possibly an altered balance between T(h)1 and T(h)2 cytokine profile in pancreatic islets. This difference could contribute to the slower rate of beta cell destruction in LADA patients, as reflected by a higher C-peptide level at clinical onset. | Is igG4-subclass of glutamic acid decarboxylase antibody more frequent in latent autoimmune diabetes in adults than in type 1 diabetes? | task845_pubmedqa_question_generation |
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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: To establish leukocyte count and leukocyte differential percentiles in normal uncomplicated pregnancy.', 'This retrospective longitudinal study was performed in an outpatient facility for routine antenatal care. The study population comprised of 726 healthy women from the 5th to the 41st week of pregnancy. Altogether, there were 1749 complete blood count evaluations, of which 481 were in the 1st trimester, 687 in the 2nd trimester and 581 in the 3rd trimester. The total and differential leukocyte counts were determined by an automated cell counter.', 'The leukocyte and neutrophil counts gradually and significantly increased form the 1st to the 3rd trimester. The monocyte count increase became significant only during the 3rd trimester. The eosinophil count did not significantly change throughout pregnancy. The basophil count significantly decreased during the 2nd trimester and returned to 1st trimester values during the 3rd trimester.
Answer: In this study, we provide total and differential leukocyte counts' mean+/-S.D., minimal and maximal values, and the 3rd, 5th, 10th, 50th, 90th, 95th, and 99th percentiles for entire pregnancy and for each trimester separately. These reference values should prove useful for diagnostic and research purposes.
Answer: Does total and differential leukocyte count percentiles in normal pregnancy?
Question: Context: Current views on the control of cell development are anchored on the notion that phenotypes are defined by networks of transcriptional activity. The large amounts of information brought about by transcriptomics should allow the definition of these networks through the analysis of cell-specific transcriptional signatures. Here we test this principle by applying an analogue to comparative anatomy at the cellular level, searching for conserved transcriptional signatures, or conserved small gene-regulatory networks (GRNs) on root hairs (RH) and pollen tubes (PT), two filamentous apical growing cells that are a striking example of conservation of structure and function in plants.', 'We developed a new method for isolation of growing and mature root hair cells, analysed their transcriptome by microarray analysis, and further compared it with pollen and other single cell transcriptomics data. Principal component analysis shows a statistical relation between the datasets of RHs and PTs which is suggestive of a common transcriptional profile pattern for the apical growing cells in a plant, with overlapping profiles and clear similarities at the level of small GTPases, vesicle-mediated transport and various specific metabolic responses. Furthermore, cis-regulatory element analysis of co-regulated genes between RHs and PTs revealed conserved binding sequences that are likely required for the expression of genes comprising the apical signature. This included a significant occurrence of motifs associated to a defined transcriptional response upon anaerobiosis.
Answer: Our results suggest that maintaining apical growth mechanisms synchronized with energy yielding might require a combinatorial network of transcriptional regulation. We propose that this study should constitute the foundation for further genetic and physiological dissection of the mechanisms underlying apical growth of plant cells.
Answer: Does transcriptional profiling of Arabidopsis root hairs and pollen define an apical cell growth signature?
Question: Context: To investigate the association between early menarche (menarche age < 12 years) and Type 2 diabetes mellitus in young and middle-aged Korean women.', 'We analysed data for 4657 women aged 20-50 years from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV) (2007-2009).', 'The prevalence of Type 2 diabetes was 2.8%. Women with early menarche had a higher prevalence of impaired fasting glucose than did women with later menarche (age ≥ 12 years) in the 20-30 age group (7.4% vs. 3.0%), and a higher prevalence of diabetes in the 30-40 (6.3% vs. 1.7%) and 40-50 (18.5% vs. 4.4%) age groups. The odds ratio (OR) of Type 2 diabetes in women with early menarche was 3.61 [95% confidence interval (CI), 1.90-6.88] after adjusting for age. In multivariate regression, the OR of Type 2 diabetes decreased to 2.52 (95% CI, 1.29-4.94) after further adjusting for BMI. However, the OR decreased to 2.04 (95% CI, 0.95-4.39) without significance after adjusting for HOMA-IR.
Answer: Early menarche increased the risk of Type 2 diabetes in young and middle-aged Korean women although adulthood adiposity attenuated the relationship. Knowledge of age at menarche is important in identifying women at risk for diabetes.
Answer: | Does early menarche increase the risk of Type 2 diabetes in young and middle-aged Korean women?
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Given the task definition and input, reply with output. 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.
Context: Reduced levels of free and total insulin-like growth factor 1 (IGF-I) have been observed in type-1 diabetes (T1D) patients. The bioavailability of IGF-I from the circulation to the target cells is controlled by multifunctional IGF-binding proteins (IGFBPs). The aim of this study was to profile serum IGFBPs in T1D and its complications.', 'We measured the IGFBP levels in 3662 patient serum samples from our ongoing Phenome and Genome of Diabetes Autoimmunity (PAGODA) study. IGFBP levels of four different groups of T1D patients (with 0, 1, 2, and ≥3 complications) were compared with healthy controls.', 'Three serum IGFBPs (IGFBP-1, -2, and -6) are significantly higher in T1D patients, and these alterations are greater in the presence of diabetic complications. IGFBP-3 is lower in patients with diabetic complications. Analyses using quintiles revealed that risk of T1D complications increases with increasing concentrations of IGFBP-2 (fifth quintile ORs: 18-60, p\u2009<\u200910(-26)), IGFBP-1 (fifth quintile ORs: 8-20, p\u2009<\u200910(-15)), and IGFBP-6 (fifth quintile ORs: 3-148, p\u2009<\u200910(-3)). IGFBP-3 has a negative association with T1D complications (fifth quintile ORs: 0.12-0.25, p\u2009<\u200910(-5)).
Answer: We found that elevated serum levels of IGFBP-1, -2, and -6 were associated with T1D, and its complications and IGFBP-3 level was found to be decreased in T1D with complications. Given the known role of these IGFBPs, the overall impact of these alterations suggests a negative effect on IGF signaling.
| Do iGF-Binding Proteins in Type-1 Diabetes Are More Severely Altered in the Presence of Complications? | task845_pubmedqa_question_generation |
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instruction:
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.
question:
Context: Alloreactive NK cells play a role in tumor eradication after allogeneic HLA mismatched stem cell transplantation (SCT). The effect of NK alloreactivity in HLA identical SCT is still under debate and in particular in transplantation for chronic myeloid leukemia (CML) the data are very limited and with conflicting outcome. The aim of our study was to evaluate the effect of KIR genes and KIR ligands on leukemia free survival (LFS) and relapse rate in a well-defined, homogeneous group of CML patients phase upon HLA identical sibling SCT.', 'We retrospectively analyzed the effect of KIRs and KIR ligands (C1 and C2) on LFS and relapse in 70 CML patients in 1st chronic phase, who had received an HLA identical sibling graft. For KIR typing we used a single PCR based KIR typing protocol that also included primers allowing for the identification of the KIR binding site on HLA-Cw (AA 77 and 80).', 'The data show clear differences in transplant outcome between patients having both ligands (C1 and C2) as compared to patients having only one ligand (C1 or C2). In the latter group, the stimulatory KIR2DS5 gene was associated with improved leukemia free survival (p=0.007; hazard ratio 4.3; 95% confidence interval 1.3-6.7) and lower relapse rates (p=0.028; HR 4.3, 95% CI 1.1-9.1). In contrast, in patients carrying both ligands, KIR2DS5 was associated with reduced LFS (p=0.0056; HR 0.3; 95% CI 0.1-0.7) and higher relapse rate (p=0.02; HR 0.35, 95% CI 0.1-0.8).
Answer: Our data indicate a role for an NK mediated anti-CML response after HLA identical sibling SCT that is influenced by KIR ligands and, more importantly, by stimulatory KIRs present in the donor.
answer:
Is kIR2DS5 associated with leukemia free survival after HLA identical stem cell transplantation in chronic myeloid leukemia patients?
question:
Context: High sensitivity C-reactive protein (hsCRP) is more sensitive than standard C-reactive protein (CRP) assay in evaluating the risk of coronary heart disease and other atherosclerotic events. By this time, there are several reports that type 2 diabetic subjects have higher serum levels of hsCRP than those of non-diabetic subjects. However, there are few reports about factors which have influence upon the level of serum hsCRP in type 2 diabetic subjects. We had evaluated the association of serum hsCRP level with risk factors of cardiovascular diseases and carotid intima-media thickness (IMT) in type 2 diabetic subjects.', 'One hundred and five patients (59 men and 46 women) with type 2 diabetes were recruited. Subjects with severe cardiovascular diseases were excluded. All subjects were undergone carotid ultrasonography for evaluation of carotid IMT. Serum hsCRP concentrations were measured.', 'Serum hsCRP level was correlated with mean left IMT (r = 0.366, P = 0.003), maximal left IMT (r = 0.370, P = 0.002), mean right IMT (r = 0.281, P = 0.023) and maximal right IMT (r = 0.370, P = 0.002), body mass index (r = 0.377, P < 0.001), waist circumference (r = 0.342, P < 0.001), waist-hip ratio (r = 0.229, P = 0.020), serum total cholesterol (r = 0.202, P = 0.024), serum triglyceride (r = 0.292, P = 0.022) and serum low-density lipoprotein (r = 0.133, P = 0.044).
Answer: Our result shows that serum hsCRP level is correlated with carotid IMT and the risk factors of cardiovascular diseases and may be useful to predict accelerated atherosclerotic process in type 2 diabetic subjects.
answer:
Is serum high sensitivity C-reactive protein associated with carotid intima-media thickness in type 2 diabetes?
question:
Context: Group I metabotropic glutamate receptors (mGluRs) have been reported to regulate N-methyl-d-aspartate (NMDA) receptor function in various brain regions. The selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) can potentiate NMDA antagonists such as PCP and MK-801-induced behavioural responses. In the present study, the role of group I mGluRs on ketamine- and propofol-induced general anaesthesia was examined.', 'Mice were pretreated with various doses of the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG), selective mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), mGluR1 antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) and mGluR5 antagonist MPEP followed by administration of ketamine (120 mg kg(-1)) or propofol (140 mg kg(-1)) to induce anaesthesia. The duration of loss of righting reflex was recorded.', 'DHPG and CHPG antagonized and MPEP potentiated ketamine-induced anaesthesia in a dose-dependent manner. CPCCOEt was ineffective. However, propofol-induced anaesthesia was not affected after manipulating mGluR1 and mGluR5 receptors.
Answer: mGluR5 receptors play an important role in modulation of anaesthesia induced by ketamine, but not propofol.
answer:
| Is ketamine , but not propofol , anaesthesia regulated by metabotropic glutamate 5 receptors?
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Detailed Instructions: 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.
Problem:Context: This study tested the hypothesis that pioglitazone reduces endothelin-1 activity in the forearm vasculature in non-diabetic patients with hypertension or hypercholesterolemia and variable degrees of insulin resistance.', 'We conducted a single center, randomized, double-blind, placebo controlled, cross-over trial in 80 patients with either hypertension or hypercholesterolemia and further classified as insulin-sensitive or insulin-resistant based on a published insulin sensitivity index. Participants received pioglitazone 45 mg daily or matching placebo for eight weeks. The main endpoint was the change in forearm vascular endothelin-1 activity, as assessed by intra-arterial infusion of the endothelin type A receptor blocker BQ-123, measured at the end of each 8-week treatment period.', 'Pioglitazone lowered plasma insulin (P < 0.001), improved insulin sensitivity (P < 0.001), increased HDL (P < 0.001), and reduced triglycerides (P = 0.003), free fatty acids (P = 0.005), and C-reactive protein (P = 0.001). However, pioglitazone did not affect the vasodilator response to BQ-123 in the whole group (P = 0.618) and in the diagnosis or insulin sensitivity subgroups. Hence, in non-diabetic patients with hypertension or hypercholesterolemia, PPARγ activation with pioglitazone does not affect endothelin-1 activity, despite enhancing insulin sensitivity and reducing plasma insulin and C-reactive protein levels.
Answer: In non-diabetic patients with hypertension or hypercholesterolemia, pioglitazone improves insulin sensitivity, lipid profile, and inflammation but does not affect endothelin activity. Our data suggest that the determinants of endothelin-1 vascular activity in vivo may differ and/or be more complex than those suggested by the results of previous in vitro studies.
Solution: | Does pPARγ activation affect endothelin activity in non-diabetic patients with hypertension or hypercholesterolemia? | task845_pubmedqa_question_generation |
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Definition: 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: Context: The commonest cause of mortality in patients with Type 2 diabetes is atherothrombosis, which can be related to abnormalities in the coagulation and fibrinolytic pathways, as well as in platelet function. Platelet microparticles (PMPs) may contribute to the prothrombotic state and may promote the progression of atherosclerosis. We hypothesized that PMPs are elevated in Type 2 diabetes and that patients with Type 2 diabetes and clinically apparent atherosclerosis would have the highest levels. Similarly, we hypothesized that soluble plasma P-selectin (sPsel) and CD40L (both molecules which are released by activated platelets), as well as %CD62P (P-selectin) and %CD63 positivity on platelets quantified by flow cytometry, would be highest in patients with Type 2 diabetes and clinically apparent atherosclerotic disease, and might be correlated to PMP levels.', 'Venous blood was obtained from 21 Type 2 diabetic patients without atherosclerotic complications, 18 diabetic patients with clinically apparent atherosclerotic disease and 21 non-diabetic control subjects. PMPs, as well as %CD62P and %CD63 positivity on platelets, were quantified by flow cytometry. sPsel and CD40L were measured using ELISA.', 'Patients with Type 2 diabetes and clinically apparent atherosclerotic disease had the highest PMP (P=0.045) and sPsel (P=0.046) levels, compared with patients without complications (who had intermediate PMP levels) and control subjects. Control subjects had the lowest CD40L levels (P<0.001) when compared with patients with Type 2 diabetes, with no difference in sCD40L levels between the two diabetic subgroups. %CD62P and %CD63 positivity did not differ between the groups. PMP levels correlated with %CD62P positivity (P=0.026) but not to %CD63 positivity (P=0.089), sCD40L (P=0.407) or sP-sel (P=0.163); sCD40L levels did not correlate with any other marker of platelet activation.
Answer: PMPs are elevated in Type 2 diabetes. In addition, patients with clinically apparent atherosclerosis had the highest levels of PMPs and sPsel. Thus, PMPs may be a marker of symptomatic atherosclerotic vascular disease in Type 2 diabetes, and may both represent a useful risk stratification tool as well as a novel therapeutic target for anti-thrombotic drugs.
Output: | Is clinically apparent atherosclerotic disease in diabetes associated with an increase in platelet microparticle levels? | task845_pubmedqa_question_generation |
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Detailed Instructions: 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.
Q: Context: The biological function of resistin (RST) is unknown, although it may have roles in obesity, diabetes, and insulin resistance. The objective of this study was to examine the effects of single nucleotide polymorphisms (SNPs) in the human RST gene on muscle, bone, and adipose tissue phenotypes and in response to resistance training (RT).', 'Subjects were white and consisted of strength (n = 482) and size (n = 409) cohorts who had not performed RT in the previous year. Subjects completed 12 weeks of structured, unilateral upper arm RT aimed at increasing the size and strength of the non-dominant arm, using their dominant arm as an untrained control. Strength measurements were taken pre- and post-12-week RT and consisted of elbow flexor isometric strength and one-repetition maximum during a biceps curl using free weights. Whole muscle, subcutaneous fat, and cortical bone volumes were measured by magnetic resonance imaging. Six RST SNPs were identified. Analysis of covariance was used to test for effects of the SNPs on pre- and post-muscle strength and whole muscle, fat, and bone volumes independent of gender, age, and body weight.', 'Five RST SNPs (-537 A>C, -420 C>G, 398 C>T, 540 G>A, 980 C>G) were associated with measured phenotypes among subjects when stratified by BMI (<25, >/ or = 25 kg/m(2)). Several gender-specific associations were observed between RST SNPs and phenotypes among individuals with a BMI > or = 25. Conversely, only two associations were observed among individuals with a BMI < 25.
Answer: These data support previous identified associations of RST with adipose tissue and demonstrate additional associations with bone and skeletal muscle that warrant further investigation.
A: | Are resistin polymorphisms associated with muscle , bone , and fat phenotypes in white men and women? | task845_pubmedqa_question_generation |
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Definition: 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: Context: The Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study showed that 40 mg Olmesartan medoxomil (OM) versus placebo delayed microalbuminuria onset in patients with type 2 diabetes and normoalbuminuria.', 'One thousand seven hundred and fifty-eight ROADMAP patients (placebo arm: 877; OM arm: 881) participated in the observational follow up (OFU) with an average of 3.3 years. They received standard medical care and micro- and macrovascular events were documented. During observational follow-up 62.9% and 60.1% in the former OM and placebo group, respectively, received treatment with a RAS blocking agent. During the OFU period the systolic blood pressure (SBP) increased to mean values of 135 mm Hg in both groups. Patients who had developed microalbuminuria during ROADMAP had a higher incidence of cardio- and cerebrovascular events (OR 1.77, CI 1.03 to 3.03, P=0.039) during the OFU period compared with patients in whom this was not the case. Diabetic retinopathy was significantly reduced in the former OM group (8 [0.9%] versus 23 [2.6%], OR: 0.34, CI 0.15 to 0.78, P=0.011) and the rate of microalbuminuria was numerically reduced. Congestive heart failure requiring hospitalization (3 [0.3%] versus 12 [1.4%], OR: 0.23, CI 0.06 to 0.85, P=0.027) was reduced and there was a trend of reduced cardio-/cerebrovascular events (OM versus Pb: 73 [8.3%] versus 86 [9.8%] patients). Seven (0.8%) deaths (including 2 CV events) were reported in former placebo patients versus 3 (0.3%) (non-CV events) in former OM patients.
Answer: Development of microalbuminuria is a valid marker for future CV events. RAS blockade with Olmesartan might cause sustained reduction (legacy effect) of micro- and macrovascular events.
Output: | Are the Randomized Olmesartan and Diabetes Microalbuminuria Prevention ( ROADMAP ) observational follow-up study : benefits of RAS blockade with olmesartan treatment sustained after study discontinuation? | task845_pubmedqa_question_generation |
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Given the task definition and input, reply with output. 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.
Context: The establishment of accurate equations for glomerular filtration rate (GFR) estimations is still far from the realization. Factors such as age, diabetes, stage of CKD, pregnancy, muscle mass and ethic nation are associated with less reliance upon commonly utilized estimation equations. We aimed to compare the routine use of 24-hour creatinine clearance (CrCl) and GFR estimates calculated by Crockoft-Gault (CG) and modification of diet in renal disease (MDRD) formulas in patients with different levels of renal dysfunction in subgroups, based on Body Mass Index (BMI) and serum albumin (Alb) levels.', 'Two hundred and seventy-nine non diabetic patients (172 men and 107 women), aged 54±23 years, with BMI 27.3±4.4 were enrolled in the study. All patients presented creatinine 1.8±1.2 (mg/dL) and Alb 3.5±1.3g/dL. The comparison of CrCl versus CG had bias 3.1 while the comparison of CrCl versus MDRD had a bias of 6.6.', 'Univariate analysis showed that age, sex and BMI were not significant biases related to the CG, MDRD and CrCl. Indeed, the bias related to the CG was significantly lower than that related to MDRD in patients with either low or high serum albumin. Interestingly, the bias associated with CG was 1.3 in non-diabetic patients with Alb ≤3.5 mg /dL suggesting that CG equation could be used interchangeable to CrCl in these patients.
Answer: CG gave a better prediction of measured CrCl than MDRD in Mediterranean, non-diabetic, non-hospitalized patients although misclassification of patients with regard to renal impairment stage was not present.
| Does comparison of creatinine clearance estimate in subgroups based on Body Mass Index and albumin? | task845_pubmedqa_question_generation |
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TASK DEFINITION: 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.
PROBLEM: Context: Dentofacial deformities are dys-morpho-functional disorders involving the temporomandibular joints (TMJ). Many authors have reported a TMJ improvement in dysfunctional subjects with malocclusion after orthodontic or combined orthodontic and surgical treatment particularly for the relief of pain. In particular, few studies have highlighted the demographic and clinical predictors of response to surgical treatment. To date, no genetic factor has yet been identified as a predictor of response to surgical treatment. The aim of this cohort study is therefore to identify single-nucleotide polymorphisms associated with postoperative temporomandibular disorders (TMD) or with TMJ symptoms after orthognathic surgery. Here, we found the AA genotype of SNP rs1643821 (ESR1 gene) as a risk factor for dysfunctional worsening after orthognathic surgery. In addition, we have identified TT genotype of SNP rs858339 (ENPP1 gene) as a protective factor against TMD in a population of patients with dentofacial deformities. Conversely, the heterozygous genotype AT was identified as a risk factor of TMD with respect to the rest of our population. All these elements are particularly important to bring new screening strategies and tailor future treatment.
Answer: This study allows us to identify sub-populations at high risk of developing postoperative temporomandibular disorders after orthognathic surgery procedures. Many other genes of interest could be potential factors influencing the dysfunctional response to orthognathic surgery, particularly genes of the Opera cohort.
SOLUTION: Do eNPP1 and ESR1 genotypes influence temporomandibular disorders development and surgical treatment response in dentofacial deformities?
PROBLEM: Context: Patients affected by chronic lymphocytic leukemia (CLL) have an increased risk of developing a second cancer. There is not a definitive explanation for this phenomenon, although some hypotheses have been postulated. The aim of the present work was to assess the presence of second cancer in untreated patients with CLL who were cytogenetically characterized, and secondly to investigate if there is a correlation between the genetics of CLL and the emergence of second cancer.', 'We performed conventional cytogenetics and Fluorescent in situ hybridization analyses in a series of 106 patients.', 'We observed that nearly 8% of cases developed second cancer, mostly epithelial tumors. The majority of them presented two common features, del(13)(q14.3) and the presence of at least two genetic alterations.
Answer: We suggest that the genetic background of CLL, particularly the presence of several genetic alterations, influences the emergence of second cancer in patients affected by CLL.
SOLUTION: Does genetics of lymphocytes influence the emergence of second cancer in chronic lymphocytic leukemia?
PROBLEM: Context: Vascular endothelial growth factor (VEGF) has been suggested to enhance glucose transport across the blood-brain barrier, thereby increasing brain glucose supply. Increased brain glucose concentration is known to suppress food intake and to decrease body mass via action on hypothalamic regulation centers. Based on the crucial role of VEGF on brain glucose supply, we hypothesized that higher VEGF concentrations are associated with lower food intake and body mass in humans.', 'Intending to investigate subjects with high variance of blood glucose, we examined patients with type 2 diabetes mellitus. Our hypothesis was tested in a population-based cohort of 190 subjects with type 2 diabetes. Plasma VEGF levels in conjunction with other parameters known to modulate food intake were measured and subsequently correlated with food intake patterns at a breakfast buffet as well as with body mass.', 'We found that subjects with higher concentrations of plasma VEGF had 17% less carbohydrate intake (P=0.003) and 4.8% lower body mass (P=0.017) than those with lower VEGF concentrations. Intake of protein and fat did not correlate with VEGF concentrations. These associations of plasma VEGF were confirmed in multiple linear regression analyses controlling for several parameters interacting with food intake.
Answer: We conclude that high plasma VEGF concentrations are associated with less carbohydrate intake and lower body mass in type 2 diabetes. The role VEGF plays in facilitating glucose access to the brain represents a new aspect of food intake regulation and energy homeostasis, with relevance for diseases with body mass disturbances.
SOLUTION: | Does high plasma VEGF relate to low carbohydrate intake in patients with type 2 diabetes?
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instruction:
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.
question:
Context: Cell death induced by intracellular glutathione depletion has been reported to be dependent on the presence of trace amounts of extracellular copper ions. Since little is known about the relationship between glutathione depletion and copper homeostasis, we have in the present study further investigated the role of low amounts of copper ions in glutathione depletion.', 'Glutathione turnover was investigated in HeLa and hepatoma cell cultures with normal and low cysteine content in the presence of copper ions (1 and 10micromol/L) and two other glutathione-stimulating agents (lipoic acid and mercury ions).', 'Copper ions (10micromol/L) caused relatively small increases in total amount of glutathione (the sum of the intracellular and the extracellular amount of glutathione) in HeLa and hepatoma cell cultures with normal cysteine levels (420nmol/mL) compared to control cell cultures, whereas lipoic acid and mercury ions strongly increased total glutathione in both types of cell cultures. Lower amount of total glutathione was observed in cell cultures with a lower cysteine levels (84nmol/mL), which is similar to that in human plasma. A strongly decreased total amount of glutathione in the presence of copper ions was observed in hepatoma cell cultures with lower cysteine levels, whereas the other agents showed effects similar to those described for cell cultures with normal cysteine levels.
Answer: Glutathione synthesis in hepatoma cell cultures is probably more sensitive to a low cysteine level than HeLa cell cultures, and the presence of copper ions further decreases the availability of cysteine probably by increasing the disulfide binding to cysteine residues in extracellular proteins, which causes a further decrease of total glutathione.
answer:
Do traces of copper ions deplete glutathione in human hepatoma cell cultures with low cysteine content?
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Context: The aim of this study was to determine the effects of exogenous expression of the catalytic subunit of telomerase (hTERT) on the lifespan, growth characteristics, and tumorigenicity of normal human ovarian surface epithelial (OSE) cells.', 'Low-passage primary cultures of normal human OSE cells were transfected with hTERT and the resulting cell lines were characterized.', 'The ectopic expression of hTERT stabilized the telomeres of the OSE cultures above 8 kb. The hTERT-transfected OSE cell lines grew beyond the normal lifespan seen in OSE cells and propagated in culture for more than 40 passages before senescing. Moreover, the hTERT-transfected cells demonstrated extensive proliferative capacity as evidenced by their ability to continuously grow even when seeded at low dilutions. The morphologic features and normal differentiation patterns seen in normal OSE cells were likewise retained by the hTERT-transfected cells. In addition, the cultures remained responsive to physiologic concentrations of epidermal growth factor and transforming growth factor-beta. Changes associated with neoplastic transformation like anchorage-independent growth, tumorigencity and karyotypic instability were not observed.
Answer: We were able to show that the ectopic expression of hTERT in normal human OSE: 1) resulted in cultures with greater growth potential and longer lifespan and 2) did not induce a transformed phenotype previously seen in viral oncogene-transfected OSE cells. The established cell lines would not only provide sufficient material for comprehensive studies to investigate the normal physiology of OSE cells, but could also help in the understanding of the early steps of ovarian carcinogenesis.
answer:
Does telomerase prolong the lifespan of normal human ovarian surface epithelial cells without inducing neoplastic phenotype?
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Context: To explore the effects of sulforaphane (SFN) on neuronal apoptosis in hippocampus and memory impairment in diabetic rats.', 'Thirty male rats were randomly divided into normal control, diabetic model and SFN treatment groups (N = 10 in each group). Streptozotocin (STZ) was applied to establish diabetic model. Water Morris maze task was applied to test learning and memory. Tunel assaying was used to detect apoptosis in hippocampus. The expressions of Caspase-3 and myeloid cell leukemia 1(MCL-1) were detected by western blotting. Neurotrophic factor levels and AKT/GSK3β pathway were also detected.', 'Compared with normal control, learning and memory were apparently impaired, with up-regulation of Caspase-3 and down-regulation of MCL-1 in diabetic rats. Apoptotic neurons were also found in CA1 region after diabetic modeling. By contrast, SFN treatment prevented the memory impairment, decreased the apoptosis of hippocampal neurons. SFN also attenuated the abnormal expression of Caspase-3 and MCL-1 in diabetic model. Mechanically, SFN treatment reversed diabetic modeling-induced decrease of p-Akt, p-GSK3β, NGF and BDNF expressions.
Answer: SFN could prevent the memory impairment and apoptosis of hippocampal neurons in diabetic rat. The possible mechanism was related to the regulation of neurotropic factors and Akt/GSK3β pathway.
answer:
| Does sulforaphane prevent Neuronal Apoptosis and Memory Impairment in Diabetic Rats?
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TASK DEFINITION: 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.
PROBLEM: Context: Perturbation of the endoplasmic reticulum (ER) homeostasis has emerged as one of the prominent features of obesity and diabetes. This occurs when the adaptive unfolded protein response (UPR) fails to restore ER function in key metabolic tissues. We previously reported increased inflammation and impaired heat shock response (HSR) in obese human subjects that were restored by physical exercise. Here, we investigated the status of ER stress chaperone; glucose-regulated protein 78 (GRP78) and its downstream UPR pathways in human obese, and their modulation by a supervised 3-month physical exercise.', "Subcutaneous adipose tissue (SAT) and blood samples were collected from non-diabetic adult human lean (n=40) and obese (n=40, at baseline and after 3months of physical exercise). Transcriptomic profiling was used as a primary screen to identify differentially expressed genes and it was carried out on SAT samples using the UPR RT(2) Profiler PCR Array. Conventional RT-PCR, immunohistochemistry, immunofluorescence, Western blot and ELISA were used to validate the transcriptomic data. Correlation analyses with the physical, clinical and biochemical outcomes were performed using Pearson's rank correlation coefficient.", 'Levels of GRP78 and its three downstream UPR arms; activating transcription factor-6 (ATF6), inositol-requiring enzyme-1α (IRE1α) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) were increased in obese subjects. More interestingly, higher levels of circulating GRP78 protein were found in obese compared to lean subjects which correlated negatively with maximum oxygen uptake (VO2 Max) but positively with high-sensitivity C-reactive protein (hsCRP) and obesity indicators such as BMI, percentage body fat (PBF) and waist circumference. GRP78 increased secretion in obese was further confirmed in vitro using 3T3-L1 preadipocyte cells under ER stress. Finally, we showed that physical exercise significantly attenuated the expression and release of GRP78 with a concomitant reduction in the phosphorylation of IRE1α and eukaryotic initiation factor-2α (eIF2α).
Answer: Our results suggest that physical exercise alleviates ER stress in human obese through attenuation of GRP78 signaling network.
SOLUTION: Does physical exercise alleviate ER stress in obese humans through reduction in the expression and release of GRP78 chaperone?
PROBLEM: Context: A functional vacuolar adenosine triphosphatase (v-ATPase) complex regulates canonical Wnt/β-catenin signaling. The goal of this study was to identify the distribution of the v-ATPase in human and murine models of pancreatic intraepithelial neoplasms (PanINs) and assess its role in Wnt/β-catenin signaling.', 'We evaluated the immunolabeling pattern of the v-ATPase in human PanIN specimens and murine PanIN-1 and PanIN-2 lesions obtained from Ptf1a(Cre/+); LSL-Kras(G12D) mice. Wnt/β-catenin signaling was interrogated in primary PanIN cells by examining the phosphorylated levels of its surface coreceptor, low-density lipoprotein receptor-related protein-6 (LRP6), and its intracellular effector, nonphosphorylated β-catenin. The response of primary PanIN cells to epidermal growth factor (EGF) was assessed in the absence and presence of the v-ATPase inhibitor, concanamycin.', 'In advanced (PanIN-2), but not early (PanIN-1), lesions, the v-ATPase assumed a polarized phenotype. Blocking the v-ATPase disrupted Wnt/β-catenin signaling in primary PanIN cells despite significantly higher levels of the total and activated Wnt cell surface coreceptor, LRP6. Vacuolar adenosine triphosphatase blockade significantly decreased the total and activated levels of EGF receptor, a determinant of PanIN progression. The activation of EGF receptor and its intracellular mediator, p44/42 mitogen-activated protein kinase, was also reduced by v-ATPase blockade. This led to diminished proliferation in response to EGF ligand.
Answer: The v-ATPase regulates Wnt/β-catenin and EGF receptor signaling in PanINs.
SOLUTION: Does polarization of the vacuolar adenosine triphosphatase delineate a transition to high-grade pancreatic intraepithelial neoplasm lesions?
PROBLEM: Context: Previously, we found an 11-gene signature could predict pelvic lymph node metastasis (PLNM), and WNT2 is one of the key genes in the signature. This study explored the expression and underlying mechanism of WNT2 in PLNM of cervical cancer.', 'WNT2 expression level in cervical cancer was detected using western blotting, quantitative PCR, and immunohistochemistry. Two WNT2-specific small interfering RNAs (siRNAs) were used to explore the effects of WNT2 on invasive and metastatic ability of cancer cells, and to reveal the possible mechanism of WNT2 affecting epithelial-mesenchymal transition (EMT). The correlation between WNT2 expression and PLNM was further investigated in clinical cervical specimens.', 'Both WNT2 mRNA and protein expression was upregulated in cervical cancer. High WNT2 expression was significantly associated with tumor size, lymphovascular space involvement, positive parametrium, and most importantly, PLNM. PLNM and WNT2 expression were independent prognostic factors for overall survival and disease-free survival. WNT2 knockdown inhibited SiHa cell motility and invasion and reversed EMT by inhibiting the WNT2/β-catenin pathway. WNT2 overexpression in cervical cancer was associated with β-catenin activation and induction of EMT, which further contributed to metastasis in cervical cancer.
Answer: WNT2 might be a novel predictor of PLNM and a promising prognostic indicator in cervical cancer.
SOLUTION: | Does wNT2 promote Cervical Carcinoma Metastasis and Induction of Epithelial-Mesenchymal Transition?
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Detailed Instructions: 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.
Q: Context: To evaluate whether Nrf2 deficiency impacts insulin resistance and lipid accumulation in liver and white adipose tissue.', 'Lep(ob/ob) mice (OB) with targeted Nrf2 deletion (OB-Nrf2KO) were generated. Pathogenesis of obesity and type 2 diabetes was measured in C57BL/6J, Nrf2KO, OB, and OB-Nrf2KO mice. Hepatic lipid content, lipid clearance, and very low-density lipoprotein (VLDL) secretion were determined between OB and OB-Nrf2KO mice.', 'OB-Nrf2KO mice exhibited decreased white adipose tissue mass and decreased adipogenic and lipogenic gene expression compared with OB mice. Nrf2 deficiency prolonged hyperglycemia in response to glucose challenge, which was paralleled by reduced insulin-stimulated Akt phosphorylation. In OB mice, Nrf2 deficiency decreased hepatic lipid accumulation, decreased peroxisome proliferator-activated receptor γ expression and nicotinamide adenine dinucleotide phosphate (NADPH) content, and enhanced VLDL secretion. However, this observation was opposite in lean mice. Additionally, OB-Nrf2KO mice exhibited increased plasma triglyceride content, decreased HDL-cholesterol content, and enhanced apolipoprotein B expression, suggesting Nrf2 deficiency caused dyslipidemia in these mice.
Answer: Nrf2 deficiency in Lep(ob/ob) mice reduced white adipose tissue mass and prevented hepatic lipid accumulation but induced insulin resistance and dyslipidemia. This study indicates a dual role of Nrf2 during metabolic dysregulation-increasing lipid accumulation in liver and white adipose tissue but preventing lipid accumulation in obese mice.
A: | Does deficiency in Nrf2 transcription factor decrease adipose tissue mass and hepatic lipid accumulation in leptin-deficient mice? | task845_pubmedqa_question_generation |
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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.
One example is below.
Q: Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
A: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Rationale: The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
Q: Context: Recent studies evaluated the disease-modifying properties of lithium in mild cognitive impairment and dementia. Although potentially effective for these purposes, chronic lithium use in regard to safety in the elderly needs to be better explored.', 'To evaluate the effect of long-term lithium treatment at subtherapeutic doses on renal function in older adults. Secondary aims were to evaluate the clinical safety and tolerability of this treatment and its effects on thyroid, immune, and glycemic functions.', 'Between February 2007 and October 2011, a 2-year randomized, double-blind, placebo-controlled trial followed by a single-blinded phase for an additional 2 years. Sixty-one patients with mild cognitive impairment (Mayo Clinic criteria) were randomized to receive lithium or placebo. Renal function was estimated by the abbreviated Modification of Diet in Renal Disease (aMDRD) and the Chronic Kidney Disease-Epidemiology study (CKD-EPI) equations. Leukocytes, serum thyroid-stimulating hormone (TSH) and free thyroxine (T₄), and serum glucose and insulin were determined. Tolerability was evaluated at 3-month intervals through systematic clinical examinations and by the UKU Side Effect Rating Scale.', 'Analysis of longitudinal regression indicated that no significant changes in renal function were detected by the aMDRD (P = .453) and CKD-EPI (P = .213) equations after 4 years of lithium treatment. Significant increases in the number of neutrophils (P = .038), serum TSH (P = .034), and body weight (P = .015) were observed in the lithium group. The lithium group presented more overall adverse events (P = .045), particularly interfering in daily activities (P < .001). In addition, those patients had a higher incidence of diabetes mellitus (P = .037) and arrhythmia (P = .028).
Answer: Chronic use of lithium at low doses did not affect renal function and was clinically safe. However, some other potentially relevant adverse events were observed and others could not be ruled out due to limitations of the study design.
A: | Does long-term , low-dose lithium treatment impair renal function in the elderly : a 2-year randomized , placebo-controlled trial followed by single-blind extension? | task845_pubmedqa_question_generation |
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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: Asteatotic eczema (AE) is characterized by itchy, dry, rough, and scaling skin. The treatments for AE are mainly emollients, usually containing urea, lactic acid, or a lactate salt. N-palmitoylethanolamine (PEA) and N-acetylethanolamine (AEA) are both endogenous lipids used as novel therapeutic tools in the treatment of many skin diseases. The purpose of this study was to compare a PEA/AEA emollient with a traditional emollient in the treatment of AE.', "A monocentric, randomized, double-blind, comparative trial was conducted in 60 AE patients to evaluate and compare the efficacy of the two emollients. The level of skin dryness among the subjects ranged from mild to moderate. The subjects' skin barrier function and the current perception threshold were tested for 28 days by clinical scoring and bioengineering technology.", 'The results showed that, although some aspects were improved in both groups, the group using the emollient containing PEA/AEA presented a better skin surface change in capacitance. However, the most impressive finding was the ability of the PEA/AEA emollient to increase the 5 Hz current perception threshold to a normal level after 7 days, with a significant difference between values at baseline and after 14 days. A current perception threshold of 5 Hz was positively and significantly correlated with skin surface hydration and negatively correlated with transepidermal water loss in the PEA/AEA emollient group.
Answer: Compared with traditional emollients, regular application of a topical PEA/AEA emollient could improve both passive and active skin functions simultaneously.
Output: Are n-palmitoylethanolamine and N-acetylethanolamine effective in asteatotic eczema : results of a randomized , double-blind , controlled study in 60 patients?
Input: Consider Input: Context: Animal and human studies suggest that programing of the hypothalamic-pituitary-adrenal (HPA) axis may be involved in the development of obesity, but human studies of biological indicators of HPA axis activity are lacking. We studied the association between levels of the stress hormone cortisol during pregnancy and overweight offspring during childhood into adolescence.', 'Salivary samples from 655 Danish pregnant women with singleton pregnancies (1989-1991) were collected once in the morning and once in the evening in their second and third trimester. We followed the offspring from two to 16 years of age with at least one measurement of height and weight, and classified their body mass index into overweight and normal weight. The adjusted relative difference in median salivary cortisol (with 95% confidence interval (CI)) during pregnancy (the four samples), in second and third trimester (morning and evening samples) between overweight and normal weight offspring was estimated. Furthermore, the adjusted median ratio between morning and evening maternal salivary cortisol level was estimated for normal weight and overweight children. All the analyses were stratified into the equal age groups: 2-6, 7-11, and 12-16 years.', 'We found non-significant higher maternal cortisol levels during pregnancy in offspring that were overweight at the age of 2-6, 7-11 and 12-16 years than in normal weight peers; adjusted relative difference in median salivary cortisol 11% (95% CI: -2; 25), 6% (95% CI: -7; 20), and 9% (95% CI: -4; 24), respectively. A statistically significantly higher level of maternal cortisol was found in the second trimester in 2-6-year-old and 12-16-year-old overweight offspring; relative difference 19% (95% CI: 3; 37), and 20% (95% CI: 3; 41), respectively. The median ratio between morning and evening maternal salivary cortisol level was similar for overweight and normal weight children; e.g. at age 2-6 years in third trimester 4.31 (95% CI: 4.05; 4.60)nmol/l and 4.28 (95% CI: 3.60; 5.09)nmol/l, respectively (P=0.93).
Answer: Our findings suggest a relatively consistent association between pregnancy cortisol levels and overweight offspring, especially in the second trimester.
Output: Are maternal salivary cortisol levels during pregnancy positively associated with overweight children?
Input: Consider Input: Context: Circulating adiponectins have multiple protective roles as anti-diabetic, anti-atherosclerotic, and anti-inflammatory factors. We examined the relationship between plasma adiponectin concentration and other cardiovascular risk in nondiabetic coronary artery disease (CAD) men and the relationship can be maintained even after adjusted for major environmental factors that contribute to adiponectin concentrations.', 'Nondiabetic CAD men (n=613) were 31-70 y and had body mass index (BMI) of 18.5-29.9 kg/m2.', "Circulating adiponectins positively correlated with age and negatively with BMI, waist circumference and % body fat (p-values of all <0.001). Plasma adiponectin concentrations were higher in never-smokers (5.07+/-0.30 microg/ml) than current (4.15+/-0.12 microg/ml) and ex-smokers (3.75+/-0.20 microg/ml) both before and after adjusted for age and adiposity (p=0.002 and p=0.008, respectively), however they were not significantly different according to alcohol drinking status. After adjusted for age, adiposity and cigarette smoking, plasma adiponectin still have positive correlations with HDL cholesterol, apolipoprotein AI and LDL particle size, and inversely with fasting triglyceride, atherogenic index, insulin resistance and C-reactive protein (CRP). However there was no significant relationships between adiponectin and apolipoprotein B, total cholesterol or LDL cholesterol. In subset analysis by tertile adiponectin concentrations (lowest: <2.92, moderate: 2.92<or=adiponectin<4.75, highest: >or=4.75 microg/ml), 'moderate' and 'highest' adiponectin groups had lower triglyceride (p<0.001), lower atherogenic index (p=0.001), lower fasting insulin (p=0.004), lower insulin resistance (p=0.001), lower CRP (p=0.001), higher HDL cholesterol (p<0.001), higher apolipoprotein AI (p=0.005) and higher LDL particle size (p<0.001) as compared with 'lowest' adiponectin group when adjusted for age, adiposity and cigarette smoking. Platelets were lower in 'highest' adiponectin groups as compared with 'lowest' and 'moderate' adiponectin group after the adjustment. However, there was no significant difference in total cholesterol (p=0.145), LDL cholesterol (p=0.145), apolipoprotein B (p=0.222) and fasting glucose (p=0.157).
Answer: An increase of adiponectin concentrations or the maintenance of higher concentration may be negatively associated with cardiovascular risk factors in nondiabetic CAD male patients, independent of adiposity and smoking status.
| Output: Is plasma adiponectin related to other cardiovascular risk factors in nondiabetic Korean men with CAD , independent of adiposity and cigarette smoking : cross-sectional analysis?
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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.
Q: Context: The polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance predisposing to diabetes mellitus type 2 and atherosclerosis. Adiponectin is a recently discovered adipocytokine with insulin-sensitizing and putative antiatherosclerotic properties. The aim of the study was to elucidate determinants of circulating adiponectin levels and to investigate the potential role of adiponectin in insulin resistance in PCOS women.', 'Plasma adiponectin and parameters of obesity, insulin resistance and hyperandrogenism were measured In 62 women with PCOS and in 35 healthy female controls.', 'Both in PCOS and controls, adiponectin levels were lower in overweight or obese women than in normal-weight women, without any difference between PCOS and controls after adjustment for body mass index (BMI). In PCOS and in controls there was a significant correlation of adiponectin with BMI (r = -0.516, P < 0.001), fasting insulin (r = -0.404, P < 0.001), homeostasis model sensitivity (HOMA %S) (r = -0.424, P < 0.001) and testosterone (r = -0.279, P < 0.01), but no correlation with androstenedione (r = -0.112, P = 0.325), 17-OH-progesterone (r =-0.031, P = 0.784) or the LH/FSH ratio (r =-0.033, P = 0.753). Multiple linear regression analysis revealed that BMI and HOMA %S but not testosterone were independently associated with adiponectin plasma levels, explaining 16% (BMI) and 13% (HOMA %S) of the variability of adiponectin, respectively. In PCOS patients insulin sensitivity, as indicated by continuous infusion of glucose with model assessment (CIGMA %S) was significantly correlated with adiponectin (r = 0.55; P < 0.001), BMI (r =-0.575; P < 0.001), waist-to-hip ratio (WHR) (r =-0.48; P = 0.001), body fat mass assessed by dual-energy X-ray-absorptiometry (DEXA) [Dexa-fat (total) (r = -0.61; P < 0.001) and Dexa-fat (trunk) (r = -0.59; P < 0.001)] and with testosterone (r = -0.42; P = 0.001). Multiple linear regression analysis demonstrated that markers of obesity such as BMI, total or truncal fat mass, age and adiponectin were independently associated with CIGMA %S, and that circulating adiponectin accounted for about 18% of the degree of insulin resistance in PCOS. By contrast, testosterone was not a significant factor, suggesting that PCOS per se did not affect insulin sensitivity independent from obesity, age and adiponectin. Metformin treatment for 6 months in insulin-resistant PCOS women (n = 9) had no effect on plasma adiponectin (P = 0.59) despite significant loss of weight and fat mass and improvement in hyperandrogenaemia.
Answer: PCOS per se is not associated with decreased levels of plasma adiponectin. However, circulating adiponectin is independently associated with the degree of insulin resistance in PCOS women and may contribute to the development and/or maintenance of insulin resistance independent from adiposity.
A: | Is adiponectin independently associated with insulin sensitivity in women with polycystic ovary syndrome? | task845_pubmedqa_question_generation |
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TASK DEFINITION: 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.
PROBLEM: Context: Central core disease is a congenital myopathy, characterized by presence of central core-like areas in muscle fibers. Patients have mild or moderate weakness, hypotonia and motor developmental delay. The disease is caused by mutations in the human ryanodine receptor gene (RYR1), which encodes a calcium-release channel. Since the RYR1 gene is huge, containing 106 exons, mutation screening has been limited to three 'hot spots', with particular attention to the C-terminal region. Recent next-generation sequencing methods are now identifying multiple numbers of variants in patients, in which interpretation and phenotype prevision is difficult.", "In a Brazilian Caucasian family, clinical, histopathological and molecular analysis identified a new case of central core disease in a 48-year female. Sanger sequencing of the C-terminal region of the RYR1 gene identified two different missense mutations: c.14256 A >\u2009C polymorphism in exon 98 and c.14693 T >\u2009C in exon 102, which have already been described as pathogenic. Trans-position of the 2 mutations was confirmed because patient's daughter, mother and sister carried only the exon 98's mutation, a synonymous variant that was subsequently found in the frequency of 013-0,05 of alleles. Further next generation sequencing study of the whole RYR1 gene in the patient revealed the presence of additional 5 common silent polymorphisms in homozygosis and 8 polymorphisms in heterozygosis.
Answer: Considering that patient's relatives showed no pathologic phenotype, and the phenotype presented by the patient is within the range observed in other central core disease patients with the same mutation, it was concluded that the c.14256 A > C polymorphism alone is not responsible for disease, and the associated additional silent polymorphisms are not acting as modifiers of the primary pathogenic mutation in the affected patient. The case described above illustrates the present reality where new methods for wide genome screening are becoming more accessible and able to identify a great variety of mutations and polymorphisms of unknown function in patients and their families.
SOLUTION: Do silent polymorphisms in the RYR1 gene modify the phenotype of the p.4898 I > T pathogenic mutation in central core disease : a case report?
PROBLEM: Context: The independent prognostic value of high-sensitivity C-reactive protein (hsCRP) has been questioned, and consequently we decided to investigate whether hsCRP was associated with subclinical cardiovascular (CV) damage independently of traditional CV risk factors.', 'In a population-based sample of 2028 apparently healthy individuals without prior stroke or myocardial infarction not receiving any CV, anti-diabetic or lipid-lowering treatment, aged 41, 51, 61 or 71 years, we measured in 1993 serum hsCRP, traditional CV risk factors (lifestyle, metabolic and hemodynamic) and assessed subclinical CV damage [atherosclerotic plaques in the carotid arteries, pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular (LV) mass and ejection fraction].', 'Adjusting for age and gender in multiple regression analyses, higher log(hsCRP) was associated with higher logPWV (beta = 0.15) and log(left ventricular mass index) (LVMI) (beta = 0.09, both P < 0.001), LV relative wall thickness (beta = 0.07, P < 0.01), logUACR (beta = 0.04, P = 0.06) and more atherosclerotic plaques (beta = 0.06, P < 0.05). However, higher log(hsCRP) was only weakly associated with higher logPWV(beta = 0.06, P < 0.05) and more atherosclerotic plaques (beta = 0.04, P = 0.06) when adjusting for other significant CV risk factors, such as daily smoking (beta = 0.18), female gender (beta = -0.17), older age (beta = 0.11), lower log(high density lipoprotein cholesterol) (beta = -0.11, all P < 0.001); wider waist (beta = 0.17), higher body mass index (beta = 0.14), higher heart rate (beta = 0.06, all P < 0.01); and higher log(plasma glucose) (beta = 0.05, P < 0.05) (adj. R2 = 0.19, P < 0.001).
Answer: After adjustment for traditional CV risk factors hsCRP was only associated with PWV and atherosclerotic plaques, indicating a possible effect of low-grade inflammation on macrovascular damage. The close relationship between traditional CV risk factors and hsCRP suggested that hsCRP was an integrated CV risk marker early in the development of atherosclerosis.
SOLUTION: Is high-sensitivity C-reactive protein only weakly related to cardiovascular damage after adjustment for traditional cardiovascular risk factors?
PROBLEM: Context: Intravascular volume loss from ischemia-reperfusion (IR) injury is a major clinical concern. We hypothesize that angiotensin II decreases IR-mediated microvascular fluid leak via the angiotensin II type 2 receptor in a cAMP dependent manner. We therefore sought to determine hydraulic permeability after IR of venules treated with 1) angiotensin II, 2) angiotensin II and cAMP synthesis inhibitor, and 3) angiotensin II and an angiotensin II type 2 receptor antagonist.', 'Rat mesenteric post-capillary venules were micro-cannulated to measure hydraulic permeability (L(p)). IR was achieved by placing animals in a 5% oxygen environment and preventing venular flow, after which blood flow was allowed to resume. L(p) was measured after IR and treatment with 1) angiotensin II (20 nm), 2) angiotensin II (20 nm) + cAMP synthesis inhibitor (DDA,10uM), and 3) angiotensin II (20 nm) + type 2 receptor antagonist (PD-123319, 300 mum) (n=6 in each group).', 'Compared with the seven-fold increase in L(p) because of IR alone: 1) angiotensin II attenuated the seven-fold increase by 50% (P<0.005), 2) cAMP inhibition did not change the effect of angiotensin II on leak, and the type 2 receptor antagonist completely blocked the effects of angiotensin II on IR mediated leak.
Answer: Treatment with angiotensin II attenuated increases in hydraulic permeability because of IR by 50%. Inhibition of cAMP synthesis did not change the effect of angiotensin II on IR mediated leak, and angiotensin II type 2 receptor inhibition completely blocked the effects of angiotensin II. These results indicate that angiotensin II decreases IR induced leak via the angiotensin II type 2 receptor in a cAMP independent manner. A better understanding of mediators that reduce intravascular fluid loss from IR-induced microvascular dysfunction may help clinicians treat uncontrolled fluid extravasation that occurs during shock and sepsis.
SOLUTION: | Does angiotensin II type 2 receptor decrease ischemia reperfusion induced fluid leak?
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Detailed Instructions: 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.
Q: Context: Diabetic nephropathy (DN) is a serious complication that commonly confronted by diabetic patients. A common theory for the pathogenesis of this renal dysfunction in diabetes is cell injury, inflammation as well as oxidative stress. In this content, the detailed molecular mechanism underlying high glucose induced renal tubular epithelial injury was elaborated.', "An in vivo rat model of diabetes by injecting streptozotocin (STZ) and an in vitro high glucose incubated renal tubular epithelial cell (HK-2) model were used. Expression levels of Keap1, nuclear Nrf2 and p65 were determined by western blotting. Level of microR-29 (miR-29) was assessed using quantitative RT-PCR. Combination of p65 and miR-29 promotor was assessed using chromatin immunoprecipitation. Keap1 3'-UTR activity was detected using luciferase reporter gene assay. Cell viability was determined using MTT assay.", 'In diabetic rat, miR-29 was downregulated and its expression is negatively correlated with both of serum creatinine and creatinine clearance. In high glucose incubated HK-2 cell, deacetylases activity of Sirt1 was attenuated that leads to decreased activity of nuclear factor kappa B (NF-κB). NF-κB was demonstrated to regulate miR-29 expression by directly binding to its promotor. The data of luciferase assay showed that miR-29 directly targets to Keap1 mRNA. While high glucose induced down regulation of miR-29 contributed to enhancement of Keap1 expression that finally reduced Nrf2 content by ubiquitinating Nrf2. Additionally, overexpression of miR-29 effectively relieved high glucose-reduced cell viability.
Answer: High glucose induces renal tubular epithelial injury via Sirt1/NF-κB/microR-29/Keap1 signal pathway.
A: | Does high glucose induce renal tubular epithelial injury via Sirt1/NF-kappaB/microR-29/Keap1 signal pathway? | task845_pubmedqa_question_generation |
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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.
Ex Input:
Context: Increasing evidence points to the inflammatory character of atherosclerosis and several parameters of inflammation have been proposed as cerebrovascular risk markers. The objective of the research was to examine the connection of serum inflammatory parameters and ultrasound (US) characteristics of the structure and size of carotid plaque. We assumed that the number of leukocytes (Le) was an indicator of carotid plaque instability and an increased risk of stroke.', 'Serum inflammatory parameters: erythrocyte sedimentation rate in the first (ESR I) and second hour (ESR II), the number of Le, high sensitivity C-reactive protein (hsCRP) and fibrinogen were measured by standard methods. All the subjects (n = 75) were divided into 3 groups (symptomatic, asymptomatic and control). US evaluation of extracranial carotid arteries was performed in a duplex system. Plaques were classified into categories according to stenosis percentage (≥ 50%, < 50%) and pursuant to echomorphological characteristics (Gray-Weale classification). In the subjects with stroke an ischemic lesion was confirmed by computed tomography.', 'The average values of biochemical parameters in the symptomatic group were: ESR I 29.57 ± 29.87 cm, ESR II 51.60 ± 36.87 cm, the number of Le 10.10 ± 3.20 x 10⁹ U/L, hsCRP 8.15 ± 5.50 mg/L and fibrinogen 4.03 ± 0.70 g/L. The average values of all testing biochemical parameters in symptomatic patients were significantly higher than in the asymptomatic ones and the control group: for ESR I (p < 0.05) and ESR II (p < 0.05); for the number of Le (p < 0.001); for hsCRP (p < 0.001) and fibrinogen (p < 0.001). Category I of echomorphological characteristics in the symptomatic group was present in 66.7% of the cases and it was significantly higher than in the asymptomatic (40.0%; p < 0.05) and the control group (20.0%; p < 0.01). Univariate logistic regression analysis confirmed that all testing biochemical parameters are indicators of stroke risk. Multivariate logistic regression analysis confirmed a statistically significant correlation of the number of Le and stroke risk, while the increase in the value by a unit of measurement was associated with the growth of risk by 3.22 times (from 1.67 to 6.22).
Answer: The number of Le is associated with the phenomenon of carotid plaque instability and may be a useful additional marker of increased risk for developing acute cerebral infarction.
Ex Output:
Does leucocyte count indicate carotid plaque instability in stroke patients?
Ex Input:
Context: Women with a family history of breast cancer face considerable uncertainty about whether to pursue standard screening, intensive screening, or prophylactic surgery. Accurate and individualized risk-estimation approaches may help these women make more informed decisions. Although highly penetrant genetic variants have been associated with familial breast cancer (FBC) risk, many individuals do not carry these variants, and many carriers never develop breast cancer. Common risk variants have a relatively modest effect on risk and show limited potential for predicting FBC development. As an alternative, we hypothesized that additional genomic data types, such as gene-expression levels, which can reflect genetic and epigenetic variation, could contribute to classifying a person's risk status. Specifically, we aimed to identify common patterns in gene-expression levels across individuals who develop FBC.", 'We profiled peripheral blood mononuclear cells from women with a family history of breast cancer (with or without a germline BRCA1/2 variant) and from controls. We used the support vector machines algorithm to differentiate between patients who developed FBC and those who did not. Our study used two independent datasets, a training set of 124 women from Utah (USA) and an external validation (test) set from Ontario (Canada) of 73 women (197 total). We controlled for expression variation associated with clinical, demographic, and treatment variables as well as lymphocyte markers.', 'Our multigene biomarker provided accurate, individual-level estimates of FBC occurrence for the Utah cohort (AUC = 0.76 [0.67-84]) . Even at their lower confidence bounds, these accuracy estimates meet or exceed estimates from alternative approaches. Our Ontario cohort resulted in similarly high levels of accuracy (AUC = 0.73 [0.59-0.86]), thus providing external validation of our findings. Individuals deemed to have "high" risk by our model would have an estimated 2.4 times greater odds of developing familial breast cancer than individuals deemed to have "low" risk.
Answer: Together, these findings suggest that gene-expression levels in peripheral blood cells reflect genomic variation associated with breast cancer risk and that such data have potential to be used as a non-invasive biomarker for familial breast cancer risk.
Ex Output:
Do gene-expression patterns in peripheral blood classify familial breast cancer susceptibility?
Ex Input:
Context: Insulin resistance and hyperglycaemia are common in severe sepsis. Mitochondrial uncoupling protein 2 (UCP2) plays a role in insulin release and sensitivity.', 'To determine if a common, functional polymorphism in the UCP2 gene promoter region (the -866 G/A polymorphism) contributes to the risk of hyperglycaemia in severe sepsis.', 'In the prospective group 120 non-diabetic patients who were carriers of the G allele had significantly higher maximum blood glucose recordings than non-carriers (mean (SD) AA 8.5 (2.2) mmol/l; GA 8.5 (2.4) mmol/l; GG 10.1 (3.1) mmol/l; p = 0.0042) and required significantly more insulin to maintain target blood glucose (p = 0.0007). In the retrospective study 103 non-diabetic patients showed a similar relationship between maximum glucose and UCP genotype (AA 6.8 (2.3) mmol/l; GA 7.8 (2.2) mmol/l; GG 9.2 (2.9) mmol/l; p = 0.0078).
Answer: A common, functional polymorphism in the promoter region of the UCP2 gene is associated with hyperglycaemia and insulin resistance in severe sepsis. This has implications for our understanding of the genetic pathophysiology of sepsis and is of use in the stratification of patients for more intensive management.
Ex Output:
| Does a common UCP2 polymorphism predispose to stress hyperglycaemia in severe sepsis?
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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.
Example input: Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
Example output: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Example explanation: The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
Q: Context: Impaired insulin sensitivity has been linked with chronic heart failure (CHF). Exercise has a beneficial effect on insulin sensitivity in healthy subjects. It is used also as an adjunctive therapy in patients with CHF. We studied the effect of randomized treatment with celiprolol, a vasodilating beta(1)-adrenoceptor antagonist, 200 mg once daily (n=20) or placebo (n=11) on serum lipid levels and insulin sensitivity in patients with CHF. In addition, all subjects participated in a 6-month exercise training protocol. Thirteen subjects in the celiprolol and eight subjects in the control group were on additional beta(1)-adrenoceptor antagonist as part of their tailored CHF therapy. Insulin sensitivity was determined using the hyperinsulinemic euglycemic clamp test (diabetic subjects excluded, n=11 for the celiprolol group and n=8 for the placebo group).', 'Insulin sensitivity index (ISI) increased by 33% (P<0.05) in the celiprolol group and by 17% (NS) in the control group. The mean increase in the whole group was 20% [from 68.2+/-11.5 to 81.7+/-10.7 ml/min/kg (mU/l), P<0.05]. No change was found in the total cholesterol level. HDL cholesterol levels increased by 12% (from 0.98+/-0.05 to 1.10+/-0.05 mmol/l, P<0. 005), and HDL/total cholesterol and HDL/LDL cholesterol ratios by 15% and 16%, respectively (P<0.005). The increase in serum fasting HDL cholesterol level was greater in the celiprolol-treated group (P<0.05). At baseline ISI correlated with maximal oxygen uptake (r=0. 65, P<0.0001) and body mass index (r=-0.55, P<0.001). The change in ISI correlated weakly with the improvement in muscle exercise capacity (r=0.53, P<0.05).
Answer: Insulin sensitivity and serum lipid levels may be favorably affected by exercise training in subjects with mild-to-moderate CHF. Celiprolol, a vasodilating beta1- selective adrenoceptor antagonist, potentiates this effect.
A: | Does celiprolol augment the effect of physical exercise on insulin sensitivity and serum lipid levels in chronic heart failure? | task845_pubmedqa_question_generation |
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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 independent prognostic value of high-sensitivity C-reactive protein (hsCRP) has been questioned, and consequently we decided to investigate whether hsCRP was associated with subclinical cardiovascular (CV) damage independently of traditional CV risk factors.', 'In a population-based sample of 2028 apparently healthy individuals without prior stroke or myocardial infarction not receiving any CV, anti-diabetic or lipid-lowering treatment, aged 41, 51, 61 or 71 years, we measured in 1993 serum hsCRP, traditional CV risk factors (lifestyle, metabolic and hemodynamic) and assessed subclinical CV damage [atherosclerotic plaques in the carotid arteries, pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular (LV) mass and ejection fraction].', 'Adjusting for age and gender in multiple regression analyses, higher log(hsCRP) was associated with higher logPWV (beta = 0.15) and log(left ventricular mass index) (LVMI) (beta = 0.09, both P < 0.001), LV relative wall thickness (beta = 0.07, P < 0.01), logUACR (beta = 0.04, P = 0.06) and more atherosclerotic plaques (beta = 0.06, P < 0.05). However, higher log(hsCRP) was only weakly associated with higher logPWV(beta = 0.06, P < 0.05) and more atherosclerotic plaques (beta = 0.04, P = 0.06) when adjusting for other significant CV risk factors, such as daily smoking (beta = 0.18), female gender (beta = -0.17), older age (beta = 0.11), lower log(high density lipoprotein cholesterol) (beta = -0.11, all P < 0.001); wider waist (beta = 0.17), higher body mass index (beta = 0.14), higher heart rate (beta = 0.06, all P < 0.01); and higher log(plasma glucose) (beta = 0.05, P < 0.05) (adj. R2 = 0.19, P < 0.001).
Answer: After adjustment for traditional CV risk factors hsCRP was only associated with PWV and atherosclerotic plaques, indicating a possible effect of low-grade inflammation on macrovascular damage. The close relationship between traditional CV risk factors and hsCRP suggested that hsCRP was an integrated CV risk marker early in the development of atherosclerosis.
Answer: Is high-sensitivity C-reactive protein only weakly related to cardiovascular damage after adjustment for traditional cardiovascular risk factors?
Question: Context: Human induced pluripotent stem cells (iPSCs) play an important role in disease modeling and drug testing. However, the current methods are time-consuming and lack an isogenic control.', 'This study sought to establish an efficient technology to generate human PSC-based disease models with isogenic control.', 'The ion channel genes KCNQ1 and KCNH2 with dominant negative mutations causing long QT syndrome types 1 and 2, respectively, were stably integrated into a safe harbor AAVS1 locus using zinc finger nuclease technology.', 'Patch-clamp recording revealed that the edited iPSC-derived cardiomyocytes (iPSC-CMs) displayed characteristic long QT syndrome phenotype and significant prolongation of the action potential duration compared with the unedited control cells. Finally, addition of nifedipine (L-type calcium channel blocker) or pinacidil (KATP-channel opener) shortened the action potential duration of iPSC-CMs, confirming the validity of isogenic iPSC lines for drug testing in the future.
Answer: Our study demonstrates that iPSC-CM-based disease models can be rapidly generated by overexpression of dominant negative gene mutants.
Answer: Does genome editing of isogenic human induced pluripotent stem cells recapitulate long QT phenotype for drug testing?
Question: Context: Smoking cessation rapidly reduces cardiovascular risk. The pathophysiological mechanisms involved are still being debated. We measured structural and functional arterial wall properties of the femoral and carotid arteries after smoking cessation to investigate their possible role in cardiovascular risk reduction.', 'Out of 127 smokers, 33 proved to stop smoking for two years. They were compared with 50 nonsmokers and 55 persistent smokers in a prospective study. Cross-sectional compliance and distensibility coefficients as well as intima-media thickness of both carotid arteries and of the right common femoral artery were measured ultrasonographically at baseline and 3, 6, 12 and 24 months after smoking cessation. The nonsmoking and persistent smokers group were measured twice at an interval of 24 months.', 'Persistent smoking and two years of smoking cessation did not affect cross-sectional compliance and distensibility coefficients. Although at baseline intimal-medial layers were thicker in smokers, the change over time in intima-media thickness did not differ significantly between all three groups.
Answer: Two years of smoking cessation was not accompanied by a slower progression or a regression in intima-media thickness nor by an improved cross-sectional compliance or distensiblity coefficient. Nevertheless, smoking cessation should be recommended as it reduces cardiovascular risk rapidly after smoking cessation.
Answer: | Does two years of smoking cessation reduce arterial wall thickness and stiffness?
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You will be given a definition of a task first, then some input of the task.
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.
Context: To test our hypothesis that initiating therapy with a combination of agents known to improve insulin secretion and insulin sensitivity in subjects with new-onset diabetes would produce greater, more durable reduction in glycated haemoglobin (HbA1c) levels, while avoiding hypoglycaemia and weight gain, compared with sequential addition of agents that lower plasma glucose but do not correct established pathophysiological abnormalities.', 'Drug-naïve, recently diagnosed subjects with type 2 diabetes mellitus (T2DM) were randomized in an open-fashion design in a single-centre study to metformin/pioglitazone/exenatide (triple therapy; n\u2009=\u2009106) or an escalating dose of metformin followed by sequential addition of sulfonylurea and glargine insulin (conventional therapy; n\u2009=\u2009115) to maintain HbA1c levels at <6.5% for 2\u2009years.', 'Participants receiving triple therapy experienced a significantly greater reduction in HbA1c level than those receiving conventional therapy (5.95 vs. 6.50%; p\u2009<\u20090.001). Despite lower HbA1c values, participants receiving triple therapy experienced a 7.5-fold lower rate of hypoglycaemia compared with participants receiving conventional therapy. Participants receiving triple therapy experienced a mean weight loss of 1.2\u2009kg versus a mean weight gain of 4.1\u2009kg (p\u2009<\u20090.01) in those receiving conventional therapy.
Answer: The results of this exploratory study show that combination therapy with metformin/pioglitazone/exenatide in patients with newly diagnosed T2DM is more effective and results in fewer hypoglycaemic events than sequential add-on therapy with metformin, sulfonylurea and then basal insulin.
Output: | Is initial combination therapy with metformin , pioglitazone and exenatide more effective than sequential add-on therapy in subjects with new-onset diabetes . Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes ( EDICT ) : a randomized trial? | task845_pubmedqa_question_generation |
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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.
[Q]: Context: To assess, in a retrospective cohort, urinary tract urothelial carcinoma (UT-UC) in patients with various stages of chronic kidney disease (CKD) and their clinicopathological features, as patients with end-stage renal disease (ESRD) have a higher incidence of UT-UC, but the relationship between early stages of CKD and characteristics of UT-UC are less well known.', 'The study included 267 patients with pathologically confirmed UT-UC from January 1994 to December 2006; all had a physical examination (blood pressure), and measurements of laboratory data (serum creatinine, serum haemoglobin) and pathological data. The glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease equation. Patients were divided into three groups by individual GFR (mL/min), i.e. >60 (no/mild CKD), 30-60 (CKD stage 3) and <30 (CKD stage 4/5).', 'The CKD stages included 81 (30.3%) patients with none/mild CKD, 121 (45.3%) with CKD stage 3 and 65 (24.3%) with CKD stage 4/5. There was a significant and parallel increase in the frequency of UT-UC as CKD severity increased from none/mild CKD to stage 3 (11% vs 55%), and from CKD stage 3 to 4/5 (55% vs 71%; P < 0.05). Pathologically, the frequency of high-grade and high T stage UT-UC in patients with CKD stage 3 (90% and 35%, respectively) and CKD stage 4/5 (91% and 29%, respectively) were significantly greater than in the group with none/mild CKD (P < 0.001). Advanced age and more distant metastasis were independent risk factors for patient survival.
Answer: The aggressiveness of UT-UC increased with the severity of CKD, and this might have important clinical consequences.
[A]: Does the aggressiveness of urinary tract urothelial carcinoma increase with the severity of chronic kidney disease?
[Q]: Context: The etiology of reduced left ventricular (LV) ejection fraction after exercise, without obstructive coronary artery disease or other established causes, is unclear. The aims of this study were to determine whether patients undergoing treadmill stress echocardiography with this abnormal LV contractile response to exercise (LVCRE) without established causes have resting LV long-axis dysfunction or microvascular dysfunction and to determine associations with this abnormal LVCRE.', 'Of 5,275 consecutive patients undergoing treadmill stress echocardiography, 1,134 underwent cardiac computed tomography angiography or invasive angiography. Having excluded patients with obstructive coronary artery disease, hypertensive response, submaximal heart rate response, resting LV ejection fraction < 50%, and valvular disease, 110 with "abnormal LVCRE" and 212 with "normal LVCRE" were analyzed. Resting mitral annular velocities were measured to assess LV long-axis function. Myocardial blush grade and corrected Thrombolysis In Myocardial Infarction frame count were determined angiographically to assess microvascular function.', "Comparing normal LVCRE with abnormal LVCRE, age (mean, 59.7 ± 11.1 vs 61.4 ± 10.0 years), hypertension (53% vs 55%), diabetes (16% vs 20%), and body mass index (mean, 29.1 ± 5.4 vs 29.5 ± 6.4 kg/m(2)) were similar (P > .05). Abnormal LVCRE had reduced resting LV long-axis function with lower septal (mean, 6.1 ± 1.9 vs 7.7 ± 2.2 cm/sec) and lateral (mean, 8.1 ± 2.9 vs 10.4 ± 3.0 cm/sec) e' velocities (P < .001) and larger resting left atrial volumes (mean, 37.3 ± 10.1 vs 31.1 ± 7.2 mL/m(2), P < .001). On multivariate analysis, female gender (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.15-1.99; P < .001), exaggerated chronotropic response (OR, 1.49; 95% CI, 1.09-2.05; P < .001), resting left atrial volume (OR, 2.38; 95% CI, 1.63-3.47; P < .001), and resting lateral e' velocity (OR, 1.70; 95% CI, 1.22-2.49; P = .003) were associated with abnormal LVCRE, but not myocardial blush grade or corrected Thrombolysis In Myocardial Infarction frame count.
Answer: An abnormal LVCRE in the absence of established causes is associated with resting LV long-axis dysfunction and is usually seen in women.
[A]: Is abnormal left ventricular contractile response to exercise in the absence of obstructive coronary artery disease associated with resting left ventricular long-axis dysfunction?
[Q]: Context: Our prior studies show that intravenous (IV) total parenteral nutrition (TPN) produces atrophy of the small intestine-related gut-associated lymphoid tissue and significant decreases in intestinal IgA levels, the major system of mucosal immunity. Others have noted increased small intestinal permeability, bacterial adherence and translocation, and decreased IgA levels in TPN-fed animals. Bombesin, a neuropeptide, may play a regulatory role in mucosal immunity. It is not clear whether bombesin attenuates the TPN-associated gut-associated lymphoid tissue atrophy.', 'To examine the effect of bombesin on gut-associated lymphoid tissue integrity and function during IV TPN feeding.', 'Randomized animal study.', 'A university laboratory.', "Male ICR mice weighing 25 to 30 g were randomized to chow plus IV saline solution (n = 12), IV TPN (n = 12), or IV TPN plus bombesin (15 micrograms/kg, administered intramuscularly three times a day) (n = 12). Animals were killed after 5 days of receiving the experimental diet. Total small intestinal IgA level was quantified by enzyme-linked immunosorbent assay. Lymphocytes were isolated from Peyer's patches, intraepithelial spaces, and lamina propria and were stained with specific antibodies for B and T cells and for T-cell expression of CD4 and CD8 by flow cytometric analysis. Data were analyzed by analysis of variance.", "Bombesin prevented the IV TPN decreases in (1) total cell yield and B-cell yield from the Peyer's patches, intraepithelial spaces, and lamina propria; (2) T-cell yield in the intraepithelial spaces and lamina propria; and (3) small intestinal IgA levels. Bombesin also reversed IV TPN decreases in CD4+ and CD8+ T cells in the intraepithelial spaces and Peyer's patches and prevented the decrease in the CD4/CD8 ratio in the lamina propria.
Answer: Bombesin prevents the TPN-associated atrophy and dysfunction of gut-associated lymphoid tissue, supporting the concept of close neuroimmunologic interaction.
[A]: | Does bombesin affect mucosal immunity and gut-associated lymphoid tissue in intravenously fed mice?
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Given the task definition and input, reply with output. 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.
Context: Total exercise duration and abnormal QRS score values are treadmill exercise testing (TET) prognostic parameters that have been shown to be significantly and independently associated with cardiac mortality. We evaluated the prognostic value of a new index (M score, Michaelides score) incorporating TET duration and QRS score values in a simple index.', 'In this study, we included 626 patients, who underwent TET and coronary arteriography. Cardiac catheterization showed the presence of coronary artery disease in 64.3% of these patients. The M score was calculated by adding the value of the Athens QRS score to the duration of TET (in minutes). The outcome measure was a composite of myocardial infarction or death. Patients were prospectively followed for 38+/-21 months (median 36 months).', "The composite endpoint was more frequent among the patients of the 1st quartile (M-score values <-5.8). In univariate analysis, mortality of the first-quartile patients was significantly higher (14 vs. 1.1%, P<0.001). In multivariate Cox's regression analysis for age, sex, diabetes, smoking status, hypertension, hypercholesterolemia, maximum ST depression at TET, angina during TET, coronary artery disease on angiography, and echocardiographic left ventricular ejection fraction, the first quartile of M-score values was found to be independently associated with the composite endpoint (relative risk = 3.26, 95% confidence interval = 2.01-5.29, P<0.001).
Answer: This study shows that a new index termed the M score, which incorporates QRS score and exercise duration, predicts mortality and occurrence of myocardial infarction at long-term follow-up of high-risk individuals, independently of TET-induced ST-segment changes.
| Does duration of treadmill exercise testing combined with QRS score predict adverse cardiac outcome at long-term follow-up? | task845_pubmedqa_question_generation |
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Detailed Instructions: 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.
Q: Context: To examine the effect of short-term improvements in glycaemic control on brachial artery endothelial function as a marker of cardiovascular health.', 'Persons with Type 2 diabetes who were poorly controlled on oral therapy were randomly assigned to monotherapy with repaglinide or combination therapy with repaglinide plus metformin. Brachial artery flow-mediated vasodilation was assessed by ultrasonography at randomization and following 16 weeks of therapy. The primary outcome was change in brachial artery endothelial function from baseline. Comparison of randomized groups was a secondary aim.', 'Eighty-six participants were randomized, and 83 were followed to study completion. Post occlusion brachial artery vasodilation was 3.74% at baseline and 3.82% following 16 weeks of therapy (P = 0.77). The treatment effect was 0.08% (95% CI: -0.48%, 0.64%). No difference was seen between treatment groups (P = 0.69). Overall, A1C was reduced from 8.3% to 7.0%, with a greater reduction in the combination therapy group (from 8.4% to 6.7%) than in the monotherapy group (from 8.3% to 7.3%, p for difference between groups = 0.01). Statistically significant reductions were observed in fasting glucose, and plasminogen activator inhibitor-1. Statistically significant increases were observed for fasting insulin, uric acid, weight and BMI.
Answer: Brachial artery endothelial function was not influenced by short-term improvements in glycaemic control. The CONTROL DM group was successful in lowering A1C. Future research should explore more intensive and longer-lasting improvements in glycaemic control on endothelial function. Some data previously published in abstract form (Diabetes 2001; 50 (Suppl. 2): A217).
A: | Does the combination oral and nutritional treatment of late-onset diabetes mellitus ( CONTROL DM ) trial result? | task845_pubmedqa_question_generation |
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Detailed Instructions: 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.
Problem:Context: The ratio between urinary albumin concentration (UAC) and urinary creatinine concentration (UCC) is widely used to estimate renal involvement. We examined how UAC and UCC associate with each other, with other risk factors, and with diabetic complications in a population-based sample of Type 2 diabetic patients.', 'A freshly voided morning urine specimen was provided by 1,284 consecutive, newly diagnosed diabetic patients aged 40 years or over in general practice. Albumin was measured by a polyethyleneglycol radioimmunoassay and creatinine by a modified Jaffe method.', 'In a multivariate model including UAC, UCC, age, sex, HbA1c, and urinary glucose concentration, UAC increased with both age (P=.042) and HbA1c (P=.014), while UCC decreased (P<.001 and P<.001, respectively). In two regression models, the prevalence of diabetic retinopathy (P<.001) and relatively high resting heart rate (P<.001) increased with increasing UAC but decreased with increasing UCC (P=.002 and P=.005, respectively).
Answer: The use of albumin/creatinine ratio (ACR) may introduce bias of unpredictable size and direction in comparisons of ACR with variables that are associated with UCC in their own right. In daily clinical practice, renal involvement in the individual patient can be estimated reliably with UAC or ACR measured in a freshly voided morning urine specimen, especially when considered together. However, the associations of the combined measure ACR should be interpreted with great caution in clinical and epidemiological research.
Solution: | Is urinary creatinine concentration inversely related to glycaemic control and the presence of some diabetic complications in patients with newly diagnosed Type 2 diabetes? | task845_pubmedqa_question_generation |
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Q: 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.
Context: High fibroblast growth factor-23 (FGF-23) levels are associated with mortality and cardiovascular events in patients with chronic kidney disease. The aim of this cross-sectional study was to investigate the relationship between plasma FGF-23 levels and coronary artery calcification and carotid artery intima-media thickness (CA-IMT) in hemodialysis (HD) patients.', 'In this cross-sectional study, plasma intact FGF-23 levels were measured in 229 patients who underwent coronary artery calcification scores (CACs) determined by multi-slice computerized tomography and CA-IMT assessed by using high-resolution color Doppler ultrasonography.', 'Median FGF-23 was 53.5 pg/ml (IQR 30.8-249.5). Median CACs was 98 (IQR 0-531), and the frequency of patients with severe calcification (CACs > 400) was 28.8%; 27.5% of cases had no calcification. Mean CA-IMT was 0.78 ± 0.20 mm, and the presence of carotid plaques was 51% with a mean length 2.1 mm. FGF-23 level was positively correlated with serum calcium (r = 0.337, p < 0.001), phosphate (r = 0.397, p < 0.001) and CACs (r = 0.218, p = 0.001). Neither CA-IMT nor the presence of carotid artery plaques correlated with FGF-23 levels. In adjusted ordinal regression analysis, FGF-23 level was an independent predictor for severe CACs together with age, gender, presence of diabetes, time on dialysis and CA-IMT (model r(2) = 0.44, p < 0.001). As a novel finding, the mean CACs was markedly higher in patients with FGF-23 level above median regardless of phosphate levels (p = 0.03).
Answer: In HD patients, plasma FGF-23 level is superior to phosphate in the prediction of coronary artery calcification. However, FGF-23 is not associated with carotid artery atherosclerosis in HD patients.
A: | Are fGF-23 levels associated with vascular calcification , but not with atherosclerosis , in hemodialysis patients? | task845_pubmedqa_question_generation |
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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.
[EX Q]: Context: Chemerin has been implicated to play opposing roles, either pro-inflammatory or anti-inflammatory, in various tissue inflammation processes primarily through the regulation of tissue recruitment of immune cells. However, the effect of chemerin in allergic asthma has not yet been explored. We sought to investigate the role of chemerin in the murine model of allergic asthma and explore the underlying mechanism.', 'We examined the effect of intranasal (i.n.) administration of chemerin during antigen challenge in murine models of asthma. Moreover, we examined whether administration of CCL2 or bone marrow-derived dendritic cells (BMDCs) transfer reversed the effects of chemerin on ovalbumin-induced asthma. We finally examined the effect of chemerin on CCL2 expression in activated lung epithelial cells in vitro.', 'The administration of chemerin attenuated allergic airway inflammation and airway hyperreactivity during antigen challenge. Chemerin treatment caused significant decreases in BALF CD4(+) T-cell accumulation and mRNA expression of Th2-attracting chemokines, CCL17 and CCL22, which was accompanied by significantly decreased BALF CD11c(+) CD11b(+) inflammatory DC accumulation and CCL2 production. Furthermore, airway administration of exogenous CCL2 or adoptive transfer of CD11c(+) CD11b(+) BMDCs abrogated the suppressive effects of chemerin on allergic asthma. Finally, in vitro study showed that chemerin inhibited CCL2 secretion by low-dose LPS-stimulated lung epithelial cells, which led to decreased chemotaxis of BMDCs.
Answer: Our study demonstrates that chemerin plays a protective role in allergic asthma by suppressing airway recruitment of inflammatory CD11c(+) CD11b(+) DCs through the inhibition of CCL2 secretion by active lung epithelial cells.
[EX A]: Does chemerin suppress murine allergic asthma by inhibiting CCL2 production and subsequent airway recruitment of inflammatory dendritic cells?
[EX Q]: Context: The gene p8 was initially described in pancreatic tissue during acute experimental pancreatitis, a disease that is characterized by a systemic immune response. Although early reports suggested that p8 affects leukocyte migration during acute pancreatitis (AP), no studies revealing its immune-modulatory effects have been performed.', 'We investigated the composition of the cellular immune system in naive p8 knockout (p8(−/−)) mice and compared with matched wild-type mice during pancreatitis.', 'In young mice, there were no relevant differences in the composition of peripheral and splenic CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD11b(+)Gr-1(-), and Gr-1 cells. In mature p8(−/−) mice, increased splenic CD4CD25FoxP3 cells, spleen siderosis, and increased marginal zones in the splenic white pulp were found. During AP, peripheral and splenic CD3(+) and CD3CD4 declined stronger in the p8(−/−) mice. The spleen of the p8(−/−) mice showed severe hypoplasia of the white pulp and mild hyperplasia of the red pulp. This was associated with a significantly increased rate of apoptosis.
Answer: We conclude that p8 has no impact on the cellular composition of the adaptive and innate immune systems in noninflammatory conditions. However, it may limit apoptosis and maintain homeostasis of the immune reaction during AP.
[EX A]: Does p8 Deficiency cause siderosis in spleens and lymphocyte apoptosis in acute pancreatitis?
[EX Q]: Context: The study was conducted to evaluate the vascular effects of chlorthalidone, a distal tubule-acting natriuretic agent, in hypertensive patients with nondiabetic metabolic syndrome, an insulin-resistant condition characterized by endothelial dysfunction and high risk for diabetes mellitus development.', 'Thirteen untreated hypertensive patients with Adult Treatment Panel-III-defined nondiabetic metabolic syndrome were assigned to 3-month treatment with chlorthalidone. The end-points were baseline and post-treatment evaluation of (1) forearm blood flow (strain-gauge plethysmography) responses to graded intra-arterial acetylcholine infusion to test endothelial-mediated vasomotor function, with sodium nitroprusside as a control for endothelium-independent vasodilatation; (2) minimum forearm vascular resistance, the ratio of mean blood pressure and maximal blood flow in response to 13-minute arterial occlusion, as a hemodynamic correlate of arteriolar structure; and (3) transcapillary albumin escape rate (the 1-hour decay rate of (125)I-albumin, 6-8 microC ev) as a measure of systemic capillary permeability. Additional measurements included baseline and posttreatment lipids, fasting, and postload glucose and insulin as well as the homeostasis model assessment, an index of insulin sensitivity.', 'Chlorthalidone reduced blood pressure, augmented acetylcholine-mediated vasodilatation, decreased minimum forearm resistance, and slowed the transcapillary albumin escape rate. Metabolic parameters did not change significantly except for an increase in low-density lipoprotein cholesterol levels.
Answer: Chlorthalidone improved endothelial function, reversed abnormal arteriolar structure, and slowed albumin permeation in hypertensive patients with nondiabetic metabolic syndrome.
[EX A]: | Does chlorthalidone improve endothelial-mediated vascular responses in hypertension complicated by nondiabetic metabolic syndrome?
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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.
One example is below.
Q: Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
A: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Rationale: The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
Q: Context: Diabetic nephropathy (DN) is a serious complication that commonly confronted by diabetic patients. A common theory for the pathogenesis of this renal dysfunction in diabetes is cell injury, inflammation as well as oxidative stress. In this content, the detailed molecular mechanism underlying high glucose induced renal tubular epithelial injury was elaborated.', "An in vivo rat model of diabetes by injecting streptozotocin (STZ) and an in vitro high glucose incubated renal tubular epithelial cell (HK-2) model were used. Expression levels of Keap1, nuclear Nrf2 and p65 were determined by western blotting. Level of microR-29 (miR-29) was assessed using quantitative RT-PCR. Combination of p65 and miR-29 promotor was assessed using chromatin immunoprecipitation. Keap1 3'-UTR activity was detected using luciferase reporter gene assay. Cell viability was determined using MTT assay.", 'In diabetic rat, miR-29 was downregulated and its expression is negatively correlated with both of serum creatinine and creatinine clearance. In high glucose incubated HK-2 cell, deacetylases activity of Sirt1 was attenuated that leads to decreased activity of nuclear factor kappa B (NF-κB). NF-κB was demonstrated to regulate miR-29 expression by directly binding to its promotor. The data of luciferase assay showed that miR-29 directly targets to Keap1 mRNA. While high glucose induced down regulation of miR-29 contributed to enhancement of Keap1 expression that finally reduced Nrf2 content by ubiquitinating Nrf2. Additionally, overexpression of miR-29 effectively relieved high glucose-reduced cell viability.
Answer: High glucose induces renal tubular epithelial injury via Sirt1/NF-κB/microR-29/Keap1 signal pathway.
A: | Does high glucose induce renal tubular epithelial injury via Sirt1/NF-kappaB/microR-29/Keap1 signal pathway? | task845_pubmedqa_question_generation |
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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.
Let me give you an example: Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
The answer to this example can be: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Here is why: The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
OK. solve this:
Context: Adipocytes express inflammatory mediators that contribute to the low-level, chronic inflammation found in obese subjects and have been linked to the onset of cardiovascular disorders and insulin resistance associated with type 2 diabetes mellitus. A reduction in inflammatory gene expression in adipocytes would be expected to reverse this low-level, inflammatory state and improve cardiovascular function and insulin sensitivity. The natural products, curcumin and resveratrol, are established anti-inflammatory compounds that mediate their effects by inhibiting activation of NF-kappaB signaling. In the present study, we examined if these natural products can inhibit NF-kappaB activation in adipocytes and in doing so reduce cytokine expression.', 'Cytokine (TNF-alpha, IL-1beta, IL-6) and COX-2 gene expression in 3T3-L1-derived adipocytes was measured by quantitative real-time PCR (qRT-PCR) with or without TNFalpha-stimulation. Cytokine protein and prostaglandin E2 (PGE2) expression were measured by ELISA. Effects of curcumin and resveratrol were evaluated by treating TNFalpha-stimulated adipocytes with each compound and 1) assessing the activation state of the NF-kappaB signaling pathway and 2) measuring inflammatory gene expression by qRT-PCR and ELISA.', 'Both preadipocytes and differentiated adipocytes express the genes for TNF-alpha, IL-6, and COX-2, key mediators of the inflammatory response. Preadipocytes were also found to express IL-1beta; however, IL-1beta expression was absent in differentiated adipocytes. TNF-alpha treatment activated NF-kappaB signaling in differentiated adipocytes by inducing IkappaB degradation and NF-kappaB translocation to the nucleus, and as a result increased IL-6 (6-fold) and COX-2 (2.5-fold) mRNA levels. TNF-alpha also activated IL-1beta gene expression in differentiated adipocytes, but had no effect on endogenous TNF-alpha mRNA levels. No detectable TNFalpha or IL-1beta was secreted by adipocytes. Curcumin and resveratrol treatment inhibited NF-kappaB activation and resulted in a reduction of TNF-alpha, IL-1beta, IL-6, and COX-2 gene expression (IC50 = 2 muM) and a reduction of secreted IL-6 and PGE2 (IC50 ~ 20 muM).
Answer: Curcumin and resveratrol are able to inhibit TNFalpha-activated NF-kappaB signaling in adipocytes and as a result significantly reduce cytokine expression. These data suggest that curcumin and resveratrol may provide a novel and safe approach to reduce or inhibit the chronic inflammatory properties of adipose tissue.
Answer: | Do curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes? | task845_pubmedqa_question_generation |
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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.
Q: Context: Women with antiphospholipid syndrome (APS) are at increased risk of recurrent pregnancy loss (RPL) and preeclampsia. Antiphospholipid antibodies (aPL) directly alter trophoblast function. Treatment with low molecular weight heparin (LMWH) reduces the risk of RPL but not preeclampsia. Moreover, LMWH stimulates trophoblast sFlt-1 release, an anti-angiogenic factor associated with preeclampsia. Since vitamin D deficiency is associated with APS and preeclampsia, this study sought to determine the effect of vitamin D on trophoblast function in the setting of aPL and LMWH.', 'A human first trimester trophoblast cell line (HTR8) and primary trophoblast cultures were treated with or without aPL in the presence and absence of vitamin D, LMWH or both. Trophoblast secretion of inflammatory cytokines and angiogenic factors were measured by ELISA.', 'Vitamin D alone or in combination with LMWH attenuated the aPL-induced trophoblast inflammatory response in the HTR8 cells and primary cultures. While vitamin D did not have any impact on aPL-mediated modulation of angiogenic factors in the primary trophoblast, it significantly inhibited LMWH-induced sFlt-1 release.
Answer: LMWH in combination with vitamin D may be more beneficial than single-agent therapy by preventing aPL-induced trophoblast inflammation and reversing LMWH-induced sFlt-1 secretion.
A: Does vitamin D reverse aPL-induced inflammation and LMWH-induced sFlt-1 release by human trophoblast?
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Q: Context: Normal glucose metabolism depends on pancreatic secretion of insulin and glucagon. The bihormonal hypothesis states that while lack of insulin leads to glucose underutilisation, glucagon excess is the principal factor in diabetic glucose overproduction. A recent study reported that streptozotocin-treated glucagon receptor knockout mice have normal glucose tolerance. We investigated the impact of acute disruption of glucagon secretin or action in a mouse model of severe diabetes by three different approaches: (1) alpha cell elimination; (2) glucagon immunoneutralisation; and (3) glucagon receptor antagonism, in order to evaluate the effect of these on glucose tolerance.', 'Severe diabetes was induced in transgenic and wild-type mice by streptozotocin. Glucose metabolism was investigated using OGTT in transgenic mice with the human diphtheria toxin receptor expressed in proglucagon producing cells allowing for diphtheria toxin (DT)-induced alpha cell ablation and in mice treated with either a specific high affinity glucagon antibody or a specific glucagon receptor antagonist.', 'Near-total alpha cell elimination was induced in transgenic mice upon DT administration and resulted in a massive decrease in pancreatic glucagon content. Oral glucose tolerance in diabetic mice was neither affected by glucagon immunoneutralisation, glucagon receptor antagonism, nor alpha cell removal, but did not deteriorate further compared with mice with intact alpha cell mass.
Answer: Disruption of glucagon action/secretion did not improve glucose tolerance in diabetic mice. Near-total alpha cell elimination may have prevented further deterioration. Our findings support insulin lack as the major factor underlying hyperglycaemia in beta cell-deficient diabetes.
A: Does acute disruption of glucagon secretion or action improve glucose tolerance in an insulin-deficient mouse model of diabetes?
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Q: Context: Prematurity and fetal growth restriction are risk factors for pulmonary hypertension (PH) in infants with bronchopulmonary dysplasia (BPD). Neonatal rats develop PH and vascular remodeling when exposed to hyperoxia. We hypothesize that postnatal growth restriction (PNGR) due to under-nutrition increases the severity of PH induced by hyperoxia in neonatal rats.', "Pups were randomized at birth to litters maintained in room air or 75% oxygen (hyperoxia), together with litters of normal milk intake (10 pups) or PNGR (17 pups). After 14 d, right ventricular hypertrophy (RVH) was assessed by Fulton's index (right ventricular weight/left ventricular plus septal weight) and PH by echocardiography. Lungs were analyzed by immunohistochemistry, morphometrics, western blotting, and metabolomics.", 'Hyperoxia and PNGR each significantly increased pulmonary arterial pressure, RVH and pulmonary arterial medial wall thickness, and significantly decreased pulmonary vessel number. These changes were significantly augmented in pups exposed to both insults. Hyperoxia and PNGR both significantly decreased expression of proteins involved in lung development and vasodilation.
Answer: PNGR induces right ventricular and pulmonary vascular remodeling and augments the effects of oxygen in neonatal rats. This may be a powerful tool to investigate the mechanisms that induce PH in low-birth-weight preterm infants with BPD.
A: | Does postnatal growth restriction augment oxygen-induced pulmonary hypertension in a neonatal rat model of bronchopulmonary dysplasia?
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Definition: 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: Context: LADA is thought to result from the chronic autoimmune destruction of the insulin-producing pancreatic beta cells. In addition to antidiabetic effects, the newly developed insulin sensitizer-thiazolidinediones have the potential to increase the insulin content of islet cells by downregulating local inflammation and autoimmune response. Therefore, we hypothesized that LADA patients might benefit from thiazolidinediones treatment.', 'LADA patients, with a fasting C-peptide (FCP) of 0.3 nmol/L or more, were enrolled and randomly assigned to receive subcutaneous insulin alone (insulin group, n = 12) or rosiglitazone plus insulin (insulin + RSG group, n = 11) to compare the impacts on islet beta cell function. Plasma glucose, HbA 1c, fasting C-peptide (FCP) and C-peptide after 2 h 75-g glucose load (PCP) were determined every 6 months. GAD-Ab and C-peptide were measured with radioimmune assays. Islet beta cell function was evaluated by PCP and DeltaCP(DeltaCP = PCP-FCP).', "All of the 23 patients have been followed up for 6 months, 17 cases for 12 months and 14 for 18 months. (1) During 6 months' follow-up, there were no significant changes for DeltaCP and PCP levels in both groups. (2) PCP and DeltaCP levels in insulin + RSG group patients stayed steady during the 12 months' observation (P = 0.161 for both PCP and DeltaCP), while in the insulin alone group, both FCP (P = 0.021) and PCP (P = 0.028) levels decreased significantly. Furthermore, PCP (P = 0.004) and DeltaCP(P = 0.015) differences between 12th month and baseline were higher in insulin + RSG group than those in the insulin group. (3) When observed up to 18 months, PCP and DeltaCP levels in insulin + RSG group patients still stayed steady, while PCP and DeltaCP levels decreased more in the insulin alone group.
Answer: This pilot study suggests that rosiglitazone combined with insulin may preserve islet beta cell function in LADA patients.
Output: | Does rosiglitazone combined with insulin preserve islet beta cell function in adult-onset latent autoimmune diabetes ( LADA )? | task845_pubmedqa_question_generation |
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You will be given a definition of a task first, then some input of the task.
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.
Context: Diabetic patients commonly suffer from disturbances in production and clearance of plasma lipoproteins, known as diabetic dyslipidemia, resulting in an increased risk of coronary heart disease. The study aimed to examine the cause of hypobetalipoproteinemia in two patients with type 1 diabetes.', 'The Diabetes Control and Complications Trial (DCCT) is a study demonstrating that intensive blood glucose control delays the onset and progression of type 1 diabetes complications. Hypobetalipoproteinemia was present in two DCCT subjects, IDs 1427 and 1078, whose LDL-C levels were 36 and 28 mg/dL, respectively, and triglyceride levels were 20 and 28 mg/dL, respectively. We performed exome sequencing on genomic DNA from the two patients with hypobetalipoproteinemia.', 'The subjects 1427 and 1078 had heterozygous loss-of-function mutations in the gene apolipoprotein B (ApoB), and these mutations resulted in premature stop codons at amino acid 1333 (ApoB-29) and 3680 (ApoB-81), respectively. Indeed, the plasma ApoB level of subject 1427 (19 mg/dL) was the lowest and that of subject 1078 (26 mg/dL) was the second to the lowest among all the 1,441 DCCT participants. Sequencing genomic DNA of family members showed that probands 1427 and 1078 inherited the mutations from the father and the mother, respectively.
Answer: The identification of ApoB loss-of-function mutations in type 1 diabetic patients presents innovative cases to study the interaction between hypobetalipoproteinemia and insulin deficiency.
Output: | Does exome sequencing identify novel ApoB loss-of-function mutations causing hypobetalipoproteinemia in type 1 diabetes? | task845_pubmedqa_question_generation |
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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.
Example Input: Context: Material loss at the taper junction of metal-on-metal total hip arthroplasties has been implicated in their early failure. The mechanisms of material loss are not fully understood; analysis of the patterns of damage at the taper can help us better understand why material loss occurs at this junction.', 'We mapped the patterns of material loss in a series of 155 metal-on-metal total hip arthroplasties received at our center by scanning the taper surface using a roundness-measuring machine. We examined these material loss maps to develop a 5-tier classification system based on visual differences between different patterns. We correlated these patterns to surgical, implant, and patient factors known to be important for head-stem taper damage.', 'We found that 63 implants had "minimal damage" at the taper (material loss <1 mm
Answer: These material loss maps allow us to suggest different mechanisms that dominate the cause of the material loss in each pattern: (1) corrosion, (2) mechanically assisted corrosion, or (3) intraoperative damage or poor size tolerances leading to toggling of trunnion in taper.
Example Output: Does damage Patterns at the Head-Stem Taper Junction help Understand the Mechanisms of Material Loss?
Example Input: Context: The single nucleotide polymorphism rs10494366 in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene is associated with QTc prolongation, through an effect on the intracellular Ca levels. As sulfonylurea stimulate insulin secretion by an increased influx of Ca, we hypothesized that this polymorphism is associated with the glucose-lowering effect and mortality risk in sulfonylurea users.', 'Associations between the NOS1AP polymorphism, prescribed doses, and mortality rates in sulfonylurea, metformin, and insulin users were assessed in the Rotterdam Study, a population-based cohort study of 7983 elderly people.', 'We identified 619 participants who were prescribed oral antidiabetic drugs during follow-up. In glibenclamide users carrying the TG genotype, the prescribed doses were higher compared with the glibenclamide users carrying the TT genotype [0.38 defined daily dose units, 95% confidence interval (CI) 0.14-0.63]. Glibenclamide users with the TG or GG genotype had an increased mortality risk compared with glibenclamide users with the TT genotype [hazard ratio (HR) 2.80, 95% CI: 1.09-7.22]. Tolbutamide users with the TG or GG genotype (HR: 0.30, 95% CI: 0.14-0.63) and glimepiride users with the TG or GG genotype (HR: 0.18, 95% CI: 0.04-0.74) had a decreased mortality risk compared with tolbutamide and glimepiride users with the TT genotype.
Answer: In participants with the TG or GG genotype at rs10494366 in the NOS1AP gene, glibenclamide is less effective in reducing glucose levels and mortality rates were higher compared with glibenclamide users with the TT genotype. In tolbutamide and glimepiride users, the TG and GG genotype were associated with a reduced mortality rate.
Example Output: Is common variation in the NOS1AP gene associated with reduced glucose-lowering effect and with increased mortality in users of sulfonylurea?
Example Input: Context: To investigate the effectiveness of a suture bridge technique for quadriceps tendon rupture repair in uraemic patients.', 'Between March 2010 and September 2012, 10 uraemic patients (14 sides) with quadriceps tendon rupture were treated with the suture bridge technique. Of them, 8 were male and 2 were female, aged from 30 to 62 years (mean, 54.2 years). The duration of uremia was 3-11 years (mean, 5.5 years): the duration of quadriceps tendon rupture was 5 days to 2 months (median, 12 days). Six cases had a trauma history, and one case had diabetes. The left side was involved in 2 cases, the right side in 4 cases, and both sides in 4 cases. The active range of motion (ROM) of the knees was (115.0 +/- 8.3) degrees in flexion, and (72.5 +/- 21.2) degrees in extension. Lysholm score was 19.5 +/- 16.3. X-ray films showed downward shifting of patella. MRI revealed discontinuity between distal quadriceps tendon and upper pole of patella.', 'The operation time was 30-50 minutes (mean, 40.3 minutes). Primary healing of incision was obtained in all patients without complications. All patients were followed up 12-25 months (mean, 16.3 months). There was no re-rupture of quadriceps tendon or loosening of internal fixation during follow-up. At last follow-up, the active ROM of the knees was (121.0 +/- 7.9) degrees in flexion, showing no significant difference when compared with preoperative one (t = -2.075, P =0.058); the active ROM was (8.2 +/- 6.1) degrees in extension, showing significant difference when compared with preoperative one (t = 11.702, P = 0.000). Lysholm score was 84.6 +/- 12.4, showing significant difference when compared with preoperative score (t = -16.226, P = 0.000). According to the American Knee Society score (KSS), the results were excellent in 4 sides, good in 9 sides, and fair in 1 side, and the total excellent and good rate was 92.9%. At last follow-up, the active ROM of the knee, Lysholm score, and KSS score were significantly better in young patients (< 45 years) than in elder patients (> or = 45 years), and in patients receiving early operation (< 2 weeks) than in patients receiving late operation (> or = 2 weeks) (P < 0.05).
Answer: For fewer traumas and early functional exercise after operation, the suture bridge technique benefits functional restoration of knee joint in uraemic patients. Operation chance and age seem to be important factors to the results. Early operation should be considered when quadriceps tendon ruptured.
Example Output: | Do [ Effectiveness of a suture bridge technique for repair of quadriceps tendon rupture in uraemic patients ]?
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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.
--------
Question: Context: The aim of this study was to investigate the association of lipoprotein(a) [Lp(a)] with the severity of coronary heart disease (CHD) in Han Chinese people.', 'Six hundred and seventy-nine patients with angiographically defined CHD were enrolled in this cross-sectional study. Fasting lipids were measured, and the severity of CHD was quantitatively assessed for each patient according to the number of stenotic coronary branches and the Gensini scoring system.', 'The levels of Lp(a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and apolipoprotein (apo) B100 increased, while high-density lipoprotein cholesterol (HDL-C) and apoAI decreased significantly with the number of stenotic vessels. The levels of Lp(a) increased and HDL-C and apoAI decreased significantly with the Gensini scores. The logistic regression analyses showed that Lp(a) and HDL-C were independently associated with the number of stenotic coronary vessels after adjusting for age, weight, body mass index, sex, smoking, alcohol consumption, hypertension, diabetes, triglycerides, TC, LDL-C, VLDL-C, apoAI, and apoB100. However, only Lp(a) was independently associated with the Gensini scores after adjustment.
Answer: Our data indicate that Lp(a) might be a useful marker in predicting the severity of coronary heart disease.
Answer: Are plasma lipoprotein ( a ) levels associated with the severity of coronaryheart disease in Han Chinese people?
Question: Context: Cirrhosis, or liver fibrosis, which is mainly triggered by cirrhosis fat-storing cells (CFSCs) activation, has traditionally been considered an irreversible disease. However, recent observations indicate that even advanced fibrosis is still reversible by removing the causative agents. Anti-fibrotic effects of bone marrow-derived stromal cells (BMSCs) have been demonstrated by inhibiting CFSCs via cytokines secretion; however, the mechanisms are still unclear.', 'The purpose of this study was to explore the underlying mechanisms by which BMSCs modulate the function of activated CFSCs.', 'After the co-culture of CFSCs with BMSCs supernatants with or without the addition of recombinant rat adrenomedullin (AM)/AM-specific siRNA, western blot analysis was mainly used to detect the differences of relative protein expression on CFSCs.', 'BMSC-secreted adrenomedullin (AM) effectively inhibited the proliferation and activation of CFSCs by suppressing the expression of Ang II and its binding receptor, AT1, which resulted in a reduction of p47-phox formation.
Answer: Our data suggested that BMSCs inhibited CFSC activation in vitro via the AM-Ang II-p47-phox signaling pathway, and since CFSC activation is an essential part of hepatic fibrosis process, this inhibition by BMSCs implies us new insights into the potential treatment of hepatic fibrosis via BMSCs.
Answer: Do bone Marrow Stromal Cells Inhibit the Activation of Liver Cirrhotic Fat-Storing Cells via Adrenomedullin Secretion?
Question: Context: Oral epithelial cells have currently been found to play an important role in inflammatory modulation in periodontitis. Mangiferin is a natural glucosylxanthone with anti-inflammatory activity. The aim of this study was to investigate the regulatory effect of mangiferin on lipopolysaccharide (LPS)-induced production of proinflammatory cytokine interleukin-6 (IL-6) in oral epithelial cells and the underlying mechanisms.', 'The levels of LPS-induced IL-6 production in OKF6/TERT-2 oral keratinocytes were detected using enzyme-linked immunosorbent assay (ELISA). The expression of Toll-like receptor (TLR) 2 and TLR4 was determined using western blot analysis. And the phosphorylation of TLR downstream nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) was examined using cell-based protein phosphorylation ELISA kits.', 'We found that mangiferin reduced LPS-upregulated IL-6 production in OKF6/TERT-2 cells. Additionally, mangiferin inhibited LPS-induced TLR2 and TLR4 overexpression, and suppressed the phosphorylation of NF-κB, p38 MAPK and JNK. Moreover, mangiferin repressed IL-6 production and TLR signaling activation in a dose-dependent manner after 24h treatment.
Answer: Mangiferin decreases LPS-induced production of IL-6 in human oral epithelial cells by suppressing TLR signaling, and this glucosylxanthone may have potential for the treatment of periodontitis.
Answer: | Does mangiferin inhibit lipopolysaccharide-induced production of interleukin-6 in human oral epithelial cells by suppressing toll-like receptor signaling?
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Part 1. Definition
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.
Part 2. Example
Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
Answer: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
Explanation: The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
Part 3. Exercise
Context: Chronic oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. However, so far, few studies reported increased circulating levels of oxidative stress markers in patients with non-alcoholic fatty liver and no study has been performed with newer markers of systemic oxidative stress. The aim was to assess the relationship between urinary 8-iso-prostaglandin F2α and serum soluble NOX2-derived peptide and the severity of liver steatosis in subjects with non-alcoholic fatty liver.', 'The study was performed in 264 consecutive patients referred for suspected metabolic disease. Steatosis was defined according to Hamaguchi ultrasonographic criteria. Oxidative stress was assessed by urinary 8-iso- prostaglandin F2α and serum soluble NOX2-derived peptide levels.', 'Patients with non-alcoholic fatty liver had higher (p\u2009<\u20090.001) mean values of urinary 8-iso-PGF2α and of serum soluble NOX2-derived peptide, alanine aminotransferase, Cytokeratin-18 and homeostasis model of insulin resistance and lower values of serum adiponectin as compared to those without. Prevalence of metabolic syndrome and of its clinical features was significantly higher in patients with non-alcoholic fatty liver. Same findings were also observed after the exclusion of obese subjects, or subjects with diabetes or with metabolic syndrome and in those not taking statin medication. In addition, the levels of urinary 8-iso-PGF2α were independent predictors of non-alcoholic fatty liver and a strong association of urinary 8-iso-PGF2α and of serum soluble NOX2-derived peptide with the severity of steatosis at ultrasound was also observed.
Answer: We demonstrated increased markers of oxidative stress in subjects with non-alcoholic fatty liver. Urinary 8-iso-PGF2α and serum soluble NOX2-derived peptide levels were independent from obesity, diabetes and metabolic syndrome and increased with the severity of liver steatosis at ultrasound.
Answer: | Is nOX2-generated oxidative stress associated with severity of ultrasound liver steatosis in patients with non-alcoholic fatty liver disease? | task845_pubmedqa_question_generation |
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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.
[Q]: Context: Completeness of cytoreduction is a significant predictor of long-term outcome after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Imaging has limited sensitivity to identify peritoneal metastases and therefore predict whether complete cytoreduction is possible. We reviewed our experience using laparoscopy to determine candidates for complete cytoreduction and HIPEC.', 'This single-center, retrospective study examined patients from 2007 to 2014 who underwent laparoscopy to determine complete cytoreduction (CC-0/1)/HIPEC candidacy. Preoperative, intraoperative, and postoperative data were collected.', 'A total of 145 laparoscopies were performed on 141 patients, 72 (51.1\xa0%) of whom were female, with a median age of 53\xa0years (range 20-79). The primary site was appendiceal in 67 (47.5\xa0%) patients, colorectal in 43 (30.5\xa0%), mesothelioma in 17 (12.1\xa0%), unknown in 9 (6.4\xa0%), small bowel in 3 (2.1\xa0%), gastric in 1, and ovarian in 1 (0.7\xa0% each). Overall, 115 (81.6\xa0%) patients had prior abdominal surgery, 111 (76.6\xa0%) had evidence of disease on imaging, and 117 (80.7\xa0%) underwent prior chemotherapy, with a median of 5.9\xa0weeks between the last treatment and laparoscopy (0.9-498.9\xa0weeks). Four (2.8\xa0%) intraoperative complications were observed (one liver laceration, two enterotomies, and one air embolus), and nine (6.2\xa0%) postoperative complications [four (2.8\xa0%) Clavien grade (CG) I, three (2.8\xa0%) CG II, one (0.7\xa0%) CG III (return to operating room) and one (0.7\xa0%) CG IV (transient ischemic attack)]. Forty-eight patients deemed candidates by laparoscopy underwent CRS/HIPEC (positive predictive value 82.8\xa0%).
Answer: Diagnostic laparoscopy is a safe, feasible, and accurate staging tool in patients with suspected peritoneal metastases being considered for CRS.
[A]: Is laparoscopy Safe and Accurate to Evaluate Peritoneal Surface Metastasis Prior to Cytoreductive Surgery?
[Q]: Context: Accumulating evidence suggests that the balance between pathogenic effector T cells (Teffs) and regulatory T cells (Tregs) may be important for controlling atherosclerotic disease. We hypothesized that a combination therapy with anti-CD3 antibody (CD3-Ab) and IL-2/anti-IL-2 monoclonal antibody complex (IL-2 complex) aimed at increasing the ratio of Tregs to Teffs would effectively inhibit atherosclerosis in mice.', 'We treated apolipoprotein E-deficient mice fed a high-cholesterol diet with vehicle, CD3-Ab, IL-2 complex, or their combination. Mice receiving the combination therapy had markedly reduced atherosclerotic lesions than mice treated with CD3-Ab or IL-2 complex alone. In addition, a striking increase in the Treg/Teff ratio of lymphoid organs and atherosclerotic lesions, along with plaque stabilization characterized by decreased macrophage content and increased collagen content was observed. The combination treatment also markedly reduced splenic Ly6C(high) inflammatory monocytes and might induce a favorable macrophage phenotype change in atherosclerotic lesions.
Answer: Our results indicate that in addition to suppressing Teff responses, enhancing Treg-mediated immune responses is more efficacious in preventing atherosclerosis, suggesting a novel therapeutic approach for atherosclerosis.
[A]: Does cD3 antibody and IL-2 complex combination therapy inhibit atherosclerosis by augmenting a regulatory immune response?
[Q]: Context: Total exercise duration and abnormal QRS score values are treadmill exercise testing (TET) prognostic parameters that have been shown to be significantly and independently associated with cardiac mortality. We evaluated the prognostic value of a new index (M score, Michaelides score) incorporating TET duration and QRS score values in a simple index.', 'In this study, we included 626 patients, who underwent TET and coronary arteriography. Cardiac catheterization showed the presence of coronary artery disease in 64.3% of these patients. The M score was calculated by adding the value of the Athens QRS score to the duration of TET (in minutes). The outcome measure was a composite of myocardial infarction or death. Patients were prospectively followed for 38+/-21 months (median 36 months).', "The composite endpoint was more frequent among the patients of the 1st quartile (M-score values <-5.8). In univariate analysis, mortality of the first-quartile patients was significantly higher (14 vs. 1.1%, P<0.001). In multivariate Cox's regression analysis for age, sex, diabetes, smoking status, hypertension, hypercholesterolemia, maximum ST depression at TET, angina during TET, coronary artery disease on angiography, and echocardiographic left ventricular ejection fraction, the first quartile of M-score values was found to be independently associated with the composite endpoint (relative risk = 3.26, 95% confidence interval = 2.01-5.29, P<0.001).
Answer: This study shows that a new index termed the M score, which incorporates QRS score and exercise duration, predicts mortality and occurrence of myocardial infarction at long-term follow-up of high-risk individuals, independently of TET-induced ST-segment changes.
[A]: | Does duration of treadmill exercise testing combined with QRS score predict adverse cardiac outcome at long-term follow-up?
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instruction:
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.
question:
Context: The aim of the present study was to determine the potential therapeutic value of the lazaroid U-83836E on blood brain barrier (BBB) breakdown and edema with respect to the changes in the synaptosomal Na+/K+ and Mg(2+)/Ca(2+)-adenosinetriphosphatase (ATPase) activities, tissue malondialdehyde levels and the neuronal viability in the rat brain subjected to cerebral trauma.', 'Traumatic brain injury (TBI) was introduced by applying a 75 gm. cm force to the right parietal cortex using the weight-drop method. The first set of animals was used for determining time course changes of the synaptosomal Na+/K+ and Mg(2+)/Ca(2+)-ATPase and the malondialdehyde levels and were sacrificed 2, 6 and 24h after lesion production. A group of the animals was treated with U-83836E proir to TBI and sacrificed 24h after cerebral injury. A second set of animals was used for evaluating the alterations in BBB disruption and tissue water content and were sacrificed 2, 6 and 24h after lesion production. Two groups of animals were treated with U-83836E and sacrificed after 2 and 24h following TBI. U-83836E was given intraperitoneally thirty minutes before trauma at a dose of 10 mg/kg. Neuronal necrosis was also evaluated in the groups of U-83836E and physiological saline-treated animals.', 'Extravasation of Evans blue into the traumatized hemisphere was maximum at 2h (p<0.001) and returned close to the control levels at 24h after TBI (p>0.05). Edema had developed progressively over time and reached the maximum degree of 2.1% (p<0.001) at 24h. U-83836E showed no effect on the BBB breakdown and the tissue water content at 2h and still had no effect on the BBB breakdown after 24h following the trauma (p>0.05), although it reduced edema after 24h (p<0.01). The losses of Na+/K+ and Mg(2+)/Ca(2+)-ATPase activities were found as 39.5% (p<0.001) and 29.4% (p<0.01) of the control value, respectively, and remained at the decreased levels throughout the experiment. Malondialdehyde level continued to increase over time reaching up to 209% (p<0.001) of the control value 24h after TBI. Both ATPase activities were improved to near control values (p>.05) by the effect of U-83836E. U-83836E inhibited the increase of lipid peroxidation (p<0.001) and also salvaged neuronal necrosis (p<0.05).
Answer: U-83836E given prophylactically after cerebral trauma appears to reduce edema, possibly by inhibiting increases in lipid peroxidation and by stabilizing ATPase. Further studies are recommended to verify the similar effects of the brain penetrating lazaroids when they are given after trauma.
answer:
Does lazaroid attenuate edema by stabilizing ATPase in the traumatized rat brain?
question:
Context: To assess the role of whole-body computed tomography (CT) for determining morphological suitability before multiorgan retrieval (MOR) in brain dead patients.', 'Fifty-one clinically brain dead patients (21 women, 30 men; mean age 61 year±15) were included in this prospective, single center study. All patients had CT angiography of the brain and whole-body CT examination. CT images were evaluated for the presence of morphological abnormalities of lungs, liver and other abdominal organs and presence of vascular anatomical variants. The results of CT examinations were compared to intraoperative findings observed during organ harvesting and/or the results of histopathological analysis of biopsy specimens. The impact of whole-body CT examination on the harvesting process was evaluated.', 'Ninety-five percent of vascular anatomical variants that were found intraoperatively were depicted on CT. CT density measurements predicted surgical finding of steatosis in 80% of patients. Whole-body CT changed the MOR strategy in 21/51 patients (41%) including 3 MOR cancellations and 8 grafts refusals, whereas organ harvesting was continued in 10 patients after histopathological analysis was performed.
Answer: Selection of potential graft donors using whole-body CT is reliable and improves graft selection during MOR.
answer:
Is simultaneous CT angiography and whole-body CT an effective imaging approach before multiorgan retrieval?
question:
Context: To examine the correlation between transcranial Doppler ultrasonography-detected emboli during coronary artery bypass graft surgery with cardiopulmonary bypass and renal dysfunction as determined by the postoperative change in creatinine.', 'Retrospective review of data from the anesthesia and cardiothoracic surgery databases.', 'Tertiary care university hospital.', 'Two hundred eighty-six patients undergoing coronary artery bypass graft surgery.', 'Transcranial Doppler ultrasonography of the right middle cerebral artery was performed after induction of general anesthesia through completion of the operation. Doppler signals were recorded and emboli counts determined using an automated counting system.', 'Renal dysfunction was assessed as the change in creatinine from the preoperative value to the maximum postoperative value (Delta-Cr). There was a significant (p = 0.0003) univariate correlation between postoperative change in creatinine and total number of Doppler-detected emboli. The effect of total number of emboli remained significant (p = 0.0038) in the multivariable analysis after adjustment for covariables (age, sex, number of grafts, left ventricular ejection fraction, hypertension, history of congestive heart failure, diabetes, cardiopulmonary bypass time, preoperative creatinine, and maximum postoperative creatinine).
Answer: Increased numbers of Doppler-detected emboli during coronary artery bypass graft surgery are associated with postoperative renal dysfunction.
answer:
| Do transcranial Doppler emboli count predicts rise in creatinine after coronary artery bypass graft surgery?
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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: Elevated levels of B-type natriuretic peptide (BNP) are associated with adverse clinical outcomes in acute coronary syndrome (ACS), but several questions remain outstanding. Firstly, it has not yet been determined whether an additional BNP sample at 7 weeks post ACS would enhance risk prediction. Secondly, we assessed whether the prognostic potential of BNP in ACS could be explained by echocardiographic abnormalities such as left ventricular hypertrophy (LVH).', 'We measured bedside BNP levels in 443 consecutive patients presenting with ACS and at 7 weeks outpatient follow-up. Main outcome measure was either all-cause mortality, readmission with ACS, or congestive heart failure) at 10 months from presentation.', 'Of the 443 patients, 120 patients presented with ST-elevation myocardial infarction (27%). There were 90 cardiovascular (CV) events at 10 months. Adjusting for age, sex, hypertension, diabetes mellitus, smoking status, renal dysfunction, left ventricular ejection fraction, and echocardiographic LVH elevated near patient BNP levels (>80 pg/mL) were still associated with subsequent CV events when measured on admission (adjusted relative risk [RR] 2.63 [95% CI 1.34-5.19)] and also at 7 weeks post ACS (adjusted RR 4.12 [95% CI 1.58-10.72]). Patients with persistent BNP elevation at 7 weeks were also at an increased risk of CV events compared to those with an initial high BNP which then fell (unadjusted RR 4.04 [95% CI 1.24-13.15]).
Answer: In ACS, bedside BNP levels predict CV events at 10 months, independent of many echocardiographic abnormalities including LVH. Furthermore, our study suggests that an additional 7 weeks post ACS BNP enhances risk stratification over and above a one-off high BNP at baseline.
Output: Does serial bedside B-type natriuretic peptide strongly predict prognosis in acute coronary syndrome independent of echocardiographic abnormalities?
Input: Consider Input: Context: Loss-of-function mutations in the progranulin gene (PGRN) were identified in frontotemporal lobar degeneration (FTLD) with ubiquitin-immunoreactive neuronal inclusions (FTLD-U). We assessed whether PGRN also contributes to genetic risk for Alzheimer disease (AD) in an extended Belgian AD patient group (n = 779, onset age 74.7 +/- 8.7 years).', 'A mutation analysis of the PGRN coding region was performed. The effect of missense mutations was assessed using in silico predictions and protein modeling. Risk effects of common genetic variants were estimated by logistic regression analysis and gene-based haplotype association analysis.', 'We observed seven missense mutations in eight patients (1.3%). Convincing pathogenic evidence was obtained for two missense mutations, p.Cys139Arg and p.Pro451Leu, affecting PGRN protein folding and leading to loss of PGRN by degradation of the misfolded protein. In addition, we showed that PGRN haplotypes were associated with increased risk for AD.
Answer: Our data support a role for PGRN in patients with clinically diagnosed Alzheimer disease (AD). Further, we hypothesize that at least some PGRN missense mutations might lead to loss of functional protein. Whether the underlying pathology in our cases proves to be AD, frontotemporal lobar degeneration, or a combination of the two must await further investigations.
Output: Does genetic variability in progranulin contribute to risk for clinically diagnosed Alzheimer disease?
Input: Consider Input: Context: Atopic dermatitis (AD) often develops in infancy as the first manifestation of the atopic phenotype. Wheezing is also common in infancy, but it is less clear whether infant wheezing should be considered as an atopic phenotype. If infant wheeze and AD share a common aetiology, this would indicate that infant wheezing is an atopic phenotype.', 'To investigate whether potential risk factors for infant wheeze and AD have similar effects on these 2 phenotypes, indicating a common etiology.', 'A total of 34.793 mother-child pairs enrolled in the Danish National Birth Cohort were followed prospectively. Information on wheezing episodes, AD, and prenatal, perinatal, and postnatal risk factors was collected by interview at 12 and 30 weeks of gestation, at 6 and 18 months of age, and by linkage to the Danish Medical Birth Register. Data were analyzed by binary and polytomous logistic regression models.', 'The following variables had significantly differential effects on infant wheezing and AD: parental hay fever, parental asthma, parental AD, sex, maternal age, maternal occupation, smoking during pregnancy, season of birth, birth weight, gestational age, head circumference, breast-feeding, number of older siblings, day care attendance, and pets in the home.
Answer: The majority of risk factors had differential effects on infant wheeze and AD indicative of a different etiology. Infant wheezing does not seem to be etiologically linked to the epidemic of atopic disease, and infant wheezing should not be used as an indicator of the atopic phenotype.
| Output: Do differential effects of risk factors on infant wheeze and atopic dermatitis emphasize a different etiology?
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Teacher: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.
Teacher: Now, understand the problem? Solve this instance: Context: Immunoglobulin-A nephropathy (IgAN) is the most common chronic glomerulonephritis worldwide. Many clinical and histopathological risk factors for progression have been found previously. Recently, metabolic risk factors, such as hyperuricaemia and hypertriglyceridaemia, also have been associated with the progression of IgAN.', 'In the present study we correlated clinical and metabolic risk factors with histopathological parameters in 202 patients with IgAN. Morphological changes in glomerular, tubulointerstitial and vascular tissue were semiquantitatively graded into three classes. Mesangial proliferation activity and the amount of inflammatory cells were also evaluated by immunohistochemical staining of Ki-67 (MIB-1), CD45 (LCA) and CD68 stainings. Serum uric acid, triglycerides and cholesterol, urine protein excretion (UPE), blood pressure and body mass index (BMI) were measured. Smoking habits and occurrence of diabetes mellitus also were evaluated. The independent role of serum uric acid in the development of renal morphological changes was evaluated in multivariate analysis.', 'Serum uric acid and UPE level correlated with several histological parameters. Uric acid level showed the strongest correlation with tubulointerstitial changes and UPE with glomerulosclerosis. The level of serum triglycerides correlated with interstitial fibrosis and hyaline arteriolosclerosis. Blood pressure correlated with hyaline arteriolosclerosis, glomerulosclerosis and tubulointerstitial changes. BMI and diabetes mellitus correlated with both tubulointerstitial and vascular changes. We found no significant correlations between histopathological parameters and smoking habits or serum cholesterol level. Serum uric acid had independent associations with the presence of tubular atrophy and interstitial fibrosis and inflammation.
Answer: We conclude that many metabolic factors are univariately associated with renal morphological findings in IgAN. These same factors are central in the metabolic or insulin resistance syndrome and may have a pathogenetic role in the progression of IgAN. Serum uric acid may have an independent role in development of tubulointerstitial lesions as well as being associated with inflammation in renal tissue of patients with IgAN.
Student: | Does uric acid correlate with the severity of histopathological parameters in IgA nephropathy? | task845_pubmedqa_question_generation |
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Given the task definition, example input & output, solve the new input case.
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.
Example: Context: Chronic rhinosinusitis (CRS) is a heterogeneous disease with an uncertain pathogenesis. Group 2 innate lymphoid cells (ILC2s) represent a recently discovered cell population which has been implicated in driving Th2 inflammation in CRS; however, their relationship with clinical disease characteristics has yet to be investigated. The aim of this study was to identify ILC2s in sinus mucosa in patients with CRS and controls and compare ILC2s across characteristics of disease. A cross-sectional study of patients with CRS undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies were obtained during surgery and control tissue from patients undergoing pituitary tumour resection through transphenoidal approach. ILC2s were identified as CD45(+) Lin(-) CD127(+) CD4(-) CD8(-) CRTH2(CD294)(+) CD161(+) cells in single cell suspensions through flow cytometry. ILC2 frequencies, measured as a percentage of CD45(+) cells, were compared across CRS phenotype, endotype, inflammatory CRS subtype and other disease characteristics including blood eosinophils, serum IgE, asthma status and nasal symptom score. 35 patients (40% female, age 48 ± 17 years) including 13 with eosinophilic CRS (eCRS), 13 with non-eCRS and 9 controls were recruited. ILC2 frequencies were associated with the presence of nasal polyps (P = 0.002) as well as high tissue eosinophilia (P = 0.004) and eosinophil-dominant CRS (P = 0.001) (Mann-Whitney U). They were also associated with increased blood eosinophilia (P = 0.005). There were no significant associations found between ILC2s and serum total IgE and allergic disease. In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (P = 0.03). ILC2s were also correlated with worsening nasal symptom score in CRS (P = 0.04).
Answer: As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. ILC2s are also linked with high tissue and blood eosinophilia and have a potential role in the activation and survival of eosinophils during the Th2 immune response. The association of innate lymphoid cells in CRS provides insights into its pathogenesis.
Output: Are group 2 innate lymphoid cells ( ILC2s ) increased in chronic rhinosinusitis with nasal polyps or eosinophilia?
The question is based on the following sentences from the two passages (i) Group 2 innate lymphoid cells (ILC2s) {ii) In the CRS with nasal polyps (CRSwNP) population, ILC2s were increased in patients with co-existing asthma (iii) As ILC2s are elevated in patients with CRSwNP, they may drive nasal polyp formation in CRS. and (iv) ILC2s are also linked with high tissue and blood eosinophilia.
New input case for you: Context: Vasopeptidase inhibitors are drugs that inhibit angiotensin-converting enzyme and neutral endopeptidase (NEP). The latter is a protease that degrades vasoactive peptides and is increased in diabetes. We have previously shown that treating streptozotocin-induced diabetic rats, an animal model of type 1 diabetes, with AVE7688, a vasopeptidase inhibitor, improves neurovascular and neural function. In this study, we determined the effect of treating Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes, with AVE7688 on vascular and neural function.', 'ZDF rats at 12 weeks of age were treated for 12 weeks with AVE7688 (500 mg/kg diet). Afterwards, vascular reactivity of epineurial arterioles of the sciatic nerve and nerve conduction velocity and blood flow was determined.', 'Vascular and neural function was significantly impaired in ZDF rats compared with age-matched lean (control) rats. Treating ZDF rats with AVE7688 improved vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles. Motor and sensory nerve conduction velocity, endoneurial blood flow and thermal nociception end-points were also improved by treatment compared with untreated ZDF rats. Superoxide and expression of NEP were increased in epineurial arterioles from ZDF rats and attenuated by treatment with AVE7688.
Answer: AVE7688 is an effective treatment for microvascular and neural disease in ZDF rats. Thus, vasopeptidase inhibitors may be an effective treatment for diabetic microvascular and neural complication in type 2 diabetes.
Output: | Does treatment of Zucker diabetic fatty rats with AVE7688 improve vascular and neural dysfunction? | task845_pubmedqa_question_generation |
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instruction:
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.
question:
Context: Adipocytes express inflammatory mediators that contribute to the low-level, chronic inflammation found in obese subjects and have been linked to the onset of cardiovascular disorders and insulin resistance associated with type 2 diabetes mellitus. A reduction in inflammatory gene expression in adipocytes would be expected to reverse this low-level, inflammatory state and improve cardiovascular function and insulin sensitivity. The natural products, curcumin and resveratrol, are established anti-inflammatory compounds that mediate their effects by inhibiting activation of NF-kappaB signaling. In the present study, we examined if these natural products can inhibit NF-kappaB activation in adipocytes and in doing so reduce cytokine expression.', 'Cytokine (TNF-alpha, IL-1beta, IL-6) and COX-2 gene expression in 3T3-L1-derived adipocytes was measured by quantitative real-time PCR (qRT-PCR) with or without TNFalpha-stimulation. Cytokine protein and prostaglandin E2 (PGE2) expression were measured by ELISA. Effects of curcumin and resveratrol were evaluated by treating TNFalpha-stimulated adipocytes with each compound and 1) assessing the activation state of the NF-kappaB signaling pathway and 2) measuring inflammatory gene expression by qRT-PCR and ELISA.', 'Both preadipocytes and differentiated adipocytes express the genes for TNF-alpha, IL-6, and COX-2, key mediators of the inflammatory response. Preadipocytes were also found to express IL-1beta; however, IL-1beta expression was absent in differentiated adipocytes. TNF-alpha treatment activated NF-kappaB signaling in differentiated adipocytes by inducing IkappaB degradation and NF-kappaB translocation to the nucleus, and as a result increased IL-6 (6-fold) and COX-2 (2.5-fold) mRNA levels. TNF-alpha also activated IL-1beta gene expression in differentiated adipocytes, but had no effect on endogenous TNF-alpha mRNA levels. No detectable TNFalpha or IL-1beta was secreted by adipocytes. Curcumin and resveratrol treatment inhibited NF-kappaB activation and resulted in a reduction of TNF-alpha, IL-1beta, IL-6, and COX-2 gene expression (IC50 = 2 muM) and a reduction of secreted IL-6 and PGE2 (IC50 ~ 20 muM).
Answer: Curcumin and resveratrol are able to inhibit TNFalpha-activated NF-kappaB signaling in adipocytes and as a result significantly reduce cytokine expression. These data suggest that curcumin and resveratrol may provide a novel and safe approach to reduce or inhibit the chronic inflammatory properties of adipose tissue.
answer:
Do curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes?
question:
Context: The membrane protein CD46, a ubiquitous cell surface pathogen receptor, can bind Streptococcus to trigger cell autophagy, which is a critical step in the control of infection.', 'In this study, we found a new splice variant designated CD46 transcript variant (CD46-TV). The splice variant is characterized by the retention of a 48\xa0bp sequence from intron 8 of the bovine CD46 gene, which encodes a putative protein enlarged by 16 amino acids. CD46-TV mRNA was found to be over expressed in mastitis-infected mammary gland tissues relative to healthy tissues. A single nucleotide polymorphism (c. 1033\u2009+\u20092184 C\u2009>\u2009T) in the exonic splicing enhancer (ESE) motif region was shown to result in the CD46-TV aberrant splice variant through constructing alternative alleles using the pSPL3 exon capturing vector and transfecting these into 293\xa0T cells. Allelic frequency in 56,682 individuals belonging to 112 Bos taurus, Bos indicus, Bos javanicus, Bos grunniens and Bos mutus, etc. suggests that the C allele (80.09%) is the ancestral allele. Association analysis found that the mean genomic estimated breeding values (gEBV) for milk somatic cell score and the occurrence of clinical mastitis, as well as the milk somatic cell score of Chinese Holsteins with the CT genotype was lower than those of individuals with either the CC or TT genotypes. The mean gEBV for udder health synthesis for the TT genotype was greater than those for the CC or CT genotypes.
Answer: Our findings suggest that the CD46 gene likely plays a critical role in the risk of mastitis caused by Streptococcus in dairy cows via an alternative splicing mechanism caused by a functional mutation in intron 8. Our data also underline the importance of variation within ESEs in regulating transcript processing.
answer:
Does a SNP in intron 8 of CD46 cause a novel transcript associated with mastitis in Holsteins?
question:
Context: A safety event drew attention to unsafe and inappropriate payer formulary alerts. These alerts display formulary, coverage, and eligibility data from the pharmacy benefits manager in response to an electronic prescription. They are intended to redirect prescribers to medications that are covered by insurance; however, these alerts were found to be inaccurate and contribute to potentially harmful alerts. Our objective was to reduce inappropriate payer formulary alerts by 30% within 1 year and to change the ePrescribing certification requirements to prevent future instances of harm.', 'Using process mapping we identified the changes that were required both locally and nationally through our electronic health record (EHR) vendor and ePrescribing transaction broker. We partnered with vendors to show the safety risk and to suggest modifications to the payer formulary alert content and ePrescribing certification criteria. On the basis of the new criteria, we modified and deactivated inappropriate alerts. Rates were followed weekly for 13 months and a control chart was used to track progress.', 'From January 2014 to January 2015, we reviewed 59\u2009325 payer formulary alerts from ambulatory care and 11\u2009630 from the emergency department and inpatient wards. Both local and national modifications resulted in significant and sustained decreases in inappropriate alerts.
Answer: Enduring and meaningful change required partnership with multiple stakeholders, including EHR vendors, ePrescribing vendors, and pharmacy benefits managers. Improving drug alerts, reducing alert fatigue, and promoting value-based prescribing in the EHR will likely require similar partnerships.
answer:
| Does payer Formulary alert as a Cause of Patient Harm and the Journey to Change Them?
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Teacher: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.
Teacher: Now, understand the problem? Solve this instance: Context: Carotenoids may reduce the risk for diabetes mellitus, but little is known about the association of insulin resistance with serum carotenoids in non-diabetic subjects. This study aimed to investigate whether the homeostasis model assessment-insulin resistance (HOMA-IR) index would be lower in the presence of high serum carotenoid concentrations in non-diabetic subjects.', 'A total of 812 subjects (256 males and 556 females) who had received health examinations in 2003 participated in the study. The associations of the serum-carotenoid concentrations and HOMA-IR were evaluated cross-sectionally. The multivariate-adjusted geometric means of HOMA-IR by the tertiles of the serum carotenoid concentration were calculated after adjusting for age, body mass index, systolic blood pressure, total cholesterol, triacylglycerols, current tobacco use, regular alcohol intake, exercise habits and total energy intake. Associations among high HOMA-IR (3.0+mUxmmol/L2) across tertiles of serum carotenoid concentration were assessed by tests for logistic regression analysis.', 'In male subjects, the multivariate adjusted geometric mean of HOMA-IR was inversely associated with the serum beta-cryptoxanthin concentrations. In female subjects, an inverse association of the serum carotenoid concentration and HOMA-IR was observed in lycopene, beta-cryptoxanthin, and zeaxanthin. The confounding factor-adjusted odds ratios (OR) for high HOMA-IR on the highest tertiles of serum alpha-carotene, beta-carotene, beta-cryptoxanthin, and zeaxanthin were 0.18 [95% confidence interval (CI): 0.06-0.52], 0.22 (95% CI: 0.07-0.67), 0.34 (95% CI: 0.12-0.96), and 0.30 (95% CI: 0.11-0.79), respectively, in male subjects. On the other hand, in female subjects, the adjusted OR for high HOMA-IR on the highest tertiles of serum lycopene and beta-cryptoxanthin were 0.39 (95% CI: 0.21-0.73) and 0.51 (95% CI: 0.28-0.95), respectively.
Answer: The serum antioxidant carotenoids were inversely associated with HOMA-estimated insulin resistance in non-diabetic subjects.
Student: | Is the homeostasis model assessment-insulin resistance index inversely associated with serum carotenoids in non-diabetic subjects? | task845_pubmedqa_question_generation |
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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: Diabetic retinopathy (DR) is a retinopathy resulting from diabetes mellitus (DM) which was classified into non-proliferative DR (NPDR) and proliferative DR (PDR). Without an early screening and effective diagnosis, patients with PDR will develop serious complications. Therefore, we sought to identify special serum microRNAs (miRNAs) that can serve as a novel non-invasive screening signature of PDR and test its specificity and sensitivity in the early diagnosis of PDR.', 'In total, we obtained serum samples from 90 PDR cases, 90 matched NPDR patients and 20 controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA). The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR (RT-qPCR) arranged in an initial and a two-stage validation sets. Moreover, additional double-blind testing was performed in 20 patients clinically suspected of having DR to evaluate the diagnostic value and accuracy of the serum miRNA profiling system in predicting PDR.', 'Three miRNAs were significantly increased in patients with PDR compared with NPDR after the multiple stages. The areas under the receiver operating characteristic (ROC) curves of the validated three-serum miRNAs signature were 0.830, 0.803 and 0.873 in the initial and two validation sets, respectively. Combination of miR-21, miR-181c, and miR-1179 possessed a moderate ability to discrimination between PDR and NPDR with an area under ROC value of 0.89. The accuracy rate of the three-miRNA profile as PDR signature was 82.6%.
Answer: These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of PDR. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of PDR from NPDR.
Answer: Do serum miRNA biomarkers serve as a fingerprint for proliferative diabetic retinopathy?
Question: Context: The present meta-analysis aimed to investigate whether there is an association between SERPINE1 rs1799768 polymorphism and sepsis risk and mortality.', 'Published reports were searched in PubMed, PubMed Central, Gene, PubChem and Google Scholar. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed in a random-effects model.', 'The results of the overall meta-analysis indicated that an increased sepsis risk was evidently associated with SERPINE1 rs1799768 polymorphism (OR = 1.30; 95% CI 1.08-1.56; p = 0.006). When studies were stratified by ethnicity, no significant association was observed between SERPINE1 rs1799768 polymorphism and sepsis risk in the Asian group. As for the Caucasian population, overall OR was 1.24 (95% CI 1.02-1.51; p = 0.03). The results of the overall meta-analysis indicated that an increased sepsis mortality risk was evidently associated with SERPINE1 rs1799768 polymorphism (OR = 1.73; 95% CI 1.31-2.28; p < 0.0001). When studies were stratified by ethnicity, significant association was observed between SERPINE1 rs1799768 polymorphism and sepsis risk mortality in the Asian group and the Caucasian population.
Answer: In conclusion, the meta-analysis suggests that there are significant associations between SERPINE1 rs1799768 polymorphism and risk of sepsis and sepsis mortality.
Answer: Does sERPINE1 rs1799768 polymorphism contribute to sepsis risk and mortality?
Question: Context: Cerebral pressure passivity (CPP) in sick newborns can be detected by evaluating coupling between mean arterial pressure (MAP) and cerebral blood flow measured by near infra-red spectroscopy hemoglobin difference (HbD). However, continuous MAP monitoring requires invasive catheterization with its inherent risks. We tested whether heart rate (HR) could serve as a reliable surrogate for MAP in the detection of CPP in sick newborns.', 'Continuous measurements of MAP, HR, and HbD were made and partitioned into 10-min epochs. Spectral coherence (COH) was computed between MAP and HbD (COHMAP-HbD) to detect CPP, between HR and HbD (COHHR-HbD) for comparison, and between MAP and HR (COHMAP-HR) to quantify baroreflex function (BRF). The agreement between COHMAP-HbD and COHHR-HbD was assessed using ROC analysis.', 'We found poor agreement between COHMAP-HbD and COHHR-HbD in left hemisphere (area under the ROC curve (AUC) 0.68) and right hemisphere (AUC 0.71). Baroreflex failure (COHMAP-HR not significant) was present in 79% of epochs. Confining comparison to epochs with intact BRF showed an AUC of 0.85 for both hemispheres.
Answer: In these sick newborns, HR was an unreliable surrogate for MAP required for the detection of CPP. This is likely due to the prevalence of BRF failure in these infants.
Answer: | Does baroreflex dysfunction in sick newborns make heart rate an unreliable surrogate for blood pressure changes?
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Detailed Instructions: 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.
Q: Context: Low vitamin D levels have been associated with obesity and living in areas that lack sunshine, such as northern Europe. The aim of this study was to investigate the vitamin D status of a group of obese children in Sweden and to investigate the associations between vitamin D status and markers of glucose metabolism and metabolic risk markers.', 'This was a prospective cross-sectional study of 202 obese children between 4.5 and 17.9 years of age who had been referred to the National Childhood Obesity Centre at Karolinska University Hospital, Stockholm. We examined age, gender, 25-hydroxyvitamin D (25(OH)D), f-glucose, f-insulin and metabolic risk markers. Vitamin D deficiency was defined as less than 30 25(OH)D nmol/L. Children with and without a vitamin D deficiency were compared.', 'Just over a third (33.2%) of our study population had vitamin D levels <30 nmol/L 25(OH)D. A significant interaction effect was found between age and 25(OH)D. An association was also found between low 25(OH)D levels and impaired fasting glycaemia (IFG) independent of age and season.
Answer: Low vitamin D levels were common among obese adolescents living in Sweden and were strongly associated with age and associated with a higher risk of IFG.
A: | Is vitamin D deficiency associated with prediabetes in obese Swedish children? | task845_pubmedqa_question_generation |
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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.
Context: Flare up of acute lower back pain associated with myofascial pain syndrome (MPS) may require various forms of treatment including activity restriction and bracing. Electrical twitch obtaining intramuscular stimulation (ETOIMS) is a promising new treatment. It involves the use of a strong monopolar electromyographic needle electrode for electrical stimulation of deep motor end plate zones in multiple muscles in order to elicit twitches.', 'An elite American football player with MPS symptoms failed to respond to standard treatments. He then received ETOIMS which completely alleviated the pain. After establishing pain control, the athlete continued with a further series of treatments to control symptoms of muscle tightness.
Answer: ETOIMS has a promising role in pain alleviation, increasing and maintaining range of motion, and in providing satisfactory athletic performance during long term follow up.
Do electrical twitch obtaining intramuscular stimulation ( ETOIMS ) for myofascial pain syndrome in a football player?
Context: To test the role of mast cells in gut inflammation and colitis using interleukin (IL)-10-deficient mice as an experimental model.', 'Mast cell-deficient (Kit (W-sh/W-sh) ) mice were crossbred with IL-10-deficient mice to obtain double knockout (DKO) mice. The growth, mucosal damage and colitis status of DKO mice were compared with their IL-10-deficient littermates.', 'DKO mice exhibited exacerbated colitis compared with their IL-10-deficient littermates, as shown by increased pathological score, higher myeloperoxidase content, enhanced Th1 type pro-inflammatory cytokines and inflammatory signaling, elevated oxidative stress, as well as pronounced goblet cell loss. In addition, deficiency in mast cells resulted in enhanced mucosal damage, increased gut permeability, and impaired epithelial tight junctions. Mast cell deficiency was also linked to systemic inflammation, as demonstrated by higher serum levels of tumor necrosis factor α and interferon γ in DKO mice than that in IL-10-deficient mice.
Answer: Mast cell deficiency in IL-10-deficient mice resulted in systematic and gut inflammation, impaired gut barrier function, and severer Th1-mediated colitis when compared to mice with only IL-10-deficiency. Inflammation and impaired gut epithelial barrier function likely form a vicious cycle to worsen colitis in the DKO mice.
Does mast cell deficiency exacerbate inflammatory bowel symptoms in interleukin-10-deficient mice?
Context: A history of preeclampsia is an independent risk factor for cardiac events and stroke. Changes in vasculature structure that contribute to these associations are not well understood.', 'The aim of this study was to quantify coronary artery calcification (CAC), a known risk factor for cardiac events, in a prospective cohort of women with and without histories of preeclampsia.', 'Women without prior cardiovascular events (40 with and 40 without histories of preeclampsia, matched for parity and age at index birth) were recruited from a large population-based cohort of women who were residents of Olmsted County, Minnesota, and who delivered from 1976 through 1982. Computed tomography was performed to measure CAC in Agatston units. All pregnancy histories and covariates were confirmed by review of the medical records. Current clinical variables were assessed at the time of imaging. Differences between women with and without histories of preeclampsia were examined using χ(2) tests and tests; CAC, in particular, was compared as a categorical and ordinal variable, with a χ(2) test and with Wilcoxon 2-sample tests and ordinal logistic regression, as appropriate.', 'Mean age (SD) at imaging was 59.5 (±4.6) years. Systolic and diastolic blood pressures, hyperlipidemia, and current diabetes status did not differ between women with and without histories of preeclampsia. However, the frequencies of having a current clinical diagnosis of hypertension (60% vs 20%, P < .001) and higher body mass index in kg/m(2) (expressed as median [25th-75th percentile], 29.8 [25.9-33.7] vs 25.3 [23.1-32.0], P = .023) were both greater in the women with histories of preeclampsia compared to those without. The frequency of a CAC score >50 Agatston units was also greater in the preeclampsia group (23% vs 0%, P = .001). Compared to women without preeclampsia, the odds of having a higher CAC score was 3.54 (confidence interval [CI], 1.39-9.02) times greater in women with prior preeclampsia without adjustment, and 2.61 (CI, 0.95-7.14) times greater after adjustment for current hypertension. After adjustment for body mass index alone, the odds of having a higher CAC based on a history of preeclampsia remained significant at 3.20 (CI, 1.21-8.49).
Answer: In this first prospective cohort study with confirmation of preeclampsia by medical record review, a history of preeclampsia is associated with an increased risk of CAC >30 years after affected pregnancies, even after controlling individually for traditional risk factors. A history of preeclampsia should be considered in risk assessment when initiating primary prevention strategies to reduce cardiovascular disease in women. Among women with histories of preeclampsia, the presence of CAC may be able to identify those at a particularly high cardiovascular risk, and should be the subject of future studies.
| Is a history of preeclampsia associated with a risk for coronary artery calcification 3 decades later?
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Given the task definition and input, reply with output. 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.
Context: The 34-gene classifier, ClearCode34, identifies prognostically distinct molecular subtypes of clear cell renal cell carcinoma (ccRCC) termed clear cell A (ccA) and clear cell B (ccB). The primary objective of this study was to describe clinical characteristics and comorbidities of relevance in patients stratified by ClearCode34.', 'In this retrospective analysis, 282 patients from Moffitt Cancer Center with ccRCC with gene expression analyses of the primary tumor were identified and ClearCode34 was applied to identify tumors as ccA or ccB. The medical record and institutional databases were queried to define patient characteristics, comorbidities, and outcomes.', 'We validated in this external cohort the superior overall survival, cancer-specific survival, and recurrence-free survival of ccA patients relative to ccB patients (P<0.001). Addressing other clinical characteristics, the ccA patients were more likely to be obese (48% vs. 34%, P = 0.021) and diabetic (26% vs. 13%, P = 0.035). The ccA patients also trended toward having been more frequent users of angiotensin system inhibitors (71% vs. 52%, P = 0.055). In multivariate analyses, ccB status is independently associated with inferior cancer-specific survival (hazard ratio = 3.26, 95% confidence interval: 1.84-5.79) and overall survival (hazard ratio = 2.50, 95% confidence interval: 1.53-4.08).
Answer: ClearCode34, after considering distinct patterns of comorbidities in each molecular subtype, remains a strong prognostic tool in patients with ccRCC. Obesity and diabetes mellitus emerged as factors that may influence ccRCC phenotypes and further studies investigating the effect of these metabolic conditions functionally onto tumor biology are warranted. Additionally, use of angiotensin system inhibitors could be studied in the context of ccRCC molecular classification in future studies to better understand its effect on ccRCC outcomes.
| Do patients with ClearCode34-identified molecular subtypes of clear cell renal cell carcinoma represent unique populations with distinct comorbidities? | task845_pubmedqa_question_generation |
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Teacher: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.
Teacher: Now, understand the problem? Solve this instance: Context: To investigate if diabetic patients without diabetic retinopathy despite long disease duration have different human leukocyte antigen (HLA) status vs those with an early onset of retinopathy.', 'Retrospective, nonrandomized, masked comparative study. Type 1 diabetic patients with a disease onset before age 30 were recruited to the study. The study population consisted of two groups of diabetic patients: those with normal retinopathy course (retinopathy developed during the first 20 years of diabetes onset) (23 patients) and those with postponed retinopathy (no obvious retinopathy in spite of passing 20 years of diabetes) (19 patients). These groups were matched with regard to level of glycemic control, blood pressure, and lipid profile. A group of 23 healthy patients served as controls. HLA-DQB1 typing of blood samples was done using a polymerase chain reaction with sequence-specific primer (PCR-SSP) method.', 'HLA-DQB1*0201/HLA-DQB1*0501 and HLA-DQB1*0201/HLA-DQB1*0504 haplotypes were more common among type 1 diabetic patients with normal retinopathy course than those with postponed retinopathy (26.1% vs 0.0%; p=0.019). HLA-DQB1*0301 and HLA-DQB1*0304 were less common among those diabetic patients with normal retinopathy course than those with a postponed retinopathy (63.2% vs 34.8%; p=0.067).
Answer: Some haplotypes seem to predispose diabetic patients to diabetic retinopathy. HLA typing may be beneficial for predicting the prognosis of diabetic retinopathy in younger diabetic patients.
Student: | Do hLA-DQB1 subtypes predict diabetic retinopathy in patients with type I diabetes mellitus? | task845_pubmedqa_question_generation |
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