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24,755,824
Does liver stiffness by transient elastography predict liver-related complications and mortality in patients with chronic liver disease?
{ "contexts": [ "Liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) is a validated method for noninvasively staging liver fibrosis. Most hepatic complications occur in patients with advanced fibrosis. Our objective was to determine the ability of LSM by TE to predict hepatic complications and mortality in a large cohort of patients with chronic liver disease.", "In consecutive adults who underwent LSM by TE between July 2008 and June 2011, we used Cox regression to determine the independent association between liver stiffness and death or hepatic complications (decompensation, hepatocellular carcinoma, and liver transplantation). The performance of LSM to predict complications was determined using the c-statistic.", "Among 2,052 patients (median age 51 years, 65% with hepatitis B or C), 87 patients (4.2%) died or developed a hepatic complication during a median follow-up period of 15.6 months (interquartile range, 11.0-23.5 months). Patients with complications had higher median liver stiffness than those without complications (13.5 vs. 6.0 kPa; P<0.00005). The 2-year incidence rates of death or hepatic complications were 2.6%, 9%, 19%, and 34% in patients with liver stiffness <10, 10-19.9, 20-39.9, and ≥40 kPa, respectively (P<0.00005). After adjustment for potential confounders, liver stiffness by TE was an independent predictor of complications (hazard ratio [HR] 1.05 per kPa; 95% confidence interval [CI] 1.03-1.06). The c-statistic of liver-stiffness for predicting complications was 0.80 (95% CI 0.75-0.85). A liver stiffness below 20 kPa effectively excluded complications (specificity 93%, negative predictive value 97%); however, the positive predictive value of higher results was sub-optimal (20%)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Carcinoma, Hepatocellular", "Chronic Disease", "Comorbidity", "Elasticity Imaging Techniques", "Female", "Humans", "Liver", "Liver Cirrhosis", "Liver Diseases", "Male", "Middle Aged", "Prognosis" ] }
Liver stiffness by TE accurately predicts the risk of death or hepatic complications in patients with chronic liver disease. TE may facilitate the estimation of prognosis and guide management of these patients.
yes
[ { "from": "human", "value": "Question: Does liver stiffness by transient elastography predict liver-related complications and mortality in patients with chronic liver disease?\nContext: {'contexts': ['Liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) is a validated method for noninvasively staging liver fibrosis. Most hepatic complications occur in patients with advanced fibrosis. Our objective was to determine the ability of LSM by TE to predict hepatic complications and mortality in a large cohort of patients with chronic liver disease.', 'In consecutive adults who underwent LSM by TE between July 2008 and June 2011, we used Cox regression to determine the independent association between liver stiffness and death or hepatic complications (decompensation, hepatocellular carcinoma, and liver transplantation). The performance of LSM to predict complications was determined using the c-statistic.', 'Among 2,052 patients (median age 51 years, 65% with hepatitis B or C), 87 patients (4.2%) died or developed a hepatic complication during a median follow-up period of 15.6 months (interquartile range, 11.0-23.5 months). Patients with complications had higher median liver stiffness than those without complications (13.5 vs. 6.0 kPa; P<0.00005). The 2-year incidence rates of death or hepatic complications were 2.6%, 9%, 19%, and 34% in patients with liver stiffness <10, 10-19.9, 20-39.9, and ≥40 kPa, respectively (P<0.00005). After adjustment for potential confounders, liver stiffness by TE was an independent predictor of complications (hazard ratio [HR] 1.05 per kPa; 95% confidence interval [CI] 1.03-1.06). The c-statistic of liver-stiffness for predicting complications was 0.80 (95% CI 0.75-0.85). A liver stiffness below 20 kPa effectively excluded complications (specificity 93%, negative predictive value 97%); however, the positive predictive value of higher results was sub-optimal (20%).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Carcinoma, Hepatocellular', 'Chronic Disease', 'Comorbidity', 'Elasticity Imaging Techniques', 'Female', 'Humans', 'Liver', 'Liver Cirrhosis', 'Liver Diseases', 'Male', 'Middle Aged', 'Prognosis']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,755,328
Does high basal level of autophagy in high-altitude residents attenuate myocardial ischemia-reperfusion injury?
{ "contexts": [ "Hypoxia can induce autophagy, which plays an important role in cardioprotection. The present study tested the hypothesis that patients with congenital heart disease living at a high altitude could resist ischemia-reperfusion injury better than those at a low altitude, through elevated basal autophagy by chronic hypoxia.", "Twelve Tibetan patients residing at a high altitude of >3000 m and 12 Han patients residing at a low altitude of <500 m with simple atrial or ventricular septal defects were prospectively recruited. All patients underwent cardiopulmonary bypass, maintaining a flow rate of approximately 2.4 to 2.8 L/min/m2 and mean arterial pressure of ≥40 to 60 mm Hg. Myocardial ischemia-reperfusion injury between the 2 groups was compared using cardiac troponin I, brain natriuretic peptide, hematoxylin eosin staining, and the terminal deoxynucleotidyl transferase dUTP nick end labeling test. Autophagy-related proteins microtubule-associated protein 1 light chain 3 II (LC3II), Beclin1, and lysosomal-associated membrane protein 2 (LAMP2) and their upstream protein BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) were evaluated with Western blotting.", "The maximal cardiac troponin I concentration and increasing x-fold of brain natriuretic peptide in the high-altitude group were obviously lower than those in the low-altitude group (3.10±0.77 vs 7.10±2.28 ng/mL and 2.51±0.94 vs 14.66±6.83, respectively). The preoperative and postoperative levels of LC3II, LAMP2, and upstream Bnip3 in the high-altitude group were obviously greater. No difference was found in the Beclin1 level between the 2 groups at baseline or ischemia-reperfusion." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Altitude", "Apoptosis Regulatory Proteins", "Autophagy", "Beclin-1", "Biomarkers", "Blotting, Western", "Cardiopulmonary Bypass", "Child", "Female", "Heart Defects, Congenital", "Humans", "Hypoxia", "In Situ Nick-End Labeling", "Lysosomal-Associated Membrane Protein 2", "Male", "Membrane Proteins", "Microtubule-Associated Proteins", "Myocardial Reperfusion Injury", "Natriuretic Peptide, Brain", "Prospective Studies", "Tibet", "Troponin I" ] }
Patients living at a high altitude with congenital heart disease resisted ischemia-reperfusion injury during cardiac surgery better than those at a low altitude, possibly through elevated basal autophagy induced by chronic hypoxia.
yes
[ { "from": "human", "value": "Question: Does high basal level of autophagy in high-altitude residents attenuate myocardial ischemia-reperfusion injury?\nContext: {'contexts': ['Hypoxia can induce autophagy, which plays an important role in cardioprotection. The present study tested the hypothesis that patients with congenital heart disease living at a high altitude could resist ischemia-reperfusion injury better than those at a low altitude, through elevated basal autophagy by chronic hypoxia.', 'Twelve Tibetan patients residing at a high altitude of >3000 m and 12 Han patients residing at a low altitude of <500 m with simple atrial or ventricular septal defects were prospectively recruited. All patients underwent cardiopulmonary bypass, maintaining a flow rate of approximately 2.4 to 2.8 L/min/m2 and mean arterial pressure of ≥40 to 60 mm Hg. Myocardial ischemia-reperfusion injury between the 2 groups was compared using cardiac troponin I, brain natriuretic peptide, hematoxylin eosin staining, and the terminal deoxynucleotidyl transferase dUTP nick end labeling test. Autophagy-related proteins microtubule-associated protein 1 light chain 3 II (LC3II), Beclin1, and lysosomal-associated membrane protein 2 (LAMP2) and their upstream protein BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) were evaluated with Western blotting.', 'The maximal cardiac troponin I concentration and increasing x-fold of brain natriuretic peptide in the high-altitude group were obviously lower than those in the low-altitude group (3.10±0.77 vs 7.10±2.28 ng/mL and 2.51±0.94 vs 14.66±6.83, respectively). The preoperative and postoperative levels of LC3II, LAMP2, and upstream Bnip3 in the high-altitude group were obviously greater. No difference was found in the Beclin1 level between the 2 groups at baseline or ischemia-reperfusion.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Altitude', 'Apoptosis Regulatory Proteins', 'Autophagy', 'Beclin-1', 'Biomarkers', 'Blotting, Western', 'Cardiopulmonary Bypass', 'Child', 'Female', 'Heart Defects, Congenital', 'Humans', 'Hypoxia', 'In Situ Nick-End Labeling', 'Lysosomal-Associated Membrane Protein 2', 'Male', 'Membrane Proteins', 'Microtubule-Associated Proteins', 'Myocardial Reperfusion Injury', 'Natriuretic Peptide, Brain', 'Prospective Studies', 'Tibet', 'Troponin I']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,749,730
Is allocentric but not egocentric orientation impaired during normal aging : an ERP study?
{ "contexts": [ "Behavioral studies of spatial navigation in aging indicate that orientation using an allocentric reference frame (object-centered orientation) is impaired, whereas orientation using egocentric processes (self-centered orientation) is not. It has been proposed that navigational deficits may result from more general alterations of perception and attention or executive functions. The purpose of this study is to assess allocentric and egocentric representation in elderly individuals, and to determine if age-related deficits in spatial navigation are related to an attentional decline.", "We assessed encoding of the position of geometrical shapes, depending specifically on an allocentric or egocentric reference frame, during ERP recording in young and old subjects.", "Aging was associated with a performance decline in allocentric, but not egocentric, encoding. Both allocentric and egocentric conditions elicited parietal early components P1 and N1, reflecting top-down modulation, and components P2 and N2, reflecting selective attention and stimulus categorization. We observed age-associated effects on N1 and N2 amplitudes and on N2 latency in both spatial conditions. Moreover, impaired allocentric performance in older subjects was associated with a greater P2 amplitude and delayed P2 latency compared with younger subjects." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Aging", "Attention", "Brain", "Electroencephalography", "Evoked Potentials", "Female", "Humans", "Male", "Middle Aged", "Orientation", "Spatial Navigation", "Young Adult" ] }
These results suggest that elderly individuals present with deficits when spatial orientation relies on allocentric representation, and are associated with age-related deficits in spatial attention.
yes
[ { "from": "human", "value": "Question: Is allocentric but not egocentric orientation impaired during normal aging : an ERP study?\nContext: {'contexts': ['Behavioral studies of spatial navigation in aging indicate that orientation using an allocentric reference frame (object-centered orientation) is impaired, whereas orientation using egocentric processes (self-centered orientation) is not. It has been proposed that navigational deficits may result from more general alterations of perception and attention or executive functions. The purpose of this study is to assess allocentric and egocentric representation in elderly individuals, and to determine if age-related deficits in spatial navigation are related to an attentional decline.', 'We assessed encoding of the position of geometrical shapes, depending specifically on an allocentric or egocentric reference frame, during ERP recording in young and old subjects.', 'Aging was associated with a performance decline in allocentric, but not egocentric, encoding. Both allocentric and egocentric conditions elicited parietal early components P1 and N1, reflecting top-down modulation, and components P2 and N2, reflecting selective attention and stimulus categorization. We observed age-associated effects on N1 and N2 amplitudes and on N2 latency in both spatial conditions. Moreover, impaired allocentric performance in older subjects was associated with a greater P2 amplitude and delayed P2 latency compared with younger subjects.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Aging', 'Attention', 'Brain', 'Electroencephalography', 'Evoked Potentials', 'Female', 'Humans', 'Male', 'Middle Aged', 'Orientation', 'Spatial Navigation', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,758,249
Does seasonal ambient air pollution correlate strongly with spontaneous abortion in Mongolia?
{ "contexts": [ "Air pollution is a major health challenge worldwide and has previously been strongly associated with adverse reproductive health. This study aimed to examine the association between spontaneous abortion and seasonal variation of air pollutants in Ulaanbaatar, Mongolia.", "Monthly average O3, SO2, NO2, CO, PM10 and PM2.5 levels were measured at Mongolian Government Air Quality Monitoring stations. The medical records of 1219 women admitted to the hospital due to spontaneous abortion between 2009-2011 were examined retrospectively. Fetal deaths per calendar month from January-December, 2011 were counted and correlated with mean monthly levels of various air pollutants by means of regression analysis.", "Regression of ambient pollutants against fetal death as a dose-response toxicity curve revealed very strong dose-response correlations for SO2 r > 0.9 (p < 0.001) while similarly strongly significant correlation coefficients were found for NO2 (r > 0.8), CO (r > 0.9), PM10 (r > 0.9) and PM2.5 (r > 0.8), (p < 0.001), indicating a strong correlation between air pollution and decreased fetal wellbeing." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Abortion, Spontaneous", "Adolescent", "Adult", "Air Pollutants", "Air Pollution", "Carbon Monoxide", "Female", "Fetal Death", "Humans", "Mongolia", "Nitrogen Dioxide", "Ozone", "Particulate Matter", "Pregnancy", "Retrospective Studies", "Seasons", "Sulfur Dioxide", "Young Adult" ] }
The present study identified alarmingly strong statistical correlations between ambient air pollutants and spontaneous abortion. Further studies need to be done to examine possible correlations between personal exposure to air pollutants and pregnancy loss.
yes
[ { "from": "human", "value": "Question: Does seasonal ambient air pollution correlate strongly with spontaneous abortion in Mongolia?\nContext: {'contexts': ['Air pollution is a major health challenge worldwide and has previously been strongly associated with adverse reproductive health. This study aimed to examine the association between spontaneous abortion and seasonal variation of air pollutants in Ulaanbaatar, Mongolia.', 'Monthly average O3, SO2, NO2, CO, PM10 and PM2.5 levels were measured at Mongolian Government Air Quality Monitoring stations. The medical records of 1219 women admitted to the hospital due to spontaneous abortion between 2009-2011 were examined retrospectively. Fetal deaths per calendar month from January-December, 2011 were counted and correlated with mean monthly levels of various air pollutants by means of regression analysis.', 'Regression of ambient pollutants against fetal death as a dose-response toxicity curve revealed very strong dose-response correlations for SO2 r\\u2009>\\u20090.9 (p\\u2009<\\u20090.001) while similarly strongly significant correlation coefficients were found for NO2 (r\\u2009>\\u20090.8), CO (r\\u2009>\\u20090.9), PM10 (r\\u2009>\\u20090.9) and PM2.5 (r\\u2009>\\u20090.8), (p\\u2009<\\u20090.001), indicating a strong correlation between air pollution and decreased fetal wellbeing.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Abortion, Spontaneous', 'Adolescent', 'Adult', 'Air Pollutants', 'Air Pollution', 'Carbon Monoxide', 'Female', 'Fetal Death', 'Humans', 'Mongolia', 'Nitrogen Dioxide', 'Ozone', 'Particulate Matter', 'Pregnancy', 'Retrospective Studies', 'Seasons', 'Sulfur Dioxide', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,759,667
Do wedge and needle liver biopsies show discordant histopathology in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery?
{ "contexts": [ "Controversy exists over whether or not single-needle liver biopsies are sufficient to compare histological parameters in patients with non-alcoholic fatty liver disease.", "To identify sampling variability, we biopsied four liver specimens per patient, based on biopsy size (needle vs wedge) and location (left vs right lobe), immediately prior to bariatric Roux-en-Y gastric bypass surgery.", "Ten prospectively enrolled, morbidly obese patients underwent 40 laparoscopy-guided biopsies; two needle and two wedge from each of 16 left and 16 right liver lobes. The Kappa coefficient for concordance compared histological parameters from left and right lobe needle- and wedge biopsies. Wedge biopsies were considered our 'Gold Standard'.", "Each patient had two wedge- and two needle liver biopsies. Kappa concordance between all needle and wedge biopsies from right and left lobes showed variability. Wedge- and needle liver biopsies from contralateral lobes had higher concordance with each other, compared to ipsilateral needle/wedge biopsy pairs. Contralateral wedge pairs had higher concordance than contralateral needle/needle pairs. There were no biopsy complications." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [] }
Wedge biopsy pairs had the best Kappa concordance but contralateral needle/needle biopsy pairs had good Kappa concordance. There were no complications from the 40 needle- and wedge liver biopsies, confirming the safety of laporoscopic multi-biopsy in both liver lobes.
yes
[ { "from": "human", "value": "Question: Do wedge and needle liver biopsies show discordant histopathology in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery?\nContext: {'contexts': ['Controversy exists over whether or not single-needle liver biopsies are sufficient to compare histological parameters in patients with non-alcoholic fatty liver disease.', 'To identify sampling variability, we biopsied four liver specimens per patient, based on biopsy size (needle vs wedge) and location (left vs right lobe), immediately prior to bariatric Roux-en-Y gastric bypass surgery.', \"Ten prospectively enrolled, morbidly obese patients underwent 40 laparoscopy-guided biopsies; two needle and two wedge from each of 16 left and 16 right liver lobes. The Kappa coefficient for concordance compared histological parameters from left and right lobe needle- and wedge biopsies. Wedge biopsies were considered our 'Gold Standard'.\", 'Each patient had two wedge- and two needle liver biopsies. Kappa concordance between all needle and wedge biopsies from right and left lobes showed variability. Wedge- and needle liver biopsies from contralateral lobes had higher concordance with each other, compared to ipsilateral needle/wedge biopsy pairs. Contralateral wedge pairs had higher concordance than contralateral needle/needle pairs. There were no biopsy complications.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,749,359
Do [ Negative symptoms predict the improvement of social functioning of patients with schizophrenia ]?
{ "contexts": [ "To identify predictive factors associated with the improvement of social functioning of schizophrenia patients in a community.", "101 schizophrenia patients undergoing community rehabilitation were assessed with the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale (PSP), Self-Esteem Scale (SES), Family Function Questionnaire (APGAR), and the World Health Organization Disability Assessment Scale II (WHODAS-II) twice 6 months apart. Pearson correlation and hierarchical multiple linear regression analyses were performed to identify the influencing and predictive factors associated with the improvement of social functioning.", "The increase of PSP score was correlated with age (r = 0.220), reduced PANSS negative score (r = 0.468), reduced PANSS general score (r = 0.392), reduced PANSS total score (r = 0.472), and reduced WHODAS-II Score (r = 0.247). The predictive factors of the change of PSP score followed the following order: change of PANSS negative score [the change of coefficient of determination (deltaR2 ) = 0.197], age of onset (deltaR2 = 0.048), change of WHODAS-II score and psychiatric rehabilitation (deltaR2 = 0.031)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Disability Evaluation", "Humans", "Psychiatric Status Rating Scales", "Schizophrenia", "Social Behavior", "Surveys and Questionnaires" ] }
Improvement of negative symptoms predicts the short-term improvement of social functioning of schizophrenia patients.
yes
[ { "from": "human", "value": "Question: Do [ Negative symptoms predict the improvement of social functioning of patients with schizophrenia ]?\nContext: {'contexts': ['To identify predictive factors associated with the improvement of social functioning of schizophrenia patients in a community.', '101 schizophrenia patients undergoing community rehabilitation were assessed with the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale (PSP), Self-Esteem Scale (SES), Family Function Questionnaire (APGAR), and the World Health Organization Disability Assessment Scale II (WHODAS-II) twice 6 months apart. Pearson correlation and hierarchical multiple linear regression analyses were performed to identify the influencing and predictive factors associated with the improvement of social functioning.', 'The increase of PSP score was correlated with age (r = 0.220), reduced PANSS negative score (r = 0.468), reduced PANSS general score (r = 0.392), reduced PANSS total score (r = 0.472), and reduced WHODAS-II Score (r = 0.247). The predictive factors of the change of PSP score followed the following order: change of PANSS negative score [the change of coefficient of determination (deltaR2 ) = 0.197], age of onset (deltaR2 = 0.048), change of WHODAS-II score and psychiatric rehabilitation (deltaR2 = 0.031).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Disability Evaluation', 'Humans', 'Psychiatric Status Rating Scales', 'Schizophrenia', 'Social Behavior', 'Surveys and Questionnaires']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,755,123
Is linagliptin fixed-dose combination with metformin bioequivalent to co-administration of linagliptin and metformin as individual tablets?
{ "contexts": [ "To demonstrate bioequivalence of linagliptin/metformin fixed-dose combination (FDC) tablets and the corresponding combination of individual tablets taken together, i.e., free-pill (FP) treatment.", "Three dosing combinations were evaluated in three separate randomized studies: linagliptin 2.5 mg with 500 mg, 850 mg, or 1,000 mg metformin. These studies used a prospective, open-label, randomized, two-way crossover design to evaluate bioequivalence in healthy volunteers (n = 287). After an overnight fast, participants received an FDC tablet once, and on a separate visit received the corresponding FP treatment. The two possible treatment sequences (FDC/FP and FP/FDC) were randomly allocated to the participants. A washout period of 35 days separated the two study treatments. The primary endpoints were maximum plasma concentration (Cmax) of linagliptin and metformin, area under the plasma concentration time curve from 0 to 72 hours (AUC0-72) for linagliptin, and from 0 to infinity (AUC0-inf) for metformin.", "The 90% confidence intervals of the adjusted geometric mean ratios of Cmax and AUC (calculated as FDC/ FP) were within the bioequivalence acceptance limits of 80 - 125%. The number of participants reporting at least one adverse event following FDC treatments was comparable to, or less than, that following FP treatments. Evaluation of vital signs and clinical laboratory tests revealed no safety issues." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Cross-Over Studies", "Drug Combinations", "Drug Therapy, Combination", "Female", "Humans", "Hypoglycemic Agents", "Linagliptin", "Male", "Metformin", "Middle Aged", "Prospective Studies", "Purines", "Quinazolines", "Tablets", "Therapeutic Equivalency" ] }
FDC tablets of linagliptin and metformin are bioequivalent to individual tablets of respective dose strengths taken together. Both treatments were well tolerated.
yes
[ { "from": "human", "value": "Question: Is linagliptin fixed-dose combination with metformin bioequivalent to co-administration of linagliptin and metformin as individual tablets?\nContext: {'contexts': ['To demonstrate bioequivalence of linagliptin/metformin fixed-dose combination (FDC) tablets and the corresponding combination of individual tablets taken together, i.e., free-pill (FP) treatment.', 'Three dosing combinations were evaluated in three separate randomized studies: linagliptin 2.5 mg with 500 mg, 850 mg, or 1,000 mg metformin. These studies used a prospective, open-label, randomized, two-way crossover design to evaluate bioequivalence in healthy volunteers (n = 287). After an overnight fast, participants received an FDC tablet once, and on a separate visit received the corresponding FP treatment. The two possible treatment sequences (FDC/FP and FP/FDC) were randomly allocated to the participants. A washout period of 35 days separated the two study treatments. The primary endpoints were maximum plasma concentration (Cmax) of linagliptin and metformin, area under the plasma concentration time curve from 0 to 72 hours (AUC0-72) for linagliptin, and from 0 to infinity (AUC0-inf) for metformin.', 'The 90% confidence intervals of the adjusted geometric mean ratios of Cmax and AUC (calculated as FDC/ FP) were within the bioequivalence acceptance limits of 80 - 125%. The number of participants reporting at least one adverse event following FDC treatments was comparable to, or less than, that following FP treatments. Evaluation of vital signs and clinical laboratory tests revealed no safety issues.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Cross-Over Studies', 'Drug Combinations', 'Drug Therapy, Combination', 'Female', 'Humans', 'Hypoglycemic Agents', 'Linagliptin', 'Male', 'Metformin', 'Middle Aged', 'Prospective Studies', 'Purines', 'Quinazolines', 'Tablets', 'Therapeutic Equivalency']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,755,128
Is c5 variant associated with decreased risk of coronary artery disease in outpatients with severe hypercholinesterasemia?
{ "contexts": [ "Although the C5 variant of cholinesterase is known to be a cause of hypercholinesterasemia, the pathophysiological significance of the C5 variant and the C5 variant-related hypercholinesterasemia in cardiovascular diseases remain unclear. The present study aimed to clarify the pathophysiological significance of the C5 variant as a risk or protective factor for coronary artery disease (CAD) in patients with severe hypercholinesterasemia.", "Severe hypercholinesterasemia was defined as serum cholinesterase (ChE) activity >= 450 IU/L (>= 2.0 SD). We screened 11,648 consecutive outpatients between 2005 and 2011 at Toho University, Sakura Medical Center. In patients with severe hypercholinesterasemia, phenotyping of the C5 variant was conducted using polyacrylamide gel electrophoresis and alpha-naphthyl butyrate staining.", "157 subjects (1.4% of 11,648 outpatients screened) were diagnosed with severe hypercholinesterasemia (mean serum ChE activity 574 ± 109 IU/L), and the frequency of the C5 variant was 45.2%. Subjects with the C5 variant had higher age, lower body mass index, milder dyslipidemia and liver dysfunction, and lower rates of hypertension and CAD compared with subjects without the C5 variant. Multivariate logistic regression model demonstrated that the presence of C5 variant independently lowered the risk of CAD, with odds ratio 0.071 (95% confidence interval (CI) 0.007 - 0.763, p = 0.029)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Biomarkers", "Cholinesterases", "Coronary Artery Disease", "Cross-Sectional Studies", "Female", "Humans", "Japan", "Logistic Models", "Male", "Middle Aged", "Multivariate Analysis", "Odds Ratio", "Outpatients", "Phenotype", "Retrospective Studies", "Risk Factors", "Up-Regulation" ] }
The prevalence of the C5 variant was relatively high, and the C5 variant is associated with decreased risk of CAD in outpatients with severe hypercholinesterasemia.
yes
[ { "from": "human", "value": "Question: Is c5 variant associated with decreased risk of coronary artery disease in outpatients with severe hypercholinesterasemia?\nContext: {'contexts': ['Although the C5 variant of cholinesterase is known to be a cause of hypercholinesterasemia, the pathophysiological significance of the C5 variant and the C5 variant-related hypercholinesterasemia in cardiovascular diseases remain unclear. The present study aimed to clarify the pathophysiological significance of the C5 variant as a risk or protective factor for coronary artery disease (CAD) in patients with severe hypercholinesterasemia.', 'Severe hypercholinesterasemia was defined as serum cholinesterase (ChE) activity >= 450 IU/L (>= 2.0 SD). We screened 11,648 consecutive outpatients between 2005 and 2011 at Toho University, Sakura Medical Center. In patients with severe hypercholinesterasemia, phenotyping of the C5 variant was conducted using polyacrylamide gel electrophoresis and alpha-naphthyl butyrate staining.', '157 subjects (1.4% of 11,648 outpatients screened) were diagnosed with severe hypercholinesterasemia (mean serum ChE activity 574 ± 109 IU/L), and the frequency of the C5 variant was 45.2%. Subjects with the C5 variant had higher age, lower body mass index, milder dyslipidemia and liver dysfunction, and lower rates of hypertension and CAD compared with subjects without the C5 variant. Multivariate logistic regression model demonstrated that the presence of C5 variant independently lowered the risk of CAD, with odds ratio 0.071 (95% confidence interval (CI) 0.007 - 0.763, p = 0.029).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Biomarkers', 'Cholinesterases', 'Coronary Artery Disease', 'Cross-Sectional Studies', 'Female', 'Humans', 'Japan', 'Logistic Models', 'Male', 'Middle Aged', 'Multivariate Analysis', 'Odds Ratio', 'Outpatients', 'Phenotype', 'Retrospective Studies', 'Risk Factors', 'Up-Regulation']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,775,383
Do younger women have a higher risk of in-hospital mortality due to acute myocardial infarction in Chile?
{ "contexts": [ "Coronary heart disease is the second cause of death in Chilean women, with higher mortality among women, especially at younger ages. The objective was to analyze in-hospital case-fatality by sex and age in patients with acute myocardial infarction in Chile and to evaluate associated factors.", "From the nationwide hospital admissions database and the GEMI registry (a multicenter registry), we selected all cases of acute myocardial infarction (code: I.21) that occurred between 2001 and 2007 in Chile. We estimated odds ratios for in-hospital case-fatality in women by age (crude and adjusted for clinical characteristics and treatment).", "In total, 49,287 cases of acute myocardial infarction were hospitalized, 31.3% of them women; 9278 patients were incorporated in the GEMI registry (27.1% women). In-hospital case-fatality was higher (P<.001) in women than men (national database, 20.4% vs 11.3%; GEMI, 14.2% vs 7.3%, irrespective of age. In-hospital case-fatality risk was higher in women aged<45 years: national odds ratio=2.3 (95% confidence interval, 1.5-3.3) and GEMI, odds ratio=2.7 (1.1-6.8). The estimated risk was lower in women aged 75 or more years in both databases, 1.3 (1.2-2.4) and 1.5 (1.2-1.9), respectively. Younger women less often received statins, odds ratio=0.7 (0.6-0.8); acetylsalicylic acid, odds ratio=0.4 (0.2-0.6); betablockers, odds ratio=0.8 (0.6-0.9), and thrombolytics, odds ratio=0.6 (0.5-0.8). An interaction was found between Killip class and sex. After adjusting for covariates, women aged<55 years with ST-segment elevation myocardial infarction and Killip class I-II, had the highest risk, odds ratio=4.3 (2.1-8.9)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Age Factors", "Aged", "Chile", "Female", "Hospital Mortality", "Humans", "Male", "Middle Aged", "Myocardial Infarction", "Prospective Studies", "Risk Assessment", "Sex Factors" ] }
In the context of a Latin American country, women aged<55 years with ST-segment elevation myocardial infarction and Killip class I-II had a higher risk of death. Known risk factors do not completely explain this excess of risk.
yes
[ { "from": "human", "value": "Question: Do younger women have a higher risk of in-hospital mortality due to acute myocardial infarction in Chile?\nContext: {'contexts': ['Coronary heart disease is the second cause of death in Chilean women, with higher mortality among women, especially at younger ages. The objective was to analyze in-hospital case-fatality by sex and age in patients with acute myocardial infarction in Chile and to evaluate associated factors.', 'From the nationwide hospital admissions database and the GEMI registry (a multicenter registry), we selected all cases of acute myocardial infarction (code: I.21) that occurred between 2001 and 2007 in Chile. We estimated odds ratios for in-hospital case-fatality in women by age (crude and adjusted for clinical characteristics and treatment).', 'In total, 49,287 cases of acute myocardial infarction were hospitalized, 31.3% of them women; 9278 patients were incorporated in the GEMI registry (27.1% women). In-hospital case-fatality was higher (P<.001) in women than men (national database, 20.4% vs 11.3%; GEMI, 14.2% vs 7.3%, irrespective of age. In-hospital case-fatality risk was higher in women aged<45 years: national odds ratio=2.3 (95% confidence interval, 1.5-3.3) and GEMI, odds ratio=2.7 (1.1-6.8). The estimated risk was lower in women aged 75 or more years in both databases, 1.3 (1.2-2.4) and 1.5 (1.2-1.9), respectively. Younger women less often received statins, odds ratio=0.7 (0.6-0.8); acetylsalicylic acid, odds ratio=0.4 (0.2-0.6); betablockers, odds ratio=0.8 (0.6-0.9), and thrombolytics, odds ratio=0.6 (0.5-0.8). An interaction was found between Killip class and sex. After adjusting for covariates, women aged<55 years with ST-segment elevation myocardial infarction and Killip class I-II, had the highest risk, odds ratio=4.3 (2.1-8.9).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Age Factors', 'Aged', 'Chile', 'Female', 'Hospital Mortality', 'Humans', 'Male', 'Middle Aged', 'Myocardial Infarction', 'Prospective Studies', 'Risk Assessment', 'Sex Factors']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,748,184
Does microRNA-194 inhibit the epithelial-mesenchymal transition in gastric cancer cells by targeting FoxM1?
{ "contexts": [ "We hypothesized that miR-194 may control Forkhead box protein M1 (FoxM1) expression in gastric cancer cells and therefore may have therapeutic potential in gastric cancer.", "The expression level of miR-194 was examined using real-time PCR in human gastric cancer and noncancerous gastric tissues, gastric cancer cell and normal gastric mucosal epithelial cell. We examined whether the miR-194 regulates cell migration and invasion, and the epithelial-mesenchymal transition Phenotype by inhibiting FoxM1 in gastric cancer cells.", "The expression of miR-194 was significantly lower in gastric cancer compared with non-cancerous gastric tissues and cells. Exogenous expression of miR-194 inhibited cell migration, invasion, and the epithelial-mesenchymal transition phenotype in gastric cancer cells. Moreover, we discovered a novel post-transcriptional regulatory mechanism of FoxM1 expression that is mediated by miR-194." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Cell Line, Tumor", "Cell Movement", "Epithelial Cells", "Epithelial-Mesenchymal Transition", "Forkhead Box Protein M1", "Forkhead Transcription Factors", "Gastric Mucosa", "Gene Expression Regulation, Neoplastic", "Humans", "MicroRNAs", "Phenotype", "RNA Interference", "Stomach Neoplasms", "Up-Regulation" ] }
Our study clearly demonstrates that miR-194 inhibits the acquisition of the EMT phenotype in gastric cancer cells by downregulating FoxM1, thereby inhibiting cell migration and invasion during cancer progression.
yes
[ { "from": "human", "value": "Question: Does microRNA-194 inhibit the epithelial-mesenchymal transition in gastric cancer cells by targeting FoxM1?\nContext: {'contexts': ['We hypothesized that miR-194 may control Forkhead box protein M1 (FoxM1) expression in gastric cancer cells and therefore may have therapeutic potential in gastric cancer.', 'The expression level of miR-194 was examined using real-time PCR in human gastric cancer and noncancerous gastric tissues, gastric cancer cell and normal gastric mucosal epithelial cell. We examined whether the miR-194 regulates cell migration and invasion, and the epithelial-mesenchymal transition Phenotype by inhibiting FoxM1 in gastric cancer cells.', 'The expression of miR-194 was significantly lower in gastric cancer compared with non-cancerous gastric tissues and cells. Exogenous expression of miR-194 inhibited cell migration, invasion, and the epithelial-mesenchymal transition phenotype in gastric cancer cells. Moreover, we discovered a novel post-transcriptional regulatory mechanism of FoxM1 expression that is mediated by miR-194.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Cell Line, Tumor', 'Cell Movement', 'Epithelial Cells', 'Epithelial-Mesenchymal Transition', 'Forkhead Box Protein M1', 'Forkhead Transcription Factors', 'Gastric Mucosa', 'Gene Expression Regulation, Neoplastic', 'Humans', 'MicroRNAs', 'Phenotype', 'RNA Interference', 'Stomach Neoplasms', 'Up-Regulation']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,748,185
Does [ Ac-hE-18A-NH2 inhibit the inflammatory response induced by ox-LDL via inhibiting NF-κB activation in RAW264.7 macrophages ]?
{ "contexts": [ "To evaluate the effect of Ac-hE-18A-NH2 on TNF-α secretion and mRNA expression in ox-LDL-stimulated RAW264.7 macrophages and to elucidate the possible mechanisms.", "Macrophages were incubated in the medium containing various concentrations of Ac-hE18A-NH2 (1-50 μg/mL) with ox-LDL (50 μg/mL) stimulated. The TNF-α level and intracellular cholesterol content were measured by commercially available quantitation kits following the manufacturer's instructions. TNF-α and ATP-binding cassette transporter A1 (ABCA1) mRNA expression were detected by real-time PCR. ABCA1 and IκB protein -expression in the macrophages were determined by Western blot. NF-κB activity was evaluated by electrophoretic mobility shift assay (EMSA).", "Ox-LDL stimulation induced a significant increase in TNF-α secretion, mRNA expression, cholesterol accumulation and nuclear factor-κB (NF-κB) activity in RAW264.7 macrophages. Ac-hE-18A-NH2 reduced TNF-α secretion and mRNA expression, up-regulated the ABCA1 mRNA and protein expression, reduced the intracellular cholesterol content, and inhibited NF- κB activation in a dose-dependent manner. Under the same condition and the same concentration, Ac-hE-18A-NH2 was more efficient than D-4F (apoA-I mimetic peptide) in inhibiting the inflammatory response induced by ox-LDL in the macrophages." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "ATP Binding Cassette Transporter 1", "Animals", "Cell Line", "Cholesterol", "Gene Expression Regulation", "I-kappa B Proteins", "Inflammation", "Lipoproteins", "Lipoproteins, LDL", "Macrophages", "Mice", "NF-kappa B", "Peptide Fragments", "Signal Transduction", "Tumor Necrosis Factor-alpha" ] }
Ac-hE-18A-NH2 may suppress TNF-α secretion and mRNA expression in ox-LDL stimulated RAW264.7 macrophages via IκB-NF-κB signaling pathway. The anti-inflammatory effect of Ac-hE-18A-NH2 is better than that of apoA-I mimic peptide D-4F.
yes
[ { "from": "human", "value": "Question: Does [ Ac-hE-18A-NH2 inhibit the inflammatory response induced by ox-LDL via inhibiting NF-κB activation in RAW264.7 macrophages ]?\nContext: {'contexts': ['To evaluate the effect of Ac-hE-18A-NH2 on TNF-α secretion and mRNA expression in ox-LDL-stimulated RAW264.7 macrophages and to elucidate the possible mechanisms.', \"Macrophages were incubated in the medium containing various concentrations of Ac-hE18A-NH2 (1-50 μg/mL) with ox-LDL (50 μg/mL) stimulated. The TNF-α level and intracellular cholesterol content were measured by commercially available quantitation kits following the manufacturer's instructions. TNF-α and ATP-binding cassette transporter A1 (ABCA1) mRNA expression were detected by real-time PCR. ABCA1 and IκB protein -expression in the macrophages were determined by Western blot. NF-κB activity was evaluated by electrophoretic mobility shift assay (EMSA).\", 'Ox-LDL stimulation induced a significant increase in TNF-α secretion, mRNA expression, cholesterol accumulation and nuclear factor-κB (NF-κB) activity in RAW264.7 macrophages. Ac-hE-18A-NH2 reduced TNF-α secretion and mRNA expression, up-regulated the ABCA1 mRNA and protein expression, reduced the intracellular cholesterol content, and inhibited NF- κB activation in a dose-dependent manner. Under the same condition and the same concentration, Ac-hE-18A-NH2 was more efficient than D-4F (apoA-I mimetic peptide) in inhibiting the inflammatory response induced by ox-LDL in the macrophages.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['ATP Binding Cassette Transporter 1', 'Animals', 'Cell Line', 'Cholesterol', 'Gene Expression Regulation', 'I-kappa B Proteins', 'Inflammation', 'Lipoproteins', 'Lipoproteins, LDL', 'Macrophages', 'Mice', 'NF-kappa B', 'Peptide Fragments', 'Signal Transduction', 'Tumor Necrosis Factor-alpha']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,764,533
Do presence of antigen-specific somatic allelic mutations and splice variants predict for immunological response to genetic vaccination?
{ "contexts": [ "Antigen-specific anti-tumor vaccines have demonstrated clinical efficacy, but immunological and clinical responses appear to be patient-dependent. We hypothesized that naturally-occurring differences in amino acid sequence of a host's target antigen might predict for immunological outcome from genetic vaccination by presentation of epitopes different from the vaccine.", "Using peripheral blood cells from 33 patients who had been treated with a DNA vaccine encoding prostatic acid phosphatase (PAP), we sequenced the exons encoding PAP and PSA genes from somatic DNA to identify single nucleotide polymorphisms. In addition, mRNA was collected to detect alternative splice variants of PAP.", "We detected four synonymous coding mutations of PAP among 33 patients; non-synonymous coding mutations were not identified. Alternative splice variants of PAP were detected in 22/27 patients tested. The presence of detectable splice variants was not predictive of immunological outcome from vaccination. Immune responses to peptides encoded by these splice variants were common (16/27) prior to immunization, but not associated with immune responses elicited with vaccination." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
These results suggest that antigen-specific immune responses detectable after treatment with this genetic vaccine are specific for the host-encoded antigen and not due to epitope differences between the vaccine and a particular individual's somatic coding sequence.
no
[ { "from": "human", "value": "Question: Do presence of antigen-specific somatic allelic mutations and splice variants predict for immunological response to genetic vaccination?\nContext: {'contexts': [\"Antigen-specific anti-tumor vaccines have demonstrated clinical efficacy, but immunological and clinical responses appear to be patient-dependent. We hypothesized that naturally-occurring differences in amino acid sequence of a host's target antigen might predict for immunological outcome from genetic vaccination by presentation of epitopes different from the vaccine.\", 'Using peripheral blood cells from 33 patients who had been treated with a DNA vaccine encoding prostatic acid phosphatase (PAP), we sequenced the exons encoding PAP and PSA genes from somatic DNA to identify single nucleotide polymorphisms. In addition, mRNA was collected to detect alternative splice variants of PAP.', 'We detected four synonymous coding mutations of PAP among 33 patients; non-synonymous coding mutations were not identified. Alternative splice variants of PAP were detected in 22/27 patients tested. The presence of detectable splice variants was not predictive of immunological outcome from vaccination. Immune responses to peptides encoded by these splice variants were common (16/27) prior to immunization, but not associated with immune responses elicited with vaccination.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: no" } ]
24,747,831
Does calreticulin contribute to C1q-dependent recruitment of microglia in the leech Hirudo medicinalis following a CNS injury?
{ "contexts": [ "The medicinal leech is considered as a complementary and appropriate model to study immune functions in the central nervous system (CNS). In a context in which an injured leech's CNS can naturally restore normal synaptic connections, the accumulation of microglia (immune cells of the CNS that are exclusively resident in leeches) has been shown to be essential at the lesion to engage the axonal sprouting. HmC1q (Hm for Hirudo medicinalis) possesses chemotactic properties that are important in the microglial cell recruitment by recognizing at least a C1q binding protein (HmC1qBP alias gC1qR).", "Recombinant forms of C1q were used in affinity purification and in vitro chemotaxis assays. Anti-calreticulin antibodies were used to neutralize C1q-mediated chemotaxis and locate the production of calreticulin in leech CNS.", "A newly characterized leech calreticulin (HmCalR) has been shown to interact with C1q and participate to the HmC1q-dependent microglia accumulation. HmCalR, which has been detected in only some microglial cells, is consequently a second binding protein for HmC1q, allowing the chemoattraction of resident microglia in the nerve repair process." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Amino Acid Sequence", "Animals", "Base Sequence", "Biotinylation", "Calreticulin", "Central Nervous System", "Chemotaxis", "Complement C1q", "Hirudo medicinalis", "Humans", "Microglia", "Molecular Sequence Data", "Phylogeny", "Protein Binding", "RNA, Messenger", "Solubility" ] }
These data give new insight into calreticulin/C1q interaction in an immune function of neuroprotection, suggesting another molecular target to use in investigation of microglia reactivity in a model of CNS injury.
yes
[ { "from": "human", "value": "Question: Does calreticulin contribute to C1q-dependent recruitment of microglia in the leech Hirudo medicinalis following a CNS injury?\nContext: {'contexts': [\"The medicinal leech is considered as a complementary and appropriate model to study immune functions in the central nervous system (CNS). In a context in which an injured leech's CNS can naturally restore normal synaptic connections, the accumulation of microglia (immune cells of the CNS that are exclusively resident in leeches) has been shown to be essential at the lesion to engage the axonal sprouting. HmC1q (Hm for Hirudo medicinalis) possesses chemotactic properties that are important in the microglial cell recruitment by recognizing at least a C1q binding protein (HmC1qBP alias gC1qR).\", 'Recombinant forms of C1q were used in affinity purification and in vitro chemotaxis assays. Anti-calreticulin antibodies were used to neutralize C1q-mediated chemotaxis and locate the production of calreticulin in leech CNS.', 'A newly characterized leech calreticulin (HmCalR) has been shown to interact with C1q and participate to the HmC1q-dependent microglia accumulation. HmCalR, which has been detected in only some microglial cells, is consequently a second binding protein for HmC1q, allowing the chemoattraction of resident microglia in the nerve repair process.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Amino Acid Sequence', 'Animals', 'Base Sequence', 'Biotinylation', 'Calreticulin', 'Central Nervous System', 'Chemotaxis', 'Complement C1q', 'Hirudo medicinalis', 'Humans', 'Microglia', 'Molecular Sequence Data', 'Phylogeny', 'Protein Binding', 'RNA, Messenger', 'Solubility']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,753,138
Does the Drosophila Chmp1 protein determine wing cell fate through regulation of epidermal growth factor receptor signaling?
{ "contexts": [ "Receptor down-regulation by the multivesicular body (MVB) pathway is critical for many cellular signaling events. MVB generation is mediated by the highly conserved ESCRT (0, I, II, and III) protein complexes. Chmp1 is an ESCRT-III component and a putative tumor suppressor in humans. However, published data on Chmp1 activity are conflicting and its role during tissue development is not well defined.", "We investigated the function of Drosophila Chmp1 and found that it is an essential gene. In the wing, loss of Chmp1 activity causes a cell fate change from intervein to vein, and interactions between Chmp1 and Drosophila Epidermal Growth Factor Receptor (DER) regulators suggest that Chmp1 negatively regulates DER signaling. Chmp1 knockdown also decreases Blistered expression, which is repressed by DER signaling. We find that Chmp1 protein localizes to the late endosome in Drosophila embryos, which is consistent with its effects on DER signaling resulting from its function in the ESCRT-III complex." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Animals", "Drosophila", "Drosophila Proteins", "ErbB Receptors", "Gene Expression Regulation, Developmental", "Signal Transduction", "Wings, Animal" ] }
Drosophila Chmp1 negatively regulates DER signaling, likely through its role in MVB formation. Loss of Chmp1 activity in the Drosophila wing induces a cell fate change from intervein to vein that should provide a useful tool for future studies of ESCRT protein activity.
yes
[ { "from": "human", "value": "Question: Does the Drosophila Chmp1 protein determine wing cell fate through regulation of epidermal growth factor receptor signaling?\nContext: {'contexts': ['Receptor down-regulation by the multivesicular body (MVB) pathway is critical for many cellular signaling events. MVB generation is mediated by the highly conserved ESCRT (0, I, II, and III) protein complexes. Chmp1 is an ESCRT-III component and a putative tumor suppressor in humans. However, published data on Chmp1 activity are conflicting and its role during tissue development is not well defined.', 'We investigated the function of Drosophila Chmp1 and found that it is an essential gene. In the wing, loss of Chmp1 activity causes a cell fate change from intervein to vein, and interactions between Chmp1 and Drosophila Epidermal Growth Factor Receptor (DER) regulators suggest that Chmp1 negatively regulates DER signaling. Chmp1 knockdown also decreases Blistered expression, which is repressed by DER signaling. We find that Chmp1 protein localizes to the late endosome in Drosophila embryos, which is consistent with its effects on DER signaling resulting from its function in the ESCRT-III complex.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Animals', 'Drosophila', 'Drosophila Proteins', 'ErbB Receptors', 'Gene Expression Regulation, Developmental', 'Signal Transduction', 'Wings, Animal']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,768,676
Do kinetic analyses reveal potent and early blockade of hepatitis C virus assembly by NS5A inhibitors?
{ "contexts": [ "All-oral regimens combining different classes of direct-acting antivirals (DAA) are highly effective for treatment of patients with chronic hepatitis C. NS5A inhibitors will likely form a component of future interferon-sparing treatment regimens. However, despite their potential, the detailed mechanism of action of NS5A inhibitors is unclear. To study their mechanisms, we compared their kinetics of antiviral suppression with those of other classes of DAA, using the hepatitis C virus genotype 1a cell culture-infectious virus H77S.3.", "We performed detailed kinetic analyses of specific steps in the hepatitis C virus life cycle using cell cultures incubated with protease inhibitors, polymerase inhibitors, or NS5A inhibitors. Assays were designed to measure active viral RNA synthesis and steady-state RNA abundance, polyprotein synthesis, virion assembly, and infectious virus production.", "Despite their high potency, NS5A inhibitors were slow to inhibit viral RNA synthesis compared with protease or polymerase inhibitors. By 24 hours after addition of an NS5A inhibitor, polyprotein synthesis was reduced <50%, even at micromolar concentrations. In contrast, inhibition of virus release by NS5A inhibitors was potent and rapid, with onset of inhibition as early as 2 hours. Cells incubated with NS5A inhibitors were rapidly depleted of intracellular infectious virus and RNA-containing hepatitis C virus particles, indicating a block in virus assembly." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Antiviral Agents", "Cell Line, Tumor", "Dose-Response Relationship, Drug", "Drug Resistance, Viral", "Enzyme Inhibitors", "Genotype", "Hepacivirus", "Humans", "Kinetics", "Mutation", "Protease Inhibitors", "RNA, Viral", "Viral Nonstructural Proteins", "Virus Assembly", "Virus Replication" ] }
DAAs that target NS5A rapidly inhibit intracellular assembly of genotype 1a virions. They also inhibit formation of functional replicase complexes, but have no activity against preformed replicase, thereby resulting in slow shut-off of viral RNA synthesis.
yes
[ { "from": "human", "value": "Question: Do kinetic analyses reveal potent and early blockade of hepatitis C virus assembly by NS5A inhibitors?\nContext: {'contexts': ['All-oral regimens combining different classes of direct-acting antivirals (DAA) are highly effective for treatment of patients with chronic hepatitis C. NS5A inhibitors will likely form a component of future interferon-sparing treatment regimens. However, despite their potential, the detailed mechanism of action of NS5A inhibitors is unclear. To study their mechanisms, we compared their kinetics of antiviral suppression with those of other classes of DAA, using the hepatitis C virus genotype 1a cell culture-infectious virus H77S.3.', 'We performed detailed kinetic analyses of specific steps in the hepatitis C virus life cycle using cell cultures incubated with protease inhibitors, polymerase inhibitors, or NS5A inhibitors. Assays were designed to measure active viral RNA synthesis and steady-state RNA abundance, polyprotein synthesis, virion assembly, and infectious virus production.', 'Despite their high potency, NS5A inhibitors were slow to inhibit viral RNA synthesis compared with protease or polymerase inhibitors. By 24 hours after addition of an NS5A inhibitor, polyprotein synthesis was reduced <50%, even at micromolar concentrations. In contrast, inhibition of virus release by NS5A inhibitors was potent and rapid, with onset of inhibition as early as 2 hours. Cells incubated with NS5A inhibitors were rapidly depleted of intracellular infectious virus and RNA-containing hepatitis C virus particles, indicating a block in virus assembly.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Antiviral Agents', 'Cell Line, Tumor', 'Dose-Response Relationship, Drug', 'Drug Resistance, Viral', 'Enzyme Inhibitors', 'Genotype', 'Hepacivirus', 'Humans', 'Kinetics', 'Mutation', 'Protease Inhibitors', 'RNA, Viral', 'Viral Nonstructural Proteins', 'Virus Assembly', 'Virus Replication']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,777,275
Are cerebrospinal fluid transferrin levels reduced in patients with early multiple sclerosis?
{ "contexts": [ "Previous magnetic resonance imaging (MRI) studies have demonstrated increased iron deposition in the basal ganglia of multiple sclerosis (MS) patients. However, it is not clear whether these alterations are associated with changes of iron metabolism in body fluids.", "The purpose of this study was to investigate if iron metabolism markers in cerebrospinal fluid (CSF) and serum of clinically isolated syndrome (CIS) and MS patients differ from controls and how they relate to clinical and imaging parameters.", "We analysed serum ferritin, transferrin and soluble transferrin-receptor and CSF ferritin and transferrin by nephelometry in non-anaemic CIS (n=60) or early MS (n=14) patients and 68 controls. In CIS/MS we additionally assessed the T2 lesion load.", "CSF transferrin was significantly decreased in CIS/MS compared to controls (p<0.001), while no significant differences were seen in serum. Higher CSF transferrin levels correlated with lower physical disability scores (r= -0.3, p<0.05). CSF transferrin levels did not correlate with other clinical data and the T2 lesion load." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Age of Onset", "Female", "Homeostasis", "Humans", "Iron", "Magnetic Resonance Imaging", "Male", "Middle Aged", "Multiple Sclerosis", "Transferrins" ] }
Our biochemical study provides evidence that altered iron homeostasis within the brain occurs in the very early phases of the disease, and suggests that the transporter protein transferrin may play a role in the increased iron deposition known to occur in the brain of MS patients.
yes
[ { "from": "human", "value": "Question: Are cerebrospinal fluid transferrin levels reduced in patients with early multiple sclerosis?\nContext: {'contexts': ['Previous magnetic resonance imaging (MRI) studies have demonstrated increased iron deposition in the basal ganglia of multiple sclerosis (MS) patients. However, it is not clear whether these alterations are associated with changes of iron metabolism in body fluids.', 'The purpose of this study was to investigate if iron metabolism markers in cerebrospinal fluid (CSF) and serum of clinically isolated syndrome (CIS) and MS patients differ from controls and how they relate to clinical and imaging parameters.', 'We analysed serum ferritin, transferrin and soluble transferrin-receptor and CSF ferritin and transferrin by nephelometry in non-anaemic CIS (n=60) or early MS (n=14) patients and 68 controls. In CIS/MS we additionally assessed the T2 lesion load.', 'CSF transferrin was significantly decreased in CIS/MS compared to controls (p<0.001), while no significant differences were seen in serum. Higher CSF transferrin levels correlated with lower physical disability scores (r= -0.3, p<0.05). CSF transferrin levels did not correlate with other clinical data and the T2 lesion load.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Age of Onset', 'Female', 'Homeostasis', 'Humans', 'Iron', 'Magnetic Resonance Imaging', 'Male', 'Middle Aged', 'Multiple Sclerosis', 'Transferrins']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,770,822
Is 131I therapy and Graves ' disease in a long term observation : euthyroidism a suitable goal . Our experience?
{ "contexts": [ "The aim of the study was to verify early and definitive outcome of radioiodine therapy in patients with Graves' disease, administering 131I calculated dose to pursue euthyroidism.", "We retrospectively analyzed 639 patients affected by Graves' disease and treated by one or more 131I calculated doses. Results dose by dose are reported. As to the first administration, outcome is related to parameters used to calculate dose and to patients' available features. Failures and hypothyroidism onset are evaluated.", "A mean dose of 10 mCi shows great effectiveness: 75% of patients were cured after one administration, 88% after two. Of the failures, 84.1% occurred in a mean time of 0.34±0.23 years and were more frequent for larger glands, accelerated intra-gland radioiodine turnover, ophtalmopathy, administration of antithyroid drugs until 131I therapy. Of hypothyroid patients, 39.8% were diagnosed within the first year. After a sharp initial rise, hypothyroidism occurred at a slower rate, with estimated yearly increases of 3.8% until 10 years and of 1.8% later. In still followed up patients, euthyroidism was observed in about half the population after 10 years and in a third after 25 years." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adult", "Aged", "Aged, 80 and over", "Female", "Graves Disease", "Humans", "Iodine Radioisotopes", "Male", "Middle Aged", "Retrospective Studies", "Time Factors", "Young Adult" ] }
131I can be the first line treatment for Graves' disease in small-medium thyroids. Calculated doses can achieve a high amount of long term euthyroid patients. Similar results could be expected by fixed doses of 10 mCi.
yes
[ { "from": "human", "value": "Question: Is 131I therapy and Graves ' disease in a long term observation : euthyroidism a suitable goal . Our experience?\nContext: {'contexts': [\"The aim of the study was to verify early and definitive outcome of radioiodine therapy in patients with Graves' disease, administering 131I calculated dose to pursue euthyroidism.\", \"We retrospectively analyzed 639 patients affected by Graves' disease and treated by one or more 131I calculated doses. Results dose by dose are reported. As to the first administration, outcome is related to parameters used to calculate dose and to patients' available features. Failures and hypothyroidism onset are evaluated.\", 'A mean dose of 10 mCi shows great effectiveness: 75% of patients were cured after one administration, 88% after two. Of the failures, 84.1% occurred in a mean time of 0.34±0.23 years and were more frequent for larger glands, accelerated intra-gland radioiodine turnover, ophtalmopathy, administration of antithyroid drugs until 131I therapy. Of hypothyroid patients, 39.8% were diagnosed within the first year. After a sharp initial rise, hypothyroidism occurred at a slower rate, with estimated yearly increases of 3.8% until 10 years and of 1.8% later. In still followed up patients, euthyroidism was observed in about half the population after 10 years and in a third after 25 years.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Aged', 'Aged, 80 and over', 'Female', 'Graves Disease', 'Humans', 'Iodine Radioisotopes', 'Male', 'Middle Aged', 'Retrospective Studies', 'Time Factors', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,764,173
Does effect of AST on age-associated changes of vocal fold in a rat model?
{ "contexts": [ "Reactive oxygen species (ROS) are associated with aging. Astaxanthin (AST) is a strong antioxidant and has been reported to prevent various ROS-induced diseases. In the current study, we investigated the effect of AST on age-associated histological and mRNA changes of vocal folds.", "Prospective animal experiment with control.", "Six-month-old Sprague-Dawley rats were fed on a normal powder diet with 0.01% (w/w) AST (aged AST-treated group) or without AST (aged sham-treated group). After 12 months of feeding, the larynges were harvested for histology, immunohistochemical detection of 4-hydroxy-2-nonenal (4-HNE), and quantitative real-time polymerase chain reaction for basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF). Thirteen-week-old rats were used as a young control group (young group).", "The expression of 4-HNE, an oxidative stress marker, significantly increased in the two aged groups compared with the young group. Histological examination showed that the deposition of hyaluronic acid in the lamina propria (LP) was significantly reduced in the aged sham-treated group compared with the young group, but no significant difference was observed between the aged AST-treated group and the young group. There were no significant differences in the mRNA expression of bFGF and HGF between the aged AST-treated group and the young group, although the expression of these genes was significantly reduced in the aged sham-treated group as compared with the young group." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Aging", "Aldehydes", "Animals", "Antioxidants", "Chromatography, High Pressure Liquid", "Disease Models, Animal", "Fibrinolytic Agents", "Fibroblast Growth Factor 2", "Follow-Up Studies", "Gene Expression Regulation", "Hepatocyte Growth Factor", "Immunohistochemistry", "Male", "Oxidative Stress", "Prospective Studies", "RNA, Messenger", "Rats", "Rats, Sprague-Dawley", "Reactive Oxygen Species", "Real-Time Polymerase Chain Reaction", "Vocal Cord Dysfunction", "Vocal Cords", "Xanthophylls" ] }
These results suggest that AST has the potential to attenuate age-associated changes of vocal folds.
yes
[ { "from": "human", "value": "Question: Does effect of AST on age-associated changes of vocal fold in a rat model?\nContext: {'contexts': ['Reactive oxygen species (ROS) are associated with aging. Astaxanthin (AST) is a strong antioxidant and has been reported to prevent various ROS-induced diseases. In the current study, we investigated the effect of AST on age-associated histological and mRNA changes of vocal folds.', 'Prospective animal experiment with control.', 'Six-month-old Sprague-Dawley rats were fed on a normal powder diet with 0.01% (w/w) AST (aged AST-treated group) or without AST (aged sham-treated group). After 12 months of feeding, the larynges were harvested for histology, immunohistochemical detection of 4-hydroxy-2-nonenal (4-HNE), and quantitative real-time polymerase chain reaction for basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF). Thirteen-week-old rats were used as a young control group (young group).', 'The expression of 4-HNE, an oxidative stress marker, significantly increased in the two aged groups compared with the young group. Histological examination showed that the deposition of hyaluronic acid in the lamina propria (LP) was significantly reduced in the aged sham-treated group compared with the young group, but no significant difference was observed between the aged AST-treated group and the young group. There were no significant differences in the mRNA expression of bFGF and HGF between the aged AST-treated group and the young group, although the expression of these genes was significantly reduced in the aged sham-treated group as compared with the young group.'], 'labels': ['OBJECTIVE', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Aging', 'Aldehydes', 'Animals', 'Antioxidants', 'Chromatography, High Pressure Liquid', 'Disease Models, Animal', 'Fibrinolytic Agents', 'Fibroblast Growth Factor 2', 'Follow-Up Studies', 'Gene Expression Regulation', 'Hepatocyte Growth Factor', 'Immunohistochemistry', 'Male', 'Oxidative Stress', 'Prospective Studies', 'RNA, Messenger', 'Rats', 'Rats, Sprague-Dawley', 'Reactive Oxygen Species', 'Real-Time Polymerase Chain Reaction', 'Vocal Cord Dysfunction', 'Vocal Cords', 'Xanthophylls']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,763,291
Is a germline missense mutation in COQ6 associated with susceptibility to familial schwannomatosis?
{ "contexts": [ "Schwannomatosis, a subtype of neurofibromatosis, is characterized by multiple benign, nonvestibular, nonintradermal schwannomas. Although the tumor suppressor SMARCB1 gene has been frequently identified as the underlying genetic cause of half of familial and ~10% of sporadic schwannomatosis, for most other cases, further causative genes remain to be discovered. Herein, we characterize the genome of a schwannomatosis family without constitutional inactivation of the SMARCB1 gene to explore novel genomic alterations predisposing individuals to the familial disease.", "We performed whole-genome/exome sequencing on genomic DNA of both schwannomatosis-affected and normal members of the family.", "We identified a novel missense mutation (p.Asp208His; c.622G>C) in the coenzyme Q10 (CoQ10) biosynthesis monooxygenase 6 gene (COQ6) in schwannomatosis-affected members. The deleterious effects of the COQ6 mutations were validated by their lack of complementation in a coq6-deficient yeast mutant. Our study further indicated that the resultant haploinsufficiency of COQ6 might lead to CoQ10 deficiency and chronic overproduction of reactive oxygen species in Schwann cells." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Amino Acid Sequence", "Animals", "Base Sequence", "Blotting, Western", "Cell Line", "Cells, Cultured", "Chromosomal Proteins, Non-Histone", "DNA Mutational Analysis", "DNA-Binding Proteins", "Family Health", "Gene Knockdown Techniques", "Genetic Complementation Test", "Genetic Predisposition to Disease", "Germ-Line Mutation", "Humans", "In Situ Hybridization, Fluorescence", "Molecular Sequence Data", "Mutation, Missense", "Neurilemmoma", "Neurofibromatoses", "Pedigree", "Rats", "Reactive Oxygen Species", "SMARCB1 Protein", "Saccharomyces cerevisiae", "Sequence Homology, Amino Acid", "Skin Neoplasms", "Transcription Factors", "Ubiquinone" ] }
Although the exact oncogenetic mechanisms in this schwannomatosis family remain to be elucidated, our data strongly indicate a probable role of COQ6 mutation and CoQ10 deficiency in the development of familial schwannomatosis.Genet Med 16 10, 787-792.
yes
[ { "from": "human", "value": "Question: Is a germline missense mutation in COQ6 associated with susceptibility to familial schwannomatosis?\nContext: {'contexts': ['Schwannomatosis, a subtype of neurofibromatosis, is characterized by multiple benign, nonvestibular, nonintradermal schwannomas. Although the tumor suppressor SMARCB1 gene has been frequently identified as the underlying genetic cause of half of familial and ~10% of sporadic schwannomatosis, for most other cases, further causative genes remain to be discovered. Herein, we characterize the genome of a schwannomatosis family without constitutional inactivation of the SMARCB1 gene to explore novel genomic alterations predisposing individuals to the familial disease.', 'We performed whole-genome/exome sequencing on genomic DNA of both schwannomatosis-affected and normal members of the family.', 'We identified a novel missense mutation (p.Asp208His; c.622G>C) in the coenzyme Q10 (CoQ10) biosynthesis monooxygenase 6 gene (COQ6) in schwannomatosis-affected members. The deleterious effects of the COQ6 mutations were validated by their lack of complementation in a coq6-deficient yeast mutant. Our study further indicated that the resultant haploinsufficiency of COQ6 might lead to CoQ10 deficiency and chronic overproduction of reactive oxygen species in Schwann cells.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Amino Acid Sequence', 'Animals', 'Base Sequence', 'Blotting, Western', 'Cell Line', 'Cells, Cultured', 'Chromosomal Proteins, Non-Histone', 'DNA Mutational Analysis', 'DNA-Binding Proteins', 'Family Health', 'Gene Knockdown Techniques', 'Genetic Complementation Test', 'Genetic Predisposition to Disease', 'Germ-Line Mutation', 'Humans', 'In Situ Hybridization, Fluorescence', 'Molecular Sequence Data', 'Mutation, Missense', 'Neurilemmoma', 'Neurofibromatoses', 'Pedigree', 'Rats', 'Reactive Oxygen Species', 'SMARCB1 Protein', 'Saccharomyces cerevisiae', 'Sequence Homology, Amino Acid', 'Skin Neoplasms', 'Transcription Factors', 'Ubiquinone']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,763,292
Do unaffected family members report improvements in daily routine sun protection 2 years following melanoma genetic testing?
{ "contexts": [ "Reducing ultraviolet radiation exposure may decrease melanoma risk in the hereditary melanoma setting. It is unknown whether genetic counseling and test reporting of CDKN2A/p16 mutation status promote long-term compliance with photoprotection recommendations, especially in unaffected mutation carriers.", "This study evaluated changes 2 years following melanoma genetic testing in self-reported practice of sun protection (sunscreen, photoprotective clothing, and ultraviolet radiation avoidance) among 37 members of two CDKN2A/p16 kindreds (10 unaffected carriers, 11 affected carriers, and 16 unaffected noncarriers; response rate = 64.9% of eligible participants).", "Multivariate profile analysis indicated that all three participant groups reported increased daily routine practice of sun protection 2 years following melanoma genetic testing (P < 0.02), with 96.9% reporting that at least one sun protection behavior was part of their daily routine, up from 78.1% at baseline (P < 0.015). Unaffected carriers (P < 0.024) and unaffected noncarriers (P < 0.027) reported significantly more frequent use of photoprotective clothing. Affected carriers maintained adherence to all sun protection behaviors. Reported sunburns in the past 6 months decreased significantly (P < 0.018)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Cyclin-Dependent Kinase Inhibitor p16", "Environmental Exposure", "Female", "Genetic Counseling", "Genetic Testing", "Humans", "Male", "Melanoma", "Middle Aged", "Patient Compliance", "Pedigree", "Skin Neoplasms", "Sunlight", "Sunscreening Agents" ] }
Members of high-risk families reported increased daily routine sun protection and decreased sunburns 2 years following melanoma genetic testing, with no net decline in sun protection following negative test results. Thus, genetic testing and counseling may motivate sustained improvements in prevention behaviors.
yes
[ { "from": "human", "value": "Question: Do unaffected family members report improvements in daily routine sun protection 2 years following melanoma genetic testing?\nContext: {'contexts': ['Reducing ultraviolet radiation exposure may decrease melanoma risk in the hereditary melanoma setting. It is unknown whether genetic counseling and test reporting of CDKN2A/p16 mutation status promote long-term compliance with photoprotection recommendations, especially in unaffected mutation carriers.', 'This study evaluated changes 2 years following melanoma genetic testing in self-reported practice of sun protection (sunscreen, photoprotective clothing, and ultraviolet radiation avoidance) among 37 members of two CDKN2A/p16 kindreds (10 unaffected carriers, 11 affected carriers, and 16 unaffected noncarriers; response rate = 64.9% of eligible participants).', 'Multivariate profile analysis indicated that all three participant groups reported increased daily routine practice of sun protection 2 years following melanoma genetic testing (P < 0.02), with 96.9% reporting that at least one sun protection behavior was part of their daily routine, up from 78.1% at baseline (P < 0.015). Unaffected carriers (P < 0.024) and unaffected noncarriers (P < 0.027) reported significantly more frequent use of photoprotective clothing. Affected carriers maintained adherence to all sun protection behaviors. Reported sunburns in the past 6 months decreased significantly (P < 0.018).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Cyclin-Dependent Kinase Inhibitor p16', 'Environmental Exposure', 'Female', 'Genetic Counseling', 'Genetic Testing', 'Humans', 'Male', 'Melanoma', 'Middle Aged', 'Patient Compliance', 'Pedigree', 'Skin Neoplasms', 'Sunlight', 'Sunscreening Agents']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,769,034
Does gALNT4 predict clinical outcome in patients with clear cell renal cell carcinoma?
{ "contexts": [ "We investigated the clinical significance of GALNT4 expression in patients with clear cell renal cell carcinoma.", "Enrolled in this study were 104 patients treated with curative nephrectomy at Zhongshan Hospital, Shanghai during 2004. Of the cohort 23 patients died of disease, 33 experienced recurrence and 3 died of another cause. GALNT4 density was assessed by immunohistochemistry in patient specimens. Univariate and multivariate Cox models, and ROC analysis were used to analyze the impact of prognostic factors on overall and relapse-free survival. Kaplan-Meier analysis with the log rank test was done to compare clinical outcomes between subgroups.", "Intratumor GALNT4 expression was significantly lower than peritumor expression. Low GALNT4 expression was associated with poor overall and relapse-free survival (p = 0.001 and 0.004, respectively). Intratumor GALNT4 expression, which negatively correlated with tumor size (p = 0.032), necrosis (p = 0.013) and TNM stage (p = 0.017), was an independent prognostic indicator for overall and relapse-free survival (HR 3.088, p = 0.020 and 2.173, p = 0.047, respectively). Extending the TNM staging system according to GALNT4 expression showed a better prognostic value for overall and relapse-free survival (AUC 0.786, p = 0.029 and 0.761, p = 0.040, respectively)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Antibodies, Neoplasm", "Biomarkers, Tumor", "Carcinoma, Renal Cell", "China", "Female", "Follow-Up Studies", "Humans", "Immunohistochemistry", "Incidence", "Kaplan-Meier Estimate", "Kidney Neoplasms", "Male", "Middle Aged", "N-Acetylgalactosaminyltransferases", "Neoplasm Recurrence, Local", "Neoplasm Staging", "Nephrectomy", "Prognosis", "Proportional Hazards Models", "Retrospective Studies", "Survival Rate" ] }
Intratumor GALNT4 expression is a potential independent prognostic factor for overall and relapse-free survival in patients with clear cell renal cell carcinoma. Further external validation and functional analysis should be performed to assess its potential prognostic and therapeutic value in patients with clear cell renal cell carcinoma.
yes
[ { "from": "human", "value": "Question: Does gALNT4 predict clinical outcome in patients with clear cell renal cell carcinoma?\nContext: {'contexts': ['We investigated the clinical significance of GALNT4 expression in patients with clear cell renal cell carcinoma.', 'Enrolled in this study were 104 patients treated with curative nephrectomy at Zhongshan Hospital, Shanghai during 2004. Of the cohort 23 patients died of disease, 33 experienced recurrence and 3 died of another cause. GALNT4 density was assessed by immunohistochemistry in patient specimens. Univariate and multivariate Cox models, and ROC analysis were used to analyze the impact of prognostic factors on overall and relapse-free survival. Kaplan-Meier analysis with the log rank test was done to compare clinical outcomes between subgroups.', 'Intratumor GALNT4 expression was significantly lower than peritumor expression. Low GALNT4 expression was associated with poor overall and relapse-free survival (p = 0.001 and 0.004, respectively). Intratumor GALNT4 expression, which negatively correlated with tumor size (p = 0.032), necrosis (p\\xa0=\\xa00.013) and TNM stage (p = 0.017), was an independent prognostic indicator for overall and relapse-free survival (HR 3.088, p = 0.020 and 2.173, p = 0.047, respectively). Extending the TNM staging system according to GALNT4 expression showed a better prognostic value for overall and relapse-free survival (AUC 0.786, p = 0.029 and 0.761, p = 0.040, respectively).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Antibodies, Neoplasm', 'Biomarkers, Tumor', 'Carcinoma, Renal Cell', 'China', 'Female', 'Follow-Up Studies', 'Humans', 'Immunohistochemistry', 'Incidence', 'Kaplan-Meier Estimate', 'Kidney Neoplasms', 'Male', 'Middle Aged', 'N-Acetylgalactosaminyltransferases', 'Neoplasm Recurrence, Local', 'Neoplasm Staging', 'Nephrectomy', 'Prognosis', 'Proportional Hazards Models', 'Retrospective Studies', 'Survival Rate']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,746,852
Does human cytomegalovirus infection induce leukotriene B4 and 5-lipoxygenase expression in human placentae and umbilical vein endothelial cells?
{ "contexts": [ "Human cytomegalovirus (HCMV) can cause congenital infection with risk of neurological disability. Maternal-fetal transmission is associated with placental inflammation. 5-lipoxygenase (5-LO) is the key enzyme in the biosynthesis of Leukotrienes (LTs), which are proinflammatory mediators. This study investigated the effect of HCMV infection on 5-LO expression and Leukotriene-B4 (LTB4) induction in human placentae and umbilical vein endothelial cells (HUVEC).", "Seven placentae from fetuses with congenital HCMV infection and brain damage and six controls were stained with HCMV-immediate-early-antigen (HCMV-IEA) and 5-LO by immunohistochemistry. 5-hydroxyeicosatetraenoic acid (5-HETE) and LTB4 were measured in culture supernatant from ex vivo HCMV-infected placental histocultures by liquid chromatography. In vitro, HCMV infected HUVEC cells were analyzed for 5-LO mRNA and protein expression by real time PCR and immunofluorescence staining.", "HCMV-IEA was abundant in all HCMV infected placentae but absent in control placentae. 5-LO expression was higher in endothelial and smooth muscle cells of HCMV-infected placentae, compared to control placentae. HCMV infection induced an up-regulation of LTB4 in ex vivo placental explants with higher levels of LTB4 at 72 h compared to controls (p = 0.002). In vitro, 5-LO transcript and protein expression were significantly induced in HCMV-infected HUVEC, compared to the control cultures (p = 0.036)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Arachidonate 5-Lipoxygenase", "Cytomegalovirus Infections", "Endothelial Cells", "Female", "Human Umbilical Vein Endothelial Cells", "Humans", "Hydroxyeicosatetraenoic Acids", "Immunohistochemistry", "Leukotriene B4", "Placenta", "Pregnancy", "RNA, Messenger", "Umbilical Veins", "Up-Regulation" ] }
The presence of HCMV coincided with high 5-LO expression in cells of in vivo HCMV infected placentae. HCMV induced up-regulation of 5-LO in both ex vivo HCMV-infected placental explants and HUVEC. HCMV induced LT-biosynthesis in congenitally infected placentae may have a role in pathogenesis of congenital HCMV disease.
yes
[ { "from": "human", "value": "Question: Does human cytomegalovirus infection induce leukotriene B4 and 5-lipoxygenase expression in human placentae and umbilical vein endothelial cells?\nContext: {'contexts': ['Human cytomegalovirus (HCMV) can cause congenital infection with risk of neurological disability. Maternal-fetal transmission is associated with placental inflammation. 5-lipoxygenase (5-LO) is the key enzyme in the biosynthesis of Leukotrienes (LTs), which are proinflammatory mediators. This study investigated the effect of HCMV infection on 5-LO expression and Leukotriene-B4 (LTB4) induction in human placentae and umbilical vein endothelial cells (HUVEC).', 'Seven placentae from fetuses with congenital HCMV infection and brain damage and six controls were stained with HCMV-immediate-early-antigen (HCMV-IEA) and 5-LO by immunohistochemistry. 5-hydroxyeicosatetraenoic acid (5-HETE) and LTB4 were measured in culture supernatant from ex vivo HCMV-infected placental histocultures by liquid chromatography. In vitro, HCMV infected HUVEC cells were analyzed for 5-LO mRNA and protein expression by real time PCR and immunofluorescence staining.', 'HCMV-IEA was abundant in all HCMV infected placentae but absent in control placentae. 5-LO expression was higher in endothelial and smooth muscle cells of HCMV-infected placentae, compared to control placentae. HCMV infection induced an up-regulation of LTB4 in ex vivo placental explants with higher levels of LTB4 at 72 h compared to controls (p = 0.002). In vitro, 5-LO transcript and protein expression were significantly induced in HCMV-infected HUVEC, compared to the control cultures (p = 0.036).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Arachidonate 5-Lipoxygenase', 'Cytomegalovirus Infections', 'Endothelial Cells', 'Female', 'Human Umbilical Vein Endothelial Cells', 'Humans', 'Hydroxyeicosatetraenoic Acids', 'Immunohistochemistry', 'Leukotriene B4', 'Placenta', 'Pregnancy', 'RNA, Messenger', 'Umbilical Veins', 'Up-Regulation']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,766,848
Is thoracoscopic lobectomy associated with acceptable morbidity and mortality in patients with predicted postoperative forced expiratory volume in 1 second or diffusing capacity for carbon monoxide less than 40 % of normal?
{ "contexts": [ "A predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1%) or diffusing capacity of the lung for carbon monoxide (DLCO%) of <40% has traditionally been considered to convey a high risk of lobectomy owing to elevated postoperative morbidity and mortality. These recommendations, however, were largely derived from the pre-video-assisted thoracoscopic surgical (VATS) era. We hypothesized that VATS lobectomy would be associated with acceptable morbidity and mortality at ppoFEV1% and ppoDLCO% values < 40%.", "PpoFEV1% and ppoDLCO% were calculated for patients undergoing open or VATS lobectomy for lung cancer in the Society of Thoracic Surgeons General Thoracic database from 2009 to 2011. Univariate comparisons, multivariate analyses, and 1:1 propensity matching were performed.", "A total of 13,376 patients underwent lobectomy (50.9% open, 49.1% VATS). A decreased ppoFEV1% and ppoDLCO% were each independent predictors for both cardiopulmonary complications and mortality in the open group (all P ≤ .008). In the VATS group, ppoFEV1% was an independent predictor of complications (P = .001) but not mortality (P = .77), and ppoDLCO% was an independent predictor of complications (P = .046) and mortality (P = .008). With decreasing ppoFEV1% or ppoDLCO%, complications and mortality increased at a greater rate in the open lobectomy than in a propensity-matched VATS group (n = 4215 each). For patients with ppoFEV1% < 40%, mortality was greater in the open (4.8%) than in the matched VATS group (0.7%, P = .003). Similar results were seen for ppoDLCO% < 40% (5.2% open, 2.0% VATS, P = .003). The rate of complications was significantly greater at ppoFEV1% < 40% in the open (21.9%) than in the matched VATS (12.8%, P = .005) group and similar results were seen with ppoDLCO% < 40% (14.9% open, 10.4% VATS, P = .016)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Female", "Forced Expiratory Volume", "Humans", "Lung", "Lung Neoplasms", "Male", "Middle Aged", "Multivariate Analysis", "Odds Ratio", "Pneumonectomy", "Propensity Score", "Pulmonary Diffusing Capacity", "Retrospective Studies", "Risk Factors", "Thoracic Surgery, Video-Assisted", "Time Factors", "Treatment Outcome" ] }
VATS lobectomy can be performed with acceptable rates of morbidity and mortality in patients with reduced ppoFEV1% or ppoDLCO%.
yes
[ { "from": "human", "value": "Question: Is thoracoscopic lobectomy associated with acceptable morbidity and mortality in patients with predicted postoperative forced expiratory volume in 1 second or diffusing capacity for carbon monoxide less than 40 % of normal?\nContext: {'contexts': ['A predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1%) or diffusing capacity of the lung for carbon monoxide (DLCO%) of <40% has traditionally been considered to convey a high risk of lobectomy owing to elevated postoperative morbidity and mortality. These recommendations, however, were largely derived from the pre-video-assisted thoracoscopic surgical (VATS) era. We hypothesized that VATS lobectomy would be associated with acceptable morbidity and mortality at ppoFEV1% and ppoDLCO% values\\xa0<\\xa040%.', 'PpoFEV1% and ppoDLCO% were calculated for patients undergoing open or VATS lobectomy for lung cancer in the Society of Thoracic Surgeons General Thoracic database from 2009 to 2011. Univariate comparisons, multivariate analyses, and 1:1 propensity matching were performed.', 'A total of 13,376 patients underwent lobectomy (50.9% open, 49.1% VATS). A decreased ppoFEV1% and ppoDLCO% were each independent predictors for both cardiopulmonary complications and mortality in the open group (all P ≤ .008). In the VATS group, ppoFEV1% was an independent predictor of complications (P\\xa0=\\xa0.001) but not mortality (P\\xa0=\\xa0.77), and ppoDLCO% was an independent predictor of complications (P\\xa0=\\xa0.046) and mortality (P\\xa0=\\xa0.008). With decreasing ppoFEV1% or ppoDLCO%, complications and mortality increased at a greater rate in the open lobectomy than in a propensity-matched VATS group (n\\xa0=\\xa04215 each). For patients with ppoFEV1%\\xa0<\\xa040%, mortality was greater in the open (4.8%) than in the matched VATS group (0.7%, P\\xa0=\\xa0.003). Similar results were seen for ppoDLCO%\\xa0<\\xa040% (5.2% open, 2.0% VATS, P\\xa0=\\xa0.003). The rate of complications was significantly greater at ppoFEV1%\\xa0<\\xa040% in the open (21.9%) than in the matched VATS (12.8%, P\\xa0=\\xa0.005) group and similar results were seen with ppoDLCO%\\xa0<\\xa040% (14.9% open, 10.4% VATS, P\\xa0=\\xa0.016).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Female', 'Forced Expiratory Volume', 'Humans', 'Lung', 'Lung Neoplasms', 'Male', 'Middle Aged', 'Multivariate Analysis', 'Odds Ratio', 'Pneumonectomy', 'Propensity Score', 'Pulmonary Diffusing Capacity', 'Retrospective Studies', 'Risk Factors', 'Thoracic Surgery, Video-Assisted', 'Time Factors', 'Treatment Outcome']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,766,841
Is hyphema a risk factor for failure of trabeculectomy in neovascular glaucoma : a retrospective analysis?
{ "contexts": [ "Several retinal ischemic diseases can cause neovascular glaucoma (NVG). Trabeculectomy with mitomycin C (MMC) is a relatively better treatment modality in the management of eyes with NVG than other glaucoma surgeries. The aim of this study was to investigate the factors that may influence the outcome of trabeculectomy with MMC for NVG.", "Forty-nine NVG eyes from 43 patients (26 males and 17 females) underwent primary trabeculectomy with MMC. The mean follow-up period was 16.8 ± 8.1 months (range, 6 to 34 months). Twenty-one eyes of 21 patients received intravitreal bevacizumab (IVB) 3.6 ± 1.8 days before trabeculectomy with MMC. A Kaplan-Meier survival-curve analysis was used to summarize the cumulative probability of success. We examined the relationship between the surgical outcome and the following surgical factors: gender, age, history of panretinal photocoagulation, history of cataract surgery, history of vitrectomy, preoperative IVB, NVG in the fellow eye, and postoperative complications (hyphema, choroidal detachment, and formation of fibrin) by multivariate analysis.", "The survival rate was 83.7% after 6 months, 70.9% after 12 months, and 60.8% after 24 months. The Kaplan-Meier survival curves showed no significant difference in the survival rate between the eyes with preoperative IVB (n = 21) and the eyes without preoperative IVB (n = 28) (p = 0.14). The multiple logistic regression analysis showed that postoperative hyphema (odds ratio, 6.54; 95% confidence interval, 1.41 to 35.97) was significantly associated with the surgical outcome (p = 0.02)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Angiogenesis Inhibitors", "Antibodies, Monoclonal, Humanized", "Bevacizumab", "Female", "Follow-Up Studies", "Glaucoma, Neovascular", "Humans", "Hyphema", "Incidence", "Intraocular Pressure", "Intravitreal Injections", "Japan", "Male", "Middle Aged", "Postoperative Hemorrhage", "Retrospective Studies", "Risk Factors", "Survival Rate", "Time Factors", "Trabeculectomy", "Treatment Outcome", "Vascular Endothelial Growth Factor A", "Visual Acuity" ] }
Postoperative hyphema was significantly correlated with the outcome of trabeculectomy for NVG. There was no significant association between preoperative IVB and postoperative hyphema or the results of trabeculectomy.
yes
[ { "from": "human", "value": "Question: Is hyphema a risk factor for failure of trabeculectomy in neovascular glaucoma : a retrospective analysis?\nContext: {'contexts': ['Several retinal ischemic diseases can cause neovascular glaucoma (NVG). Trabeculectomy with mitomycin C (MMC) is a relatively better treatment modality in the management of eyes with NVG than other glaucoma surgeries. The aim of this study was to investigate the factors that may influence the outcome of trabeculectomy with MMC for NVG.', 'Forty-nine NVG eyes from 43 patients (26 males and 17 females) underwent primary trabeculectomy with MMC. The mean follow-up period was 16.8 ± 8.1 months (range, 6 to 34 months). Twenty-one eyes of 21 patients received intravitreal bevacizumab (IVB) 3.6 ± 1.8 days before trabeculectomy with MMC. A Kaplan-Meier survival-curve analysis was used to summarize the cumulative probability of success. We examined the relationship between the surgical outcome and the following surgical factors: gender, age, history of panretinal photocoagulation, history of cataract surgery, history of vitrectomy, preoperative IVB, NVG in the fellow eye, and postoperative complications (hyphema, choroidal detachment, and formation of fibrin) by multivariate analysis.', 'The survival rate was 83.7% after 6 months, 70.9% after 12 months, and 60.8% after 24 months. The Kaplan-Meier survival curves showed no significant difference in the survival rate between the eyes with preoperative IVB (n = 21) and the eyes without preoperative IVB (n = 28) (p = 0.14). The multiple logistic regression analysis showed that postoperative hyphema (odds ratio, 6.54; 95% confidence interval, 1.41 to 35.97) was significantly associated with the surgical outcome (p = 0.02).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Angiogenesis Inhibitors', 'Antibodies, Monoclonal, Humanized', 'Bevacizumab', 'Female', 'Follow-Up Studies', 'Glaucoma, Neovascular', 'Humans', 'Hyphema', 'Incidence', 'Intraocular Pressure', 'Intravitreal Injections', 'Japan', 'Male', 'Middle Aged', 'Postoperative Hemorrhage', 'Retrospective Studies', 'Risk Factors', 'Survival Rate', 'Time Factors', 'Trabeculectomy', 'Treatment Outcome', 'Vascular Endothelial Growth Factor A', 'Visual Acuity']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,760,110
Is early systemic sclerosis : serum profiling of factors involved in endothelial , T-cell , and fibroblast interplay marked by elevated interleukin-33 levels?
{ "contexts": [ "To assess the serum profile of factors involved in endothelial, T-cell, and fibroblast interplay in patients with Raynaud's phenomenon (RP) associated with nailfold vodeocapillaroscopy (NVC) scleroderma findings and/or systemic sclerosis (SSc) marker autoantibodies, recently labeled as early SSc patients.", "Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), CCL2, CXCL8, IL-13, IL-33, and transforming growth factor-β (TGF-β) were measured in 24 early SSc patients, 48 definite SSc patients, and 24 osteoarthritis/fibromyalgia controls by multiplex suspension immunoassay. All SSc patients were investigated for the presence/absence of preclinical and clinical organ involvement, SSc marker autoantibodies, and NVC abnormalities.", "Serum sICAM-1, CCL2, CXCL8, and IL-13 were increased in all SSc patients as compared to controls, and paralleled the severity of the disease subset (early SSc < limited cutaneous SSc < diffuse cutaneous SSc; p < 0.0001). Surprisingly, IL-33 was significantly higher in early SSc patients as compared to both controls (p < 0.01) and definite SSc patients (p < 0.05). In early SSc there were no differences in the investigated markers according to the functional and serological features assessed." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Animals", "Antibodies, Antinuclear", "Biomarkers", "Capillaries", "Cell Communication", "Cells, Cultured", "Chemokine CCL2", "Disease Progression", "Endothelial Cells", "Female", "Fibroblasts", "Humans", "Intercellular Adhesion Molecule-1", "Interleukin-13", "Interleukin-33", "Interleukin-8", "Interleukins", "Male", "Mice", "Microscopic Angioscopy", "Middle Aged", "Raynaud Disease", "Scleroderma, Systemic", "T-Lymphocytes" ] }
Our study suggests that an endothelial, T-cell and fibroblast activation can be present in patients with early SSc and it is associated with a distinct profile of circulating factors involved in the cross-talk of these cells. The marked increase of IL-33 in early SSc patients suggests new routes of investigation of cell-cell dynamics in target tissues predating overt disease manifestations, thus opening to new therapeutic approaches.
yes
[ { "from": "human", "value": "Question: Is early systemic sclerosis : serum profiling of factors involved in endothelial , T-cell , and fibroblast interplay marked by elevated interleukin-33 levels?\nContext: {'contexts': [\"To assess the serum profile of factors involved in endothelial, T-cell, and fibroblast interplay in patients with Raynaud's phenomenon (RP) associated with nailfold vodeocapillaroscopy (NVC) scleroderma findings and/or systemic sclerosis (SSc) marker autoantibodies, recently labeled as early SSc patients.\", 'Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), CCL2, CXCL8, IL-13, IL-33, and transforming growth factor-β (TGF-β) were measured in 24 early SSc patients, 48 definite SSc patients, and 24 osteoarthritis/fibromyalgia controls by multiplex suspension immunoassay. All SSc patients were investigated for the presence/absence of preclinical and clinical organ involvement, SSc marker autoantibodies, and NVC abnormalities.', 'Serum sICAM-1, CCL2, CXCL8, and IL-13 were increased in all SSc patients as compared to controls, and paralleled the severity of the disease subset (early SSc < limited cutaneous SSc < diffuse cutaneous SSc; p\\u2009<\\u20090.0001). Surprisingly, IL-33 was significantly higher in early SSc patients as compared to both controls (p\\u2009<\\u20090.01) and definite SSc patients (p\\u2009<\\u20090.05). In early SSc there were no differences in the investigated markers according to the functional and serological features assessed.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Animals', 'Antibodies, Antinuclear', 'Biomarkers', 'Capillaries', 'Cell Communication', 'Cells, Cultured', 'Chemokine CCL2', 'Disease Progression', 'Endothelial Cells', 'Female', 'Fibroblasts', 'Humans', 'Intercellular Adhesion Molecule-1', 'Interleukin-13', 'Interleukin-33', 'Interleukin-8', 'Interleukins', 'Male', 'Mice', 'Microscopic Angioscopy', 'Middle Aged', 'Raynaud Disease', 'Scleroderma, Systemic', 'T-Lymphocytes']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,747,991
Do reactive oxygen species regulate the quiescence of CD34-positive cells derived from human embryonic stem cells?
{ "contexts": [ "Reactive oxygen species (ROS) are involved in a wide range of cellular processes. However, few studies have examined the generation and function of ROS in human embryonic vascular development. In this study, the sources of ROS and their roles in the vascular differentiation of human embryonic stem cells (hESCs) were investigated.", "During vascular differentiation of hESCs, CD34(+) cells had quiescence-related gene expression profiles and a large fraction of these cells were in G0 phase. In addition, levels of ROS, which were primarily generated through NOX4, were substantially higher in hESC-derived CD34(+) cells than in hESC-derived CD34(-) cells. To determine whether excess levels of ROS induce quiescence of hESC-derived CD34(+) cells, ROS levels were moderately reduced using selenium to enhance antioxidant activities of thioredoxin reductase and glutathione peroxidase. In comparison to untreated CD34(+) cells, selenium-treated CD34(+) cells exhibited changes in gene expression that favoured cell cycle progression, and had a greater proliferation and a smaller fraction of cells in G0 phase. Thus, selenium treatment increased the number of hESC-derived CD34(+) cells, thereby enhancing the efficiency with which hESCs differentiated into vascular endothelial and smooth muscle cells." ], "labels": [ "OBJECTIVE", "RESULTS" ], "meshes": [ "Antigens, CD34", "Cell Differentiation", "Cell Proliferation", "Cells, Cultured", "Embryonic Stem Cells", "Endothelial Cells", "Glutathione Peroxidase", "Humans", "Myocytes, Smooth Muscle", "NADPH Oxidase 4", "NADPH Oxidases", "Reactive Oxygen Species", "Resting Phase, Cell Cycle", "Selenium", "Thioredoxin-Disulfide Reductase" ] }
This study reveals that NOX4 produces ROS in CD34(+) cells during vascular differentiation of hESCs, and shows that modulation of ROS levels using antioxidants such as selenium may be a novel approach to increase the vascular differentiation efficiency of hESCs.
yes
[ { "from": "human", "value": "Question: Do reactive oxygen species regulate the quiescence of CD34-positive cells derived from human embryonic stem cells?\nContext: {'contexts': ['Reactive oxygen species (ROS) are involved in a wide range of cellular processes. However, few studies have examined the generation and function of ROS in human embryonic vascular development. In this study, the sources of ROS and their roles in the vascular differentiation of human embryonic stem cells (hESCs) were investigated.', 'During vascular differentiation of hESCs, CD34(+) cells had quiescence-related gene expression profiles and a large fraction of these cells were in G0 phase. In addition, levels of ROS, which were primarily generated through NOX4, were substantially higher in hESC-derived CD34(+) cells than in hESC-derived CD34(-) cells. To determine whether excess levels of ROS induce quiescence of hESC-derived CD34(+) cells, ROS levels were moderately reduced using selenium to enhance antioxidant activities of thioredoxin reductase and glutathione peroxidase. In comparison to untreated CD34(+) cells, selenium-treated CD34(+) cells exhibited changes in gene expression that favoured cell cycle progression, and had a greater proliferation and a smaller fraction of cells in G0 phase. Thus, selenium treatment increased the number of hESC-derived CD34(+) cells, thereby enhancing the efficiency with which hESCs differentiated into vascular endothelial and smooth muscle cells.'], 'labels': ['OBJECTIVE', 'RESULTS'], 'meshes': ['Antigens, CD34', 'Cell Differentiation', 'Cell Proliferation', 'Cells, Cultured', 'Embryonic Stem Cells', 'Endothelial Cells', 'Glutathione Peroxidase', 'Humans', 'Myocytes, Smooth Muscle', 'NADPH Oxidase 4', 'NADPH Oxidases', 'Reactive Oxygen Species', 'Resting Phase, Cell Cycle', 'Selenium', 'Thioredoxin-Disulfide Reductase']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,768,677
Does genome-wide association study identify variants associated with autoimmune hepatitis type 1?
{ "contexts": [ "Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH.", "We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region.", "We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 × 10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 × 10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 × 10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 × 10(-6)). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Autoimmunity", "CARD Signaling Adaptor Proteins", "Case-Control Studies", "Female", "Gene Frequency", "Genetic Predisposition to Disease", "Genome-Wide Association Study", "Germany", "HLA-DRB1 Chains", "Hepatitis, Autoimmune", "Humans", "Major Histocompatibility Complex", "Male", "Middle Aged", "Netherlands", "Phenotype", "Polymorphism, Single Nucleotide", "Proteins", "Risk Factors" ] }
In a genome-wide association study, we associated AIH type 1 with variants in the major histocompatibility complex region, and identified variants of SH2B3and CARD10 as likely risk factors. These findings support a complex genetic basis for AIH pathogenesis and indicate that part of the genetic susceptibility overlaps with that for other immune-mediated liver diseases.
yes
[ { "from": "human", "value": "Question: Does genome-wide association study identify variants associated with autoimmune hepatitis type 1?\nContext: {'contexts': ['Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH.', 'We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region.', 'We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 × 10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 × 10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 × 10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 × 10(-6)). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Autoimmunity', 'CARD Signaling Adaptor Proteins', 'Case-Control Studies', 'Female', 'Gene Frequency', 'Genetic Predisposition to Disease', 'Genome-Wide Association Study', 'Germany', 'HLA-DRB1 Chains', 'Hepatitis, Autoimmune', 'Humans', 'Major Histocompatibility Complex', 'Male', 'Middle Aged', 'Netherlands', 'Phenotype', 'Polymorphism, Single Nucleotide', 'Proteins', 'Risk Factors']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,766,572
Is motor development in 3-month-old healthy term-born infants associated with cognitive and behavioural outcomes at early school age?
{ "contexts": [ "To determine whether motor development at 3 months of age is associated with cognitive, motor, and behavioural outcomes in healthy children at early school age.", "In this cohort study, we included 74 term-born, healthy children (44 males, 30 females; median gestational age 40.1 wks, range 38.0-42.6 wks). From video recordings (median 12.9 wks, range 9.3-18.6 wks), we assessed the quality of fidgety movements, and calculated a motor optimality score. At school age (median 5 y 11 mo, range 5 y 8 mo-7 y 6 mo), we performed detailed cognitive, motor, and behavioural assessments. We examined whether aspects of motor development were associated with functional outcomes.", "An age-adequate motor repertoire, in particular the presence of antigravity, midline leg, and manipulation movements, was related to poorer cognition, whereas variable finger postures was related to better cognition. Children with a monotonous concurrent motor repertoire had better ball skills but experienced more behavioural problems. The presence of antigravity movements tended to be associated with abnormal recognition (odds ratio [OR] 4.4, 95% confidence interval [CI], 0.9-21; R(2) =0.17; p=0.070), where the absence of variable finger postures was associated with borderline and abnormal visual-spatial perception (OR 20, 95% CI, 1.7-238; R(2) =0.39; p=0.018)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Child", "Child Behavior", "Child, Preschool", "Cognition", "Cognition Disorders", "Female", "Follow-Up Studies", "Humans", "Infant", "Infant Behavior", "Male", "Motor Activity", "Motor Skills", "Perceptual Disorders", "Prognosis", "Space Perception", "Surveys and Questionnaires", "Video Recording", "Visual Perception" ] }
Detailed aspects of motor development at 3 months of age are associated with cognition and behaviour, but not with motor outcome, in healthy children at early school age. Our findings suggest that early motor development may be the basis for later cognitive and behavioural performance. Since the associations were only moderate, possible environmental influences should be acknowledged.
yes
[ { "from": "human", "value": "Question: Is motor development in 3-month-old healthy term-born infants associated with cognitive and behavioural outcomes at early school age?\nContext: {'contexts': ['To determine whether motor development at 3 months of age is associated with cognitive, motor, and behavioural outcomes in healthy children at early school age.', 'In this cohort study, we included 74 term-born, healthy children (44 males, 30 females; median gestational age 40.1 wks, range 38.0-42.6 wks). From video recordings (median 12.9 wks, range 9.3-18.6 wks), we assessed the quality of fidgety movements, and calculated a motor optimality score. At school age (median 5 y 11 mo, range 5 y 8 mo-7 y 6 mo), we performed detailed cognitive, motor, and behavioural assessments. We examined whether aspects of motor development were associated with functional outcomes.', 'An age-adequate motor repertoire, in particular the presence of antigravity, midline leg, and manipulation movements, was related to poorer cognition, whereas variable finger postures was related to better cognition. Children with a monotonous concurrent motor repertoire had better ball skills but experienced more behavioural problems. The presence of antigravity movements tended to be associated with abnormal recognition (odds ratio [OR] 4.4, 95% confidence interval [CI], 0.9-21; R(2) =0.17; p=0.070), where the absence of variable finger postures was associated with borderline and abnormal visual-spatial perception (OR 20, 95% CI, 1.7-238; R(2) =0.39; p=0.018).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Child', 'Child Behavior', 'Child, Preschool', 'Cognition', 'Cognition Disorders', 'Female', 'Follow-Up Studies', 'Humans', 'Infant', 'Infant Behavior', 'Male', 'Motor Activity', 'Motor Skills', 'Perceptual Disorders', 'Prognosis', 'Space Perception', 'Surveys and Questionnaires', 'Video Recording', 'Visual Perception']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,749,982
Do serine proteases and protease-activated receptor 2 mediate the proinflammatory and algesic actions of diverse stimulants?
{ "contexts": [ "Although serine proteases and agonists of protease-activated receptor 2 (PAR2) cause inflammation and pain, the spectrum of proteases that are activated by proinflammatory and algesic stimuli and their contribution to inflammatory pain are uncertain.", "Enzymic assays and selective inhibitors were used to characterize protease activity in mice after intraplantar injections of formalin, bradykinin, PAR2 activating peptide (AP) or vehicle. The capacity of these proteases and of recombinant mouse trypsin 4 to cleave fragments of PAR2 and to activate PAR2 in cell lines was determined. Protease inhibitors and par2 (-/-) mice were used to assess the contributions of proteases and PAR2 to pain and inflammation.", "Intraplantar injection of formalin, bradykinin or PAR2-AP led to the activation of proteases that were susceptible to the serine protease inhibitor melagatran but resistant to soybean trypsin inhibitor (SBTI). Melagatran inhibited mouse trypsin 4, which degraded SBTI. Proteases generated in inflamed tissues cleaved PAR2-derived peptides. These proteases and trypsin 4 increased [Ca(2+) ]i in PAR2-transfected but not in untransfected cells, and melagatran suppressed this activity. Melagatran or PAR2 deletion suppressed oedema and mechanical hypersensitivity induced by intraplantar formalin, bradykinin and PAR2-AP, but had no effect on capsaicin-induced pain." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Azetidines", "Benzylamines", "Bradykinin", "Cell Line", "Female", "Foot", "Formaldehyde", "Inflammation", "Male", "Mice, Inbred C57BL", "Mice, Transgenic", "Oligopeptides", "Pain", "Receptor, PAR-2", "Serine Proteases", "Serine Proteinase Inhibitors", "Trypsin" ] }
Diverse proinflammatory and algesic agents activate melagatran-sensitive serine proteases that cause inflammation and pain by a PAR2-mediated mechanism. By inducing self-activating proteases, PAR2 amplifies and sustains inflammation and pain. Serine protease inhibitors can attenuate the inflammatory and algesic effects of diverse stimuli, representing a useful therapeutic strategy.
yes
[ { "from": "human", "value": "Question: Do serine proteases and protease-activated receptor 2 mediate the proinflammatory and algesic actions of diverse stimulants?\nContext: {'contexts': ['Although serine proteases and agonists of protease-activated receptor 2 (PAR2) cause inflammation and pain, the spectrum of proteases that are activated by proinflammatory and algesic stimuli and their contribution to inflammatory pain are uncertain.', 'Enzymic assays and selective inhibitors were used to characterize protease activity in mice after intraplantar injections of formalin, bradykinin, PAR2 activating peptide (AP) or vehicle. The capacity of these proteases and of recombinant mouse trypsin 4 to cleave fragments of PAR2 and to activate PAR2 in cell lines was determined. Protease inhibitors and par2 (-/-) mice were used to assess the contributions of proteases and PAR2 to pain and inflammation.', 'Intraplantar injection of formalin, bradykinin or PAR2-AP led to the activation of proteases that were susceptible to the serine protease inhibitor melagatran but resistant to soybean trypsin inhibitor (SBTI). Melagatran inhibited mouse trypsin 4, which degraded SBTI. Proteases generated in inflamed tissues cleaved PAR2-derived peptides. These proteases and trypsin 4 increased [Ca(2+) ]i in PAR2-transfected but not in untransfected cells, and melagatran suppressed this activity. Melagatran or PAR2 deletion suppressed oedema and mechanical hypersensitivity induced by intraplantar formalin, bradykinin and PAR2-AP, but had no effect on capsaicin-induced pain.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Azetidines', 'Benzylamines', 'Bradykinin', 'Cell Line', 'Female', 'Foot', 'Formaldehyde', 'Inflammation', 'Male', 'Mice, Inbred C57BL', 'Mice, Transgenic', 'Oligopeptides', 'Pain', 'Receptor, PAR-2', 'Serine Proteases', 'Serine Proteinase Inhibitors', 'Trypsin']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,769,283
Does taurine supplementation decrease homocysteine levels and liver injury induced by a choline-deficient diet?
{ "contexts": [ "The aim of this study is to examine the effects of taurine supplementation on homocysteine (Hcy) metabolism and liver injury in rats fed a choline-deficient diet.", "Thirty rats were divided into three groups (n=10), to receive one of the following diets for 4 weeks: control diet (C), choline-deficient diet (CDD), or choline-deficient diet supplemented with taurine (CDDT). The CDD and the CDDT consisted of AIN-93 without the recommended choline content of 2.5%, and the CDDT was supplemented by the addition of 2.5% taurine.", "Four weeks of ingesting a CDD resulted in a significant increase in plasma Hcy (50%) as well as a decrease in liver S-adenosylmethionine (SAM) concentration and S-adenosylmethionine/S-adenosylhomocysteine ratio. No changes were found in plasma methionine and cysteine plasma levels compared to control group. Four weeks of ingesting a CDD also caused a significant (P<0.05) increase in hepatic total fat, hepatic malondialdehyde (MDA), and plasma alanine aminotransferase (ALT) levels. In addition, reduced hepatic glutathione (GSH) levels and reduced/oxidized glutathione ratios (GSH/GSSG) were found in rats fed a CDD compared to controls. Taurine supplementation of the CDD normalized genes involved in the remethylation pathway, BHMT and CHDH, which were impaired by CDD alone. However, taurine supplementation failed to prevent CDD-induced Hcy metabolism disturbances and hepatic injury. Also, taurine added to CDD caused decreased expression of PEMT, CHKa, and CHKb, key genes involved in phosphatidylcholine (PC) synthesis and liver fat accumulation." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Alanine Transaminase", "Analysis of Variance", "Animals", "Choline Deficiency", "Cysteine", "Diet", "Dietary Supplements", "Gene Expression Regulation", "Homocysteine", "Liver", "Malondialdehyde", "Methionine", "Rats", "Taurine" ] }
Taurine supplementation failed to ameliorate impaired Hcy metabolism and liver injury caused by CDD intake.
no
[ { "from": "human", "value": "Question: Does taurine supplementation decrease homocysteine levels and liver injury induced by a choline-deficient diet?\nContext: {'contexts': ['The aim of this study is to examine the effects of taurine supplementation on homocysteine (Hcy) metabolism and liver injury in rats fed a choline-deficient diet.', 'Thirty rats were divided into three groups (n=10), to receive one of the following diets for 4 weeks: control diet (C), choline-deficient diet (CDD), or choline-deficient diet supplemented with taurine (CDDT). The CDD and the CDDT consisted of AIN-93 without the recommended choline content of 2.5%, and the CDDT was supplemented by the addition of 2.5% taurine.', 'Four weeks of ingesting a CDD resulted in a significant increase in plasma Hcy (50%) as well as a decrease in liver S-adenosylmethionine (SAM) concentration and S-adenosylmethionine/S-adenosylhomocysteine ratio. No changes were found in plasma methionine and cysteine plasma levels compared to control group. Four weeks of ingesting a CDD also caused a significant (P<0.05) increase in hepatic total fat, hepatic malondialdehyde (MDA), and plasma alanine aminotransferase (ALT) levels. In addition, reduced hepatic glutathione (GSH) levels and reduced/oxidized glutathione ratios (GSH/GSSG) were found in rats fed a CDD compared to controls. Taurine supplementation of the CDD normalized genes involved in the remethylation pathway, BHMT and CHDH, which were impaired by CDD alone. However, taurine supplementation failed to prevent CDD-induced Hcy metabolism disturbances and hepatic injury. Also, taurine added to CDD caused decreased expression of PEMT, CHKa, and CHKb, key genes involved in phosphatidylcholine (PC) synthesis and liver fat accumulation.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Alanine Transaminase', 'Analysis of Variance', 'Animals', 'Choline Deficiency', 'Cysteine', 'Diet', 'Dietary Supplements', 'Gene Expression Regulation', 'Homocysteine', 'Liver', 'Malondialdehyde', 'Methionine', 'Rats', 'Taurine']}" }, { "from": "gpt", "value": "Answer: no" } ]
24,776,048
Is nighttime ambulatory blood pressure associated with atrial remodelling and neurohormonal activation in patients with idiopathic atrial fibrillation?
{ "contexts": [ "Hypertension is a risk factor for atrial fibrillation. Activation of the renin-angiotensin-system seems to be involved in atrial enlargement, with release of atrial and brain natriuretic peptides. The aim of this study was to evaluate the relationship between ambulatory blood pressure and levels of natriuretic peptides, with left atrial size in normotensives with idiopathic atrial fibrillation.", "This was a cross-sectional study in patients with idiopathic atrial fibrillation. The following measurements were recorded during the course of the study: office and 24-h ambulatory blood pressure, atrial and brain natriuretic peptides, plasma renin, aldosterone, and angiotensin-converting enzyme.", "Forty-eight patients (mean age 55 [10] years; 70.6% male) were included in the study. Mean office sitting blood pressure values were 132.49 (14.9)/80.96 (9.2) mmHg. Mean 24-h ambulatory systolic and diastolic blood pressure values were 121.10 (8.3)/72.11 (6.8) mmHg (daytime, 126.8 [9.7]/77.58 [7.9] mmHg; nighttime, 114.56 [11.6]/68.6 [8.8] mmHg). A clear trend towards increased left atrial size with higher ambulatory blood pressure values was noted, which was statistically significant for nighttime values (r=0.34; P=.020 for systolic and r=0.51; p=.0001 for diastolic). A significant correlation between atrial natriuretic peptide and nighttime systolic (r=0.297; P=.047) and diastolic (r=0.312; P=.037) blood pressure was observed. Significant correlations were also observed between left atrial size and atrial natriuretic peptide levels (r=0.577; p<.0001) and brain natriuretic peptide levels (r=0.379; P=.012)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Atrial Fibrillation", "Atrial Remodeling", "Blood Pressure", "Blood Pressure Monitoring, Ambulatory", "Cohort Studies", "Cross-Sectional Studies", "Female", "Heart Atria", "Humans", "Male", "Middle Aged", "Neurotransmitter Agents" ] }
Nighttime blood pressure is associated with left atrial size and the release of natriuretic peptides in normotensive patients with idiopathic atrial fibrillation.
yes
[ { "from": "human", "value": "Question: Is nighttime ambulatory blood pressure associated with atrial remodelling and neurohormonal activation in patients with idiopathic atrial fibrillation?\nContext: {'contexts': ['Hypertension is a risk factor for atrial fibrillation. Activation of the renin-angiotensin-system seems to be involved in atrial enlargement, with release of atrial and brain natriuretic peptides. The aim of this study was to evaluate the relationship between ambulatory blood pressure and levels of natriuretic peptides, with left atrial size in normotensives with idiopathic atrial fibrillation.', 'This was a cross-sectional study in patients with idiopathic atrial fibrillation. The following measurements were recorded during the course of the study: office and 24-h ambulatory blood pressure, atrial and brain natriuretic peptides, plasma renin, aldosterone, and angiotensin-converting enzyme.', 'Forty-eight patients (mean age 55 [10] years; 70.6% male) were included in the study. Mean office sitting blood pressure values were 132.49 (14.9)/80.96 (9.2) mmHg. Mean 24-h ambulatory systolic and diastolic blood pressure values were 121.10 (8.3)/72.11 (6.8) mmHg (daytime, 126.8 [9.7]/77.58 [7.9] mmHg; nighttime, 114.56 [11.6]/68.6 [8.8] mmHg). A clear trend towards increased left atrial size with higher ambulatory blood pressure values was noted, which was statistically significant for nighttime values (r=0.34; P=.020 for systolic and r=0.51; p=.0001 for diastolic). A significant correlation between atrial natriuretic peptide and nighttime systolic (r=0.297; P=.047) and diastolic (r=0.312; P=.037) blood pressure was observed. Significant correlations were also observed between left atrial size and atrial natriuretic peptide levels (r=0.577; p<.0001) and brain natriuretic peptide levels (r=0.379; P=.012).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Atrial Fibrillation', 'Atrial Remodeling', 'Blood Pressure', 'Blood Pressure Monitoring, Ambulatory', 'Cohort Studies', 'Cross-Sectional Studies', 'Female', 'Heart Atria', 'Humans', 'Male', 'Middle Aged', 'Neurotransmitter Agents']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,777,302
Do biomarkers S100B and neuron-specific enolase predict outcome in hypothermia-treated encephalopathic newborns*?
{ "contexts": [ "To evaluate if serum S100B protein and neuron-specific enolase measured during therapeutic hypothermia are predictive of neurodevelopmental outcome at 15 months in children with neonatal encephalopathy.", "Prospective longitudinal cohort study.", "A level IV neonatal ICU in a freestanding children's hospital.", "Term newborns with moderate to severe neonatal encephalopathy referred for therapeutic hypothermia during the study period.", "Serum neuron-specific enolase and S100B were measured at 0, 12, 24, and 72 hours of hypothermia.", "Of the 83 infants enrolled, 15 (18%) died in the newborn period. Survivors were evaluated by the Bayley Scales of Infant Development-II at 15 months. Outcomes were assessed in 49 of 68 survivors (72%) at a mean age of 15.2 ± 2.7 months. Neurodevelopmental outcome was classified by Bayley Scales of Infant Development-II Mental Developmental Index and Psychomotor Developmental Index scores, reflecting cognitive and motor outcomes, respectively. Four-level outcome classifications were defined a priori: normal = Mental Developmental Index/Psychomotor Developmental Index within 1 SD (> 85), mild = Mental Developmental Index/Psychomotor Developmental Index less than 1 SD (70-85), moderate/severe = Mental Developmental Index/Psychomotor Developmental Index less than 2 SD (< 70), or died. Elevated serum S100B and neuron-specific enolase levels measured during hypothermia were associated with increasing outcome severity after controlling for baseline and socioeconomic characteristics in ordinal regression models. Adjusted odds ratios for cognitive outcome were 2.5 (95% CI, 1.3-4.8) for S100B and 2.1 (95% CI, 1.2-3.6) for neuron-specific enolase, and for motor outcome, 2.6 (95% CI, 1.2-5.6) for S100B and 2.1 (95% CI, 1.2-3.6) for neuron-specific enolase." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Biomarkers", "Brain Diseases", "Child Development", "Child, Preschool", "Cognition", "Cohort Studies", "Developmental Disabilities", "Female", "Humans", "Hypothermia, Induced", "Infant", "Infant, Newborn", "Intensive Care, Neonatal", "Male", "Motor Skills", "Phosphopyruvate Hydratase", "Predictive Value of Tests", "S100 Calcium Binding Protein beta Subunit", "Treatment Outcome" ] }
Serum S100B and neuron-specific enolase levels in babies with neonatal encephalopathy are associated with neurodevelopmental outcome at 15 months. These putative biomarkers of brain injury may help direct care during therapeutic hypothermia.
yes
[ { "from": "human", "value": "Question: Do biomarkers S100B and neuron-specific enolase predict outcome in hypothermia-treated encephalopathic newborns*?\nContext: {'contexts': ['To evaluate if serum S100B protein and neuron-specific enolase measured during therapeutic hypothermia are predictive of neurodevelopmental outcome at 15 months in children with neonatal encephalopathy.', 'Prospective longitudinal cohort study.', \"A level IV neonatal ICU in a freestanding children's hospital.\", 'Term newborns with moderate to severe neonatal encephalopathy referred for therapeutic hypothermia during the study period.', 'Serum neuron-specific enolase and S100B were measured at 0, 12, 24, and 72 hours of hypothermia.', 'Of the 83 infants enrolled, 15 (18%) died in the newborn period. Survivors were evaluated by the Bayley Scales of Infant Development-II at 15 months. Outcomes were assessed in 49 of 68 survivors (72%) at a mean age of 15.2 ± 2.7 months. Neurodevelopmental outcome was classified by Bayley Scales of Infant Development-II Mental Developmental Index and Psychomotor Developmental Index scores, reflecting cognitive and motor outcomes, respectively. Four-level outcome classifications were defined a priori: normal = Mental Developmental Index/Psychomotor Developmental Index within 1 SD (> 85), mild = Mental Developmental Index/Psychomotor Developmental Index less than 1 SD (70-85), moderate/severe = Mental Developmental Index/Psychomotor Developmental Index less than 2 SD (< 70), or died. Elevated serum S100B and neuron-specific enolase levels measured during hypothermia were associated with increasing outcome severity after controlling for baseline and socioeconomic characteristics in ordinal regression models. Adjusted odds ratios for cognitive outcome were 2.5 (95% CI, 1.3-4.8) for S100B and 2.1 (95% CI, 1.2-3.6) for neuron-specific enolase, and for motor outcome, 2.6 (95% CI, 1.2-5.6) for S100B and 2.1 (95% CI, 1.2-3.6) for neuron-specific enolase.'], 'labels': ['OBJECTIVE', 'METHODS', 'METHODS', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Biomarkers', 'Brain Diseases', 'Child Development', 'Child, Preschool', 'Cognition', 'Cohort Studies', 'Developmental Disabilities', 'Female', 'Humans', 'Hypothermia, Induced', 'Infant', 'Infant, Newborn', 'Intensive Care, Neonatal', 'Male', 'Motor Skills', 'Phosphopyruvate Hydratase', 'Predictive Value of Tests', 'S100 Calcium Binding Protein beta Subunit', 'Treatment Outcome']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,777,300
Is vasoactive-inotropic score associated with outcome after infant cardiac surgery : an analysis from the Pediatric Cardiac Critical Care Consortium and Virtual PICU System Registries?
{ "contexts": [ "To empirically derive the optimal measure of pharmacologic cardiovascular support in infants undergoing cardiac surgery with bypass and to assess the association between this score and clinical outcomes in a multi-institutional cohort.", "Prospective, multi-institutional cohort study.", "Cardiac ICUs at four academic children's hospitals participating in the Pediatric Cardiac Critical Care Consortium during the study period.", "Children younger than 1 year at the time of surgery treated postoperatively in the cardiac ICU.", "None.", "Three hundred ninety-one infants undergoing surgery with bypass were enrolled consecutively from November 2011 to April 2012. Hourly doses of all vasoactive agents were recorded for the first 48 hours after cardiac ICU admission. Multiple derivations of an inotropic score were tested, and maximum vasoactive-inotropic score in the first 24 hours was further analyzed for association with clinical outcomes. The primary composite \"poor outcome\" variable included at least one of mortality, mechanical circulatory support, cardiac arrest, renal replacement therapy, or neurologic injury. High vasoactive-inotropic score was empirically defined as more than or equal to 20. Multivariable logistic regression was performed controlling for center and patient characteristics. Patients with high vasoactive-inotropic score had significantly greater odds of a poor outcome (odds ratio, 6.5; 95% CI, 2.9-14.6), mortality (odds ratio, 13.2; 95% CI, 3.7-47.6), and prolonged time to first extubation and cardiac ICU length of stay compared with patients with low vasoactive-inotropic score. Stratified analyses by age (neonate vs infant) and surgical complexity (low vs high) showed similar associations with increased morbidity and mortality for patients with high vasoactive-inotropic score." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Airway Extubation", "Cardiac Surgical Procedures", "Cardiopulmonary Bypass", "Cardiotonic Agents", "Critical Care", "Female", "Humans", "Infant", "Infant, Newborn", "Length of Stay", "Male", "Postoperative Care", "Prospective Studies", "Registries", "Severity of Illness Index", "Time Factors", "Treatment Outcome", "Vasoconstrictor Agents" ] }
Maximum vasoactive-inotropic score calculated in the first 24 hours after cardiac ICU admission was strongly and significantly associated with morbidity and mortality in this multi-institutional cohort of infants undergoing cardiac surgery. Maximum vasoactive-inotropic score more than or equal to 20 predicts an increased likelihood of a poor composite clinical outcome. The findings were consistent in stratified analyses by age and surgical complexity.
yes
[ { "from": "human", "value": "Question: Is vasoactive-inotropic score associated with outcome after infant cardiac surgery : an analysis from the Pediatric Cardiac Critical Care Consortium and Virtual PICU System Registries?\nContext: {'contexts': ['To empirically derive the optimal measure of pharmacologic cardiovascular support in infants undergoing cardiac surgery with bypass and to assess the association between this score and clinical outcomes in a multi-institutional cohort.', 'Prospective, multi-institutional cohort study.', \"Cardiac ICUs at four academic children's hospitals participating in the Pediatric Cardiac Critical Care Consortium during the study period.\", 'Children younger than 1 year at the time of surgery treated postoperatively in the cardiac ICU.', 'None.', 'Three hundred ninety-one infants undergoing surgery with bypass were enrolled consecutively from November 2011 to April 2012. Hourly doses of all vasoactive agents were recorded for the first 48 hours after cardiac ICU admission. Multiple derivations of an inotropic score were tested, and maximum vasoactive-inotropic score in the first 24 hours was further analyzed for association with clinical outcomes. The primary composite \"poor outcome\" variable included at least one of mortality, mechanical circulatory support, cardiac arrest, renal replacement therapy, or neurologic injury. High vasoactive-inotropic score was empirically defined as more than or equal to 20. Multivariable logistic regression was performed controlling for center and patient characteristics. Patients with high vasoactive-inotropic score had significantly greater odds of a poor outcome (odds ratio, 6.5; 95% CI, 2.9-14.6), mortality (odds ratio, 13.2; 95% CI, 3.7-47.6), and prolonged time to first extubation and cardiac ICU length of stay compared with patients with low vasoactive-inotropic score. Stratified analyses by age (neonate vs infant) and surgical complexity (low vs high) showed similar associations with increased morbidity and mortality for patients with high vasoactive-inotropic score.'], 'labels': ['OBJECTIVE', 'METHODS', 'METHODS', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Airway Extubation', 'Cardiac Surgical Procedures', 'Cardiopulmonary Bypass', 'Cardiotonic Agents', 'Critical Care', 'Female', 'Humans', 'Infant', 'Infant, Newborn', 'Length of Stay', 'Male', 'Postoperative Care', 'Prospective Studies', 'Registries', 'Severity of Illness Index', 'Time Factors', 'Treatment Outcome', 'Vasoconstrictor Agents']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,777,306
Does the extent of the perihemorrhagic perfusion zone correlate with hematoma volume in patients with lobar intracerebral hemorrhage?
{ "contexts": [ "Existing data on perfusion imaging assumes the perihemorrhagic zone (PHZ) in patients with intracerebral hemorrhage (ICH) to be size steady. This study investigates the size of the perihemorrhagic zone (PHZ) in patients with lobar ICH in relation to hematoma volume during the course of treatment using perfusion CT (PCT).", "The present analysis is based on a previously reported cohort of 20 patients undergoing surgical evacuation for lobar SICH, with pre- and early postoperative PCT scanning. Time to peak of the residue function (T max) was measured based on the 360° cortical banding method and singular value decomposition. The size of PHZ was determined before and after treatment and correlated with hematoma volume.", "Preoperative mean hematoma volume constituted 63.0 ml (interquartile ranges (IQR) 39.7-99.4 ml), which correlated significantly (r=0.563, p=0.010) with mean PHZ size (5.67 cm, IQR 5.44-8.17 cm). Following a surgical hematoma evacuation, mean hematoma volume was reduced to 2.5 ml IQR 0.0-9.5 ml, which also resulted in a significant reduction of PHZ size to 0.45 cm(IQR 0.0-1.36 cm; p<0.001). There was no association between postoperative hematoma volume and size of the PHZ." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Cerebral Angiography", "Cerebral Hemorrhage", "Female", "Hematoma", "Humans", "Imaging, Three-Dimensional", "Male", "Middle Aged", "Reproducibility of Results", "Sensitivity and Specificity", "Statistics as Topic", "Tomography, X-Ray Computed" ] }
Our findings illustrate that the extent of the PHZ cannot be generally assumed to be constant in size and that this differs significantly following hematoma reduction in patients with space occupying lobar SICH.
yes
[ { "from": "human", "value": "Question: Does the extent of the perihemorrhagic perfusion zone correlate with hematoma volume in patients with lobar intracerebral hemorrhage?\nContext: {'contexts': ['Existing data on perfusion imaging assumes the perihemorrhagic zone (PHZ) in patients with intracerebral hemorrhage (ICH) to be size steady. This study investigates the size of the perihemorrhagic zone (PHZ) in patients with lobar ICH in relation to hematoma volume during the course of treatment using perfusion CT (PCT).', 'The present analysis is based on a previously reported cohort of 20 patients undergoing surgical evacuation for lobar SICH, with pre- and early postoperative PCT scanning. Time to peak of the residue function (T max) was measured based on the 360° cortical banding method and singular value decomposition. The size of PHZ was determined before and after treatment and correlated with hematoma volume.', 'Preoperative mean hematoma volume constituted 63.0 ml (interquartile ranges (IQR) 39.7-99.4 ml), which correlated significantly (r=0.563, p=0.010) with mean PHZ size (5.67 cm, IQR 5.44-8.17 cm). Following a surgical hematoma evacuation, mean hematoma volume was reduced to 2.5 ml IQR 0.0-9.5 ml, which also resulted in a significant reduction of PHZ size to 0.45 cm(IQR 0.0-1.36 cm; p<0.001). There was no association between postoperative hematoma volume and size of the PHZ.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Cerebral Angiography', 'Cerebral Hemorrhage', 'Female', 'Hematoma', 'Humans', 'Imaging, Three-Dimensional', 'Male', 'Middle Aged', 'Reproducibility of Results', 'Sensitivity and Specificity', 'Statistics as Topic', 'Tomography, X-Ray Computed']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,767,980
Does high expression of Cullin1 indicate poor prognosis for NSCLC patients?
{ "contexts": [ "Cullin1 is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex which ubiquitinates a broad range of proteins participating in biochemical events like cell-cycle progression, signal transduction, and transcription. Cullin1 is involved in the progression of several cancers, such as melanoma, breast cancer, and gastric cancer.", "To investigate the role of Cullin1 in the development of non-small-cell lung cancer (NSCLC), we examined the expression of Cullin1 in 8-paired fresh NSCLC tissues. We then constructed immunohistochemistry (IHC) on 114 paraffin-embedded slices and evaluated the correlation between Cullin1 expression and clinicopathologic variables, as well as patients' overall survival.", "We found that Cullin1 was highly expressed in NSCLC tissues and significantly associated with NSCLC's histological differentiation (P=0.002), clinical stage (P=0.010) and Ki-67 (P=0.021). Furthermore, we showed a strong correlation between high Cullin1 expression and worse overall survival rates in NSCLC patients (P<0.001). Cox regression analysis revealed that Cullin1 expression was an independent prognostic factor to predict 5-year patient outcome in NSCLC cancer (P=0.033)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Biomarkers, Tumor", "Blotting, Western", "Carcinoma, Non-Small-Cell Lung", "Cullin Proteins", "Female", "Humans", "Immunohistochemistry", "Kaplan-Meier Estimate", "Lung Neoplasms", "Male", "Middle Aged", "Prognosis", "Proportional Hazards Models" ] }
These data suggested that Cullin1 might promote the progression of NSCLC and be a biotarget for NSCLC's therapy.
yes
[ { "from": "human", "value": "Question: Does high expression of Cullin1 indicate poor prognosis for NSCLC patients?\nContext: {'contexts': ['Cullin1 is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex which ubiquitinates a broad range of proteins participating in biochemical events like cell-cycle progression, signal transduction, and transcription. Cullin1 is involved in the progression of several cancers, such as melanoma, breast cancer, and gastric cancer.', \"To investigate the role of Cullin1 in the development of non-small-cell lung cancer (NSCLC), we examined the expression of Cullin1 in 8-paired fresh NSCLC tissues. We then constructed immunohistochemistry (IHC) on 114 paraffin-embedded slices and evaluated the correlation between Cullin1 expression and clinicopathologic variables, as well as patients' overall survival.\", \"We found that Cullin1 was highly expressed in NSCLC tissues and significantly associated with NSCLC's histological differentiation (P=0.002), clinical stage (P=0.010) and Ki-67 (P=0.021). Furthermore, we showed a strong correlation between high Cullin1 expression and worse overall survival rates in NSCLC patients (P<0.001). Cox regression analysis revealed that Cullin1 expression was an independent prognostic factor to predict 5-year patient outcome in NSCLC cancer (P=0.033).\"], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Biomarkers, Tumor', 'Blotting, Western', 'Carcinoma, Non-Small-Cell Lung', 'Cullin Proteins', 'Female', 'Humans', 'Immunohistochemistry', 'Kaplan-Meier Estimate', 'Lung Neoplasms', 'Male', 'Middle Aged', 'Prognosis', 'Proportional Hazards Models']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,751,514
Does nanoencapsulation in lipid-core nanocapsules control mometasone furoate skin permeability rate and its penetration to the deeper skin layers?
{ "contexts": [ "The influence of nanoencapsulation of mometasone furoate (MF) in poly(ε-caprolactone) lipid-core nanocapsules (LNC) on its in vitro human skin permeation and penetration was evaluated.", "Semisolid formulations were prepared by increasing the viscosity of LNC using a carbomer (Carbopol(®) Ultrez at 0.5% w/v). Two complementary techniques (the static Franz diffusion cell model and the Saarbrücken penetration model) were used to evaluate skin permeation/penetration.", "The drug release rate was decreased by nanoencapsulation. The skin permeability of MF was controlled by the nanoencapsulation as well as by increasing the viscosity. Furthermore, the formulation containing the nanoencapsulated MF controlled the amount of drug reaching the deeper skin layers without changing its accumulation in the stratum corneum." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Humans", "Lipids", "Mometasone Furoate", "Nanocapsules", "Particle Size", "Permeability", "Polyesters", "Pregnadienediols", "Skin", "Skin Absorption" ] }
This formulation is suitable for prolonged treatment of skin disorders which should avoid systemic absorption.
yes
[ { "from": "human", "value": "Question: Does nanoencapsulation in lipid-core nanocapsules control mometasone furoate skin permeability rate and its penetration to the deeper skin layers?\nContext: {'contexts': ['The influence of nanoencapsulation of mometasone furoate (MF) in poly(ε-caprolactone) lipid-core nanocapsules (LNC) on its in vitro human skin permeation and penetration was evaluated.', 'Semisolid formulations were prepared by increasing the viscosity of LNC using a carbomer (Carbopol(®) Ultrez at 0.5% w/v). Two complementary techniques (the static Franz diffusion cell model and the Saarbrücken penetration model) were used to evaluate skin permeation/penetration.', 'The drug release rate was decreased by nanoencapsulation. The skin permeability of MF was controlled by the nanoencapsulation as well as by increasing the viscosity. Furthermore, the formulation containing the nanoencapsulated MF controlled the amount of drug reaching the deeper skin layers without changing its accumulation in the stratum corneum.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Humans', 'Lipids', 'Mometasone Furoate', 'Nanocapsules', 'Particle Size', 'Permeability', 'Polyesters', 'Pregnadienediols', 'Skin', 'Skin Absorption']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,775,561
Does quality improvement intervention reduce episodes of long-term acute care hospital central line-associated infections?
{ "contexts": [ "Reducing central line-associated bloodstream infections (CLABSIs) poses a set of unique challenges in long-term acute care hospitals (LTACHS). Patients are often admitted to LTACHs with central lines in place from the previous hospitalization; thus, LTACHs lack control over insertion techniques and respective central line care and maintenance. This study aimed to demonstrate the impact of a methodical bathing approach with 2% chlorhexidine gluconate (CHG) cloths and a correlation with a reduced prevalence of CLABSIs in our LTACH population.", "This retrospective observational quality initiative conducted in a 105-bed LTACH used plan-do-study-act methodology to assess the effects of a revised bathing approach using 2% CHG.", "Statistical significance demonstrated a 65% reduction in CLABSI on the pilot unit after the 6-month initial trial. The results of the quality initiative were evaluated through the end of 2012." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Anti-Infective Agents, Local", "Baths", "Catheter-Related Infections", "Catheterization, Central Venous", "Chlorhexidine", "Hospitals", "Humans", "Incidence", "Infection Control", "Pilot Projects", "Quality Improvement", "Retrospective Studies" ] }
The decision was made to implement the revised bathing protocol throughout the entire LTACH hospital stay.
yes
[ { "from": "human", "value": "Question: Does quality improvement intervention reduce episodes of long-term acute care hospital central line-associated infections?\nContext: {'contexts': ['Reducing central line-associated bloodstream infections (CLABSIs) poses a set of unique challenges in long-term acute care hospitals (LTACHS). Patients are often admitted to LTACHs with central lines in place from the previous hospitalization; thus, LTACHs lack control over insertion techniques and respective central line care and maintenance. This study aimed to demonstrate the impact of a methodical bathing approach with 2% chlorhexidine gluconate (CHG) cloths and a correlation with a reduced prevalence of CLABSIs in our LTACH population.', 'This retrospective observational quality initiative conducted in a 105-bed LTACH used plan-do-study-act methodology to assess the effects of a revised bathing approach using 2% CHG.', 'Statistical significance demonstrated a 65% reduction in CLABSI on the pilot unit after the 6-month initial trial. The results of the quality initiative were evaluated through the end of\\xa02012.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Anti-Infective Agents, Local', 'Baths', 'Catheter-Related Infections', 'Catheterization, Central Venous', 'Chlorhexidine', 'Hospitals', 'Humans', 'Incidence', 'Infection Control', 'Pilot Projects', 'Quality Improvement', 'Retrospective Studies']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,771,315
Do a system for context-aware intraoperative augmented reality in dental implant surgery?
{ "contexts": [ "Large volumes of information in the OR are ignored by surgeons when the amount outpaces human mental processing abilities. We developed an augmented reality (AR) system for dental implant surgery that acts as an automatic information filter, selectively displaying only relevant information. The purpose is to reduce information overflow and offer intuitive image guidance. The system was evaluated in a pig cadaver experiment.", "Information filtering is implemented via rule-based situation interpretation with description logics. The interpretation is based on intraoperative distances measurement between anatomical structures and the dental drill with optical tracking. For AR, a head-mounted display is used, which was calibrated with a novel method based on SPAAM. To adapt to surgeon specific preferences, we offer two alternative display formats: one with static and another with contact analog AR.", "The system made the surgery easier and showed ergonomical benefits, as assessed by a questionnaire. All relevant phases were recognized reliably. The new calibration showed significant improvements, while the deviation of the realized implants was <2.5 mm." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Calibration", "Dental Implantation", "Dental Implants", "Swine", "User-Computer Interface" ] }
The system allowed the surgeon to fully concentrate on the surgery itself. It offered greater flexibility since the surgeon received all relevant information, but was free to deviate from it. Accuracy of the realized implants remains an open issue and part of future work.
yes
[ { "from": "human", "value": "Question: Do a system for context-aware intraoperative augmented reality in dental implant surgery?\nContext: {'contexts': ['Large volumes of information in the OR are ignored by surgeons when the amount outpaces human mental processing abilities. We developed an augmented reality (AR) system for dental implant surgery that acts as an automatic information filter, selectively displaying only relevant information. The purpose is to reduce information overflow and offer intuitive image guidance. The system was evaluated in a pig cadaver experiment.', 'Information filtering is implemented via rule-based situation interpretation with description logics. The interpretation is based on intraoperative distances measurement between anatomical structures and the dental drill with optical tracking. For AR, a head-mounted display is used, which was calibrated with a novel method based on SPAAM. To adapt to surgeon specific preferences, we offer two alternative display formats: one with static and another with contact analog AR.', 'The system made the surgery easier and showed ergonomical benefits, as assessed by a questionnaire. All relevant phases were recognized reliably. The new calibration showed significant improvements, while the deviation of the realized implants was <2.5 mm.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Calibration', 'Dental Implantation', 'Dental Implants', 'Swine', 'User-Computer Interface']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,768,926
Does remote ischemic preconditioning differentially affect NADPH oxidase isoforms during hepatic ischemia-reperfusion?
{ "contexts": [ "We investigated the function of major superoxide-generating enzymes after remote ischemic preconditioning (IPC) and hepatic ischemia-reperfusion (IR), with the specific aim of assessing the importance of the most relevant NADPH oxidase (NOX) isoforms, NOX2 and NOX4, in the mechanism of action.", "60-min partial liver ischemia was induced in Sprague-Dawley rats in the presence or absence of remote IPC (2 × 10-min limb IR), and hepatic microcirculatory variables were determined through intravital video microscopy and lightguide spectrophotometry during reperfusion. Inflammatory enzyme activities (myeloperoxidase (MPO) and xanthine oxidoreductase (XOR)), cytokine production (TNF-α and HMGB-1), liver necroenzyme levels (AST, ALT and LDH) and NOX2 and NOX4 protein expression changes (Western blot analysis) were assayed biochemically.", "In this setting, remote IPC significantly decreased the IR-induced hepatic NOX2 expression, but the NOX4 expression remained unchanged. The remote IPC provided significant, but incomplete protection against the leukocyte-endothelial cell interactions and flow deterioration. Hepatocellular damage (AST, ALT and LDH release), cytokine levels, and XOR and MPO activities also diminished." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Analysis of Variance", "Animals", "Blotting, Western", "Cytokines", "HMGB1 Protein", "Ischemic Preconditioning", "Liver", "Membrane Glycoproteins", "Microcirculation", "Microscopy, Video", "NADPH Oxidase 2", "NADPH Oxidase 4", "NADPH Oxidases", "Peroxidase", "Rats", "Rats, Sprague-Dawley", "Reperfusion Injury", "Spectrophotometry", "Tumor Necrosis Factor-alpha", "Xanthine Dehydrogenase" ] }
Remote IPC limited the IR-induced microcirculatory dysfunction, but the protective effect did not affect all NOX homologs (at least not NOX4). The residual damage and inflammatory activation could well be linked to the unchanging NOX4 activity.
yes
[ { "from": "human", "value": "Question: Does remote ischemic preconditioning differentially affect NADPH oxidase isoforms during hepatic ischemia-reperfusion?\nContext: {'contexts': ['We investigated the function of major superoxide-generating enzymes after remote ischemic preconditioning (IPC) and hepatic ischemia-reperfusion (IR), with the specific aim of assessing the importance of the most relevant NADPH oxidase (NOX) isoforms, NOX2 and NOX4, in the mechanism of action.', '60-min partial liver ischemia was induced in Sprague-Dawley rats in the presence or absence of remote IPC (2 × 10-min limb IR), and hepatic microcirculatory variables were determined through intravital video microscopy and lightguide spectrophotometry during reperfusion. Inflammatory enzyme activities (myeloperoxidase (MPO) and xanthine oxidoreductase (XOR)), cytokine production (TNF-α and HMGB-1), liver necroenzyme levels (AST, ALT and LDH) and NOX2 and NOX4 protein expression changes (Western blot analysis) were assayed biochemically.', 'In this setting, remote IPC significantly decreased the IR-induced hepatic NOX2 expression, but the NOX4 expression remained unchanged. The remote IPC provided significant, but incomplete protection against the leukocyte-endothelial cell interactions and flow deterioration. Hepatocellular damage (AST, ALT and LDH release), cytokine levels, and XOR and MPO activities also diminished.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Analysis of Variance', 'Animals', 'Blotting, Western', 'Cytokines', 'HMGB1 Protein', 'Ischemic Preconditioning', 'Liver', 'Membrane Glycoproteins', 'Microcirculation', 'Microscopy, Video', 'NADPH Oxidase 2', 'NADPH Oxidase 4', 'NADPH Oxidases', 'Peroxidase', 'Rats', 'Rats, Sprague-Dawley', 'Reperfusion Injury', 'Spectrophotometry', 'Tumor Necrosis Factor-alpha', 'Xanthine Dehydrogenase']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,757,624
Is native arterio-venous fistula the vascular access of choice for hemodialysis in end stage renal disease?
{ "contexts": [ "THE AIM OF THE STUDY WAS: Is primary Arterio-venous fistula the vascular access of choice for adequate dialysis and better patient outcome in end stage renal disease.", "The present study was done in the department of cardiovascular and thoracic surgery at Sher-i-Kashmir institute of medical sciences, Soura, Srinagar Kashmir. Native Arterio-Venous (AV) fistulas were made in the patients with end stage renal disease for performing hemodialysis. They were followed for patency and adequacy of blood flow during hemodialysis. All the patients were operated under local anesthesia.", "The results showed that 77% of the AV fistulas based on radial artery with side-to-side anastomosis and 80% of those with end-to-side anastomosis were functionally patent after one year. After two years, the patency rate in side-to-side and end-to-side anastomosis was 50% and 55%, respectively. In addition, the patency rate was 90% in brachial artery based AV fistula with end-to-side anastomosis, whether done primarily or secondarily, at the end of one year. However, a rapid decline was observed in the patency rate during the third year in both radial artery based and brachial artery based AV fistulas." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [] }
We concluded that Arterialised arm superficial veins after primary AV fistula was the optimal and rational vascular access for hemodialysis providing adequate blood flow during this process. Besides, failure of primary AV fistula should be replaced by secondary AV fistula preferably based on brachial artery.
yes
[ { "from": "human", "value": "Question: Is native arterio-venous fistula the vascular access of choice for hemodialysis in end stage renal disease?\nContext: {'contexts': ['THE AIM OF THE STUDY WAS: Is primary Arterio-venous fistula the vascular access of choice for adequate dialysis and better patient outcome in end stage renal disease.', 'The present study was done in the department of cardiovascular and thoracic surgery at Sher-i-Kashmir institute of medical sciences, Soura, Srinagar Kashmir. Native Arterio-Venous (AV) fistulas were made in the patients with end stage renal disease for performing hemodialysis. They were followed for patency and adequacy of blood flow during hemodialysis. All the patients were operated under local anesthesia.', 'The results showed that 77% of the AV fistulas based on radial artery with side-to-side anastomosis and 80% of those with end-to-side anastomosis were functionally patent after one year. After two years, the patency rate in side-to-side and end-to-side anastomosis was 50% and 55%, respectively. In addition, the patency rate was 90% in brachial artery based AV fistula with end-to-side anastomosis, whether done primarily or secondarily, at the end of one year. However, a rapid decline was observed in the patency rate during the third year in both radial artery based and brachial artery based AV fistulas.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,745,590
Does renal excretion of fluoride after fluoride mouth rinse in children?
{ "contexts": [ "This study was conducted to determine if there was an increase in the urinary excretion of fluoride, after the use of fluoride mouth rinses in children.", "The sample consisted of 58 children aged 5-8 years, randomly selected, residents in non-fluoridated water areas. Urine samples were collected prior to mouthwash and also 2 hours after use. The control sample, which received no treatment, consisted of 16 children of equivalent age and from the same community. Urinary excretion of fluoride was analysed by determining the pH, creatinine, F- ion and fluoride (mg)/creatinine (g) (F/Cr) ratio in urine. Results In the studied sample, the mean F/Cr ratio before fluoride mouth rinse was 0.26 mg/g and it rose to 1.58 mg/g 2 hours after mouth rinse. This difference of 1.33 mg/g was statistically highly significant (p<.001). In the control group no significant changes occurred. The average 2 hours afterward F/Cr ratios were 0.29 and 0.27 respectively (p=0.426)." ], "labels": [ "OBJECTIVE", "METHODS" ], "meshes": [ "Cariostatic Agents", "Child", "Child, Preschool", "Creatinine", "Female", "Fluorides", "Follow-Up Studies", "Humans", "Hydrogen-Ion Concentration", "Ion-Selective Electrodes", "Male", "Mouthwashes", "Potentiometry" ] }
After the use of a fluoride mouthwash, in children, there is a statistically significant increase of fluoride ion in urine, which can be attributed to the application of this product.
yes
[ { "from": "human", "value": "Question: Does renal excretion of fluoride after fluoride mouth rinse in children?\nContext: {'contexts': ['This study was conducted to determine if there was an increase in the urinary excretion of fluoride, after the use of fluoride mouth rinses in children.', 'The sample consisted of 58 children aged 5-8 years, randomly selected, residents in non-fluoridated water areas. Urine samples were collected prior to mouthwash and also 2 hours after use. The control sample, which received no treatment, consisted of 16 children of equivalent age and from the same community. Urinary excretion of fluoride was analysed by determining the pH, creatinine, F- ion and fluoride (mg)/creatinine (g) (F/Cr) ratio in urine. Results In the studied sample, the mean F/Cr ratio before fluoride mouth rinse was 0.26 mg/g and it rose to 1.58 mg/g 2 hours after mouth rinse. This difference of 1.33 mg/g was statistically highly significant (p<.001). In the control group no significant changes occurred. The average 2 hours afterward F/Cr ratios were 0.29 and 0.27 respectively (p=0.426).'], 'labels': ['OBJECTIVE', 'METHODS'], 'meshes': ['Cariostatic Agents', 'Child', 'Child, Preschool', 'Creatinine', 'Female', 'Fluorides', 'Follow-Up Studies', 'Humans', 'Hydrogen-Ion Concentration', 'Ion-Selective Electrodes', 'Male', 'Mouthwashes', 'Potentiometry']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,771,535
Does pathologic heterogeneity persist in early active multiple sclerosis lesions?
{ "contexts": [ "Multiple sclerosis (MS) lesions demonstrate immunopathological heterogeneity in patterns of demyelination. Previous cross-sectional studies reported immunopatterns of demyelination were identical among multiple active demyelinating lesions from the same individual, but differed between individuals, leading to the hypothesis of intraindividual pathological homogeneity and interindividual heterogeneity. Other groups suggested a time-dependent heterogeneity of lesions. The objective of our present study was to analyze tissue samples collected longitudinally to determine whether patterns of demyelination persist over time within a given patient.", "Archival tissue samples derived from patients with pathologically confirmed central nervous system inflammatory demyelinating disease who had undergone either diagnostic serial biopsy or biopsy followed by autopsy were analyzed immunohistochemically. The inclusion criteria consisted of the presence of early active demyelinating lesions--required for immunopattern classification--obtained from the same patient at 2 or more time points.", "Among 1,321 surgical biopsies consistent with MS, 22 cases met the study inclusion criteria. Twenty-one patients (95%) showed a persistence of immunopathological patterns in tissue sampled from different time points. This persistence was demonstrated for all major patterns of demyelination. A single patient showed features suggestive of both pattern II and pattern III on biopsy, but only pattern II among all active lesions examined at autopsy." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adult", "Aged", "Cohort Studies", "Demyelinating Diseases", "Disease Progression", "Early Diagnosis", "Female", "Follow-Up Studies", "Humans", "Longitudinal Studies", "Male", "Middle Aged", "Multiple Sclerosis", "Retrospective Studies", "Young Adult" ] }
These findings continue to support the concept of patient-dependent immunopathological heterogeneity in early MS and suggest that the mechanisms and targets of tissue injury may differ among patient subgroups. These observations have potentially significant implications for individualized therapeutic approaches.
yes
[ { "from": "human", "value": "Question: Does pathologic heterogeneity persist in early active multiple sclerosis lesions?\nContext: {'contexts': ['Multiple sclerosis (MS) lesions demonstrate immunopathological heterogeneity in patterns of demyelination. Previous cross-sectional studies reported immunopatterns of demyelination were identical among multiple active demyelinating lesions from the same individual, but differed between individuals, leading to the hypothesis of intraindividual pathological homogeneity and interindividual heterogeneity. Other groups suggested a time-dependent heterogeneity of lesions. The objective of our present study was to analyze tissue samples collected longitudinally to determine whether patterns of demyelination persist over time within a given patient.', 'Archival tissue samples derived from patients with pathologically confirmed central nervous system inflammatory demyelinating disease who had undergone either diagnostic serial biopsy or biopsy followed by autopsy were analyzed immunohistochemically. The inclusion criteria consisted of the presence of early active demyelinating lesions--required for immunopattern classification--obtained from the same patient at 2 or more time points.', 'Among 1,321 surgical biopsies consistent with MS, 22 cases met the study inclusion criteria. Twenty-one patients (95%) showed a persistence of immunopathological patterns in tissue sampled from different time points. This persistence was demonstrated for all major patterns of demyelination. A single patient showed features suggestive of both pattern II and pattern III on biopsy, but only pattern II among all active lesions examined at autopsy.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Aged', 'Cohort Studies', 'Demyelinating Diseases', 'Disease Progression', 'Early Diagnosis', 'Female', 'Follow-Up Studies', 'Humans', 'Longitudinal Studies', 'Male', 'Middle Aged', 'Multiple Sclerosis', 'Retrospective Studies', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,771,538
Are progranulin protein levels differently regulated in plasma and CSF?
{ "contexts": [ "We aimed to investigate the relationship between plasma and CSF progranulin (PGRN) levels.", "Plasma and CSF PGRN were measured in a cohort of 345 subjects from the Mayo Clinic Study of Aging by ELISA. Single nucleotide polymorphism genotyping was performed using TaqMan assays. Associations between PGRN and sex, age at sample collection, diagnosis, single nucleotide polymorphism genotypes (GRN, SORT1, and APOE), and Pittsburgh compound B score were explored separately in CSF and plasma using single variable linear regression models. Pearson partial correlation coefficient was used to estimate the correlation of PGRN in CSF and plasma.", "Plasma (p = 0.0031) and CSF (p = 0.0044) PGRN significantly increased with age, whereas plasma PGRN levels were 7% lower (p = 0.0025) and CSF PGRN levels 5% higher (p = 0.0024) in male compared with female participants. Correcting for age and sex, higher plasma PGRN was associated with higher CSF PGRN (partial r = 0.17, p = 0.004). In plasma, both rs5848 (GRN; p = 0.002) and rs646776 (SORT1; p = 3.56E-7) were associated with PGRN, while only rs5848 showed highly significant association in CSF (p = 5.59E-14). Age, sex, rs5848 genotype, and plasma PGRN together accounted for only 18% of the variability observed in CSF PGRN." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Age Factors", "Aged", "Aged, 80 and over", "Female", "Genetic Association Studies", "Humans", "Intercellular Signaling Peptides and Proteins", "Male", "Polymorphism, Single Nucleotide", "Progranulins", "Sex Factors" ] }
While some correlation exists between plasma and CSF PGRN, age, sex, and genetic factors differently affect PGRN levels. Therefore, caution should be taken when using plasma PGRN to predict PGRN changes in the brain. These findings further highlight that plasma PGRN levels may not accurately predict clinical features or response to future frontotemporal lobar degeneration therapies.
yes
[ { "from": "human", "value": "Question: Are progranulin protein levels differently regulated in plasma and CSF?\nContext: {'contexts': ['We aimed to investigate the relationship between plasma and CSF progranulin (PGRN) levels.', 'Plasma and CSF PGRN were measured in a cohort of 345 subjects from the Mayo Clinic Study of Aging by ELISA. Single nucleotide polymorphism genotyping was performed using TaqMan assays. Associations between PGRN and sex, age at sample collection, diagnosis, single nucleotide polymorphism genotypes (GRN, SORT1, and APOE), and Pittsburgh compound B score were explored separately in CSF and plasma using single variable linear regression models. Pearson partial correlation coefficient was used to estimate the correlation of PGRN in CSF and plasma.', 'Plasma (p = 0.0031) and CSF (p = 0.0044) PGRN significantly increased with age, whereas plasma PGRN levels were 7% lower (p = 0.0025) and CSF PGRN levels 5% higher (p = 0.0024) in male compared with female participants. Correcting for age and sex, higher plasma PGRN was associated with higher CSF PGRN (partial r = 0.17, p = 0.004). In plasma, both rs5848 (GRN; p = 0.002) and rs646776 (SORT1; p = 3.56E-7) were associated with PGRN, while only rs5848 showed highly significant association in CSF (p = 5.59E-14). Age, sex, rs5848 genotype, and plasma PGRN together accounted for only 18% of the variability observed in CSF PGRN.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Age Factors', 'Aged', 'Aged, 80 and over', 'Female', 'Genetic Association Studies', 'Humans', 'Intercellular Signaling Peptides and Proteins', 'Male', 'Polymorphism, Single Nucleotide', 'Progranulins', 'Sex Factors']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,759,440
Does peer passenger influence on male adolescent drivers ' visual scanning behavior during simulated driving?
{ "contexts": [ "There is a higher likelihood of crashes and fatalities when an adolescent drives with peer passengers, especially for male drivers and male passengers. Simulated driving of male adolescent drivers with male peer passengers was studied to examine passenger influences on distraction and inattention.", "Male adolescents drove in a high-fidelity driving simulator with a male confederate who posed either as a risk-accepting passenger or as a risk-averse passenger. Drivers' eye movements were recorded. The visual scanning behavior of the drivers was compared when driving alone with when driving with a passenger and when driving with a risk-accepting passenger with a risk-averse passenger.", "The visual scanning of a driver significantly narrowed horizontally and vertically when driving with a peer passenger. There were no significant differences in the times the drivers' eyes were off the forward roadway when driving with a passenger versus when driving alone. Some significant correlations were found between personality characteristics and the outcome measures." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Accidents, Traffic", "Adolescent", "Adolescent Behavior", "Attention", "Automobile Driving", "Humans", "Male", "Peer Group", "Psychomotor Performance", "Risk Assessment", "Risk-Taking", "Social Behavior" ] }
The presence of a male peer passenger was associated with a reduction in the visual scanning range of male adolescent drivers. This reduction could be a result of potential cognitive load imposed on the driver due to the presence of a passenger and the real or perceived normative influences or expectations from the passenger.
yes
[ { "from": "human", "value": "Question: Does peer passenger influence on male adolescent drivers ' visual scanning behavior during simulated driving?\nContext: {'contexts': ['There is a higher likelihood of crashes and fatalities when an adolescent drives with peer passengers, especially for male drivers and male passengers. Simulated driving of male adolescent drivers with male peer passengers was studied to examine passenger influences on distraction and inattention.', \"Male adolescents drove in a high-fidelity driving simulator with a male confederate who posed either as a risk-accepting passenger or as a risk-averse passenger. Drivers' eye movements were recorded. The visual scanning behavior of the drivers was compared when driving alone with when driving with a passenger and when driving with a risk-accepting passenger with a risk-averse passenger.\", \"The visual scanning of a driver significantly narrowed horizontally and vertically when driving with a peer passenger. There were no significant differences in the times the drivers' eyes were off the forward roadway when driving with a passenger versus when driving alone. Some significant correlations were found between personality characteristics and the outcome measures.\"], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Accidents, Traffic', 'Adolescent', 'Adolescent Behavior', 'Attention', 'Automobile Driving', 'Humans', 'Male', 'Peer Group', 'Psychomotor Performance', 'Risk Assessment', 'Risk-Taking', 'Social Behavior']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,755,885
Is hAGE ( DDX43 ) a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer?
{ "contexts": [ "HAGE protein is a known immunogenic cancer-specific antigen.", "The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated.", "Eight percent of patients with EP-BC exhibited high HAGE expression (HAGE+) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGE+expression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+residual disease (P=0.0003)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Antineoplastic Agents, Hormonal", "Antineoplastic Combined Chemotherapy Protocols", "Biomarkers, Tumor", "Breast Neoplasms", "Carcinoma", "Combined Modality Therapy", "Cyclophosphamide", "DEAD-box RNA Helicases", "Drug Resistance, Neoplasm", "Female", "Fluorouracil", "Humans", "Kaplan-Meier Estimate", "Lymphocytes, Tumor-Infiltrating", "Mastectomy", "Menopause", "Methotrexate", "Mitotic Index", "Neoplasm Invasiveness", "Neoplasm Proteins", "Neoplasms, Hormone-Dependent", "Prognosis", "Proportional Hazards Models", "Receptor, ErbB-2", "Receptors, Estrogen", "Receptors, Progesterone", "Tamoxifen", "Treatment Outcome" ] }
This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC.
yes
[ { "from": "human", "value": "Question: Is hAGE ( DDX43 ) a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer?\nContext: {'contexts': ['HAGE protein is a known immunogenic cancer-specific antigen.', 'The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated.', 'Eight percent of patients with EP-BC exhibited high HAGE expression (HAGE+) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGE+expression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+residual disease (P=0.0003).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Antineoplastic Agents, Hormonal', 'Antineoplastic Combined Chemotherapy Protocols', 'Biomarkers, Tumor', 'Breast Neoplasms', 'Carcinoma', 'Combined Modality Therapy', 'Cyclophosphamide', 'DEAD-box RNA Helicases', 'Drug Resistance, Neoplasm', 'Female', 'Fluorouracil', 'Humans', 'Kaplan-Meier Estimate', 'Lymphocytes, Tumor-Infiltrating', 'Mastectomy', 'Menopause', 'Methotrexate', 'Mitotic Index', 'Neoplasm Invasiveness', 'Neoplasm Proteins', 'Neoplasms, Hormone-Dependent', 'Prognosis', 'Proportional Hazards Models', 'Receptor, ErbB-2', 'Receptors, Estrogen', 'Receptors, Progesterone', 'Tamoxifen', 'Treatment Outcome']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,751,148
Does intrathecal antagonism of microglial TLR4 reduce inflammatory damage to blood-spinal cord barrier following ischemia/reperfusion injury in rats?
{ "contexts": [ "Inflammatory reaction in blood-spinal cord barrier (BSCB) plays a crucial role in ischemia/reperfusion (I/R) injury. It has been shown that microglia could be activated through Toll-like receptors (TLRs). Therefore, we hypothesize that TLR4 is involved in the microglial activation and BSCB disruption after I/R.", "To verify our hypothesis, we analyzed the behavioral data, changes of BSCB permeability, as well as expressions of microglial marker Iba-1 and TLR4 in spinal cord I/R model induced by 14 min aortic occlusion. Double immunostaining reveals that after I/R, Iba-1 immunoreactivity increased gradually 12 h after reperfusion and maintained at a such level throughout 36 h. Such increasing pattern of Iba-1 expression is consistent with the increases in Evan's Blue (EB) extravasation, spinal water content and mechanical allodynia demonstrated by lowed withdrawal threshold to Von Frey filaments. Moreover, double immunostaining suggested that TLR4 was highly expressed in microglia. Intrathecal infusion of minocycline and TAK-242 (TLR4 inhibitor) treatment attenuated I/R-induced allodynia and BSCB leakage. In contrast, LPS induced TLR4 expression aggregated above-mentioned injuries. Furthermore, the nuclear factor-kappa B (NF-κB) activity has a similar profile as TLR4 activity. It is consisted with the results of NF-κB mRNA and protein expression changes and activation of downstream cytokine, IL-1β. Expectedly, intrathecal infusion of pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor, showed similar protective effects as minocycline and TAK-242. In addition, our data show that TLR4 closely involved in I/R-induced inflammatory damage induced neuronal apoptosis. Significantly, neutralizing TLR4 function largely reduced neuronal apoptosis determined by NeuN immunoreactivity in ventral gray matter and increased percentage of double-label cells with cleaved caspase3, whereas LPS reversed these effects. Similarly, inhibitions of microglia and NF-κB with minocycline or PDTC treatment accordingly perform the same protective effects on I/R injury." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Animals", "Calcium-Binding Proteins", "Inflammation", "Interleukin-1beta", "Male", "Microfilament Proteins", "Microglia", "NF-kappa B", "Neurons", "Permeability", "Protein Transport", "RNA, Messenger", "Rats", "Rats, Sprague-Dawley", "Reperfusion Injury", "Signal Transduction", "Spinal Cord", "Toll-Like Receptor 4" ] }
The results indicate that compromised BSCB caused by I/R injury lead to spinal microglial activation and TLR4, its membrane-bound receptor, up-regulation, which then initiate neuro-inflammation and neuro-apoptosis via NF-κB/ IL-1β pathway. To inhibit the positive feedback loop of TLR4-microglia-NF-κB/ IL-1β pathway by minocycline, TAK-242 (TLR4 inhibitor) and pyrrolidine dithiocarbamate (PDTC, NF-κB inhibitor) may provide new targets for treating I/R injury in clinic.
yes
[ { "from": "human", "value": "Question: Does intrathecal antagonism of microglial TLR4 reduce inflammatory damage to blood-spinal cord barrier following ischemia/reperfusion injury in rats?\nContext: {'contexts': ['Inflammatory reaction in blood-spinal cord barrier (BSCB) plays a crucial role in ischemia/reperfusion (I/R) injury. It has been shown that microglia could be activated through Toll-like receptors (TLRs). Therefore, we hypothesize that TLR4 is involved in the microglial activation and BSCB disruption after I/R.', \"To verify our hypothesis, we analyzed the behavioral data, changes of BSCB permeability, as well as expressions of microglial marker Iba-1 and TLR4 in spinal cord I/R model induced by 14\\xa0min aortic occlusion. Double immunostaining reveals that after I/R, Iba-1 immunoreactivity increased gradually 12\\xa0h after reperfusion and maintained at a such level throughout 36\\xa0h. Such increasing pattern of Iba-1 expression is consistent with the increases in Evan's Blue (EB) extravasation, spinal water content and mechanical allodynia demonstrated by lowed withdrawal threshold to Von Frey filaments. Moreover, double immunostaining suggested that TLR4 was highly expressed in microglia. Intrathecal infusion of minocycline and TAK-242 (TLR4 inhibitor) treatment attenuated I/R-induced allodynia and BSCB leakage. In contrast, LPS induced TLR4 expression aggregated above-mentioned injuries. Furthermore, the nuclear factor-kappa B (NF-κB) activity has a similar profile as TLR4 activity. It is consisted with the results of NF-κB mRNA and protein expression changes and activation of downstream cytokine, IL-1β. Expectedly, intrathecal infusion of pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor, showed similar protective effects as minocycline and TAK-242. In addition, our data show that TLR4 closely involved in I/R-induced inflammatory damage induced neuronal apoptosis. Significantly, neutralizing TLR4 function largely reduced neuronal apoptosis determined by NeuN immunoreactivity in ventral gray matter and increased percentage of double-label cells with cleaved caspase3, whereas LPS reversed these effects. Similarly, inhibitions of microglia and NF-κB with minocycline or PDTC treatment accordingly perform the same protective effects on I/R injury.\"], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Animals', 'Calcium-Binding Proteins', 'Inflammation', 'Interleukin-1beta', 'Male', 'Microfilament Proteins', 'Microglia', 'NF-kappa B', 'Neurons', 'Permeability', 'Protein Transport', 'RNA, Messenger', 'Rats', 'Rats, Sprague-Dawley', 'Reperfusion Injury', 'Signal Transduction', 'Spinal Cord', 'Toll-Like Receptor 4']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,752,402
Does clinical presentation and disease course of inflammatory bowel disease differ by race in a large tertiary care hospital?
{ "contexts": [ "While the incidence of inflammatory bowel disease (IBD) among African-Americans (AAs) is increasing, there is limited understanding of phenotypic differences and outcomes by race.", "To describe disease characteristics of AA patients compared to Caucasian (Ca) patients in a tertiary care population.", "We performed a cross-sectional review of the IBD registry at the University of Chicago from January 2008 to January 2013. Data regarding race, phenotype, disease onset, disease duration, medical therapy, and surgical treatment were abstracted from the database, then compared via Pearson's chi-square analysis, Kruskal-Wallis analysis, and logistic regression with a significance level of p < 0.05.", "A total of 1,235 patients with Crohn's disease (CD) and 541 patients with ulcerative colitis (UC) included 108 AA CD patients and 28 AA UC patients. AA CD patients had an increased rate of IBD-related arthralgias (36.5 vs. 23.9 %, p < 0.01) and surgery (p < 0.01), less ileal involvement (57.8 vs. 71.0 %, p < 0.01), and no differences for other extraintestinal manifestations or disease locations compared to Ca CD patients. AA UC patients were older at diagnosis, had an increased rate of arthralgias (28.6 vs. 14.6 %, p = 0.047) and ankylosing spondylitis/sacroiliitis (7.1 vs. 1.6 %, p = 0.035), with no differences for disease extent or rate of IBD-related surgeries compared to Ca UC patients. There were no differences in medication usage by race for CD and UC patients." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adult", "African Americans", "Age Factors", "Arthralgia", "Chicago", "Colitis, Ulcerative", "Crohn Disease", "Cross-Sectional Studies", "European Continental Ancestry Group", "Female", "Humans", "Ileal Diseases", "Male", "Middle Aged", "Phenotype", "Registries", "Sacroiliitis", "Severity of Illness Index", "Spondylitis, Ankylosing", "Tertiary Care Centers", "Young Adult" ] }
We identified significant differences in disease characteristics and extraintestinal manifestations between AA and Ca IBD patients in a large tertiary care population. These results have implications for future genotype-phenotype studies.
yes
[ { "from": "human", "value": "Question: Does clinical presentation and disease course of inflammatory bowel disease differ by race in a large tertiary care hospital?\nContext: {'contexts': ['While the incidence of inflammatory bowel disease (IBD) among African-Americans (AAs) is increasing, there is limited understanding of phenotypic differences and outcomes by race.', 'To describe disease characteristics of AA patients compared to Caucasian (Ca) patients in a tertiary care population.', \"We performed a cross-sectional review of the IBD registry at the University of Chicago from January 2008 to January 2013. Data regarding race, phenotype, disease onset, disease duration, medical therapy, and surgical treatment were abstracted from the database, then compared via Pearson's chi-square analysis, Kruskal-Wallis analysis, and logistic regression with a significance level of p < 0.05.\", \"A total of 1,235 patients with Crohn's disease (CD) and 541 patients with ulcerative colitis (UC) included 108 AA CD patients and 28 AA UC patients. AA CD patients had an increased rate of IBD-related arthralgias (36.5 vs. 23.9 %, p < 0.01) and surgery (p < 0.01), less ileal involvement (57.8 vs. 71.0 %, p < 0.01), and no differences for other extraintestinal manifestations or disease locations compared to Ca CD patients. AA UC patients were older at diagnosis, had an increased rate of arthralgias (28.6 vs. 14.6 %, p = 0.047) and ankylosing spondylitis/sacroiliitis (7.1 vs. 1.6 %, p = 0.035), with no differences for disease extent or rate of IBD-related surgeries compared to Ca UC patients. There were no differences in medication usage by race for CD and UC patients.\"], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'African Americans', 'Age Factors', 'Arthralgia', 'Chicago', 'Colitis, Ulcerative', 'Crohn Disease', 'Cross-Sectional Studies', 'European Continental Ancestry Group', 'Female', 'Humans', 'Ileal Diseases', 'Male', 'Middle Aged', 'Phenotype', 'Registries', 'Sacroiliitis', 'Severity of Illness Index', 'Spondylitis, Ankylosing', 'Tertiary Care Centers', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,763,440
Are withanolides potent novel targeted therapeutic agents against adrenocortical carcinomas?
{ "contexts": [ "Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with poor prognosis, as a majority of patients present with advanced disease. Current adjuvant strategies for metastatic patients include mitotane or other cytotoxic agents and carry a significant morbidity as well as a low (<10 %) 5-year survival. Withanolides, including withaferin A, are novel chemotherapeutic agents with potent targeted effects in medullary thyroid cancer and a number of solid malignancies with low toxicity in vivo. We hypothesize that novel naturally derived withanolides will have potent targeted anti-cancer activity against ACCs.", "In vitro cell viability of ACC cell lines (Y1 and SW13) was measured using MTS cell proliferation assay. Cell cycle and apoptotic analysis studied using annexin V/propidium iodide staining on flow cytometry (FC) and targeted molecular mechanisms of withanolide cytotoxicity were assessed using standard Western blot analysis.", "All the withanolides potently reduced ACC cell viability on MTS assay with 7- to 185-fold higher selectivity than normal fibroblasts. Cell cycle analysis demonstrated a shift in cell cycle arrest from G1/G0 to G2/M with induction of apoptosis at nanomolar concentrations of withanolides. Unlike current ACC therapeutics, withanolides modulated expression of several key oncogenic pathway proteins in ACCs by Western blot, including Jagged 1, MAPK, and Akt/mTOR pathway proteins in a dose-dependent manner after 24 h drug treatment of SW13 cells." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adrenal Gland Neoplasms", "Adrenocortical Carcinoma", "Apoptosis", "Cell Cycle", "Cell Proliferation", "Cell Survival", "Drug Delivery Systems", "Humans", "Sensitivity and Specificity", "Tumor Cells, Cultured", "Withanolides" ] }
These results demonstrate the first evidence of the anticancer efficacy of withanolides in ACC cells and provide support for future translational evaluation of these compounds as novel therapeutic agents for ACC patients.
yes
[ { "from": "human", "value": "Question: Are withanolides potent novel targeted therapeutic agents against adrenocortical carcinomas?\nContext: {'contexts': ['Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with poor prognosis, as a majority of patients present with advanced disease. Current adjuvant strategies for metastatic patients include mitotane or other cytotoxic agents and carry a significant morbidity as well as a low (<10 %) 5-year survival. Withanolides, including withaferin A, are novel chemotherapeutic agents with potent targeted effects in medullary thyroid cancer and a number of solid malignancies with low toxicity in vivo. We hypothesize that novel naturally derived withanolides will have potent targeted anti-cancer activity against ACCs.', 'In vitro cell viability of ACC cell lines (Y1 and SW13) was measured using MTS cell proliferation assay. Cell cycle and apoptotic analysis studied using annexin V/propidium iodide staining on flow cytometry (FC) and targeted molecular mechanisms of withanolide cytotoxicity were assessed using standard Western blot analysis.', 'All the withanolides potently reduced ACC cell viability on MTS assay with 7- to 185-fold higher selectivity than normal fibroblasts. Cell cycle analysis demonstrated a shift in cell cycle arrest from G1/G0 to G2/M with induction of apoptosis at nanomolar concentrations of withanolides. Unlike current ACC therapeutics, withanolides modulated expression of several key oncogenic pathway proteins in ACCs by Western blot, including Jagged 1, MAPK, and Akt/mTOR pathway proteins in a dose-dependent manner after 24 h drug treatment of SW13 cells.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adrenal Gland Neoplasms', 'Adrenocortical Carcinoma', 'Apoptosis', 'Cell Cycle', 'Cell Proliferation', 'Cell Survival', 'Drug Delivery Systems', 'Humans', 'Sensitivity and Specificity', 'Tumor Cells, Cultured', 'Withanolides']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,750,069
Do mesenchymal stem cells regulate airway contractile tissue remodeling in murine experimental asthma?
{ "contexts": [ "Mesenchymal stem cells may offer therapeutic potential for asthma due to their immunomodulatory properties and host tolerability, yet prior evidence suggests that bloodborne progenitor cells may participate in airway remodeling. Here, we tested whether mesenchymal stem cells administered as anti-inflammatory therapy may favor airway remodeling and therefore be detrimental.", "Adipose tissue-derived mesenchymal stem cells were retrovirally transduced to express green fluorescent protein and intravenously injected into mice with established experimental asthma induced by repeat intranasal house dust mite extract. Controls were house dust mite-instilled animals receiving intravenous vehicle or phosphate-buffered saline-instilled animals receiving mesenchymal stem cells. Data on lung function, airway inflammation, and remodeling were collected at 72 h after injection or after 2 weeks of additional intranasal challenge.", "The mesenchymal stem cells homed to the lungs and rapidly downregulated airway inflammation in association with raised T-helper-1 lung cytokines, but such effect declined under sustained allergen challenge despite a persistent presence of mesenchymal stem cells. Conversely, airway hyperresponsiveness and contractile tissue underwent a late reduction regardless of continuous pathogenic stimuli and inflammatory rebound. Tracking of green fluorescent protein did not show mesenchymal stem cell integration or differentiation in airway wall tissues." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Airway Remodeling", "Animals", "Asthma", "Bronchoalveolar Lavage Fluid", "Cell Movement", "Cytokines", "Disease Models, Animal", "Gene Expression", "Genes, Reporter", "Genetic Vectors", "Immunoglobulin E", "Mesenchymal Stem Cell Transplantation", "Mesenchymal Stem Cells", "Mice", "Retroviridae", "Transduction, Genetic" ] }
Therapeutic mesenchymal stem cell infusion in murine experimental asthma is free of unwanted pro-remodeling effects and ameliorates airway hyper-responsiveness and contractile tissue remodeling. These outcomes support furthering the development of mesenchymal stem cell-based asthma therapies, although caution and solid preclinical data building are warranted.
yes
[ { "from": "human", "value": "Question: Do mesenchymal stem cells regulate airway contractile tissue remodeling in murine experimental asthma?\nContext: {'contexts': ['Mesenchymal stem cells may offer therapeutic potential for asthma due to their immunomodulatory properties and host tolerability, yet prior evidence suggests that bloodborne progenitor cells may participate in airway remodeling. Here, we tested whether mesenchymal stem cells administered as anti-inflammatory therapy may favor airway remodeling and therefore be detrimental.', 'Adipose tissue-derived mesenchymal stem cells were retrovirally transduced to express green fluorescent protein and intravenously injected into mice with established experimental asthma induced by repeat intranasal house dust mite extract. Controls were house dust mite-instilled animals receiving intravenous vehicle or phosphate-buffered saline-instilled animals receiving mesenchymal stem cells. Data on lung function, airway inflammation, and remodeling were collected at 72 h after injection or after 2 weeks of additional intranasal challenge.', 'The mesenchymal stem cells homed to the lungs and rapidly downregulated airway inflammation in association with raised T-helper-1 lung cytokines, but such effect declined under sustained allergen challenge despite a persistent presence of mesenchymal stem cells. Conversely, airway hyperresponsiveness and contractile tissue underwent a late reduction regardless of continuous pathogenic stimuli and inflammatory rebound. Tracking of green fluorescent protein did not show mesenchymal stem cell integration or differentiation in airway wall tissues.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Airway Remodeling', 'Animals', 'Asthma', 'Bronchoalveolar Lavage Fluid', 'Cell Movement', 'Cytokines', 'Disease Models, Animal', 'Gene Expression', 'Genes, Reporter', 'Genetic Vectors', 'Immunoglobulin E', 'Mesenchymal Stem Cell Transplantation', 'Mesenchymal Stem Cells', 'Mice', 'Retroviridae', 'Transduction, Genetic']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,754,736
Is vEGF , VEGFR3 , and PDGFRB protein expression influenced by RAS mutations in medullary thyroid carcinoma?
{ "contexts": [ "Tyrosine kinase inhibitors (TKIs) have achieved remarkable clinical results in medullary thyroid carcinoma (MTC) patients. However, the considerable variability in patient response to treatment with TKIs remains largely unexplained. There is evidence that it could be due, at least in part, to alterations in genes associated with the disease via their effect on the expression of TKI targets. The objective of this study was to evaluate the influence of RAS mutations on the expression levels in MTC tumors of eight key TKI target proteins.", "We assessed by immunohistochemistry the expression of EGFR, KIT, MET, PDGFRB, VEGF, VEGFR1, VEGFR2, and VEGFR3 in a series of 84 primary MTC tumors that had previously been molecularly characterized, including 14 RAS-positive, 18 RET(M918T)-positive, and 24 RET(C634)-positive tumors, as well as 15 wild-type tumors with no mutations in the RET or RAS genes.", "In contrast to RET-positive tumors, RAS-positive tumors expressed neither PDGFRB nor MET (p=0.0060 and 0.047, respectively). Similarly, fewer RAS-positive than RET-related tumors expressed VEGFR3 (p=0.00062). Finally, wild-type tumors expressed VEGF more often than both RAS- and RET-positive tumors (p=0.0082 and 0.011, respectively)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Carcinoma, Neuroendocrine", "DNA Mutational Analysis", "Gene Expression Profiling", "Gene Expression Regulation, Neoplastic", "Humans", "Immunohistochemistry", "Mutation", "Proto-Oncogene Proteins c-ret", "Receptor, Platelet-Derived Growth Factor beta", "Thyroid Neoplasms", "Treatment Outcome", "Vascular Endothelial Growth Factor A", "Vascular Endothelial Growth Factor Receptor-3", "ras Proteins" ] }
This is the first study identifying that the expression of TKI targets differs according to the presence of RAS mutations in MTC. This information could potentially be used to select the most beneficial TKI treatment for these patients.
yes
[ { "from": "human", "value": "Question: Is vEGF , VEGFR3 , and PDGFRB protein expression influenced by RAS mutations in medullary thyroid carcinoma?\nContext: {'contexts': ['Tyrosine kinase inhibitors (TKIs) have achieved remarkable clinical results in medullary thyroid carcinoma (MTC) patients. However, the considerable variability in patient response to treatment with TKIs remains largely unexplained. There is evidence that it could be due, at least in part, to alterations in genes associated with the disease via their effect on the expression of TKI targets. The objective of this study was to evaluate the influence of RAS mutations on the expression levels in MTC tumors of eight key TKI target proteins.', 'We assessed by immunohistochemistry the expression of EGFR, KIT, MET, PDGFRB, VEGF, VEGFR1, VEGFR2, and VEGFR3 in a series of 84 primary MTC tumors that had previously been molecularly characterized, including 14 RAS-positive, 18 RET(M918T)-positive, and 24 RET(C634)-positive tumors, as well as 15 wild-type tumors with no mutations in the RET or RAS genes.', 'In contrast to RET-positive tumors, RAS-positive tumors expressed neither PDGFRB nor MET (p=0.0060 and 0.047, respectively). Similarly, fewer RAS-positive than RET-related tumors expressed VEGFR3 (p=0.00062). Finally, wild-type tumors expressed VEGF more often than both RAS- and RET-positive tumors (p=0.0082 and 0.011, respectively).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Carcinoma, Neuroendocrine', 'DNA Mutational Analysis', 'Gene Expression Profiling', 'Gene Expression Regulation, Neoplastic', 'Humans', 'Immunohistochemistry', 'Mutation', 'Proto-Oncogene Proteins c-ret', 'Receptor, Platelet-Derived Growth Factor beta', 'Thyroid Neoplasms', 'Treatment Outcome', 'Vascular Endothelial Growth Factor A', 'Vascular Endothelial Growth Factor Receptor-3', 'ras Proteins']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,750,276
Are adverse drug events a major cause of acute medical admission?
{ "contexts": [ "Adverse drug events (ADE) contribute significantly to hospital admissions. Prospective New Zealand data are scant, and the ability of clinical coding to identify ADE associated admissions is uncertain. Outcomes after cessation of causative medications are unknown.", "To assess the frequency, nature and causality of ADE associated with acute admissions to General Medicine at Christchurch Hospital.", "Prospective observational study of patients admitted to our medical team over 20 weeks.", "Of 336 admissions, 96 (28.6%) were ADE related. Sixty-five (19.3%) were caused by an ADE, and 31 (9.2%) were contributed to by an ADE. The mean age of non-ADE patients was 64.3 years (range 16-91), which was similar to the mean age of ADE patients (65.9 years; 21-92). However, if intentional overdoses and recreational drug use were excluded, ADE patients were significantly older at 72.4 years (21-92) (P = 0.0007). ADE patients took more regular medications on admission (mean 6.6, range 0-22) than non-ADE patients (mean 5.0, 0-18), (P = 0.003). The average length of stay was similar. The commonest medications implicated were vasodilators, psychotropics and diuretics. The most common adverse effects were postural hypotension and/or vasovagal syncope (29% of ADE), intentional overdoses and recreational drug use (15%) and acute renal failure and/or clinical dehydration (10%). Seventy-six patients had culprit medications stopped or reduced, and this potentially contributed to six readmissions. Coding identified 61% of ADE associated admissions." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adult", "Aged", "Aged, 80 and over", "Drug-Related Side Effects and Adverse Reactions", "Emergency Service, Hospital", "Female", "Follow-Up Studies", "Humans", "Hypotension, Orthostatic", "Male", "Middle Aged", "New Zealand", "Patient Admission", "Prospective Studies", "Syncope, Vasovagal", "Young Adult" ] }
ADE are a common cause of hospital admission. The most frequent problems are postural hypotension and vasovagal syncope, intentional drug misuse and dehydration.
yes
[ { "from": "human", "value": "Question: Are adverse drug events a major cause of acute medical admission?\nContext: {'contexts': ['Adverse drug events (ADE) contribute significantly to hospital admissions. Prospective New Zealand data are scant, and the ability of clinical coding to identify ADE associated admissions is uncertain. Outcomes after cessation of causative medications are unknown.', 'To assess the frequency, nature and causality of ADE associated with acute admissions to General Medicine at Christchurch Hospital.', 'Prospective observational study of patients admitted to our medical team over 20 weeks.', 'Of 336 admissions, 96 (28.6%) were ADE related. Sixty-five (19.3%) were caused by an ADE, and 31 (9.2%) were contributed to by an ADE. The mean age of non-ADE patients was 64.3 years (range 16-91), which was similar to the mean age of ADE patients (65.9 years; 21-92). However, if intentional overdoses and recreational drug use were excluded, ADE patients were significantly older at 72.4 years (21-92) (P = 0.0007). ADE patients took more regular medications on admission (mean 6.6, range 0-22) than non-ADE patients (mean 5.0, 0-18), (P = 0.003). The average length of stay was similar. The commonest medications implicated were vasodilators, psychotropics and diuretics. The most common adverse effects were postural hypotension and/or vasovagal syncope (29% of ADE), intentional overdoses and recreational drug use (15%) and acute renal failure and/or clinical dehydration (10%). Seventy-six patients had culprit medications stopped or reduced, and this potentially contributed to six readmissions. Coding identified 61% of ADE associated admissions.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Aged', 'Aged, 80 and over', 'Drug-Related Side Effects and Adverse Reactions', 'Emergency Service, Hospital', 'Female', 'Follow-Up Studies', 'Humans', 'Hypotension, Orthostatic', 'Male', 'Middle Aged', 'New Zealand', 'Patient Admission', 'Prospective Studies', 'Syncope, Vasovagal', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,766,689
Do clinical experience with 3-dimensional surface matching-based deep inspiration breath hold for left-sided breast cancer radiation therapy?
{ "contexts": [ "Three-dimensional (3D) surface matching is a novel method to administer deep inspiration breath-hold (DIBH) radiation therapy for left-sided breast cancer to reduce cardiac exposure. We analyzed port (x-ray) films to assess patient setup accuracy and treatment times to assess the practical workflow of this system.", "The data from 50 left-sided breast cancer patients treated with DIBH were studied. AlignRT (London, UK) was used. The distance between the field edge and the anterior pericardial shadow as seen on the routine port films (dPORT), and the corresponding distance seen on the digitally reconstructed radiographs (DRR) from the planning (dDRR) were compared as a quantitative measure of setup accuracy. Variations of dPORT - dDRR over the treatment course were assessed. In a subset of 21 patients treated with tangential beams alone, the daily treatment durations were analyzed to assess the practical workflow of this system.", "Considering all 50 patients, the mean absolute systematic uncertainty between dPORT and dDRR was 0.20 cm (range, 0 to 1.22 cm), the mean systematic uncertainty was -0.07 cm (range, -1.22 to 0.67 cm), and their mean random uncertainty was 0.19 cm (range, 0 to 0.84 cm). There was no significant change in dPORT - dDRR during the course of treatment. The mean patient treatment duration for the 21 patients studied was 11 minutes 48 seconds. On intrapatient assessments, 15/21 had nonsignificant trends toward reduced treatment durations during their course of therapy. On interpatient comparisons, the mean treatment times declined as we gained more experience with this technique." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Breast Neoplasms", "Breath Holding", "Female", "Humans", "Imaging, Three-Dimensional", "Inhalation", "Lung", "Radiotherapy Planning, Computer-Assisted", "Reproducibility of Results", "Tomography, X-Ray Computed" ] }
The DIBH patient setup appears to provide a fairly reproducible degree of cardiac sparing with random uncertainties of ≈ 0.2 cm. The treatment durations are clinically acceptable and appear not to change significantly over time on an intrapatient basis, and to improve over time on an interpatient basis.
yes
[ { "from": "human", "value": "Question: Do clinical experience with 3-dimensional surface matching-based deep inspiration breath hold for left-sided breast cancer radiation therapy?\nContext: {'contexts': ['Three-dimensional (3D) surface matching is a novel method to administer deep inspiration breath-hold (DIBH) radiation therapy for left-sided breast cancer to reduce cardiac exposure. We analyzed port (x-ray) films to assess patient setup accuracy and treatment times to assess the practical workflow of this system.', 'The data from 50 left-sided breast cancer patients treated with DIBH were studied. AlignRT (London, UK) was used. The distance between the field edge and the anterior pericardial shadow as seen on the routine port films (dPORT), and the corresponding distance seen on the digitally reconstructed radiographs (DRR) from the planning (dDRR) were compared as a quantitative measure of setup accuracy. Variations of dPORT - dDRR over the treatment course were assessed. In a subset of 21 patients treated with tangential beams alone, the daily treatment durations were analyzed to assess the practical workflow of this system.', 'Considering all 50 patients, the mean absolute systematic uncertainty between dPORT and dDRR was 0.20 cm (range, 0 to 1.22 cm), the mean systematic uncertainty was -0.07 cm (range, -1.22 to 0.67 cm), and their mean random uncertainty was 0.19 cm (range, 0 to 0.84 cm). There was no significant change in dPORT - dDRR during the course of treatment. The mean patient treatment duration for the 21 patients studied was 11 minutes 48 seconds. On intrapatient assessments, 15/21 had nonsignificant trends toward reduced treatment durations during their course of therapy. On interpatient comparisons, the mean treatment times declined as we gained more experience with this technique.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Breast Neoplasms', 'Breath Holding', 'Female', 'Humans', 'Imaging, Three-Dimensional', 'Inhalation', 'Lung', 'Radiotherapy Planning, Computer-Assisted', 'Reproducibility of Results', 'Tomography, X-Ray Computed']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,776,621
Is elevated serum androstenedione associated with a more severe phenotype in women with polycystic ovary syndrome ( PCOS )?
{ "contexts": [ "To evaluate the impact of elevated serum Δ4A levels on the hormonal and metabolic features of the different phenotypes of PCOS.", "1276 women with PCOS according to the Rotterdam criteria were included, in whom serum hormonal levels were determined.", "In PCOS women as a whole, as well as in patients presenting clinical and/or biochemical hyperandrogenemia (phenotypes I and II), Δ4A levels >3.8 ng/ml were positively related to LH, LH/FSH ratio, T, DHEAS, 17 OH progesterone and FAI and negatively related to T/Δ4A ratio. In the milder phenotype III, a positive correlation between Δ4A levels >3.8 ng/ml and T, DHEAS, 17 OH progesterone and FAI and a negative one between increased Δ4A and T/Δ4A ratio were reported. In the whole PCOS group with androstenedione >3.8 ng/ml, an increased ovarian volume was observed, while a greater mean follicular number was found only in phenotypes I and II." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Androstenedione", "Biomarkers", "Female", "Humans", "Hyperandrogenism", "Insulin Resistance", "Linear Models", "Multivariate Analysis", "Ovarian Follicle", "Phenotype", "Polycystic Ovary Syndrome", "Predictive Value of Tests", "Prognosis", "Severity of Illness Index", "Ultrasonography", "Up-Regulation" ] }
Increased serum Δ4A levels, which are associated with more severe PCOS phenotypes, possibly contribute to the worsening of PCOS features and therefore could be a valuable marker of biochemical hyperandrogenemia.
yes
[ { "from": "human", "value": "Question: Is elevated serum androstenedione associated with a more severe phenotype in women with polycystic ovary syndrome ( PCOS )?\nContext: {'contexts': ['To evaluate the impact of elevated serum Δ4A levels on the hormonal and metabolic features of the different phenotypes of PCOS.', '1276 women with PCOS according to the Rotterdam criteria were included, in whom serum hormonal levels were determined.', 'In PCOS women as a whole, as well as in patients presenting clinical and/or biochemical hyperandrogenemia (phenotypes I and II), Δ4A levels >3.8 ng/ml were positively related to LH, LH/FSH ratio, T, DHEAS, 17 OH progesterone and FAI and negatively related to T/Δ4A ratio. In the milder phenotype III, a positive correlation between Δ4A levels >3.8 ng/ml and T, DHEAS, 17 OH progesterone and FAI and a negative one between increased Δ4A and T/Δ4A ratio were reported. In the whole PCOS group with androstenedione >3.8 ng/ml, an increased ovarian volume was observed, while a greater mean follicular number was found only in phenotypes I and II.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Androstenedione', 'Biomarkers', 'Female', 'Humans', 'Hyperandrogenism', 'Insulin Resistance', 'Linear Models', 'Multivariate Analysis', 'Ovarian Follicle', 'Phenotype', 'Polycystic Ovary Syndrome', 'Predictive Value of Tests', 'Prognosis', 'Severity of Illness Index', 'Ultrasonography', 'Up-Regulation']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,748,189
Does [ Glycyrrhizin inhibit human neutrophil elastase-induced mucin 5AC overproduction in human bronchial epithelial cells ]?
{ "contexts": [ "To investigate the effect of glycyrrhizin (Gly) on human neutrophil elastase (HNE)- induced mucin (MUC) 5AC overproduction in human bronchial epithelial cells (16HBE), and the potential signaling pathway involved in this process.", "The cultured cells were divided into 3 groups: a control group, cultured in serum-free DMEM medium; an HNE group, pretreated with HNE alone; and a Gly group, incubated with HNE and Gly. After stimulation with a variety of Gly concentrations, the cytotoxicity was assessed by methyl thiazolyl tetrazolium method. The mRNA expressions of p38, nuclear factor κB (NF-κB) p65, inhibitory κBα (IκBα) and MUC5AC were detected by real-time PCR. The phosphorylation levels of p38 (p-p38), NF-κB p65 (p-NF-κB p65) and IκBα (p-IκBα) were measured by Western blot while the levels of MUC5AC protein were analyzed by emzyme-linked immunosorbent assay and immunofluorescence.", "Compared with the control group, the expression levels of MUC5AC mRNA and protein in the HNE group were both significantly increased. There was a significant increase in p-p38 and p-NF-κB p65, while the production of IκBα was much lower than that in the control group. Gly significantly inhibited the increase of MUC5AC, p38 and NF-κB p65, but increased the activity of IκBα." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Bronchi", "Cell Line", "Epithelial Cells", "Glycyrrhizic Acid", "Humans", "I-kappa B Proteins", "Leukocyte Elastase", "Mucin 5AC", "NF-KappaB Inhibitor alpha", "Phosphorylation", "Real-Time Polymerase Chain Reaction", "Signal Transduction", "Transcription Factor RelA", "p38 Mitogen-Activated Protein Kinases" ] }
Glycyrrhizin can inhibit MUC5AC overproduction via p38-NF-κB p65/IκBα signaling pathway.
yes
[ { "from": "human", "value": "Question: Does [ Glycyrrhizin inhibit human neutrophil elastase-induced mucin 5AC overproduction in human bronchial epithelial cells ]?\nContext: {'contexts': ['To investigate the effect of glycyrrhizin (Gly) on human neutrophil elastase (HNE)- induced mucin (MUC) 5AC overproduction in human bronchial epithelial cells (16HBE), and the potential signaling pathway involved in this process.', 'The cultured cells were divided into 3 groups: a control group, cultured in serum-free DMEM medium; an HNE group, pretreated with HNE alone; and a Gly group, incubated with HNE and Gly. After stimulation with a variety of Gly concentrations, the cytotoxicity was assessed by methyl thiazolyl tetrazolium method. The mRNA expressions of p38, nuclear factor κB (NF-κB) p65, inhibitory κBα (IκBα) and MUC5AC were detected by real-time PCR. The phosphorylation levels of p38 (p-p38), NF-κB p65 (p-NF-κB p65) and IκBα (p-IκBα) were measured by Western blot while the levels of MUC5AC protein were analyzed by emzyme-linked immunosorbent assay and immunofluorescence.', 'Compared with the control group, the expression levels of MUC5AC mRNA and protein in the HNE group were both significantly increased. There was a significant increase in p-p38 and p-NF-κB p65, while the production of IκBα was much lower than that in the control group. Gly significantly inhibited the increase of MUC5AC, p38 and NF-κB p65, but increased the activity of IκBα.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Bronchi', 'Cell Line', 'Epithelial Cells', 'Glycyrrhizic Acid', 'Humans', 'I-kappa B Proteins', 'Leukocyte Elastase', 'Mucin 5AC', 'NF-KappaB Inhibitor alpha', 'Phosphorylation', 'Real-Time Polymerase Chain Reaction', 'Signal Transduction', 'Transcription Factor RelA', 'p38 Mitogen-Activated Protein Kinases']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,756,916
Does laparoscopic hernia complexity predict operative time and length of stay?
{ "contexts": [ "Laparoscopic ventral hernia repair (LVHR) is associated with shorter hospitalization and lower complication rates compared to open ventral hernia repair. We sought to determine if hernia-related factors, such as defect size and re-operative status correlate with postoperative complications, operative times and length of stay (LOS).", "The study is a retrospective review of 30-day perioperative outcomes following LVHR in 91 patients who underwent surgery at a single institution from August 2009 through June 2012. A single surgeon performed all procedures.", "Indications for surgery were recurrent incisional hernia in 33 % of patients and primary incisional or ventral abdominal hernias in the rest. Coated polyester mesh with an average size of 348 cm(2) (±214; range 113-1,036) was used. Mean operative time was 132 min (±66.1; range 53-412). The mean LOS was 4.0 days (±3.5; range 1-22). Complications occurred in 13 patients for overall morbidity of 16.5 % and no mortality. There was one recurrence in 30 days (1.1 %). Patients who had a surgery >120 min or a LOS >1 day were statistically more likely to have multiple hernias, larger defect sizes (>40 cm(2)), larger mesh sizes (>300 cm(2)) or a history of recurrent hernia (P < 0.05). No other clinical or demographic variable evaluated in this study correlated with operative time or LOS." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Female", "Hernia, Ventral", "Herniorrhaphy", "Humans", "Laparoscopy", "Length of Stay", "Male", "Middle Aged", "Operative Time", "Polyesters", "Polyethylene Terephthalates", "Postoperative Complications", "Recurrence", "Reoperation", "Retrospective Studies", "Surgical Mesh", "Wisconsin" ] }
LVHR is safe with a low incidence of perioperative complications. Patients with multiple, larger and recurrent hernias have longer operative times and LOS. This information can be used to guide preoperative planning for the patient, surgeon and treating institution.
yes
[ { "from": "human", "value": "Question: Does laparoscopic hernia complexity predict operative time and length of stay?\nContext: {'contexts': ['Laparoscopic ventral hernia repair (LVHR) is associated with shorter hospitalization and lower complication rates compared to open ventral hernia repair. We sought to determine if hernia-related factors, such as defect size and re-operative status correlate with postoperative complications, operative times and length of stay (LOS).', 'The study is a retrospective review of 30-day perioperative outcomes following LVHR in 91 patients who underwent surgery at a single institution from August 2009 through June 2012. A single surgeon performed all procedures.', 'Indications for surgery were recurrent incisional hernia in 33\\xa0% of patients and primary incisional or ventral abdominal hernias in the rest. Coated polyester mesh with an average size of 348\\xa0cm(2) (±214; range 113-1,036) was used. Mean operative time was 132\\xa0min (±66.1; range 53-412). The mean LOS was 4.0\\xa0days (±3.5; range 1-22). Complications occurred in 13 patients for overall morbidity of 16.5\\xa0% and no mortality. There was one recurrence in 30\\xa0days (1.1\\xa0%). Patients who had a surgery >120\\xa0min or a LOS >1\\xa0day were statistically more likely to have multiple hernias, larger defect sizes (>40\\xa0cm(2)), larger mesh sizes (>300\\xa0cm(2)) or a history of recurrent hernia (P\\xa0<\\xa00.05). No other clinical or demographic variable evaluated in this study correlated with operative time or LOS.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Female', 'Hernia, Ventral', 'Herniorrhaphy', 'Humans', 'Laparoscopy', 'Length of Stay', 'Male', 'Middle Aged', 'Operative Time', 'Polyesters', 'Polyethylene Terephthalates', 'Postoperative Complications', 'Recurrence', 'Reoperation', 'Retrospective Studies', 'Surgical Mesh', 'Wisconsin']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,767,568
Do bioactive chitosan nanoparticles and photodynamic therapy inhibit collagen degradation in vitro?
{ "contexts": [ "Collagen is the major structural protein of human dentin. Degradation of collagen by bacterial enzymes can facilitate microbial penetration, compromise structural/interfacial integrity, and lower resistance to fracture of dentin. We evaluated the ability of photodynamic therapy (PDT), bioactive chitosan nanoparticles (CSnp), or PDT in combination with CSnp to inhibit bacterial collagenase-mediated degradation of collagen.", "Rat type 1 fibrillar collagen matrices were untreated or treated with 2.5% glutaraldehyde (GD), 2.5% GD followed by 1% CSnp, 1% CSnp, PDT (rose bengal activated with 540 nm light at 40 J/cm(2)), or 1% CSnp followed by PDT. Samples, except those used as untreated controls, were exposed to Clostridium histolyticum collagenase (125 CDU/mL) for 24 hours. The soluble digestion products were assessed by hydroxyproline assay, and the remaining adherent collagen was quantified by picrosirius red staining. Fourier transform infrared spectroscopy, immunoblotting, and scanning electron microscopy were used to study the interaction between CSnp/PDT with type 1 collagen. The data were analyzed by 1-way analysis of variance and post hoc Tukey test.", "As assessed by hydroxyproline release into the medium, collagen treated with CSnp, PDT, or a combination of CSnp and PDT exhibited less degradation than untreated controls (3.6-fold, 1.7-fold, and 7.9-fold reduction, respectively; P < .05). Compared with all other treatments, GD-treated collagen was the most resistant to collagenolytic degradation (239.6-fold reduction, P < .05). The abundance of post-treatment residual collagen, as measured by picrosirius red staining, was inversely related to the extent of collagen degradation. Analysis of collagen cross-links with Fourier transform infrared spectroscopy showed that PDT or GD treatments enhanced collagen cross-linking. Immunoblotting of sedimented CSnp indicated that CSnp and collagenase bound with low affinity. However, CSnp-bound collagenase showed a significant reduction in collagenolytic activity compared with controls (P < .05)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Azo Compounds", "Biocompatible Materials", "Chitosan", "Collagen", "Collagen Type I", "Coloring Agents", "Cross-Linking Reagents", "Glutaral", "Hydroxyproline", "Immunoblotting", "Matrix Metalloproteinase Inhibitors", "Microbial Collagenase", "Microscopy, Electron, Scanning", "Nanoparticles", "Photochemotherapy", "Rats", "Spectroscopy, Fourier Transform Infrared" ] }
Combined photochemical cross-linking of rat tail collagen by PDT and binding to CSnp inhibit collagenolytic activity.
yes
[ { "from": "human", "value": "Question: Do bioactive chitosan nanoparticles and photodynamic therapy inhibit collagen degradation in vitro?\nContext: {'contexts': ['Collagen is the major structural protein of human dentin. Degradation of collagen by bacterial enzymes can facilitate microbial penetration, compromise structural/interfacial integrity, and lower resistance to fracture of dentin. We evaluated the ability of photodynamic therapy (PDT), bioactive chitosan nanoparticles (CSnp), or PDT in combination with CSnp to inhibit bacterial collagenase-mediated degradation of collagen.', 'Rat type 1 fibrillar collagen matrices were untreated or treated with 2.5% glutaraldehyde (GD), 2.5% GD followed by 1% CSnp, 1% CSnp, PDT (rose bengal activated with 540 nm light at 40 J/cm(2)), or 1% CSnp followed by PDT. Samples, except those used as untreated controls, were exposed to Clostridium histolyticum collagenase (125 CDU/mL) for 24 hours. The soluble digestion products were assessed by hydroxyproline assay, and the remaining adherent collagen was quantified by picrosirius red staining. Fourier transform infrared spectroscopy, immunoblotting, and scanning electron microscopy were used to study the interaction between CSnp/PDT with type 1 collagen. The data were analyzed by 1-way analysis of variance and post hoc Tukey test.', 'As assessed by hydroxyproline release into the medium, collagen treated with CSnp, PDT, or a combination of CSnp and PDT exhibited less degradation than untreated controls (3.6-fold, 1.7-fold, and 7.9-fold reduction, respectively; P < .05). Compared with all other treatments, GD-treated collagen was the most resistant to collagenolytic degradation (239.6-fold reduction, P < .05). The abundance of post-treatment residual collagen, as measured by picrosirius red staining, was inversely related to the extent of collagen degradation. Analysis of collagen cross-links with Fourier transform infrared spectroscopy showed that PDT or GD treatments enhanced collagen cross-linking. Immunoblotting of sedimented CSnp indicated that CSnp and collagenase bound with low affinity. However, CSnp-bound collagenase showed a significant reduction in collagenolytic activity compared with controls (P < .05).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Azo Compounds', 'Biocompatible Materials', 'Chitosan', 'Collagen', 'Collagen Type I', 'Coloring Agents', 'Cross-Linking Reagents', 'Glutaral', 'Hydroxyproline', 'Immunoblotting', 'Matrix Metalloproteinase Inhibitors', 'Microbial Collagenase', 'Microscopy, Electron, Scanning', 'Nanoparticles', 'Photochemotherapy', 'Rats', 'Spectroscopy, Fourier Transform Infrared']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,776,785
Is acquisition of conditioned eyeblink responses modulated by cerebellar tDCS?
{ "contexts": [ "Classical conditioning of the eyeblink reflex is a simple form of motor learning which depends on the integrity of the cerebellum. Acquisition of conditioned eyeblink responses is markedly reduced in patients with cerebellar disorders. Noninvasive transcranial direct current stimulation (tDCS) has been reported to modify the excitability of the cerebellar cortex.", "The aim of the study was to assess whether acquisition of conditioned eyeblink responses (CR) is altered by cerebellar tDCS.", "A standard delay conditioning paradigm with a 540 ms tone as conditioned stimulus (CS) coterminating with a 100 ms air puff as unconditioned stimulus (US) was used in a total of 30 healthy subjects (18 female, 12 male, mean age 23.4 ± 1.9 years). One hundred paired CS-US trials and 30 extinction CS alone trials were given. tDCS (2 mA intensity, ramp like onset) was applied over the right cerebellar hemisphere ipsilaterally to the US during the acquisition phase. Subjects were randomly assigned to three groups (n = 10) using anodal, cathodal or sham stimulation. The investigator as well as the participants was blinded to the stimulation modality.", "CR acquisition was significantly enhanced by anodal tDCS (mean total CR incidence 73.4 ± 25.2%) and significantly reduced by cathodal stimulation (12.6 ± 17.2%) compared to sham stimulation (43.8 ± 24.1%). During anodal tDCS CR onset occurred significantly earlier, that is mean onset of responses was shifted closer to CS onset." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Blinking", "Cerebellum", "Conditioning, Classical", "Conditioning, Eyelid", "Extinction, Psychological", "Female", "Humans", "Male", "Time Factors", "Transcranial Direct Current Stimulation", "Young Adult" ] }
Acquisition and timing of conditioned eyeblink responses is modified by cerebellar tDCS in a polarity dependent manner.
yes
[ { "from": "human", "value": "Question: Is acquisition of conditioned eyeblink responses modulated by cerebellar tDCS?\nContext: {'contexts': ['Classical conditioning of the eyeblink reflex is a simple form of motor learning which depends on the integrity of the cerebellum. Acquisition of conditioned eyeblink responses is markedly reduced in patients with cerebellar disorders. Noninvasive transcranial direct current stimulation (tDCS) has been reported to modify the excitability of the cerebellar cortex.', 'The aim of the study was to assess whether acquisition of conditioned eyeblink responses (CR) is altered by cerebellar tDCS.', 'A standard delay conditioning paradigm with a 540 ms tone as conditioned stimulus (CS) coterminating with a 100 ms air puff as unconditioned stimulus (US) was used in a total of 30 healthy subjects (18 female, 12 male, mean age 23.4 ± 1.9 years). One hundred paired CS-US trials and 30 extinction CS alone trials were given. tDCS (2 mA intensity, ramp like onset) was applied over the right cerebellar hemisphere ipsilaterally to the US during the acquisition phase. Subjects were randomly assigned to three groups (n = 10) using anodal, cathodal or sham stimulation. The investigator as well as the participants was blinded to the stimulation modality.', 'CR acquisition was significantly enhanced by anodal tDCS (mean total CR incidence 73.4 ± 25.2%) and significantly reduced by cathodal stimulation (12.6 ± 17.2%) compared to sham stimulation (43.8 ± 24.1%). During anodal tDCS CR onset occurred significantly earlier, that is mean onset of responses was shifted closer to CS onset.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Blinking', 'Cerebellum', 'Conditioning, Classical', 'Conditioning, Eyelid', 'Extinction, Psychological', 'Female', 'Humans', 'Male', 'Time Factors', 'Transcranial Direct Current Stimulation', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,769,603
Does lung cancer stigma predict timing of medical help-seeking behavior?
{ "contexts": [ "To examine relationships among demographic variables, healthcare system distrust, lung cancer stigma, smoking status, and timing of medical help-seeking behavior in individuals with symptoms suggestive of lung cancer after controlling for ethnicity, socioeconomic status, and social desirability.", "Descriptive, cross-sectional, correlational study.", "Outpatient oncology clinics in Louisville, KY.", "94 patients diagnosed in the past three weeks to six years with all stages of lung cancer.", "Self-report, written survey packets were administered in person followed by a semistructured interview to assess symptoms and timing characteristics of practice-identified patients with lung cancer.", "Timing of medical help-seeking behavior, healthcare system distrust, lung cancer stigma, and smoking status.", "Lung cancer stigma was independently associated with timing of medical help-seeking behavior in patients with lung cancer. Healthcare system distrust and smoking status were not independently associated with timing of medical help-seeking behavior." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "METHODS", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Attitude to Health", "Cross-Sectional Studies", "Decision Making", "Female", "Humans", "Kentucky", "Lung Neoplasms", "Male", "Middle Aged", "Oncology Service, Hospital", "Patient Acceptance of Health Care", "Smoking", "Social Stigma", "Socioeconomic Factors", "Statistics as Topic", "Time Factors" ] }
FINDINGS suggest that stigma influences medical help-seeking behavior for lung cancer symptoms, serving as a barrier to prompt medical help-seeking behavior.
yes
[ { "from": "human", "value": "Question: Does lung cancer stigma predict timing of medical help-seeking behavior?\nContext: {'contexts': ['To examine relationships among demographic variables, healthcare system distrust, lung cancer stigma, smoking status, and timing of medical help-seeking behavior in individuals with symptoms suggestive of lung cancer after controlling for ethnicity, socioeconomic status, and social desirability.', 'Descriptive, cross-sectional, correlational study.', 'Outpatient oncology clinics in Louisville, KY.', '94 patients diagnosed in the past three weeks to six years with all stages of lung cancer.', 'Self-report, written survey packets were administered in person followed by a semistructured interview to assess symptoms and timing characteristics of practice-identified patients with lung cancer.', 'Timing of medical help-seeking behavior, healthcare system distrust, lung cancer stigma, and smoking status.', 'Lung cancer stigma was independently associated with timing of medical help-seeking behavior in patients with lung cancer. Healthcare system distrust and smoking status were not independently associated with timing of medical help-seeking behavior.'], 'labels': ['OBJECTIVE', 'METHODS', 'METHODS', 'METHODS', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Attitude to Health', 'Cross-Sectional Studies', 'Decision Making', 'Female', 'Humans', 'Kentucky', 'Lung Neoplasms', 'Male', 'Middle Aged', 'Oncology Service, Hospital', 'Patient Acceptance of Health Care', 'Smoking', 'Social Stigma', 'Socioeconomic Factors', 'Statistics as Topic', 'Time Factors']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,747,515
Does polymerase I and transcript release factor act as an essential modulator of glioblastoma chemoresistance?
{ "contexts": [ "This study is to investigate if polymerase I and transcript release factor (PTRF) acts as a modulator in glioblastoma (GBM) chemoresistance.", "Multidrug resistant (MDR) GBM cell line U251AR was established by exposing the U251 cell line to imatinib. The 2D-DIGE and MALDI-TOF/TOF-MS were performed on U251 and U251AR cell lines to screen MDR-related proteins. The expression of PTRF was determined by Western blot and quantitative RT-PCR analyses.", "When compared with the parental U251 cells, expression of 21 proteins was significantly altered in U251AR cells. Among the 21 differentially expressed proteins, the expression of PTRF was up-regulated by 2.14 folds in U251AR cells when compared with that in the parental U251 cells. Knockdown of PTRF in GBM cell lines significantly increased chemosensitivity of cells to various chemical drugs and decreased the expression levels of caveolin1, a major structural component of caveolae. Expression levels of PTRF and caveolin1 were significantly up-regulated in the relapsed GBM patients. The mRNA level of PTRF and caveolin1 showed a positive correlation in the same GBM specimens." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Benzamides", "Caveolin 1", "Cell Line, Tumor", "Drug Resistance, Neoplasm", "Gene Expression Regulation, Neoplastic", "Gene Knockdown Techniques", "Glioblastoma", "Humans", "Imatinib Mesylate", "Piperazines", "Proteomics", "Pyrimidines", "RNA-Binding Proteins", "Recurrence" ] }
Our results indicate that PTRF acts as a modulator in GBM chemoresistance.
yes
[ { "from": "human", "value": "Question: Does polymerase I and transcript release factor act as an essential modulator of glioblastoma chemoresistance?\nContext: {'contexts': ['This study is to investigate if polymerase I and transcript release factor (PTRF) acts as a modulator in glioblastoma (GBM) chemoresistance.', 'Multidrug resistant (MDR) GBM cell line U251AR was established by exposing the U251 cell line to imatinib. The 2D-DIGE and MALDI-TOF/TOF-MS were performed on U251 and U251AR cell lines to screen MDR-related proteins. The expression of PTRF was determined by Western blot and quantitative RT-PCR analyses.', 'When compared with the parental U251 cells, expression of 21 proteins was significantly altered in U251AR cells. Among the 21 differentially expressed proteins, the expression of PTRF was up-regulated by 2.14 folds in U251AR cells when compared with that in the parental U251 cells. Knockdown of PTRF in GBM cell lines significantly increased chemosensitivity of cells to various chemical drugs and decreased the expression levels of caveolin1, a major structural component of caveolae. Expression levels of PTRF and caveolin1 were significantly up-regulated in the relapsed GBM patients. The mRNA level of PTRF and caveolin1 showed a positive correlation in the same GBM specimens.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Benzamides', 'Caveolin 1', 'Cell Line, Tumor', 'Drug Resistance, Neoplasm', 'Gene Expression Regulation, Neoplastic', 'Gene Knockdown Techniques', 'Glioblastoma', 'Humans', 'Imatinib Mesylate', 'Piperazines', 'Proteomics', 'Pyrimidines', 'RNA-Binding Proteins', 'Recurrence']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,760,264
Is complement factor 3 associated with insulin resistance and with incident type 2 diabetes over a 7-year follow-up period : the CODAM Study?
{ "contexts": [ "Immune dysregulation can affect insulin resistance (IR) and β-cell function and hence contribute to development of type 2 diabetes mellitus (T2DM). The complement system, as a regulator of immune and inflammatory homeostasis, may be a relevant contributor therein. However, longitudinal studies focusing on complement as a determinant of T2DM and IR are scarce. Therefore, we prospectively investigated the association of plasma complement factor 3 (C3) with (estimates of) IR in muscle, liver, and adipocytes, as well as with glucose tolerance, including incident T2DM.", "Fasting C3, nonesterified fatty acids, glucose, and insulin (the latter two during oral glucose tolerance tests) were measured at baseline (n = 545) and after 7 years of follow-up (n = 394) in a prospective cohort study.", "Over the 7-year period, C3 levels (per 0.1 g/L) were longitudinally associated with higher homeostasis model assessment of IR (HOMA2-IR; β = 15.2% [95% CI 12.9-17.6]), hepatic IR (β = 6.1% [95% CI 4.7-7.4]), adipocyte IR (β = 16.0% [95% CI 13.0-19.1]), fasting glucose (β = 1.8% [95% CI 1.2-2.4]), 2-h glucose (β = 5.2% [95% CI 3.7-6.7]), and area under the curve for glucose (β = 3.6% [95% CI 2.7-4.6]). In addition, greater changes in C3 (per 0.1 g/L) were associated with greater changes in HOMA2-IR (β = 0.08 [95% CI 0.02-0.15]) and greater changes in hepatic IR (β = 0.87 [95% CI 0.12-1.61]) over 7 years, but not glucose tolerance. Moreover, baseline C3 was associated with the 7-year incidence of T2DM (odds ratio 1.5 [95% CI 1.1-2.0])." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adipocytes", "Aged", "Blood Glucose", "Cohort Studies", "Complement C3", "Diabetes Mellitus, Type 2", "Fasting", "Fatty Acids, Nonesterified", "Female", "Follow-Up Studies", "Glucose Tolerance Test", "Homeostasis", "Humans", "Insulin", "Insulin Resistance", "Insulin-Secreting Cells", "Longitudinal Studies", "Male", "Middle Aged", "Prospective Studies" ] }
Changes in C3 were associated with changes in several measures of IR and may reflect progression of metabolic dysregulation, which eventually leads to abnormalities in glucose tolerance and T2DM.
yes
[ { "from": "human", "value": "Question: Is complement factor 3 associated with insulin resistance and with incident type 2 diabetes over a 7-year follow-up period : the CODAM Study?\nContext: {'contexts': ['Immune dysregulation can affect insulin resistance (IR) and β-cell function and hence contribute to development of type 2 diabetes mellitus (T2DM). The complement system, as a regulator of immune and inflammatory homeostasis, may be a relevant contributor therein. However, longitudinal studies focusing on complement as a determinant of T2DM and IR are scarce. Therefore, we prospectively investigated the association of plasma complement factor 3 (C3) with (estimates of) IR in muscle, liver, and adipocytes, as well as with glucose tolerance, including incident T2DM.', 'Fasting C3, nonesterified fatty acids, glucose, and insulin (the latter two during oral glucose tolerance tests) were measured at baseline (n = 545) and after 7 years of follow-up (n = 394) in a prospective cohort study.', 'Over the 7-year period, C3 levels (per 0.1 g/L) were longitudinally associated with higher homeostasis model assessment of IR (HOMA2-IR; β = 15.2% [95% CI 12.9-17.6]), hepatic IR (β = 6.1% [95% CI 4.7-7.4]), adipocyte IR (β = 16.0% [95% CI 13.0-19.1]), fasting glucose (β = 1.8% [95% CI 1.2-2.4]), 2-h glucose (β = 5.2% [95% CI 3.7-6.7]), and area under the curve for glucose (β = 3.6% [95% CI 2.7-4.6]). In addition, greater changes in C3 (per 0.1 g/L) were associated with greater changes in HOMA2-IR (β = 0.08 [95% CI 0.02-0.15]) and greater changes in hepatic IR (β = 0.87 [95% CI 0.12-1.61]) over 7 years, but not glucose tolerance. Moreover, baseline C3 was associated with the 7-year incidence of T2DM (odds ratio 1.5 [95% CI 1.1-2.0]).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adipocytes', 'Aged', 'Blood Glucose', 'Cohort Studies', 'Complement C3', 'Diabetes Mellitus, Type 2', 'Fasting', 'Fatty Acids, Nonesterified', 'Female', 'Follow-Up Studies', 'Glucose Tolerance Test', 'Homeostasis', 'Humans', 'Insulin', 'Insulin Resistance', 'Insulin-Secreting Cells', 'Longitudinal Studies', 'Male', 'Middle Aged', 'Prospective Studies']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,777,944
Do rapid chemical characterisation of stilbenes in the root bark of Norway spruce by off-line HPLC/DAD-NMR?
{ "contexts": [ "Stilbenes are plant secondary metabolites that have shown promising and varied biological activities. Stilbenes are presently actively studied for the exploitation of this primary raw material resource, involving the concept of biorefining. Methods for the rapid discovery of new and known stilbene structures from various plant sources are thus keenly sought.", "To establish a simple and rapid technique of off-line HPLC with a diode-array detector (DAD) and NMR for the unambiguous structural elucidation of stilbene structures in the root bark of Norway spruce [Picea abies (L.) Karst.].", "The stilbene containing fraction was extracted from the plant bark with an ethanol:water mixture (95:5, v/v) preceded by defatting of hydrophobic compounds with n-hexane using the accelerated solvent extraction technique. A portion of the ethanol-water soluble extract was hydrolysed with β-glucosidase to prepare stilbene aglycones. The extracts were further purified and enriched using a polymeric adsorbent. Stilbene-enriched extracts were directly characterised by off-line HPLC/DAD-NMR in conjunction with HPLC/DAD and HPLC/DAD with electrospray ionisation MS(n).", "Trans-isorhapontin and trans-astringin were identified as the major, and trans-piceid as a minor, stilbene glucosides of the bark of roots of Picea abies. Not only stilbene glucosides but also the corresponding stilbene aglycones, such as trans-resveratrol, trans-piceatannol and trans-isorhapontigenin, were rapidly identified from the hydrolysed extract. The acquired heteronuclear single-quantum coherence and heteronuclear multiple bond correlation spectra were used to assign the complete carbon NMR chemical shifts of trans-isorhapontin and trans-astringin without the need of acquiring a (13)C-NMR spectrum." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Chromatography, High Pressure Liquid", "Glucosides", "Magnetic Resonance Spectroscopy", "Picea", "Plant Bark", "Plant Extracts", "Plant Roots", "Spectrometry, Mass, Electrospray Ionization", "Stilbenes" ] }
The off-line HPLC/DAD-NMR method is expedient for the unambiguous identication of structurally similar stilbenes in plant extracts.
yes
[ { "from": "human", "value": "Question: Do rapid chemical characterisation of stilbenes in the root bark of Norway spruce by off-line HPLC/DAD-NMR?\nContext: {'contexts': ['Stilbenes are plant secondary metabolites that have shown promising and varied biological activities. Stilbenes are presently actively studied for the exploitation of this primary raw material resource, involving the concept of biorefining. Methods for the rapid discovery of new and known stilbene structures from various plant sources are thus keenly sought.', 'To establish a simple and rapid technique of off-line HPLC with a diode-array detector (DAD) and NMR for the unambiguous structural elucidation of stilbene structures in the root bark of Norway spruce [Picea abies (L.) Karst.].', 'The stilbene containing fraction was extracted from the plant bark with an ethanol:water mixture (95:5, v/v) preceded by defatting of hydrophobic compounds with n-hexane using the accelerated solvent extraction technique. A portion of the ethanol-water soluble extract was hydrolysed with β-glucosidase to prepare stilbene aglycones. The extracts were further purified and enriched using a polymeric adsorbent. Stilbene-enriched extracts were directly characterised by off-line HPLC/DAD-NMR in conjunction with HPLC/DAD and HPLC/DAD with electrospray ionisation MS(n).', 'Trans-isorhapontin and trans-astringin were identified as the major, and trans-piceid as a minor, stilbene glucosides of the bark of roots of Picea abies. Not only stilbene glucosides but also the corresponding stilbene aglycones, such as trans-resveratrol, trans-piceatannol and trans-isorhapontigenin, were rapidly identified from the hydrolysed extract. The acquired heteronuclear single-quantum coherence and heteronuclear multiple bond correlation spectra were used to assign the complete carbon NMR chemical shifts of trans-isorhapontin and trans-astringin without the need of acquiring a (13)C-NMR spectrum.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Chromatography, High Pressure Liquid', 'Glucosides', 'Magnetic Resonance Spectroscopy', 'Picea', 'Plant Bark', 'Plant Extracts', 'Plant Roots', 'Spectrometry, Mass, Electrospray Ionization', 'Stilbenes']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,775,269
Is self-reported depression increasing among socio-economically disadvantaged adolescents - repeated cross-sectional surveys from Finland from 2000 to 2011?
{ "contexts": [ "Adolescent depression is more common in lower socio-economic groups. Whether this pattern has changed over time, is not known.We examined the prevalence of self-reported depression and its changes in socio-economic groups from 2000 to 2011 among Finnish adolescents.", "Data were based on classroom surveys every second year from 2000-2001 to 2010-2011 using nationwide samples of 14-16-year old Finns (n = 618,084). Data were collected using self-administered questionnaires including questions on health, health behaviours, and school experiences. Depression was measured with a Finnish modification of the 13-item Beck Depression Inventory, and divided into no, mild, moderate and severe depression. The association between depression and the social background (parents' education and employment) over time was studied using a multinomial regression analysis.", "The prevalence of self-reported severe depression slightly increased from 2000-2001 to 2010-2011 in girls. In boys a slight increase was observed when adjusting for background variables. The differences in the prevalence of depression between the social background groups persisted over the entire study period. In both sexes, severe depression nearly doubled among those adolescents whose parents were unemployed and had a low education level; among boys, the prevalence was 6.5% in 2000-2001 and 12.8% in 2010-2011, and among girls 6.4% and 11.4% respectively." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adolescent Health Services", "Cross-Sectional Studies", "Depressive Disorder", "Female", "Finland", "Humans", "Male", "Poverty", "Psychiatric Status Rating Scales", "Self Report", "Social Class", "Surveys and Questionnaires", "Vulnerable Populations" ] }
The largest increases in prevalence of severe depression are seen among socio-economically disadvantaged adolescents. This suggests that inequalities in mental health may become an increasing concern.
yes
[ { "from": "human", "value": "Question: Is self-reported depression increasing among socio-economically disadvantaged adolescents - repeated cross-sectional surveys from Finland from 2000 to 2011?\nContext: {'contexts': ['Adolescent depression is more common in lower socio-economic groups. Whether this pattern has changed over time, is not known.We examined the prevalence of self-reported depression and its changes in socio-economic groups from 2000 to 2011 among Finnish adolescents.', \"Data were based on classroom surveys every second year from 2000-2001 to 2010-2011 using nationwide samples of 14-16-year old Finns (n\\u2009=\\u2009618,084). Data were collected using self-administered questionnaires including questions on health, health behaviours, and school experiences. Depression was measured with a Finnish modification of the 13-item Beck Depression Inventory, and divided into no, mild, moderate and severe depression. The association between depression and the social background (parents' education and employment) over time was studied using a multinomial regression analysis.\", 'The prevalence of self-reported severe depression slightly increased from 2000-2001 to 2010-2011 in girls. In boys a slight increase was observed when adjusting for background variables. The differences in the prevalence of depression between the social background groups persisted over the entire study period. In both sexes, severe depression nearly doubled among those adolescents whose parents were unemployed and had a low education level; among boys, the prevalence was 6.5% in 2000-2001 and 12.8% in 2010-2011, and among girls 6.4% and 11.4% respectively.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adolescent Health Services', 'Cross-Sectional Studies', 'Depressive Disorder', 'Female', 'Finland', 'Humans', 'Male', 'Poverty', 'Psychiatric Status Rating Scales', 'Self Report', 'Social Class', 'Surveys and Questionnaires', 'Vulnerable Populations']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,760,091
Is lower mortality rate in people with dementia associated with better cognitive and functional performance in an outpatient cohort?
{ "contexts": [ "We describe a three-year experience with patients with dementia.", "clinical, cognitive and functional evaluation was performed by a multidisciplinary team for persons above 60 years. Mortality was assessed after three years.", "Mini-Mental State Examination (MMSE) (n=2,074) was 15.7 (8.4). Male patients MMSE (n=758) was 15.6 (8.3) and female's (n=1315) was 15.8 (8.3). Instrumental Activities of Daily Living Scale (n=2023) was 16.5 (7.6); females (n=1277) was 16.9 (7.2) and males (n=745) was 15.7(8.2). From these patients, 12.6% (n=209) died within three years. Baseline cognition of patients still alive was higher (p<0.001) than MMSE of those who died [MMSE=16.3 (8.1) vs. 10.6 (7.6)]. Mortality rate decreased 6% (IR=0.94) for each additional point on MMSE. Higher functional status decreases the mortality rate approximately 11% (IR=0.89) independently of age, gender, and education." ], "labels": [ "UNLABELLED", "METHODS", "RESULTS" ], "meshes": [ "Activities of Daily Living", "Age Factors", "Aged", "Aged, 80 and over", "Brazil", "Cognition", "Cohort Studies", "Dementia", "Educational Status", "Female", "Humans", "Male", "Mental Status Schedule", "Middle Aged", "Neuropsychological Tests", "Outpatients", "Reference Values", "Severity of Illness Index", "Socioeconomic Factors", "Surveys and Questionnaires" ] }
Three-year mortality rates are dependent on baseline functional and cognitive status.
yes
[ { "from": "human", "value": "Question: Is lower mortality rate in people with dementia associated with better cognitive and functional performance in an outpatient cohort?\nContext: {'contexts': ['We describe a three-year experience with patients with dementia.', 'clinical, cognitive and functional evaluation was performed by a multidisciplinary team for persons above 60 years. Mortality was assessed after three years.', \"Mini-Mental State Examination (MMSE) (n=2,074) was 15.7 (8.4). Male patients MMSE (n=758) was 15.6 (8.3) and female's (n=1315) was 15.8 (8.3). Instrumental Activities of Daily Living Scale (n=2023) was 16.5 (7.6); females (n=1277) was 16.9 (7.2) and males (n=745) was 15.7(8.2). From these patients, 12.6% (n=209) died within three years. Baseline cognition of patients still alive was higher (p<0.001) than MMSE of those who died [MMSE=16.3 (8.1) vs. 10.6 (7.6)]. Mortality rate decreased 6% (IR=0.94) for each additional point on MMSE. Higher functional status decreases the mortality rate approximately 11% (IR=0.89) independently of age, gender, and education.\"], 'labels': ['UNLABELLED', 'METHODS', 'RESULTS'], 'meshes': ['Activities of Daily Living', 'Age Factors', 'Aged', 'Aged, 80 and over', 'Brazil', 'Cognition', 'Cohort Studies', 'Dementia', 'Educational Status', 'Female', 'Humans', 'Male', 'Mental Status Schedule', 'Middle Aged', 'Neuropsychological Tests', 'Outpatients', 'Reference Values', 'Severity of Illness Index', 'Socioeconomic Factors', 'Surveys and Questionnaires']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,751,683
Is a genetic variant in primary miR-378 associated with risk and prognosis of hepatocellular carcinoma in a Chinese population?
{ "contexts": [ "MiR-378 has been reported to be related to cell survival, tumor growth and angiogenesis and may participate in hepatocellular carcinoma (HCC) development and prognosis. Genetic variants in primary miR-378 (pri-miR-378) may impact miR-378 expression and contribute to HCC risk and survival. This study aimed to assess the associations between a genetic variant in primary miR-378 and HCC susceptibility and prognosis.", "We conducted a case-control study to analyze the association of rs1076064 in pri-miR-378 with hepatocellular carcinoma risk in 1300 HCC patients with positive hepatitis B virus (HBV) and 1344 HBV carriers. Then, we evaluated the correlation between the polymorphism and hepatocellular carcinoma prognosis in 331 HCC patients at either intermediate or advanced stage without surgical treatment.", "The variant genotypes of rs1076064 were associated with a decreased HCC risk in HBV carriers [Adjusted odds ratio (OR) = 0.90, 95% confidence intervals (CI) = 0.81-1.00, P = 0.047]. Moreover, HCC patients with the variant genotypes were associated with a better survival [Adjusted hazard ratio (HR) = 0.70, 95% CIs = 0.59-0.83, P<0.0001 in an additive genetic model]. The reporter gene assay showed that the variant G allele of rs1076064 exerted higher promoter activity than the A allele." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Alleles", "Carcinoma, Hepatocellular", "Cell Line, Tumor", "Gene Frequency", "Genetic Predisposition to Disease", "Hepatitis B", "Humans", "Kaplan-Meier Estimate", "Liver Neoplasms", "MicroRNAs", "Multivariate Analysis", "Polymorphism, Single Nucleotide", "Prognosis", "Promoter Regions, Genetic", "Proportional Hazards Models", "Risk Factors", "Survival Analysis" ] }
These findings indicate that rs1076064 may be a biomarker for HCC susceptibility and prognosis through altering pri-miR-378 transcription.
yes
[ { "from": "human", "value": "Question: Is a genetic variant in primary miR-378 associated with risk and prognosis of hepatocellular carcinoma in a Chinese population?\nContext: {'contexts': ['MiR-378 has been reported to be related to cell survival, tumor growth and angiogenesis and may participate in hepatocellular carcinoma (HCC) development and prognosis. Genetic variants in primary miR-378 (pri-miR-378) may impact miR-378 expression and contribute to HCC risk and survival. This study aimed to assess the associations between a genetic variant in primary miR-378 and HCC susceptibility and prognosis.', 'We conducted a case-control study to analyze the association of rs1076064 in pri-miR-378 with hepatocellular carcinoma risk in 1300 HCC patients with positive hepatitis B virus (HBV) and 1344 HBV carriers. Then, we evaluated the correlation between the polymorphism and hepatocellular carcinoma prognosis in 331 HCC patients at either intermediate or advanced stage without surgical treatment.', 'The variant genotypes of rs1076064 were associated with a decreased HCC risk in HBV carriers [Adjusted odds ratio (OR)\\u200a=\\u200a0.90, 95% confidence intervals (CI)\\u200a=\\u200a0.81-1.00, P\\u200a=\\u200a0.047]. Moreover, HCC patients with the variant genotypes were associated with a better survival [Adjusted hazard ratio (HR)\\u200a=\\u200a0.70, 95% CIs\\u200a=\\u200a0.59-0.83, P<0.0001 in an additive genetic model]. The reporter gene assay showed that the variant G allele of rs1076064 exerted higher promoter activity than the A allele.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Alleles', 'Carcinoma, Hepatocellular', 'Cell Line, Tumor', 'Gene Frequency', 'Genetic Predisposition to Disease', 'Hepatitis B', 'Humans', 'Kaplan-Meier Estimate', 'Liver Neoplasms', 'MicroRNAs', 'Multivariate Analysis', 'Polymorphism, Single Nucleotide', 'Prognosis', 'Promoter Regions, Genetic', 'Proportional Hazards Models', 'Risk Factors', 'Survival Analysis']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,755,251
Does expression microarray identify the unliganded glucocorticoid receptor as a regulator of gene expression in mammary epithelial cells?
{ "contexts": [ "While glucocorticoids and the liganded glucocorticoid receptor (GR) have a well-established role in the maintenance of differentiation and suppression of apoptosis in breast tissue, the involvement of unliganded GR in cellular processes is less clear. Our previous studies implicated unliganded GR as a positive regulator of the BRCA1 tumour suppressor gene in the absence of glucocorticoid hormone, which suggested it could play a similar role in the regulation of other genes.", "An shRNA vector directed against GR was used to create mouse mammary cell lines with depleted endogenous levels of this receptor in order to further characterize the role of GR in breast cells. An expression microarray screen for targets of unliganded GR was performed using our GR-depleted cell lines maintained in the absence of glucocorticoids. Candidate genes positively regulated by unliganded GR were identified, classified by Gene Ontology and Ingenuity Pathway Analysis, and validated using quantitative real-time reverse transcriptase PCR. Chromatin immunoprecipitation and dual luciferase expression assays were conducted to further investigate the mechanism through which unliganded GR regulates these genes.", "Expression microarray analysis revealed 260 targets negatively regulated and 343 targets positively regulated by unliganded GR. A number of the positively regulated targets were involved in pro-apoptotic networks, possibly opposing the activity of liganded GR targets. Validation and further analysis of five candidates from the microarray indicated that two of these, Hsd11b1 and Ch25h, were regulated by unliganded GR in a manner similar to Brca1 during glucocorticoid treatment. Furthermore, GR was shown to interact directly with and upregulate the Ch25h promoter in the absence, but not the presence, of hydrocortisone (HC), confirming our previously described model of gene regulation by unliganded GR." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Apoptosis", "BRCA1 Protein", "Breast Neoplasms", "Cell Differentiation", "Cell Line", "Epithelial Cells", "Female", "Gene Expression Regulation", "Mammary Glands, Animal", "Mice", "Microarray Analysis", "Promoter Regions, Genetic", "Receptors, Glucocorticoid", "Signal Transduction", "Transcriptional Activation" ] }
This work presents the first identification of targets of unliganded GR. We propose that the balance between targets of liganded and unliganded GR signaling is responsible for controlling differentiation and apoptosis, respectively, and suggest that gene regulation by unliganded GR may represent a mechanism for reducing the risk of breast tumourigenesis by the elimination of abnormal cells.
yes
[ { "from": "human", "value": "Question: Does expression microarray identify the unliganded glucocorticoid receptor as a regulator of gene expression in mammary epithelial cells?\nContext: {'contexts': ['While glucocorticoids and the liganded glucocorticoid receptor (GR) have a well-established role in the maintenance of differentiation and suppression of apoptosis in breast tissue, the involvement of unliganded GR in cellular processes is less clear. Our previous studies implicated unliganded GR as a positive regulator of the BRCA1 tumour suppressor gene in the absence of glucocorticoid hormone, which suggested it could play a similar role in the regulation of other genes.', 'An shRNA vector directed against GR was used to create mouse mammary cell lines with depleted endogenous levels of this receptor in order to further characterize the role of GR in breast cells. An expression microarray screen for targets of unliganded GR was performed using our GR-depleted cell lines maintained in the absence of glucocorticoids. Candidate genes positively regulated by unliganded GR were identified, classified by Gene Ontology and Ingenuity Pathway Analysis, and validated using quantitative real-time reverse transcriptase PCR. Chromatin immunoprecipitation and dual luciferase expression assays were conducted to further investigate the mechanism through which unliganded GR regulates these genes.', 'Expression microarray analysis revealed 260 targets negatively regulated and 343 targets positively regulated by unliganded GR. A number of the positively regulated targets were involved in pro-apoptotic networks, possibly opposing the activity of liganded GR targets. Validation and further analysis of five candidates from the microarray indicated that two of these, Hsd11b1 and Ch25h, were regulated by unliganded GR in a manner similar to Brca1 during glucocorticoid treatment. Furthermore, GR was shown to interact directly with and upregulate the Ch25h promoter in the absence, but not the presence, of hydrocortisone (HC), confirming our previously described model of gene regulation by unliganded GR.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Apoptosis', 'BRCA1 Protein', 'Breast Neoplasms', 'Cell Differentiation', 'Cell Line', 'Epithelial Cells', 'Female', 'Gene Expression Regulation', 'Mammary Glands, Animal', 'Mice', 'Microarray Analysis', 'Promoter Regions, Genetic', 'Receptors, Glucocorticoid', 'Signal Transduction', 'Transcriptional Activation']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,769,028
Is gSTP1 promoter methylation associated with recurrence in early stage prostate cancer?
{ "contexts": [ "Recurrent prostate cancer remains a major problem. Staging, grading and prostate specific antigen level at surgery are helpful but still imperfect predictors of recurrence. For this reason there is an imperative need for additional biomarkers that add to the prediction of currently used prognostic factors.", "We evaluated the extent of promoter methylation of genes previously reported as aberrantly methylated in prostate cancer (AIM1, APC, CCND2, GPX3, GSTP1, MCAM, RARβ2, SSBP2 and TIMP3) by quantitative fluorogenic methylation-specific polymerase chain reaction. We used cancer tissue from a nested case-control study of 452 patients surgically treated for prostate cancer. Recurrence cases and controls were compared and the association between methylation extent and recurrence risk was estimated by logistic regression adjusting for patient age at prostatectomy, prostatectomy year, stage, grade, surgical margins and preprostatectomy prostate specific antigen. All statistical tests were 2-sided with p ≤0.05 considered statistically significant.", "The extent of GSTP1 methylation was higher in patients with recurrence than in controls (p = 0.01), especially patients with early disease, ie organ confined or limited extraprostatic extension (p = 0.001). After multivariate adjustment GSTP1 promoter methylation at or above the median was associated with an increased risk of recurrence, including in men with early disease (each p = 0.05)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "DNA Methylation", "DNA, Neoplasm", "Follow-Up Studies", "Glutathione S-Transferase pi", "Humans", "Incidence", "Male", "Maryland", "Middle Aged", "Neoplasm Recurrence, Local", "Prognosis", "Promoter Regions, Genetic", "Prostatectomy", "Prostatic Neoplasms", "Retrospective Studies" ] }
Greater GSTP1 promoter methylation in cancer tissue was independently associated with the risk of recurrence in patients with early prostate cancer. This suggests that GSTP1 promoter methylation may be a potential tissue based recurrence marker.
yes
[ { "from": "human", "value": "Question: Is gSTP1 promoter methylation associated with recurrence in early stage prostate cancer?\nContext: {'contexts': ['Recurrent prostate cancer remains a major problem. Staging, grading and prostate specific antigen level at surgery are helpful but still imperfect predictors of recurrence. For this reason there is an imperative need for additional biomarkers that add to the prediction of currently used prognostic factors.', 'We evaluated the extent of promoter methylation of\\xa0genes previously reported as aberrantly methylated in prostate cancer (AIM1,\\xa0APC, CCND2, GPX3, GSTP1, MCAM, RARβ2, SSBP2 and TIMP3) by quantitative fluorogenic methylation-specific polymerase chain reaction. We used cancer tissue from a nested case-control study of 452 patients surgically treated for prostate cancer. Recurrence cases and controls were compared and the association between methylation extent and recurrence risk was estimated by logistic regression adjusting for patient age at prostatectomy, prostatectomy year, stage, grade, surgical margins and preprostatectomy prostate specific antigen. All statistical tests were 2-sided with p ≤0.05 considered statistically significant.', 'The extent of GSTP1 methylation was higher in patients with recurrence than in controls (p = 0.01), especially patients with early disease, ie organ confined or limited extraprostatic extension (p = 0.001). After multivariate adjustment GSTP1 promoter methylation at or above the median was associated with an increased risk of recurrence, including in men with early disease (each p\\xa0= 0.05).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['DNA Methylation', 'DNA, Neoplasm', 'Follow-Up Studies', 'Glutathione S-Transferase pi', 'Humans', 'Incidence', 'Male', 'Maryland', 'Middle Aged', 'Neoplasm Recurrence, Local', 'Prognosis', 'Promoter Regions, Genetic', 'Prostatectomy', 'Prostatic Neoplasms', 'Retrospective Studies']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,769,029
Does functional magnetic resonance imaging during urodynamic testing identify brain structures initiating micturition?
{ "contexts": [ "Normal voiding in neurologically intact patients is triggered by the release of tonic inhibition from suprapontine centers, allowing the pontine micturition center to trigger the voiding reflex. Supraspinal mechanisms of voluntary voiding in humans are just beginning to be described via functional neuroimaging. We further elucidated brain activity processes during voiding using functional magnetic resonance imaging in normal females to gain better understanding of normal voiding as well as changes that may occur in voiding dysfunction.", "We screened 13 healthy premenopausal female volunteers using baseline clinic urodynamics to document normal voiding parameters. We then recorded brain activity via functional magnetic resonance imaging and simultaneous urodynamics, including the pressure flow voiding phase. After motion correction of functional magnetic resonance images we performed activation and connectivity analyses in 10 subjects.", "Group analysis revealed consistent activation areas, including regions for motor control (cerebellum, thalamus, caudate, lentiform nucleus, red nucleus, supplementary motor area and post-central gyrus), emotion (anterior/posterior cingulate gyrus and insula), executive function (left superior frontal gyrus) and a focal region in the pons. Connectivity analysis demonstrated strong interconnectivity of the pontine micturition center with many short-range and long-range cortical clusters." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Brain", "Female", "Healthy Volunteers", "Humans", "Image Processing, Computer-Assisted", "Magnetic Resonance Imaging", "Middle Aged", "Neural Pathways", "Reflex", "Surveys and Questionnaires", "Urination", "Urodynamics" ] }
Our study is one of the first reports of brain activation centers associated with micturition initiation in normal healthy females. Results show activation of a brain network consisting of regions for motor control, executive function and emotion processing. Further studies are planned to create and validate a model of brain activity during normal voiding in women.
yes
[ { "from": "human", "value": "Question: Does functional magnetic resonance imaging during urodynamic testing identify brain structures initiating micturition?\nContext: {'contexts': ['Normal voiding in neurologically intact patients is triggered by the release of tonic inhibition from suprapontine centers, allowing the pontine micturition center to trigger the voiding reflex. Supraspinal mechanisms of voluntary voiding in humans are just beginning to be described via functional neuroimaging. We further elucidated brain activity processes during voiding using functional magnetic resonance imaging in normal females to gain better understanding of normal voiding as well as changes that may occur in voiding dysfunction.', 'We screened 13 healthy premenopausal female volunteers using baseline clinic urodynamics to document normal voiding parameters. We then recorded brain activity via functional magnetic resonance imaging and simultaneous urodynamics, including the pressure flow voiding phase. After motion correction of functional magnetic resonance images we performed activation and connectivity analyses in 10 subjects.', 'Group analysis revealed consistent activation areas, including regions for motor control (cerebellum, thalamus, caudate, lentiform nucleus, red nucleus, supplementary motor area and post-central gyrus), emotion (anterior/posterior cingulate gyrus and insula), executive function (left superior frontal gyrus) and a focal region in the pons. Connectivity analysis demonstrated strong interconnectivity of the pontine micturition center with many short-range and long-range cortical clusters.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Brain', 'Female', 'Healthy Volunteers', 'Humans', 'Image Processing, Computer-Assisted', 'Magnetic Resonance Imaging', 'Middle Aged', 'Neural Pathways', 'Reflex', 'Surveys and Questionnaires', 'Urination', 'Urodynamics']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,748,541
Is hIC2 a novel dosage-dependent regulator of cardiac development located within the distal 22q11 deletion syndrome region?
{ "contexts": [ "22q11 deletion syndrome arises from recombination between low-copy repeats on chromosome 22. Typical deletions result in hemizygosity for TBX1 associated with congenital cardiovascular disease. Deletions distal to the typically deleted region result in a similar cardiac phenotype but lack in extracardiac features of the syndrome, suggesting that a second haploinsufficient gene maps to this interval.", "The transcription factor HIC2 is lost in most distal deletions, as well as in a minority of typical deletions. We used mouse models to test the hypothesis that HIC2 hemizygosity causes congenital heart disease.", "We created a genetrap mouse allele of Hic2. The genetrap reporter was expressed in the heart throughout the key stages of cardiac morphogenesis. Homozygosity for the genetrap allele was embryonic lethal before embryonic day E10.5, whereas the heterozygous condition exhibited a partially penetrant late lethality. One third of heterozygous embryos had a cardiac phenotype. MRI demonstrated a ventricular septal defect with over-riding aorta. Conditional targeting indicated a requirement for Hic2 within the Nkx2.5+ and Mesp1+ cardiovascular progenitor lineages. Microarray analysis revealed increased expression of Bmp10." ], "labels": [ "BACKGROUND", "OBJECTIVE", "RESULTS" ], "meshes": [ "22q11 Deletion Syndrome", "Adaptor Proteins, Signal Transducing", "Animals", "Bone Morphogenetic Proteins", "Disease Models, Animal", "Gene Expression Regulation", "Heart", "Heart Defects, Congenital", "Humans", "Kruppel-Like Transcription Factors", "Mice", "Mitogen-Activated Protein Kinase 1", "Morphogenesis", "Mutagenesis", "Nuclear Proteins", "T-Box Domain Proteins", "Tumor Suppressor Proteins" ] }
Our results demonstrate a novel role for Hic2 in cardiac development. Hic2 is the first gene within the distal 22q11 interval to have a demonstrated haploinsufficient cardiac phenotype in mice. Together our data suggest that HIC2 haploinsufficiency likely contributes to the cardiac defects seen in distal 22q11 deletion syndrome.
yes
[ { "from": "human", "value": "Question: Is hIC2 a novel dosage-dependent regulator of cardiac development located within the distal 22q11 deletion syndrome region?\nContext: {'contexts': ['22q11 deletion syndrome arises from recombination between low-copy repeats on chromosome 22. Typical deletions result in hemizygosity for TBX1 associated with congenital cardiovascular disease. Deletions distal to the typically deleted region result in a similar cardiac phenotype but lack in extracardiac features of the syndrome, suggesting that a second haploinsufficient gene maps to this interval.', 'The transcription factor HIC2 is lost in most distal deletions, as well as in a minority of typical deletions. We used mouse models to test the hypothesis that HIC2 hemizygosity causes congenital heart disease.', 'We created a genetrap mouse allele of Hic2. The genetrap reporter was expressed in the heart throughout the key stages of cardiac morphogenesis. Homozygosity for the genetrap allele was embryonic lethal before embryonic day E10.5, whereas the heterozygous condition exhibited a partially penetrant late lethality. One third of heterozygous embryos had a cardiac phenotype. MRI demonstrated a ventricular septal defect with over-riding aorta. Conditional targeting indicated a requirement for Hic2 within the Nkx2.5+ and Mesp1+ cardiovascular progenitor lineages. Microarray analysis revealed increased expression of Bmp10.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'RESULTS'], 'meshes': ['22q11 Deletion Syndrome', 'Adaptor Proteins, Signal Transducing', 'Animals', 'Bone Morphogenetic Proteins', 'Disease Models, Animal', 'Gene Expression Regulation', 'Heart', 'Heart Defects, Congenital', 'Humans', 'Kruppel-Like Transcription Factors', 'Mice', 'Mitogen-Activated Protein Kinase 1', 'Morphogenesis', 'Mutagenesis', 'Nuclear Proteins', 'T-Box Domain Proteins', 'Tumor Suppressor Proteins']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,755,152
Does cD3 antibody and IL-2 complex combination therapy inhibit atherosclerosis by augmenting a regulatory immune response?
{ "contexts": [ "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." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Animals", "Anti-Inflammatory Agents", "Antibodies, Monoclonal", "Antigen-Antibody Complex", "Aorta", "Aortic Diseases", "Apolipoproteins E", "Atherosclerosis", "CD3 Complex", "Cholesterol, Dietary", "Disease Models, Animal", "Drug Therapy, Combination", "Immunity, Cellular", "Interleukin-2", "Macrophages", "Mice", "Mice, Knockout", "Phenotype", "T-Lymphocytes, Helper-Inducer", "T-Lymphocytes, Regulatory" ] }
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.
yes
[ { "from": "human", "value": "Question: Does cD3 antibody and IL-2 complex combination therapy inhibit atherosclerosis by augmenting a regulatory immune response?\nContext: {'contexts': ['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.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Animals', 'Anti-Inflammatory Agents', 'Antibodies, Monoclonal', 'Antigen-Antibody Complex', 'Aorta', 'Aortic Diseases', 'Apolipoproteins E', 'Atherosclerosis', 'CD3 Complex', 'Cholesterol, Dietary', 'Disease Models, Animal', 'Drug Therapy, Combination', 'Immunity, Cellular', 'Interleukin-2', 'Macrophages', 'Mice', 'Mice, Knockout', 'Phenotype', 'T-Lymphocytes, Helper-Inducer', 'T-Lymphocytes, Regulatory']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,766,859
Is gATA5 and endothelial nitric oxide synthase expression in the ascending aorta related to aortic size and valve morphology?
{ "contexts": [ "The pathogenesis of aortic dilatation in patients with congenital aortic valve anomalies is poorly understood. Recent studies suggest that alterations of gene expression may be related to ascending aortic aneurysm formation in these patients. Knockout of endothelial nitric oxide synthase (eNOS) and GATA5 is associated with bicuspid aortic valves in mice. To study the role of eNOS and GATA5 in human congenital aortic valve disease and aortic dilatation, we investigated their gene expression in aortic tissue from patients with unicuspid, bicuspid, and tricuspid aortic valves.", "Samples from 84 patients (33 tricuspid, 32 bicuspid, and 19 unicuspid) were harvested intraoperatively from the ascending aorta. GATA5 and eNOS expression was determined by real-time polymerase chain reaction.", "GATA5 and eNOS expression in the aortic wall from patients with unicuspid aortic valves (GATA5: mean [M], 2.14; standard deviation [SD], 1.72; eNOS: M, 3.40; SD, 3.83) was significantly higher than in tricuspid aortic valves (GATA5: M, 1.12; SD, 0.80; eNOS: M, 1.00; SD, 0.74; each p < 0.05). Patients with bicuspid aortic valves (GATA5: M, 1.29, SD, 1.33; eNOS: M, 1.66; SD, 1.31) had a significantly higher eNOS expression than patients with tricuspid aortic valves (p < 0.05). The expression levels of eNOS and GATA5 correlated positively with each other and negatively with the ascending aortic diameter." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aorta", "Aortic Valve", "Female", "GATA5 Transcription Factor", "Gene Expression Regulation", "Humans", "Male", "Middle Aged", "Nitric Oxide Synthase Type III", "RNA, Messenger" ] }
Our data suggest that GATA5, possibly through upregulation of eNOS, plays a role in the development of aortic dilatation in patients with unicuspid and bicuspid aortic valves. The differential gene expression in patients with unicuspid compared with bicuspid aortic valves suggests that the pathogenesis of both aortic valve anomalies may be different.
yes
[ { "from": "human", "value": "Question: Is gATA5 and endothelial nitric oxide synthase expression in the ascending aorta related to aortic size and valve morphology?\nContext: {'contexts': ['The pathogenesis of aortic dilatation in patients with congenital aortic valve anomalies is poorly understood. Recent studies suggest that alterations of gene expression may be related to ascending aortic aneurysm formation in these patients. Knockout of endothelial nitric oxide synthase (eNOS) and GATA5 is associated with bicuspid aortic valves in mice. To study the role of eNOS and GATA5 in human congenital aortic valve disease and aortic dilatation, we investigated their gene expression in aortic tissue from patients with unicuspid, bicuspid, and tricuspid aortic valves.', 'Samples from 84 patients (33 tricuspid, 32\\xa0bicuspid, and 19 unicuspid) were harvested intraoperatively from the ascending aorta. GATA5 and eNOS expression was determined by real-time polymerase chain reaction.', 'GATA5 and eNOS expression in the aortic wall from patients with unicuspid aortic valves (GATA5: mean [M], 2.14; standard deviation [SD], 1.72; eNOS: M, 3.40; SD, 3.83) was significantly higher than in tricuspid aortic valves (GATA5: M, 1.12; SD, 0.80; eNOS: M, 1.00; SD, 0.74; each p < 0.05). Patients with bicuspid aortic valves (GATA5: M, 1.29, SD, 1.33; eNOS: M, 1.66; SD, 1.31) had a significantly higher eNOS expression than patients with tricuspid aortic valves (p < 0.05). The expression levels of eNOS and GATA5 correlated positively with each other and negatively with the ascending aortic diameter.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aorta', 'Aortic Valve', 'Female', 'GATA5 Transcription Factor', 'Gene Expression Regulation', 'Humans', 'Male', 'Middle Aged', 'Nitric Oxide Synthase Type III', 'RNA, Messenger']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,758,515
Does modulation of imidazoline I2 binding sites by CR4056 relieve postoperative hyperalgesia in male and female rats?
{ "contexts": [ "CR4056 is a novel imidazoline-2 (I2 ) ligand exhibiting potent analgesic activity in animal models of pain. In this study, we investigated the effects of CR4056 in a well-established model of postoperative pain where rats develop hyperalgesia in the injured hind paw.", "By measuring paw withdrawal threshold to mechanical pressure, we studied the pharmacology of CR4056, potential sex differences in pain perception and response to treatment, and the pharmacodynamic interaction of CR4056 with morphine.", "Oral CR4056 and subcutaneous morphine dose-dependently reversed the hyperalgesic response. Analgesic effects of CR4056 were completely suppressed by the non-selective imidazoline I2 /α2 -adrenoceptor antagonist idazoxan, were partially reduced (~30%; P < 0.05) by the selective α2 -adrenoceptor antagonist yohimbine, but were not influenced by the non-selective I1 /α2 -adrenoceptor antagonist efaroxan or by the μ opioid receptor antagonist naloxone. We found no differences in responses to CR4056 or morphine between male and female rats. However, females had a lower pain threshold than males, and needed lower doses of drugs to reach a significant analgesia. When CR4056 and morphine were combined, their median effective doses were lower than expected for additive effects, both in males and in females. Isobolographic analysis confirmed a synergism between CR4056 and morphine." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adrenergic alpha-2 Receptor Antagonists", "Analgesics", "Analgesics, Opioid", "Animals", "Benzofurans", "Binding Sites", "Drug Synergism", "Female", "Hyperalgesia", "Idazoxan", "Imidazoles", "Imidazoline Receptors", "Male", "Morphine", "Naloxone", "Narcotic Antagonists", "Pain, Postoperative", "Quinazolines", "Rats, Sprague-Dawley", "Yohimbine" ] }
CR4056 is a novel pharmacological agent under development for postoperative pain both as stand-alone treatment and in association with morphine. CR4056 has successfully completed Phase I studies for tolerability and pharmacokinetics in healthy volunteers, and is currently entering the first proof-of-concept study in patients.
yes
[ { "from": "human", "value": "Question: Does modulation of imidazoline I2 binding sites by CR4056 relieve postoperative hyperalgesia in male and female rats?\nContext: {'contexts': ['CR4056 is a novel imidazoline-2 (I2 ) ligand exhibiting potent analgesic activity in animal models of pain. In this study, we investigated the effects of CR4056 in a well-established model of postoperative pain where rats develop hyperalgesia in the injured hind paw.', 'By measuring paw withdrawal threshold to mechanical pressure, we studied the pharmacology of CR4056, potential sex differences in pain perception and response to treatment, and the pharmacodynamic interaction of CR4056 with morphine.', 'Oral CR4056 and subcutaneous morphine dose-dependently reversed the hyperalgesic response. Analgesic effects of CR4056 were completely suppressed by the non-selective imidazoline I2 /α2 -adrenoceptor antagonist idazoxan, were partially reduced (~30%; P < 0.05) by the selective α2 -adrenoceptor antagonist yohimbine, but were not influenced by the non-selective I1 /α2 -adrenoceptor antagonist efaroxan or by the μ opioid receptor antagonist naloxone. We found no differences in responses to CR4056 or morphine between male and female rats. However, females had a lower pain threshold than males, and needed lower doses of drugs to reach a significant analgesia. When CR4056 and morphine were combined, their median effective doses were lower than expected for additive effects, both in males and in females. Isobolographic analysis confirmed a synergism between CR4056 and morphine.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adrenergic alpha-2 Receptor Antagonists', 'Analgesics', 'Analgesics, Opioid', 'Animals', 'Benzofurans', 'Binding Sites', 'Drug Synergism', 'Female', 'Hyperalgesia', 'Idazoxan', 'Imidazoles', 'Imidazoline Receptors', 'Male', 'Morphine', 'Naloxone', 'Narcotic Antagonists', 'Pain, Postoperative', 'Quinazolines', 'Rats, Sprague-Dawley', 'Yohimbine']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,758,948
Does the HeartShield device reduce the risk for right ventricular damage in patients with deep sternal wound infection?
{ "contexts": [ "Right ventricular rupture, resulting in serious bleeding, is a life-threatening complication associated with negative-pressure wound therapy (NPWT) in cardiac surgery. The use of a rigid barrier between the heart and the sharp sternal edges has been successfully tested on pigs. In the present article, we demonstrate increased safety in NPWT through the use of the HeartShield device.", "Six patients were treated with a specially designed device in combination with NPWT. The device consists of a horizontally placed disk covered in foam. The back of the T-shaped device sticks up between the sternal edges and up above skin level. This part of the device is also covered in foam. Drainage is performed through two holes at the top of the device. The device and foam are changed every second to third day, and -120 mm Hg of continuous therapy is used. Six patients were treated with traditional NPWT, serving as control group.", "No signs of calluslike formation were seen on the right ventricle in the group treated with the HeartShield device. In the conventional NPWT control group, all six patients had calluslike formation (>1 × 2 cm2) on the anterior part of the right ventricle. All patients in the HeartShield group had grade 1 epicardial petechial bleeding (<0.5 cm2) on the right ventricle. In the control group, one patient had grade 1 (<0.5 cm2), three patients had grade 2 (0.5-2.0 cm2), and two patients had grade 3 (>2.0 cm2) epicardial petechial bleeding on the right ventricle. No major bleeding or mortality was observed in either group during the course of the study." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Aged, 80 and over", "Drainage", "Equipment Design", "Female", "Follow-Up Studies", "Heart Injuries", "Heart Ventricles", "Humans", "Male", "Negative-Pressure Wound Therapy", "Retrospective Studies", "Sternotomy", "Sternum", "Surgical Wound Infection" ] }
The use of the HeartShield device significantly minimizes the contact between the right ventricle and the sternal edges, thereby decreasing the risk for life-threatening complications due to bleeding.
yes
[ { "from": "human", "value": "Question: Does the HeartShield device reduce the risk for right ventricular damage in patients with deep sternal wound infection?\nContext: {'contexts': ['Right ventricular rupture, resulting in serious bleeding, is a life-threatening complication associated with negative-pressure wound therapy (NPWT) in cardiac surgery. The use of a rigid barrier between the heart and the sharp sternal edges has been successfully tested on pigs. In the present article, we demonstrate increased safety in NPWT through the use of the HeartShield device.', 'Six patients were treated with a specially designed device in combination with NPWT. The device consists of a horizontally placed disk covered in foam. The back of the T-shaped device sticks up between the sternal edges and up above skin level. This part of the device is also covered in foam. Drainage is performed through two holes at the top of the device. The device and foam are changed every second to third day, and -120 mm Hg of continuous therapy is used. Six patients were treated with traditional NPWT, serving as control group.', 'No signs of calluslike formation were seen on the right ventricle in the group treated with the HeartShield device. In the conventional NPWT control group, all six patients had calluslike formation (>1 × 2 cm2) on the anterior part of the right ventricle. All patients in the HeartShield group had grade 1 epicardial petechial bleeding (<0.5 cm2) on the right ventricle. In the control group, one patient had grade 1 (<0.5 cm2), three patients had grade 2 (0.5-2.0 cm2), and two patients had grade 3 (>2.0 cm2) epicardial petechial bleeding on the right ventricle. No major bleeding or mortality was observed in either group during the course of the study.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Aged, 80 and over', 'Drainage', 'Equipment Design', 'Female', 'Follow-Up Studies', 'Heart Injuries', 'Heart Ventricles', 'Humans', 'Male', 'Negative-Pressure Wound Therapy', 'Retrospective Studies', 'Sternotomy', 'Sternum', 'Surgical Wound Infection']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,753,805
Does the tissue Doppler imaging derived post-systolic velocity notch originate at the aortic annulus?
{ "contexts": [ "A distinct velocity pattern represented by a \"notch\" is observed during the time interval between the end of the systolic and the onset of the early diastolic velocity wave on longitudinal myocardial velocity curve. The origin of the post-systolic velocity notch (PSN) has not been resolved.", "The high frame rate color tissue Doppler imaging of the apical longitudinal axis was performed in 32 healthy subjects.", "The time delays of the PSN onset at the posterior aortic wall (AW), the mid anteroseptal wall (MAS) and the posterior mitral annulus (MA) relatively to the anterior aortic annulus (AA) were found to be significantly longer than zero (5.1 ± 2.2, 6.0 ± 2.3, 6.8 ± 2.8 ms; p < 0.001). The amplitude was the highest at the AA when compared to the AW, the MAS and the MA (4.77 ± 1.28 vs. 2.88 ± 1.11, 2.15 ± 0.73, 2.44 ± 1.17 cm/s; p < 0.001). A second PSN spike was identifiable in 10/32 (31%) of the studied subjects at the AA. Of these, 9 (28%) exhibited a second PSN spike at the AW, 3 (9%) at the MAS and no one at the MA." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
The AA represents the site of the earliest onset and maximal amplitude of the PSN on the longitudinal velocity curve suggesting its mechanism to be that of an energy release at the instant of the aortic valve closure causing an apically directed acceleration of the myocardium. A substantial number of healthy subjects exhibit a second PSN spike predominantly at the level of the AA. Its mechanism remains to be elucidated.
yes
[ { "from": "human", "value": "Question: Does the tissue Doppler imaging derived post-systolic velocity notch originate at the aortic annulus?\nContext: {'contexts': ['A distinct velocity pattern represented by a \"notch\" is observed during the time interval between the end of the systolic and the onset of the early diastolic velocity wave on longitudinal myocardial velocity curve. The origin of the post-systolic velocity notch (PSN) has not been resolved.', 'The high frame rate color tissue Doppler imaging of the apical longitudinal axis was performed in 32 healthy subjects.', 'The time delays of the PSN onset at the posterior aortic wall (AW), the mid anteroseptal wall (MAS) and the posterior mitral annulus (MA) relatively to the anterior aortic annulus (AA) were found to be significantly longer than zero (5.1 ± 2.2, 6.0 ± 2.3, 6.8 ± 2.8 ms; p < 0.001). The amplitude was the highest at the AA when compared to the AW, the MAS and the MA (4.77 ± 1.28 vs. 2.88 ± 1.11, 2.15 ± 0.73, 2.44 ± 1.17 cm/s; p < 0.001). A second PSN spike was identifiable in 10/32 (31%) of the studied subjects at the AA. Of these, 9 (28%) exhibited a second PSN spike at the AW, 3 (9%) at the MAS and no one at the MA.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,762,166
Is guideline-concordant administration of prothrombin complex concentrate and vitamin K associated with decreased mortality in patients with severe bleeding under vitamin K antagonist treatment ( EPAHK study )?
{ "contexts": [ "In vitamin K antagonist (VKA)-treated patients with severe hemorrhage, guidelines recommend prompt VKA reversal with prothrombin complex concentrate (PCC) and vitamin K. The aim of this observational cohort study was to evaluate the impact of guideline concordant administration of PCC and vitamin K on seven-day mortality.", "Data from consecutive patients treated with PCC were prospectively collected in 44 emergency departments. Type of hemorrhage, coagulation parameters, type of treatment and seven-day mortality mortality were recorded. Guideline-concordant administration of PCC and vitamin K (GC-PCC-K) were defined by at least 20 IU/kg factor IX equivalent PCC and at least 5 mg of vitamin K performed within a predefined time frame of eight hours after admission. Multivariate analysis was used to assess the effect of appropriate reversal on seven-day mortality in all patients and in those with intracranial hemorrhage (ICH).", "Data from 822 VKA-treated patients with severe hemorrhage were collected over 14 months. Bleeding was gastrointestinal (32%), intracranial (32%), muscular (13%), and \"other\" (23%). In the whole cohort, seven-day mortality was 13% and 33% in patients with ICH. GC-PCC-K was performed in 38% of all patients and 44% of ICH patients. Multivariate analysis showed a two-fold decrease in seven-day mortality in patients with GC-PCC-K (odds ratio (OR) = 2.15 (1.20 to 3.88); P = 0.011); this mortality reduction was also observed when only ICH was considered (OR = 3.23 (1.53 to 6.79); P = 0.002)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Aged, 80 and over", "Blood Coagulation Factors", "Cohort Studies", "Drug Therapy, Combination", "Female", "Hemorrhage", "Humans", "Male", "Middle Aged", "Mortality", "Practice Guidelines as Topic", "Prospective Studies", "Treatment Outcome", "Vitamin K" ] }
Guideline-concordant VKA reversal with PCC and vitamin K within eight hours after admission was associated with a significant decrease in seven-day mortality.
yes
[ { "from": "human", "value": "Question: Is guideline-concordant administration of prothrombin complex concentrate and vitamin K associated with decreased mortality in patients with severe bleeding under vitamin K antagonist treatment ( EPAHK study )?\nContext: {'contexts': ['In vitamin K antagonist (VKA)-treated patients with severe hemorrhage, guidelines recommend prompt VKA reversal with prothrombin complex concentrate (PCC) and vitamin K. The aim of this observational cohort study was to evaluate the impact of guideline concordant administration of PCC and vitamin K on seven-day mortality.', 'Data from consecutive patients treated with PCC were prospectively collected in 44 emergency departments. Type of hemorrhage, coagulation parameters, type of treatment and seven-day mortality mortality were recorded. Guideline-concordant administration of PCC and vitamin K (GC-PCC-K) were defined by at least 20 IU/kg factor IX equivalent PCC and at least 5 mg of vitamin K performed within a predefined time frame of eight hours after admission. Multivariate analysis was used to assess the effect of appropriate reversal on seven-day mortality in all patients and in those with intracranial hemorrhage (ICH).', 'Data from 822 VKA-treated patients with severe hemorrhage were collected over 14 months. Bleeding was gastrointestinal (32%), intracranial (32%), muscular (13%), and \"other\" (23%). In the whole cohort, seven-day mortality was 13% and 33% in patients with ICH. GC-PCC-K was performed in 38% of all patients and 44% of ICH patients. Multivariate analysis showed a two-fold decrease in seven-day mortality in patients with GC-PCC-K (odds ratio (OR)\\u2009=\\u20092.15 (1.20 to 3.88); P\\u2009=\\u20090.011); this mortality reduction was also observed when only ICH was considered (OR\\u2009=\\u20093.23 (1.53 to 6.79); P\\u2009=\\u20090.002).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Aged, 80 and over', 'Blood Coagulation Factors', 'Cohort Studies', 'Drug Therapy, Combination', 'Female', 'Hemorrhage', 'Humans', 'Male', 'Middle Aged', 'Mortality', 'Practice Guidelines as Topic', 'Prospective Studies', 'Treatment Outcome', 'Vitamin K']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,748,885
Does hyperhomocysteinemia independently cause and promotes atherosclerosis in LDL receptor-deficient mice?
{ "contexts": [ "Hyperhomocysteine is an independent risk factor of coronary heart disease (CHD). However, whether hyperhomocysteine affects the progression of atherosclerosis is unclear. In the present study, we examined the effect of hyperhomocysteine on the formation of atherosclerosis in low-density lipoprotein receptor-deficient (LDLr(-/-)) mice.", "Forty-eight 7-week-old LDLr(-/-) mice were assigned to the following groups: mice fed a standard rodent diet (control group), mice fed a high-methionine diet (high-methionine group), mice fed a high-fat diet (high-fat group), and mice fed a diet high in both methionine and fat (high-methionine and high-fat group). At the age of 19, 23, and 27 weeks, four mice at each interval in every group were sacrificed.", "At the end of the study, mice did not show atherosclerotic lesions in the aortic sinus and aortic surface until 27 weeks old in the control group. However, atherosclerotic lesions developed in the other three groups at 19 weeks. The amount of atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P < 0.001). Atherosclerotic lesions on the aortic surface in the high-methionine and high-fat group were the most severe. The mean area of atherosclerotic lesions in the aortic sinus compared with atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P < 0.001). Atherosclerotic lesions in the aortic sinus in the high-methionine and high-fat group were the most severe." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
Homocysteinemia accelerates atherosclerotic lesions and induces early atherosclerosis independently in LDLr(-/-) mice. Reducing the level of homocysteinemia may be beneficial for prevention and treatment of CHD.
yes
[ { "from": "human", "value": "Question: Does hyperhomocysteinemia independently cause and promotes atherosclerosis in LDL receptor-deficient mice?\nContext: {'contexts': ['Hyperhomocysteine is an independent risk factor of coronary heart disease (CHD). However, whether hyperhomocysteine affects the progression of atherosclerosis is unclear. In the present study, we examined the effect of hyperhomocysteine on the formation of atherosclerosis in low-density lipoprotein receptor-deficient (LDLr(-/-)) mice.', 'Forty-eight 7-week-old LDLr(-/-) mice were assigned to the following groups: mice fed a standard rodent diet (control group), mice fed a high-methionine diet (high-methionine group), mice fed a high-fat diet (high-fat group), and mice fed a diet high in both methionine and fat (high-methionine and high-fat group). At the age of 19, 23, and 27 weeks, four mice at each interval in every group were sacrificed.', 'At the end of the study, mice did not show atherosclerotic lesions in the aortic sinus and aortic surface until 27 weeks old in the control group. However, atherosclerotic lesions developed in the other three groups at 19 weeks. The amount of atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P < 0.001). Atherosclerotic lesions on the aortic surface in the high-methionine and high-fat group were the most severe. The mean area of atherosclerotic lesions in the aortic sinus compared with atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P < 0.001). Atherosclerotic lesions in the aortic sinus in the high-methionine and high-fat group were the most severe.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,751,903
Does pEG-IFN alpha but not ribavirin alter NK cell phenotype and function in patients with chronic hepatitis C?
{ "contexts": [ "Ribavirin (RBV) remains part of several interferon-free treatment strategies even though its mechanisms of action are still not fully understood. One hypothesis is that RBV increases responsiveness to type I interferons. Pegylated Interferon alpha (PEG-IFNa) has recently been shown to alter natural killer (NK) cell function possibly contributing to control of hepatitis C virus (HCV) infection. However, the effects of ribavirin alone or in combination with IFNa on NK cells are unknown.", "Extensive ex vivo phenotyping and functional analysis of NK cells from hepatitis C patients was performed during antiviral therapy. Patients were treated for 6 weeks with RBV monotherapy (n = 11), placebo (n = 13) or PEG-IFNa-2a alone (n = 6) followed by PEG-IFNa/RBV combination therapy. The effects of RBV and PEG-IFNa-2a on NK cells were also studied in vitro after co-culture with K562 or Huh7.5 cells.", "Ribavirin monotherapy had no obvious effects on NK cell phenotype or function, neither ex vivo in patients nor in vitro. In contrast, PEG-IFNa-2a therapy was associated with an increase of CD56bright cells and distinct changes in expression profiles leading to an activated NK cell phenotype, increased functionality and decline of terminally differentiated NK cells. Ribavirin combination therapy reduced some of the IFN effects. An activated NK cell phenotype during therapy was inversely correlated with HCV viral load." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Antiviral Agents", "Cell Count", "Cell Degranulation", "Cell Differentiation", "Cytokines", "Drug Therapy, Combination", "Hepatitis C, Chronic", "Humans", "Interferon-alpha", "Killer Cells, Natural", "Lymphocyte Activation", "Middle Aged", "Phenotype", "Polyethylene Glycols", "RNA, Viral", "Recombinant Proteins", "Ribavirin", "Viral Load" ] }
PEG-IFNa activates NK cells possibly contributing to virological responses independently of RBV. The role of NK cells during future IFN-free combination therapies including RBV remains to be determined.
yes
[ { "from": "human", "value": "Question: Does pEG-IFN alpha but not ribavirin alter NK cell phenotype and function in patients with chronic hepatitis C?\nContext: {'contexts': ['Ribavirin (RBV) remains part of several interferon-free treatment strategies even though its mechanisms of action are still not fully understood. One hypothesis is that RBV increases responsiveness to type I interferons. Pegylated Interferon alpha (PEG-IFNa) has recently been shown to alter natural killer (NK) cell function possibly contributing to control of hepatitis C virus (HCV) infection. However, the effects of ribavirin alone or in combination with IFNa on NK cells are unknown.', 'Extensive ex vivo phenotyping and functional analysis of NK cells from hepatitis C patients was performed during antiviral therapy. Patients were treated for 6 weeks with RBV monotherapy (n\\u200a=\\u200a11), placebo (n\\u200a=\\u200a13) or PEG-IFNa-2a alone (n\\u200a=\\u200a6) followed by PEG-IFNa/RBV combination therapy. The effects of RBV and PEG-IFNa-2a on NK cells were also studied in vitro after co-culture with K562 or Huh7.5 cells.', 'Ribavirin monotherapy had no obvious effects on NK cell phenotype or function, neither ex vivo in patients nor in vitro. In contrast, PEG-IFNa-2a therapy was associated with an increase of CD56bright cells and distinct changes in expression profiles leading to an activated NK cell phenotype, increased functionality and decline of terminally differentiated NK cells. Ribavirin combination therapy reduced some of the IFN effects. An activated NK cell phenotype during therapy was inversely correlated with HCV viral load.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Antiviral Agents', 'Cell Count', 'Cell Degranulation', 'Cell Differentiation', 'Cytokines', 'Drug Therapy, Combination', 'Hepatitis C, Chronic', 'Humans', 'Interferon-alpha', 'Killer Cells, Natural', 'Lymphocyte Activation', 'Middle Aged', 'Phenotype', 'Polyethylene Glycols', 'RNA, Viral', 'Recombinant Proteins', 'Ribavirin', 'Viral Load']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,759,826
Are artemisinin-based combination therapies efficacious and safe for treatment of uncomplicated malaria in HIV-infected Ugandan children?
{ "contexts": [ "Artemisinin-based combination therapies (ACTs) are highly efficacious and safe, but data from human immunodeficiency virus (HIV)-infected children concurrently receiving antiretroviral therapy (ART) and ACTs are limited.", "We evaluated 28-day outcomes following malaria treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in 2 cohorts of HIV-infected Ugandan children taking various ART regimens. In one cohort, children <6 years of age were randomized to lopinavir/ritonavir (LPV/r) or nonnucleoside reverse transcriptase inhibitor-based ART and treated with AL for uncomplicated malaria. In another cohort, children <12 months of age were started on nevirapine-based ART if they were eligible, and randomized to AL or DP for the treatment of their first and all subsequent uncomplicated malaria episodes.", "There were 773 and 165 treatments for malaria with AL and DP, respectively. Initial response to therapy was excellent, with 99% clearance of parasites and <1% risk of repeat therapy within 3 days. Recurrent parasitemia within 28 days was common following AL treatment. The risk of recurrent parasitemia was significantly lower among children taking LPV/r-based ART compared with children taking nevirapine-based ART following AL treatment (15.3% vs 35.5%, P = .009), and those treated with DP compared with AL (8.6% vs 36.2%, P < .001). Both ACT regimens were safe and well tolerated." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Antimalarials", "Artemisinins", "Child, Preschool", "Cohort Studies", "Drug Therapy, Combination", "Female", "HIV Infections", "HIV Protease Inhibitors", "Humans", "Infant", "Lopinavir", "Malaria", "Male", "Nevirapine", "Parasitemia", "Quinolines", "Reverse Transcriptase Inhibitors", "Ritonavir", "Treatment Outcome", "Uganda" ] }
Treatment of uncomplicated malaria with AL or DP was efficacious and safe in HIV-infected children taking ART. However, there was a high risk of recurrent parasitemia following AL treatment, which was significantly lower in children taking LPV/r-based ART compared with nevirapine-based ART.
yes
[ { "from": "human", "value": "Question: Are artemisinin-based combination therapies efficacious and safe for treatment of uncomplicated malaria in HIV-infected Ugandan children?\nContext: {'contexts': ['Artemisinin-based combination therapies (ACTs) are highly efficacious and safe, but data from human immunodeficiency virus (HIV)-infected children concurrently receiving antiretroviral therapy (ART) and ACTs are limited.', 'We evaluated 28-day outcomes following malaria treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in 2 cohorts of HIV-infected Ugandan children taking various ART regimens. In one cohort, children <6 years of age were randomized to lopinavir/ritonavir (LPV/r) or nonnucleoside reverse transcriptase inhibitor-based ART and treated with AL for uncomplicated malaria. In another cohort, children <12 months of age were started on nevirapine-based ART if they were eligible, and randomized to AL or DP for the treatment of their first and all subsequent uncomplicated malaria episodes.', 'There were 773 and 165 treatments for malaria with AL and DP, respectively. Initial response to therapy was excellent, with 99% clearance of parasites and <1% risk of repeat therapy within 3 days. Recurrent parasitemia within 28 days was common following AL treatment. The risk of recurrent parasitemia was significantly lower among children taking LPV/r-based ART compared with children taking nevirapine-based ART following AL treatment (15.3% vs 35.5%, P = .009), and those treated with DP compared with AL (8.6% vs 36.2%, P < .001). Both ACT regimens were safe and well tolerated.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Antimalarials', 'Artemisinins', 'Child, Preschool', 'Cohort Studies', 'Drug Therapy, Combination', 'Female', 'HIV Infections', 'HIV Protease Inhibitors', 'Humans', 'Infant', 'Lopinavir', 'Malaria', 'Male', 'Nevirapine', 'Parasitemia', 'Quinolines', 'Reverse Transcriptase Inhibitors', 'Ritonavir', 'Treatment Outcome', 'Uganda']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,775,913
Does hematuria duration predict kidney function at 1 year in ANCA-associated glomerulonephritis?
{ "contexts": [ "Hematuria is considered a marker of active renal disease in ANCA-associated glomerulonephritis (ANCA-GN) with induction immunosuppression often continued until hematuria has resolved. We aim to determine whether longer hematuria duration is associated with lower estimated glomerular filtration rate (eGFR) at 1 year.", "We conducted a retrospective study of 55 patients with biopsy-proven ANCA-GN. Linear regression models were constructed to determine predictors of eGFR at 1 year. The primary exposure was hematuria (>5 rbc/hpf) duration, defined as <90 days vs. ≥ 90 days following renal biopsy. Covariates included age, gender, ANCA type, baseline eGFR, and baseline proteinuria.", "Mean age at diagnosis was 58 years (53% male, 80% Caucasian, 38% PR3-ANCA, and 45% MPO-ANCA). At baseline, all patients had hematuria, 95% had proteinuria, and mean serum creatinine was 3.1 [standard deviation (SD) = 2.3]mg/dL. Overall, 93% were treated with steroids in combination with either cyclophosphamide or rituximab. Mean hematuria duration was 92 (SD = 77) days with 34 (62%) patients having hematuria resolution within 90 days. Older age and lower baseline eGFR were associated with lower eGFR at 1 year (p = 0.03 and p < 0.001, respectively). Hematuria resolution (<90 days vs. ≥ 90 days) was not predictive of eGFR at 1 year (p = 0.93)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Antibodies, Antineutrophil Cytoplasmic", "Biopsy", "Female", "Glomerular Filtration Rate", "Glomerulonephritis", "Hematuria", "Humans", "Kidney", "Linear Models", "Male", "Middle Aged", "Predictive Value of Tests", "Retrospective Studies", "Time Factors" ] }
In ANCA-GN, hematuria duration does not predict eGFR at 1 year. Our findings provide support that among individuals who are otherwise considered to be in clinical remission, the persistence of hematuria should not delay transition from induction to maintenance immunosuppression.
no
[ { "from": "human", "value": "Question: Does hematuria duration predict kidney function at 1 year in ANCA-associated glomerulonephritis?\nContext: {'contexts': ['Hematuria is considered a marker of active renal disease in ANCA-associated glomerulonephritis (ANCA-GN) with induction immunosuppression often continued until hematuria has resolved. We aim to determine whether longer hematuria duration is associated with lower estimated glomerular filtration rate (eGFR) at 1 year.', 'We conducted a retrospective study of 55 patients with biopsy-proven ANCA-GN. Linear regression models were constructed to determine predictors of eGFR at 1 year. The primary exposure was hematuria (>5 rbc/hpf) duration, defined as <90 days vs. ≥ 90 days following renal biopsy. Covariates included age, gender, ANCA type, baseline eGFR, and baseline proteinuria.', 'Mean age at diagnosis was 58 years (53% male, 80% Caucasian, 38% PR3-ANCA, and 45% MPO-ANCA). At baseline, all patients had hematuria, 95% had proteinuria, and mean serum creatinine was 3.1 [standard deviation (SD) = 2.3]mg/dL. Overall, 93% were treated with steroids in combination with either cyclophosphamide or rituximab. Mean hematuria duration was 92 (SD = 77) days with 34 (62%) patients having hematuria resolution within 90 days. Older age and lower baseline eGFR were associated with lower eGFR at 1 year (p = 0.03 and p < 0.001, respectively). Hematuria resolution (<90 days vs. ≥ 90 days) was not predictive of eGFR at 1 year (p = 0.93).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Antibodies, Antineutrophil Cytoplasmic', 'Biopsy', 'Female', 'Glomerular Filtration Rate', 'Glomerulonephritis', 'Hematuria', 'Humans', 'Kidney', 'Linear Models', 'Male', 'Middle Aged', 'Predictive Value of Tests', 'Retrospective Studies', 'Time Factors']}" }, { "from": "gpt", "value": "Answer: no" } ]
24,775,912
Does sUMOylation of Grb2 enhance the ERK activity by increasing its binding with Sos1?
{ "contexts": [ "Grb2 (Growth factor receptor-bound protein 2) is a key adaptor protein in maintaining the ERK activity via linking Sos1 (Son of sevenless homolog 1) or other proteins to activated RTKs, such as EGFR. Currently, little knowledge is available concerning the post-translational modification (PTM) of Grb2 except for its phosphorylation. Since emerging evidences have highlighted the importance of SUMOylation (Small ubiquitin-related modifier), a reversible PTM, in modulating protein functions, we wondered if Grb2 could be SUMOylated and thereby influences its functions especially involved in the Ras/MEK/ERK pathway.", "SUMOylation of Grb2 was analyzed with the in vivo SUMOylation assay using the Ni2+-NTA affinity pulldown and the in vitro E.coli-based SUMOylation assay. To test the ERK activity and cell transformation, the murine fibroblast cell line NIH/3T3 and the murine colon cancer cell line CMT-93 were used for the experiments including Grb2 knockdown, ectopic re-expression, cell transformation and migration. Immunoprecipitation (IP) was employed for seeking proteins that interact with SUMO modified Grb2. Xenograft tumor model in mice was conducted to verify that Grb2 SUMOylation regulated tumorigenesis in vivo.", "Grb2 can be SUMOylated by SUMO1 at lysine 56 (K56), which is located in the linker region between the N-terminal SH3 domain and the SH2 domain. Knockdown of Grb2 reduced the ERK activity and suppressed cell motility and tumorigenesis in vitro and in vivo, which were all rescued by stable ectopic re-expression of wild-type Grb2 but not the mutant Grb2K56R. Furthermore, Grb2 SUMOylation at K56 increased the formation of Grb2-Sos1 complex, which sequentially leads to the activation of Ras/MEK/MAPK pathway." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Amino Acid Sequence", "Animals", "Carcinogenesis", "Cell Line, Tumor", "Colonic Neoplasms", "Extracellular Signal-Regulated MAP Kinases", "GRB2 Adaptor Protein", "Gene Expression Regulation, Neoplastic", "MAP Kinase Signaling System", "Male", "Mice", "Mice, Nude", "Molecular Sequence Data", "NIH 3T3 Cells", "Phosphorylation", "Protein Binding", "Protein Processing, Post-Translational", "RNA, Small Interfering", "SOS1 Protein", "Sumoylation", "Xenograft Model Antitumor Assays", "ras Proteins" ] }
Our results provide evidences that Grb2 is SUMOylated in vivo and this modification enhances ERK activities via increasing the formation of Grb2-Sos1 complex, and may consequently promote cell motility, transformation and tumorigenesis.
yes
[ { "from": "human", "value": "Question: Does sUMOylation of Grb2 enhance the ERK activity by increasing its binding with Sos1?\nContext: {'contexts': ['Grb2 (Growth factor receptor-bound protein 2) is a key adaptor protein in maintaining the ERK activity via linking Sos1 (Son of sevenless homolog 1) or other proteins to activated RTKs, such as EGFR. Currently, little knowledge is available concerning the post-translational modification (PTM) of Grb2 except for its phosphorylation. Since emerging evidences have highlighted the importance of SUMOylation (Small ubiquitin-related modifier), a reversible PTM, in modulating protein functions, we wondered if Grb2 could be SUMOylated and thereby influences its functions especially involved in the Ras/MEK/ERK pathway.', 'SUMOylation of Grb2 was analyzed with the in vivo SUMOylation assay using the Ni2+-NTA affinity pulldown and the in vitro E.coli-based SUMOylation assay. To test the ERK activity and cell transformation, the murine fibroblast cell line NIH/3T3 and the murine colon cancer cell line CMT-93 were used for the experiments including Grb2 knockdown, ectopic re-expression, cell transformation and migration. Immunoprecipitation (IP) was employed for seeking proteins that interact with SUMO modified Grb2. Xenograft tumor model in mice was conducted to verify that Grb2 SUMOylation regulated tumorigenesis in vivo.', 'Grb2 can be SUMOylated by SUMO1 at lysine 56 (K56), which is located in the linker region between the N-terminal SH3 domain and the SH2 domain. Knockdown of Grb2 reduced the ERK activity and suppressed cell motility and tumorigenesis in vitro and in vivo, which were all rescued by stable ectopic re-expression of wild-type Grb2 but not the mutant Grb2K56R. Furthermore, Grb2 SUMOylation at K56 increased the formation of Grb2-Sos1 complex, which sequentially leads to the activation of Ras/MEK/MAPK pathway.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Amino Acid Sequence', 'Animals', 'Carcinogenesis', 'Cell Line, Tumor', 'Colonic Neoplasms', 'Extracellular Signal-Regulated MAP Kinases', 'GRB2 Adaptor Protein', 'Gene Expression Regulation, Neoplastic', 'MAP Kinase Signaling System', 'Male', 'Mice', 'Mice, Nude', 'Molecular Sequence Data', 'NIH 3T3 Cells', 'Phosphorylation', 'Protein Binding', 'Protein Processing, Post-Translational', 'RNA, Small Interfering', 'SOS1 Protein', 'Sumoylation', 'Xenograft Model Antitumor Assays', 'ras Proteins']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,757,639
Does gender modify the effects of education and income on sleep quality of the patients with coronary artery disease?
{ "contexts": [ "This study aimed to investigate the interaction between gender and other socio-economic characteristics on sleep quality of the patients with Coronary Artery Disease (CAD).", "This cross sectional study was conducted on 717 patients with CAD. The socio- economic status (education level, income, marital status, and place of residence) was considered as the independent variable. Besides, the study outcome was the quality of sleep which was measured using Pittsburgh Sleep Quality Index (PSQI). Gender was considered as a possible effect modifier. Two-way ANOVA was used to evaluate the interaction between gender and socio-economic factors on sleep quality. As defined by Baron and Kenny, moderator was defined as a variable that affected the direction or magnitude of the association of interest.", "Female gender, low education level, and low income were predictive of poor sleep quality. Among female (10.0 ± 4.3 vs. 7.6 ± 5.0, P < 0.05), but not male patients (6.7 ± 4.2 vs. 7.0 ± 4.2, P > 0.05), low education was associated with poor sleep quality. Also, among female (10.0 ± 4.3 vs. 5.7 ± 2.5, P < 0.05), but not male patients (7.0 ± 4.2 vs. 6.0 ± 3.8, P > 0.05), low income was predictive of poor sleep quality. Gender did not modify the effect of other socio-economic factors on sleep quality." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
Among female but not male patients with CAD, low education and income were associated with poor sleep quality. This information helps us better understand the mechanisms behind the poor sleep quality of the female patients with CAD. This is important because poor sleep is a prognostic factor among the CAD patients.
yes
[ { "from": "human", "value": "Question: Does gender modify the effects of education and income on sleep quality of the patients with coronary artery disease?\nContext: {'contexts': ['This study aimed to investigate the interaction between gender and other socio-economic characteristics on sleep quality of the patients with Coronary Artery Disease (CAD).', 'This cross sectional study was conducted on 717 patients with CAD. The socio- economic status (education level, income, marital status, and place of residence) was considered as the independent variable. Besides, the study outcome was the quality of sleep which was measured using Pittsburgh Sleep Quality Index (PSQI). Gender was considered as a possible effect modifier. Two-way ANOVA was used to evaluate the interaction between gender and socio-economic factors on sleep quality. As defined by Baron and Kenny, moderator was defined as a variable that affected the direction or magnitude of the association of interest.', 'Female gender, low education level, and low income were predictive of poor sleep quality. Among female (10.0 ± 4.3 vs. 7.6 ± 5.0, P < 0.05), but not male patients (6.7 ± 4.2 vs. 7.0 ± 4.2, P > 0.05), low education was associated with poor sleep quality. Also, among female (10.0 ± 4.3 vs. 5.7 ± 2.5, P < 0.05), but not male patients (7.0 ± 4.2 vs. 6.0 ± 3.8, P > 0.05), low income was predictive of poor sleep quality. Gender did not modify the effect of other socio-economic factors on sleep quality.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,778,452
Does human cardiac extracellular matrix support myocardial lineage commitment of pluripotent stem cells?
{ "contexts": [ "Cross-talk between organ-specific extracellular matrix (ECM) and stem cells is often assumed but has not been directly demonstrated. We developed a protocol for the preparation of human cardiac ECM (cECM) and studied whether cECM has effects on pluripotent stem cell differentiation that may be useful for future cardiac regeneration strategies in patients with end-stage heart failure.", "Of note, 0.3 mm-thick cECM slices were prepared from samples of myocardium from patients with end-stage non-ischaemic dilated cardiomyopathy, using a three-step protocol involving hypotonic lysis buffer, sodium dodecyl sulphate (SDS) and foetal bovine serum (FBS). Murine embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and mesenchymal stromal cells (MSCs) were seeded and grown in standard culture, on cECM or on non-specific ECM preparations (Matrigel® or Geltrex®). Cell attachment, apoptosis induction (Caspase 3/7 activity) and metabolic activity (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium conversion) were followed. Transcriptional activation of genes involved in pluripotency; early and late myocardial development; and endothelial, ectodermal or endodermal commitment were monitored by quantitative real-time polymerase chain reaction (rtPCR). Protein expression of selected markers was confirmed by immunohistology.", "cECM supported the proliferation of ESCs and iPSCs, and Caspase 3/7 activity was significantly lower compared with standard culture. Cardiac lineage commitment was favoured when ESCs or iPSCs were grown on cECM, as evidenced by the significantly increased mRNA expression of cardiac alpha myosin heavy polypeptide 6 (Myh6), cardiac troponin T2 (Tnnt2) and NK2 homeobox 5 (Nkx2.5) as well as positive immunohistology for cardiac troponin T and heavy-chain cardiac myosin protein. In contrast, Matrigel or Geltrex did not induce cardiac-specific markers. MSCs showed no evidence of cardiomyocyte differentiation." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Apoptosis", "Biomarkers", "Cardiac Myosins", "Cell Differentiation", "Cell Line", "Extracellular Matrix", "Humans", "Mice", "Myocytes, Cardiac", "Pluripotent Stem Cells", "Troponin T" ] }
Human cardiac ECM seems to direct differentiation of pluripotent stem cells towards a cardiomyocyte phenotype. This phenomenon supports the use of cardiac ECM preparations for guided stem cell differentiation and myocardial repair, and may ultimately increase the therapeutic efficacy of cell therapy in heart failure patients.
yes
[ { "from": "human", "value": "Question: Does human cardiac extracellular matrix support myocardial lineage commitment of pluripotent stem cells?\nContext: {'contexts': ['Cross-talk between organ-specific extracellular matrix (ECM) and stem cells is often assumed but has not been directly demonstrated. We developed a protocol for the preparation of human cardiac ECM (cECM) and studied whether cECM has effects on pluripotent stem cell differentiation that may be useful for future cardiac regeneration strategies in patients with end-stage heart failure.', 'Of note, 0.3 mm-thick cECM slices were prepared from samples of myocardium from patients with end-stage non-ischaemic dilated cardiomyopathy, using a three-step protocol involving hypotonic lysis buffer, sodium dodecyl sulphate (SDS) and foetal bovine serum (FBS). Murine embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and mesenchymal stromal cells (MSCs) were seeded and grown in standard culture, on cECM or on non-specific ECM preparations (Matrigel® or Geltrex®). Cell attachment, apoptosis induction (Caspase 3/7 activity) and metabolic activity (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium conversion) were followed. Transcriptional activation of genes involved in pluripotency; early and late myocardial development; and endothelial, ectodermal or endodermal commitment were monitored by quantitative real-time polymerase chain reaction (rtPCR). Protein expression of selected markers was confirmed by immunohistology.', 'cECM supported the proliferation of ESCs and iPSCs, and Caspase 3/7 activity was significantly lower compared with standard culture. Cardiac lineage commitment was favoured when ESCs or iPSCs were grown on cECM, as evidenced by the significantly increased mRNA expression of cardiac alpha myosin heavy polypeptide 6 (Myh6), cardiac troponin T2 (Tnnt2) and NK2 homeobox 5 (Nkx2.5) as well as positive immunohistology for cardiac troponin T and heavy-chain cardiac myosin protein. In contrast, Matrigel or Geltrex did not induce cardiac-specific markers. MSCs showed no evidence of cardiomyocyte differentiation.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Apoptosis', 'Biomarkers', 'Cardiac Myosins', 'Cell Differentiation', 'Cell Line', 'Extracellular Matrix', 'Humans', 'Mice', 'Myocytes, Cardiac', 'Pluripotent Stem Cells', 'Troponin T']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,751,211
Is 14-3-3η a novel mediator associated with the pathogenesis of rheumatoid arthritis and joint damage?
{ "contexts": [ "The aim of this study was to investigate whether 14-3-3η, a specific isoform of a family of proteins regulating processes such as cellular signalling, activates cell-signalling pathways and induces factors known to contribute to the pathophysiology of rheumatoid arthritis (RA). We also investigated whether 14-3-3η is associated with more severe disease in both early and established RA.", "We investigated the effect of 14-3-3η on the activation of RA-relevant signalling cascades and induction of proinflammatory mediators that contribute to the joint damage process. 14-3-3η titres from 33 patients with early RA (mean RA duration = 1.8 months) and from 40 patients with established RA were measured in serum drawn at the 3-year time point of the Behandel Strategieën study. The relationship between 14-3-3η titres and standard clinical variables was investigated by correlation analysis. The association with radiographic damage and radiographic progression over at least a 2-year period was investigated using univariate and multivariate regression analyses.", "14-3-3η activated selected members of the mitogen-activated protein kinase (MAPK) family, mainly extracellular regulated kinase 1/2 and c-Jun kinase, but not p38MAPK. Activation by 14-3-3η, using levels spanning the concentration range found in RA patient serum, resulted in the induction of inflammatory transcripts such as interleukin 1 (IL-1) and IL-6 and factors linked to the joint damage process, such as receptor activator of nuclear factor κB ligand and matrix metalloproteinase 1. Serum 14-3-3η correlated significantly with rheumatoid factor (RF) (r = 0.43) and anticitrullinated protein antibodies (ACPAs) (r = 0.31) in the early RA cohort, but not with C-reactive protein (CRP) or the Disease Activity Score in 28 joints in either cohort. Serum 14-3-3η concentrations were significantly higher in patients with radiographically assessed joint damage and in those who had radiographic progression. By multivariate analysis, we show that 14-3-3η complemented markers such as CRP, RF and ACPA in informing RA radiographic status and/or progression." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "14-3-3 Proteins", "Adult", "Aged", "Arthritis, Rheumatoid", "Biomarkers", "Disease Progression", "Enzyme-Linked Immunosorbent Assay", "Female", "Humans", "Joints", "Male", "Middle Aged", "Radiography" ] }
Extracellular 14-3-3η activates key signalling cascades and induces factors associated with the pathogenesis of RA at concentrations found in patients with RA, and its expression is higher in patients with radiographic damage and RA progression.
yes
[ { "from": "human", "value": "Question: Is 14-3-3η a novel mediator associated with the pathogenesis of rheumatoid arthritis and joint damage?\nContext: {'contexts': ['The aim of this study was to investigate whether 14-3-3η, a specific isoform of a family of proteins regulating processes such as cellular signalling, activates cell-signalling pathways and induces factors known to contribute to the pathophysiology of rheumatoid arthritis (RA). We also investigated whether 14-3-3η is associated with more severe disease in both early and established RA.', 'We investigated the effect of 14-3-3η on the activation of RA-relevant signalling cascades and induction of proinflammatory mediators that contribute to the joint damage process. 14-3-3η titres from 33 patients with early RA (mean RA duration\\u2009=\\u20091.8 months) and from 40 patients with established RA were measured in serum drawn at the 3-year time point of the Behandel Strategieën study. The relationship between 14-3-3η titres and standard clinical variables was investigated by correlation analysis. The association with radiographic damage and radiographic progression over at least a 2-year period was investigated using univariate and multivariate regression analyses.', '14-3-3η activated selected members of the mitogen-activated protein kinase (MAPK) family, mainly extracellular regulated kinase 1/2 and c-Jun kinase, but not p38MAPK. Activation by 14-3-3η, using levels spanning the concentration range found in RA patient serum, resulted in the induction of inflammatory transcripts such as interleukin 1 (IL-1) and IL-6 and factors linked to the joint damage process, such as receptor activator of nuclear factor κB ligand and matrix metalloproteinase 1. Serum 14-3-3η correlated significantly with rheumatoid factor (RF) (r\\u2009=\\u20090.43) and anticitrullinated protein antibodies (ACPAs) (r\\u2009=\\u20090.31) in the early RA cohort, but not with C-reactive protein (CRP) or the Disease Activity Score in 28 joints in either cohort. Serum 14-3-3η concentrations were significantly higher in patients with radiographically assessed joint damage and in those who had radiographic progression. By multivariate analysis, we show that 14-3-3η complemented markers such as CRP, RF and ACPA in informing RA radiographic status and/or progression.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['14-3-3 Proteins', 'Adult', 'Aged', 'Arthritis, Rheumatoid', 'Biomarkers', 'Disease Progression', 'Enzyme-Linked Immunosorbent Assay', 'Female', 'Humans', 'Joints', 'Male', 'Middle Aged', 'Radiography']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,752,772
Does early sac shrinkage predict a low risk of late complications after endovascular aortic aneurysm repair?
{ "contexts": [ "Aneurysm shrinkage has been proposed as a marker of successful endovascular aneurysm repair (EVAR). Patients with early postoperative shrinkage may experience fewer subsequent complications, and consequently require less intensive surveillance.", "Patients undergoing EVAR from 2000 to 2011 at three vascular centres (in 2 countries), who had two imaging examinations (postoperative and after 6-18 months), were included. Maximum diameter, complications and secondary interventions during follow-up were registered. Patients were categorized according to early sac dynamics. The primary endpoint was freedom from late complications. Secondary endpoints were freedom from secondary intervention, postimplant rupture and direct (type I/III) endoleaks.", "Some 597 EVARs (71.1 per cent of all EVARs) were included. No shrinkage was observed in 284 patients (47.6 per cent), moderate shrinkage (5-9 mm) in 142 (23.8 per cent) and major shrinkage (at least 10 mm) in 171 patients (28.6 per cent). Four years after the index imaging, the rate of freedom from complications was 84.3 (95 per cent confidence interval 78.7 to 89.8), 88.1 (80.6 to 95.5) and 94.4 (90.1 to 98.7) per cent respectively. No shrinkage was an independent risk factor for late complications compared with major shrinkage (hazard ratio (HR) 3.11; P < 0.001). Moderate compared with major shrinkage (HR 2.10; P = 0.022), early postoperative complications (HR 3.34; P < 0.001) and increasing abdominal aortic aneurysm baseline diameter (HR 1.02; P = 0.001) were also risk factors for late complications. Freedom from secondary interventions and direct endoleaks was greater for patients with major sac shrinkage." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Analysis of Variance", "Aortic Aneurysm, Abdominal", "Aortic Rupture", "Chi-Square Distribution", "Endoleak", "Endovascular Procedures", "Female", "Humans", "Male", "Netherlands", "Organ Size", "Radiography", "Reoperation", "Sweden", "Ultrasonography" ] }
Early change in aneurysm sac diameter is a strong predictor of late complications after EVAR. Patients with major sac shrinkage have a very low risk of complications for up to 5 years. This parameter may be used to tailor postoperative surveillance.
yes
[ { "from": "human", "value": "Question: Does early sac shrinkage predict a low risk of late complications after endovascular aortic aneurysm repair?\nContext: {'contexts': ['Aneurysm shrinkage has been proposed as a marker of successful endovascular aneurysm repair (EVAR). Patients with early postoperative shrinkage may experience fewer subsequent complications, and consequently require less intensive surveillance.', 'Patients undergoing EVAR from 2000 to 2011 at three vascular centres (in 2 countries), who had two imaging examinations (postoperative and after 6-18 months), were included. Maximum diameter, complications and secondary interventions during follow-up were registered. Patients were categorized according to early sac dynamics. The primary endpoint was freedom from late complications. Secondary endpoints were freedom from secondary intervention, postimplant rupture and direct (type I/III) endoleaks.', 'Some 597 EVARs (71.1 per cent of all EVARs) were included. No shrinkage was observed in 284 patients (47.6 per cent), moderate shrinkage (5-9 mm) in 142 (23.8 per cent) and major shrinkage (at least 10 mm) in 171 patients (28.6 per cent). Four years after the index imaging, the rate of freedom from complications was 84.3 (95 per cent confidence interval 78.7 to 89.8), 88.1 (80.6 to 95.5) and 94.4 (90.1 to 98.7) per cent respectively. No shrinkage was an independent risk factor for late complications compared with major shrinkage (hazard ratio (HR) 3.11; P < 0.001). Moderate compared with major shrinkage (HR 2.10; P = 0.022), early postoperative complications (HR 3.34; P < 0.001) and increasing abdominal aortic aneurysm baseline diameter (HR 1.02; P = 0.001) were also risk factors for late complications. Freedom from secondary interventions and direct endoleaks was greater for patients with major sac shrinkage.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Analysis of Variance', 'Aortic Aneurysm, Abdominal', 'Aortic Rupture', 'Chi-Square Distribution', 'Endoleak', 'Endovascular Procedures', 'Female', 'Humans', 'Male', 'Netherlands', 'Organ Size', 'Radiography', 'Reoperation', 'Sweden', 'Ultrasonography']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,766,087
Does stigma predict residential treatment length for substance use disorder?
{ "contexts": [ "Stigma has been suggested as a possible contributor to the high rates of treatment attrition in substance-dependent individuals, but no published empirical studies have examined this association.", "The present paper assessed the relationship between baseline stigma variables and length of treatment stay in a sample of patients in a residential addictions treatment unit.", "The relationship between baseline stigma variables (self-stigma, enacted stigma, and shame) and length of stay for participants (n=103) in a residential addictions treatment unit was examined.", "Higher self-stigma predicted longer stay in residential addictions treatment, even after controlling for age, marital status, race, overall mental health, social support, enacted stigma, and internalized shame. However, other stigma variables (i.e. internalized shame, stigma-related rejection) did not reliably predict length of treatment stay." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Acceptance and Commitment Therapy", "Adult", "Female", "Humans", "Length of Stay", "Male", "Middle Aged", "Residential Treatment", "Shame", "Social Stigma", "Social Support", "Substance Abuse Treatment Centers", "Substance-Related Disorders", "Surveys and Questionnaires" ] }
These results are consistent with other findings suggesting that people with higher self-stigma may have a lowered sense of self-efficacy and heightened fear of being stigmatized and therefore retreat into more protected settings such as residential treatment, potentially resulting in higher treatment costs. Specialized clinical interventions may be necessary to help participants cope with reduced self-efficacy and fear of being stigmatized.
yes
[ { "from": "human", "value": "Question: Does stigma predict residential treatment length for substance use disorder?\nContext: {'contexts': ['Stigma has been suggested as a possible contributor to the high rates of treatment attrition in substance-dependent individuals, but no published empirical studies have examined this association.', 'The present paper assessed the relationship between baseline stigma variables and length of treatment stay in a sample of patients in a residential addictions treatment unit.', 'The relationship between baseline stigma variables (self-stigma, enacted stigma, and shame) and length of stay for participants (n=103) in a residential addictions treatment unit was examined.', 'Higher self-stigma predicted longer stay in residential addictions treatment, even after controlling for age, marital status, race, overall mental health, social support, enacted stigma, and internalized shame. However, other stigma variables (i.e. internalized shame, stigma-related rejection) did not reliably predict length of treatment stay.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Acceptance and Commitment Therapy', 'Adult', 'Female', 'Humans', 'Length of Stay', 'Male', 'Middle Aged', 'Residential Treatment', 'Shame', 'Social Stigma', 'Social Support', 'Substance Abuse Treatment Centers', 'Substance-Related Disorders', 'Surveys and Questionnaires']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,750,318
Does standardizing corneal nerve fibre length for nerve tortuosity increase its association with measures of diabetic neuropathy?
{ "contexts": [ "Recent studies on corneal markers have advocated corneal nerve fibre length as the most important measure of diabetic peripheral neuropathy. The aim of this study was to determine if standardizing corneal nerve fibre length for tortuosity increases its association with other measures of diabetic peripheral neuropathy.", "Two hundred and thirty-one individuals with diabetes with either predominantly mild or absent neuropathic changes and 61 control subjects underwent evaluation of diabetic neuropathy symptom score, neuropathy disability score, testing with 10-g monofilament, quantitative sensory testing (warm, cold, vibration detection) and nerve conduction studies. Corneal nerve fibre length and corneal nerve fibre tortuosity were measured using corneal confocal microscopy. A tortuosity-standardised corneal nerve fibre length variable was generated by dividing corneal nerve fibre length by corneal nerve fibre tortuosity. Differences in corneal nerve morphology between individuals with and without diabetic peripheral neuropathy and control subjects were determined and associations were estimated between corneal morphology and established tests of, and risk factors for, diabetic peripheral neuropathy.", "The tortuosity-standardised corneal nerve fibre length variable was better than corneal nerve fibre length in demonstrating differences between individuals with diabetes, with and without neuropathy (tortuosity-standardised corneal nerve fibre length variable: 70.5 ± 27.3 vs. 84.9 ± 28.7, P < 0.001, receiver operating characteristic area under the curve = 0.67; corneal nerve fibre length: 15.9 ± 6.9 vs. 18.4 ± 6.2 mm/mm², P = 0.004, receiver operating characteristic area under the curve = 0.64). Furthermore, the tortuosity-standardised corneal nerve fibre length variable demonstrated a significant difference between the control subjects and individuals with diabetes, without neuropathy, while corneal nerve fibre length did not (tortuosity-standardised corneal nerve fibre length variable: 94.3 ± 27.1 vs. 84.9 ± 28.7, P = 0.028; corneal nerve fibre length: 20.1 ± 6.3 vs. 18.4 ± 6.2 mm/mm², P = 0.084). Correlations between corneal nerve fibre length and established measures of neuropathy and risk factors for neuropathy were higher when a correction was made for the nerve tortuosity." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Cohort Studies", "Cornea", "Diabetes Mellitus, Type 1", "Diabetes Mellitus, Type 2", "Diabetic Neuropathies", "Diabetic Retinopathy", "Diagnostic Techniques, Ophthalmological", "Early Diagnosis", "Female", "Humans", "Male", "Middle Aged", "Nerve Fibers", "Neural Conduction", "Peripheral Nervous System Diseases", "Queensland", "ROC Curve", "Risk Factors", "Severity of Illness Index", "Software" ] }
Standardizing corneal nerve fibre length for tortuosity enhances the ability to differentiate individuals with diabetes, with and without neuropathy.
yes
[ { "from": "human", "value": "Question: Does standardizing corneal nerve fibre length for nerve tortuosity increase its association with measures of diabetic neuropathy?\nContext: {'contexts': ['Recent studies on corneal markers have advocated corneal nerve fibre length as the most important measure of diabetic peripheral neuropathy. The aim of this study was to determine if standardizing corneal nerve fibre length for tortuosity increases its association with other measures of diabetic peripheral neuropathy.', 'Two hundred and thirty-one individuals with diabetes with either predominantly mild or absent neuropathic changes and 61 control subjects underwent evaluation of diabetic neuropathy symptom score, neuropathy disability score, testing with 10-g monofilament, quantitative sensory testing (warm, cold, vibration detection) and nerve conduction studies. Corneal nerve fibre length and corneal nerve fibre tortuosity were measured using corneal confocal microscopy. A tortuosity-standardised corneal nerve fibre length variable was generated by dividing corneal nerve fibre length by corneal nerve fibre tortuosity. Differences in corneal nerve morphology between individuals with and without diabetic peripheral neuropathy and control subjects were determined and associations were estimated between corneal morphology and established tests of, and risk factors for, diabetic peripheral neuropathy.', 'The tortuosity-standardised corneal nerve fibre length variable was better than corneal nerve fibre length in demonstrating differences between individuals with diabetes, with and without neuropathy (tortuosity-standardised corneal nerve fibre length variable: 70.5 ± 27.3 vs. 84.9 ± 28.7, P < 0.001, receiver operating characteristic area under the curve = 0.67; corneal nerve fibre length: 15.9 ± 6.9 vs. 18.4 ± 6.2 mm/mm², P = 0.004, receiver operating characteristic area under the curve = 0.64). Furthermore, the tortuosity-standardised corneal nerve fibre length variable demonstrated a significant difference between the control subjects and individuals with diabetes, without neuropathy, while corneal nerve fibre length did not (tortuosity-standardised corneal nerve fibre length variable: 94.3 ± 27.1 vs. 84.9 ± 28.7, P = 0.028; corneal nerve fibre length: 20.1 ± 6.3 vs. 18.4 ± 6.2 mm/mm², P = 0.084). Correlations between corneal nerve fibre length and established measures of neuropathy and risk factors for neuropathy were higher when a correction was made for the nerve tortuosity.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Cohort Studies', 'Cornea', 'Diabetes Mellitus, Type 1', 'Diabetes Mellitus, Type 2', 'Diabetic Neuropathies', 'Diabetic Retinopathy', 'Diagnostic Techniques, Ophthalmological', 'Early Diagnosis', 'Female', 'Humans', 'Male', 'Middle Aged', 'Nerve Fibers', 'Neural Conduction', 'Peripheral Nervous System Diseases', 'Queensland', 'ROC Curve', 'Risk Factors', 'Severity of Illness Index', 'Software']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,770,422
Is allodynia associated with a higher prevalence of depression in migraine patients?
{ "contexts": [ "There is a strong association between migraine and depression. The aim of this study is to identify migraine-specific factors involved in this association.", "We conducted a cross-sectional study in a large, well-defined cohort of migraine patients (n=2533). We assessed lifetime depression using validated questionnaires, and diagnosed migraine based on the International Classification of Headache Disorders III-beta criteria. Multivariate regression analyses were conducted.", "Of the 2533 migraineurs that were eligible, 1137 (45%) suffered from lifetime depression. The following independent factors were associated with an increased depression prevalence: i) migraine-specific risk factors: high migraine attack frequency and the presence of allodynia, ii) general factors: being a bad sleeper, female gender, high BMI, being single, smoking, and a low alcohol consumption." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adult", "Aged", "Cross-Sectional Studies", "Depression", "Female", "Humans", "Hyperalgesia", "Male", "Middle Aged", "Migraine Disorders", "Prevalence", "Surveys and Questionnaires", "Young Adult" ] }
This study identified allodynia, in addition to high migraine attack frequency, as a new migraine-specific factor associated with depression.
yes
[ { "from": "human", "value": "Question: Is allodynia associated with a higher prevalence of depression in migraine patients?\nContext: {'contexts': ['There is a strong association between migraine and depression. The aim of this study is to identify migraine-specific factors involved in this association.', 'We conducted a cross-sectional study in a large, well-defined cohort of migraine patients (n=2533). We assessed lifetime depression using validated questionnaires, and diagnosed migraine based on the International Classification of Headache Disorders III-beta criteria. Multivariate regression analyses were conducted.', 'Of the 2533 migraineurs that were eligible, 1137 (45%) suffered from lifetime depression. The following independent factors were associated with an increased depression prevalence: i) migraine-specific risk factors: high migraine attack frequency and the presence of allodynia, ii) general factors: being a bad sleeper, female gender, high BMI, being single, smoking, and a low alcohol consumption.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Aged', 'Cross-Sectional Studies', 'Depression', 'Female', 'Humans', 'Hyperalgesia', 'Male', 'Middle Aged', 'Migraine Disorders', 'Prevalence', 'Surveys and Questionnaires', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,755,284
Does tissue factor predict response to chemotherapy in esophageal cancer?
{ "contexts": [ "Neoadjuvant chemotherapy (NACT) improves the prognosis of patients with esophageal cancer who respond, but it is not effective in nonresponders. Therefore, it is crucial to establish a reliable method of predicting response before initiation of chemotherapy. Hypercoagulability, which is thought to be because of upregulation of tissue factor (TF) in cancer cells, was reported to be associated with chemoresistance. The aim of this study was to investigate the association between TF expression and response to NACT in esophageal cancer.", "In 67 patients with advanced esophageal cancer, TF expression in pretreatment biopsy samples was evaluated immunohistochemically and correlated with clinicopathologic factors and response to chemotherapy.", "TF was expressed by 43.3% of the tumors, but there were no correlations observed with any clinicopathologic parameters examined. Clinical and histologic responses to chemotherapy were significantly worse in TF-positive patients compared with TF-negative patients. Multivariate analysis revealed that TF expression was significantly associated with a poor clinical response (P = 0.0431). TF expression was also independently associated with poor progression-free survival (P = 0.0353)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Biopsy", "Carcinoma, Squamous Cell", "Disease Progression", "Disease-Free Survival", "Drug Resistance, Neoplasm", "Esophageal Neoplasms", "Esophagus", "Female", "Humans", "Male", "Middle Aged", "Neoadjuvant Therapy", "Neoplasm Grading", "Predictive Value of Tests", "Prognosis", "Thrombophilia", "Thromboplastin" ] }
TF expression levels in pretreatment biopsy samples are useful for predicting response to NACT in advanced esophageal cancer. Further studies of mechanisms underlying the relationship between TF expression and chemosensitivity are needed.
yes
[ { "from": "human", "value": "Question: Does tissue factor predict response to chemotherapy in esophageal cancer?\nContext: {'contexts': ['Neoadjuvant chemotherapy (NACT) improves the prognosis of patients with esophageal cancer who respond, but it is not effective in nonresponders. Therefore, it is crucial to establish a reliable method of predicting response before initiation of chemotherapy. Hypercoagulability, which is thought to be because of upregulation of tissue factor (TF) in cancer cells, was reported to be associated with chemoresistance. The aim of this study was to investigate the association between TF expression and response to NACT in esophageal cancer.', 'In 67 patients with advanced esophageal cancer, TF expression in pretreatment biopsy samples was evaluated immunohistochemically and correlated with clinicopathologic factors and response to chemotherapy.', 'TF was expressed by 43.3% of the tumors, but there were no correlations observed with any clinicopathologic parameters examined. Clinical and histologic responses to chemotherapy were significantly worse in TF-positive patients compared with TF-negative patients. Multivariate analysis revealed that TF expression was significantly associated with a poor clinical response (P\\xa0=\\xa00.0431). TF expression was also independently associated with poor progression-free survival (P\\xa0=\\xa00.0353).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Biopsy', 'Carcinoma, Squamous Cell', 'Disease Progression', 'Disease-Free Survival', 'Drug Resistance, Neoplasm', 'Esophageal Neoplasms', 'Esophagus', 'Female', 'Humans', 'Male', 'Middle Aged', 'Neoadjuvant Therapy', 'Neoplasm Grading', 'Predictive Value of Tests', 'Prognosis', 'Thrombophilia', 'Thromboplastin']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,772,521
Are the Randomized Olmesartan and Diabetes Microalbuminuria Prevention ( ROADMAP ) observational follow-up study : benefits of RAS blockade with olmesartan treatment sustained after study discontinuation?
{ "contexts": [ "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." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Aged", "Albuminuria", "Angiotensin II Type 1 Receptor Blockers", "Blood Pressure", "Cardiovascular Diseases", "Diabetes Mellitus, Type 2", "Diabetic Angiopathies", "Diabetic Nephropathies", "Female", "Follow-Up Studies", "Humans", "Imidazoles", "Kidney", "Logistic Models", "Male", "Middle Aged", "Odds Ratio", "Olmesartan Medoxomil", "Proportional Hazards Models", "Renin-Angiotensin System", "Risk Assessment", "Risk Factors", "Tetrazoles", "Time Factors", "Treatment Outcome" ] }
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.
yes
[ { "from": "human", "value": "Question: Are the Randomized Olmesartan and Diabetes Microalbuminuria Prevention ( ROADMAP ) observational follow-up study : benefits of RAS blockade with olmesartan treatment sustained after study discontinuation?\nContext: {'contexts': ['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.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Aged', 'Albuminuria', 'Angiotensin II Type 1 Receptor Blockers', 'Blood Pressure', 'Cardiovascular Diseases', 'Diabetes Mellitus, Type 2', 'Diabetic Angiopathies', 'Diabetic Nephropathies', 'Female', 'Follow-Up Studies', 'Humans', 'Imidazoles', 'Kidney', 'Logistic Models', 'Male', 'Middle Aged', 'Odds Ratio', 'Olmesartan Medoxomil', 'Proportional Hazards Models', 'Renin-Angiotensin System', 'Risk Assessment', 'Risk Factors', 'Tetrazoles', 'Time Factors', 'Treatment Outcome']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,772,522
Is nuclear localization of a1A-adrenergic receptors required for signaling in cardiac myocytes : an “ inside-out ” a1-AR signaling pathway?
{ "contexts": [ "Recent studies indicate that a1-adrenergic receptors (a1-ARs) are cardioprotective by preventing cardiac myocyte death and augmenting contractility in heart failure. Although G-protein-coupled receptors are assumed to localize to and signal at the plasma membrane, we previously demonstrated that endogenous a1-ARs localize to the nuclei in adult cardiac myocytes. However, the functional consequence of this nuclear localization remains unclear. Here, we attempted to reconcile nuclear localization of a1-ARs with their physiologic function by examining a1-AR-induced contractility in adult cardiac myocytes.", "By measuring shortening in unloaded, cultured adult cardiac myocytes, we found that the a1A-subtype regulated contractility through phosphorylation of cardiac troponin I (cTnI) at the protein kinase C (PKC) site, threonine 144. Reconstitution of an a1A-subtype nuclear localization mutant in cardiac myocytes lacking a1-ARs failed to rescue nuclear a1A-mediated phosphorylation of cTnI and myocyte contractility. Leptomycin B, the nuclear export inhibitor, also blocked a1A-mediated phosphorylation of cTnI. These data indicate that a1-AR signaling originates in the nucleus. Consistent with these observations, we localized the a1A-subtype to the inner nuclear membrane, identified PKCa, d, and e in the nucleus, and found that a1-ARs activate PKCd in nuclei isolated from adult cardiac myocytes. Finally, we found that a PKCd nuclear localization mutant blunted a1-induced phosphorylation of cTnI." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Animals", "Enzyme Activation", "HeLa Cells", "Humans", "Mice", "Mice, Inbred C57BL", "Mice, Knockout", "Mutation", "Myocardial Contraction", "Myocytes, Cardiac", "Nuclear Envelope", "Phosphorylation", "Protein Kinase C-delta", "Receptors, Adrenergic, alpha-1", "Signal Transduction", "Time Factors", "Transfection", "Troponin I" ] }
Together, our data identify a novel, “inside-out” nuclear a1A-subtype/PKCd/cTnI-signaling pathway that regulates contractile function in adult cardiac myocytes. Importantly, these data help resolve the discrepancy between nuclear localization of a1-ARs and a1-AR-mediated physiologic function.
yes
[ { "from": "human", "value": "Question: Is nuclear localization of a1A-adrenergic receptors required for signaling in cardiac myocytes : an “ inside-out ” a1-AR signaling pathway?\nContext: {'contexts': ['Recent studies indicate that a1-adrenergic receptors (a1-ARs) are cardioprotective by preventing cardiac myocyte death and augmenting contractility in heart failure. Although G-protein-coupled receptors are assumed to localize to and signal at the plasma membrane, we previously demonstrated that endogenous a1-ARs localize to the nuclei in adult cardiac myocytes. However, the functional consequence of this nuclear localization remains unclear. Here, we attempted to reconcile nuclear localization of a1-ARs with their physiologic function by examining a1-AR-induced contractility in adult cardiac myocytes.', 'By measuring shortening in unloaded, cultured adult cardiac myocytes, we found that the a1A-subtype regulated contractility through phosphorylation of cardiac troponin I (cTnI) at the protein kinase C (PKC) site, threonine 144. Reconstitution of an a1A-subtype nuclear localization mutant in cardiac myocytes lacking a1-ARs failed to rescue nuclear a1A-mediated phosphorylation of cTnI and myocyte contractility. Leptomycin B, the nuclear export inhibitor, also blocked a1A-mediated phosphorylation of cTnI. These data indicate that a1-AR signaling originates in the nucleus. Consistent with these observations, we localized the a1A-subtype to the inner nuclear membrane, identified PKCa, d, and e in the nucleus, and found that a1-ARs activate PKCd in nuclei isolated from adult cardiac myocytes. Finally, we found that a PKCd nuclear localization mutant blunted a1-induced phosphorylation of cTnI.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Animals', 'Enzyme Activation', 'HeLa Cells', 'Humans', 'Mice', 'Mice, Inbred C57BL', 'Mice, Knockout', 'Mutation', 'Myocardial Contraction', 'Myocytes, Cardiac', 'Nuclear Envelope', 'Phosphorylation', 'Protein Kinase C-delta', 'Receptors, Adrenergic, alpha-1', 'Signal Transduction', 'Time Factors', 'Transfection', 'Troponin I']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,755,105
Does activation of mTOR contribute to foam cell formation in the radial arteries of patients with end-stage renal disease?
{ "contexts": [ "Our previous in-vivo and in-vitro studies demonstrated that inflammation accelerated the progression of atherosclerosis via the dysregulation of the low-density lipoprotein receptor (LDLr) pathway. The current study aimed to investigate the effects and their underlying mechanisms of inflammation on lipid accumulation in the radial arteries of endstage renal disease (ESRD) patients with arteriovenostomy.", "30 ESRD patients with arteriovenostomy were included. The patients were divided into two groups based on their plasma levels of C-reactive protein: a control (n = 16) and an inflamed group (n = 14). The expression of tumor necrosis factor-alpha (TNF-alpha) and monocyte chemotactic protein-1 of the radial arteries were increased in the inflamed group. Foam cell formation and lipid droplet accumulation were examined by hematoxylin and eosin (H & E) and Oil Red O staining. Intracellular cholesterol trafficking-related proteins were examined by immunohistochemistry and immunofluorescent staining.", "There was significant lipid accumulation in the radial arteries of the inflamed group compared with the control. Further analysis demonstrated that this accumulation was correlated with the increased protein expression of LDLr, sterol regulatory element-binding protein-2 (SREBP-2), and SREBP cleavageactivating protein (SCAP). Confocal microscopy showed that inflammation enhanced the translocation of SCAP escorting SREBP-2 from the endoplasmic reticulum to the Golgi, thereby activating LDLr gene transcription. Interestingly, upregulated LDLr expression was positively associated with the increased protein expression of mammalian target of rapamycin (mTOR), which had enhanced coexpression with SREBP-2. This finding suggests that the activation of mTOR may be involved in LDLr pathway disruption through the upregulation of SREBP-2 expression." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Atherosclerosis", "Biomarkers", "C-Reactive Protein", "Case-Control Studies", "Chemokine CCL2", "Enzyme Activation", "Foam Cells", "Humans", "Inflammation Mediators", "Kidney Failure, Chronic", "Middle Aged", "Radial Artery", "Receptors, LDL", "Renal Dialysis", "TOR Serine-Threonine Kinases", "Tumor Necrosis Factor-alpha" ] }
Inflammation contributed to foam cell formation in the radial arteries of ESRD patients via the dysregulation of the LDLr pathway, which could be modulated by the activation of the mTOR pathway.
yes
[ { "from": "human", "value": "Question: Does activation of mTOR contribute to foam cell formation in the radial arteries of patients with end-stage renal disease?\nContext: {'contexts': ['Our previous in-vivo and in-vitro studies demonstrated that inflammation accelerated the progression of atherosclerosis via the dysregulation of the low-density lipoprotein receptor (LDLr) pathway. The current study aimed to investigate the effects and their underlying mechanisms of inflammation on lipid accumulation in the radial arteries of endstage renal disease (ESRD) patients with arteriovenostomy.', '30 ESRD patients with arteriovenostomy were included. The patients were divided into two groups based on their plasma levels of C-reactive protein: a control (n = 16) and an inflamed group (n = 14). The expression of tumor necrosis factor-alpha (TNF-alpha) and monocyte chemotactic protein-1 of the radial arteries were increased in the inflamed group. Foam cell formation and lipid droplet accumulation were examined by hematoxylin and eosin (H & E) and Oil Red O staining. Intracellular cholesterol trafficking-related proteins were examined by immunohistochemistry and immunofluorescent staining.', 'There was significant lipid accumulation in the radial arteries of the inflamed group compared with the control. Further analysis demonstrated that this accumulation was correlated with the increased protein expression of LDLr, sterol regulatory element-binding protein-2 (SREBP-2), and SREBP cleavageactivating protein (SCAP). Confocal microscopy showed that inflammation enhanced the translocation of SCAP escorting SREBP-2 from the endoplasmic reticulum to the Golgi, thereby activating LDLr gene transcription. Interestingly, upregulated LDLr expression was positively associated with the increased protein expression of mammalian target of rapamycin (mTOR), which had enhanced coexpression with SREBP-2. This finding suggests that the activation of mTOR may be involved in LDLr pathway disruption through the upregulation of SREBP-2 expression.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Atherosclerosis', 'Biomarkers', 'C-Reactive Protein', 'Case-Control Studies', 'Chemokine CCL2', 'Enzyme Activation', 'Foam Cells', 'Humans', 'Inflammation Mediators', 'Kidney Failure, Chronic', 'Middle Aged', 'Radial Artery', 'Receptors, LDL', 'Renal Dialysis', 'TOR Serine-Threonine Kinases', 'Tumor Necrosis Factor-alpha']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,761,460
Are nitric oxide , IL-6 and IL-13 increased in the exhaled breath condensates of children with allergic rhinitis?
{ "contexts": [ "To evaluate nitric oxide and interleukin (IL)-6, IL-8 and IL-13 in the exhaled breath of children with allergic rhinitis (AR), before and after intranasal allergen exposure.", "A total of 49 children with AR – comprising 20 who also had episodic asthma (AR+A) and 29 without asthma (AR) – were compared with 34 healthy controls. Nitric oxide concentrations in exhaled air (eNO) and IL-6, IL-8 and IL-13 in exhaled breath condensates (EBC) were measured in winter, outside the natural allergen exposure season, before and after an intranasal allergen challenge.", "The mean concentrations of eNO, IL-6 and IL-13 were significantly higher in the two AR groups. The concentration of IL-8 was below the assay detection limit in all EBC samples. The intranasal allergen challenge increased IL-13/EBC levels in both AR groups, but did not influence mean concentrations of eNO, IL-6 or IL-8. No challenge-related changes in IL-13/EBC were observed in the allergen-exposed controls or placebo-exposed children." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Allergens", "Breath Tests", "Child", "Female", "Humans", "Interleukin-13", "Interleukin-6", "Male", "Nitric Oxide", "Rhinitis, Allergic" ] }
Despite local application, the intranasal allergen challenge increased IL-13/EBC concentration in the AR children. As EBC reflects the status of lower airway segments, our observation may support the 'united airways' hypothesis, suggesting a functional link between the upper and lower airways.
yes
[ { "from": "human", "value": "Question: Are nitric oxide , IL-6 and IL-13 increased in the exhaled breath condensates of children with allergic rhinitis?\nContext: {'contexts': ['To evaluate nitric oxide and interleukin (IL)-6, IL-8 and IL-13 in the exhaled breath of children with allergic rhinitis (AR), before and after intranasal allergen exposure.', 'A total of 49 children with AR – comprising 20 who also had episodic asthma (AR+A) and 29 without asthma (AR) – were compared with 34 healthy controls. Nitric oxide concentrations in exhaled air (eNO) and IL-6, IL-8 and IL-13 in exhaled breath condensates (EBC) were measured in winter, outside the natural allergen exposure season, before and after an intranasal allergen challenge.', 'The mean concentrations of eNO, IL-6 and IL-13 were significantly higher in the two AR groups. The concentration of IL-8 was below the assay detection limit in all EBC samples. The intranasal allergen challenge increased IL-13/EBC levels in both AR groups, but did not influence mean concentrations of eNO, IL-6 or IL-8. No challenge-related changes in IL-13/EBC were observed in the allergen-exposed controls or placebo-exposed children.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Allergens', 'Breath Tests', 'Child', 'Female', 'Humans', 'Interleukin-13', 'Interleukin-6', 'Male', 'Nitric Oxide', 'Rhinitis, Allergic']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,754,904
Are human placenta-derived neurospheres susceptible to transformation after extensive in vitro expansion?
{ "contexts": [ "The cancer stem cell model links neoplastic cells with normal stem cell biology, but little is known on how normal stem cells are transformed into cancer stem cells.", "To investigate the processes underlying the transformation of normal stem cells we developed in vitro a cancer stem cell model from human amniotic and chorionic placenta membranes. In this model we studied the expression of specific stem cell molecules by flow cytometry, and genes, by real time RT-PCR. Microscopy immunfluorescence was employed to investigate the proliferative and differentiation patterns. Fluorescence microscopy and FACS were employed to investigate the proliferative and differentiation patterns. To evaluate the tumorigenic potential of our model we injected the cells into NOD.CB17-Prkdcscid/NCrHsd mice.", "Normal human stem cells from amniotic and chorionic placenta membranes were converted into neural cell lineages, under specific conditions, to form secondary neurospheres with a capacity for self-renewal. After extensive in vitro culture, these cells underwent spontaneous transformations and acquired a neuroblastoma (NB)-like phenotype with an elevated proliferative potential that is comparable to established neuroblastoma cell lines. The ability of these cells to transform their phenotype was evidenced by increased clonogenic ability in vitro; by augmented expression level of certain proliferation- and transformation-related genes (e.g., CCNA2, MYCN, ENPP2, GRIA3, and KIT); by the presence of multinucleated and hyperdiploid cells. We further demonstrated that the transformed phenotype is an NB by measuring the expression of NB-specific markers, disialoganglioside GD2 and N-Myc proteins." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Animals", "Cell Differentiation", "Cell Proliferation", "Cell Transformation, Neoplastic", "Cohort Studies", "Female", "Humans", "Male", "Mice, Inbred NOD", "Neoplastic Stem Cells", "Neuroblastoma", "Placenta", "Pregnancy" ] }
We have developed a cancer stem cell model starting from normal human stem cells derived from amniotic and chorionic placenta membranes. These cells are able to differentiate into neural cell lineages and to undergo spontaneous transformations and acquire an NB-like phenotype.
yes
[ { "from": "human", "value": "Question: Are human placenta-derived neurospheres susceptible to transformation after extensive in vitro expansion?\nContext: {'contexts': ['The cancer stem cell model links neoplastic cells with normal stem cell biology, but little is known on how normal stem cells are transformed into cancer stem cells.', 'To investigate the processes underlying the transformation of normal stem cells we developed in vitro a cancer stem cell model from human amniotic and chorionic placenta membranes. In this model we studied the expression of specific stem cell molecules by flow cytometry, and genes, by real time RT-PCR. Microscopy immunfluorescence was employed to investigate the proliferative and differentiation patterns. Fluorescence microscopy and FACS were employed to investigate the proliferative and differentiation patterns. To evaluate the tumorigenic potential of our model we injected the cells into NOD.CB17-Prkdcscid/NCrHsd mice.', 'Normal human stem cells from amniotic and chorionic placenta membranes were converted into neural cell lineages, under specific conditions, to form secondary neurospheres with a capacity for self-renewal. After extensive in vitro culture, these cells underwent spontaneous transformations and acquired a neuroblastoma (NB)-like phenotype with an elevated proliferative potential that is comparable to established neuroblastoma cell lines. The ability of these cells to transform their phenotype was evidenced by increased clonogenic ability in vitro; by augmented expression level of certain proliferation- and transformation-related genes (e.g., CCNA2, MYCN, ENPP2, GRIA3, and KIT); by the presence of multinucleated and hyperdiploid cells. We further demonstrated that the transformed phenotype is an NB by measuring the expression of NB-specific markers, disialoganglioside GD2 and N-Myc proteins.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Animals', 'Cell Differentiation', 'Cell Proliferation', 'Cell Transformation, Neoplastic', 'Cohort Studies', 'Female', 'Humans', 'Male', 'Mice, Inbred NOD', 'Neoplastic Stem Cells', 'Neuroblastoma', 'Placenta', 'Pregnancy']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,770,635
Are hDGF and ADAM9 novel molecular staging biomarkers , prognostic biomarkers and predictive biomarkers for adjuvant chemotherapy in surgically resected stage I non-small cell lung cancer?
{ "contexts": [ "This study was to investigate whether the expression of a disintegrin and metalloproteinase-9 (ADAM9) is correlated with the expression of hepatoma-derived growth factor (HDGF) in surgically resected non-small cell lung cancer (NSCLC), to evaluate the significance of HDGF and ADAM9 as novel molecular staging biomarkers, prognostic biomarkers and predictive biomarkers for postoperative adjuvant chemotherapy in surgically resected stage I NSCLC, to provide essential consistence proof to the possible novel pathway of HDGF-ADAM9 pathway.", "Sixty-three cases of resected stage I NSCLC with mediastinal N2 lymph node dissection were immunohistochemically analyzed for HDGF and ADAM9 protein expression. Multivariate analysis and survival analysis were conducted.", "HDGF and ADAM9 were observed highly expressed in NSCLC compared with normal control lung tissues (P < 0.05). HDGF high expression cases showed significantly lower survival rate (55.6 vs. 84.7 %, P = 0.009). HDGF high expression was an independent factor of shortened survival time in resected stage I NSCLC (P = 0.015). ADAM9 high expression cases showed significantly lower survival rate (56.9 vs. 88.7 %, P = 0.015). ADAM9 high expression was an independent factor of shortened survival time in resected stage I NSCLC (P = 0.021). Pearson's correlation analysis revealed that ADAM9 expression was correlated positively and significantly with HDGF expression in 63 cases of stage I NSCLC (r = 0.547, P = 0.000)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "ADAM Proteins", "Adenocarcinoma", "Adult", "Aged", "Biomarkers, Tumor", "Carcinoma, Non-Small-Cell Lung", "Chemotherapy, Adjuvant", "Female", "Humans", "Intercellular Signaling Peptides and Proteins", "Kaplan-Meier Estimate", "Lung Neoplasms", "Lymphatic Metastasis", "Male", "Membrane Proteins", "Middle Aged", "Neoplasm Staging", "Prognosis", "Proportional Hazards Models" ] }
These results clearly demonstrate that ADAM9 high expression is correlated positively and significantly with HDGF high expression, which provides essential evidence for the novel HDGF-ADAM9 pathway, through which HDGF promotes invasion and metastasis of NSCLC cells; HDGF and ADAM9 are novel molecular staging biomarkers, prognostic biomarkers, which might become useful predictive biomarkers for the selection of postoperative adjuvant chemotherapy treatment in surgically resected stage I NSCLC.
yes
[ { "from": "human", "value": "Question: Are hDGF and ADAM9 novel molecular staging biomarkers , prognostic biomarkers and predictive biomarkers for adjuvant chemotherapy in surgically resected stage I non-small cell lung cancer?\nContext: {'contexts': ['This study was to investigate whether the expression of a disintegrin and metalloproteinase-9 (ADAM9) is correlated with the expression of hepatoma-derived growth factor (HDGF) in surgically resected non-small cell lung cancer (NSCLC), to evaluate the significance of HDGF and ADAM9 as novel molecular staging biomarkers, prognostic biomarkers and predictive biomarkers for postoperative adjuvant chemotherapy in surgically resected stage I NSCLC, to provide essential consistence proof to the possible novel pathway of HDGF-ADAM9 pathway.', 'Sixty-three cases of resected stage I NSCLC with mediastinal N2 lymph node dissection were immunohistochemically analyzed for HDGF and ADAM9 protein expression. Multivariate analysis and survival analysis were conducted.', \"HDGF and ADAM9 were observed highly expressed in NSCLC compared with normal control lung tissues (P < 0.05). HDGF high expression cases showed significantly lower survival rate (55.6 vs. 84.7 %, P = 0.009). HDGF high expression was an independent factor of shortened survival time in resected stage I NSCLC (P = 0.015). ADAM9 high expression cases showed significantly lower survival rate (56.9 vs. 88.7 %, P = 0.015). ADAM9 high expression was an independent factor of shortened survival time in resected stage I NSCLC (P = 0.021). Pearson's correlation analysis revealed that ADAM9 expression was correlated positively and significantly with HDGF expression in 63 cases of stage I NSCLC (r = 0.547, P = 0.000).\"], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['ADAM Proteins', 'Adenocarcinoma', 'Adult', 'Aged', 'Biomarkers, Tumor', 'Carcinoma, Non-Small-Cell Lung', 'Chemotherapy, Adjuvant', 'Female', 'Humans', 'Intercellular Signaling Peptides and Proteins', 'Kaplan-Meier Estimate', 'Lung Neoplasms', 'Lymphatic Metastasis', 'Male', 'Membrane Proteins', 'Middle Aged', 'Neoplasm Staging', 'Prognosis', 'Proportional Hazards Models']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,748,670
Do brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS?
{ "contexts": [ "Based on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time.", "Forty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeated-measures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression.", "Patients with MS declined in cognitive efficiency and memory (p < 0.001). MLBG moderated decline in cognitive efficiency (p = 0.031, ηp (2) = 0.122), with larger MLBG protecting against decline. MLBG did not moderate memory decline (p = 0.234, ηp (2) = 0.039). Intellectual enrichment moderated decline in cognitive efficiency (p = 0.031, ηp (2) = 0.126) and memory (p = 0.037, ηp (2) = 0.115), with greater intellectual enrichment protecting against decline. MS disease progression was more negatively associated with change in cognitive efficiency and memory among patients with lower vs higher MLBG and intellectual enrichment." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Atrophy", "Brain", "Cognition Disorders", "Cognitive Reserve", "Disease Progression", "Female", "Humans", "Intelligence", "Magnetic Resonance Imaging", "Male", "Memory", "Middle Aged", "Multiple Sclerosis", "Neuropsychological Tests", "Vocabulary" ] }
We provide longitudinal support for theories of brain reserve and cognitive reserve in MS. Larger MLBG protects against decline in cognitive efficiency, and greater intellectual enrichment protects against decline in cognitive efficiency and memory. Consideration of these protective factors should improve prediction of future cognitive decline in patients with MS.
yes
[ { "from": "human", "value": "Question: Do brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS?\nContext: {'contexts': ['Based on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time.', 'Forty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeated-measures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression.', 'Patients with MS declined in cognitive efficiency and memory (p < 0.001). MLBG moderated decline in cognitive efficiency (p = 0.031, ηp (2) = 0.122), with larger MLBG protecting against decline. MLBG did not moderate memory decline (p = 0.234, ηp (2) = 0.039). Intellectual enrichment moderated decline in cognitive efficiency (p = 0.031, ηp (2) = 0.126) and memory (p = 0.037, ηp (2) = 0.115), with greater intellectual enrichment protecting against decline. MS disease progression was more negatively associated with change in cognitive efficiency and memory among patients with lower vs higher MLBG and intellectual enrichment.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Atrophy', 'Brain', 'Cognition Disorders', 'Cognitive Reserve', 'Disease Progression', 'Female', 'Humans', 'Intelligence', 'Magnetic Resonance Imaging', 'Male', 'Memory', 'Middle Aged', 'Multiple Sclerosis', 'Neuropsychological Tests', 'Vocabulary']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,768,901
Is perilipin-5 regulated by statins and controls triglyceride contents in the hepatocyte?
{ "contexts": [ "Perilipin-5 (PLIN5) is a member of the perilipin family of lipid droplet (LD)-associated proteins. PLIN5 is expressed in oxidative tissues including the liver, and is critical during LD biogenesis. Studies showed that statins reduce hepatic triglyceride contents in some patients with non-alcoholic fatty liver disease and in rodent models of diet-induced hepatosteatosis. Whether statins alter triglyceride synthesis, storage, and/or utilization within the hepatocyte is unknown, though. Here we tested the hypothesis that statins alter the metabolism of LD in the hepatocyte during physiological conditions, such as fasting-induced steatosis.", "Mice were gavaged with saline or atorvastatin, and the expression of LD-associated genes was determined in fed and fasted animals. The accumulation of triglycerides and LD was studied in mouse or human primary hepatocytes in response to statins, and following knock-down of SREBP2 or PLIN5.", "We show that statins decrease the levels of PLIN5, but not other LD-associated genes, in both mouse liver and mouse/human primary hepatocytes, which is paralleled by a significant reduction in both intracellular triglycerides and the number of LD. We identify an atypical negative sterol regulatory sequence in the proximal promoter of mouse/human PLIN5 that recruits the transcription factor SREBP2 and confers response to statins. Finally, we show that the statin-dependent reduction of hepatocyte triglyceride contents is mimicked by partial knock-down of PLIN5; conversely, ectopic overexpression of PLIN5 reverts the statin effect." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Hepatocytes", "Hydroxymethylglutaryl-CoA Reductase Inhibitors", "Intracellular Signaling Peptides and Proteins", "Lipid Droplets", "Male", "Mice", "Mice, Inbred C57BL", "Muscle Proteins", "Sterol Regulatory Element Binding Protein 2", "Triglycerides" ] }
PLIN5 is a physiological regulator of triglyceride metabolism in the liver, and likely contributes to the pleiotropic effects of statins.
yes
[ { "from": "human", "value": "Question: Is perilipin-5 regulated by statins and controls triglyceride contents in the hepatocyte?\nContext: {'contexts': ['Perilipin-5 (PLIN5) is a member of the perilipin family of lipid droplet (LD)-associated proteins. PLIN5 is expressed in oxidative tissues including the liver, and is critical during LD biogenesis. Studies showed that statins reduce hepatic triglyceride contents in some patients with non-alcoholic fatty liver disease and in rodent models of diet-induced hepatosteatosis. Whether statins alter triglyceride synthesis, storage, and/or utilization within the hepatocyte is unknown, though. Here we tested the hypothesis that statins alter the metabolism of LD in the hepatocyte during physiological conditions, such as fasting-induced steatosis.', 'Mice were gavaged with saline or atorvastatin, and the expression of LD-associated genes was determined in fed and fasted animals. The accumulation of triglycerides and LD was studied in mouse or human primary hepatocytes in response to statins, and following knock-down of SREBP2 or PLIN5.', 'We show that statins decrease the levels of PLIN5, but not other LD-associated genes, in both mouse liver and mouse/human primary hepatocytes, which is paralleled by a significant reduction in both intracellular triglycerides and the number of LD. We identify an atypical negative sterol regulatory sequence in the proximal promoter of mouse/human PLIN5 that recruits the transcription factor SREBP2 and confers response to statins. Finally, we show that the statin-dependent reduction of hepatocyte triglyceride contents is mimicked by partial knock-down of PLIN5; conversely, ectopic overexpression of PLIN5 reverts the statin effect.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Hepatocytes', 'Hydroxymethylglutaryl-CoA Reductase Inhibitors', 'Intracellular Signaling Peptides and Proteins', 'Lipid Droplets', 'Male', 'Mice', 'Mice, Inbred C57BL', 'Muscle Proteins', 'Sterol Regulatory Element Binding Protein 2', 'Triglycerides']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,759,065
Are sTI patients effective recruiters of undiagnosed cases of HIV : results of a social contact recruitment study in Malawi?
{ "contexts": [ "Patients with newly diagnosed HIV may be part of social networks with elevated prevalence of undiagnosed HIV infection. Social network recruitment by persons with newly diagnosed HIV may efficiently identify undiagnosed cases of HIV infection. We assessed social network recruitment as a strategy for identifying undiagnosed cases of HIV infection.", "In a sexually transmitted infection (STI) clinic in Lilongwe, Malawi, 3 groups of 45 \"seeds\" were enrolled: STI patients with newly diagnosed HIV, STI patients who were HIV-uninfected, and community controls. Seeds were asked to recruit up to 5 social \"contacts\" (sexual or nonsexual). Mean number of contacts recruited per group was calculated. HIV prevalence ratios (PRs) and number of contacts needed to test to identify 1 new case of HIV were compared between groups using generalized estimating equations with exchangeable correlation matrices.", "Mean number of contacts recruited was 1.3 for HIV-infected clinic seeds, 1.8 for HIV-uninfected clinic seeds, and 2.3 for community seeds. Contacts of HIV-infected clinic seeds had a higher HIV prevalence (PR: 3.2, 95% confidence interval: 1.3 to 7.8) than contacts of community seeds, but contacts of HIV-uninfected clinic seeds did not (PR: 1.1, 95% confidence interval: 0.4 to 3.3). Results were similar when restricted to nonsexual contacts. To identify 1 new case of HIV, it was necessary to test 8 contacts of HIV-infected clinic seeds, 10 contacts of HIV-uninfected clinic seeds, and 18 contacts of community seeds." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adult", "Female", "HIV Infections", "Humans", "Malawi", "Male", "Middle Aged", "Prevalence", "Social Support", "Young Adult" ] }
Social contact recruitment by newly diagnosed STI patients efficiently led to new HIV diagnoses. Research to replicate findings and guide implementation is needed.
yes
[ { "from": "human", "value": "Question: Are sTI patients effective recruiters of undiagnosed cases of HIV : results of a social contact recruitment study in Malawi?\nContext: {'contexts': ['Patients with newly diagnosed HIV may be part of social networks with elevated prevalence of undiagnosed HIV infection. Social network recruitment by persons with newly diagnosed HIV may efficiently identify undiagnosed cases of HIV infection. We assessed social network recruitment as a strategy for identifying undiagnosed cases of HIV infection.', 'In a sexually transmitted infection (STI) clinic in Lilongwe, Malawi, 3 groups of 45 \"seeds\" were enrolled: STI patients with newly diagnosed HIV, STI patients who were HIV-uninfected, and community controls. Seeds were asked to recruit up to 5 social \"contacts\" (sexual or nonsexual). Mean number of contacts recruited per group was calculated. HIV prevalence ratios (PRs) and number of contacts needed to test to identify 1 new case of HIV were compared between groups using generalized estimating equations with exchangeable correlation matrices.', 'Mean number of contacts recruited was 1.3 for HIV-infected clinic seeds, 1.8 for HIV-uninfected clinic seeds, and 2.3 for community seeds. Contacts of HIV-infected clinic seeds had a higher HIV prevalence (PR: 3.2, 95% confidence interval: 1.3 to 7.8) than contacts of community seeds, but contacts of HIV-uninfected clinic seeds did not (PR: 1.1, 95% confidence interval: 0.4 to 3.3). Results were similar when restricted to nonsexual contacts. To identify 1 new case of HIV, it was necessary to test 8 contacts of HIV-infected clinic seeds, 10 contacts of HIV-uninfected clinic seeds, and 18 contacts of community seeds.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Female', 'HIV Infections', 'Humans', 'Malawi', 'Male', 'Middle Aged', 'Prevalence', 'Social Support', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,778,098
Does endocardial focal activation originating from Purkinje fibers play a role in the maintenance of long duration ventricular fibrillation?
{ "contexts": [ "To determine the role of repetitive endocardial focal activations and Purkinje fibers in the maintenance of long duration ventricular fibrillation (LDVF, VF>1 minute) in canine hearts in vivo.", "The study was conducted in electrophysiological laboratory of Shanghai Ruijin hospital from July 2010 to August 2012. A 64-electrode basket was introduced through a carotid artery into the left ventricle (LV) of 11 beagle dogs for global endocardial electrical mapping. In the Lugol's solution group (n=5), the subendocardium was ablated by washing with Lugol's solution. In the control group, (n=6) saline was used for ablation. Before and after saline or Lugol ablation, we determined QRS duration and QT/QTc interval in sinus rhythm (SR). We also measured the activation rates in the first 2 seconds of each minute during 7 minutes of VF for each group. If VF terminated spontaneously in less than 7 minutes, the VF segments used in activation rate analysis were reduced accordingly.", "At the beginning of VF there was no difference between the groups in the activation rate. However, after 1 minute of LDVF the Lugol's solution group had significantly slower activation rate than the control group. In the control group, all episodes of LDVF (6/6) were successfully sustained for 7 minutes, while in the Lugol's solution group 4/5 episodes of LDVF spontaneously terminated before 7 minutes (4.8±1.4 minutes) (P=0.015). In the control group, at 5.1±1.3 minutes of LDVF, a successive, highly organized focal LV endocardial activation pattern was observed. During this period, activations partly arose in PF and spread to the working ventricular myocardium. Mapping analysis showed that these events were consistent with repetitive endocardial focal activations. No evidence of similar focal activations was observed in the Lugol's solution group." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Action Potentials", "Animals", "Dogs", "Electric Countershock", "Endocardium", "Iodides", "Male", "Purkinje Fibers", "Time Factors", "Ventricular Fibrillation" ] }
Repetitive endocardial focal activations in the LV endocardium may be associated with activation of subendocardial PFs. This mechanism may play an important role in the maintenance of LDVF.
yes
[ { "from": "human", "value": "Question: Does endocardial focal activation originating from Purkinje fibers play a role in the maintenance of long duration ventricular fibrillation?\nContext: {'contexts': ['To determine the role of repetitive endocardial focal activations and Purkinje fibers in the maintenance of long duration ventricular fibrillation (LDVF, VF>1 minute) in canine hearts in vivo.', \"The study was conducted in electrophysiological laboratory of Shanghai Ruijin hospital from July 2010 to August 2012. A 64-electrode basket was introduced through a carotid artery into the left ventricle (LV) of 11 beagle dogs for global endocardial electrical mapping. In the Lugol's solution group (n=5), the subendocardium was ablated by washing with Lugol's solution. In the control group, (n=6) saline was used for ablation. Before and after saline or Lugol ablation, we determined QRS duration and QT/QTc interval in sinus rhythm (SR). We also measured the activation rates in the first 2 seconds of each minute during 7 minutes of VF for each group. If VF terminated spontaneously in less than 7 minutes, the VF segments used in activation rate analysis were reduced accordingly.\", \"At the beginning of VF there was no difference between the groups in the activation rate. However, after 1 minute of LDVF the Lugol's solution group had significantly slower activation rate than the control group. In the control group, all episodes of LDVF (6/6) were successfully sustained for 7 minutes, while in the Lugol's solution group 4/5 episodes of LDVF spontaneously terminated before 7 minutes (4.8±1.4 minutes) (P=0.015). In the control group, at 5.1±1.3 minutes of LDVF, a successive, highly organized focal LV endocardial activation pattern was observed. During this period, activations partly arose in PF and spread to the working ventricular myocardium. Mapping analysis showed that these events were consistent with repetitive endocardial focal activations. No evidence of similar focal activations was observed in the Lugol's solution group.\"], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Action Potentials', 'Animals', 'Dogs', 'Electric Countershock', 'Endocardium', 'Iodides', 'Male', 'Purkinje Fibers', 'Time Factors', 'Ventricular Fibrillation']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,768,652
Does molecular profiling of contact dermatitis skin identify allergen-dependent differences in immune response?
{ "contexts": [ "Allergic contact dermatitis (ACD) is the most common occupational disease. Although murine contact hypersensitivity provides a framework for understanding ACD, it carries important differences from its human counterpart. Unlike the contact hypersensitivity model, which is induced by potent sensitizers (ie, dinitrofluorobenzene), human ACD is induced by weak-to-moderate sensitizers (ie, nickel), which cannot induce reactions in mice. Distinct hapten-specific immune-polarizing responses to potent inducers were suggested in mice, with unclear relevance to human ACD.", "We explored the possibility of distinct T-cell polarization responses in skin to common clinically relevant ACD allergens.", "Gene-expression and cellular studies were performed on common allergens (ie, nickel, fragrance, and rubber) compared with petrolatum-occluded skin, using RT-PCR, gene arrays, and immunohistochemistry.", "Despite similar clinical reactions in all allergen groups, distinct immune polarizations characterized different allergens. Although the common ACD transcriptome consisted of 149 differentially expressed genes across all allergens versus petrolatum, a much larger gene set was uniquely altered by individual allergens. Nickel demonstrated the highest immune activation, with potent inductions of innate immunity, TH1/TH17 and a TH22 component. Fragrance, and to a lesser extent rubber, demonstrated a strong TH2 bias, some TH22 polarization, and smaller TH1/TH17 contributions." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Allergens", "Animals", "Antigens, CD", "Cytokines", "Dermatitis, Allergic Contact", "Female", "Gene Expression Profiling", "Haptens", "Humans", "Male", "Mice", "Middle Aged", "Nickel", "Patch Tests", "Perfume", "Petrolatum", "Rubber", "Skin", "Species Specificity", "T-Lymphocyte Subsets", "Th1-Th2 Balance", "Transcriptome" ] }
Our study offers new insights into the pathogenesis of ACD, expanding the understanding of T-cell activation and associated cytokines in allergen-reactive tissues. It is the first study that defines the common transcriptome of clinically relevant sensitizers in human skin and identifies unique pathways preferentially activated by different allergens, suggesting that ACD cannot be considered a single entity.
yes
[ { "from": "human", "value": "Question: Does molecular profiling of contact dermatitis skin identify allergen-dependent differences in immune response?\nContext: {'contexts': ['Allergic contact dermatitis (ACD) is the most common occupational disease. Although murine contact hypersensitivity provides a framework for understanding ACD, it carries important differences from its human counterpart. Unlike the contact hypersensitivity model, which is induced by potent sensitizers (ie, dinitrofluorobenzene), human ACD is induced by weak-to-moderate sensitizers (ie, nickel), which cannot induce reactions in mice. Distinct hapten-specific immune-polarizing responses to potent inducers were suggested in mice, with unclear relevance to human ACD.', 'We explored the possibility of distinct T-cell polarization responses in skin to common clinically relevant ACD allergens.', 'Gene-expression and cellular studies were performed on common allergens (ie, nickel, fragrance, and rubber) compared with petrolatum-occluded skin, using RT-PCR, gene arrays, and immunohistochemistry.', 'Despite similar clinical reactions in all allergen groups, distinct immune polarizations characterized different allergens. Although the common ACD transcriptome consisted of 149 differentially expressed genes across all allergens versus petrolatum, a much larger gene set was uniquely altered by individual allergens. Nickel demonstrated the highest immune activation, with potent inductions of innate immunity, TH1/TH17 and a TH22 component. Fragrance, and to a lesser extent rubber, demonstrated a strong TH2 bias, some TH22 polarization, and smaller TH1/TH17 contributions.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Allergens', 'Animals', 'Antigens, CD', 'Cytokines', 'Dermatitis, Allergic Contact', 'Female', 'Gene Expression Profiling', 'Haptens', 'Humans', 'Male', 'Mice', 'Middle Aged', 'Nickel', 'Patch Tests', 'Perfume', 'Petrolatum', 'Rubber', 'Skin', 'Species Specificity', 'T-Lymphocyte Subsets', 'Th1-Th2 Balance', 'Transcriptome']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,746,336
Does implementing goal-directed protocols reduce length of stay after cardiac surgery?
{ "contexts": [ "To test the effect of a high reliability organization (HRO) intervention on patient lengths of stay in the CVICU and hospital. The authors proposed that (1) higher safety related evidence based protocol (SREBP) team compliance scores and (2) lower SREBP milestone scores are associated with shorter lengths of CVICU and hospital stay.", "A prospective, longitudinal observational evaluation was used to assess the effects of SREBP-focused rounding processes and a milestone-tracking tool.", "United States, university academic medical center's 27-bed CVICU.", "Six hundred sixty-five adult cardiac surgery patients and the CVICU care team (100 registered nurses and 16 clinical providers) participated.", "Team compliance was the proportion of SREBP-related team behaviors exhibited during daily rounds. Patients' milestone scores were the cumulative difference between actual and expected times for 4 SREBP milestones over 48 hours. Milestones achieved earlier than expected indicated reduced complication risk, and milestones achieved later than expected indicated increased risk. As team compliance increased, CVICU length of stay decreased 0.66 (95% CI: -0.04 to 1.28; p = 0.08) days; hospital stay decreased 0.89 times (95% CI: 0.77-1.03; p = 0.008). As the mean milestone scores increased from -7 to 12, length of ICU stay increased 2.63 (95% CI: 1.66-3.59; p<0.001) days; hospital length of stay increased 1.44 times (95% CI: 1.23-1.7; p = 0.05)." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Cardiac Surgical Procedures", "Clinical Protocols", "Critical Care", "Evidence-Based Medicine", "Female", "Goals", "Guideline Adherence", "Humans", "Length of Stay", "Longitudinal Studies", "Male", "Middle Aged", "Patient Care Team", "Patient Safety", "Prospective Studies", "Stroke Volume" ] }
A milestone-driven pathway supported by team rounding was associated with decreased lengths of CVICU and hospital stay. However, tracking patient trajectories by milestones suggests a more complex relationship than anticipated and presents new opportunities for SREBP implementation and research.
yes
[ { "from": "human", "value": "Question: Does implementing goal-directed protocols reduce length of stay after cardiac surgery?\nContext: {'contexts': ['To test the effect of a high reliability organization (HRO) intervention on patient lengths of stay in the CVICU and hospital. The authors proposed that (1) higher safety related evidence based protocol (SREBP) team compliance scores and (2) lower SREBP milestone scores are associated with shorter lengths of CVICU and hospital stay.', 'A prospective, longitudinal observational evaluation was used to assess the effects of SREBP-focused rounding processes and a milestone-tracking tool.', \"United States, university academic medical center's 27-bed CVICU.\", 'Six hundred sixty-five adult cardiac surgery patients and the CVICU care team (100 registered nurses and 16 clinical providers) participated.', \"Team compliance was the proportion of SREBP-related team behaviors exhibited during daily rounds. Patients' milestone scores were the cumulative difference between actual and expected times for 4 SREBP milestones over 48 hours. Milestones achieved earlier than expected indicated reduced complication risk, and milestones achieved later than expected indicated increased risk. As team compliance increased, CVICU length of stay decreased 0.66 (95% CI: -0.04 to 1.28; p = 0.08) days; hospital stay decreased 0.89 times (95% CI: 0.77-1.03; p = 0.008). As the mean milestone scores increased from -7 to 12, length of ICU stay increased 2.63 (95% CI: 1.66-3.59; p<0.001) days; hospital length of stay increased 1.44 times (95% CI: 1.23-1.7; p = 0.05).\"], 'labels': ['OBJECTIVE', 'METHODS', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Cardiac Surgical Procedures', 'Clinical Protocols', 'Critical Care', 'Evidence-Based Medicine', 'Female', 'Goals', 'Guideline Adherence', 'Humans', 'Length of Stay', 'Longitudinal Studies', 'Male', 'Middle Aged', 'Patient Care Team', 'Patient Safety', 'Prospective Studies', 'Stroke Volume']}" }, { "from": "gpt", "value": "Answer: yes" } ]
24,747,451
Does mesenteric lymph diversion abrogate 5-lipoxygenase activation in the kidney following trauma and hemorrhagic shock?
{ "contexts": [ "Early acute kidney injury (AKI) following trauma is associated with multiorgan failure and mortality. Leukotrienes have been implicated both in AKI and in acute lung injury. Activated 5-lipoxygenase (5-LO) colocalizes with 5-LO-activating protein (FLAP) in the first step of leukotriene production following trauma and hemorrhagic shock (T/HS). Diversion of postshock mesenteric lymph, which is rich in the 5-LO substrate of arachidonate, attenuates lung injury and decreases 5-LO/FLAP associations in the lung after T/HS. We hypothesized that mesenteric lymph diversion (MLD) will also attenuate postshock 5-LO-mediated AKI.", "Rats underwent T/HS (laparotomy, hemorrhagic shock to a mean arterial pressure of 30 mm Hg for 45 minutes, and resuscitation), and MLD was accomplished via cannulation of the mesenteric duct. Extent of kidney injury was determined via histology score and verified by urinary neutrophil gelatinase-associated lipocalin assay. Kidney sections were immunostained for 5-LO and FLAP, and colocalization was determined by fluorescence resonance energy transfer signal intensity. The end leukotriene products of 5-LO were determined in urine.", "AKI was evident in the T/HS group by derangement in kidney tubule architecture and confirmed by neutrophil gelatinase-associated lipocalin assay, whereas MLD during T/HS preserved renal tubule morphology at a sham level. MLD during T/HS decreased the associations between 5-LO and FLAP demonstrated by fluorescence resonance energy transfer microscopy and decreased leukotriene production in urine." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Acute Kidney Injury", "Acute Lung Injury", "Animals", "Arachidonate 5-Lipoxygenase", "Biomarkers", "Disease Models, Animal", "Enzyme Activation", "Injury Severity Score", "Kidney", "Leukotrienes", "Lymph Nodes", "Male", "Mesentery", "Multiple Organ Failure", "Random Allocation", "Rats", "Rats, Sprague-Dawley", "Sensitivity and Specificity", "Shock, Hemorrhagic", "Wounds and Injuries" ] }
5-LO and FLAP colocalize in the interstitium of the renal medulla following T/HS. MLD attenuates this phenomenon, which coincides with pathologic changes seen in tubules during kidney injury and biochemical evidence of AKI. These data suggest that gut-derived leukotriene substrate predisposes the kidney and the lung to subsequent injury.
yes
[ { "from": "human", "value": "Question: Does mesenteric lymph diversion abrogate 5-lipoxygenase activation in the kidney following trauma and hemorrhagic shock?\nContext: {'contexts': ['Early acute kidney injury (AKI) following trauma is associated with multiorgan failure and mortality. Leukotrienes have been implicated both in AKI and in acute lung injury. Activated 5-lipoxygenase (5-LO) colocalizes with 5-LO-activating protein (FLAP) in the first step of leukotriene production following trauma and hemorrhagic shock (T/HS). Diversion of postshock mesenteric lymph, which is rich in the 5-LO substrate of arachidonate, attenuates lung injury and decreases 5-LO/FLAP associations in the lung after T/HS. We hypothesized that mesenteric lymph diversion (MLD) will also attenuate postshock 5-LO-mediated AKI.', 'Rats underwent T/HS (laparotomy, hemorrhagic shock to a mean arterial pressure of 30 mm Hg for 45 minutes, and resuscitation), and MLD was accomplished via cannulation of the mesenteric duct. Extent of kidney injury was determined via histology score and verified by urinary neutrophil gelatinase-associated lipocalin assay. Kidney sections were immunostained for 5-LO and FLAP, and colocalization was determined by fluorescence resonance energy transfer signal intensity. The end leukotriene products of 5-LO were determined in urine.', 'AKI was evident in the T/HS group by derangement in kidney tubule architecture and confirmed by neutrophil gelatinase-associated lipocalin assay, whereas MLD during T/HS preserved renal tubule morphology at a sham level. MLD during T/HS decreased the associations between 5-LO and FLAP demonstrated by fluorescence resonance energy transfer microscopy and decreased leukotriene production in urine.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Acute Kidney Injury', 'Acute Lung Injury', 'Animals', 'Arachidonate 5-Lipoxygenase', 'Biomarkers', 'Disease Models, Animal', 'Enzyme Activation', 'Injury Severity Score', 'Kidney', 'Leukotrienes', 'Lymph Nodes', 'Male', 'Mesentery', 'Multiple Organ Failure', 'Random Allocation', 'Rats', 'Rats, Sprague-Dawley', 'Sensitivity and Specificity', 'Shock, Hemorrhagic', 'Wounds and Injuries']}" }, { "from": "gpt", "value": "Answer: yes" } ]