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26,528,065
Is combined glutathione S transferase M1/T1 null genotypes associated with type 2 diabetes mellitus?
{ "contexts": [ "Due to new genetic insights, a considerably large number of genes and polymorphic gene variants are screened and linked with the complex pathogenesis of type 2 diabetes (DM). Our study aimed to investigate the association between the two isoforms of the glutathione S-transferase genes (Glutathione S transferase isoemzyme type M1- GSTM1 and Glutathione S transferase isoemzyme type T1-GSTT1) and the prevalence of DM in the Northern Romanian population.", "We conducted a cross-sectional, randomized, case-control study evaluating the frequency of GSTM1 and GSTT1 null alleles in patients diagnosed with DM. A total of 106 patients diagnosed with DM and 124 healthy controls were included in the study. GSTM1 and GSTT1 null alleles genotyping was carried out using Multiplex PCR amplification of relevant gene fragments, followed by gel electrophoresis analysis of the resulting amplicons.", "Molecular analysis did not reveal an increased frequency of the null GSTM1 and GSTT1 alleles (mutant genotypes) respectively in the DM group compared to controls (p=0.171, OR=1.444 CI=0.852-2.447; p=0.647, OR=0.854, CI=0.436-1.673). Nevertheless, the combined GSTM1/GSTT1 null genotypes were statistically significantly higher in DM patients compared to control subjects (p=0.0021, OR=0.313, CI=0.149-0.655)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
The main finding of our study is that the combined, double GSTM1/GSTT1 null genotypes are to be considered among the polymorphic genetic risk factors for type 2 DM.
yes
[ { "from": "human", "value": "Question: Is combined glutathione S transferase M1/T1 null genotypes associated with type 2 diabetes mellitus?\nContext: {'contexts': ['Due to new genetic insights, a considerably large number of genes and polymorphic gene variants are screened and linked with the complex pathogenesis of type 2 diabetes (DM). Our study aimed to investigate the association between the two isoforms of the glutathione S-transferase genes (Glutathione S transferase isoemzyme type M1- GSTM1 and Glutathione S transferase isoemzyme type T1-GSTT1) and the prevalence of DM in the Northern Romanian population.', 'We conducted a cross-sectional, randomized, case-control study evaluating the frequency of GSTM1 and GSTT1 null alleles in patients diagnosed with DM. A total of 106 patients diagnosed with DM and 124 healthy controls were included in the study. GSTM1 and GSTT1 null alleles genotyping was carried out using Multiplex PCR amplification of relevant gene fragments, followed by gel electrophoresis analysis of the resulting amplicons.', 'Molecular analysis did not reveal an increased frequency of the null GSTM1 and GSTT1 alleles (mutant genotypes) respectively in the DM group compared to controls (p=0.171, OR=1.444 CI=0.852-2.447; p=0.647, OR=0.854, CI=0.436-1.673). Nevertheless, the combined GSTM1/GSTT1 null genotypes were statistically significantly higher in DM patients compared to control subjects (p=0.0021, OR=0.313, CI=0.149-0.655).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,551,442
Is vigorous exercise associated with superior metabolic profiles in polycystic ovary syndrome independent of total exercise expenditure?
{ "contexts": [ "To characterize metabolic features of women with polycystic ovary syndrome (PCOS) by exercise behavior and determine relative health benefits of different exercise intensities.", "Cross-sectional study.", "Tertiary academic institution.", "Three hundred and twenty-six women aged 14-52 years-old with PCOS by Rotterdam criteria examined between 2006 and 2013.", "International Physical Activity Questionnaire (IPAQ) administered to classify patients into three groups based on Department of Health and Human Services (DHHS) Guidelines of vigorous, moderate, and inactive, along with physical examination and serum testing.", "Blood pressure, body mass index (BMI), waist circumference, fasting lipids, fasting glucose and insulin, 2-hour 75-gram oral glucose tolerance, homeostatic model assessment of insulin resistance (HOMA-IR).", "The DHHS guidelines for adequate physical activity were met by 182 (56%) women. Compared with moderate exercisers and inactive women, the vigorous exercisers had lower BMI and lower HOMA-IR; higher levels of high-density lipoprotein cholesterol and sex hormone-binding globulin; and a reduced prevalence of the metabolic syndrome. In a multivariate logistic regression analysis controlling for age, BMI, and total energy expenditure, every hour of vigorous exercise reduced a patient's odds of metabolic syndrome by 22% (odds ratio 0.78; 95% confidence interval, 0.62, 0.99)." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "METHODS", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adult", "Biomarkers", "Blood Glucose", "Blood Pressure", "Body Mass Index", "Cross-Sectional Studies", "Energy Metabolism", "Exercise", "Female", "Glucose Tolerance Test", "Humans", "Insulin", "Insulin Resistance", "Lipids", "Logistic Models", "Metabolic Syndrome", "Middle Aged", "Multivariate Analysis", "Odds Ratio", "Polycystic Ovary Syndrome", "Prevalence", "Protective Factors", "Risk Factors", "Sedentary Behavior", "Surveys and Questionnaires", "Tertiary Care Centers", "Waist Circumference", "Young Adult" ] }
Women with PCOS who met DHHS guidelines for exercise demonstrated superior metabolic health parameters. Vigorous but not moderate activity is associated with reduced odds of the metabolic syndrome, independent of age, BMI, and total energy expenditure. PCOS patients should be encouraged to meet activity guidelines via vigorous physical activity.
yes
[ { "from": "human", "value": "Question: Is vigorous exercise associated with superior metabolic profiles in polycystic ovary syndrome independent of total exercise expenditure?\nContext: {'contexts': ['To characterize metabolic features of women with polycystic ovary syndrome (PCOS) by exercise behavior and determine relative health benefits of different exercise intensities.', 'Cross-sectional study.', 'Tertiary academic institution.', 'Three hundred and twenty-six women aged 14-52 years-old with PCOS by Rotterdam criteria examined between 2006 and\\xa02013.', 'International Physical Activity Questionnaire (IPAQ) administered to classify patients into three groups based on Department of Health and Human Services (DHHS) Guidelines of vigorous, moderate, and inactive, along with physical examination and serum testing.', 'Blood pressure, body mass index (BMI), waist circumference, fasting lipids, fasting glucose and insulin, 2-hour 75-gram oral glucose tolerance, homeostatic model assessment of insulin resistance (HOMA-IR).', \"The DHHS guidelines for adequate physical activity were met by 182 (56%) women. Compared with moderate exercisers and inactive women, the vigorous exercisers had lower BMI and lower HOMA-IR; higher levels of high-density lipoprotein cholesterol and sex hormone-binding globulin; and a reduced prevalence of the metabolic syndrome. In a multivariate logistic regression analysis controlling for age, BMI, and total energy expenditure, every hour of vigorous exercise reduced a patient's odds of metabolic syndrome by 22% (odds ratio 0.78; 95% confidence interval, 0.62, 0.99).\"], 'labels': ['OBJECTIVE', 'METHODS', 'METHODS', 'METHODS', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Biomarkers', 'Blood Glucose', 'Blood Pressure', 'Body Mass Index', 'Cross-Sectional Studies', 'Energy Metabolism', 'Exercise', 'Female', 'Glucose Tolerance Test', 'Humans', 'Insulin', 'Insulin Resistance', 'Lipids', 'Logistic Models', 'Metabolic Syndrome', 'Middle Aged', 'Multivariate Analysis', 'Odds Ratio', 'Polycystic Ovary Syndrome', 'Prevalence', 'Protective Factors', 'Risk Factors', 'Sedentary Behavior', 'Surveys and Questionnaires', 'Tertiary Care Centers', 'Waist Circumference', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,546,362
Do glutaminase-containing microvesicles from HIV-1-infected macrophages and immune-activated microglia induce neurotoxicity?
{ "contexts": [ "HIV-1-infected and/or immune-activated microglia and macrophages are pivotal in the pathogenesis of HIV-1-associated neurocognitive disorders (HAND). Glutaminase, a metabolic enzyme that facilitates glutamate generation, is upregulated and may play a pathogenic role in HAND. Our previous studies have demonstrated that glutaminase is released to the extracellular fluid during HIV-1 infection and neuroinflammation. However, key molecular mechanisms that regulate glutaminase release remain unknown. Recent advances in understanding intercellular trafficking have identified microvesicles (MVs) as a novel means of shedding cellular contents. We posit that during HIV-1 infection and immune activation, microvesicles may mediate glutaminase release, generating excessive and neurotoxic levels of glutamate.", "MVs isolated through differential centrifugation from cell-free supernatants of monocyte-derived macrophages (MDM) and BV2 microglia cell lines were first confirmed in electron microscopy and immunoblotting. As expected, we found elevated number of MVs, glutaminase immunoreactivities, as well as glutaminase enzyme activity in the supernatants of HIV-1 infected MDM and lipopolysaccharide (LPS)-activated microglia when compared with controls. The elevated glutaminase was blocked by GW4869, a neutral sphingomyelinase inhibitor known to inhibit MVs release, suggesting a critical role of MVs in mediating glutaminase release. More importantly, MVs from HIV-1-infected MDM and LPS-activated microglia induced significant neuronal injury in rat cortical neuron cultures. The MV neurotoxicity was blocked by a glutaminase inhibitor or GW4869, suggesting that the neurotoxic potential of HIV-1-infected MDM and LPS-activated microglia is dependent on the glutaminase-containing MVs." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Animals", "Cells, Cultured", "Glutaminase", "HIV-1", "Lipopolysaccharides", "Macrophages", "Microglia", "Neurons", "Rats, Sprague-Dawley" ] }
These findings support MVs as a potential pathway/mechanism of excessive glutamate generation and neurotoxicity in HAND and therefore MVs may serve as a novel therapeutic target.
yes
[ { "from": "human", "value": "Question: Do glutaminase-containing microvesicles from HIV-1-infected macrophages and immune-activated microglia induce neurotoxicity?\nContext: {'contexts': ['HIV-1-infected and/or immune-activated microglia and macrophages are pivotal in the pathogenesis of HIV-1-associated neurocognitive disorders (HAND). Glutaminase, a metabolic enzyme that facilitates glutamate generation, is upregulated and may play a pathogenic role in HAND. Our previous studies have demonstrated that glutaminase is released to the extracellular fluid during HIV-1 infection and neuroinflammation. However, key molecular mechanisms that regulate glutaminase release remain unknown. Recent advances in understanding intercellular trafficking have identified microvesicles (MVs) as a novel means of shedding cellular contents. We posit that during HIV-1 infection and immune activation, microvesicles may mediate glutaminase release, generating excessive and neurotoxic levels of glutamate.', 'MVs isolated through differential centrifugation from cell-free supernatants of monocyte-derived macrophages (MDM) and BV2 microglia cell lines were first confirmed in electron microscopy and immunoblotting. As expected, we found elevated number of MVs, glutaminase immunoreactivities, as well as glutaminase enzyme activity in the supernatants of HIV-1 infected MDM and lipopolysaccharide (LPS)-activated microglia when compared with controls. The elevated glutaminase was blocked by GW4869, a neutral sphingomyelinase inhibitor known to inhibit MVs release, suggesting a critical role of MVs in mediating glutaminase release. More importantly, MVs from HIV-1-infected MDM and LPS-activated microglia induced significant neuronal injury in rat cortical neuron cultures. The MV neurotoxicity was blocked by a glutaminase inhibitor or GW4869, suggesting that the neurotoxic potential of HIV-1-infected MDM and LPS-activated microglia is dependent on the glutaminase-containing MVs.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Animals', 'Cells, Cultured', 'Glutaminase', 'HIV-1', 'Lipopolysaccharides', 'Macrophages', 'Microglia', 'Neurons', 'Rats, Sprague-Dawley']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,531,321
Do fasting hyperinsulinaemia and 2-h glycaemia predict coronary heart disease in patients with type 2 diabetes?
{ "contexts": [ "Patients with diabetes are at greater risk of cardiovascular events. Insulin resistance (IR) and hyperinsulinaemia are both related to an increased cardiovascular risk, but whether IR predicts coronary heart disease (CHD) independently of other risk factors in patients with type 2 diabetes (T2D) is a topic of considerable controversy. The aim of the present study was to evaluate the prospective relationship of fasting insulin, HOMA-IR, fasting plasma glucose (FPG) and 2-h post-load glucose (2hPG) load with CHD incidence among such patients.", "A total of 2607 patients with T2D were enrolled in a community-dwelling cohort and followed for an average of 7.2 years. Conventional CHD risk factors, FPG, 2hPG, fasting insulin levels and HOMA-IR index were measured at baseline. Cox regression hazard ratios (HRs) were used to assess CHD risk.", "A total of 299 'hard' CHD events were registered (in 114 women and 185 men). Increasing levels of fasting insulinaemia were positively associated with CHD incidence. This correlation persisted after controlling for gender, body mass index, blood pressure, lipid profile, medication use and HbA1c [HR for each increase in quartile (fully adjusted model): 1.18 (95% CI: 1.06-1.32); P<0.01]. 2hPG showed a non-linear association with incident CHD [HR of highest vs lowest quartile: 1.64 (95% CI: 1.03-2.61)]. Fasting glycaemia was not associated with CHD risk, whereas HOMA-IR had a direct and independent correlation with CHD risk [HR for each one-quartile increase: 1.19 (95% CI: 1.07-1.34); P<0.01]." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Blood Glucose", "Cohort Studies", "Coronary Disease", "Diabetes Mellitus, Type 2", "Fasting", "Female", "Glucose Tolerance Test", "Humans", "Hyperinsulinism", "Insulin Resistance", "Male", "Middle Aged", "Risk Factors" ] }
Fasting insulin levels are positively associated with incidence of CHD in T2D. Furthermore, 2hPG appears to be a significant predictor of incident CHD independently of other risk factors, including HbA1c. These findings suggest that strategies targeting the reduction of insulinaemia and post-load glycaemia may be useful for preventing cardiovascular complications.
yes
[ { "from": "human", "value": "Question: Do fasting hyperinsulinaemia and 2-h glycaemia predict coronary heart disease in patients with type 2 diabetes?\nContext: {'contexts': ['Patients with diabetes are at greater risk of cardiovascular events. Insulin resistance (IR) and hyperinsulinaemia are both related to an increased cardiovascular risk, but whether IR predicts coronary heart disease (CHD) independently of other risk factors in patients with type 2 diabetes (T2D) is a topic of considerable controversy. The aim of the present study was to evaluate the prospective relationship of fasting insulin, HOMA-IR, fasting plasma glucose (FPG) and 2-h post-load glucose (2hPG) load with CHD incidence among such patients.', 'A total of 2607 patients with T2D were enrolled in a community-dwelling cohort and followed for an average of 7.2 years. Conventional CHD risk factors, FPG, 2hPG, fasting insulin levels and HOMA-IR index were measured at baseline. Cox regression hazard ratios (HRs) were used to assess CHD risk.', \"A total of 299 'hard' CHD events were registered (in 114 women and 185 men). Increasing levels of fasting insulinaemia were positively associated with CHD incidence. This correlation persisted after controlling for gender, body mass index, blood pressure, lipid profile, medication use and HbA1c [HR for each increase in quartile (fully adjusted model): 1.18 (95% CI: 1.06-1.32); P<0.01]. 2hPG showed a non-linear association with incident CHD [HR of highest vs lowest quartile: 1.64 (95% CI: 1.03-2.61)]. Fasting glycaemia was not associated with CHD risk, whereas HOMA-IR had a direct and independent correlation with CHD risk [HR for each one-quartile increase: 1.19 (95% CI: 1.07-1.34); P<0.01].\"], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Blood Glucose', 'Cohort Studies', 'Coronary Disease', 'Diabetes Mellitus, Type 2', 'Fasting', 'Female', 'Glucose Tolerance Test', 'Humans', 'Hyperinsulinism', 'Insulin Resistance', 'Male', 'Middle Aged', 'Risk Factors']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,548,998
Is mechanical stress associated with right ventricular response to pulmonary valve replacement in patients with repaired tetralogy of Fallot?
{ "contexts": [ "Patients with repaired tetralogy of Fallot account for a substantial proportion of cases with late-onset right ventricular failure. The current surgical approach, which includes pulmonary valve replacement/insertion, has yielded mixed results. Therefore, it may be clinically useful to identify parameters that can be used to predict right ventricular function response to pulmonary valve replacement.", "Cardiac magnetic resonance data before and 6 months after pulmonary valve replacement were obtained from 16 patients with repaired tetralogy of Fallot (8 male, 8 female; median age, 42.75 years). Right ventricular ejection fraction change from pre- to postpulmonary valve replacement was used as the outcome. The patients were divided into group 1 (n = 8, better outcome) and group 2 (n = 8, worst outcome). Cardiac magnetic resonance-based patient-specific computational right ventricular/left ventricular models were constructed, and right ventricular mechanical stress and strain, wall thickness, curvature, and volumes were obtained for analysis.", "Our results indicated that right ventricular wall stress was the best single predictor for postpulmonary valve replacement outcome with an area under the receiver operating characteristic curve of 0.819. Mean values of stress, strain, wall thickness, and longitudinal curvature differed significantly between the 2 groups with right ventricular wall stress showing the largest difference. Mean right ventricular stress in group 2 was 103% higher than in group 1." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Area Under Curve", "Biomechanical Phenomena", "Cardiac Surgical Procedures", "Female", "Heart Valve Prosthesis Implantation", "Humans", "Image Interpretation, Computer-Assisted", "Magnetic Resonance Imaging, Cine", "Male", "Models, Cardiovascular", "Predictive Value of Tests", "Pulmonary Valve Insufficiency", "ROC Curve", "Recovery of Function", "Stress, Mechanical", "Stroke Volume", "Tetralogy of Fallot", "Time Factors", "Treatment Outcome", "Ventricular Dysfunction, Right", "Ventricular Function, Right", "Ventricular Remodeling" ] }
Computational modeling and right ventricular stress may be used as tools to identify right ventricular function response to pulmonary valve replacement. Large-scale clinical studies are needed to validate these preliminary findings.
yes
[ { "from": "human", "value": "Question: Is mechanical stress associated with right ventricular response to pulmonary valve replacement in patients with repaired tetralogy of Fallot?\nContext: {'contexts': ['Patients with repaired tetralogy of Fallot account for a substantial proportion of cases with late-onset right ventricular failure. The current surgical approach, which includes pulmonary valve replacement/insertion, has yielded mixed results. Therefore, it may be clinically useful to identify parameters that can be used to predict right ventricular function response to pulmonary valve replacement.', 'Cardiac magnetic resonance data before and 6 months after pulmonary valve replacement were obtained from 16 patients with repaired tetralogy of Fallot (8 male, 8 female; median age, 42.75 years). Right ventricular ejection fraction change from pre- to postpulmonary valve replacement was used as the outcome. The patients were divided into group 1 (n = 8, better outcome) and group 2 (n = 8, worst outcome). Cardiac magnetic resonance-based patient-specific computational right ventricular/left ventricular models were constructed, and right ventricular mechanical stress and strain, wall thickness, curvature, and volumes were obtained for analysis.', 'Our results indicated that right ventricular wall stress was the best single predictor for postpulmonary valve replacement outcome with an area under the receiver operating characteristic curve of 0.819. Mean values of stress, strain, wall thickness, and longitudinal curvature differed significantly between the 2 groups with right ventricular wall stress showing the largest difference. Mean right ventricular stress in group 2 was 103% higher than in group 1.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Area Under Curve', 'Biomechanical Phenomena', 'Cardiac Surgical Procedures', 'Female', 'Heart Valve Prosthesis Implantation', 'Humans', 'Image Interpretation, Computer-Assisted', 'Magnetic Resonance Imaging, Cine', 'Male', 'Models, Cardiovascular', 'Predictive Value of Tests', 'Pulmonary Valve Insufficiency', 'ROC Curve', 'Recovery of Function', 'Stress, Mechanical', 'Stroke Volume', 'Tetralogy of Fallot', 'Time Factors', 'Treatment Outcome', 'Ventricular Dysfunction, Right', 'Ventricular Function, Right', 'Ventricular Remodeling']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,529,046
Do nucleoside Reverse Transcriptase Inhibitors Suppress Laser-Induced Choroidal Neovascularization in Mice?
{ "contexts": [ "To evaluate the efficacy of nucleoside reverse transcriptase inhibitors (NRTIs) in the laser-induced mouse model of choroidal neovascularization (CNV).", "We evaluated the NRTIs lamivudine (3TC), zidovudine (AZT), and abacavir (ABC) and the P2X7 antagonist A438079. Choroidal neovascularization was induced by laser injury in C57BL/6J wild-type, Nlrp3-/-, and P2rx7-/- mice, and CNV volume was measured after 7 days by confocal microscopy. Drugs were administered by intravitreous injection immediately after the laser injury. Vascular endothelial growth factor-A in RPE-choroid lysates was measured 3 days after laser injury by ELISA. HEK293 cells expressing human and mouse P2X7 were exposed to the selective P2X7 receptor agonist 2', 3'-(benzoyl-4-benzoyl)-ATP (Bz-ATP) with or without 3TC, and VEGF-A levels in media were measured by ELISA.", "Intravitreous injection of 3TC, AZT, and ABC significantly suppressed laser-induced CNV in C57BL/6J wild-type and Nlrp3-/- mice (P < 0.05) but not in P2rx7-/- mice. Intravitreous injection of A438079 also suppressed the laser-induced CNV (P < 0.05). The NRTIs 3TC, AZT, and ABC blocked VEGF-A levels in the RPE/choroid after laser injury in wild-type (P < 0.05) but not P2rx7-/- mice. Moreover, there was no additive effect of 3TC on CNV inhibition when coadministered with a neutralizing VEGF-A antibody. Stimulation of human and mouse P2X7-expressing HEK293 cells with Bz-ATP increased VEGF secretion (P < 0.001), which was abrogated by 3TC (P < 0.001). Stimulation of primary human RPE cells with Bz-ATP increased VEGFA and IL6 mRNA levels, which were abrogated by 3TC." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Choroidal Neovascularization", "Disease Models, Animal", "Enzyme-Linked Immunosorbent Assay", "Eye Proteins", "Fluorescein Angiography", "Fundus Oculi", "HEK293 Cells", "Humans", "Intravitreal Injections", "Lasers", "Mice", "Mice, Inbred C57BL", "Microscopy, Confocal", "Reverse Transcriptase Inhibitors" ] }
Multiple clinically relevant NRTIs suppressed laser-induced CNV and downregulated VEGF-A, via P2X7.
yes
[ { "from": "human", "value": "Question: Do nucleoside Reverse Transcriptase Inhibitors Suppress Laser-Induced Choroidal Neovascularization in Mice?\nContext: {'contexts': ['To evaluate the efficacy of nucleoside reverse transcriptase inhibitors (NRTIs) in the laser-induced mouse model of choroidal neovascularization (CNV).', \"We evaluated the NRTIs lamivudine (3TC), zidovudine (AZT), and abacavir (ABC) and the P2X7 antagonist A438079. Choroidal neovascularization was induced by laser injury in C57BL/6J wild-type, Nlrp3-/-, and P2rx7-/- mice, and CNV volume was measured after 7 days by confocal microscopy. Drugs were administered by intravitreous injection immediately after the laser injury. Vascular endothelial growth factor-A in RPE-choroid lysates was measured 3 days after laser injury by ELISA. HEK293 cells expressing human and mouse P2X7 were exposed to the selective P2X7 receptor agonist 2', 3'-(benzoyl-4-benzoyl)-ATP (Bz-ATP) with or without 3TC, and VEGF-A levels in media were measured by ELISA.\", 'Intravitreous injection of 3TC, AZT, and ABC significantly suppressed laser-induced CNV in C57BL/6J wild-type and Nlrp3-/- mice (P < 0.05) but not in P2rx7-/- mice. Intravitreous injection of A438079 also suppressed the laser-induced CNV (P < 0.05). The NRTIs 3TC, AZT, and ABC blocked VEGF-A levels in the RPE/choroid after laser injury in wild-type (P < 0.05) but not P2rx7-/- mice. Moreover, there was no additive effect of 3TC on CNV inhibition when coadministered with a neutralizing VEGF-A antibody. Stimulation of human and mouse P2X7-expressing HEK293 cells with Bz-ATP increased VEGF secretion (P < 0.001), which was abrogated by 3TC (P < 0.001). Stimulation of primary human RPE cells with Bz-ATP increased VEGFA and IL6 mRNA levels, which were abrogated by 3TC.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Choroidal Neovascularization', 'Disease Models, Animal', 'Enzyme-Linked Immunosorbent Assay', 'Eye Proteins', 'Fluorescein Angiography', 'Fundus Oculi', 'HEK293 Cells', 'Humans', 'Intravitreal Injections', 'Lasers', 'Mice', 'Mice, Inbred C57BL', 'Microscopy, Confocal', 'Reverse Transcriptase Inhibitors']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,553,429
Is obesity associated with increased postoperative complications after operative management of tibial shaft fractures?
{ "contexts": [ "To assess the association of obesity and postoperative complications after operative management of tibial shaft fractures.", "Patients who underwent operative management of a tibial shaft fracture were identified in a national database by Current Procedural Terminology (CPT) codes for: (1) open reduction and internal fixation (ORIF) and (2) intramedullary nailing (IMN) procedures in the setting of International Classification of Diseases, Ninth Revision (ICD-9) codes for tibial shaft fracture. These groups were then divided into non-obese, obese, and morbidly obese cohorts using ICD-9 codes. Each cohort was then assessed for grouped complications within 90 days, removal of implants within 6 months, and nonunion within 9 months postoperatively. Odds ratios and 95% confidence intervals were calculated.", "From 2005 to 2012, 14,638 patients who underwent operative management of tibial shaft fractures were identified, including 4425 (30.2%) ORIF and 10,213 (69.8%) IMN. Overall, 1091 patients (7.4%) were coded as obese and 820 (5.6%) morbidly obese. In each operative group, obesity and morbid obesity was associated with a substantial increase in the rate of major and minor medical complications, venous thromboembolism, infection, procedures for implant removal, and nonunion." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Databases, Factual", "Female", "Fracture Fixation, Intramedullary", "Fracture Healing", "Fractures, Malunited", "Humans", "Male", "Middle Aged", "Obesity, Morbid", "Odds Ratio", "Patient Education as Topic", "Postoperative Complications", "Preoperative Care", "Retrospective Studies", "Surgical Wound Infection", "Tibial Fractures", "United States", "Venous Thromboembolism" ] }
In patients who undergo either ORIF or IMN for tibial shaft fractures, obesity and its related medical comorbidities are associated with significantly increased rates of postoperative medical complications, infection, nonunion, and implant removal compared to non-obese patients.
yes
[ { "from": "human", "value": "Question: Is obesity associated with increased postoperative complications after operative management of tibial shaft fractures?\nContext: {'contexts': ['To assess the association of obesity and postoperative complications after operative management of tibial shaft fractures.', 'Patients who underwent operative management of a tibial shaft fracture were identified in a national database by Current Procedural Terminology (CPT) codes for: (1) open reduction and internal fixation (ORIF) and (2) intramedullary nailing (IMN) procedures in the setting of International Classification of Diseases, Ninth Revision (ICD-9) codes for tibial shaft fracture. These groups were then divided into non-obese, obese, and morbidly obese cohorts using ICD-9 codes. Each cohort was then assessed for grouped complications within 90 days, removal of implants within 6 months, and nonunion within 9 months postoperatively. Odds ratios and 95% confidence intervals were calculated.', 'From 2005 to 2012, 14,638 patients who underwent operative management of tibial shaft fractures were identified, including 4425 (30.2%) ORIF and 10,213 (69.8%) IMN. Overall, 1091 patients (7.4%) were coded as obese and 820 (5.6%) morbidly obese. In each operative group, obesity and morbid obesity was associated with a substantial increase in the rate of major and minor medical complications, venous thromboembolism, infection, procedures for implant removal, and nonunion.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Databases, Factual', 'Female', 'Fracture Fixation, Intramedullary', 'Fracture Healing', 'Fractures, Malunited', 'Humans', 'Male', 'Middle Aged', 'Obesity, Morbid', 'Odds Ratio', 'Patient Education as Topic', 'Postoperative Complications', 'Preoperative Care', 'Retrospective Studies', 'Surgical Wound Infection', 'Tibial Fractures', 'United States', 'Venous Thromboembolism']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,542,235
Does mR Elastography demonstrate Increased Brain Stiffness in Normal Pressure Hydrocephalus?
{ "contexts": [ "Normal pressure hydrocephalus is a reversible neurologic disorder characterized by a triad of cognitive impairment, gait abnormality, and urinary incontinence that is commonly treated with ventriculoperitoneal shunt placement. However, multiple overlapping symptoms often make it difficult to differentiate normal pressure hydrocephalus from other types of dementia, and improved diagnostic techniques would help patient management. MR elastography is a novel diagnostic tool that could potentially identify patients with normal pressure hydrocephalus. The purpose of this study was to assess brain stiffness changes in patients with normal pressure hydrocephalus compared with age- and sex-matched cognitively healthy individuals.", "MR elastography was performed on 10 patients with normal pressure hydrocephalus and 21 age- and sex-matched volunteers with no known neurologic disorders. Image acquisition was conducted on a 3T MR imaging scanner. Shear waves with 60-Hz vibration frequency were transmitted into the brain by a pillowlike passive driver. A novel postprocessing technique resistant to noise and edge artifacts was implemented to determine regional brain stiffness. The Wilcoxon rank sum test and linear regression were used for statistical analysis.", "A significant increase in stiffness was observed in the cerebrum (P = .001), occipital lobe (P < .001), parietal lobe (P = .001), and the temporal lobe (P = .02) in the normal pressure hydrocephalus group compared with healthy controls. However, no significant difference was noted in other regions of the brain, including the frontal lobe (P = .07), deep gray and white matter (P = .43), or cerebellum (P = .20)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Brain", "Elasticity Imaging Techniques", "Female", "Humans", "Hydrocephalus, Normal Pressure", "Image Interpretation, Computer-Assisted", "Magnetic Resonance Imaging", "Male", "Middle Aged" ] }
This study demonstrates increased brain stiffness in patients with normal pressure hydrocephalus compared with age- and sex-matched healthy controls; these findings should motivate future studies investigating the use of MR elastography for this condition and the efficacy of shunt therapy.
yes
[ { "from": "human", "value": "Question: Does mR Elastography demonstrate Increased Brain Stiffness in Normal Pressure Hydrocephalus?\nContext: {'contexts': ['Normal pressure hydrocephalus is a reversible neurologic disorder characterized by a triad of cognitive impairment, gait abnormality, and urinary incontinence that is commonly treated with ventriculoperitoneal shunt placement. However, multiple overlapping symptoms often make it difficult to differentiate normal pressure hydrocephalus from other types of dementia, and improved diagnostic techniques would help patient management. MR elastography is a novel diagnostic tool that could potentially identify patients with normal pressure hydrocephalus. The purpose of this study was to assess brain stiffness changes in patients with normal pressure hydrocephalus compared with age- and sex-matched cognitively healthy individuals.', 'MR elastography was performed on 10 patients with normal pressure hydrocephalus and 21 age- and sex-matched volunteers with no known neurologic disorders. Image acquisition was conducted on a 3T MR imaging scanner. Shear waves with 60-Hz vibration frequency were transmitted into the brain by a pillowlike passive driver. A novel postprocessing technique resistant to noise and edge artifacts was implemented to determine regional brain stiffness. The Wilcoxon rank sum test and linear regression were used for statistical analysis.', 'A significant increase in stiffness was observed in the cerebrum (P = .001), occipital lobe (P < .001), parietal lobe (P = .001), and the temporal lobe (P = .02) in the normal pressure hydrocephalus group compared with healthy controls. However, no significant difference was noted in other regions of the brain, including the frontal lobe (P = .07), deep gray and white matter (P = .43), or cerebellum (P = .20).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Brain', 'Elasticity Imaging Techniques', 'Female', 'Humans', 'Hydrocephalus, Normal Pressure', 'Image Interpretation, Computer-Assisted', 'Magnetic Resonance Imaging', 'Male', 'Middle Aged']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,553,403
Are copper surfaces associated with significantly lower concentrations of bacteria on selected surfaces within a pediatric intensive care unit?
{ "contexts": [ "Health care-associated infections result in significant patient morbidity and mortality. Although cleaning can remove pathogens present on hospital surfaces, those surfaces may be inadequately cleaned or recontaminated within minutes. Because of copper's inherent and continuous antimicrobial properties, copper surfaces offer a solution to complement cleaning. The objective of this study was to quantitatively assess the bacterial microbial burden coincident with an assessment of the ability of antimicrobial copper to limit the microbial burden associated with 3 surfaces in a pediatric intensive care unit.", "A pragmatic trial was conducted enrolling 1,012 patients from 2 high acuity care units within a 249-bed tertiary care pediatric hospital over 12 months. The microbial burden was determined from 3 frequently encountered surfaces, regardless of room occupancy, twice monthly, from 16 rooms, 8 outfitted normally and 8 outfitted with antimicrobial copper.", "Copper surfaces were found to be equivalently antimicrobial in pediatric settings to activities reported for adult medical intensive care units. The log10 reduction to the microbial burden from antimicrobial copper surfaced bed rails was 1.996 (99%). Surprisingly, introduction of copper objects to 8 study rooms was found to suppress the microbial burden recovered from objects assessed in control rooms by log10 of 1.863 (73%)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Anti-Infective Agents", "Bacteria", "Bacterial Infections", "Child", "Chile", "Copper", "Cross Infection", "Disinfection", "Environmental Microbiology", "Humans", "Intensive Care Units, Pediatric", "Tertiary Care Centers" ] }
Copper surfaces warrant serious consideration when contemplating the introduction of no-touch disinfection technologies for reducing burden to limit acquisition of HAIs.
yes
[ { "from": "human", "value": "Question: Are copper surfaces associated with significantly lower concentrations of bacteria on selected surfaces within a pediatric intensive care unit?\nContext: {'contexts': [\"Health care-associated infections result in significant patient morbidity and mortality. Although cleaning can remove pathogens present on hospital surfaces, those surfaces may be inadequately cleaned or recontaminated within minutes. Because of copper's inherent and continuous antimicrobial properties, copper surfaces offer a solution to complement cleaning. The objective of this study was to quantitatively assess the bacterial microbial burden coincident with an assessment of the ability of antimicrobial copper to limit the microbial burden associated with 3 surfaces in a pediatric intensive care unit.\", 'A pragmatic trial was conducted enrolling 1,012 patients from 2 high acuity care units within a\\xa0249-bed tertiary care pediatric hospital over 12 months. The microbial burden was determined from 3\\xa0frequently encountered surfaces, regardless of room occupancy, twice monthly, from 16 rooms, 8\\xa0outfitted normally and 8 outfitted with antimicrobial copper.', 'Copper surfaces were found to be equivalently antimicrobial in pediatric settings to activities reported for adult medical intensive care units. The log10 reduction to the microbial burden from antimicrobial copper surfaced bed rails was 1.996 (99%). Surprisingly, introduction of copper objects to 8\\xa0study rooms was found to suppress the microbial burden recovered from objects assessed in control rooms by log10 of 1.863 (73%).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Anti-Infective Agents', 'Bacteria', 'Bacterial Infections', 'Child', 'Chile', 'Copper', 'Cross Infection', 'Disinfection', 'Environmental Microbiology', 'Humans', 'Intensive Care Units, Pediatric', 'Tertiary Care Centers']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,546,586
Does increased pretreatment serum IFN-β/α ratio predict non-response to tumour necrosis factor α inhibition in rheumatoid arthritis?
{ "contexts": [ "Studies suggest that circulating type I interferon (IFN) may predict response to biological agents in rheumatoid arthritis (RA). Prediction of response prior to initiating therapy would represent a major advancement.", "We studied sera from a test set of 32 patients with RA from the Auto-immune Biomarkers Collaborative Network Consortium and a validation set of 92 patients with RA from the Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository registry. The test set included those with good response or no response to tumour necrosis factor (TNF) inhibitors at 14 weeks by European League Against Rheumatism criteria. The validation set included subjects with good, moderate or no response at 12 weeks. Total serum type I IFN activity, IFN-α and IFN-β activity were measured using a functional reporter cell assay.", "In the test set, an increased ratio of IFN-β to IFN-α (IFN-β/α activity ratio) in pretreatment serum associated with lack of response to TNF inhibition (p=0.013). Anti-cyclic citrullinated peptide antibody titre and class of TNF inhibitor did not influence this relationship. A receiver-operator curve supported a ratio of 1.3 as the optimal cut-off. In the validation set, subjects with an IFN-β/α activity ratio >1.3 were significantly more likely to have non-response than good response (OR=6.67, p=0.018). The test had 77% specificity and 45% sensitivity for prediction of non-response compared with moderate or good response. Meta-analysis of test and validation sets confirmed strong predictive capacity of IFN-β/α activity ratio (p=0.005)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Antirheumatic Agents", "Arthritis, Rheumatoid", "Biomarkers", "Databases, Factual", "Female", "Humans", "Interferon-alpha", "Interferon-beta", "Male", "Middle Aged", "Predictive Value of Tests", "Prognosis", "Registries", "Sensitivity and Specificity", "Treatment Outcome", "Tumor Necrosis Factor-alpha", "Young Adult" ] }
Increased pretreatment serum IFN-β/α ratio strongly associated with non-response to TNF inhibition. This study supports further investigation of serum type I IFN in predicting outcome of TNF inhibition in RA.
yes
[ { "from": "human", "value": "Question: Does increased pretreatment serum IFN-β/α ratio predict non-response to tumour necrosis factor α inhibition in rheumatoid arthritis?\nContext: {'contexts': ['Studies suggest that circulating type I interferon (IFN) may predict response to biological agents in rheumatoid arthritis (RA). Prediction of response prior to initiating therapy would represent a major advancement.', 'We studied sera from a test set of 32 patients with RA from the Auto-immune Biomarkers Collaborative Network Consortium and a validation set of 92 patients with RA from the Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository registry. The test set included those with good response or no response to tumour necrosis factor (TNF) inhibitors at 14\\u2005weeks by European League Against Rheumatism criteria. The validation set included subjects with good, moderate or no response at 12\\u2005weeks. Total serum type I IFN activity, IFN-α and IFN-β activity were measured using a functional reporter cell assay.', 'In the test set, an increased ratio of IFN-β to IFN-α (IFN-β/α activity ratio) in pretreatment serum associated with lack of response to TNF inhibition (p=0.013). Anti-cyclic citrullinated peptide antibody titre and class of TNF inhibitor did not influence this relationship. A receiver-operator curve supported a ratio of 1.3 as the optimal cut-off. In the validation set, subjects with an IFN-β/α activity ratio >1.3 were significantly more likely to have non-response than good response (OR=6.67, p=0.018). The test had 77% specificity and 45% sensitivity for prediction of non-response compared with moderate or good response. Meta-analysis of test and validation sets confirmed strong predictive capacity of IFN-β/α activity ratio (p=0.005).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Antirheumatic Agents', 'Arthritis, Rheumatoid', 'Biomarkers', 'Databases, Factual', 'Female', 'Humans', 'Interferon-alpha', 'Interferon-beta', 'Male', 'Middle Aged', 'Predictive Value of Tests', 'Prognosis', 'Registries', 'Sensitivity and Specificity', 'Treatment Outcome', 'Tumor Necrosis Factor-alpha', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,540,171
Is degree of Rectal Distension Seen on Prostate Radiotherapy Planning CT Scan a Negative Prognostic Factor in the Modern Era of Image-Guided Radiotherapy?
{ "contexts": [ "Studies have shown that rectal distension has a significant impact on treatment failure in patients receiving radical radiotherapy for prostate cancer. A distended rectum contributes to excessive organ movement during treatment, resulting in significant underdosing of the target volume and higher treatment failure rates. The increasing use of highly conformal, precise radiotherapy techniques places greater importance on reducing this risk. We tested whether imaging during radiotherapy helps minimise the negative impact that rectal distension has on long-term tumour control.", "The rectal diameter (anterior/posterior and lateral) was prospectively measured at radiotherapy planning in 172 consecutive patients undergoing radical radiotherapy with three-dimensional conformal radiotherapy. Daily, and then weekly, imaging during radiotherapy ensured that prostate movement remained within predefined tolerances. Patients were followed up for a median of 72 months with regular prostate-specific antigen (PSA) measurements to ascertain biochemical PSA relapse and survival information." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Aged", "Biomarkers, Tumor", "Dilatation, Pathologic", "Disease Progression", "Disease-Free Survival", "Follow-Up Studies", "Humans", "Imaging, Three-Dimensional", "Kaplan-Meier Estimate", "Male", "Middle Aged", "Neoplasm Recurrence, Local", "Predictive Value of Tests", "Prognosis", "Prospective Studies", "Prostate-Specific Antigen", "Prostatic Neoplasms", "Radiotherapy Dosage", "Radiotherapy Planning, Computer-Assisted", "Radiotherapy, Computer-Assisted", "Radiotherapy, Conformal", "Radiotherapy, Image-Guided", "Rectum", "Risk Factors", "Time Factors", "Tomography, X-Ray Computed", "Treatment Failure" ] }
In this cohort of predominately high-risk localised prostate cancer, rectal distension had no significant impact on PSA relapse. We suggest that regular imaging during radiotherapy negates the risk caused by rectal distension on local treatment failure.
no
[ { "from": "human", "value": "Question: Is degree of Rectal Distension Seen on Prostate Radiotherapy Planning CT Scan a Negative Prognostic Factor in the Modern Era of Image-Guided Radiotherapy?\nContext: {'contexts': ['Studies have shown that rectal distension has a significant impact on treatment failure in patients receiving radical radiotherapy for prostate cancer. A distended rectum contributes to excessive organ movement during treatment, resulting in significant underdosing of the target volume and higher treatment failure rates. The increasing use of highly conformal, precise radiotherapy techniques places greater importance on reducing this risk. We tested whether imaging during radiotherapy helps minimise the negative impact that rectal distension has on long-term tumour control.', 'The rectal diameter (anterior/posterior and lateral) was prospectively measured at radiotherapy planning in 172 consecutive patients undergoing radical radiotherapy with three-dimensional conformal radiotherapy. Daily, and then weekly, imaging during radiotherapy ensured that prostate movement remained within predefined tolerances. Patients were followed up for a median of 72 months with regular prostate-specific antigen (PSA) measurements to ascertain biochemical PSA relapse and survival information.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Aged', 'Biomarkers, Tumor', 'Dilatation, Pathologic', 'Disease Progression', 'Disease-Free Survival', 'Follow-Up Studies', 'Humans', 'Imaging, Three-Dimensional', 'Kaplan-Meier Estimate', 'Male', 'Middle Aged', 'Neoplasm Recurrence, Local', 'Predictive Value of Tests', 'Prognosis', 'Prospective Studies', 'Prostate-Specific Antigen', 'Prostatic Neoplasms', 'Radiotherapy Dosage', 'Radiotherapy Planning, Computer-Assisted', 'Radiotherapy, Computer-Assisted', 'Radiotherapy, Conformal', 'Radiotherapy, Image-Guided', 'Rectum', 'Risk Factors', 'Time Factors', 'Tomography, X-Ray Computed', 'Treatment Failure']}" }, { "from": "gpt", "value": "Answer: no" } ]
26,538,180
Does boron-deficiency-responsive microRNAs and their targets in Citrus sinensis leave?
{ "contexts": [ "MicroRNAs play important roles in the adaptive responses of plants to nutrient deficiencies. Most research, however, has focused on nitrogen (N), phosphorus (P), sulfur (S), copper (Cu) and iron (Fe) deficiencies, limited data are available on the differential expression of miRNAs and their target genes in response to deficiencies of other nutrient elements. In this study, we identified the known and novel miRNAs as well as the boron (B)-deficiency-responsive miRNAs from citrus leaves in order to obtain the potential miRNAs related to the tolerance of citrus to B-deficiency.", "Seedlings of 'Xuegan' [Citrus sinensis (L.) Osbeck] were supplied every other day with B-deficient (0 μM H3BO3) or -sufficient (10 μM H3BO3) nutrient solution for 15 weeks. Thereafter, we sequenced two small RNA libraries from B-deficient and -sufficient (control) citrus leaves, respectively, using Illumina sequencing.", "Ninety one (83 known and 8 novel) up- and 81 (75 known and 6 novel) down-regulated miRNAs were isolated from B-deficient leaves. The great alteration of miRNA expression might contribute to the tolerance of citrus to B-deficiency. The adaptive responses of miRNAs to B-deficiency might related to several aspects: (a) attenuation of plant growth and development by repressing auxin signaling due to decreased TIR1 level and ARF-mediated gene expression by altering the expression of miR393, miR160 and miR3946; (b) maintaining leaf phenotype and enhancing the stress tolerance by up-regulating NACs targeted by miR159, miR782, miR3946 and miR7539; (c) activation of the stress responses and antioxidant system through down-regulating the expression of miR164, miR6260, miR5929, miR6214, miR3946 and miR3446; (d) decreasing the expression of major facilitator superfamily protein genes targeted by miR5037, thus lowering B export from plants. Also, B-deficiency-induced down-regulation of miR408 might play a role in plant tolerance to B-deficiency by regulating Cu homeostasis and enhancing superoxide dismutase activity." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Boron", "Citrus sinensis", "MicroRNAs", "Plant Leaves", "RNA, Plant" ] }
Our study reveals some novel responses of citrus to B-deficiency, which increase our understanding of the adaptive mechanisms of citrus to B-deficiency at the miRNA (post-transcriptional) level.
yes
[ { "from": "human", "value": "Question: Does boron-deficiency-responsive microRNAs and their targets in Citrus sinensis leave?\nContext: {'contexts': ['MicroRNAs play important roles in the adaptive responses of plants to nutrient deficiencies. Most research, however, has focused on nitrogen (N), phosphorus (P), sulfur (S), copper (Cu) and iron (Fe) deficiencies, limited data are available on the differential expression of miRNAs and their target genes in response to deficiencies of other nutrient elements. In this study, we identified the known and novel miRNAs as well as the boron (B)-deficiency-responsive miRNAs from citrus leaves in order to obtain the potential miRNAs related to the tolerance of citrus to B-deficiency.', \"Seedlings of 'Xuegan' [Citrus sinensis (L.) Osbeck] were supplied every other day with B-deficient (0 μM H3BO3) or -sufficient (10 μM H3BO3) nutrient solution for 15 weeks. Thereafter, we sequenced two small RNA libraries from B-deficient and -sufficient (control) citrus leaves, respectively, using Illumina sequencing.\", 'Ninety one (83 known and 8 novel) up- and 81 (75 known and 6 novel) down-regulated miRNAs were isolated from B-deficient leaves. The great alteration of miRNA expression might contribute to the tolerance of citrus to B-deficiency. The adaptive responses of miRNAs to B-deficiency might related to several aspects: (a) attenuation of plant growth and development by repressing auxin signaling due to decreased TIR1 level and ARF-mediated gene expression by altering the expression of miR393, miR160 and miR3946; (b) maintaining leaf phenotype and enhancing the stress tolerance by up-regulating NACs targeted by miR159, miR782, miR3946 and miR7539; (c) activation of the stress responses and antioxidant system through down-regulating the expression of miR164, miR6260, miR5929, miR6214, miR3946 and miR3446; (d) decreasing the expression of major facilitator superfamily protein genes targeted by miR5037, thus lowering B export from plants. Also, B-deficiency-induced down-regulation of miR408 might play a role in plant tolerance to B-deficiency by regulating Cu homeostasis and enhancing superoxide dismutase activity.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Boron', 'Citrus sinensis', 'MicroRNAs', 'Plant Leaves', 'RNA, Plant']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,554,648
Is overexpression of major CDKN3 transcripts associated with poor survival in lung adenocarcinoma?
{ "contexts": [ "The cyclin-dependent kinase inhibitor 3 (CDKN3) has been perceived as a tumour suppressor. Paradoxically, CDKN3 is often overexpressed in human cancer. It was unclear if CDKN3 overexpression is linked to alternative splicing variants or mutations that produce dominant-negative CDKN3.", "We analysed CDKN3 expression and its association with patient survival in three cohorts of lung adenocarcinoma. We also examined CDKN3 mutations in the Cancer Genome Atlas (TCGA) and the Moffitt Cancer Center's Total Cancer Care (TCC) projects. CDKN3 transcripts were further analysed in a panel of cell lines and lung adenocarcinoma tissues. CDKN3 mRNA and protein levels in different cell cycle phases were examined.", "CDKN3 is overexpressed in non small cell lung cancer. High CDKN3 expression is associated with poor overall survival in lung adenocarcinoma. Two CDKN3 transcripts were detected in all samples. These CDKN3 transcripts represent the full length CDKN3 mRNA and a normal transcript lacking exon 2, which encodes an out of frame 23-amino acid peptide with little homology to CDKN3. CDKN3 mutations were found to be very rare. CDKN3 mRNA and protein were elevated during the mitosis phase of cell cycle." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adenocarcinoma", "Amino Acid Sequence", "Cohort Studies", "Cyclin-Dependent Kinase Inhibitor Proteins", "Dual-Specificity Phosphatases", "Humans", "Lung Neoplasms", "Molecular Sequence Data", "RNA, Messenger", "Survival Analysis" ] }
CDKN3 overexpression is prognostic of poor overall survival in lung adenocarcinoma. CDKN3 overexpression in lung adenocarcinoma is not attributed to alternative splicing or mutation but is likely due to increased mitotic activity, arguing against CDKN3 as a tumour suppressor.
yes
[ { "from": "human", "value": "Question: Is overexpression of major CDKN3 transcripts associated with poor survival in lung adenocarcinoma?\nContext: {'contexts': ['The cyclin-dependent kinase inhibitor 3 (CDKN3) has been perceived as a tumour suppressor. Paradoxically, CDKN3 is often overexpressed in human cancer. It was unclear if CDKN3 overexpression is linked to alternative splicing variants or mutations that produce dominant-negative CDKN3.', \"We analysed CDKN3 expression and its association with patient survival in three cohorts of lung adenocarcinoma. We also examined CDKN3 mutations in the Cancer Genome Atlas (TCGA) and the Moffitt Cancer Center's Total Cancer Care (TCC) projects. CDKN3 transcripts were further analysed in a panel of cell lines and lung adenocarcinoma tissues. CDKN3 mRNA and protein levels in different cell cycle phases were examined.\", 'CDKN3 is overexpressed in non small cell lung cancer. High CDKN3 expression is associated with poor overall survival in lung adenocarcinoma. Two CDKN3 transcripts were detected in all samples. These CDKN3 transcripts represent the full length CDKN3 mRNA and a normal transcript lacking exon 2, which encodes an out of frame 23-amino acid peptide with little homology to CDKN3. CDKN3 mutations were found to be very rare. CDKN3 mRNA and protein were elevated during the mitosis phase of cell cycle.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adenocarcinoma', 'Amino Acid Sequence', 'Cohort Studies', 'Cyclin-Dependent Kinase Inhibitor Proteins', 'Dual-Specificity Phosphatases', 'Humans', 'Lung Neoplasms', 'Molecular Sequence Data', 'RNA, Messenger', 'Survival Analysis']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,551,585
Does fGFR4 be a Potential Predictive Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma?
{ "contexts": [ "The aim of this study was to investigate whether fibroblast growth factor receptor 4 (FGFR4) could serve as a potential therapeutic target, prognostic biomarker or biomarker predicting radiotherapy sensitivity in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC).", "FGFR4 immunohistochemistry and FGFR4/CEN5q FISH were performed on tissue microarrays from 212 OSCC and 238 OPSCC patients. FGFR4 genotypes were determined by PCR and DNA sequencing in 76 random OPSCC samples. The response to radiotherapy was evaluated 3 months after the last radiotherapy treatment session by a head and neck radiation oncologist and/or surgeon during clinic visits. The results were correlated to overall survival and response to radiotherapy.", "The FGFR4 protein was overexpressed in 64% (153/238) of OPSCCs and 41% (87/212) of OSCCs. The FGFR4 gene was amplified in 0.47% (1/212) of OSCCs and 0.42% (1/238) of OPSCCs, and the FGFR4 Gly388Arg polymorphism was detected in 62% (47/76) of OPSCCs. FGFR4 protein expression, FGFR4 gene copy numbers and FGFR4 genotypes were not related to overall survival or response to radiotherapy in OSCC or OPSCC." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Biomarkers, Tumor", "Carcinoma, Squamous Cell", "Female", "Genotype", "Humans", "Immunohistochemistry", "Male", "Middle Aged", "Mouth Neoplasms", "Oropharyngeal Neoplasms", "Polymerase Chain Reaction", "Polymorphism, Genetic", "Prognosis", "Receptor, Fibroblast Growth Factor, Type 4", "Sequence Analysis, DNA", "Tissue Array Analysis", "Up-Regulation" ] }
FGFR4 is frequently overexpressed in OSCC and OPSCC in the absence of gene amplification, and may serve as a potential predictive marker for FGFR4-directed targeted therapy in OSCC and OPSCC.
yes
[ { "from": "human", "value": "Question: Does fGFR4 be a Potential Predictive Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma?\nContext: {'contexts': ['The aim of this study was to investigate whether fibroblast growth factor receptor 4 (FGFR4) could serve as a potential therapeutic target, prognostic biomarker or biomarker predicting radiotherapy sensitivity in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC).', 'FGFR4 immunohistochemistry and FGFR4/CEN5q FISH were performed on tissue microarrays from 212 OSCC and 238 OPSCC patients. FGFR4 genotypes were determined by PCR and DNA sequencing in 76 random OPSCC samples. The response to radiotherapy was evaluated 3 months after the last radiotherapy treatment session by a head and neck radiation oncologist and/or surgeon during clinic visits. The results were correlated to overall survival and response to radiotherapy.', 'The FGFR4 protein was overexpressed in 64% (153/238) of OPSCCs and 41% (87/212) of OSCCs. The FGFR4 gene was amplified in 0.47% (1/212) of OSCCs and 0.42% (1/238) of OPSCCs, and the FGFR4 Gly388Arg polymorphism was detected in 62% (47/76) of OPSCCs. FGFR4 protein expression, FGFR4 gene copy numbers and FGFR4 genotypes were not related to overall survival or response to radiotherapy in OSCC or OPSCC.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Biomarkers, Tumor', 'Carcinoma, Squamous Cell', 'Female', 'Genotype', 'Humans', 'Immunohistochemistry', 'Male', 'Middle Aged', 'Mouth Neoplasms', 'Oropharyngeal Neoplasms', 'Polymerase Chain Reaction', 'Polymorphism, Genetic', 'Prognosis', 'Receptor, Fibroblast Growth Factor, Type 4', 'Sequence Analysis, DNA', 'Tissue Array Analysis', 'Up-Regulation']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,524,959
Do baseline cerebral oximetry values depend on non-modifiable patient characteristics?
{ "contexts": [ "The aim of the present study was to evaluate baseline regional cerebral oxygen saturation (rSO2) values and identify factors influencing preoperative rSO2 in elective minor surgery.", "Observational analysis post-hoc.", "Observational post-hoc analysis of data for the patient sample (n=50) of a previously conducted clinical trial in patients undergoing tumourectomy for breast cancer or inguinal hernia repair. Exclusion criteria included pre-existing cerebrovascular diseases, anaemia, baseline pulse oximetry <97% and low quality rSO2 sensor signals. Demographic data, comorbidities, and ASA physical status as well as height and weight were collected prospectively from all patients. Baseline rSO2 values were recorded while the patient breathed room air, using the INVOS 5100C monitor™ (Covidien, Dublin, Ireland).", "Thirty-seven women (72%) and 13 men (28%) 48 ± 13 years of age were enrolled in this study. Baseline rSO2 was 62.01 ± 10.38%. Baseline rSO2 was significantly different between men (67.6 ± 11.2%) and women (60 ± 9.4%), (P=0.023). There were also differences between baseline rSO2 and ASA physical status (ASA I: 67.6 ± 10.7%, ASA II: 61.6 ± 8.4%, ASA III: 55.8 ± 13.9%, P=0.045). Baseline rSO2 had a positive correlation with body weight (r=0.347, P=0.014) and height (r=0.345, P=0.014). We also found significant differences in baseline rSO2 among patients with and without chronic renal failure (P=0.005). No differences were found in any other studied variables." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adult", "Aged", "Aging", "Body Height", "Body Mass Index", "Body Weight", "Brain Chemistry", "Elective Surgical Procedures", "Female", "Humans", "Kidney Failure, Chronic", "Male", "Middle Aged", "Monitoring, Intraoperative", "Oximetry", "Oxygen", "Preoperative Care", "Reference Values", "Sex Characteristics", "Young Adult" ] }
Non-modifiable patient characteristics (ASA physical status, sex, chronic renal failure, body weight and height) influence baseline rSO2.
yes
[ { "from": "human", "value": "Question: Do baseline cerebral oximetry values depend on non-modifiable patient characteristics?\nContext: {'contexts': ['The aim of the present study was to evaluate baseline regional cerebral oxygen saturation (rSO2) values and identify factors influencing preoperative rSO2 in elective minor surgery.', 'Observational analysis post-hoc.', 'Observational post-hoc analysis of data for the patient sample (n=50) of a previously conducted clinical trial in patients undergoing tumourectomy for breast cancer or inguinal hernia repair. Exclusion criteria included pre-existing cerebrovascular diseases, anaemia, baseline pulse oximetry <97% and low quality rSO2 sensor signals. Demographic data, comorbidities, and ASA physical status as well as height and weight were collected prospectively from all patients. Baseline rSO2 values were recorded while the patient breathed room air, using the INVOS 5100C monitor™ (Covidien, Dublin, Ireland).', 'Thirty-seven women (72%) and 13 men (28%) 48 ± 13 years of age were enrolled in this study. Baseline rSO2 was 62.01 ± 10.38%. Baseline rSO2 was significantly different between men (67.6 ± 11.2%) and women (60 ± 9.4%), (P=0.023). There were also differences between baseline rSO2 and ASA physical status (ASA I: 67.6 ± 10.7%, ASA II: 61.6 ± 8.4%, ASA III: 55.8 ± 13.9%, P=0.045). Baseline rSO2 had a positive correlation with body weight (r=0.347, P=0.014) and height (r=0.345, P=0.014). We also found significant differences in baseline rSO2 among patients with and without chronic renal failure (P=0.005). No differences were found in any other studied variables.'], 'labels': ['OBJECTIVE', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Aged', 'Aging', 'Body Height', 'Body Mass Index', 'Body Weight', 'Brain Chemistry', 'Elective Surgical Procedures', 'Female', 'Humans', 'Kidney Failure, Chronic', 'Male', 'Middle Aged', 'Monitoring, Intraoperative', 'Oximetry', 'Oxygen', 'Preoperative Care', 'Reference Values', 'Sex Characteristics', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,525,607
Is global DNA hypomethylation associated with the development and poor prognosis of tongue squamous cell carcinoma?
{ "contexts": [ "Oral cancer is the 4th leading cause of cancer death for males and the top cancer in young adult males in Taiwan. Tongue squamous cell carcinoma (TSCC) is a common oral cancer and generally associated with poor prognosis. Global DNA hypomethylation at the 5 position of cytosine (5mC) is a well-known epigenetic feature of cancer. Therefore, the purpose of this study was to investigate the relationship of the global 5mC content with the tumorigenesis and prognosis of patients with TSCC.", "The levels of global 5mC were evaluated by immunohistochemistry using tissue microarray slides of 248 surgically resected TSCC and 202 corresponding tumor adjacent normal (TAN) tissues.", "We found that the level of 5mC in TSCC (P < 0.001) was significantly decreased as compared to TAN. Among TSCC tissues, decreased levels of 5mC were associated with female gender (P = 0.036). In addition, the global hypomethylation was associated with the poor disease-specific survival in TSCC patients (adjusted hazard ratio: 1.55, P = 0.043), especially for patients in older age group (> 50 years, P = 0.013), with moderate or poor cell differentiation (P = 0.044), early stage of disease (I-II, P = 0.046), small tumor size (T1-T2, P = 0.005), without lymph node involvement (P = 0.041), and ever received postoperative radiotherapy (P = 0.009)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "5-Methylcytosine", "Adult", "Biomarkers, Tumor", "Carcinogenesis", "Carcinoma, Squamous Cell", "Cell Differentiation", "DNA Methylation", "Epigenomics", "Female", "Head and Neck Neoplasms", "Humans", "Immunohistochemistry", "Lymph Nodes", "Lymphatic Metastasis", "Male", "Middle Aged", "Neoplasm Staging", "Prognosis", "Squamous Cell Carcinoma of Head and Neck", "Survival Rate", "Tongue Neoplasms" ] }
Global hypomethylation was an independent biomarker for the development and poor prognosis of TSCC.
yes
[ { "from": "human", "value": "Question: Is global DNA hypomethylation associated with the development and poor prognosis of tongue squamous cell carcinoma?\nContext: {'contexts': ['Oral cancer is the 4th leading cause of cancer death for males and the top cancer in young adult males in Taiwan. Tongue squamous cell carcinoma (TSCC) is a common oral cancer and generally associated with poor prognosis. Global DNA hypomethylation at the 5 position of cytosine (5mC) is a well-known epigenetic feature of cancer. Therefore, the purpose of this study was to investigate the relationship of the global 5mC content with the tumorigenesis and prognosis of patients with TSCC.', 'The levels of global 5mC were evaluated by immunohistochemistry using tissue microarray slides of 248 surgically resected TSCC and 202 corresponding tumor adjacent normal (TAN) tissues.', 'We found that the level of 5mC in TSCC (P < 0.001) was significantly decreased as compared to TAN. Among TSCC tissues, decreased levels of 5mC were associated with female gender (P = 0.036). In addition, the global hypomethylation was associated with the poor disease-specific survival in TSCC patients (adjusted hazard ratio: 1.55, P = 0.043), especially for patients in older age group (> 50 years, P = 0.013), with moderate or poor cell differentiation (P = 0.044), early stage of disease (I-II, P = 0.046), small tumor size (T1-T2, P = 0.005), without lymph node involvement (P = 0.041), and ever received postoperative radiotherapy (P = 0.009).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['5-Methylcytosine', 'Adult', 'Biomarkers, Tumor', 'Carcinogenesis', 'Carcinoma, Squamous Cell', 'Cell Differentiation', 'DNA Methylation', 'Epigenomics', 'Female', 'Head and Neck Neoplasms', 'Humans', 'Immunohistochemistry', 'Lymph Nodes', 'Lymphatic Metastasis', 'Male', 'Middle Aged', 'Neoplasm Staging', 'Prognosis', 'Squamous Cell Carcinoma of Head and Neck', 'Survival Rate', 'Tongue Neoplasms']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,542,848
Do postzygotic barriers isolate sympatric species of Cyrtandra ( Gesneriaceae ) in Hawaiian montane forest understories?
{ "contexts": [ "Recent reviews of reproductive isolation (RI) in plants propose that boundaries between closely related species are maintained predominantly through prezygotic mechanisms. However, few experimental studies have explored how boundaries are maintained in long-lived species. Hawaiian Cyrtandra presents an intriguing challenge to our understanding of RI, as it comprises 60 shrub or small tree species that are almost exclusively restricted to wet forests, where sympatry of multiple species is common.", "We assessed the relative strengths of pre- and postzygotic barriers among four species of Cyrtandra occurring at the extremes of the main Hawaiian Island's natural island-age gradient, Kaua'i (4.7 Myr) and Hawai'i Island (0.6 Myr), to contrast the strengths and stages of reproductive isolation among species at different stages of divergence.", "A combination of F1 seed germination, F1 seedling survival, and F1 seedling growth isolated (61-91%) three of the species from sympatric relatives. In contrast, the fourth species was isolated (59%) from its sympatric relative through phenological differences alone. Significant postzygotic barriers in between-island crosses were also observed in one species." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Biological Evolution", "Flowers", "Forests", "Genetic Speciation", "Geography", "Hawaii", "Hybridization, Genetic", "Islands", "Magnoliopsida", "Phenotype", "Plant Leaves", "Reproductive Isolation", "Seedlings", "Seeds", "Sympatry" ] }
Results suggest that boundaries between sympatric Cyrtandra species in Hawaii are maintained predominantly through postzygotic barriers. Observations from between-island crosses indicate that postzygotic barriers can arise in allopatry, which may be important in the initial divergence of populations. Future studies of RI in Cyrtandra should include a broader range of species to determine if postzygotic isolating barriers are foremost in the maintenance of species boundaries in this large genus.
yes
[ { "from": "human", "value": "Question: Do postzygotic barriers isolate sympatric species of Cyrtandra ( Gesneriaceae ) in Hawaiian montane forest understories?\nContext: {'contexts': ['Recent reviews of reproductive isolation (RI) in plants propose that boundaries between closely related species are maintained predominantly through prezygotic mechanisms. However, few experimental studies have explored how boundaries are maintained in long-lived species. Hawaiian Cyrtandra presents an intriguing challenge to our understanding of RI, as it comprises 60 shrub or small tree species that are almost exclusively restricted to wet forests, where sympatry of multiple species is common.', \"We assessed the relative strengths of pre- and postzygotic barriers among four species of Cyrtandra occurring at the extremes of the main Hawaiian Island's natural island-age gradient, Kaua'i (4.7 Myr) and Hawai'i Island (0.6 Myr), to contrast the strengths and stages of reproductive isolation among species at different stages of divergence.\", 'A combination of F1 seed germination, F1 seedling survival, and F1 seedling growth isolated (61-91%) three of the species from sympatric relatives. In contrast, the fourth species was isolated (59%) from its sympatric relative through phenological differences alone. Significant postzygotic barriers in between-island crosses were also observed in one species.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Biological Evolution', 'Flowers', 'Forests', 'Genetic Speciation', 'Geography', 'Hawaii', 'Hybridization, Genetic', 'Islands', 'Magnoliopsida', 'Phenotype', 'Plant Leaves', 'Reproductive Isolation', 'Seedlings', 'Seeds', 'Sympatry']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,542,842
Is selection on pollen and pistil traits during pollen competition affected by both sexual conflict and mixed mating in a self-compatible herb?
{ "contexts": [ "Although much attention has focused on the diversity of plant mating systems, only a few studies have considered the joint effects of mating system and sexual conflict in plant evolution. In mixed-mating Collinsia heterophylla, a sexual conflict over timing of stigma receptivity is proposed: pollen with a capacity to induce early onset of stigma receptivity secures paternity for early-arriving pollen (at the expense of reduced maternal seed set), whereas late onset of stigma receptivity mitigates the negative effects of early-arriving pollen. Here we investigated whether selection on pollen and pistil traits involved in sexual conflict is affected by the presence of both outcross- and self-pollen (mixed mating) during pollen competition.", "We conducted two-donor crosses at different floral developmental stages to explore male fitness (siring ability) and female fitness (seed set) in relation to male and female identity, pollen and pistil traits, and type of competitor pollen (outcross vs. self).", "Late-fertilizing pollen rather than rapidly growing pollen tubes was most successful in terms of siring success, especially in competition with self-pollen after pollination at early floral stages. Late stigma receptivity increased seed set after early-stage pollinations, in agreement with selection against antagonistic pollen." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Crosses, Genetic", "Models, Biological", "Plantago", "Plants, Medicinal", "Pollen", "Pollination", "Quantitative Trait, Heritable", "Seeds", "Self-Fertilization" ] }
Selection on pollen and pistil traits in C. heterophylla is affected by both sexual conflict and mixed mating, suggesting the importance of jointly considering these factors in plant evolution.
yes
[ { "from": "human", "value": "Question: Is selection on pollen and pistil traits during pollen competition affected by both sexual conflict and mixed mating in a self-compatible herb?\nContext: {'contexts': ['Although much attention has focused on the diversity of plant mating systems, only a few studies have considered the joint effects of mating system and sexual conflict in plant evolution. In mixed-mating Collinsia heterophylla, a sexual conflict over timing of stigma receptivity is proposed: pollen with a capacity to induce early onset of stigma receptivity secures paternity for early-arriving pollen (at the expense of reduced maternal seed set), whereas late onset of stigma receptivity mitigates the negative effects of early-arriving pollen. Here we investigated whether selection on pollen and pistil traits involved in sexual conflict is affected by the presence of both outcross- and self-pollen (mixed mating) during pollen competition.', 'We conducted two-donor crosses at different floral developmental stages to explore male fitness (siring ability) and female fitness (seed set) in relation to male and female identity, pollen and pistil traits, and type of competitor pollen (outcross vs. self).', 'Late-fertilizing pollen rather than rapidly growing pollen tubes was most successful in terms of siring success, especially in competition with self-pollen after pollination at early floral stages. Late stigma receptivity increased seed set after early-stage pollinations, in agreement with selection against antagonistic pollen.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Crosses, Genetic', 'Models, Biological', 'Plantago', 'Plants, Medicinal', 'Pollen', 'Pollination', 'Quantitative Trait, Heritable', 'Seeds', 'Self-Fertilization']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,550,029
Does identification of structural alert for liver and kidney toxicity using repeated dose toxicity data?
{ "contexts": [ "The potential for a compound to cause hepatotoxicity and nephrotoxicity is a matter of extreme interest for human health risk assessment. To assess liver and kidney toxicity, repeated-dose toxicity (RDT) studies are conducted mainly on rodents. However, these tests are expensive, time-consuming and require large numbers of animals. For early toxicity screening, in silico models can be applied, reducing the costs, time and animals used. Among in silico approaches, structure-activity relationship (SAR) methods, based on the identification of chemical substructures (structural alerts, SAs) related to a particular activity (toxicity), are widely employed.", "We identified and evaluated some SAs related to liver and kidney toxicity, using RDT data on rats taken from the hazard evaluation support system (HESS) database. We considered only SAs that gave the best percentages of true positives (TP)." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [] }
It was not possible to assign an unambiguous mode of action for all the SAs, but a mechanistic explanation is provided for some of them. Such achievements may help in the early identification of liver and renal toxicity of substances.
yes
[ { "from": "human", "value": "Question: Does identification of structural alert for liver and kidney toxicity using repeated dose toxicity data?\nContext: {'contexts': ['The potential for a compound to cause hepatotoxicity and nephrotoxicity is a matter of extreme interest for human health risk assessment. To assess liver and kidney toxicity, repeated-dose toxicity (RDT) studies are conducted mainly on rodents. However, these tests are expensive, time-consuming and require large numbers of animals. For early toxicity screening, in silico models can be applied, reducing the costs, time and animals used. Among in silico approaches, structure-activity relationship (SAR) methods, based on the identification of chemical substructures (structural alerts, SAs) related to a particular activity (toxicity), are widely employed.', 'We identified and evaluated some SAs related to liver and kidney toxicity, using RDT data on rats taken from the hazard evaluation support system (HESS) database. We considered only SAs that gave the best percentages of true positives (TP).'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,544,874
Does cytochrome P450 Oxidoreductase influence CYP2B6 Activity in Cyclophosphamide Bioactivation?
{ "contexts": [ "Cyclophosphamide is commonly used as an important component in conditioning prior to hematopoietic stem cell transplantation, a curative treatment for several hematological diseases. Cyclophosphamide is a prodrug activated mainly by cytochrome P450 2B6 (CYP2B6) in the liver. A high degree of inter- and intra-individual variation in cyclophosphamide kinetics has been reported in several studies.", "Hydroxylation of cyclophosphamide was investigated in vitro using three microsomal batches of CYP2B6*1 with different ratios of POR/CYP expression levels. Twenty patients undergoing hematopoietic stem cell transplantation were also included in the study. All patients received an i.v. infusion of cyclophosphamide (60 mg/kg/day, for two days) as a part of their conditioning. Blood samples were collected from each patient before cyclophosphamide infusion, 6 h after the first dose and before and 6 h after the second dose. POR gene expression was measured by mRNA analysis and the pharmacokinetics of cyclophosphamide and its active metabolite were determined.", "A strong correlation between the in vitro intrinsic clearance of cyclophosphamide and the POR/CYP ratio was found. The apparent Km for CYP2B6.1 was almost constant (3-4 mM), while the CLint values were proportional to the POR/CYP ratio (3-34 μL/min/nmol CYP). In patients, the average expression of the POR gene in blood was significantly (P <0.001) up-regulated after cyclophosphamide infusion, with high inter-individual variations and significant correlation with the concentration ratio of the active metabolite 4-hydroxy-cyclophosphamide/cyclophosphamide. Nine patients were carriers for POR*28; four patients had relatively high POR expression." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adult", "Child", "Cyclophosphamide", "Cytochrome P-450 CYP2B6", "Cytochrome P-450 Enzyme System", "Gene Expression Regulation, Enzymologic", "Hematologic Diseases", "Hematopoietic Stem Cell Transplantation", "Humans", "Microsomes", "Middle Aged", "Prodrugs", "Young Adult" ] }
This investigation shows for the first time that POR besides CYP2B6 can influence cyclophosphamide metabolism. Our results indicate that not only CYPs are important, but also POR expression and/or activity may influence cyclophosphamide bioactivation, affecting therapeutic efficacy and treatment related toxicity and hence on clinical outcome. Thus, both POR and CYP genotype and expression levels may have to be taken into account when personalizing treatment schedules to achieve optimal therapeutic drug plasma concentrations of cyclophosphamide.
yes
[ { "from": "human", "value": "Question: Does cytochrome P450 Oxidoreductase influence CYP2B6 Activity in Cyclophosphamide Bioactivation?\nContext: {'contexts': ['Cyclophosphamide is commonly used as an important component in conditioning prior to hematopoietic stem cell transplantation, a curative treatment for several hematological diseases. Cyclophosphamide is a prodrug activated mainly by cytochrome P450 2B6 (CYP2B6) in the liver. A high degree of inter- and intra-individual variation in cyclophosphamide kinetics has been reported in several studies.', 'Hydroxylation of cyclophosphamide was investigated in vitro using three microsomal batches of CYP2B6*1 with different ratios of POR/CYP expression levels. Twenty patients undergoing hematopoietic stem cell transplantation were also included in the study. All patients received an i.v. infusion of cyclophosphamide (60 mg/kg/day, for two days) as a part of their conditioning. Blood samples were collected from each patient before cyclophosphamide infusion, 6 h after the first dose and before and 6 h after the second dose. POR gene expression was measured by mRNA analysis and the pharmacokinetics of cyclophosphamide and its active metabolite were determined.', 'A strong correlation between the in vitro intrinsic clearance of cyclophosphamide and the POR/CYP ratio was found. The apparent Km for CYP2B6.1 was almost constant (3-4 mM), while the CLint values were proportional to the POR/CYP ratio (3-34 μL/min/nmol CYP). In patients, the average expression of the POR gene in blood was significantly (P <0.001) up-regulated after cyclophosphamide infusion, with high inter-individual variations and significant correlation with the concentration ratio of the active metabolite 4-hydroxy-cyclophosphamide/cyclophosphamide. Nine patients were carriers for POR*28; four patients had relatively high POR expression.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Child', 'Cyclophosphamide', 'Cytochrome P-450 CYP2B6', 'Cytochrome P-450 Enzyme System', 'Gene Expression Regulation, Enzymologic', 'Hematologic Diseases', 'Hematopoietic Stem Cell Transplantation', 'Humans', 'Microsomes', 'Middle Aged', 'Prodrugs', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,526,196
Does targeting glycolysis by 3-bromopyruvate improve tamoxifen cytotoxicity of breast cancer cell lines?
{ "contexts": [ "Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate.", "An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor.", "Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Antineoplastic Combined Chemotherapy Protocols", "Apoptosis", "Breast Neoplasms", "Cell Line, Tumor", "Cell Proliferation", "Female", "Glycolysis", "Humans", "Mice", "Neoplasm Recurrence, Local", "Neovascularization, Pathologic", "Pyruvates", "Tamoxifen", "Xenograft Model Antitumor Assays" ] }
3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment.
yes
[ { "from": "human", "value": "Question: Does targeting glycolysis by 3-bromopyruvate improve tamoxifen cytotoxicity of breast cancer cell lines?\nContext: {'contexts': ['Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate.', 'An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor.', 'Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Antineoplastic Combined Chemotherapy Protocols', 'Apoptosis', 'Breast Neoplasms', 'Cell Line, Tumor', 'Cell Proliferation', 'Female', 'Glycolysis', 'Humans', 'Mice', 'Neoplasm Recurrence, Local', 'Neovascularization, Pathologic', 'Pyruvates', 'Tamoxifen', 'Xenograft Model Antitumor Assays']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,554,243
Does lipopolysaccharide enhance Beta2-Glycoprotein I Activation of Nuclear Factor κB in Liver Cancer Cells?
{ "contexts": [ "Beta2-glycoprotein I (β2GPI) is a highly abundant glycoprotein in plasma. Our previous study demonstrated strong β2GPI expression in hepatitis B-related hepatocellular carcinoma (HCC) tissue and the combination of β2GPI and hepatitis B surface antigen (HBsAg) was shown to significantly activate the nuclear factor kappa B (NF-κB). To investigate whether lipopolysaccharide (LPS) enhances β2GPI activation of NF-βB and the expression of downstream factors (e.g., tumor necrosis factor alpha, TNF-α; interleukin-1 beta, IL-1β; alpha-fetoprotein, AFP) in the human hepatoma cell line, SMMC-7721.", "Experimental samples were divided into 4 groups as follows: Group A--blank cell group (SMMC-7721); group B--low, medium, and high LPS concentration groups (1 ng/mL; 10 ng/mL; and 100 ng/mL, respectively); group C--β2GPI transfected group; and group D--β2GPI + low, medium, or high concentrations from the LPS affected group. Activation of NF-κB was evaluated using laser scanning confocal microscopy. Expression of downstream factors was measured by ELISA.", "Degrees of NF-κB activation in groups B, C, and D were varied. NF-κB activation in group D was the most significant, and the expressions of downstream factors, TNF-α and IL-1β, were the highest level of activation among the groups (p < 0.05), showing an LPS dose-dependency." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Carcinoma, Hepatocellular", "Cell Line, Tumor", "Gene Expression Regulation, Neoplastic", "Humans", "Interleukin-1beta", "Lipopolysaccharides", "Liver Neoplasms", "NF-kappa B", "Neoplasm Proteins", "Signal Transduction", "Tumor Necrosis Factor-alpha", "alpha-Fetoproteins", "beta 2-Glycoprotein I" ] }
LPS enhanced the signal transduction of β2GPI in liver cancer cells leading to activation of NF-κB, which triggered downstream signal transduction and increased the expression of downstream factors. This suggests that LPS enhancement of β2GPI signal transduction may play a role in promoting the development of liver cancer.
yes
[ { "from": "human", "value": "Question: Does lipopolysaccharide enhance Beta2-Glycoprotein I Activation of Nuclear Factor κB in Liver Cancer Cells?\nContext: {'contexts': ['Beta2-glycoprotein I (β2GPI) is a highly abundant glycoprotein in plasma. Our previous study demonstrated strong β2GPI expression in hepatitis B-related hepatocellular carcinoma (HCC) tissue and the combination of β2GPI and hepatitis B surface antigen (HBsAg) was shown to significantly activate the nuclear factor kappa B (NF-κB). To investigate whether lipopolysaccharide (LPS) enhances β2GPI activation of NF-βB and the expression of downstream factors (e.g., tumor necrosis factor alpha, TNF-α; interleukin-1 beta, IL-1β; alpha-fetoprotein, AFP) in the human hepatoma cell line, SMMC-7721.', 'Experimental samples were divided into 4 groups as follows: Group A--blank cell group (SMMC-7721); group B--low, medium, and high LPS concentration groups (1 ng/mL; 10 ng/mL; and 100 ng/mL, respectively); group C--β2GPI transfected group; and group D--β2GPI + low, medium, or high concentrations from the LPS affected group. Activation of NF-κB was evaluated using laser scanning confocal microscopy. Expression of downstream factors was measured by ELISA.', 'Degrees of NF-κB activation in groups B, C, and D were varied. NF-κB activation in group D was the most significant, and the expressions of downstream factors, TNF-α and IL-1β, were the highest level of activation among the groups (p < 0.05), showing an LPS dose-dependency.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Carcinoma, Hepatocellular', 'Cell Line, Tumor', 'Gene Expression Regulation, Neoplastic', 'Humans', 'Interleukin-1beta', 'Lipopolysaccharides', 'Liver Neoplasms', 'NF-kappa B', 'Neoplasm Proteins', 'Signal Transduction', 'Tumor Necrosis Factor-alpha', 'alpha-Fetoproteins', 'beta 2-Glycoprotein I']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,554,245
Is photodynamic Therapy-Induced Apoptosis of Keloid Fibroblasts Mediated by Radical Oxygen Species In Vitro?
{ "contexts": [ "It has been demonstrated that photodynamic therapy (PDT) is a promising treatment approach for hyperplastic dermatosis and results in a beneficial outcome. In the present study, PDT involving hematoporphyrin monomethyl ether (HMME) was applied to keloid fibroblasts (KFB), and the effects and the mechanism of action were explored.", "Keloid fibroblastic cells were divided into four groups (PDT group, light alone group, HMME alone group, normal cultured group). Cell proliferation and apoptosis were observed. Radical oxygen species (ROS) were detected by means of dihydroethidium (DHE) and dihydrorhodamine (DHR123). ROS in the PDT group were also assessed after addition of tiron.", "Cell proliferation was inhibited in the PDT group (p < 0.05), while the rate of apoptosis was also clearly increased (p < 0.05). The levels of ROS were significantly higher in the PDT group than was observed in the other three groups (p < 0.05). With the addition of tiron the damaging effects were reduced." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt", "Apoptosis", "Cell Division", "Cells, Cultured", "Fibroblasts", "Hematoporphyrins", "Humans", "In Vitro Techniques", "Keloid", "Microscopy, Fluorescence", "Oxidative Stress", "Photochemotherapy", "Reactive Oxygen Species", "Superoxides" ] }
Our data indicated that HMME-mediated PDT could inhibit keloid fibroblast proliferation and could also induce apoptosis. This process was associated with the production of ROS.
yes
[ { "from": "human", "value": "Question: Is photodynamic Therapy-Induced Apoptosis of Keloid Fibroblasts Mediated by Radical Oxygen Species In Vitro?\nContext: {'contexts': ['It has been demonstrated that photodynamic therapy (PDT) is a promising treatment approach for hyperplastic dermatosis and results in a beneficial outcome. In the present study, PDT involving hematoporphyrin monomethyl ether (HMME) was applied to keloid fibroblasts (KFB), and the effects and the mechanism of action were explored.', 'Keloid fibroblastic cells were divided into four groups (PDT group, light alone group, HMME alone group, normal cultured group). Cell proliferation and apoptosis were observed. Radical oxygen species (ROS) were detected by means of dihydroethidium (DHE) and dihydrorhodamine (DHR123). ROS in the PDT group were also assessed after addition of tiron.', 'Cell proliferation was inhibited in the PDT group (p < 0.05), while the rate of apoptosis was also clearly increased (p < 0.05). The levels of ROS were significantly higher in the PDT group than was observed in the other three groups (p < 0.05). With the addition of tiron the damaging effects were reduced.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt', 'Apoptosis', 'Cell Division', 'Cells, Cultured', 'Fibroblasts', 'Hematoporphyrins', 'Humans', 'In Vitro Techniques', 'Keloid', 'Microscopy, Fluorescence', 'Oxidative Stress', 'Photochemotherapy', 'Reactive Oxygen Species', 'Superoxides']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,554,247
Is increased Neutrophil to Lymphocyte Ratio Associated with In-Hospital Mortality in Patients with Aortic Dissection?
{ "contexts": [ "i ne prognostic relevance of hematological parameters in cardiovascular diseases has been well demonstrated. The purpose of the present study is to investigate the association between the hematological parameters, particularly neutrophil to lymphocyte ratio (NLR), and outcomes of aortic dissection (AD).", "Two hundred patients diagnosed with AD were retrospectively recruited and compared with 76 subjects with ascending aortic dilatation (AAD) and 92 subjects with normal aortic diameters. The independent relation between hematological parameters and in-hospital mortality was analyzed by regression analysis.", "The NLR was significantly higher in the AD group compared to the AAD and control groups (median 8.83 [8.13] vs. median 1.95 [1.10] vs. median 1.71 [0.77], respectively; p = 0.01). The NLR was higher in the deceased (n = 57) compared to the surviving patients (n = 143) (median 10.37 [10.86] vs. median 7.84 [8.17]; p = 0.01). Receiver operating curve (ROC) analysis revealed that a NLR measurement higher than > 8.78 predicted in-hospital mortality for patients with acute aortic dissection with a sensitivity of 67.4% and a specificity of 57.2% (AUC: 0.672; p = 0.01). In multivariate logistic regression analysis, increased aortic diameter, acute dissection, and increased levels of NLR remained as the independent markers of in-hospital mortality within the study population." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Aneurysm, Dissecting", "Aortic Aneurysm", "Female", "Hospital Mortality", "Humans", "Hypertension", "Leukocyte Count", "Lymphocyte Count", "Lymphocytes", "Male", "Middle Aged", "Neutrophils", "Prognosis", "ROC Curve", "Retrospective Studies" ] }
In patients with AD, NLR levels were increased compared to patients with AAD and controls and were independently associated with in-hospital mortality. This finding implicates that admission hematological parameters may have clinical importance in evaluating the mortality risk in patients with AD.
yes
[ { "from": "human", "value": "Question: Is increased Neutrophil to Lymphocyte Ratio Associated with In-Hospital Mortality in Patients with Aortic Dissection?\nContext: {'contexts': ['i ne prognostic relevance of hematological parameters in cardiovascular diseases has been well demonstrated. The purpose of the present study is to investigate the association between the hematological parameters, particularly neutrophil to lymphocyte ratio (NLR), and outcomes of aortic dissection (AD).', 'Two hundred patients diagnosed with AD were retrospectively recruited and compared with 76 subjects with ascending aortic dilatation (AAD) and 92 subjects with normal aortic diameters. The independent relation between hematological parameters and in-hospital mortality was analyzed by regression analysis.', 'The NLR was significantly higher in the AD group compared to the AAD and control groups (median 8.83 [8.13] vs. median 1.95 [1.10] vs. median 1.71 [0.77], respectively; p = 0.01). The NLR was higher in the deceased (n = 57) compared to the surviving patients (n = 143) (median 10.37 [10.86] vs. median 7.84 [8.17]; p = 0.01). Receiver operating curve (ROC) analysis revealed that a NLR measurement higher than > 8.78 predicted in-hospital mortality for patients with acute aortic dissection with a sensitivity of 67.4% and a specificity of 57.2% (AUC: 0.672; p = 0.01). In multivariate logistic regression analysis, increased aortic diameter, acute dissection, and increased levels of NLR remained as the independent markers of in-hospital mortality within the study population.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Aneurysm, Dissecting', 'Aortic Aneurysm', 'Female', 'Hospital Mortality', 'Humans', 'Hypertension', 'Leukocyte Count', 'Lymphocyte Count', 'Lymphocytes', 'Male', 'Middle Aged', 'Neutrophils', 'Prognosis', 'ROC Curve', 'Retrospective Studies']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,540,915
Do [ The sequencing analyze of 915 newborn with GJB2 heterozygous mutation in Beijing ]?
{ "contexts": [ "To determine GJB2 allelic mutant and estimate probability of hereditary hearing loss in newborn with GJB2 heterozygous mutation in Beijing.", "We performed genetic testing for sequencing of GJB2 gene for searching GJB2 allelic mutant in 915 newborn who received newborn deafness gene screening (GJB2 c. 235delC, GJB2 c. 299_300delAT, GJB2 c. 176191del16, GJB2 c. 35delG) in Beijing Tongren hospital, and the mutation were classified to pathogenic mutation,undefined variant and polymorphism.", "Four hundred (43.72%, 400/915) newborn were detected to carry at least one mutation allele in GJB2. 3 (0.33%, 3/915) newborn had pathogenic mutations (c. 94C>T, c. 380G>T, c. 344T>G); 62 (6.76%, 62/915) newborn carried 14 undefined variant, 36 newborn had c. 109G>A (58.06%, 36/62),13 newborn had c. 368C>A (20.97%,13/62), six (c. 268C>G, c. 282C>T, c. 294G>C, 456C>T, c. 501G>A, c. 587T>C) are novel; 335 (36.61%, 335/915) newborn were polymorphism." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Alleles", "Beijing", "Connexin 26", "Connexins", "DNA Mutational Analysis", "Deafness", "Genetic Testing", "Heterozygote", "Humans", "Infant, Newborn", "Mutation", "Neonatal Screening", "Polymorphism, Genetic" ] }
The probability of hereditary hearing loss is 7.09% in newborn with GJB2 heterozygous mutation in Beijing. It is noteworthy that c. 109G>A, c. 368C>A occupy a high proportion.
yes
[ { "from": "human", "value": "Question: Do [ The sequencing analyze of 915 newborn with GJB2 heterozygous mutation in Beijing ]?\nContext: {'contexts': ['To determine GJB2 allelic mutant and estimate probability of hereditary hearing loss in newborn with GJB2 heterozygous mutation in Beijing.', 'We performed genetic testing for sequencing of GJB2 gene for searching GJB2 allelic mutant in 915 newborn who received newborn deafness gene screening (GJB2 c. 235delC, GJB2 c. 299_300delAT, GJB2 c. 176191del16, GJB2 c. 35delG) in Beijing Tongren hospital, and the mutation were classified to pathogenic mutation,undefined variant and polymorphism.', 'Four hundred (43.72%, 400/915) newborn were detected to carry at least one mutation allele in GJB2. 3 (0.33%, 3/915) newborn had pathogenic mutations (c. 94C>T, c. 380G>T, c. 344T>G); 62 (6.76%, 62/915) newborn carried 14 undefined variant, 36 newborn had c. 109G>A (58.06%, 36/62),13 newborn had c. 368C>A (20.97%,13/62), six (c. 268C>G, c. 282C>T, c. 294G>C, 456C>T, c. 501G>A, c. 587T>C) are novel; 335 (36.61%, 335/915) newborn were polymorphism.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Alleles', 'Beijing', 'Connexin 26', 'Connexins', 'DNA Mutational Analysis', 'Deafness', 'Genetic Testing', 'Heterozygote', 'Humans', 'Infant, Newborn', 'Mutation', 'Neonatal Screening', 'Polymorphism, Genetic']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,527,560
Do obese patients have similar short-term outcomes to non-obese in laparoscopic colorectal surgery?
{ "contexts": [ "To determine whether obese patients undergoing laparoscopic surgery within an enhanced recovery program had worse short-term outcomes.", "A prospective study of consecutive patients undergoing laparoscopic colorectal resection was carried out between 2008 and 2011 in a single institution. Patients were divided in groups based on body mass index (BMI). Short-term outcomes including operative data, length of stay, complications and readmission rates were recorded and compared between the groups. Continuous data were analysed using t-test or one-way Analysis of Variance. χ(2) test was used to compare categorical data.", "Two hundred and fifty four patients were included over the study period. The majority of individuals (41.7%) recruited were of a healthy weight (BMI < 25), whilst 50 patients were classified as obese (19.6%). Patients were matched in terms of the presence of co-morbidities and previous abdominal surgery. Obese patients were found to have a statistically significant difference in The American Society of Anesthesiologists grade. Length of surgery and intra-operative blood loss were no different according to BMI." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [] }
Obesity (BMI > 25) does not lead to worse short-term outcomes in laparoscopic colorectal surgery and therefore such patients should not be precluded from laparoscopic surgery.
yes
[ { "from": "human", "value": "Question: Do obese patients have similar short-term outcomes to non-obese in laparoscopic colorectal surgery?\nContext: {'contexts': ['To determine whether obese patients undergoing laparoscopic surgery within an enhanced recovery program had worse short-term outcomes.', 'A prospective study of consecutive patients undergoing laparoscopic colorectal resection was carried out between 2008 and 2011 in a single institution. Patients were divided in groups based on body mass index (BMI). Short-term outcomes including operative data, length of stay, complications and readmission rates were recorded and compared between the groups. Continuous data were analysed using t-test or one-way Analysis of Variance. χ(2) test was used to compare categorical data.', 'Two hundred and fifty four patients were included over the study period. The majority of individuals (41.7%) recruited were of a healthy weight (BMI < 25), whilst 50 patients were classified as obese (19.6%). Patients were matched in terms of the presence of co-morbidities and previous abdominal surgery. Obese patients were found to have a statistically significant difference in The American Society of Anesthesiologists grade. Length of surgery and intra-operative blood loss were no different according to BMI.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,524,703
Is moderate Alcohol Consumption Associated with Reduced All-cause Mortality?
{ "contexts": [ "A large body of research suggests that light or moderate alcohol consumption is associated with reduced all-cause mortality. However, concerns remain that the observed relationship is due to selection bias, misclassification of ex-drinkers, or residual confounding.", "The association between alcohol consumption and all-cause mortality was analyzed using Cox regression. The analysis was performed using data from the Health and Retirement Study, a longitudinal cohort of 24,029 individuals from a nationally representative sample of US adults aged more than 50 years. Drinking level was based on alcohol consumption measured at 3 points over the 4 years before the start of follow-up. Occasional drinkers-those who reported drinking on at least 1 occasion, but always less than once per week-served as the reference category. There was extensive adjustment for sociodemographic variables, health status, and functional status.", "During 206,966 person-years of follow up, 7902 individuals died. No level of regular alcohol consumption was associated with reduced all-cause mortality. The hazard ratio and 95% confidence interval in fully adjusted analyses was 1.02 (0.94-1.11) for <7 drinks/week, 1.14 (1.02-1.28) for 7 to <14 drinks/week, 1.13 (0.96-1.35) for 14 to <21 drinks/week, and 1.45 (1.16-1.81) for ≥ 21 drinks/week." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Alcohol Drinking", "Cause of Death", "Female", "Health Status", "Humans", "Male", "Middle Aged", "Proportional Hazards Models", "Risk Factors", "Socioeconomic Factors" ] }
Moderate alcohol consumption is not associated with reduced all-cause mortality in older adults. The previously observed association may have been due to residual confounding.
no
[ { "from": "human", "value": "Question: Is moderate Alcohol Consumption Associated with Reduced All-cause Mortality?\nContext: {'contexts': ['A large body of research suggests that light or moderate alcohol consumption is associated with reduced all-cause mortality. However, concerns remain that the observed relationship is due to selection bias, misclassification of ex-drinkers, or residual confounding.', 'The association between alcohol consumption and all-cause mortality was analyzed using Cox regression. The analysis was performed using data from the Health and Retirement Study, a longitudinal cohort of 24,029 individuals from a nationally representative sample of US adults aged more than 50 years. Drinking level was based on alcohol consumption measured at 3 points over the 4 years before the start of follow-up. Occasional drinkers-those who reported drinking on at least 1 occasion, but always less than once per week-served as the reference category. There was extensive adjustment for sociodemographic variables, health status, and functional status.', 'During 206,966 person-years of follow up, 7902 individuals died. No level of regular alcohol consumption was associated with reduced all-cause mortality. The hazard ratio and 95% confidence interval in fully adjusted analyses was 1.02 (0.94-1.11) for <7 drinks/week, 1.14 (1.02-1.28) for 7 to <14 drinks/week, 1.13 (0.96-1.35) for 14 to <21 drinks/week, and 1.45 (1.16-1.81) for ≥ 21 drinks/week.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Alcohol Drinking', 'Cause of Death', 'Female', 'Health Status', 'Humans', 'Male', 'Middle Aged', 'Proportional Hazards Models', 'Risk Factors', 'Socioeconomic Factors']}" }, { "from": "gpt", "value": "Answer: no" } ]
26,528,354
Do polyunsaturated fatty acids trigger apoptosis of colon cancer cells through a mitochondrial pathway?
{ "contexts": [ "Colorectal cancer is common in developed countries. Polyunsaturated fatty acids (PUFAs) have been reported to possess tumoricidal action, but the exact mechanism of their action is not clear.", "In the present study, we studied the effect of various n-6 and n-3 fatty acids on the survival of the colon cancer cells LoVo and RKO and evaluated the possible involvement of a mitochondrial pathway in their ability to induce apoptosis.", "It was observed that n-3 α-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid (ALA, EPA and DHA respectively) and n-6 linoleic acid, gamma-linolenic acid and arachidonic acid (LA, GLA and AA respectively) induced apoptosis of the colon cancer cells LoVo and RKO at concentrations above 120 μM (p < 0.01 compared to control). The semi-differentiated colon cancer cell line RKO was more sensitive to the cytotoxic action of PUFAs compared to the undifferentiated colon cancer cell line LoVo. PUFA-treated cells showed an increased number of lipid droplets in their cytoplasm. PUFA-induced apoptosis of LoVo and RKO cells is mediated through a mitochondria-mediated pathway as evidenced by loss of mitochondrial membrane potential, generation of ROS, accumulation of intracellular Ca(2+), activation of caspase-9 and caspase-3, decreased ATP level and increase in the Bax/Bcl2 expression ratio." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
PUFAs induced apoptosis of colon cancer cells through a mitochondrial dependent pathway.
yes
[ { "from": "human", "value": "Question: Do polyunsaturated fatty acids trigger apoptosis of colon cancer cells through a mitochondrial pathway?\nContext: {'contexts': ['Colorectal cancer is common in developed countries. Polyunsaturated fatty acids (PUFAs) have been reported to possess tumoricidal action, but the exact mechanism of their action is not clear.', 'In the present study, we studied the effect of various n-6 and n-3 fatty acids on the survival of the colon cancer cells LoVo and RKO and evaluated the possible involvement of a mitochondrial pathway in their ability to induce apoptosis.', 'It was observed that n-3 α-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid (ALA, EPA and DHA respectively) and n-6 linoleic acid, gamma-linolenic acid and arachidonic acid (LA, GLA and AA respectively) induced apoptosis of the colon cancer cells LoVo and RKO at concentrations above 120 μM (p < 0.01 compared to control). The semi-differentiated colon cancer cell line RKO was more sensitive to the cytotoxic action of PUFAs compared to the undifferentiated colon cancer cell line LoVo. PUFA-treated cells showed an increased number of lipid droplets in their cytoplasm. PUFA-induced apoptosis of LoVo and RKO cells is mediated through a mitochondria-mediated pathway as evidenced by loss of mitochondrial membrane potential, generation of ROS, accumulation of intracellular Ca(2+), activation of caspase-9 and caspase-3, decreased ATP level and increase in the Bax/Bcl2 expression ratio.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,528,359
Is melatonin more effective than ascorbic acid and β-carotene in improvement of gastric mucosal damage induced by intensive stress?
{ "contexts": [ "Oxidative stress has been considered to play a primary role in the pathogenesis of stress-induced gastric damage. The aim of this study was to investigate the effects of melatonin, ascorbic acid and β-carotene on stress-induced gastric mucosal damage.", "Fifty-six male Wistar albino rats were divided into control, stress, stress + standard diet, stress + saline, stress + melatonin, stress + ascorbic acid and stress + β-carotene groups. The rats from stress groups were exposed to starvation, immobilization and cold by immobilizing for 8 h at +4°C following 72-hour food restriction. Following stress application, melatonin, ascorbic acid and β-carotene were administered for 7 days. Specimens of gastric tissue were prepared for microscopic and biochemical examinations.", "Mean histopathological damage scores and mean tissue malondialdehyde levels were significantly decreased but mean tissue glutathione levels and glutathione peroxidase and superoxide dismutase activities were increased in treatment groups vs. stress groups in general. Mean histopathological damage scores of the stress + Mel group was lower than those of stress + D, stress + S, stress + β-car (p < 0.05) and stress + Asc groups (p < 0.005). Additionally, mean tissue catalase activity of the stress + Mel group was higher than that of stress + S (p < 0.005), stress + D (p < 0.05) and stress + β-car groups (p < 0.05)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
Melatonin is more effective than ascorbic acid and β-carotene in improvement of gastric damage induced by intensive stress. We suggest that as well as the direct antioxidant and free radical scavenging potency of melatonin, its indirect effect via the brain-gut axis might account for its greater beneficial action against stress-induced gastric damage.
yes
[ { "from": "human", "value": "Question: Is melatonin more effective than ascorbic acid and β-carotene in improvement of gastric mucosal damage induced by intensive stress?\nContext: {'contexts': ['Oxidative stress has been considered to play a primary role in the pathogenesis of stress-induced gastric damage. The aim of this study was to investigate the effects of melatonin, ascorbic acid and β-carotene on stress-induced gastric mucosal damage.', 'Fifty-six male Wistar albino rats were divided into control, stress, stress + standard diet, stress + saline, stress + melatonin, stress + ascorbic acid and stress + β-carotene groups. The rats from stress groups were exposed to starvation, immobilization and cold by immobilizing for 8 h at +4°C following 72-hour food restriction. Following stress application, melatonin, ascorbic acid and β-carotene were administered for 7 days. Specimens of gastric tissue were prepared for microscopic and biochemical examinations.', 'Mean histopathological damage scores and mean tissue malondialdehyde levels were significantly decreased but mean tissue glutathione levels and glutathione peroxidase and superoxide dismutase activities were increased in treatment groups vs. stress groups in general. Mean histopathological damage scores of the stress + Mel group was lower than those of stress + D, stress + S, stress + β-car (p < 0.05) and stress + Asc groups (p < 0.005). Additionally, mean tissue catalase activity of the stress + Mel group was higher than that of stress + S (p < 0.005), stress + D (p < 0.05) and stress + β-car groups (p < 0.05).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,530,319
Are signs of immune activation and local inflammation present in the bronchial tissue of patients with untreated early rheumatoid arthritis?
{ "contexts": [ "Events in the lungs might contribute to generation of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). We investigated if signs of immune activation are present in bronchial biopsies and bronchoalveolar lavage (BAL) of patients with early-untreated RA without clinical signs of lung involvement.", "Twenty-four patients with RA with symptom duration <1 year and naïve to disease-modifying antirheumatic drugs were subjected to bronchoscopy where BAL and mucosal bronchial biopsies were retrieved. For comparison, 15 bronchial biopsies and 79 BAL samples from healthy volunteers were available. Histological examination was performed to evaluate lymphocyte infiltration, presence of immune cells (T and B cells, plasma cells, dendritic cells and macrophages) and immune activation markers. Cell composition of BAL samples was analysed by differential counting and T cell subsets by flow cytometry.", "Lymphocyte infiltration was more frequently found in ACPA-positive patients (50%) as compared with ACPA-negative patients (17%) and controls (13%). Germinal centres, B cells and plasma cells were only found in ACPA-positive patients. The frequency of T cells in bronchial biopsies of patients with ACPA-positive RA was positively associated with expression of immune activation markers. BAL samples of patients with ACPA-positive, but not ACPA-negative, RA had significantly higher relative numbers of lymphocytes and expressed higher levels of activation markers compared with controls." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Arthritis, Rheumatoid", "Autoantibodies", "B-Lymphocytes", "Biomarkers", "Bronchi", "Bronchitis", "Bronchoalveolar Lavage Fluid", "Case-Control Studies", "Early Diagnosis", "Female", "Humans", "Lymphocyte Count", "Male", "Middle Aged", "Peptides, Cyclic", "Plasma Cells", "T-Lymphocyte Subsets" ] }
Signs of immune cell accumulation and activation are present both in the bronchial tissue and in BAL of untreated patients with early RA without concomitant lung disease, strengthening the role of the lung compartment as an important player in ACPA-positive RA.
yes
[ { "from": "human", "value": "Question: Are signs of immune activation and local inflammation present in the bronchial tissue of patients with untreated early rheumatoid arthritis?\nContext: {'contexts': ['Events in the lungs might contribute to generation of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). We investigated if signs of immune activation are present in bronchial biopsies and bronchoalveolar lavage (BAL) of patients with early-untreated RA without clinical signs of lung involvement.', 'Twenty-four patients with RA with symptom duration <1\\u2005year and naïve to disease-modifying antirheumatic drugs were subjected to bronchoscopy where BAL and mucosal bronchial biopsies were retrieved. For comparison, 15 bronchial biopsies and 79 BAL samples from healthy volunteers were available. Histological examination was performed to evaluate lymphocyte infiltration, presence of immune cells (T and B cells, plasma cells, dendritic cells and macrophages) and immune activation markers. Cell composition of BAL samples was analysed by differential counting and T cell subsets by flow cytometry.', 'Lymphocyte infiltration was more frequently found in ACPA-positive patients (50%) as compared with ACPA-negative patients (17%) and controls (13%). Germinal centres, B cells and plasma cells were only found in ACPA-positive patients. The frequency of T cells in bronchial biopsies of patients with ACPA-positive RA was positively associated with expression of immune activation markers. BAL samples of patients with ACPA-positive, but not ACPA-negative, RA had significantly higher relative numbers of lymphocytes and expressed higher levels of activation markers compared with controls.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Arthritis, Rheumatoid', 'Autoantibodies', 'B-Lymphocytes', 'Biomarkers', 'Bronchi', 'Bronchitis', 'Bronchoalveolar Lavage Fluid', 'Case-Control Studies', 'Early Diagnosis', 'Female', 'Humans', 'Lymphocyte Count', 'Male', 'Middle Aged', 'Peptides, Cyclic', 'Plasma Cells', 'T-Lymphocyte Subsets']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,544,611
Is cannabis use disorder associated with greater illness severity in tobacco smoking patients with bipolar disorder?
{ "contexts": [ "Cannabis use disorders (CUD) may influence the course of bipolar disorder (BD), but key confounding factors such as tobacco smoking have not been adequately addressed. This study examined whether CUD was associated with a more severe illness course in tobacco smoking BD patients.", "A sample of French and Norwegian tobacco smoking patients with BD I and II (N=642) was investigated. DSM-IV diagnoses and other characteristics were obtained through personal interviews using structured questionnaires. The association between CUD and illness course was assessed in regression analyses.", "In bivariate analyses, CUD was associated with earlier BD onset, higher frequency of manic (in BD I) and depressive episodes and hospitalizations per illness year, and a higher occurrence of psychotic episodes. After controlling for potential confounders, the relationships with earlier BD onset (B=-5.60 95% CI=-7.65 to -3.64), and increased rates of manic episodes (OR=1.93, 95% CI: 1.15 to 3.23) and hospitalizations (OR=2.93, 95% CI: 1.85 to 4.64) remained statistically significant." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Age of Onset", "Bipolar Disorder", "Diagnostic and Statistical Manual of Mental Disorders", "Female", "Hospitalization", "Humans", "Male", "Marijuana Abuse", "Retrospective Studies", "Smoking", "Surveys and Questionnaires" ] }
Despite the multivariate approach, differences between the two samples may lead to spurious findings related to hidden confounders. Substance use and mood episode information was collected retrospectively, and potential birth cohort effects could not be controlled for.
yes
[ { "from": "human", "value": "Question: Is cannabis use disorder associated with greater illness severity in tobacco smoking patients with bipolar disorder?\nContext: {'contexts': ['Cannabis use disorders (CUD) may influence the course of bipolar disorder (BD), but key confounding factors such as tobacco smoking have not been adequately addressed. This study examined whether CUD was associated with a more severe illness course in tobacco smoking BD patients.', 'A sample of French and Norwegian tobacco smoking patients with BD I and II (N=642) was investigated. DSM-IV diagnoses and other characteristics were obtained through personal interviews using structured questionnaires. The association between CUD and illness course was assessed in regression analyses.', 'In bivariate analyses, CUD was associated with earlier BD onset, higher frequency of manic (in BD I) and depressive episodes and hospitalizations per illness year, and a higher occurrence of psychotic episodes. After controlling for potential confounders, the relationships with earlier BD onset (B=-5.60 95% CI=-7.65 to -3.64), and increased rates of manic episodes (OR=1.93, 95% CI: 1.15 to 3.23) and hospitalizations (OR=2.93, 95% CI: 1.85 to 4.64) remained statistically significant.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Age of Onset', 'Bipolar Disorder', 'Diagnostic and Statistical Manual of Mental Disorders', 'Female', 'Hospitalization', 'Humans', 'Male', 'Marijuana Abuse', 'Retrospective Studies', 'Smoking', 'Surveys and Questionnaires']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,549,599
Is anxiety associated with increased risk of dementia in older Swedish twins?
{ "contexts": [ "We asked whether anxiety is associated with prospective risk of dementia, and the extent to which genetic influences mediate this association.", "Nondemented twins (n = 1082) from the Swedish Adoption Twin Study of Aging completed an assessment of anxiety symptoms in 1984 and were followed for 28 years.", "Baseline anxiety score, independent of depressive symptoms, was significantly associated with incident dementia over follow-up (hazard ratio [HR] = 1.04; 95% confidence interval [CI] = 1.01-1.06). There was 48% increased risk of becoming demented for those who had experienced high anxiety at any time compared with those who had not. In co-twin analyses, the association between anxiety symptoms and dementia was greater for dizygotic (HR = 1.11; 95% CI = 1.02-1.20) compared with monozygotic twins (HR = 1.06; 95% CI = 0.95-1.20), indicating genetic mediation." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Anxiety", "Dementia", "Female", "Follow-Up Studies", "Humans", "Incidence", "Male", "Middle Aged", "Prospective Studies", "Psychiatric Status Rating Scales", "Risk", "Sweden", "Twins, Dizygotic", "Twins, Monozygotic" ] }
Anxiety symptoms were associated with increased risk of dementia. Genetic factors common to dementia and anxiety partially mediated this association.
yes
[ { "from": "human", "value": "Question: Is anxiety associated with increased risk of dementia in older Swedish twins?\nContext: {'contexts': ['We asked whether anxiety is associated with prospective risk of dementia, and the extent to which genetic influences mediate this association.', 'Nondemented twins (n = 1082) from the Swedish Adoption Twin Study of Aging completed an assessment of anxiety symptoms in 1984 and were followed for 28 years.', 'Baseline anxiety score, independent of depressive symptoms, was significantly associated with incident dementia over follow-up (hazard ratio [HR] = 1.04; 95% confidence interval [CI] = 1.01-1.06). There was 48% increased risk of becoming demented for those who had experienced high anxiety at any time compared with those who had not. In co-twin analyses, the association between anxiety symptoms and dementia was greater for dizygotic (HR = 1.11; 95% CI = 1.02-1.20) compared with monozygotic twins (HR = 1.06; 95% CI = 0.95-1.20), indicating genetic mediation.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Anxiety', 'Dementia', 'Female', 'Follow-Up Studies', 'Humans', 'Incidence', 'Male', 'Middle Aged', 'Prospective Studies', 'Psychiatric Status Rating Scales', 'Risk', 'Sweden', 'Twins, Dizygotic', 'Twins, Monozygotic']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,542,776
Are excessive reactive oxygen species therapeutic targets for intervertebral disc degeneration?
{ "contexts": [ "Oxidative stress has been reported to be involved in numerous human diseases, including musculoskeletal disorders such as osteoarthritis. However, the interaction between intervertebral disc (IVD) degeneration and oxidative stress is not well understood. The purpose of the present study was to elucidate the contribution of oxidative stress to IVD degeneration and the efficacy of antioxidant treatment for degenerative discs.", "The expression level of an oxidative stress marker, nitrotyrosine, was assessed by immunohistochemistry and Western blotting. For evaluating intracellular reactive oxygen species (ROS) levels and oxidative stress in rat annulus fibrosus (AF) cells, flow cytometry and luciferase assay with an OKD48 construct were performed. The grade of IVD degeneration was assessed by magnetic resonance imaging and histological analysis.", "A high frequency of nitrotyrosine-positive cells was observed in rat and human degenerative discs. mRNA expression of catabolic factors such as tumor necrosis factor-alpha (TNF-alpha), matrix metalloprotease-3 (MMP-3), and cyclooxygenase-2 (COX-2) was significantly induced by treatment with H2O2 or buthionine sulfoximine, whereas that of aggrecan, an important chondrogenic proteoglycan, was reduced in a dose-dependent manner. Treatment with mitogen-activated protein kinase (MAPK) inhibitors blocked the inductive effect of excessive ROS on COX-2 mRNA expression. Western blotting confirmed the phosphorylation of MAPKs in H2O2 and BSO-treated AF cells. Conversely, we showed that TNF-α induced oxidative stress with increased intracellular ROS levels in AF cells. Treatment with the antioxidant N-acetyl cysteine (NAC) abrogated the catabolic effect of excessive ROS and TNF-alpha in vitro. Finally, we showed that oral administration of NAC prevented IVD degeneration in rat degenerative model." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Acetylcysteine", "Adult", "Aged", "Animals", "Antioxidants", "Blotting, Western", "Female", "Flow Cytometry", "Humans", "Intervertebral Disc", "Intervertebral Disc Degeneration", "Magnetic Resonance Imaging", "Male", "Middle Aged", "Rats", "Rats, Wistar", "Reactive Oxygen Species", "Real-Time Polymerase Chain Reaction" ] }
A positive feedback loop was formed between excessive ROS and TNF-alpha in AF cells. Thus, oxidative stress contributes to the progression of IVD degeneration and NAC can be a therapeutic option for IVD degeneration.
yes
[ { "from": "human", "value": "Question: Are excessive reactive oxygen species therapeutic targets for intervertebral disc degeneration?\nContext: {'contexts': ['Oxidative stress has been reported to be involved in numerous human diseases, including musculoskeletal disorders such as osteoarthritis. However, the interaction between intervertebral disc (IVD) degeneration and oxidative stress is not well understood. The purpose of the present study was to elucidate the contribution of oxidative stress to IVD degeneration and the efficacy of antioxidant treatment for degenerative discs.', 'The expression level of an oxidative stress marker, nitrotyrosine, was assessed by immunohistochemistry and Western blotting. For evaluating intracellular reactive oxygen species (ROS) levels and oxidative stress in rat annulus fibrosus (AF) cells, flow cytometry and luciferase assay with an OKD48 construct were performed. The grade of IVD degeneration was assessed by magnetic resonance imaging and histological analysis.', 'A high frequency of nitrotyrosine-positive cells was observed in rat and human degenerative discs. mRNA expression of catabolic factors such as tumor necrosis factor-alpha (TNF-alpha), matrix metalloprotease-3 (MMP-3), and cyclooxygenase-2 (COX-2) was significantly induced by treatment with H2O2 or buthionine sulfoximine, whereas that of aggrecan, an important chondrogenic proteoglycan, was reduced in a dose-dependent manner. Treatment with mitogen-activated protein kinase (MAPK) inhibitors blocked the inductive effect of excessive ROS on COX-2 mRNA expression. Western blotting confirmed the phosphorylation of MAPKs in H2O2 and BSO-treated AF cells. Conversely, we showed that TNF-α induced oxidative stress with increased intracellular ROS levels in AF cells. Treatment with the antioxidant N-acetyl cysteine (NAC) abrogated the catabolic effect of excessive ROS and TNF-alpha in vitro. Finally, we showed that oral administration of NAC prevented IVD degeneration in rat degenerative model.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Acetylcysteine', 'Adult', 'Aged', 'Animals', 'Antioxidants', 'Blotting, Western', 'Female', 'Flow Cytometry', 'Humans', 'Intervertebral Disc', 'Intervertebral Disc Degeneration', 'Magnetic Resonance Imaging', 'Male', 'Middle Aged', 'Rats', 'Rats, Wistar', 'Reactive Oxygen Species', 'Real-Time Polymerase Chain Reaction']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,545,364
Is overexpression of the long non-coding RNA PVT1 correlated with leukemic cell proliferation in acute promyelocytic leukemia?
{ "contexts": [ "Acute promyelocytic leukemia (APL) is associated with chromosomal translocation t(15;17), which results in the proliferation of morphologically abnormal promyelocytes. Gain of supernumerary copies of the 8q24 chromosomal region, which harbors MYC and PVT1, has been shown to be the most common secondary alteration in human APL. Increased MYC can accelerate the development of myeloid leukemia in APL. However, the role that the expression of the long non-coding RNA (lncRNA) PVT1 plays in the pathogenesis of APL remains largely unknown.", "In this study, we first analyzed the lncRNA PVT1 expression level in peripheral blood cells from 28 patients with de novo APL, and significantly upregulated PVT1 was found in APL patients compared with healthy donors. We then observed significantly lower MYC and PVT1 expression during all-trans retinoic acid (ATRA)-induced differentiation and cell cycle arrest in the APL cell line. MYC knockdown in NB4 cells led to PVT1 downregulation. Moreover, PVT1 knockdown by RNA interference led to suppression of the MYC protein level, and cell proliferation was inhibited." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Adult", "Antineoplastic Agents", "Cell Differentiation", "Cell Line, Tumor", "Cell Proliferation", "Female", "Gene Expression Regulation, Leukemic", "Humans", "Leukemia, Promyelocytic, Acute", "Male", "Proto-Oncogene Proteins c-myc", "RNA Interference", "RNA, Long Noncoding", "Reverse Transcriptase Polymerase Chain Reaction", "Tretinoin" ] }
Our findings reveal that the lncRNA PVT1 may play an important role in the proliferation of APL cells and may be useful for future therapeutic management.
yes
[ { "from": "human", "value": "Question: Is overexpression of the long non-coding RNA PVT1 correlated with leukemic cell proliferation in acute promyelocytic leukemia?\nContext: {'contexts': ['Acute promyelocytic leukemia (APL) is associated with chromosomal translocation t(15;17), which results in the proliferation of morphologically abnormal promyelocytes. Gain of supernumerary copies of the 8q24 chromosomal region, which harbors MYC and PVT1, has been shown to be the most common secondary alteration in human APL. Increased MYC can accelerate the development of myeloid leukemia in APL. However, the role that the expression of the long non-coding RNA (lncRNA) PVT1 plays in the pathogenesis of APL remains largely unknown.', 'In this study, we first analyzed the lncRNA PVT1 expression level in peripheral blood cells from 28 patients with de novo APL, and significantly upregulated PVT1 was found in APL patients compared with healthy donors. We then observed significantly lower MYC and PVT1 expression during all-trans retinoic acid (ATRA)-induced differentiation and cell cycle arrest in the APL cell line. MYC knockdown in NB4 cells led to PVT1 downregulation. Moreover, PVT1 knockdown by RNA interference led to suppression of the MYC protein level, and cell proliferation was inhibited.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Adult', 'Antineoplastic Agents', 'Cell Differentiation', 'Cell Line, Tumor', 'Cell Proliferation', 'Female', 'Gene Expression Regulation, Leukemic', 'Humans', 'Leukemia, Promyelocytic, Acute', 'Male', 'Proto-Oncogene Proteins c-myc', 'RNA Interference', 'RNA, Long Noncoding', 'Reverse Transcriptase Polymerase Chain Reaction', 'Tretinoin']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,550,120
Does angiogenesis and proliferation of bile duct enhance ischemic tolerance in rats with cirrhosis?
{ "contexts": [ "Primary biliary cirrhosis (PBC), an autoimmune disease of the liver, is marked by slow progressive destruction of bile ducts. These patients with PBC often undergo orthotopic liver transplantation (OLT). Ischemic bile duct lesion (IBDL) is a major source of morbidity and even mortality after OLT. Cirrhosis of the liver has a higher tolerance to ischemia than a normal liver, but the mechanism remains unknown. Angiogenesis and proliferation of bile duct often responses in bile duct ischemia, which may enhance ischemic tolerance in patients with cirrhosis.", "To test the hypothesis, a rat model with cirrhosis was established. Biochemical indexes of ischemic severity were measured including total bilirubin (TBIL) and direct bilirubin (DBIL). Immunohistochemical assay was performed for Ki67 (a biomarker for the proliferation of bile duct) and CD34 (a biomarker of angiogenesis).", "The levels were lower for TBIL and DBIL in the bile duct from rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). The levels were higher for Ki67 and CD34 from a rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [] }
The results suggest that a liver with cirrhosis has a better ischemic tolerance than a normal liver. Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis. More research on the pathogenesis of IBDLs is needed for developing more specific preventive or therapeutic strategies.
yes
[ { "from": "human", "value": "Question: Does angiogenesis and proliferation of bile duct enhance ischemic tolerance in rats with cirrhosis?\nContext: {'contexts': ['Primary biliary cirrhosis (PBC), an autoimmune disease of the liver, is marked by slow progressive destruction of bile ducts. These patients with PBC often undergo orthotopic liver transplantation (OLT). Ischemic bile duct lesion (IBDL) is a major source of morbidity and even mortality after OLT. Cirrhosis of the liver has a higher tolerance to ischemia than a normal liver, but the mechanism remains unknown. Angiogenesis and proliferation of bile duct often responses in bile duct ischemia, which may enhance ischemic tolerance in patients with cirrhosis.', 'To test the hypothesis, a rat model with cirrhosis was established. Biochemical indexes of ischemic severity were measured including total bilirubin (TBIL) and direct bilirubin (DBIL). Immunohistochemical assay was performed for Ki67 (a biomarker for the proliferation of bile duct) and CD34 (a biomarker of angiogenesis).', 'The levels were lower for TBIL and DBIL in the bile duct from rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). The levels were higher for Ki67 and CD34 from a rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,541,582
Does sevoflurane postconditioning improve long-term learning and memory of neonatal hypoxia-ischemia brain damage rats via the PI3K/Akt-mPTP pathway?
{ "contexts": [ "Volatile anesthetic postconditioning has been documented to provide neuroprotection in adult animals. Our aim was to investigate whether sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage (HIBD) rats, and whether the PI3K/Akt pathway and mitochondrial permeability transition pore (mPTP) opening participate in the effect.", "Seven-day-old Sprague-Dawley rats were subjected to brain HI and randomly allocated to 10 groups (n=24 each group) and treated as follows: (1) Sham, without hypoxia-ischemia; (2) HI/Control, received cerebral hypoxia-ischemia; (3) HI+Atractyloside (Atr), (4) HI+Cyclosporin A (CsA), (5) HI+sevoflurane (Sev), (6) HI+Sev+ LY294002 (LY), (7) HI+Sev+ L-NAME (L-N), (8) HI+Sev+ SB216763 (SB), (9) HI+Sev+Atr, and (10) HI+Sev+CsA. Twelve rats in each group underwent behavioral testing and their brains were harvested for hippocampus neuron count and morphology study. Brains of the other 12 animals were harvested 24h after intervention to examine the expression of Akt, p-Akt, eNOS, p-eNOS, GSK-3β, p-GSK-3β by Western bolting and mPTP opening.", "Sevoflurane postconditioning significantly improved the long-term cognitive performance of the rats, increased the number of surviving neurons in CA1 and CA3 hippocampal regions, and protected the histomorphology of the left hippocampus. These effects were abolished by inhibitors of PI3K/eNOS/GSK-3β. Although blocking mPTP opening simulated sevoflurane postconditioning-induced neuroprotection, it failed to enhance it." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Cell Death", "Disease Models, Animal", "Female", "Hippocampus", "Hypoxia-Ischemia, Brain", "Ischemic Postconditioning", "Learning", "Male", "Memory", "Methyl Ethers", "Mitochondrial Membrane Transport Proteins", "Neuroprotective Agents", "Phosphatidylinositol 3-Kinases", "Proto-Oncogene Proteins c-akt", "Random Allocation", "Rats, Sprague-Dawley", "Sevoflurane" ] }
Sevoflurane postconditioning exerts a neuroprotective effect against HIBD in neonatal rats via PI3K/Akt/eNOS and PI3K/Akt/GSK-3β pathways, and blockage of mPTP opening may be involved in attenuation of histomorphological injury.
yes
[ { "from": "human", "value": "Question: Does sevoflurane postconditioning improve long-term learning and memory of neonatal hypoxia-ischemia brain damage rats via the PI3K/Akt-mPTP pathway?\nContext: {'contexts': ['Volatile anesthetic postconditioning has been documented to provide neuroprotection in adult animals. Our aim was to investigate whether sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage (HIBD) rats, and whether the PI3K/Akt pathway and mitochondrial permeability transition pore (mPTP) opening participate in the effect.', 'Seven-day-old Sprague-Dawley rats were subjected to brain HI and randomly allocated to 10 groups (n=24 each group) and treated as follows: (1) Sham, without hypoxia-ischemia; (2) HI/Control, received cerebral hypoxia-ischemia; (3) HI+Atractyloside (Atr), (4) HI+Cyclosporin A (CsA), (5) HI+sevoflurane (Sev), (6) HI+Sev+ LY294002 (LY), (7) HI+Sev+ L-NAME (L-N), (8) HI+Sev+ SB216763 (SB), (9) HI+Sev+Atr, and (10) HI+Sev+CsA. Twelve rats in each group underwent behavioral testing and their brains were harvested for hippocampus neuron count and morphology study. Brains of the other 12 animals were harvested 24h after intervention to examine the expression of Akt, p-Akt, eNOS, p-eNOS, GSK-3β, p-GSK-3β by Western bolting and mPTP opening.', 'Sevoflurane postconditioning significantly improved the long-term cognitive performance of the rats, increased the number of surviving neurons in CA1 and CA3 hippocampal regions, and protected the histomorphology of the left hippocampus. These effects were abolished by inhibitors of PI3K/eNOS/GSK-3β. Although blocking mPTP opening simulated sevoflurane postconditioning-induced neuroprotection, it failed to enhance it.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Cell Death', 'Disease Models, Animal', 'Female', 'Hippocampus', 'Hypoxia-Ischemia, Brain', 'Ischemic Postconditioning', 'Learning', 'Male', 'Memory', 'Methyl Ethers', 'Mitochondrial Membrane Transport Proteins', 'Neuroprotective Agents', 'Phosphatidylinositol 3-Kinases', 'Proto-Oncogene Proteins c-akt', 'Random Allocation', 'Rats, Sprague-Dawley', 'Sevoflurane']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,525,371
Does bariatric surgery acutely change the expression of inflammatory and lipogenic genes in obese adipose tissue?
{ "contexts": [ "Adipose tissue of obese subjects is known to exhibit increased inflammatory activity linked to altered expression of factors involved in glucose and lipid metabolism. The surgical procedure constitutes an injury per se, evoking a systemic inflammatory response.", "To evaluate changes in the expression of key-genes in adipose tissue after common surgical procedures performed in obese patients.", "A tertiary hospital.", "Paired subcutaneous (SAT) and visceral (VAT) adipose tissue samples were collected at the beginning and the end of surgery in 33 obese patients that underwent laparoscopic Roux-en-Y gastric bypass (RYGB, n = 17) or laparoscopic vertical sleeve gastrectomy (SG, n = 16). The expression of genes involved in inflammation, glucose and lipid metabolism was assessed.", "The surgical procedure led to increased expression of interleukin 6, interleukin 8 (P<.0001 in both depots), tumor necrosis factor α (P = .001 in SAT), and lipopolysaccharide binding protein (P = .0004 in VAT). Surgery also induced concomitant decreased expression of GLUT4, IRS1 (P = .046 in VAT), and adiponectin, whereas the messenger RNA of lipogenic genes [fatty acid synthase (P = .024); sterol regulatory element binding transcription factor 1 (P = .011) and aquaporin 9 (P<.0001) in SAT; and PPARγ (P = .018) and solute carrier family 27 (fatty acid transporter), member 2 (P = .028) in VAT] increased in parallel to inflammation. Changes in gene expression during surgery were enhanced in patients following RYGB, when compared with SG." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Bariatric Surgery", "Cytokines", "Female", "Gene Expression Regulation", "Humans", "Inflammation", "Lipid Metabolism", "Male", "Middle Aged", "Obesity, Morbid", "RNA, Messenger", "Real-Time Polymerase Chain Reaction", "Subcutaneous Fat" ] }
Bariatric surgery acutely changes the expression of inflammatory and lipogenic genes in adipose tissue. This information should be considered cautiously when designing studies to assess adipose tissue gene expression in morbidly obese patients. The same timing of sampling is mandatory.
yes
[ { "from": "human", "value": "Question: Does bariatric surgery acutely change the expression of inflammatory and lipogenic genes in obese adipose tissue?\nContext: {'contexts': ['Adipose tissue of obese subjects is known to exhibit increased inflammatory activity linked to altered expression of factors involved in glucose and lipid metabolism. The surgical procedure constitutes an injury per se, evoking a systemic inflammatory response.', 'To evaluate changes in the expression of key-genes in adipose tissue after common surgical procedures performed in obese patients.', 'A tertiary hospital.', 'Paired subcutaneous (SAT) and visceral (VAT) adipose tissue samples were collected at the beginning and the end of surgery in 33 obese patients that underwent laparoscopic Roux-en-Y gastric bypass (RYGB, n = 17) or laparoscopic vertical sleeve gastrectomy (SG, n = 16). The expression of genes involved in inflammation, glucose and lipid metabolism was assessed.', 'The surgical procedure led to increased expression of interleukin 6, interleukin 8 (P<.0001 in both depots), tumor necrosis factor α (P = .001 in SAT), and lipopolysaccharide binding protein (P = .0004 in VAT). Surgery also induced concomitant decreased expression of GLUT4, IRS1 (P = .046 in VAT), and adiponectin, whereas the messenger RNA of lipogenic genes [fatty acid synthase (P = .024); sterol regulatory element binding transcription factor 1 (P = .011) and aquaporin 9 (P<.0001) in SAT; and PPARγ (P = .018) and solute carrier family 27 (fatty acid transporter), member 2 (P = .028) in VAT] increased in parallel to inflammation. Changes in gene expression during surgery were enhanced in patients following RYGB, when compared with SG.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Bariatric Surgery', 'Cytokines', 'Female', 'Gene Expression Regulation', 'Humans', 'Inflammation', 'Lipid Metabolism', 'Male', 'Middle Aged', 'Obesity, Morbid', 'RNA, Messenger', 'Real-Time Polymerase Chain Reaction', 'Subcutaneous Fat']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,530,229
Do unmet needs mediate the relationship between symptoms and quality of life in breast cancer survivors?
{ "contexts": [ "This study aimed to compare the symptoms, unmet needs, and QoL reported by women at 6 months to <2 years and 2 to 5 years following surgery and adjuvant treatment for breast cancer. It also evaluated the relationships among symptoms, unmet needs, and QoL using structural equation modeling.", "In this study, 113 and 137 survivors following breast cancer treatment 6 months to <2 years and 2 to 5 years, respectively, completed the Memorial Symptom Assessment Scale, the Supportive Care Needs Survey-34, and the Medical Outcomes Study 12-item Short Form Health Survey version 2.0 during their medical follow-up.", "The mean numbers of symptoms and unmet needs were 5.43 and 3.0, respectively, for survivors at <2 years, and 5.24 and 2.42, respectively, for survivors at 2 to 5 years following treatment. The most common reported symptoms were related primarily to physical domains. No significant differences were found between the two survivor groups on the MSAS scores. Survivors at <2 years reported significantly higher scores in Psychological and Health Care System/Information needs (p < 0.01), and lower composite scores in physical and mental QoL (p < 0.05) than those at 2 to 5 years post-treatment. Significant direct and indirect effects were found of symptom burden through unmet needs on survivors' physical and mental QoL after adjustment for survival time, and the models showed a good fit." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Breast Neoplasms", "Chemoradiotherapy, Adjuvant", "Cost of Illness", "Cross-Sectional Studies", "Female", "Humans", "Mastectomy", "Middle Aged", "Needs Assessment", "Outcome Assessment (Health Care)", "Quality of Life", "Singapore", "Survivors", "Symptom Assessment", "Time" ] }
Results suggest that breast cancer survivors continue to endure many symptoms independent of the survivorship period. The unmet needs mediate the relationship between symptom burden and survivors' QoL.
yes
[ { "from": "human", "value": "Question: Do unmet needs mediate the relationship between symptoms and quality of life in breast cancer survivors?\nContext: {'contexts': ['This study aimed to compare the symptoms, unmet needs, and QoL reported by women at 6 months to <2 years and 2 to 5 years following surgery and adjuvant treatment for breast cancer. It also evaluated the relationships among symptoms, unmet needs, and QoL using structural equation modeling.', 'In this study, 113 and 137 survivors following breast cancer treatment 6 months to <2 years and 2 to 5 years, respectively, completed the Memorial Symptom Assessment Scale, the Supportive Care Needs Survey-34, and the Medical Outcomes Study 12-item Short Form Health Survey version 2.0 during their medical follow-up.', \"The mean numbers of symptoms and unmet needs were 5.43 and 3.0, respectively, for survivors at <2 years, and 5.24 and 2.42, respectively, for survivors at 2 to 5 years following treatment. The most common reported symptoms were related primarily to physical domains. No significant differences were found between the two survivor groups on the MSAS scores. Survivors at <2 years reported significantly higher scores in Psychological and Health Care System/Information needs (p\\u2009<\\u20090.01), and lower composite scores in physical and mental QoL (p\\u2009<\\u20090.05) than those at 2 to 5 years post-treatment. Significant direct and indirect effects were found of symptom burden through unmet needs on survivors' physical and mental QoL after adjustment for survival time, and the models showed a good fit.\"], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Breast Neoplasms', 'Chemoradiotherapy, Adjuvant', 'Cost of Illness', 'Cross-Sectional Studies', 'Female', 'Humans', 'Mastectomy', 'Middle Aged', 'Needs Assessment', 'Outcome Assessment (Health Care)', 'Quality of Life', 'Singapore', 'Survivors', 'Symptom Assessment', 'Time']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,541,479
Is epidural analgesia superior to local infiltration analgesia in children with cerebral palsy undergoing unilateral hip reconstruction?
{ "contexts": [ "Treatment of postoperative pain in children with cerebral palsy (CP) is a major challenge. We investigated the effect of epidural analgesia, high-volume local infiltration analgesia (LIA), and an approximated placebo control on early postoperative pain in children with CP who were undergoing unilateral hip reconstruction.", "Between 2009 and 2014, we included 18 children with CP. The first part of the study was a randomized double-blind trial with allocation to either LIA or placebo for postoperative pain management, in addition to intravenous or oral analgesia. In the second part of the study, the children were consecutively included for postoperative pain management with epidural analgesia in addition to intravenous or oral analgesia. The primary outcome was postoperative pain 4 h postoperatively using 2 pain assessment tools (r-FLACC and VAS-OBS) ranging from 0 to 10. The secondary outcome was opioid consumption over the 21-h study period.", "The mean level of pain 4 h postoperatively was lower in the epidural group (r-FLACC: 0.7; VAS-OBS: 0.6) than in both the LIA group (r-FLACC: 4.8, p = 0.01; VAS-OBS: 5.2, p = 0.02) and the placebo group (r-FLACC: 5.2, p = 0.01; VAS-OBS: 6.5, p < 0.001). Corrected for body weight, the mean opioid consumption was lower in the epidural group than in the LIA group and the placebo group (both p < 0.001)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Analgesia", "Analgesia, Epidural", "Analgesics, Opioid", "Arthroplasty, Replacement, Hip", "Cerebral Palsy", "Child", "Child, Preschool", "Double-Blind Method", "Female", "Humans", "Male", "Pain Management", "Pain Measurement", "Pain, Postoperative", "Prospective Studies", "Treatment Outcome" ] }
Epidural analgesia is superior to local infiltration analgesia for early postoperative pain management in children with cerebral palsy who undergo unilateral hip reconstruction.
yes
[ { "from": "human", "value": "Question: Is epidural analgesia superior to local infiltration analgesia in children with cerebral palsy undergoing unilateral hip reconstruction?\nContext: {'contexts': ['Treatment of postoperative pain in children with cerebral palsy (CP) is a major challenge. We investigated the effect of epidural analgesia, high-volume local infiltration analgesia (LIA), and an approximated placebo control on early postoperative pain in children with CP who were undergoing unilateral hip reconstruction.', 'Between 2009 and 2014, we included 18 children with CP. The first part of the study was a randomized double-blind trial with allocation to either LIA or placebo for postoperative pain management, in addition to intravenous or oral analgesia. In the second part of the study, the children were consecutively included for postoperative pain management with epidural analgesia in addition to intravenous or oral analgesia. The primary outcome was postoperative pain 4 h postoperatively using 2 pain assessment tools (r-FLACC and VAS-OBS) ranging from 0 to 10. The secondary outcome was opioid consumption over the 21-h study period.', 'The mean level of pain 4 h postoperatively was lower in the epidural group (r-FLACC: 0.7; VAS-OBS: 0.6) than in both the LIA group (r-FLACC: 4.8, p\\u2009=\\u20090.01; VAS-OBS: 5.2, p\\u2009=\\u20090.02) and the placebo group (r-FLACC: 5.2, p\\u2009=\\u20090.01; VAS-OBS: 6.5, p\\u2009<\\u20090.001). Corrected for body weight, the mean opioid consumption was lower in the epidural group than in the LIA group and the placebo group (both p\\u2009<\\u20090.001).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Analgesia', 'Analgesia, Epidural', 'Analgesics, Opioid', 'Arthroplasty, Replacement, Hip', 'Cerebral Palsy', 'Child', 'Child, Preschool', 'Double-Blind Method', 'Female', 'Humans', 'Male', 'Pain Management', 'Pain Measurement', 'Pain, Postoperative', 'Prospective Studies', 'Treatment Outcome']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,526,856
Do prevalence of pseudobulbar affect symptoms and clinical correlates in nursing home residents?
{ "contexts": [ "Pseudobulbar affect (PBA) is a neurological disorder of emotional expression, characterized by uncontrollable episodes of crying or laughing in patients with certain neurological disorders affecting the brain. The purposes of this study were to estimate the prevalence of PBA in US nursing home residents and examine the relationship between PBA symptoms and other clinical correlates, including the use of psychopharmacological medications.", "A retrospective study was conducted between 2013 and 2014 with a convenience sample of residents from nine Michigan nursing homes. Chronic-care residents were included in the \"predisposed population\" if they had a neurological disorder affecting the brain and no evidence of psychosis, delirium, or disruptive behavior (per chart review). Residents were screened for PBA symptoms by a geropsychologist using the Center for Neurologic Study-Lability Scale (CNS-LS). Additional clinical information was collected using a diagnostic evaluation checklist and the most recent Minimum Data Set 3.0 assessment.", "Of 811 residents screened, complete data were available for 804, and 412 (51%) met the criteria for the \"predisposed population.\" PBA symptom prevalence, based on having a CNS-LS score ≥13, was 17.5% in the predisposed population and 9.0% among all nursing home residents. Those with PBA symptoms were more likely to have a documented mood disorder and be using a psychopharmacological medication, including antipsychotics, than those without PBA symptoms." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Antipsychotic Agents", "Crying", "Female", "Humans", "Laughter", "Male", "Michigan", "Middle Aged", "Mood Disorders", "Nervous System Diseases", "Nursing Homes", "Prevalence", "Psychotropic Drugs", "Retrospective Studies" ] }
Pseudobulbar affect symptoms were present in 17.5% of nursing home residents with neurological conditions, and 9.0% of residents overall. Increasing awareness and improving diagnostic accuracy of PBA may help optimize treatment. Copyright © 2015 John Wiley & Sons, Ltd.
yes
[ { "from": "human", "value": "Question: Do prevalence of pseudobulbar affect symptoms and clinical correlates in nursing home residents?\nContext: {'contexts': ['Pseudobulbar affect (PBA) is a neurological disorder of emotional expression, characterized by uncontrollable episodes of crying or laughing in patients with certain neurological disorders affecting the brain. The purposes of this study were to estimate the prevalence of PBA in US nursing home residents and examine the relationship between PBA symptoms and other clinical correlates, including the use of psychopharmacological medications.', 'A retrospective study was conducted between 2013 and 2014 with a convenience sample of residents from nine Michigan nursing homes. Chronic-care residents were included in the \"predisposed population\" if they had a neurological disorder affecting the brain and no evidence of psychosis, delirium, or disruptive behavior (per chart review). Residents were screened for PBA symptoms by a geropsychologist using the Center for Neurologic Study-Lability Scale (CNS-LS). Additional clinical information was collected using a diagnostic evaluation checklist and the most recent Minimum Data Set 3.0 assessment.', 'Of 811 residents screened, complete data were available for 804, and 412 (51%) met the criteria for the \"predisposed population.\" PBA symptom prevalence, based on having a CNS-LS score ≥13, was 17.5% in the predisposed population and 9.0% among all nursing home residents. Those with PBA symptoms were more likely to have a documented mood disorder and be using a psychopharmacological medication, including antipsychotics, than those without PBA symptoms.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Antipsychotic Agents', 'Crying', 'Female', 'Humans', 'Laughter', 'Male', 'Michigan', 'Middle Aged', 'Mood Disorders', 'Nervous System Diseases', 'Nursing Homes', 'Prevalence', 'Psychotropic Drugs', 'Retrospective Studies']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,552,486
Do mycobacterium tuberculosis secretory proteins downregulate T cell activation by interfering with proximal and downstream T cell signalling events?
{ "contexts": [ "Mycobacterium tuberculosis (M. tuberculosis) modulates host immune response, mainly T cell responses for its own survival leading to disease or latent infection. The molecules and mechanisms utilized to accomplish immune subversion by M. tuberculosis are not fully understood. Understanding the molecular mechanism of T cell response to M. tuberculosis is important for development of efficacious vaccine against TB.", "Here, we investigated effect of M. tuberculosis antigens Ag85A and ESAT-6 on T cell signalling events in CD3/CD28 induced Peripheral blood mononuclear cells (PBMCs) of PPD+ve healthy individuals and pulmonary TB patients. We studied CD3 induced intracellular calcium mobilization in PBMCs of healthy individuals and TB patients by spectrofluorimetry, CD3 and CD28 induced activation of mitogen activated protein kinases (MAPKs) in PBMCs of healthy individuals and TB patients by western blotting and binding of transcription factors NFAT and NFκB by Electrophorectic mobility shift assay (EMSA).", "We observed CD3 triggered modulations in free intracellular calcium concentrations in PPD+ve healthy individuals and pulmonary TB patients after the treatment of M. tuberculosis antigens. As regards the downstream signalling events, phosphorylation of MAPKs, Extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38 was curtailed by M. tuberculosis antigens in TB patients whereas, in PPD+ve healthy individuals only ERK1/2 phosphorylation was inhibited. Besides, the terminal signalling events like binding of transcription factors NFAT and NFκB was also altered by M. tuberculosis antigens. Altogether, our results suggest that M. tuberculosis antigens, specifically ESAT-6, interfere with TCR/CD28-induced upstream as well as downstream signalling events which might be responsible for defective IL-2 production which further contributed in T-cell unresponsiveness, implicated in the progression of disease." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Acyltransferases", "Antigens, Bacterial", "Bacterial Proteins", "CD28 Antigens", "Calcium", "Humans", "Intracellular Space", "Leukocytes, Mononuclear", "Lymphocyte Activation", "Mitogen-Activated Protein Kinases", "Mycobacterium tuberculosis", "NF-kappa B", "NFATC Transcription Factors", "Receptors, Antigen, T-Cell", "Signal Transduction", "T-Lymphocytes" ] }
To the best of our knowledge, this is the first study to investigate effect of Ag85A and ESAT-6 on TCR- and TCR/CD28- induced upstream and downstream signalling events of T-cell activation in TB patients. This study showed the effect of secretory antigens of M. tuberculosis in the modulation of T cell signalling pathways. This inflection is accomplished by altering the proximal and distal events of signalling cascade which could be involved in T-cell dysfunctioning during the progression of the disease.
yes
[ { "from": "human", "value": "Question: Do mycobacterium tuberculosis secretory proteins downregulate T cell activation by interfering with proximal and downstream T cell signalling events?\nContext: {'contexts': ['Mycobacterium tuberculosis (M. tuberculosis) modulates host immune response, mainly T cell responses for its own survival leading to disease or latent infection. The molecules and mechanisms utilized to accomplish immune subversion by M. tuberculosis are not fully understood. Understanding the molecular mechanism of T cell response to M. tuberculosis is important for development of efficacious vaccine against TB.', 'Here, we investigated effect of M. tuberculosis antigens Ag85A and ESAT-6 on T cell signalling events in CD3/CD28 induced Peripheral blood mononuclear cells (PBMCs) of PPD+ve healthy individuals and pulmonary TB patients. We studied CD3 induced intracellular calcium mobilization in PBMCs of healthy individuals and TB patients by spectrofluorimetry, CD3 and CD28 induced activation of mitogen activated protein kinases (MAPKs) in PBMCs of healthy individuals and TB patients by western blotting and binding of transcription factors NFAT and NFκB by Electrophorectic mobility shift assay (EMSA).', 'We observed CD3 triggered modulations in free intracellular calcium concentrations in PPD+ve healthy individuals and pulmonary TB patients after the treatment of M. tuberculosis antigens. As regards the downstream signalling events, phosphorylation of MAPKs, Extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38 was curtailed by M. tuberculosis antigens in TB patients whereas, in PPD+ve healthy individuals only ERK1/2 phosphorylation was inhibited. Besides, the terminal signalling events like binding of transcription factors NFAT and NFκB was also altered by M. tuberculosis antigens. Altogether, our results suggest that M. tuberculosis antigens, specifically ESAT-6, interfere with TCR/CD28-induced upstream as well as downstream signalling events which might be responsible for defective IL-2 production which further contributed in T-cell unresponsiveness, implicated in the progression of disease.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Acyltransferases', 'Antigens, Bacterial', 'Bacterial Proteins', 'CD28 Antigens', 'Calcium', 'Humans', 'Intracellular Space', 'Leukocytes, Mononuclear', 'Lymphocyte Activation', 'Mitogen-Activated Protein Kinases', 'Mycobacterium tuberculosis', 'NF-kappa B', 'NFATC Transcription Factors', 'Receptors, Antigen, T-Cell', 'Signal Transduction', 'T-Lymphocytes']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,537,003
Does biochar-amended potting medium reduce the susceptibility of rice to root-knot nematode infections?
{ "contexts": [ "Biochar is a solid coproduct of biomass pyrolysis, and soil amended with biochar has been shown to enhance the productivity of various crops and induce systemic plant resistance to fungal pathogens. The aim of this study was to explore the ability of wood biochar to induce resistance to the root-knot nematode (RKN) Meloidogyne graminicola in rice (Oryza sativa cv. Nipponbare) and examine its histochemical and molecular impact on plant defense mechanisms.", "A 1.2 % concentration of biochar added to the potting medium of rice was found to be the most effective at reducing nematode development in rice roots, whereas direct toxic effects of biochar exudates on nematode viability, infectivity or development were not observed. The increased plant resistance was associated with biochar-primed H2O2 accumulation as well as with the transcriptional enhancement of genes involved in the ethylene (ET) signaling pathway. The increased susceptibility of the Ein2b-RNAi line, which is deficient in ET signaling, further confirmed that biochar-induced priming acts at least partly through ET signaling." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Animals", "Charcoal", "Oryza", "Plant Diseases", "Soil", "Tylenchoidea" ] }
These results suggest that biochar amendments protect rice plants challenged by nematodes. This priming effect partially depends on the ET signaling pathway and enhanced H2O2 accumulation.
yes
[ { "from": "human", "value": "Question: Does biochar-amended potting medium reduce the susceptibility of rice to root-knot nematode infections?\nContext: {'contexts': ['Biochar is a solid coproduct of biomass pyrolysis, and soil amended with biochar has been shown to enhance the productivity of various crops and induce systemic plant resistance to fungal pathogens. The aim of this study was to explore the ability of wood biochar to induce resistance to the root-knot nematode (RKN) Meloidogyne graminicola in rice (Oryza sativa cv. Nipponbare) and examine its histochemical and molecular impact on plant defense mechanisms.', 'A 1.2 % concentration of biochar added to the potting medium of rice was found to be the most effective at reducing nematode development in rice roots, whereas direct toxic effects of biochar exudates on nematode viability, infectivity or development were not observed. The increased plant resistance was associated with biochar-primed H2O2 accumulation as well as with the transcriptional enhancement of genes involved in the ethylene (ET) signaling pathway. The increased susceptibility of the Ein2b-RNAi line, which is deficient in ET signaling, further confirmed that biochar-induced priming acts at least partly through ET signaling.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Animals', 'Charcoal', 'Oryza', 'Plant Diseases', 'Soil', 'Tylenchoidea']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,527,653
Does p53 Activity dominate That of p73 upon Mdm4 Loss in Development and Tumorigenesis?
{ "contexts": [ "Mdm4 negatively regulates the p53 tumor suppressor. Mdm4 loss in mice leads to an embryonic lethal phenotype that is p53-dependent. Biochemical studies indicate that Mdm4 also binds p73, a member of the p53 family, with higher affinity than p53. In this study, the significance of the Mdm4 and p73 interaction in vivo during embryogenesis and tumorigenesis was examined. The data revealed that p73 loss did not rescue either the early Mdm4-deficient embryonic lethality or the runted phenotype of Mdm4(Δ2/Δ2) p53(+/-) embryos. Furthermore, studies in the developing central nervous system wherein both genes have prominent roles indicated that loss of p73 also did not rescue the Mdm4-null brain phenotype as did p53 loss. This p53 dependency occurred despite evidence for p73-specific transcriptional activity. In tumor studies, the combination of Mdm4 overexpression and p73 loss did not alter survival of mice or the tumor spectrum as compared with Mdm4 overexpression alone. In summary, these data demonstrate that the Mdm4-p73 axis cannot override the dominant role of p53 in development and tumorigenesis." ], "labels": [ "UNLABELLED" ], "meshes": [ "Animals", "Apoptosis", "Carcinogenesis", "DNA-Binding Proteins", "Embryonic Development", "Mice", "Mice, Transgenic", "Nuclear Proteins", "Proto-Oncogene Proteins", "Tumor Protein p73", "Tumor Suppressor Protein p53", "Tumor Suppressor Proteins", "Ubiquitin-Protein Ligases" ] }
Genetic characterization of the Mdm4 and p73 interaction during development and tumorigenesis suggests new insight into the role of p53 family members, which may influence treatment options for patients.
yes
[ { "from": "human", "value": "Question: Does p53 Activity dominate That of p73 upon Mdm4 Loss in Development and Tumorigenesis?\nContext: {'contexts': ['Mdm4 negatively regulates the p53 tumor suppressor. Mdm4 loss in mice leads to an embryonic lethal phenotype that is p53-dependent. Biochemical studies indicate that Mdm4 also binds p73, a member of the p53 family, with higher affinity than p53. In this study, the significance of the Mdm4 and p73 interaction in vivo during embryogenesis and tumorigenesis was examined. The data revealed that p73 loss did not rescue either the early Mdm4-deficient embryonic lethality or the runted phenotype of Mdm4(Δ2/Δ2) p53(+/-) embryos. Furthermore, studies in the developing central nervous system wherein both genes have prominent roles indicated that loss of p73 also did not rescue the Mdm4-null brain phenotype as did p53 loss. This p53 dependency occurred despite evidence for p73-specific transcriptional activity. In tumor studies, the combination of Mdm4 overexpression and p73 loss did not alter survival of mice or the tumor spectrum as compared with Mdm4 overexpression alone. In summary, these data demonstrate that the Mdm4-p73 axis cannot override the dominant role of p53 in development and tumorigenesis.'], 'labels': ['UNLABELLED'], 'meshes': ['Animals', 'Apoptosis', 'Carcinogenesis', 'DNA-Binding Proteins', 'Embryonic Development', 'Mice', 'Mice, Transgenic', 'Nuclear Proteins', 'Proto-Oncogene Proteins', 'Tumor Protein p73', 'Tumor Suppressor Protein p53', 'Tumor Suppressor Proteins', 'Ubiquitin-Protein Ligases']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,539,739
Do lymphocyte depletion and subset alteration correlate to renal function in chronic kidney disease patients?
{ "contexts": [ "It is widely accepted that chronic renal failure is associated with severe alterations of immune system. However, few studies looked into the immune alteration in earlier stage of chronic kidney disease (CKD) patients. To characterize immune defect in CKD patients, we performed lymphocyte subset analysis and explored its relationship to renal function in this population.", "472 CKD patients were enrolled in this study. Lymphocyte subsets (CD19(+), CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD56(+)CD16(+)) were determined by flow cytometry. Clinical and laboratory data were collected. Patterns of immune cells in different stages of CKD were compared. Multivariate linear regression was used to evaluate the relationship between lymphocyte subset group and renal function. Correlation analysis was used to assess the relationship between lymphocyte subset and other clinical and laboratory data.", "Decreased lymphocyte counts occurred long before the end stage of renal disease. Increased NK cell percentage was negatively related to estimated glomerular filtration rate (eGFR) (r = -0.259, p < 0.001) while B cell percentage was positively related to eGFR (r = 0.249, p < 0.001). Further multivariate linear regression showed increased B cell percentage (β = 16.470, 95%CI [1.018-31.922], p = 0.037) and decreased NK cell percentage (β = -10.659, 95%CI [-20.063 to -1.254], p = 0.026) were independently correlated with higher eGFR, respectively. Patients with lower NK cell percentage and higher B cell percentage tended to have the best renal function." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Cross-Sectional Studies", "Female", "Humans", "Kidney Function Tests", "Killer Cells, Natural", "Lymphocyte Subsets", "Male", "Middle Aged", "Renal Insufficiency, Chronic" ] }
Lymphocyte depletion and subset alteration occurred during the progress of CKD. Further studies are needed to clarify the role of immune system in CKD and to expand our knowledge about the effect of uremia on the structure and function of immune system.
yes
[ { "from": "human", "value": "Question: Do lymphocyte depletion and subset alteration correlate to renal function in chronic kidney disease patients?\nContext: {'contexts': ['It is widely accepted that chronic renal failure is associated with severe alterations of immune system. However, few studies looked into the immune alteration in earlier stage of chronic kidney disease (CKD) patients. To characterize immune defect in CKD patients, we performed lymphocyte subset analysis and explored its relationship to renal function in this population.', '472 CKD patients were enrolled in this study. Lymphocyte subsets (CD19(+), CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD56(+)CD16(+)) were determined by flow cytometry. Clinical and laboratory data were collected. Patterns of immune cells in different stages of CKD were compared. Multivariate linear regression was used to evaluate the relationship between lymphocyte subset group and renal function. Correlation analysis was used to assess the relationship between lymphocyte subset and other clinical and laboratory data.', 'Decreased lymphocyte counts occurred long before the end stage of renal disease. Increased NK cell percentage was negatively related to estimated glomerular filtration rate (eGFR) (r = -0.259, p < 0.001) while B cell percentage was positively related to eGFR (r = 0.249, p < 0.001). Further multivariate linear regression showed increased B cell percentage (β = 16.470, 95%CI [1.018-31.922], p = 0.037) and decreased NK cell percentage (β = -10.659, 95%CI [-20.063 to -1.254], p = 0.026) were independently correlated with higher eGFR, respectively. Patients with lower NK cell percentage and higher B cell percentage tended to have the best renal function.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Cross-Sectional Studies', 'Female', 'Humans', 'Kidney Function Tests', 'Killer Cells, Natural', 'Lymphocyte Subsets', 'Male', 'Middle Aged', 'Renal Insufficiency, Chronic']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,525,528
Does locomotor Adaptability Task promote Intense and Task-Appropriate Output From the Paretic Leg During Walking?
{ "contexts": [ "To test the hypothesis that participants with stroke will exhibit appropriate increase in muscle activation of the paretic leg when taking a long step with the nonparetic leg compared to during steady-state walking, with a consequent increase in biomechanical output and symmetry during the stance phase of the modified gait cycle.", "Single-session observational study.", "Clinical research center in an outpatient hospital setting.", "Adults with chronic poststroke hemiparesis (N=15).", "Participants walked on an instrumented treadmill while kinetic, kinematic, and electromyogram data were recorded. Participants performed steady-state walking and a separate trial of the long-step adaptability task in which they were instructed to intermittently take a longer step with the nonparetic leg.", "Forward progression, propulsive force, and neuromuscular activation during walking.", "Participants performed the adaptability task successfully and demonstrated greater neuromuscular activation in appropriate paretic leg muscles, particularly increased activity in paretic plantarflexor muscles. Propulsion and forward progression by the paretic leg were also increased." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "METHODS", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Electromyography", "Female", "Humans", "Leg", "Male", "Middle Aged", "Paresis", "Stroke", "Stroke Rehabilitation", "Treatment Outcome", "Walking" ] }
These findings support the assertion that the nonparetic long-step task may be effective for use in poststroke locomotor rehabilitation to engage the paretic leg and promote recovery of walking.
yes
[ { "from": "human", "value": "Question: Does locomotor Adaptability Task promote Intense and Task-Appropriate Output From the Paretic Leg During Walking?\nContext: {'contexts': ['To test the hypothesis that participants with stroke will exhibit appropriate increase in muscle activation of the paretic leg when taking a long step with the nonparetic leg compared to during steady-state walking, with a consequent increase in biomechanical output and symmetry during the stance phase of the modified gait cycle.', 'Single-session observational study.', 'Clinical research center in an outpatient hospital setting.', 'Adults with chronic poststroke hemiparesis (N=15).', 'Participants walked on an instrumented treadmill while kinetic, kinematic, and electromyogram data were recorded. Participants performed steady-state walking and a separate trial of the long-step adaptability task in which they were instructed to intermittently take a longer step with the nonparetic leg.', 'Forward progression, propulsive force, and neuromuscular activation during walking.', 'Participants performed the adaptability task successfully and demonstrated greater neuromuscular activation in appropriate paretic leg muscles, particularly increased activity in paretic plantarflexor muscles. Propulsion and forward progression by the paretic leg were also increased.'], 'labels': ['OBJECTIVE', 'METHODS', 'METHODS', 'METHODS', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Electromyography', 'Female', 'Humans', 'Leg', 'Male', 'Middle Aged', 'Paresis', 'Stroke', 'Stroke Rehabilitation', 'Treatment Outcome', 'Walking']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,546,790
Are anticipatory and consummatory effects of ( hedonic ) chocolate intake associated with increased circulating levels of the orexigenic peptide ghrelin and endocannabinoids in obese adults?
{ "contexts": [ "Hedonic hunger refers to consumption of food just for pleasure and not to maintain energy homeostasis. Recently, consumption of food for pleasure was reported to be associated with increased circulating levels of both the orexigenic peptide ghrelin and the endocannabinoid 2-arachidonoyl-glycerol (2-AG) in normal-weight subjects. To date, the effects of hedonic hunger, and in particular of chocolate craving, on these mediators in obese subjects are still unknown.", "To explore the role of some gastrointestinal orexigenic and anorexigenic peptides and endocannabinoids (and some related congeners) in chocolate consumption, we measured changes in circulating levels of ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), anandamide (AEA), 2-AG, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) in 10 satiated severely obese subjects after consumption of chocolate and, on a separate day, of a non-palatable isocaloric food with the same bromatologic composition. Evaluation of hunger and satiety was also performed by visual analogic scale.", "The anticipatory phase and the consumption of food for pleasure were associated with increased circulating levels of ghrelin, AEA, 2-AG, and OEA. In contrast, the levels of GLP-1, PYY, and PEA did not differ before and after the exposure/ingestion of either chocolate or non-palatable foods. Hunger and satiety were higher and lower, respectively, in the hedonic session than in the non-palatable one." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
When motivation to eat is generated by exposure to, and consumption of, chocolate a peripheral activation of specific endogenous rewarding chemical signals, including ghrelin, AEA, and 2-AG, is observed in obese subjects. Although preliminary, these findings predict the effectiveness of ghrelin and endocannabinoid antagonists in the treatment of obesity.
yes
[ { "from": "human", "value": "Question: Are anticipatory and consummatory effects of ( hedonic ) chocolate intake associated with increased circulating levels of the orexigenic peptide ghrelin and endocannabinoids in obese adults?\nContext: {'contexts': ['Hedonic hunger refers to consumption of food just for pleasure and not to maintain energy homeostasis. Recently, consumption of food for pleasure was reported to be associated with increased circulating levels of both the orexigenic peptide ghrelin and the endocannabinoid 2-arachidonoyl-glycerol (2-AG) in normal-weight subjects. To date, the effects of hedonic hunger, and in particular of chocolate craving, on these mediators in obese subjects are still unknown.', 'To explore the role of some gastrointestinal orexigenic and anorexigenic peptides and endocannabinoids (and some related congeners) in chocolate consumption, we measured changes in circulating levels of ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), anandamide (AEA), 2-AG, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) in 10 satiated severely obese subjects after consumption of chocolate and, on a separate day, of a non-palatable isocaloric food with the same bromatologic composition. Evaluation of hunger and satiety was also performed by visual analogic scale.', 'The anticipatory phase and the consumption of food for pleasure were associated with increased circulating levels of ghrelin, AEA, 2-AG, and OEA. In contrast, the levels of GLP-1, PYY, and PEA did not differ before and after the exposure/ingestion of either chocolate or non-palatable foods. Hunger and satiety were higher and lower, respectively, in the hedonic session than in the non-palatable one.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,546,793
Is social interaction associated with changes in infants ' motor activity?
{ "contexts": [ "In developmental research, infants are commonly assumed to be early stakeholders in interactions with their caregivers. The tools that infants can use to interact with others vary from visual contact to smiling or vocalizing, and also include motor activity. However, surprisingly few studies have explored how the nature and context of social interactions affect infants' engagement in motor activity.", "We investigated the kinematic properties of foot and face movements produced by 11 infants aged between 5 and 9 months during six contrasting dyadic episodes (i.e. passive presence of a stranger or the infant's mother, weak or intense interaction with the stranger/mother as she sings a nursery play song).", "The infants' face and foot motor activity was significantly reduced during the interactive episodes, compared with the episodes without any interaction, in both the mother and stranger conditions. Furthermore, the level of their motor activity was significantly lower in the stranger condition than in the mother one for some parameters." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
These results are in line with those reported by previous studies and confirm the relevance of using motor activity to delineate the early forms of interactive episodes in infants.
yes
[ { "from": "human", "value": "Question: Is social interaction associated with changes in infants ' motor activity?\nContext: {'contexts': [\"In developmental research, infants are commonly assumed to be early stakeholders in interactions with their caregivers. The tools that infants can use to interact with others vary from visual contact to smiling or vocalizing, and also include motor activity. However, surprisingly few studies have explored how the nature and context of social interactions affect infants' engagement in motor activity.\", \"We investigated the kinematic properties of foot and face movements produced by 11 infants aged between 5 and 9 months during six contrasting dyadic episodes (i.e. passive presence of a stranger or the infant's mother, weak or intense interaction with the stranger/mother as she sings a nursery play song).\", \"The infants' face and foot motor activity was significantly reduced during the interactive episodes, compared with the episodes without any interaction, in both the mother and stranger conditions. Furthermore, the level of their motor activity was significantly lower in the stranger condition than in the mother one for some parameters.\"], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,545,669
Does gANODERMA LUCIDUM improve PHYSICAL FITNESS IN WOMEN WITH FIBROMYALGIA?
{ "contexts": [ "fibromyalgia is a chronic disease characterized by generalized pain, stiffness, poor physical conditioning, non-restorative sleep and poor health-related quality of life. Ganoderma lucidum a type of mushroom that has demonstrated several benefits in different populations. Ceratonia siliqua is a natural therapy rich in antioxidants with potential benefits on health.", "to evaluate the effects of 6-week treatment of Ganoderma lucidum and Ceratonia siliqua on physical fitness in patients suffering from fibromyalgia.", "sixty-four women with fibromyalgia participated in the study. They took 6 g of Ganoderma lucidum or Ceratonia siliqua per day for 6 weeks. Different fitness tests were selected in order to evaluate functional capacity.", "after the 6-week treatment period, Ganoderma lucidum significantly improved aerobic endurance, lower body flexibility, and velocity (p < .05). No significant improvement in any physical test was observed in the Ceratonia siliqua group." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Antioxidants", "Dietary Supplements", "Double-Blind Method", "Exercise", "Fabaceae", "Female", "Fibromyalgia", "Humans", "Middle Aged", "Muscle Strength", "Physical Endurance", "Physical Fitness", "Reishi" ] }
Ganoderma lucidum may improve physical fitness in women with fibromyalgia, whereas, Ceratonia siliqua seemed to be ineffective at increasing physical fitness. These results may indicate that Ganoderma lucidum might be a useful dietary supplement to enhance physical performance of the patients suffering from fibromyalgia.
yes
[ { "from": "human", "value": "Question: Does gANODERMA LUCIDUM improve PHYSICAL FITNESS IN WOMEN WITH FIBROMYALGIA?\nContext: {'contexts': ['fibromyalgia is a chronic disease characterized by generalized pain, stiffness, poor physical conditioning, non-restorative sleep and poor health-related quality of life. Ganoderma lucidum a type of mushroom that has demonstrated several benefits in different populations. Ceratonia siliqua is a natural therapy rich in antioxidants with potential benefits on health.', 'to evaluate the effects of 6-week treatment of Ganoderma lucidum and Ceratonia siliqua on physical fitness in patients suffering from fibromyalgia.', 'sixty-four women with fibromyalgia participated in the study. They took 6 g of Ganoderma lucidum or Ceratonia siliqua per day for 6 weeks. Different fitness tests were selected in order to evaluate functional capacity.', 'after the 6-week treatment period, Ganoderma lucidum significantly improved aerobic endurance, lower body flexibility, and velocity (p < .05). No significant improvement in any physical test was observed in the Ceratonia siliqua group.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Antioxidants', 'Dietary Supplements', 'Double-Blind Method', 'Exercise', 'Fabaceae', 'Female', 'Fibromyalgia', 'Humans', 'Middle Aged', 'Muscle Strength', 'Physical Endurance', 'Physical Fitness', 'Reishi']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,525,280
Is expression of epigenetic modifiers significantly altered by exposure to secondhand smoke?
{ "contexts": [ "Secondhand smoke (SHS) is a major risk factor for lung cancer in nonsmokers. DNA damage-derived mutagenicity is a well-established mechanism of SHS-carcinogenicity; however very little is known about the impact of SHS exposure on the epigenome.", "We have investigated whether exposure to SHS can modulate the expression of key epigenetic regulators responsible for the establishment and/or maintenance of DNA methylation and histone modification patterns in vivo. We have sub-chronically exposed mice to a mutagenic but non-tumorigenic dose of SHS, and subsequently determined the expression levels of major epigenetic modifiers in the lungs of SHS-exposed mice, immediately after termination of exposure and following 7-month recovery in clean air." ], "labels": [ "OBJECTIVE", "METHODS" ], "meshes": [ "Acetylation", "Animals", "Biomarkers", "DNA (Cytosine-5-)-Methyltransferases", "Epigenesis, Genetic", "Gene Expression Regulation, Neoplastic", "Histones", "Lung", "Male", "Mice", "Tobacco Smoke Pollution" ] }
Quantification of the expression of genes encoding DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b and Dnmt3l), methyl binding domain proteins (Mecp2, Mbd2 and Mbd3) and histone deacetylases (Hdac1 and Hdac2) by quantitative reverse-transcription polymerase chain reaction analysis showed modest but not statistically significant differences in the relative transcription of these key epigenetic regulators between SHS-exposed mice and age-matched controls. The non-significant changes in the expression of main epigenetic modifiers in SHS-exposed mice imply that SHS may predominantly induce genotoxic effects, particularly at non-tumorigenic doses, whereas epigenetic effects may only be secondary and manifest en route to tumor formation.
no
[ { "from": "human", "value": "Question: Is expression of epigenetic modifiers significantly altered by exposure to secondhand smoke?\nContext: {'contexts': ['Secondhand smoke (SHS) is a major risk factor for lung cancer in nonsmokers. DNA damage-derived mutagenicity is a well-established mechanism of SHS-carcinogenicity; however very little is known about the impact of SHS exposure on the epigenome.', 'We have investigated whether exposure to SHS can modulate the expression of key epigenetic regulators responsible for the establishment and/or maintenance of DNA methylation and histone modification patterns in vivo. We have sub-chronically exposed mice to a mutagenic but non-tumorigenic dose of SHS, and subsequently determined the expression levels of major epigenetic modifiers in the lungs of SHS-exposed mice, immediately after termination of exposure and following 7-month recovery in clean air.'], 'labels': ['OBJECTIVE', 'METHODS'], 'meshes': ['Acetylation', 'Animals', 'Biomarkers', 'DNA (Cytosine-5-)-Methyltransferases', 'Epigenesis, Genetic', 'Gene Expression Regulation, Neoplastic', 'Histones', 'Lung', 'Male', 'Mice', 'Tobacco Smoke Pollution']}" }, { "from": "gpt", "value": "Answer: no" } ]
26,546,610
Does a novel N-acetyl-glucosamine lectin of Lonchocarpus araripensis attenuate acute cellular inflammation in mice?
{ "contexts": [ "This study had investigated the anti-inflammatory activity of a seed lectin (LAL) isolated from Lonchocarpus araripensis.", "LAL was purified by affinity chromatography (chitin column) and ion exchange chromatography (DEAE-Sephacel). In vitro LAL was tested for hemagglutinating activity against rabbit erythrocytes. In vivo LAL was assessed for the anti-inflammatory activity via intravenous injection (i.v.) in Swiss mice (25-30 g; n = 6/group) in models of paw edema and peritonitis.", "ANOVA (p < 0.05).", "LAL revealed two bands of 30 and 60 kDa (SDS-PAGE) and exhibited hemagglutinating activity. LAL (10 mg/kg) inhibited the paw edema (77%) and vascular permeability (26%) induced by carrageenan, and the paw edema induced by serotonin (80%), bradykinin (49%), sodium nitroprusside (83%), TNF-α (75%) and PGE2 (64%). LAL also inhibited the neutrophil migration induced by fMLP (70%) or carrageenan (69%). The intravital microscopy showed that LAL inhibited rolling (83%) and adhesion (70%) of leukocytes. LAL anti-inflammatory effect was reversed by its association with N-acetyl-glucosamine. The nine-daily treatment with LAL (10 mg/kg; i.v.) showed no toxicity." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Acetylglucosamine", "Animals", "Anti-Inflammatory Agents", "Capillary Permeability", "Edema", "Erythrocytes", "Fabaceae", "Hemagglutination", "In Vitro Techniques", "Inflammation", "Lectins", "Male", "Mice", "Peritonitis", "Rabbits", "Seeds" ] }
The novel N-acetyl-D-glucosamine-binding lectin isolated from L. araripensis seeds presents anti-inflammatory effect involving the lectin domain and the inhibition of 5-HT, BK, PGE2, NO, TNF-α and leukocyte rolling and adhesion.
yes
[ { "from": "human", "value": "Question: Does a novel N-acetyl-glucosamine lectin of Lonchocarpus araripensis attenuate acute cellular inflammation in mice?\nContext: {'contexts': ['This study had investigated the anti-inflammatory activity of a seed lectin (LAL) isolated from Lonchocarpus araripensis.', 'LAL was purified by affinity chromatography (chitin column) and ion exchange chromatography (DEAE-Sephacel). In vitro LAL was tested for hemagglutinating activity against rabbit erythrocytes. In vivo LAL was assessed for the anti-inflammatory activity via intravenous injection (i.v.) in Swiss mice (25-30 g; n = 6/group) in models of paw edema and peritonitis.', 'ANOVA (p < 0.05).', 'LAL revealed two bands of 30 and 60 kDa (SDS-PAGE) and exhibited hemagglutinating activity. LAL (10 mg/kg) inhibited the paw edema (77%) and vascular permeability (26%) induced by carrageenan, and the paw edema induced by serotonin (80%), bradykinin (49%), sodium nitroprusside (83%), TNF-α (75%) and PGE2 (64%). LAL also inhibited the neutrophil migration induced by fMLP (70%) or carrageenan (69%). The intravital microscopy showed that LAL inhibited rolling (83%) and adhesion (70%) of leukocytes. LAL anti-inflammatory effect was reversed by its association with N-acetyl-glucosamine. The nine-daily treatment with LAL (10 mg/kg; i.v.) showed no toxicity.'], 'labels': ['OBJECTIVE', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Acetylglucosamine', 'Animals', 'Anti-Inflammatory Agents', 'Capillary Permeability', 'Edema', 'Erythrocytes', 'Fabaceae', 'Hemagglutination', 'In Vitro Techniques', 'Inflammation', 'Lectins', 'Male', 'Mice', 'Peritonitis', 'Rabbits', 'Seeds']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,546,611
Is mortality in patients with non-functioning pituitary adenoma increased : systematic analysis of 546 cases with long follow-up?
{ "contexts": [ "Non-functioning pituitary adenomas (NFAs) have a prevalence of 7-22/100,000 people. A significant number of patients suffer from morbidities related to the tumor, possible recurrence(s), and treatments utilized. Our aim was to assess mortality of patients with macroNFA and predictive factors.", "Retrospective cohort study in a tertiary referral center in the UK.", "A total of 546 patients operated for a macroNFA between 1963 and 2011 were studied. Mortality data were retrieved through the National Health Service Central Register and hospital records and recorded as standardized mortality ratio (SMR). Mortality was estimated for the total and various subgroups with clinical follow-up data.", "Median follow-up was 8 years (range: 1 month-48.5 years). SMR was 3.6 (95% CI, 2.9-4.5), for those operated before 1990, 4.7 (95% CI, 2.7-7.6) and for those after 1990, 3.5 (95% CI, 2.8-4.4). Main causes of death were cardio/cerebrovascular (33.7%), infections (30.1%), and malignancy (28.9%). Cox regression analysis demonstrated that only age at diagnosis remained an independent predictor of mortality (hazard ratio 1.10; 95% CI, 1.07-1.13, P<0.001), whereas sex, presentation with acute apoplexy, extent of tumor removal, radiotherapy, recurrence, untreated GH deficiency, FSH/LH deficiency, ACTH deficiency, TSH deficiency, and treatment with desmopressin had no impact." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Adenoma", "Adult", "Age Factors", "Aged", "Aged, 80 and over", "Cause of Death", "Female", "Follow-Up Studies", "Humans", "Male", "Middle Aged", "Pituitary Neoplasms", "Registries", "United Kingdom" ] }
Despite the improvement of treatments over the last three decades, the mortality of patients with NFAs in our series remains high. Apart from age, factors related with the management/outcome of the tumor are not independent predictors, and pituitary hormone deficits managed with the currently-used substitution protocols do not adversely affect mortality.
yes
[ { "from": "human", "value": "Question: Is mortality in patients with non-functioning pituitary adenoma increased : systematic analysis of 546 cases with long follow-up?\nContext: {'contexts': ['Non-functioning pituitary adenomas (NFAs) have a prevalence of 7-22/100,000 people. A significant number of patients suffer from morbidities related to the tumor, possible recurrence(s), and treatments utilized. Our aim was to assess mortality of patients with macroNFA and predictive factors.', 'Retrospective cohort study in a tertiary referral center in the UK.', 'A total of 546 patients operated for a macroNFA between 1963 and 2011 were studied. Mortality data were retrieved through the National Health Service Central Register and hospital records and recorded as standardized mortality ratio (SMR). Mortality was estimated for the total and various subgroups with clinical follow-up data.', 'Median follow-up was 8 years (range: 1 month-48.5 years). SMR was 3.6 (95% CI, 2.9-4.5), for those operated before 1990, 4.7 (95% CI, 2.7-7.6) and for those after 1990, 3.5 (95% CI, 2.8-4.4). Main causes of death were cardio/cerebrovascular (33.7%), infections (30.1%), and malignancy (28.9%). Cox regression analysis demonstrated that only age at diagnosis remained an independent predictor of mortality (hazard ratio 1.10; 95% CI, 1.07-1.13, P<0.001), whereas sex, presentation with acute apoplexy, extent of tumor removal, radiotherapy, recurrence, untreated GH deficiency, FSH/LH deficiency, ACTH deficiency, TSH deficiency, and treatment with desmopressin had no impact.'], 'labels': ['OBJECTIVE', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Adenoma', 'Adult', 'Age Factors', 'Aged', 'Aged, 80 and over', 'Cause of Death', 'Female', 'Follow-Up Studies', 'Humans', 'Male', 'Middle Aged', 'Pituitary Neoplasms', 'Registries', 'United Kingdom']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,546,617
Does combination of Photodynamic Therapy and Specific Immunotherapy Efficiently eradicate Established Tumors?
{ "contexts": [ "The efficacy of immunotherapy against advanced cancer may be improved by combination strategies. Photodynamic therapy (PDT) is a local tumor ablation method based on localized activation of a photosensitizer, leading to oxygen radical-induced tumor cell death. PDT can enhance antitumor immune responses by release of antigen and danger signals, supporting combination protocols of PDT with immunotherapy.", "We investigated the local and systemic immune effects of PDT after treatment of established tumors. In two independent aggressive mouse tumor models, TC-1 and RMA, we combined PDT with therapeutic vaccination using synthetic long peptides (SLP) containing epitopes from tumor antigens.", "PDT of established tumors using the photosensitizer Bremachlorin resulted in significant delay of tumor outgrowth. Combination treatment of PDT with therapeutic SLP vaccination cured one third of mice. Importantly, all cured mice were fully protected against subsequent tumor rechallenge, and combination treatment of primary tumors led to eradication of distant secondary tumors, indicating the induction of a systemic antitumor immune response. Indeed, PDT by itself induced a significant CD8(+) T-cell response against the tumor, which was increased when combined with SLP vaccination and essential for the therapeutic effect of combination therapy." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Antigens, Neoplasm", "CD8-Positive T-Lymphocytes", "Cancer Vaccines", "Cell Line, Tumor", "Combined Modality Therapy", "Disease Models, Animal", "Female", "Humans", "Immunomodulation", "Immunotherapy", "Mice", "Neoplasms", "Photochemotherapy", "Photosensitizing Agents", "Tumor Burden", "Vaccines, Subunit" ] }
We show that immunotherapy can be efficiently combined with PDT to eradicate established tumors, based on strong local tumor ablation and the induction of a robust systemic immune response. These results suggest combination of active immunotherapy with tumor ablation by PDT as a feasible novel treatment strategy for advanced cancer.
yes
[ { "from": "human", "value": "Question: Does combination of Photodynamic Therapy and Specific Immunotherapy Efficiently eradicate Established Tumors?\nContext: {'contexts': ['The efficacy of immunotherapy against advanced cancer may be improved by combination strategies. Photodynamic therapy (PDT) is a local tumor ablation method based on localized activation of a photosensitizer, leading to oxygen radical-induced tumor cell death. PDT can enhance antitumor immune responses by release of antigen and danger signals, supporting combination protocols of PDT with immunotherapy.', 'We investigated the local and systemic immune effects of PDT after treatment of established tumors. In two independent aggressive mouse tumor models, TC-1 and RMA, we combined PDT with therapeutic vaccination using synthetic long peptides (SLP) containing epitopes from tumor antigens.', 'PDT of established tumors using the photosensitizer Bremachlorin resulted in significant delay of tumor outgrowth. Combination treatment of PDT with therapeutic SLP vaccination cured one third of mice. Importantly, all cured mice were fully protected against subsequent tumor rechallenge, and combination treatment of primary tumors led to eradication of distant secondary tumors, indicating the induction of a systemic antitumor immune response. Indeed, PDT by itself induced a significant CD8(+) T-cell response against the tumor, which was increased when combined with SLP vaccination and essential for the therapeutic effect of combination therapy.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Antigens, Neoplasm', 'CD8-Positive T-Lymphocytes', 'Cancer Vaccines', 'Cell Line, Tumor', 'Combined Modality Therapy', 'Disease Models, Animal', 'Female', 'Humans', 'Immunomodulation', 'Immunotherapy', 'Mice', 'Neoplasms', 'Photochemotherapy', 'Photosensitizing Agents', 'Tumor Burden', 'Vaccines, Subunit']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,531,184
Does age affect the clinical and radiological outcomes after open-wedge high tibial osteotomy?
{ "contexts": [ "Open-wedge high tibial osteotomy (OWHTO) is a well-established procedure in the management of medial compartment osteoarthritis and osteonecrosis of the medial femoral condyle. Several studies have evaluated factors that negatively influence outcomes. However, few reports have investigated the effect of age on HTO outcome. We evaluated the influence of the age on the outcome after HTO.", "The TomoFix", "There were no statistical differences in the background factors between the two groups. Postoperatively, the mean JOA score showed a significant improvement in both groups. The mean OKS after surgery was 41.6 ± 5.9 in group A and 41.4 ± 5.9 in group B. There were no statistical differences in the postoperative knee alignment and clinical outcomes between the two groups." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Age Factors", "Aged", "Bone Plates", "Female", "Humans", "Knee Joint", "Male", "Osteoarthritis, Knee", "Osteonecrosis", "Osteotomy", "Radiography", "Retrospective Studies", "Tibia", "Treatment Outcome" ] }
OWHTO using the rigid long plate was an effective procedure independent of patient's age. The results showed that age did not influence the clinical and radiological outcomes after OWHTO.
no
[ { "from": "human", "value": "Question: Does age affect the clinical and radiological outcomes after open-wedge high tibial osteotomy?\nContext: {'contexts': ['Open-wedge high tibial osteotomy (OWHTO) is a well-established procedure in the management of medial compartment osteoarthritis and osteonecrosis of the medial femoral condyle. Several studies have evaluated factors that negatively influence outcomes. However, few reports have investigated the effect of age on HTO outcome. We evaluated the influence of the age on the outcome after HTO.', 'The TomoFix', 'There were no statistical differences in the background factors between the two groups. Postoperatively, the mean JOA score showed a significant improvement in both groups. The mean OKS after surgery was 41.6\\xa0±\\xa05.9 in group A and 41.4\\xa0±\\xa05.9 in group B. There were no statistical differences in the postoperative knee alignment and clinical outcomes between the two groups.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Age Factors', 'Aged', 'Bone Plates', 'Female', 'Humans', 'Knee Joint', 'Male', 'Osteoarthritis, Knee', 'Osteonecrosis', 'Osteotomy', 'Radiography', 'Retrospective Studies', 'Tibia', 'Treatment Outcome']}" }, { "from": "gpt", "value": "Answer: no" } ]
26,531,183
Do patient-reported allergies cause inferior outcomes after total knee arthroplasty?
{ "contexts": [ "The main objective of this study was to analyse the outcomes after total knee arthroplasty (TKA) of a group of patients with at least one self-reported allergy and a group of patients without reported allergies. We hypothesized there is a significant negative influence on clinical outcome scores after TKA in patients with self-reported allergies.", "Four-hundred and seventy-five patients who had undergone TKA were analysed preoperatively and 1 year after surgery. The WOMAC, KSS and SF-36 scores were obtained. The patients' Yesavage depression questionnaire score was also recorded. The scores of the 330 (69.5 %) patients without self-reported allergies were compared to the scores of the 145 (30.5 %) patients with at least one self-reported allergy in the medical record.", "Preoperative scores were similar in both groups. The WOMAC post-operative scores (23.6 vs 20.4; p = 0.037) and the KSS-Knee score (91.1 vs 87.6; p = 0.027) were worse in the group of patients with self-reported allergies than in the group without allergies. The scores from the Yesavage depression questionnaire and in the SF-36 were similar in both groups." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Arthroplasty, Replacement, Knee", "Female", "Humans", "Hypersensitivity", "Knee Joint", "Male", "Patient Outcome Assessment", "Prognosis", "Prospective Studies", "Self Report", "Spain" ] }
Patients with at least one self-reported allergy have worse post-operative outcomes in terms of the WOMAC and KSS-Knee scores after TKA than patients without allergies. These poor outcomes do not seem to be related to depression. Therefore, more research is needed to explain them. Reported allergies could be considered a prognostic factor and used when counselling TKA patients.
yes
[ { "from": "human", "value": "Question: Do patient-reported allergies cause inferior outcomes after total knee arthroplasty?\nContext: {'contexts': ['The main objective of this study was to analyse the outcomes after total knee arthroplasty (TKA) of a group of patients with at least one self-reported allergy and a group of patients without reported allergies. We hypothesized there is a significant negative influence on clinical outcome scores after TKA in patients with self-reported allergies.', \"Four-hundred and seventy-five patients who had undergone TKA were analysed preoperatively and 1\\xa0year after surgery. The WOMAC, KSS and SF-36 scores were obtained. The patients' Yesavage depression questionnaire score was also recorded. The scores of the 330 (69.5\\xa0%) patients without self-reported allergies were compared to the scores of the 145 (30.5\\xa0%) patients with at least one self-reported allergy in the medical record.\", 'Preoperative scores were similar in both groups. The WOMAC post-operative scores (23.6 vs 20.4; p\\xa0=\\xa00.037) and the KSS-Knee score (91.1 vs 87.6; p\\xa0=\\xa00.027) were worse in the group of patients with self-reported allergies than in the group without allergies. The scores from the Yesavage depression questionnaire and in the SF-36 were similar in both groups.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Arthroplasty, Replacement, Knee', 'Female', 'Humans', 'Hypersensitivity', 'Knee Joint', 'Male', 'Patient Outcome Assessment', 'Prognosis', 'Prospective Studies', 'Self Report', 'Spain']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,547,127
Do electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines?
{ "contexts": [ "Evaluate the cytotoxicity and genotoxicity of short- and long-term e-cigarette vapor exposure on a panel of normal epithelial and head and neck squamous cell carcinoma (HNSCC) cell lines.", "HaCaT, UMSCC10B, and HN30 were treated with nicotine-containing and nicotine-free vapor extract from two popular e-cigarette brands for periods ranging from 48 h to 8 weeks. Cytotoxicity was assessed using Annexin V flow cytometric analysis, trypan blue exclusion, and clonogenic assays. Genotoxicity in the form of DNA strand breaks was quantified using the neutral comet assay and γ-H2AX immunostaining.", "E-cigarette-exposed cells showed significantly reduced cell viability and clonogenic survival, along with increased rates of apoptosis and necrosis, regardless of e-cigarette vapor nicotine content. They also exhibited significantly increased comet tail length and accumulation of γ-H2AX foci, demonstrating increased DNA strand breaks." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Carcinoma, Squamous Cell", "Cell Death", "Cell Line, Tumor", "DNA Damage", "Electronic Nicotine Delivery Systems", "Epithelial Cells", "Head and Neck Neoplasms", "Humans", "Nicotine", "Nicotinic Agonists", "Volatilization" ] }
E-cigarette vapor, both with and without nicotine, is cytotoxic to epithelial cell lines and is a DNA strand break-inducing agent. Further assessment of the potential carcinogenic effects of e-cigarette vapor is urgently needed.
yes
[ { "from": "human", "value": "Question: Do electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines?\nContext: {'contexts': ['Evaluate the cytotoxicity and genotoxicity of short- and long-term e-cigarette vapor exposure on a panel of normal epithelial and head and neck squamous cell carcinoma (HNSCC) cell lines.', 'HaCaT, UMSCC10B, and HN30 were treated with nicotine-containing and nicotine-free vapor extract from two popular e-cigarette brands for periods ranging from 48 h to 8 weeks. Cytotoxicity was assessed using Annexin V flow cytometric analysis, trypan blue exclusion, and clonogenic assays. Genotoxicity in the form of DNA strand breaks was quantified using the neutral comet assay and γ-H2AX immunostaining.', 'E-cigarette-exposed cells showed significantly reduced cell viability and clonogenic survival, along with increased rates of apoptosis and necrosis, regardless of e-cigarette vapor nicotine content. They also exhibited significantly increased comet tail length and accumulation of γ-H2AX foci, demonstrating increased DNA strand breaks.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Carcinoma, Squamous Cell', 'Cell Death', 'Cell Line, Tumor', 'DNA Damage', 'Electronic Nicotine Delivery Systems', 'Epithelial Cells', 'Head and Neck Neoplasms', 'Humans', 'Nicotine', 'Nicotinic Agonists', 'Volatilization']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,551,455
Does long non-coding MIAT mediate high glucose-induced renal tubular epithelial injury?
{ "contexts": [ "Long non-coding RNAs (lncRNAs) constitute a novel class of non-coding RNAs that take part in occurrence and development of diabetes complication via regulating gene expression. However, litter is known about lncRNAs in the setting of diabetes induced nephropathy. The aim of this study was to examine whether lncRNA-myocardial infarction-associated transcript (MIAT) is involved in diabetes induced renal tubules injury.", "Adult Wister rats were randomly assigned to receive intraperitoneal STZ (65 mg/kg) to induce diabetes. Rats treated with equal volume of citrate buffer were as control. Renal function was evaluated by analysis of serum creatinine and blood urea nitrogen (BUN) every four weeks after STZ administration. Also tubules of all rats were collected for determination of MIAT and Nrf2 level at the corresponding phase. The in vitro high glucose-triggered human renal tubular epithelial cell line (HK-2) was used to explore the mechanism underling MIAT regulated high glucose-induced tubular damage.", "In diabetic rats, MIAT showed the lower level and its expression is negatively correlated with serum creatinine and BUN. Consistent with diabetic rat, exposed to high glucose, HK-2 cells expressed lower level of MIAT and Nrf2, and also showed reduction in cell viability. By pcDNA-MIAT plasmid transfection, we observed that MIAT overexpression reversed inhibitory action of Nrf2 expression by high glucose. Moreover, the data of RNA pull-down and RIP showed that MIAT controlled Nrf2 cellular through enhancing Nrf2 stability, which was confirmed by CHX and MG132 administration. Inhibitory effect of cell viability by silencing MIAT was also reversed by Nrf2 overexpression." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Cell Survival", "Diabetic Nephropathies", "Dose-Response Relationship, Drug", "Glucose", "Kidney Tubules", "Male", "RNA, Long Noncoding", "Rats", "Rats, Wistar" ] }
In summary, our data suggested that MIAT/Nrf2 served as an important signaling pathway for high glucose induced renal tubular epithelial injury.
yes
[ { "from": "human", "value": "Question: Does long non-coding MIAT mediate high glucose-induced renal tubular epithelial injury?\nContext: {'contexts': ['Long non-coding RNAs (lncRNAs) constitute a novel class of non-coding RNAs that take part in occurrence and development of diabetes complication via regulating gene expression. However, litter is known about lncRNAs in the setting of diabetes induced nephropathy. The aim of this study was to examine whether lncRNA-myocardial infarction-associated transcript (MIAT) is involved in diabetes induced renal tubules injury.', 'Adult Wister rats were randomly assigned to receive intraperitoneal STZ (65\\xa0mg/kg) to induce diabetes. Rats treated with equal volume of citrate buffer were as control. Renal function was evaluated by analysis of serum creatinine and blood urea nitrogen (BUN) every four weeks after STZ administration. Also tubules of all rats were collected for determination of MIAT and Nrf2 level at the corresponding phase. The in\\xa0vitro high glucose-triggered human renal tubular epithelial cell line (HK-2) was used to explore the mechanism underling MIAT regulated high glucose-induced tubular damage.', 'In diabetic rats, MIAT showed the lower level and its expression is negatively correlated with serum creatinine and BUN. Consistent with diabetic rat, exposed to high glucose, HK-2 cells expressed lower level of MIAT and Nrf2, and also showed reduction in cell viability. By pcDNA-MIAT plasmid transfection, we observed that MIAT overexpression reversed inhibitory action of Nrf2 expression by high glucose. Moreover, the data of RNA pull-down and RIP showed that MIAT controlled Nrf2 cellular through enhancing Nrf2 stability, which was confirmed by CHX and MG132 administration. Inhibitory effect of cell viability by silencing MIAT was also reversed by Nrf2 overexpression.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Cell Survival', 'Diabetic Nephropathies', 'Dose-Response Relationship, Drug', 'Glucose', 'Kidney Tubules', 'Male', 'RNA, Long Noncoding', 'Rats', 'Rats, Wistar']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,526,814
Do flowers of the early-branching papilionoid legume Petaladenium urceoliferum display unique morphological and ontogenetic features?
{ "contexts": [ "Floral development can help to shed light on puzzling features across flowering plants. The enigmatic Amazonian monospecific genus Petaladenium of the legume family (Leguminosae) had rarely been collected and only recently became available for ontogenetic studies. The fimbriate-glandular wing petals of P. urceoliferum are unique among the more than 19000 legume species. Ontogenetic data illuminate the systematic position of the genus and foster our understanding on floral evolution during the early diversification of the papilionoid legumes.", "Flower buds were collected in the field, fixed in 70% ethanol, and investigated using scanning electron microscopy (SEM). Results were compared with existing material from early-diverging papilionoid legumes.", "Formation of sepals and petals shows bidirectional tendencies. Stamens arise in two whorls, and the single carpel arises concomitantly with the outer stamen whorl. Gland formation starts early on the edges of the wing petals. The carpel reopens for a short time when the initiation of ovules is visible. Stomata at the base of the hypanthium indicate that the flower functions like other standard flag blossoms." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Biological Evolution", "Fabaceae", "Flowers" ] }
The floral ontogeny confirms the close affinity of P. urceoliferum with the florally heterogeneous, early-diverging papilionoid Amburaneae clade. The results strengthen the theory of a distinct experimental phase among early-branching papilionoid legumes during which a wider range of floral morphologies arose. Polysymmetry, monosymmetry, variable organ numbers, and a wide range of ontogenetic patterns laid the foundation for a successful canalization toward the more restricted but well-adapted dorsiventral papilionoid flag blossom.
yes
[ { "from": "human", "value": "Question: Do flowers of the early-branching papilionoid legume Petaladenium urceoliferum display unique morphological and ontogenetic features?\nContext: {'contexts': ['Floral development can help to shed light on puzzling features across flowering plants. The enigmatic Amazonian monospecific genus Petaladenium of the legume family (Leguminosae) had rarely been collected and only recently became available for ontogenetic studies. The fimbriate-glandular wing petals of P. urceoliferum are unique among the more than 19000 legume species. Ontogenetic data illuminate the systematic position of the genus and foster our understanding on floral evolution during the early diversification of the papilionoid legumes.', 'Flower buds were collected in the field, fixed in 70% ethanol, and investigated using scanning electron microscopy (SEM). Results were compared with existing material from early-diverging papilionoid legumes.', 'Formation of sepals and petals shows bidirectional tendencies. Stamens arise in two whorls, and the single carpel arises concomitantly with the outer stamen whorl. Gland formation starts early on the edges of the wing petals. The carpel reopens for a short time when the initiation of ovules is visible. Stomata at the base of the hypanthium indicate that the flower functions like other standard flag blossoms.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Biological Evolution', 'Fabaceae', 'Flowers']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,530,813
Is the arterial tumor enhancement pattern on contrast-enhanced computed tomography associated with primary cancer death after radiofrequency ablation for small hepatocellular carcinoma?
{ "contexts": [ "Critical recurrences after radiofrequency ablation for hepatocellular carcinoma (HCC), such as intrahepatic metastases or dissemination, and extrahepatic metastases or seeding, which are difficult to treat radically, almost certainly lead to primary cancer death. The present study aimed to clarify whether the arterial tumor enhancement pattern on contrast-enhanced computed tomography (CECT) is associated with critical recurrence and cancer death after RFA for small HCC.", "Between April 2001 and September 2011, 226 patients with initial small hypervascular HCC (≤3 cm in diameter and ≤3 tumors) were treated by RFA. Arterial tumor enhancement patterns on CECT before RFA were categorized by whether non-enhanced areas were included inside the tumor stain.", "The heterogeneous enhancement group included 44 patients, and the homogeneous enhancement group included 182 patients. The cumulative 5-year critical recurrence rates of the heterogeneous and homogeneous enhancement groups were 42 and 22% (p = 0.005), respectively. Univariate analysis for factors related to critical recurrence showed significant differences in sex, arterial enhancement pattern, and response to antiviral therapy. These factors were independent on multivariate analysis. The cumulative 5-year primary cancer death rates of the heterogeneous and homogeneous enhancement groups were 29 and 13% (p = 0.002), respectively. Univariate analysis for factors related to primary cancer death showed significant differences in arterial enhancement pattern and response to antiviral therapy. These factors were independent on multivariate analysis." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Aged, 80 and over", "Arteries", "Carcinoma, Hepatocellular", "Catheter Ablation", "Contrast Media", "Female", "Humans", "Liver Neoplasms", "Male", "Middle Aged", "Neoplasm Recurrence, Local", "Tomography, X-Ray Computed", "Treatment Outcome" ] }
Arterial heterogeneous tumor enhancement on CECT is associated with critical recurrence and cancer death after RFA for small HCC.
yes
[ { "from": "human", "value": "Question: Is the arterial tumor enhancement pattern on contrast-enhanced computed tomography associated with primary cancer death after radiofrequency ablation for small hepatocellular carcinoma?\nContext: {'contexts': ['Critical recurrences after radiofrequency ablation for hepatocellular carcinoma (HCC), such as intrahepatic metastases or dissemination, and extrahepatic metastases or seeding, which are difficult to treat radically, almost certainly lead to primary cancer death. The present study aimed to clarify whether the arterial tumor enhancement pattern on contrast-enhanced computed tomography (CECT) is associated with critical recurrence and cancer death after RFA for small HCC.', 'Between April 2001 and September 2011, 226 patients with initial small hypervascular HCC (≤3 cm in diameter and ≤3 tumors) were treated by RFA. Arterial tumor enhancement patterns on CECT before RFA were categorized by whether non-enhanced areas were included inside the tumor stain.', 'The heterogeneous enhancement group included 44 patients, and the homogeneous enhancement group included 182 patients. The cumulative 5-year critical recurrence rates of the heterogeneous and homogeneous enhancement groups were 42 and 22% (p = 0.005), respectively. Univariate analysis for factors related to critical recurrence showed significant differences in sex, arterial enhancement pattern, and response to antiviral therapy. These factors were independent on multivariate analysis. The cumulative 5-year primary cancer death rates of the heterogeneous and homogeneous enhancement groups were 29 and 13% (p = 0.002), respectively. Univariate analysis for factors related to primary cancer death showed significant differences in arterial enhancement pattern and response to antiviral therapy. These factors were independent on multivariate analysis.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Aged, 80 and over', 'Arteries', 'Carcinoma, Hepatocellular', 'Catheter Ablation', 'Contrast Media', 'Female', 'Humans', 'Liver Neoplasms', 'Male', 'Middle Aged', 'Neoplasm Recurrence, Local', 'Tomography, X-Ray Computed', 'Treatment Outcome']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,553,304
Is informed consent instead of assent appropriate in children from the age of twelve : Policy implications of new findings on children 's competence to consent to clinical research?
{ "contexts": [ "For many decades, the debate on children's competence to give informed consent in medical settings concentrated on ethical and legal aspects, with little empirical underpinnings. Recently, data from empirical research became available to advance the discussion. It was shown that children's competence to consent to clinical research could be accurately assessed by the modified MacArthur Competence Assessment Tool for Clinical Research. Age limits for children to be deemed competent to decide on research participation have been studied: generally children of 11.2 years and above were decision-making competent, while children of 9.6 years and younger were not. Age was pointed out to be the key determining factor in children's competence. In this article we reflect on policy implications of these findings, considering legal, ethical, developmental and clinical perspectives." ], "labels": [ "BACKGROUND" ], "meshes": [] }
Although assessment of children's competence has a normative character, ethics, law and clinical practice can benefit from research data. The findings may help to do justice to the capacities children possess and challenges they may face when deciding about treatment and research options. We discuss advantages and drawbacks of standardized competence assessment in children on a case-by-case basis compared to application of a fixed age limit, and conclude that a selective implementation of case-by-case competence assessment in specific populations is preferable. We recommend the implementation of age limits based on empirical evidence. Furthermore, we elaborate on a suitable model for informed consent involving children and parents that would do justice to developmental aspects of children and the specific characteristics of the parent-child dyad. Previous research outcomes showed that children's medical decision-making capacities could be operationalized into a standardized assessment instrument. Recommendations for policies include a dual consent procedure, including both child as well as parents, for children from the age of 12 until they reach majority. For children between 10 and 12 years of age, and in case of children older than 12 years in special research populations of mentally compromised patients, we suggest a case-by-case assessment of children's competence to consent. Since such a dual consent procedure is fundamentally different from a procedure of parental permission and child assent, and would imply a considerable shift regarding some current legislations, practical implications are elaborated.
yes
[ { "from": "human", "value": "Question: Is informed consent instead of assent appropriate in children from the age of twelve : Policy implications of new findings on children 's competence to consent to clinical research?\nContext: {'contexts': [\"For many decades, the debate on children's competence to give informed consent in medical settings concentrated on ethical and legal aspects, with little empirical underpinnings. Recently, data from empirical research became available to advance the discussion. It was shown that children's competence to consent to clinical research could be accurately assessed by the modified MacArthur Competence Assessment Tool for Clinical Research. Age limits for children to be deemed competent to decide on research participation have been studied: generally children of 11.2 years and above were decision-making competent, while children of 9.6 years and younger were not. Age was pointed out to be the key determining factor in children's competence. In this article we reflect on policy implications of these findings, considering legal, ethical, developmental and clinical perspectives.\"], 'labels': ['BACKGROUND'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,530,998
Is vacuum-assisted biopsy a viable alternative to surgical biopsy in the investigation of breast lesions of uncertain malignant potential?
{ "contexts": [ "In patients presenting with a breast lesion, when initial core biopsy histology falls into the category of \"uncertain malignant potential\" (i.e. a B3 lesion), the next line of investigation has traditionally been a surgical biopsy (SBx). Vacuum-assisted biopsy (VAB) may be a viable minimally invasive alternative to SBx for B3 lesions. The primary aims of this study were to establish whether VAB reduces the need for surgical biopsy and determine VAB sensitivity for carcinoma following initial B3 histology.", "B3 lesion data was collected from 2004 to 2013 retrospectively, from a single institution that utilises both VAB and SBx.", "A total of 413 lesions were categorised B3 on initial biopsy. Mean age was 61 years (range: 24-91 years). Mean follow up was 52 months (range: 19-60 months). 156 patients (38%) underwent VAB. Only 20% of patients underwent VAB in 2004, with an increase to 95% by 2013. VAB histology revealed twelve carcinomas, all of which progressed to surgical excision. In six cases, a SBx was required following VAB in order to provide further diagnostic information. In one case, carcinoma was missed on VAB." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Biopsy, Needle", "Breast Neoplasms", "Carcinoma", "Female", "Humans", "Middle Aged", "Predictive Value of Tests", "Retrospective Studies", "Vacuum", "Young Adult" ] }
The increase in VAB use over time suggests that the procedure is well tolerated. The results demonstrate a VAB sensitivity of 92% for carcinoma diagnosis. In 96% of cases (150 of 156), VAB results were conclusive enough to avoid a subsequent SBx. This data suggests that VAB may be a preferable alternative to surgical biopsy for many B3 lesions.
yes
[ { "from": "human", "value": "Question: Is vacuum-assisted biopsy a viable alternative to surgical biopsy in the investigation of breast lesions of uncertain malignant potential?\nContext: {'contexts': ['In patients presenting with a breast lesion, when initial core biopsy histology falls into the category of \"uncertain malignant potential\" (i.e. a B3 lesion), the next line of investigation has traditionally been a surgical biopsy (SBx). Vacuum-assisted biopsy (VAB) may be a viable minimally invasive alternative to SBx for B3 lesions. The primary aims of this study were to establish whether VAB reduces the need for surgical biopsy and determine VAB sensitivity for carcinoma following initial B3 histology.', 'B3 lesion data was collected from 2004 to 2013 retrospectively, from a single institution that utilises both VAB and SBx.', 'A total of 413 lesions were categorised B3 on initial biopsy. Mean age was 61 years (range: 24-91 years). Mean follow up was 52 months (range: 19-60 months). 156 patients (38%) underwent VAB. Only 20% of patients underwent VAB in 2004, with an increase to 95% by 2013. VAB histology revealed twelve carcinomas, all of which progressed to surgical excision. In six cases, a SBx was required following VAB in order to provide further diagnostic information. In one case, carcinoma was missed on VAB.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Biopsy, Needle', 'Breast Neoplasms', 'Carcinoma', 'Female', 'Humans', 'Middle Aged', 'Predictive Value of Tests', 'Retrospective Studies', 'Vacuum', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,531,071
Is anticholinergic burden associated with recurrent and injurious falls in older individuals?
{ "contexts": [ "While the anticholinergic activity of medications has been linked to cognitive decline, few studies have linked anticholinergic burden with falls in older people. We evaluated the relationship between anticholinergic burden and recurrent and injurious falls among community-dwelling older adults.", "This case-control study was performed on 428 participants aged ≥65 years, 263 cases with two or more falls or one injurious fall in the preceding 12 months, and 165 controls with no falls in the preceding 12 months. Anticholinergic burden was determined using the anticholinergic cognitive burden (ACB) scale. Upper and lower limb functional abilities were assessed with timed up and go (TUG), functional reach (FR) and grip strength (GS). Logistic regression analysis was employed to calculate the mediation effect of TUG, FR and GS on ACB associated falls.", "Univariate analysis revealed a significant association between an ACB score of ≥1 with falls (OR, 1.8; 95% CI; 1.1-3.0; p=0.01) and significantly poorer TUG and FR. The association between ACB≥1 and falls was no longer significant after adjustment for either TUG (OR for ACB associated falls, 1.4; 95% CI, 0.88-2.4; p=0.14) or FR (OR for ACB associated falls, 1.4; 95% CI, 0.89-2.4, p=0.12) but remained significant with GS." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Accidental Falls", "Aged", "Aged, 80 and over", "Case-Control Studies", "Cholinergic Antagonists", "Exercise Test", "Female", "Gait", "Hand Strength", "Humans", "Male", "Postural Balance", "Recurrence", "Wounds and Injuries" ] }
The association between recurrent and injurious falls and the use of any medications listed in the ACB scale was mediated through gait and balance impairment but not by muscular weakness, providing a novel insight into the potential mechanistic link between ACB and falls. Future studies should determine whether TUG and FR measurements could help inform risk to benefit decisions where ACB medications are being considered.
yes
[ { "from": "human", "value": "Question: Is anticholinergic burden associated with recurrent and injurious falls in older individuals?\nContext: {'contexts': ['While the anticholinergic activity of medications has been linked to cognitive decline, few studies have linked anticholinergic burden with falls in older people. We evaluated the relationship between anticholinergic burden and recurrent and injurious falls among community-dwelling older adults.', 'This case-control study was performed on 428 participants aged ≥65 years, 263 cases with two or more falls or one injurious fall in the preceding 12 months, and 165 controls with no falls in the preceding 12 months. Anticholinergic burden was determined using the anticholinergic cognitive burden (ACB) scale. Upper and lower limb functional abilities were assessed with timed up and go (TUG), functional reach (FR) and grip strength (GS). Logistic regression analysis was employed to calculate the mediation effect of TUG, FR and GS on ACB associated falls.', 'Univariate analysis revealed a significant association between an ACB score of ≥1 with falls (OR, 1.8; 95% CI; 1.1-3.0; p=0.01) and significantly poorer TUG and FR. The association between ACB≥1 and falls was no longer significant after adjustment for either TUG (OR for ACB associated falls, 1.4; 95% CI, 0.88-2.4; p=0.14) or FR (OR for ACB associated falls, 1.4; 95% CI, 0.89-2.4, p=0.12) but remained significant with GS.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Accidental Falls', 'Aged', 'Aged, 80 and over', 'Case-Control Studies', 'Cholinergic Antagonists', 'Exercise Test', 'Female', 'Gait', 'Hand Strength', 'Humans', 'Male', 'Postural Balance', 'Recurrence', 'Wounds and Injuries']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,530,761
Does a Radiation-Induced Hippocampal Vascular Injury Surrogate Marker predict Late Neurocognitive Dysfunction?
{ "contexts": [ "We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT).", "Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K(trans), and the fraction of blood plasma volume, Vp. The temporal changes in the means of hippocampal transfer constant K(trans) and Vp after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT.", "The mean K(trans) Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=-0.95, P<.0006) and 18-months (r=-0.88, P<.02) post-RT." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Age Factors", "Aged", "Aged, 80 and over", "Blood-Brain Barrier", "Brain Neoplasms", "Cognition Disorders", "Cranial Irradiation", "Dose-Response Relationship, Radiation", "Female", "Glioma", "Hippocampus", "Humans", "Male", "Memory Disorders", "Middle Aged", "Pituitary Neoplasms", "Prospective Studies", "Radiation Dosage", "Radiation Injuries", "Radiotherapy, Conformal", "Radiotherapy, Intensity-Modulated", "Regression Analysis", "Sex Factors", "Time Factors", "Vascular System Injuries" ] }
The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.
yes
[ { "from": "human", "value": "Question: Does a Radiation-Induced Hippocampal Vascular Injury Surrogate Marker predict Late Neurocognitive Dysfunction?\nContext: {'contexts': ['We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT).', 'Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K(trans), and the fraction of blood plasma volume, Vp. The temporal changes in the means of hippocampal transfer constant K(trans) and Vp after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT.', 'The mean K(trans) Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=-0.95, P<.0006) and 18-months (r=-0.88, P<.02) post-RT.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Age Factors', 'Aged', 'Aged, 80 and over', 'Blood-Brain Barrier', 'Brain Neoplasms', 'Cognition Disorders', 'Cranial Irradiation', 'Dose-Response Relationship, Radiation', 'Female', 'Glioma', 'Hippocampus', 'Humans', 'Male', 'Memory Disorders', 'Middle Aged', 'Pituitary Neoplasms', 'Prospective Studies', 'Radiation Dosage', 'Radiation Injuries', 'Radiotherapy, Conformal', 'Radiotherapy, Intensity-Modulated', 'Regression Analysis', 'Sex Factors', 'Time Factors', 'Vascular System Injuries']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,537,234
Does prolonged use of human insulin increase breast cancer risk in Taiwanese women with type 2 diabetes?
{ "contexts": [ "Human insulin is commonly used to treat hyperglycemia in patients with diabetes, but its potential link with female breast cancer is under debate. This study investigated whether human insulin use might be associated with breast cancer risk in Taiwanese women with type 2 diabetes.", "The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 482,033 women with type 2 diabetes were followed up for breast cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, cumulative dose and cumulative duration of insulin) were calculated and the adjusted hazard ratios were estimated by Cox regression. The potential risk modification by concomitant treatment with metformin, statin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) was also evaluated.", "There were 59,798 ever-users and 422,235 never-users of human insulin, with respective numbers of incident breast cancer of 559 (0.93 %) and 4,711 (1.12 %), and respective incidence of 207.9 and 215.1 per 100,000 person-years. The overall adjusted hazard ratio (95 % confidence interval) did not show a significant association with insulin [1.033 (0.936-1.139)]. However, patients in the third tertiles of dose-response parameters might show a significantly higher risk of breast cancer while compared to never-users: 1.185 (1.026-1.368), 1.260 (1.096-1.450) and 1.257 (1.094-1.446) for ≥67 months for time since starting insulin, ≥39,000 units for cumulative dose of insulin, and ≥21.8 months for cumulative duration of insulin, respectively. Additional analyses suggested that the breast cancer risk associated with human insulin use might be beneficially modified by concomitant use of metformin, statin and ACEI/ARB." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Breast Neoplasms", "Diabetes Mellitus, Type 2", "Drug Administration Schedule", "Female", "Humans", "Hypoglycemic Agents", "Incidence", "Isophane Insulin, Human", "Middle Aged", "Retrospective Studies", "Risk Assessment", "Risk Factors", "Taiwan" ] }
This study discloses a significantly higher risk of breast cancer associated with prolonged use of human insulin. The increased risk of breast cancer associated with human insulin use may be modified by medications such as metformin, statin and ACEI/ARB.
yes
[ { "from": "human", "value": "Question: Does prolonged use of human insulin increase breast cancer risk in Taiwanese women with type 2 diabetes?\nContext: {'contexts': ['Human insulin is commonly used to treat hyperglycemia in patients with diabetes, but its potential link with female breast cancer is under debate. This study investigated whether human insulin use might be associated with breast cancer risk in Taiwanese women with type 2 diabetes.', 'The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 482,033 women with type 2 diabetes were followed up for breast cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, cumulative dose and cumulative duration of insulin) were calculated and the adjusted hazard ratios were estimated by Cox regression. The potential risk modification by concomitant treatment with metformin, statin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) was also evaluated.', 'There were 59,798 ever-users and 422,235 never-users of human insulin, with respective numbers of incident breast cancer of 559 (0.93 %) and 4,711 (1.12 %), and respective incidence of 207.9 and 215.1 per 100,000 person-years. The overall adjusted hazard ratio (95 % confidence interval) did not show a significant association with insulin [1.033 (0.936-1.139)]. However, patients in the third tertiles of dose-response parameters might show a significantly higher risk of breast cancer while compared to never-users: 1.185 (1.026-1.368), 1.260 (1.096-1.450) and 1.257 (1.094-1.446) for ≥67 months for time since starting insulin, ≥39,000 units for cumulative dose of insulin, and ≥21.8 months for cumulative duration of insulin, respectively. Additional analyses suggested that the breast cancer risk associated with human insulin use might be beneficially modified by concomitant use of metformin, statin and ACEI/ARB.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Breast Neoplasms', 'Diabetes Mellitus, Type 2', 'Drug Administration Schedule', 'Female', 'Humans', 'Hypoglycemic Agents', 'Incidence', 'Isophane Insulin, Human', 'Middle Aged', 'Retrospective Studies', 'Risk Assessment', 'Risk Factors', 'Taiwan']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,546,482
Do patients with ClearCode34-identified molecular subtypes of clear cell renal cell carcinoma represent unique populations with distinct comorbidities?
{ "contexts": [ "The 34-gene classifier, ClearCode34, identifies prognostically distinct molecular subtypes of clear cell renal cell carcinoma (ccRCC) termed clear cell A (ccA) and clear cell B (ccB). The primary objective of this study was to describe clinical characteristics and comorbidities of relevance in patients stratified by ClearCode34.", "In this retrospective analysis, 282 patients from Moffitt Cancer Center with ccRCC with gene expression analyses of the primary tumor were identified and ClearCode34 was applied to identify tumors as ccA or ccB. The medical record and institutional databases were queried to define patient characteristics, comorbidities, and outcomes.", "We validated in this external cohort the superior overall survival, cancer-specific survival, and recurrence-free survival of ccA patients relative to ccB patients (P<0.001). Addressing other clinical characteristics, the ccA patients were more likely to be obese (48% vs. 34%, P = 0.021) and diabetic (26% vs. 13%, P = 0.035). The ccA patients also trended toward having been more frequent users of angiotensin system inhibitors (71% vs. 52%, P = 0.055). In multivariate analyses, ccB status is independently associated with inferior cancer-specific survival (hazard ratio = 3.26, 95% confidence interval: 1.84-5.79) and overall survival (hazard ratio = 2.50, 95% confidence interval: 1.53-4.08)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Biomarkers, Tumor", "Carcinoma, Renal Cell", "Comorbidity", "Female", "Follow-Up Studies", "Humans", "Kidney Neoplasms", "Male", "Middle Aged", "Multivariate Analysis", "Neoplasm Metastasis", "Neoplasm Recurrence, Local", "Neoplasm Staging", "Prognosis", "Retrospective Studies", "Survival Rate", "Transcriptome" ] }
ClearCode34, after considering distinct patterns of comorbidities in each molecular subtype, remains a strong prognostic tool in patients with ccRCC. Obesity and diabetes mellitus emerged as factors that may influence ccRCC phenotypes and further studies investigating the effect of these metabolic conditions functionally onto tumor biology are warranted. Additionally, use of angiotensin system inhibitors could be studied in the context of ccRCC molecular classification in future studies to better understand its effect on ccRCC outcomes.
yes
[ { "from": "human", "value": "Question: Do patients with ClearCode34-identified molecular subtypes of clear cell renal cell carcinoma represent unique populations with distinct comorbidities?\nContext: {'contexts': ['The 34-gene classifier, ClearCode34, identifies prognostically distinct molecular subtypes of clear cell renal cell carcinoma (ccRCC) termed clear cell A (ccA) and clear cell B (ccB). The primary objective of this study was to describe clinical characteristics and comorbidities of relevance in patients stratified by ClearCode34.', 'In this retrospective analysis, 282 patients from Moffitt Cancer Center with ccRCC with gene expression analyses of the primary tumor were identified and ClearCode34 was applied to identify tumors as ccA or ccB. The medical record and institutional databases were queried to define patient characteristics, comorbidities, and outcomes.', 'We validated in this external cohort the superior overall survival, cancer-specific survival, and recurrence-free survival of ccA patients relative to ccB patients (P<0.001). Addressing other clinical characteristics, the ccA patients were more likely to be obese (48% vs. 34%, P = 0.021) and diabetic (26% vs. 13%, P = 0.035). The ccA patients also trended toward having been more frequent users of angiotensin system inhibitors (71% vs. 52%, P = 0.055). In multivariate analyses, ccB status is independently associated with inferior cancer-specific survival (hazard ratio = 3.26, 95% confidence interval: 1.84-5.79) and overall survival (hazard ratio = 2.50, 95% confidence interval: 1.53-4.08).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Biomarkers, Tumor', 'Carcinoma, Renal Cell', 'Comorbidity', 'Female', 'Follow-Up Studies', 'Humans', 'Kidney Neoplasms', 'Male', 'Middle Aged', 'Multivariate Analysis', 'Neoplasm Metastasis', 'Neoplasm Recurrence, Local', 'Neoplasm Staging', 'Prognosis', 'Retrospective Studies', 'Survival Rate', 'Transcriptome']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,547,353
Is [ Nucleolin expression correlated with carcinogenesis and progression of cervical squamous cell carcinoma ]?
{ "contexts": [ "To investigate the differential expressions of nucleolin in invasive cervical squamous cell carcinoma, cervical intraepithelial neoplasms (CIN) and normal cervical epithelial tissues and explore the role of nucleolin in the carcinogenesis and progression of cervical squamous cell carcinoma.", "Fifty specimens of invasive cervical squamous cell carcinoma, 65 specimens of CIN, and 60 adjacent normal cervical epithelial tissue specimens were examined immunohistochemically for nucleolin expression. The correlation of nucleolin expression levels with histological grades of invasive cervical squamous cell carcinoma and CIN were analyzed.", "The specimens of invasive cervical squamous cell carcinoma showed a significantly higher positivity rate for nucleolin expression than CIN and normal cervical epithelial tissues, and the rate in CIN tissues was significantly higher than that in normal cervical epithelial tissues (P<0.01). The expression level of nucleolin was significantly higher in invasive cervical squamous cell carcinoma than in CIN and normal cervical epithelia tissues, and higher in CIN than in normal cervical epithelia tissues, whose immunostaining scores were 7.6±0.3, 6.1±0.2, and 3.0±0.2, respectively (P<0.01). The mean nucleolin immunostaining score was significantly higher in poorly and moderately differentiated than in highly differentiated cervical squamous cell carcinoma (7.9 vs 7.1, P<0.01), and higher in high grade CIN than in low grade CIN tissues (6.0 vs 4.0, P<0.01)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Carcinogenesis", "Carcinoma in Situ", "Carcinoma, Squamous Cell", "Cervical Intraepithelial Neoplasia", "Disease Progression", "Female", "Humans", "Phosphoproteins", "RNA-Binding Proteins", "Uterine Cervical Neoplasms" ] }
Overexpression of nucleolin plays an important role during carcinogenesis of cervical squamous cell carcinoma and is positively correlated with tumor progression of CIN and cervical squamous cell carcinoma.
yes
[ { "from": "human", "value": "Question: Is [ Nucleolin expression correlated with carcinogenesis and progression of cervical squamous cell carcinoma ]?\nContext: {'contexts': ['To investigate the differential expressions of nucleolin in invasive cervical squamous cell carcinoma, cervical intraepithelial neoplasms (CIN) and normal cervical epithelial tissues and explore the role of nucleolin in the carcinogenesis and progression of cervical squamous cell carcinoma.', 'Fifty specimens of invasive cervical squamous cell carcinoma, 65 specimens of CIN, and 60 adjacent normal cervical epithelial tissue specimens were examined immunohistochemically for nucleolin expression. The correlation of nucleolin expression levels with histological grades of invasive cervical squamous cell carcinoma and CIN were analyzed.', 'The specimens of invasive cervical squamous cell carcinoma showed a significantly higher positivity rate for nucleolin expression than CIN and normal cervical epithelial tissues, and the rate in CIN tissues was significantly higher than that in normal cervical epithelial tissues (P<0.01). The expression level of nucleolin was significantly higher in invasive cervical squamous cell carcinoma than in CIN and normal cervical epithelia tissues, and higher in CIN than in normal cervical epithelia tissues, whose immunostaining scores were 7.6±0.3, 6.1±0.2, and 3.0±0.2, respectively (P<0.01). The mean nucleolin immunostaining score was significantly higher in poorly and moderately differentiated than in highly differentiated cervical squamous cell carcinoma (7.9 vs 7.1, P<0.01), and higher in high grade CIN than in low grade CIN tissues (6.0 vs 4.0, P<0.01).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Carcinogenesis', 'Carcinoma in Situ', 'Carcinoma, Squamous Cell', 'Cervical Intraepithelial Neoplasia', 'Disease Progression', 'Female', 'Humans', 'Phosphoproteins', 'RNA-Binding Proteins', 'Uterine Cervical Neoplasms']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,547,355
Do impaired post-tetanic potentiation of muscle twitch in myasthenia gravis?
{ "contexts": [ "The aim of this study was to evaluate post-tetanic potentiation of muscle twitch in myasthenia gravis (MG).", "Post-tetanic potentiation was evaluated by recording the compound muscle action potential (CMAP) of abductor pollicis brevis and movement-related potential (MRP) of the thumb using an accelerometer after tetanic stimulation of the median nerve at the wrist. After baseline recording, tetanic stimulation was delivered to the median nerve at a frequency of 10 Hz for 10s. The CMAP and MRP were successively recorded at baseline and at 5, 10, 30, 60, 90 and 120 s after tetanic stimulation. The chronological changes of CMAPs and MRPs were recorded bilaterally in 11 patients with MG, 9 patients with myopathies (disease controls), and 25 healthy control subjects.", "Maximal acceleration of MRP was significantly elevated during 10s after tetanic stimulation without any CMAP changes in all groups. However, statistical analysis detected a significant decrease in post-tetanic potentiation of maximal acceleration of MRP in MG patients only compared to healthy controls, but not in myopathy patients, which may imply impairment of excitation-contraction coupling in MG." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Accelerometry", "Action Potentials", "Adult", "Aged", "Excitation Contraction Coupling", "Female", "Hand Strength", "Humans", "Male", "Middle Aged", "Muscle Contraction", "Muscle, Skeletal", "Myasthenia Gravis", "Refractory Period, Electrophysiological", "Young Adult" ] }
Post-tetanic potentiation of muscle twitch is significantly diminished in MG, suggesting impaired excitation-contraction coupling.
yes
[ { "from": "human", "value": "Question: Do impaired post-tetanic potentiation of muscle twitch in myasthenia gravis?\nContext: {'contexts': ['The aim of this study was to evaluate post-tetanic potentiation of muscle twitch in myasthenia gravis (MG).', 'Post-tetanic potentiation was evaluated by recording the compound muscle action potential (CMAP) of abductor pollicis brevis and movement-related potential (MRP) of the thumb using an accelerometer after tetanic stimulation of the median nerve at the wrist. After baseline recording, tetanic stimulation was delivered to the median nerve at a frequency of 10 Hz for 10s. The CMAP and MRP were successively recorded at baseline and at 5, 10, 30, 60, 90 and 120 s after tetanic stimulation. The chronological changes of CMAPs and MRPs were recorded bilaterally in 11 patients with MG, 9 patients with myopathies (disease controls), and 25 healthy control subjects.', 'Maximal acceleration of MRP was significantly elevated during 10s after tetanic stimulation without any CMAP changes in all groups. However, statistical analysis detected a significant decrease in post-tetanic potentiation of maximal acceleration of MRP in MG patients only compared to healthy controls, but not in myopathy patients, which may imply impairment of excitation-contraction coupling in MG.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Accelerometry', 'Action Potentials', 'Adult', 'Aged', 'Excitation Contraction Coupling', 'Female', 'Hand Strength', 'Humans', 'Male', 'Middle Aged', 'Muscle Contraction', 'Muscle, Skeletal', 'Myasthenia Gravis', 'Refractory Period, Electrophysiological', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,554,390
Does a novel acetylcholinesterase inhibitor and calcium channel blocker SCR-1693 improve Aβ25-35-impaired mouse cognitive function?
{ "contexts": [ "The mechanism involved in AD is complex, which has prompted to develop compounds that could simultaneously interact with several potential targets. Here, we report a new synthesized compound SCR-1693 which is designed to target both AChE and calcium channels that are potential for AD therapy.", "We investigated the effects of SCR-1693 on AChE and calcium channels, the effects of neuroprotection and anti-amnesia in icv-Aβ25-35-injected mice, and the potential mechanisms.", "AChE activity assay, intracellular Ca(2+) content and calcium currents measurement, and Aβ25-35-induced cellular death determine were performed for validation of designed targets and neuroprotection of SCR-1693. Mice were orally administrated with SCR-1693 once daily after an Aβ25-35 injection. The Morris water maze and Y-maze test, and hippocampal protein detection were conducted on days 5-10, day 11, and day 8. The pyramidal neuron number, hippocampal AChE activity, and synaptic transmission were measured on day 12.", "SCR-1693 acted as a selective, reversible, and noncompetitive inhibitor of AChE, and a nonselective voltage-gated calcium channel blocker. SCR-1693 also inhibited the increase of AChE activity in the mouse hippocampus. SCR-1693 was more effective than donepezil and memantine in preventing Aβ25-35-induced long-term and short-term memory impairment, maintaining the basal transmission of Schaffer collateral-CA1 synapses, and sustaining LTP in mouse hippocampus. SCR-1693 attenuated Aβ25-35-induced death of SH-SY5Y cell and the loss of hippocampal pyramidal neurons, and regulated Aβ25-35-induced signal cascade in neurons." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Amyloid beta-Peptides", "Animals", "CHO Cells", "Calcium Channel Blockers", "Cell Line, Tumor", "Cholinesterase Inhibitors", "Cognition", "Cognition Disorders", "Cricetinae", "Cricetulus", "Dose-Response Relationship, Drug", "HEK293 Cells", "Humans", "Male", "Maze Learning", "Mice", "Mice, Inbred ICR", "Peptide Fragments", "Rats", "Rats, Wistar", "Tacrine" ] }
All these findings indicated that SCR-1693, as a double-target-direction agent, is a considerable candidate for AD therapy.
yes
[ { "from": "human", "value": "Question: Does a novel acetylcholinesterase inhibitor and calcium channel blocker SCR-1693 improve Aβ25-35-impaired mouse cognitive function?\nContext: {'contexts': ['The mechanism involved in AD is complex, which has prompted to develop compounds that could simultaneously interact with several potential targets. Here, we report a new synthesized compound SCR-1693 which is designed to target both AChE and calcium channels that are potential for AD therapy.', 'We investigated the effects of SCR-1693 on AChE and calcium channels, the effects of neuroprotection and anti-amnesia in icv-Aβ25-35-injected mice, and the potential mechanisms.', 'AChE activity assay, intracellular Ca(2+) content and calcium currents measurement, and Aβ25-35-induced cellular death determine were performed for validation of designed targets and neuroprotection of SCR-1693. Mice were orally administrated with SCR-1693 once daily after an Aβ25-35 injection. The Morris water maze and Y-maze test, and hippocampal protein detection were conducted on days 5-10, day 11, and day 8. The pyramidal neuron number, hippocampal AChE activity, and synaptic transmission were measured on day 12.', 'SCR-1693 acted as a selective, reversible, and noncompetitive inhibitor of AChE, and a nonselective voltage-gated calcium channel blocker. SCR-1693 also inhibited the increase of AChE activity in the mouse hippocampus. SCR-1693 was more effective than donepezil and memantine in preventing Aβ25-35-induced long-term and short-term memory impairment, maintaining the basal transmission of Schaffer collateral-CA1 synapses, and sustaining LTP in mouse hippocampus. SCR-1693 attenuated Aβ25-35-induced death of SH-SY5Y cell and the loss of hippocampal pyramidal neurons, and regulated Aβ25-35-induced signal cascade in neurons.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Amyloid beta-Peptides', 'Animals', 'CHO Cells', 'Calcium Channel Blockers', 'Cell Line, Tumor', 'Cholinesterase Inhibitors', 'Cognition', 'Cognition Disorders', 'Cricetinae', 'Cricetulus', 'Dose-Response Relationship, Drug', 'HEK293 Cells', 'Humans', 'Male', 'Maze Learning', 'Mice', 'Mice, Inbred ICR', 'Peptide Fragments', 'Rats', 'Rats, Wistar', 'Tacrine']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,528,707
Is rANK/OPG ratio of expression in primary clear-cell renal cell carcinoma associated with bone metastasis and prognosis in patients treated with anti-VEGFR-TKIs?
{ "contexts": [ "Bone metastases (BMs) are associated with poor outcome in metastatic clear-cell renal carcinoma (m-ccRCC) treated with anti-vascular endothelial growth factor tyrosine kinase inhibitors (anti-VEGFR-TKIs). We aimed to investigate whether expression in the primary tumour of genes involved in the development of BM is associated with outcome in m-ccRCC patients treated with anti-VEGFR-TKIs.", "Metastatic clear-cell renal cell carcinoma patients with available fresh-frozen tumour and treated with anti-VEGFR-TKIs. Quantitative real-time PCR (qRT-PCR) for receptor activator of NF-kB (RANK), RANK-ligand (RANKL), osteoprotegerin (OPG), the proto-oncogene SRC and DKK1 (Dickkopf WNT signalling pathway inhibitor-1). Time-to-event analysis by Kaplan-Meier estimates and Cox regression.", "We included 129 m-ccRCC patients treated between 2005 and 2013. An elevated RANK/OPG ratio was associated with shorter median time to metastasis (HR 0.50 (95% CI 0.29-0.87); P=0.014), shorter time to BM (HR 0.54 (95% CI 0.31-0.97); P=0.037), shorter median overall survival (mOS) since initial diagnosis (HR 2.27 (95% CI 1.44-3.60); P=0.0001), shorter median progression-free survival (HR 0.44 (95% CI 0.28-0.71); P=0.001) and mOS (HR 0.31 (95% CI 0.19-0.52); P<0.0001) on first-line anti-VEGFR-TKIs in the metastatic setting. Higher RANK expression was associated with shorter mOS on first-line anti-VEGFR-TKIs (HR 0.46 (95% CI 0.29-0.73); P=0.001)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Bone Neoplasms", "Carcinoma, Renal Cell", "Disease-Free Survival", "Female", "Genes, src", "Humans", "Intercellular Signaling Peptides and Proteins", "Kidney Neoplasms", "Male", "Middle Aged", "Osteoprotegerin", "Prognosis", "Protein Kinase Inhibitors", "Protein-Tyrosine Kinases", "RANK Ligand", "Receptor Activator of Nuclear Factor-kappa B", "Receptors, Vascular Endothelial Growth Factor", "Signal Transduction" ] }
RANK/OPG ratio of expression in primary ccRCC is associated with BM and prognosis in patients treated with anti-VEGFR-TKIs. Prospective validation is warranted.
yes
[ { "from": "human", "value": "Question: Is rANK/OPG ratio of expression in primary clear-cell renal cell carcinoma associated with bone metastasis and prognosis in patients treated with anti-VEGFR-TKIs?\nContext: {'contexts': ['Bone metastases (BMs) are associated with poor outcome in metastatic clear-cell renal carcinoma (m-ccRCC) treated with anti-vascular endothelial growth factor tyrosine kinase inhibitors (anti-VEGFR-TKIs). We aimed to investigate whether expression in the primary tumour of genes involved in the development of BM is associated with outcome in m-ccRCC patients treated with anti-VEGFR-TKIs.', 'Metastatic clear-cell renal cell carcinoma patients with available fresh-frozen tumour and treated with anti-VEGFR-TKIs. Quantitative real-time PCR (qRT-PCR) for receptor activator of NF-kB (RANK), RANK-ligand (RANKL), osteoprotegerin (OPG), the proto-oncogene SRC and DKK1 (Dickkopf WNT signalling pathway inhibitor-1). Time-to-event analysis by Kaplan-Meier estimates and Cox regression.', 'We included 129 m-ccRCC patients treated between 2005 and 2013. An elevated RANK/OPG ratio was associated with shorter median time to metastasis (HR 0.50 (95% CI 0.29-0.87); P=0.014), shorter time to BM (HR 0.54 (95% CI 0.31-0.97); P=0.037), shorter median overall survival (mOS) since initial diagnosis (HR 2.27 (95% CI 1.44-3.60); P=0.0001), shorter median progression-free survival (HR 0.44 (95% CI 0.28-0.71); P=0.001) and mOS (HR 0.31 (95% CI 0.19-0.52); P<0.0001) on first-line anti-VEGFR-TKIs in the metastatic setting. Higher RANK expression was associated with shorter mOS on first-line anti-VEGFR-TKIs (HR 0.46 (95% CI 0.29-0.73); P=0.001).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Bone Neoplasms', 'Carcinoma, Renal Cell', 'Disease-Free Survival', 'Female', 'Genes, src', 'Humans', 'Intercellular Signaling Peptides and Proteins', 'Kidney Neoplasms', 'Male', 'Middle Aged', 'Osteoprotegerin', 'Prognosis', 'Protein Kinase Inhibitors', 'Protein-Tyrosine Kinases', 'RANK Ligand', 'Receptor Activator of Nuclear Factor-kappa B', 'Receptors, Vascular Endothelial Growth Factor', 'Signal Transduction']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,526,356
Does a Her2-let-7-β2-AR circuit affect prognosis in patients with Her2-positive breast cancer?
{ "contexts": [ "Our previous studies show that β2-adrenergic receptor (β2-AR) is highly expressed in most Her2-overexpressing breast cancers. However, the mechanisms underlying upregulation of the β2-AR expression in Her2-overexpressing breast cancer cells are not fully understood. The clinical significance of the β2-AR overexpression in breast cancer is unclear.", "Human breast cancer cells MCF-7 and MCF-7/Her2 were transfected with the let-7 mimics or inhibitors. The expression of β2-AR was analyzed by Western blot. The β2-AR status in primary and metastatic sites of breast cancer and the human breast cancer tissue microarrays containing 49 primary tumors and 50 metastatic lymph node tissues was analyzed by immunohistochemistry. The correlation of lymph node metastasis with the β2-AR level was determined in 59 primary tumor tissues from the patients with Her2-positive breast cancer. The clinical prognostic significance of the β2-AR overexpression in the patients with Her2-positive breast cancers was evaluated by a retrospective study.", "The let-7f level in Her2-overexpressing breast cancer cells SKBR3 and BT474 was significantly lower than that in MCF-7 cells, which express low level of Her2. Ectopic expression of Her2 in MCF-7 cells (MCF-7/Her2) represses the expression of microRNA let-7f, which is previously identified to regulate baseline β2-AR expression. The treatment with MEK1/2 inhibitors PD98059 or PD184352 effectively restored the let-7f level, suggesting that Her2-overexpression-mediated ERK constitutive activation inhibited let-7f, leading to the upregulation of the β2-AR expression. The transfection with the let-7f mimics markedly downregulated the β2-AR level, whereas the let-7 inhibitor significantly upregulated the β2-AR expression in both parental MCF-7 and MCF-7/Her2 cells. In addition, treatment of MCF-7/Her2 cells with isoproterenol resulted in a concentration-dependent reduction of the let-7f expression, demonstrating that the inhibitory effect of Her2 overexpression on let-7f can be reinforced by agonist-triggered β2-AR activation. We further demonstrate that high level of β2-AR associates with lymph node metastasis and poor outcome in the patients with Her2-positive breast cancer." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Breast Neoplasms", "Female", "Gene Expression Regulation, Neoplastic", "Humans", "MCF-7 Cells", "MicroRNAs", "Prognosis", "Receptor, ErbB-2", "Receptors, Adrenergic, beta-2", "Signal Transduction" ] }
The mutual and reciprocal interaction between Her2, β2-AR, and let-7f may maintain a high level of β2-AR in breast cancer cells. Our data suggest that β2-AR may be a new useful biomarker for predicting prognosis in Her2-positive breast cancer and may also be a promising selective therapeutic target for the aggressive subtype of breast cancer.
yes
[ { "from": "human", "value": "Question: Does a Her2-let-7-β2-AR circuit affect prognosis in patients with Her2-positive breast cancer?\nContext: {'contexts': ['Our previous studies show that β2-adrenergic receptor (β2-AR) is highly expressed in most Her2-overexpressing breast cancers. However, the mechanisms underlying upregulation of the β2-AR expression in Her2-overexpressing breast cancer cells are not fully understood. The clinical significance of the β2-AR overexpression in breast cancer is unclear.', 'Human breast cancer cells MCF-7 and MCF-7/Her2 were transfected with the let-7 mimics or inhibitors. The expression of β2-AR was analyzed by Western blot. The β2-AR status in primary and metastatic sites of breast cancer and the human breast cancer tissue microarrays containing 49 primary tumors and 50 metastatic lymph node tissues was analyzed by immunohistochemistry. The correlation of lymph node metastasis with the β2-AR level was determined in 59 primary tumor tissues from the patients with Her2-positive breast cancer. The clinical prognostic significance of the β2-AR overexpression in the patients with Her2-positive breast cancers was evaluated by a retrospective study.', 'The let-7f level in Her2-overexpressing breast cancer cells SKBR3 and BT474 was significantly lower than that in MCF-7 cells, which express low level of Her2. Ectopic expression of Her2 in MCF-7 cells (MCF-7/Her2) represses the expression of microRNA let-7f, which is previously identified to regulate baseline β2-AR expression. The treatment with MEK1/2 inhibitors PD98059 or PD184352 effectively restored the let-7f level, suggesting that Her2-overexpression-mediated ERK constitutive activation inhibited let-7f, leading to the upregulation of the β2-AR expression. The transfection with the let-7f mimics markedly downregulated the β2-AR level, whereas the let-7 inhibitor significantly upregulated the β2-AR expression in both parental MCF-7 and MCF-7/Her2 cells. In addition, treatment of MCF-7/Her2 cells with isoproterenol resulted in a concentration-dependent reduction of the let-7f expression, demonstrating that the inhibitory effect of Her2 overexpression on let-7f can be reinforced by agonist-triggered β2-AR activation. We further demonstrate that high level of β2-AR associates with lymph node metastasis and poor outcome in the patients with Her2-positive breast cancer.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Breast Neoplasms', 'Female', 'Gene Expression Regulation, Neoplastic', 'Humans', 'MCF-7 Cells', 'MicroRNAs', 'Prognosis', 'Receptor, ErbB-2', 'Receptors, Adrenergic, beta-2', 'Signal Transduction']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,544,895
Does mutant GDF15 present a poor prognostic outcome for patients with oral squamous cell carcinoma?
{ "contexts": [ "To investigate the mutation status of growth differentiation factor 15 (GDF15) in patients with oral squamous cell carcinoma (OSCC), as well as the prognostic value of missense GDF15 mutations.", "Formalin-fixed paraffin-embedded biopsy samples from 46 OSCC patients were involved in this study. GDF15 and TP53 mutations were sequenced using the Ion Torrent Personal Genome Machine, GDF15 protein expression was detected using immunohistochemistry. Torrent Suite Software v.3.6, Integrative Genomics Viewer; v.2.3, statistical software SPSS18.0 for Windows were used for analysis. All hypothesis-generating tests were two-sided at a significance level of 0.05.", "Twenty-nine GDF15 mutations were identified in 19 out of 46 patients (41.3%), including eighteen missense mutations, two nonsense mutations and nine synonymous mutations. The patients with missense GDF15 mutations had poorer prognostic outcomes than those with wild-type GDF15, including overall survival (P = 0.035), disease-free survival (P = 0.032), locoregional recurrence-free survival (P = 0.015), and distant metastasis-free survival (P = 0.070). Missense GDF15mutations was an independent increased risk factor of overall survival (HR = 5.993, 95% CI:1.856-19.346, P = 0.003), disease-free survival (HR = 3.764, 95% CI:1.295-10.945, P = 0.015), locoregional recurrence-free survival (HR = 4.555, 95% CI:1.494-13.889, P = 0.008), and distant metastasis-free survival (HR = 4.420, 95% CI:1.145-13.433, P = 0.009)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Biomarkers, Tumor", "Carcinoma, Squamous Cell", "Female", "Follow-Up Studies", "Growth Differentiation Factor 15", "High-Throughput Nucleotide Sequencing", "Humans", "Immunoenzyme Techniques", "Male", "Middle Aged", "Mouth Neoplasms", "Mutation, Missense", "Neoplasm Recurrence, Local", "Neoplasm Staging", "Prognosis", "Survival Rate", "Tumor Suppressor Protein p53" ] }
Patients with missense GDF15 mutations have significantly poorer outcomes than those with wild-type GDF15, missense GDF15 mutations could be used as an independent increased risk factor of poor prognosis in OSCC patients.
yes
[ { "from": "human", "value": "Question: Does mutant GDF15 present a poor prognostic outcome for patients with oral squamous cell carcinoma?\nContext: {'contexts': ['To investigate the mutation status of growth differentiation factor 15 (GDF15) in patients with oral squamous cell carcinoma (OSCC), as well as the prognostic value of missense GDF15 mutations.', 'Formalin-fixed paraffin-embedded biopsy samples from 46 OSCC patients were involved in this study. GDF15 and TP53 mutations were sequenced using the Ion Torrent Personal Genome Machine, GDF15 protein expression was detected using immunohistochemistry. Torrent Suite Software v.3.6, Integrative Genomics Viewer; v.2.3, statistical software SPSS18.0 for Windows were used for analysis. All hypothesis-generating tests were two-sided at a significance level of 0.05.', 'Twenty-nine GDF15 mutations were identified in 19 out of 46 patients (41.3%), including eighteen missense mutations, two nonsense mutations and nine synonymous mutations. The patients with missense GDF15 mutations had poorer prognostic outcomes than those with wild-type GDF15, including overall survival (P = 0.035), disease-free survival (P = 0.032), locoregional recurrence-free survival (P = 0.015), and distant metastasis-free survival (P = 0.070). Missense GDF15mutations was an independent increased risk factor of overall survival (HR = 5.993, 95% CI:1.856-19.346, P = 0.003), disease-free survival (HR = 3.764, 95% CI:1.295-10.945, P = 0.015), locoregional recurrence-free survival (HR = 4.555, 95% CI:1.494-13.889, P = 0.008), and distant metastasis-free survival (HR = 4.420, 95% CI:1.145-13.433, P = 0.009).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Biomarkers, Tumor', 'Carcinoma, Squamous Cell', 'Female', 'Follow-Up Studies', 'Growth Differentiation Factor 15', 'High-Throughput Nucleotide Sequencing', 'Humans', 'Immunoenzyme Techniques', 'Male', 'Middle Aged', 'Mouth Neoplasms', 'Mutation, Missense', 'Neoplasm Recurrence, Local', 'Neoplasm Staging', 'Prognosis', 'Survival Rate', 'Tumor Suppressor Protein p53']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,546,573
Does thiosulfate mediate Cytoprotective Effects of Hydrogen Sulfide Against Neuronal Ischemia?
{ "contexts": [ "Hydrogen sulfide (H2S) exhibits protective effects in various disease models including cerebral ischemia-reperfusion (I/R) injury. Nonetheless, mechanisms and identity of molecules responsible for neuroprotective effects of H2S remain incompletely defined. In the current study, we observed that thiosulfate, an oxidation product of H2S, mediates protective effects of an H2S donor compound sodium sulfide (Na2S) against neuronal I/R injury.", "We observed that thiosulfate in cell culture medium is not only required but also sufficient to mediate cytoprotective effects of Na2S against oxygen glucose deprivation and reoxygenation of human neuroblastoma cell line (SH-SY5Y) and murine primary cortical neurons. Systemic administration of sodium thiosulfate (STS) improved survival and neurological function of mice subjected to global cerebral I/R injury. Beneficial effects of STS, as well as Na2S, were associated with marked increase of thiosulfate, but not H2S, in plasma and brain tissues. These results suggest that thiosulfate is a circulating \"carrier\" molecule of beneficial effects of H2S. Protective effects of thiosulfate were associated with inhibition of caspase-3 activity by persulfidation at Cys163 in caspase-3. We discovered that an SLC13 family protein, sodium sulfate cotransporter 2 (SLC13A4, NaS-2), facilitates transport of thiosulfate, but not sulfide, across the cell membrane, regulating intracellular concentrations and thus mediating cytoprotective effects of Na2S and STS." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Animals", "Anion Transport Proteins", "Apoptosis", "Brain Ischemia", "Caspase 3", "Cell Hypoxia", "Cell Line, Tumor", "Cytoprotection", "Dose-Response Relationship, Drug", "Gestational Age", "Glucose", "Humans", "Mice", "Mice, Inbred C57BL", "Mitochondria", "Neurons", "Neuroprotective Agents", "Oxidation-Reduction", "Reperfusion Injury", "Sulfate Transporters", "Sulfites", "Symporters", "Thiosulfates", "Time Factors" ] }
The protective effects of H2S are mediated by thiosulfate that is transported across cell membrane by NaS-2 and exerts antiapoptotic effects via persulfidation of caspase-3. Given the established safety track record, thiosulfate may be therapeutic against ischemic brain injury.
yes
[ { "from": "human", "value": "Question: Does thiosulfate mediate Cytoprotective Effects of Hydrogen Sulfide Against Neuronal Ischemia?\nContext: {'contexts': ['Hydrogen sulfide (H2S) exhibits protective effects in various disease models including cerebral ischemia-reperfusion (I/R) injury. Nonetheless, mechanisms and identity of molecules responsible for neuroprotective effects of H2S remain incompletely defined. In the current study, we observed that thiosulfate, an oxidation product of H2S, mediates protective effects of an H2S donor compound sodium sulfide (Na2S) against neuronal I/R injury.', 'We observed that thiosulfate in cell culture medium is not only required but also sufficient to mediate cytoprotective effects of Na2S against oxygen glucose deprivation and reoxygenation of human neuroblastoma cell line (SH-SY5Y) and murine primary cortical neurons. Systemic administration of sodium thiosulfate (STS) improved survival and neurological function of mice subjected to global cerebral I/R injury. Beneficial effects of STS, as well as Na2S, were associated with marked increase of thiosulfate, but not H2S, in plasma and brain tissues. These results suggest that thiosulfate is a circulating \"carrier\" molecule of beneficial effects of H2S. Protective effects of thiosulfate were associated with inhibition of caspase-3 activity by persulfidation at Cys163 in caspase-3. We discovered that an SLC13 family protein, sodium sulfate cotransporter 2 (SLC13A4, NaS-2), facilitates transport of thiosulfate, but not sulfide, across the cell membrane, regulating intracellular concentrations and thus mediating cytoprotective effects of Na2S and STS.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Animals', 'Anion Transport Proteins', 'Apoptosis', 'Brain Ischemia', 'Caspase 3', 'Cell Hypoxia', 'Cell Line, Tumor', 'Cytoprotection', 'Dose-Response Relationship, Drug', 'Gestational Age', 'Glucose', 'Humans', 'Mice', 'Mice, Inbred C57BL', 'Mitochondria', 'Neurons', 'Neuroprotective Agents', 'Oxidation-Reduction', 'Reperfusion Injury', 'Sulfate Transporters', 'Sulfites', 'Symporters', 'Thiosulfates', 'Time Factors']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,540,164
Is zFX a Strong Predictor of Poor Prognosis in Renal Cell Carcinoma?
{ "contexts": [ "This study was designed to assay the expression of zinc finger protein X-linked (ZFX) in renal cell carcinoma (RCC) tissues and evaluate the correlation between ZFX expression and prognosis of RCC patients.", "The expressions of ZFX mRNA in 53 RCC tissues and 51 normal tissues were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) technology was used to measure the expression of ZFX protein. Then chi-square test was conducted to verify the association between ZFX expression and clinical parameters. Next, we explored the overall survival rate of RCC patients with Kaplan-Meier analysis. Finally, the correlation between ZFX expression and the prognosis of RCC patients was evaluated by Cox regression analysis.", "The qRT-PCR result showed that the ZFX was significantly up-regulated in RCC tissues. As for the IHC consequence, the positive rate of ZFX expression in RCC specimens was 79.2%, while that in the normal control tissues was only 17.6%. Chi-square test showed that ZFX expression shared no close relationship with age, sex, or smoking (P>0.05), but was tightly associated with TNM stage, tumor size, and lymph node metastasis (P<0.05). Kaplan-Meier analysis showed that patients with ZFX positive expression had higher mortality than those with negative expression (P<0.05). Cox regression analysis revealed that ZFX expression had tight correlation with prognosis of RCC patients (HR=4.997, P=0.045, 95%CI=1.033-24.180)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Carcinoma, Renal Cell", "Disease Progression", "Female", "Gene Expression Regulation, Neoplastic", "Humans", "Immunohistochemistry", "Kaplan-Meier Estimate", "Kidney Neoplasms", "Kruppel-Like Transcription Factors", "Male", "Middle Aged", "Prognosis", "Proportional Hazards Models", "Real-Time Polymerase Chain Reaction", "Regression Analysis", "Survival Rate", "Zinc Fingers" ] }
Our findings show that ZFX could be considered as a predictor for prognosis of RCC patients.
yes
[ { "from": "human", "value": "Question: Is zFX a Strong Predictor of Poor Prognosis in Renal Cell Carcinoma?\nContext: {'contexts': ['This study was designed to assay the expression of zinc finger protein X-linked (ZFX) in renal cell carcinoma (RCC) tissues and evaluate the correlation between ZFX expression and prognosis of RCC patients.', 'The expressions of ZFX mRNA in 53 RCC tissues and 51 normal tissues were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) technology was used to measure the expression of ZFX protein. Then chi-square test was conducted to verify the association between ZFX expression and clinical parameters. Next, we explored the overall survival rate of RCC patients with Kaplan-Meier analysis. Finally, the correlation between ZFX expression and the prognosis of RCC patients was evaluated by Cox regression analysis.', 'The qRT-PCR result showed that the ZFX was significantly up-regulated in RCC tissues. As for the IHC consequence, the positive rate of ZFX expression in RCC specimens was 79.2%, while that in the normal control tissues was only 17.6%. Chi-square test showed that ZFX expression shared no close relationship with age, sex, or smoking (P>0.05), but was tightly associated with TNM stage, tumor size, and lymph node metastasis (P<0.05). Kaplan-Meier analysis showed that patients with ZFX positive expression had higher mortality than those with negative expression (P<0.05). Cox regression analysis revealed that ZFX expression had tight correlation with prognosis of RCC patients (HR=4.997, P=0.045, 95%CI=1.033-24.180).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Carcinoma, Renal Cell', 'Disease Progression', 'Female', 'Gene Expression Regulation, Neoplastic', 'Humans', 'Immunohistochemistry', 'Kaplan-Meier Estimate', 'Kidney Neoplasms', 'Kruppel-Like Transcription Factors', 'Male', 'Middle Aged', 'Prognosis', 'Proportional Hazards Models', 'Real-Time Polymerase Chain Reaction', 'Regression Analysis', 'Survival Rate', 'Zinc Fingers']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,543,079
Does oligo-based High-resolution aCGH Analysis enhance Routine Cytogenetic Diagnostics in Haematological Malignancies?
{ "contexts": [ "The purpose of the present study was to evaluate the detection rate of genomic aberrations in haematological malignancies using oligobased array-CGH (oaCGH) analysis in combination with karyotyping and fluorescence in situ hybridization (FISH) analyses, and its feasibility in a clinical pragmatic approach.", "The 4x180K Cancer Cytochip array was applied in 96 patients with various haematological malignancies in a prospective setting and in 41 acute myeloid leukemia (AML) patients retrospectively.", "Combined use of oaCGH analysis and karyotyping improved the overall detection rate in comparison to karyotyping-alone and vice versa. In cases with normal karyotypes oaCGH analysis detected genomic aberrations in 66% (39/60) of cases. In the group of simple karyotypes oaCGH analysis extended karyotypic findings in 39% (12/31) while oaCGH analysis extended the karyotypic findings in 89% (39/44) of cases with complex karyotypes. In 7% (5/75) of cases oaCGH analysis failed in detecting the observed abnormalities by karyotyping." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Chromosome Aberrations", "Chromosome Banding", "Comparative Genomic Hybridization", "Cytogenetics", "Female", "Gene Rearrangement", "Hematologic Neoplasms", "Humans", "In Situ Hybridization, Fluorescence", "Karyotyping", "Leukemia, Myeloid, Acute", "Male", "Middle Aged", "Oligonucleotide Array Sequence Analysis", "Prospective Studies", "Retrospective Studies" ] }
oaCGH analysis is a valuable asset in routine cytogenetics of haematological malignancies.
yes
[ { "from": "human", "value": "Question: Does oligo-based High-resolution aCGH Analysis enhance Routine Cytogenetic Diagnostics in Haematological Malignancies?\nContext: {'contexts': ['The purpose of the present study was to evaluate the detection rate of genomic aberrations in haematological malignancies using oligobased array-CGH (oaCGH) analysis in combination with karyotyping and fluorescence in situ hybridization (FISH) analyses, and its feasibility in a clinical pragmatic approach.', 'The 4x180K Cancer Cytochip array was applied in 96 patients with various haematological malignancies in a prospective setting and in 41 acute myeloid leukemia (AML) patients retrospectively.', 'Combined use of oaCGH analysis and karyotyping improved the overall detection rate in comparison to karyotyping-alone and vice versa. In cases with normal karyotypes oaCGH analysis detected genomic aberrations in 66% (39/60) of cases. In the group of simple karyotypes oaCGH analysis extended karyotypic findings in 39% (12/31) while oaCGH analysis extended the karyotypic findings in 89% (39/44) of cases with complex karyotypes. In 7% (5/75) of cases oaCGH analysis failed in detecting the observed abnormalities by karyotyping.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Chromosome Aberrations', 'Chromosome Banding', 'Comparative Genomic Hybridization', 'Cytogenetics', 'Female', 'Gene Rearrangement', 'Hematologic Neoplasms', 'Humans', 'In Situ Hybridization, Fluorescence', 'Karyotyping', 'Leukemia, Myeloid, Acute', 'Male', 'Middle Aged', 'Oligonucleotide Array Sequence Analysis', 'Prospective Studies', 'Retrospective Studies']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,524,729
Does systematic Tracking of Disrupted Modules identify Altered Pathways Associated with Congenital Heart Defects in Down Syndrome?
{ "contexts": [ "This work aimed to identify altered pathways in congenital heart defects (CHD) in Down syndrome (DS) by systematically tracking the dysregulated modules of reweighted protein-protein interaction (PPI) networks.", "We performed systematic identification and comparison of modules across normal and disease conditions by integrating PPI and gene-expression data. Based on Pearson correlation coefficient (PCC), normal and disease PPI networks were inferred and reweighted. Then, modules in the PPI network were explored by clique-merging algorithm; altered modules were identified via maximum weight bipartite matching and ranked in non-increasing order. Finally, pathways enrichment analysis of genes in altered modules was carried out based on Database for Annotation, Visualization, and Integrated Discovery (DAVID) to study the biological pathways in CHD in DS.", "Our analyses revealed that 348 altered modules were identified by comparing modules in normal and disease PPI networks. Pathway functional enrichment analysis of disrupted module genes showed that the 4 most significantly altered pathways were: ECM-receptor interaction, purine metabolism, focal adhesion, and dilated cardiomyopathy." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Algorithms", "Cardiomyopathy, Dilated", "Cell Adhesion", "Computational Biology", "Databases, Factual", "Down Syndrome", "Extracellular Matrix", "Gene Expression Profiling", "Gene Expression Regulation", "Genome, Human", "Heart Defects, Congenital", "Humans", "Models, Statistical", "Oligonucleotide Array Sequence Analysis", "Protein Interaction Mapping", "Purines" ] }
We successfully identified 4 altered pathways and we predicted that these pathways would be good indicators for CHD in DS.
yes
[ { "from": "human", "value": "Question: Does systematic Tracking of Disrupted Modules identify Altered Pathways Associated with Congenital Heart Defects in Down Syndrome?\nContext: {'contexts': ['This work aimed to identify altered pathways in congenital heart defects (CHD) in Down syndrome (DS) by systematically tracking the dysregulated modules of reweighted protein-protein interaction (PPI) networks.', 'We performed systematic identification and comparison of modules across normal and disease conditions by integrating PPI and gene-expression data. Based on Pearson correlation coefficient (PCC), normal and disease PPI networks were inferred and reweighted. Then, modules in the PPI network were explored by clique-merging algorithm; altered modules were identified via maximum weight bipartite matching and ranked in non-increasing order. Finally, pathways enrichment analysis of genes in altered modules was carried out based on Database for Annotation, Visualization, and Integrated Discovery (DAVID) to study the biological pathways in CHD in DS.', 'Our analyses revealed that 348 altered modules were identified by comparing modules in normal and disease PPI networks. Pathway functional enrichment analysis of disrupted module genes showed that the 4 most significantly altered pathways were: ECM-receptor interaction, purine metabolism, focal adhesion, and dilated cardiomyopathy.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Algorithms', 'Cardiomyopathy, Dilated', 'Cell Adhesion', 'Computational Biology', 'Databases, Factual', 'Down Syndrome', 'Extracellular Matrix', 'Gene Expression Profiling', 'Gene Expression Regulation', 'Genome, Human', 'Heart Defects, Congenital', 'Humans', 'Models, Statistical', 'Oligonucleotide Array Sequence Analysis', 'Protein Interaction Mapping', 'Purines']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,531,875
Does iloprost and vitamin C attenuate acute myocardial injury induced by suprarenal aortic ischemia-reperfusion in rabbits?
{ "contexts": [ "The aim of this study was to evaluate antioxidant and cytoprotective effects of iloprost and Vitamin C in a distant organ after abdominal aorta ischemia-reperfusion injury.", "Twenty-eight New Zealand rabbits weighing 2,400-2,800 g were used for this study. The rabbits were divided into four equal groups. These groups are control group, sham group, iloprost group, and iloprost+vitamin C group. Suprarenal aorta was occluded with a vascular clamp. Following 30 minutes of ischemia, the vascular clamp was removed. Rabbits in group 3 received 10 ng/kg/min iloprost and those in group 4 received 10 ng/kg/min iloprost and 10 mg/kg vitamin C. At the end of the reperfusion period, the rabbits were sacrificed by a high intraperitoneal dose of xylazine+ketamine injection. Myocardial tissue samples were taken for electron microscopic analysis. We evaluated SOD, MDA and catalase in myocardial tissue samples.", "Iloprost and iloprost+vitamin C groups significantly reduced the oxidative stress markers in tissue samples (p<0.05) and significantly decreased the myofibrillar injury and mitochondrial morphology changes in the myocardial tissue as shown with electron microscopy (p<0.05). Myocardial edema was significantly alleviated by iloprost and iloprost+vitamin C administration (p<0.05)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Aorta, Abdominal", "Ascorbic Acid", "Drug Therapy, Combination", "Iloprost", "Myocardial Reperfusion Injury", "Oxidative Stress", "Platelet Aggregation Inhibitors", "Rabbits", "Reperfusion Injury", "Vitamins" ] }
This study clearly showed that myocardial injury and edema occurred after ischemia-reperfusion of abdominal aorta and that groups administered with iloprost and iloprost+vitamin C showed an attenuation of ischemia-reperfusion injury in distant organs (Tab. 3, Fig. 4, Ref. 30).
yes
[ { "from": "human", "value": "Question: Does iloprost and vitamin C attenuate acute myocardial injury induced by suprarenal aortic ischemia-reperfusion in rabbits?\nContext: {'contexts': ['The aim of this study was to evaluate antioxidant and cytoprotective effects of iloprost and Vitamin C in a distant organ after abdominal aorta ischemia-reperfusion injury.', 'Twenty-eight New Zealand rabbits weighing 2,400-2,800 g were used for this study. The rabbits were divided into four equal groups. These groups are control group, sham group, iloprost group, and iloprost+vitamin C group. Suprarenal aorta was occluded with a vascular clamp. Following 30 minutes of ischemia, the vascular clamp was removed. Rabbits in group 3 received 10 ng/kg/min iloprost and those in group 4 received 10 ng/kg/min iloprost and 10 mg/kg vitamin C. At the end of the reperfusion period, the rabbits were sacrificed by a high intraperitoneal dose of xylazine+ketamine injection. Myocardial tissue samples were taken for electron microscopic analysis. We evaluated SOD, MDA and catalase in myocardial tissue samples.', 'Iloprost and iloprost+vitamin C groups significantly reduced the oxidative stress markers in tissue samples (p<0.05) and significantly decreased the myofibrillar injury and mitochondrial morphology changes in the myocardial tissue as shown with electron microscopy (p<0.05). Myocardial edema was significantly alleviated by iloprost and iloprost+vitamin C administration (p<0.05).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Aorta, Abdominal', 'Ascorbic Acid', 'Drug Therapy, Combination', 'Iloprost', 'Myocardial Reperfusion Injury', 'Oxidative Stress', 'Platelet Aggregation Inhibitors', 'Rabbits', 'Reperfusion Injury', 'Vitamins']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,524,940
Does pain intensity attenuate movement control of the lumbar spine in low back pain?
{ "contexts": [ "Pain intensity attenuates muscular activity, proprioception, and tactile acuity, with consequent changes of joint kinematics. People suffering from low back pain (LBP) frequently show movement control impairments of the lumbar spine in sagittal plane. This cross-sectional, observational study investigated if the intensity of LBP attenuates lumbar movement control. The hypothesis was that lumbar movement control becomes more limited with increased pain intensity.", "The effect of LBP intensity, measured with a numeric rating scale (NRS), on lumbar movement control was tested using three movement control tests. The lumbar range of motion (ROM), the ratio of lumbar and hip ROM as indicators of direction specific movement control, and the recurrence and determinism of repetitive lumbar movement patterns were assessed in ninety-four persons suffering from LBP of different intensity and measured with an inertial measurement unit system. Generalized linear models were fitted for each outcome.", "Lumbar ROM (+ 0.03°, p = 0.24) and ratio of lumbar and hip ROM (0.01, p = 0.84) were unaffected by LBP intensity. Each one point increase on the NRS resulted in a decrease of recurrence and determinism of lumbar movement patterns (-3.11 to -0.06, p ⩽ 0.05)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Biomechanical Phenomena", "Female", "Humans", "Low Back Pain", "Lumbar Vertebrae", "Male", "Middle Aged", "Movement", "Muscle, Skeletal", "Postural Balance", "Range of Motion, Articular" ] }
Our results indicate changes in movement control in people suffering from LBP. Whether decreased recurrence and determinism of lumbar movement patterns are intensifiers of LBP intensity or a consequence thereof should be addressed in a future prospective study.
yes
[ { "from": "human", "value": "Question: Does pain intensity attenuate movement control of the lumbar spine in low back pain?\nContext: {'contexts': ['Pain intensity attenuates muscular activity, proprioception, and tactile acuity, with consequent changes of joint kinematics. People suffering from low back pain (LBP) frequently show movement control impairments of the lumbar spine in sagittal plane. This cross-sectional, observational study investigated if the intensity of LBP attenuates lumbar movement control. The hypothesis was that lumbar movement control becomes more limited with increased pain intensity.', 'The effect of LBP intensity, measured with a numeric rating scale (NRS), on lumbar movement control was tested using three movement control tests. The lumbar range of motion (ROM), the ratio of lumbar and hip ROM as indicators of direction specific movement control, and the recurrence and determinism of repetitive lumbar movement patterns were assessed in ninety-four persons suffering from LBP of different intensity and measured with an inertial measurement unit system. Generalized linear models were fitted for each outcome.', 'Lumbar ROM (+ 0.03°, p = 0.24) and ratio of lumbar and hip ROM (0.01, p = 0.84) were unaffected by LBP intensity. Each one point increase on the NRS resulted in a decrease of recurrence and determinism of lumbar movement patterns (-3.11 to -0.06, p ⩽ 0.05).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Biomechanical Phenomena', 'Female', 'Humans', 'Low Back Pain', 'Lumbar Vertebrae', 'Male', 'Middle Aged', 'Movement', 'Muscle, Skeletal', 'Postural Balance', 'Range of Motion, Articular']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,543,727
Does sildenafil treatment attenuate ventricular remodeling in an experimental model of aortic regurgitation?
{ "contexts": [ "Currently there is no reliable medical treatment for aortic regurgitation (AR).", "Thirty-nine Sprague-Dawley rats underwent creation of AR or sham operation. Treated rats were assigned to early or late institution of sildenafil therapy (100 mg/kg/day) for a total of 10 weeks. Treatment-effects were measured by serial echocardiography, invasive hemodynamic measurements, and tissue analysis.", "Rats assigned to early treatment developed less remodeling than untreated rats. Thus, left ventricular (LV) dilation was blunted by sildenafil with end-systolic diameter being significantly smaller (6.6 ± 0.4 vs. 7.7 ± 0.4 mm, respectively, p < 0.05). Also, LV wall thickness was significantly decreased in treated rats compared to controls (2.23 ± 0.08 vs. 2.16 ± 0.05 mm, p < 0.01). Fractional shortening was improved by treatment (p < 0.05). Myocardial fibrosis was borderline decreased by treatment (p = 0.09). Akt was increased in treated compared to controls (p < 0.05)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
Sildenafil slightly inhibits LV remodeling and improves fractional shortening in rats with AR when treatment is initiated early.
yes
[ { "from": "human", "value": "Question: Does sildenafil treatment attenuate ventricular remodeling in an experimental model of aortic regurgitation?\nContext: {'contexts': ['Currently there is no reliable medical treatment for aortic regurgitation (AR).', 'Thirty-nine Sprague-Dawley rats underwent creation of AR or sham operation. Treated rats were assigned to early or late institution of sildenafil therapy (100\\xa0mg/kg/day) for a total of 10\\xa0weeks. Treatment-effects were measured by serial echocardiography, invasive hemodynamic measurements, and tissue analysis.', 'Rats assigned to early treatment developed less remodeling than untreated rats. Thus, left ventricular (LV) dilation was blunted by sildenafil with end-systolic diameter being significantly smaller (6.6\\xa0±\\xa00.4 vs. 7.7\\xa0±\\xa00.4\\xa0mm, respectively, p\\xa0<\\xa00.05). Also, LV wall thickness was significantly decreased in treated rats compared to controls (2.23\\xa0±\\xa00.08 vs. 2.16\\xa0±\\xa00.05\\xa0mm, p\\xa0<\\xa00.01). Fractional shortening was improved by treatment (p\\xa0<\\xa00.05). Myocardial fibrosis was borderline decreased by treatment (p\\xa0=\\xa00.09). Akt was increased in treated compared to controls (p\\xa0<\\xa00.05).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,527,864
Does 4-Hydroxyisoleucine ameliorate an insulin resistant-like state in 3T3-L1 adipocytes by regulating TACE/TIMP3 expression?
{ "contexts": [ "Obesity-associated insulin resistance (IR) is highly correlated with soluble tumor necrosis factor-α (sTNF-α), which is released from transmembranous TNF-α by TNF-α converting enzyme (TACE). In vivo, TACE activity is suppressed by tissue inhibitor of metalloproteinase 3 (TIMP3). Agents that can interact with TACE/TIMP3 to improve obesity-related IR would be highly valuable. In the current study, we assessed whether (2S,3R,4S)-4-hydroxyisoleucine (4-HIL) could modulate TACE/TIMP3 and ameliorate an obesity-induced IR-like state in 3T3-L1 adipocytes.", "3T3-L1 adipocytes were incubated in the presence of 25 mM glucose and 0.6 nM insulin to induce an IR-like state, and were then treated with different concentrations of 4-HIL or 10 µM pioglitazone (positive control). The glucose uptake rate was determined using the 2-deoxy-[(3)H]-D-glucose method, and the levels of sTNF-α in the cell supernatant were determined using ELISA. The protein expression of TACE, TIMP3, and insulin signaling-related molecules was measured using western blotting.", "Exposure to high glucose and insulin for 18 hours increased the levels of sTNF-α in the cell supernatant. The phosphorylation of insulin receptor substrate-1 (IRS-1) Ser(307) and Akt Ser(473) was increased, whereas the protein expression of IRS-1, Akt, and glucose transporter-4 was decreased. The insulin-induced glucose uptake was reduced by 67% in 3T3-L1 adipocytes, which indicated the presence of an IR-like state. The above indexes, which demonstrated the successful induction of an IR-like state, were reversed by 4-HIL in a dose-dependent manner by downregulating and upregulating the protein expression of TACE and TIMP3 proteins, respectively." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "3T3-L1 Cells", "ADAM Proteins", "ADAM17 Protein", "Adipocytes", "Animals", "Deoxyglucose", "Dose-Response Relationship, Drug", "Insulin", "Insulin Resistance", "Isoleucine", "Mice", "Pioglitazone", "Signal Transduction", "Thiazolidinediones", "Time Factors", "Tissue Inhibitor of Metalloproteinases" ] }
4-HIL improved an obesity-associated IR-like state in 3T3-L1 adipocytes by targeting TACE/TIMP3 and the insulin signaling pathway.
yes
[ { "from": "human", "value": "Question: Does 4-Hydroxyisoleucine ameliorate an insulin resistant-like state in 3T3-L1 adipocytes by regulating TACE/TIMP3 expression?\nContext: {'contexts': ['Obesity-associated insulin resistance (IR) is highly correlated with soluble tumor necrosis factor-α (sTNF-α), which is released from transmembranous TNF-α by TNF-α converting enzyme (TACE). In vivo, TACE activity is suppressed by tissue inhibitor of metalloproteinase 3 (TIMP3). Agents that can interact with TACE/TIMP3 to improve obesity-related IR would be highly valuable. In the current study, we assessed whether (2S,3R,4S)-4-hydroxyisoleucine (4-HIL) could modulate TACE/TIMP3 and ameliorate an obesity-induced IR-like state in 3T3-L1 adipocytes.', '3T3-L1 adipocytes were incubated in the presence of 25 mM glucose and 0.6 nM insulin to induce an IR-like state, and were then treated with different concentrations of 4-HIL or 10 µM pioglitazone (positive control). The glucose uptake rate was determined using the 2-deoxy-[(3)H]-D-glucose method, and the levels of sTNF-α in the cell supernatant were determined using ELISA. The protein expression of TACE, TIMP3, and insulin signaling-related molecules was measured using western blotting.', 'Exposure to high glucose and insulin for 18 hours increased the levels of sTNF-α in the cell supernatant. The phosphorylation of insulin receptor substrate-1 (IRS-1) Ser(307) and Akt Ser(473) was increased, whereas the protein expression of IRS-1, Akt, and glucose transporter-4 was decreased. The insulin-induced glucose uptake was reduced by 67% in 3T3-L1 adipocytes, which indicated the presence of an IR-like state. The above indexes, which demonstrated the successful induction of an IR-like state, were reversed by 4-HIL in a dose-dependent manner by downregulating and upregulating the protein expression of TACE and TIMP3 proteins, respectively.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['3T3-L1 Cells', 'ADAM Proteins', 'ADAM17 Protein', 'Adipocytes', 'Animals', 'Deoxyglucose', 'Dose-Response Relationship, Drug', 'Insulin', 'Insulin Resistance', 'Isoleucine', 'Mice', 'Pioglitazone', 'Signal Transduction', 'Thiazolidinediones', 'Time Factors', 'Tissue Inhibitor of Metalloproteinases']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,534,856
Is a Western dietary pattern associated with higher blood pressure in Iranian adolescents?
{ "contexts": [ "The dietary determinants of adolescent blood pressure (BP) are not well understood. We determined the association between major dietary patterns and BP in a sample of Iranian adolescents.", "This cross-sectional study was conducted among a representative sample (n = 557) of Shirazi adolescents aged 12-19 years. Participants' systolic and diastolic BP was measured using a validated oscillometric BP monitor. Usual dietary intakes during the past 12 months were assessed using a valid and reproducible 168-item semiquantitative food frequency questionnaire through face-to-face interviews. Principal component factor analysis was used to identify major dietary patterns based on a set of 25 predefined food groups.", "Overall, three major dietary patterns were identified, among which only the Western pattern (abundant in soft drinks, sweets and desserts, salt, mayonnaise, tea and coffee, salty snacks, high-fat dairy products, French fries, and red or processed meats) had a significant association with BP. After adjusting for potential confounders in the analysis of covariance models, multivariable adjusted means of the systolic and mean BP of subjects in the highest tertile of the Western pattern score were significantly higher than those in the lowest tertile (for systolic BP: mean difference 6.9 mmHg, P = 0.001; and for mean BP: mean difference 4.2 mmHg, P = 0.003). A similar but statistically insignificant difference was observed in terms of diastolic BP." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Asian Continental Ancestry Group", "Blood Pressure", "Body Mass Index", "Body Weight", "Child", "Cross-Sectional Studies", "Diet, Western", "Energy Intake", "Exercise", "Female", "Humans", "Hypertension", "Iran", "Male", "Principal Component Analysis", "Surveys and Questionnaires", "Young Adult" ] }
The findings suggest that a Western dietary pattern is associated with higher BP in Iranian adolescents. However, additional large-scale prospective studies with adequate methodological quality are required to confirm these findings.
yes
[ { "from": "human", "value": "Question: Is a Western dietary pattern associated with higher blood pressure in Iranian adolescents?\nContext: {'contexts': ['The dietary determinants of adolescent blood pressure (BP) are not well understood. We determined the association between major dietary patterns and BP in a sample of Iranian adolescents.', \"This cross-sectional study was conducted among a representative sample (n\\xa0=\\xa0557) of Shirazi adolescents aged 12-19\\xa0years. Participants' systolic and diastolic BP was measured using a validated oscillometric BP monitor. Usual dietary intakes during the past 12\\xa0months were assessed using a valid and reproducible 168-item semiquantitative food frequency questionnaire through face-to-face interviews. Principal component factor analysis was used to identify major dietary patterns based on a set of 25 predefined food groups.\", 'Overall, three major dietary patterns were identified, among which only the Western pattern (abundant in soft drinks, sweets and desserts, salt, mayonnaise, tea and coffee, salty snacks, high-fat dairy products, French fries, and red or processed meats) had a significant association with BP. After adjusting for potential confounders in the analysis of covariance models, multivariable adjusted means of the systolic and mean BP of subjects in the highest tertile of the Western pattern score were significantly higher than those in the lowest tertile (for systolic BP: mean difference 6.9\\xa0mmHg, P\\xa0=\\xa00.001; and for mean BP: mean difference 4.2\\xa0mmHg, P\\xa0=\\xa00.003). A similar but statistically insignificant difference was observed in terms of diastolic BP.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Asian Continental Ancestry Group', 'Blood Pressure', 'Body Mass Index', 'Body Weight', 'Child', 'Cross-Sectional Studies', 'Diet, Western', 'Energy Intake', 'Exercise', 'Female', 'Humans', 'Hypertension', 'Iran', 'Male', 'Principal Component Analysis', 'Surveys and Questionnaires', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,525,778
Are e-cadherin regulators differentially expressed in the epithelium and stroma of keratocystic odontogenic tumors?
{ "contexts": [ "The epithelial-mesenchymal transition (EMT) is the process where cells lose their epithelial features and acquire properties of typical mesenchymal cells. The dissociation of tumor cells due to changes in cell-cell adhesion is one of the key principles of tumor invasion and EMT. Thus, the knowledge of the molecular features of EMT in keratocyst odontogenic tumor (KOT) can provide useful markers to aid in the diagnosis and prognosis and perhaps contribute to an alternative therapeutic approach as it shows an aggressive clinical behavior and high recurrence rates. This study aimed to evaluate the EMT in KOT by the immunoexpression of E-cadherin, N-cadherin, Snail, and Slug and comparing to radicular cysts and dental follicles.", "Thirty-two KOTs, 15 radicular cysts, and 08 dental follicles were used for immunohistochemistry, evaluating the extent, intensity, labeling pattern, cellular compartment in the epithelium and stroma, and the presence of inflammation.", "E-cadherin was preserved in most cases of keratocystic odontogenic tumor. N-cadherin was increased in the tumor epithelium, a result that was positively correlated with the heterogeneous and nuclear immunoexpression of Slug in the epithelium; Slug also correlated with high Snail immunoexpression. N-cadherin was positively correlated with Slug in the stroma of keratocystic odontogenic tumors." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adult", "Aged", "Animals", "Antigens, CD", "Biomarkers, Tumor", "Cadherins", "Cell Adhesion", "Child", "Dental Sac", "Epithelial-Mesenchymal Transition", "Epithelium", "Female", "Humans", "Middle Aged", "Odontogenic Cysts", "Odontogenic Tumors", "Prognosis", "Radicular Cyst", "Snail Family Transcription Factors", "Young Adult" ] }
The high immunoexpression of Snail and nuclear Slug in keratocystic odontogenic tumors suggests these proteins as transcription factors without necessarily participating in 'cadherin switching'. However, the knowledge of their induction of the epithelial-mesenchymal transition in odontogenic tumors is still limited.
yes
[ { "from": "human", "value": "Question: Are e-cadherin regulators differentially expressed in the epithelium and stroma of keratocystic odontogenic tumors?\nContext: {'contexts': ['The epithelial-mesenchymal transition (EMT) is the process where cells lose their epithelial features and acquire properties of typical mesenchymal cells. The dissociation of tumor cells due to changes in cell-cell adhesion is one of the key principles of tumor invasion and EMT. Thus, the knowledge of the molecular features of EMT in keratocyst odontogenic tumor (KOT) can provide useful markers to aid in the diagnosis and prognosis and perhaps contribute to an alternative therapeutic approach as it shows an aggressive clinical behavior and high recurrence rates. This study aimed to evaluate the EMT in KOT by the immunoexpression of E-cadherin, N-cadherin, Snail, and Slug and comparing to radicular cysts and dental follicles.', 'Thirty-two KOTs, 15 radicular cysts, and 08 dental follicles were used for immunohistochemistry, evaluating the extent, intensity, labeling pattern, cellular compartment in the epithelium and stroma, and the presence of inflammation.', 'E-cadherin was preserved in most cases of keratocystic odontogenic tumor. N-cadherin was increased in the tumor epithelium, a result that was positively correlated with the heterogeneous and nuclear immunoexpression of Slug in the epithelium; Slug also correlated with high Snail immunoexpression. N-cadherin was positively correlated with Slug in the stroma of keratocystic odontogenic tumors.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Aged', 'Animals', 'Antigens, CD', 'Biomarkers, Tumor', 'Cadherins', 'Cell Adhesion', 'Child', 'Dental Sac', 'Epithelial-Mesenchymal Transition', 'Epithelium', 'Female', 'Humans', 'Middle Aged', 'Odontogenic Cysts', 'Odontogenic Tumors', 'Prognosis', 'Radicular Cyst', 'Snail Family Transcription Factors', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,547,756
Does the Density of Interstitial Cells of Cajal be Diminished in Choledochal Cysts?
{ "contexts": [ "Interstitial cells of Cajal (ICC) have been shown to be present in the extrahepatic biliary tract of animals and humans. However, ICC distribution in choledochal cysts (CC) has not been investigated. A study was conducted to investigate the distribution of ICC in the extrahepatic biliary tract, including CC, in pediatric human specimens.", "The specimens were divided into two main groups as gallbladders and common bile ducts. Gallbladders were obtained from the cholelithiasis, CC operations and autopsies. Common bile ducts were obtained from autopsies. Tissues were stained using c-kit immunohistochemical staining. ICC were assessed semi-quantitatively by applying morphological criteria and were counted as the number of cells/0.24 mm(2) in each area under light microscopy.", "A total of 35 gallbladders and 14 CC were obtained from operations. Ten gallbladders plus common bile ducts were obtained from autopsies. The mean numbers of ICC in the gallbladders of cholelithiasis and the gallbladders of CC were 12.2 ± 4.9 and 5.3 ± 1.2, respectively (p = 0.003). The mean numbers of ICC in the common bile ducts and CC were 9.8 ± 2.9 and 3.4 ± 1.4, respectively (p = 0.001)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Case-Control Studies", "Cell Count", "Child", "Child, Preschool", "Cholecystectomy", "Choledochal Cyst", "Cholelithiasis", "Common Bile Duct", "Female", "Gallbladder", "Humans", "Immunohistochemistry", "Infant", "Interstitial Cells of Cajal", "Male", "Proto-Oncogene Proteins c-kit" ] }
The scarcity of ICC in the extrahepatic biliary tract may be responsible for the etiopathogenesis of the CC.
yes
[ { "from": "human", "value": "Question: Does the Density of Interstitial Cells of Cajal be Diminished in Choledochal Cysts?\nContext: {'contexts': ['Interstitial cells of Cajal (ICC) have been shown to be present in the extrahepatic biliary tract of animals and humans. However, ICC distribution in choledochal cysts (CC) has not been investigated. A study was conducted to investigate the distribution of ICC in the extrahepatic biliary tract, including CC, in pediatric human specimens.', 'The specimens were divided into two main groups as gallbladders and common bile ducts. Gallbladders were obtained from the cholelithiasis, CC operations and autopsies. Common bile ducts were obtained from autopsies. Tissues were stained using c-kit immunohistochemical staining. ICC were assessed semi-quantitatively by applying morphological criteria and were counted as the number of cells/0.24 mm(2) in each area under light microscopy.', 'A total of 35 gallbladders and 14 CC were obtained from operations. Ten gallbladders plus common bile ducts were obtained from autopsies. The mean numbers of ICC in the gallbladders of cholelithiasis and the gallbladders of CC were 12.2 ± 4.9 and 5.3 ± 1.2, respectively (p = 0.003). The mean numbers of ICC in the common bile ducts and CC were 9.8 ± 2.9 and 3.4 ± 1.4, respectively (p = 0.001).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Case-Control Studies', 'Cell Count', 'Child', 'Child, Preschool', 'Cholecystectomy', 'Choledochal Cyst', 'Cholelithiasis', 'Common Bile Duct', 'Female', 'Gallbladder', 'Humans', 'Immunohistochemistry', 'Infant', 'Interstitial Cells of Cajal', 'Male', 'Proto-Oncogene Proteins c-kit']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,547,754
Is nerve Growth Factor Expression Associated with Perineural Invasion in Extrahepatic Cholangiocarcinoma?
{ "contexts": [ "Although the presence of perineural invasion has been recognized as a poor prognostic factor in extrahepatic cholangiocarcinoma, the molecular mechanisms of perineural invasion in extrahepatic cholangiocarcinoma remain unclear. Nerve growth factor has been reported to be a candidate predictive biomarker of perineural invasion in some cancers.", "To investigate the impact of intratumoral nerve growth factor expression in resected extrahepatic cholangiocarcinoma on survival.", "Intratumoral nerve growth factor expression was investigated immunohistochemically in 112 patients with resected extrahepatic cholangiocarcinoma. Associations between nerve growth factor expression and clinicopathological factors were statistically evaluated, and risk factors for poor survival were analyzed using univariate and multivariate analyses.", "High and low nerve growth factor expression was observed in 62 (55%) and 50 (45%) patients, respectively. For all 112 patients, no significant correlation was found between nerve growth factor expression and presence of perineural invasion (P = 0.942). Moreover, nerve growth factor expression was not associated with recurrence-free survival (P = 0.861) and overall survival (P = 0.973). In multivariate analysis, lymph node metastasis (P = 0.004) was identified as an independent risk factor for early recurrence and the presence of perineural invasion (P = 0.002) and lymph node metastasis (P < 0.001) was identified as independent risk factors for poor survival." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Bile Duct Neoplasms", "Cholangiocarcinoma", "Disease-Free Survival", "Female", "Humans", "Immunohistochemistry", "Male", "Middle Aged", "Multivariate Analysis", "Neoplasm Invasiveness", "Neoplasm Recurrence, Local", "Nerve Growth Factor", "Peripheral Nerves", "Prognosis", "Proportional Hazards Models", "Retrospective Studies", "Survival Rate" ] }
Intratumoral nerve growth factor expression is not associated with perineural invasion or recurrence-free and overall survival in patients with resected extrahepatic cholangiocarcinoma.
no
[ { "from": "human", "value": "Question: Is nerve Growth Factor Expression Associated with Perineural Invasion in Extrahepatic Cholangiocarcinoma?\nContext: {'contexts': ['Although the presence of perineural invasion has been recognized as a poor prognostic factor in extrahepatic cholangiocarcinoma, the molecular mechanisms of perineural invasion in extrahepatic cholangiocarcinoma remain unclear. Nerve growth factor has been reported to be a candidate predictive biomarker of perineural invasion in some cancers.', 'To investigate the impact of intratumoral nerve growth factor expression in resected extrahepatic cholangiocarcinoma on survival.', 'Intratumoral nerve growth factor expression was investigated immunohistochemically in 112 patients with resected extrahepatic cholangiocarcinoma. Associations between nerve growth factor expression and clinicopathological factors were statistically evaluated, and risk factors for poor survival were analyzed using univariate and multivariate analyses.', 'High and low nerve growth factor expression was observed in 62 (55%) and 50 (45%) patients, respectively. For all 112 patients, no significant correlation was found between nerve growth factor expression and presence of perineural invasion (P = 0.942). Moreover, nerve growth factor expression was not associated with recurrence-free survival (P = 0.861) and overall survival (P = 0.973). In multivariate analysis, lymph node metastasis (P = 0.004) was identified as an independent risk factor for early recurrence and the presence of perineural invasion (P = 0.002) and lymph node metastasis (P < 0.001) was identified as independent risk factors for poor survival.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Bile Duct Neoplasms', 'Cholangiocarcinoma', 'Disease-Free Survival', 'Female', 'Humans', 'Immunohistochemistry', 'Male', 'Middle Aged', 'Multivariate Analysis', 'Neoplasm Invasiveness', 'Neoplasm Recurrence, Local', 'Nerve Growth Factor', 'Peripheral Nerves', 'Prognosis', 'Proportional Hazards Models', 'Retrospective Studies', 'Survival Rate']}" }, { "from": "gpt", "value": "Answer: no" } ]
26,542,767
Do novel HSP90 inhibitors effectively target functions of thyroid cancer stem cell preventing migration and invasion?
{ "contexts": [ "Thyroid cancer stem cells (CSCs) with ALDH and CD44 markers contribute to tumor growth and aggressiveness. We hypothesized that novel HSP90 inhibitors (KU711, WGA-TA) and 17-AAG can effectively target the function of thyroid CSCs in vitro and prevent migration and invasion.", "Validated papillary (TPC1), follicular (FTC238,WRO), and anaplastic (ACT1) human thyroid cancer cell lines were treated with 3 HSP90 inhibitors. CSCs were quantified for aldehyde dehydrogenase by flow cytometry, CD44 expression by Western blot, and thyrosphere formation assay. Cellular pathway proteins were analyzed by Western blot and migration/invasion by Boyden-chambers.", "WGA-TA and 17-AAG induced HSP70 compensation (not observed with KU711) on Western blot in all cell lines (>1,000 fold vs controls). Only WGA-TA degraded HSP90-Cdc37 complexing by 60-70% versus controls. Expression of HSP90 clients β-catenin, BRAF, Akt, and phospho-Akt were significantly inhibited by WGA-TA treatment (50-80%, 50-90%, >80%, and >90%) compared with controls, KU711, and 17-AAG treatment. KU711 and WGA-TA decreased CD44 expression in all cell lines (25-60% vs controls/17-AAG), decreased ALDEFLOR activity by 69-98% (P < .005), and decreased sphere formation by 64-99% (P < .05 each). Finally, cell migration was decreased by 31-98%, 100%, and 30-38%, and invasion by 75-100%, 100%, and 47% by KU711,WGA-TA, and 17-AAG treatment (P < .05) each, respectively." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Anticarcinogenic Agents", "Cell Line, Tumor", "Cell Movement", "Cell Proliferation", "HSP90 Heat-Shock Proteins", "Humans", "Neoplasm Invasiveness", "Neoplastic Stem Cells", "Thyroid Gland", "Thyroid Neoplasms" ] }
KU711 and WGA-TA are novel HSP90 inhibitors targeting CSC function and inhibiting cell migration/invasion in differentiated and anaplastic thyroid cancers, warranting further translational evaluation in vivo.
yes
[ { "from": "human", "value": "Question: Do novel HSP90 inhibitors effectively target functions of thyroid cancer stem cell preventing migration and invasion?\nContext: {'contexts': ['Thyroid cancer stem cells (CSCs) with ALDH and CD44 markers contribute to tumor growth and aggressiveness. We hypothesized that novel HSP90 inhibitors (KU711, WGA-TA) and 17-AAG can effectively target the function of thyroid CSCs in vitro and prevent migration and invasion.', 'Validated papillary (TPC1), follicular (FTC238,WRO), and anaplastic (ACT1) human thyroid cancer cell lines were treated with 3 HSP90 inhibitors. CSCs were quantified for aldehyde dehydrogenase by flow cytometry, CD44 expression by Western blot, and thyrosphere formation assay. Cellular pathway proteins were analyzed by Western blot and migration/invasion by Boyden-chambers.', 'WGA-TA and 17-AAG induced HSP70 compensation (not observed with KU711) on Western blot in all cell lines (>1,000 fold vs controls). Only WGA-TA degraded HSP90-Cdc37 complexing by 60-70% versus controls. Expression of HSP90 clients β-catenin, BRAF, Akt, and phospho-Akt were significantly inhibited by WGA-TA treatment (50-80%, 50-90%, >80%, and >90%) compared with controls, KU711, and 17-AAG treatment. KU711 and WGA-TA decreased CD44 expression in all cell lines (25-60% vs controls/17-AAG), decreased ALDEFLOR activity by 69-98% (P < .005), and decreased sphere formation by 64-99% (P < .05 each). Finally, cell migration was decreased by 31-98%, 100%, and 30-38%, and invasion by 75-100%, 100%, and 47% by KU711,WGA-TA, and 17-AAG treatment (P < .05) each, respectively.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Anticarcinogenic Agents', 'Cell Line, Tumor', 'Cell Movement', 'Cell Proliferation', 'HSP90 Heat-Shock Proteins', 'Humans', 'Neoplasm Invasiveness', 'Neoplastic Stem Cells', 'Thyroid Gland', 'Thyroid Neoplasms']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,542,686
Is late follicular progesterone to estradiol ratio influenced by protocols or gonadotropins used?
{ "contexts": [ "Increased progesterone level during follicular phase seemed to be associated with decreased pregnancy rate.", "A prospective cohort study, 1.1.2012 - 31.8.13. The Progesterone (P) and Progesterone/Estrogen (P/E2) level on ovulation induction day were compared between the protocols and the different gonadotropins used. Roc analysis was calculated to determine the cutoff of P/E2 to predict delivery rates. P/E2 ratio was calculated as PX1000/e2 level.", "One hundred thirty-nine patients were enrolled to the study. No difference in the P level at hCG stimulation day between different protocols, however, E2 and P/E2 ratio were significantly lower in the long protocol compare with antagonist protocol 1757.7 ± 923.2 vs. 1342.9 ± 1223; P = 0.003 and 0.48 ± 0.31 vs. 0.83 ± 0.87; P = 0.038). The endometrium was significantly thicker in the long group compare with short and antagonist. Significantly more top-quality embryos (TOP) were achieved in the antagonist group. Comparable results between the types of gonadotropins used in regards with cycle characteristics and pregnancy and delivery rates. The P/E2 ratio which can predict live birth rate was found to be 0.45, AUC = 0.632, p = 0.02 and 95 % CI 0.525-0.738 and a significantly higher pregnancy and delivery rates at a P/E2 bellow 0.45." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Drug Therapy, Combination", "Endometrium", "Estradiol", "Female", "Follicle Stimulating Hormone", "Follicular Phase", "Humans", "Menotropins", "Ovulation Induction", "Pregnancy", "Pregnancy Rate", "Progesterone", "Prospective Studies", "Treatment Outcome" ] }
Endometrial receptivity is determined by the complex interactions of E2 and P.
no
[ { "from": "human", "value": "Question: Is late follicular progesterone to estradiol ratio influenced by protocols or gonadotropins used?\nContext: {'contexts': ['Increased progesterone level during follicular phase seemed to be associated with decreased pregnancy rate.', 'A prospective cohort study, 1.1.2012 - 31.8.13. The Progesterone (P) and Progesterone/Estrogen (P/E2) level on ovulation induction day were compared between the protocols and the different gonadotropins used. Roc analysis was calculated to determine the cutoff of P/E2 to predict delivery rates. P/E2 ratio was calculated as PX1000/e2 level.', 'One hundred thirty-nine patients were enrolled to the study. No difference in the P level at hCG stimulation day between different protocols, however, E2 and P/E2 ratio were significantly lower in the long protocol compare with antagonist protocol 1757.7\\u2009±\\u2009923.2 vs. 1342.9\\u2009±\\u20091223; P\\u2009=\\u20090.003 and 0.48\\u2009±\\u20090.31 vs. 0.83\\u2009±\\u20090.87; P\\u2009=\\u20090.038). The endometrium was significantly thicker in the long group compare with short and antagonist. Significantly more top-quality embryos (TOP) were achieved in the antagonist group. Comparable results between the types of gonadotropins used in regards with cycle characteristics and pregnancy and delivery rates. The P/E2 ratio which can predict live birth rate was found to be 0.45, AUC\\u2009=\\u20090.632, p\\u2009=\\u20090.02 and 95\\xa0% CI 0.525-0.738 and a significantly higher pregnancy and delivery rates at a P/E2 bellow 0.45.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Drug Therapy, Combination', 'Endometrium', 'Estradiol', 'Female', 'Follicle Stimulating Hormone', 'Follicular Phase', 'Humans', 'Menotropins', 'Ovulation Induction', 'Pregnancy', 'Pregnancy Rate', 'Progesterone', 'Prospective Studies', 'Treatment Outcome']}" }, { "from": "gpt", "value": "Answer: no" } ]
26,525,229
Does airway factor XIII associate with type 2 inflammation and airway obstruction in asthmatic patients?
{ "contexts": [ "Coagulation Factor XIII (FXIII) plays an important role in wound healing by stabilizing fibrin clots and cross-linking extracellular matrix proteins. FXIII is expressed in cells of the monocyte/macrophage and dendritic cell lineages in response to type 2 cytokines.", "We sought to determine the association between FXIII and asthma pathobiology.", "We analyzed the expression of FXIII mRNA and protein levels in bronchoalveolar lavage samples obtained before and after segmental allergen challenge from patients with mild asthma and in induced sputum samples collected from patients with mild-to-moderate and severe asthma.", "FXIII mRNA and protein levels were highly upregulated in bronchoalveolar cells and fluid after allergen challenge and mRNA levels correlated with protein levels. In sputum of asthmatic patients, FXIII expression was positively correlated with type 2 immune response and dendritic cell markers (CD209 and CD207). FXIII expression was also associated with increased airflow limitation (FEV1/forced vital capacity and residual volume/total lung capacity ratios) and greater reversibility to β-agonists." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Airway Obstruction", "Asthma", "Biomarkers", "Bronchial Provocation Tests", "Bronchoalveolar Lavage Fluid", "Dendritic Cells", "Factor XIII", "Female", "Gene Expression", "Humans", "Immunoglobulin E", "Male", "Middle Aged", "RNA, Messenger", "Respiratory Function Tests", "Severity of Illness Index", "Skin Tests", "Young Adult" ] }
FXIII expression was upregulated in the airways of asthmatic patients after allergen exposure. Expression in the sputum of asthmatic patients correlated with the type 2 immune response and airflow limitation. Excessive activity of FXIII could contribute to the pathophysiology of airway obstruction in asthmatic patients.
yes
[ { "from": "human", "value": "Question: Does airway factor XIII associate with type 2 inflammation and airway obstruction in asthmatic patients?\nContext: {'contexts': ['Coagulation Factor XIII (FXIII) plays an important role in wound healing by stabilizing fibrin clots and cross-linking extracellular matrix proteins. FXIII is expressed in cells of the monocyte/macrophage and dendritic cell lineages in response to type 2 cytokines.', 'We sought to determine the association between FXIII and asthma pathobiology.', 'We analyzed the expression of FXIII mRNA and protein levels in bronchoalveolar lavage samples obtained before and after segmental allergen challenge from patients with mild asthma and in induced sputum samples collected from patients with mild-to-moderate and severe asthma.', 'FXIII mRNA and protein levels were highly upregulated in bronchoalveolar cells and fluid after allergen challenge and mRNA levels correlated with protein levels. In sputum of asthmatic patients, FXIII expression was positively correlated with type 2 immune response and dendritic cell markers (CD209 and CD207). FXIII expression was also associated with increased airflow limitation (FEV1/forced vital capacity and residual volume/total lung capacity ratios) and greater reversibility to β-agonists.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Airway Obstruction', 'Asthma', 'Biomarkers', 'Bronchial Provocation Tests', 'Bronchoalveolar Lavage Fluid', 'Dendritic Cells', 'Factor XIII', 'Female', 'Gene Expression', 'Humans', 'Immunoglobulin E', 'Male', 'Middle Aged', 'RNA, Messenger', 'Respiratory Function Tests', 'Severity of Illness Index', 'Skin Tests', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,530,191
Does [ Nicotinic acid increase cellular transport of high density lipoprotein cholesterol in patients with hypoalphalipoproteinemia ]?
{ "contexts": [ "Plasma high density lipoproteins (HDL) are involved in reverse cholesterol transport mediated by the scavenger receptor class B type I (SR-BI). Nicotinic acid increases HDL cholesterol levels, even though its specific impact on SR-BI dependent-cellular cholesterol transport remains unknown.", "To determine the effect of nicotinic acid on HDL particle functionality in cholesterol efflux and uptake mediated by SR-BI in cultured cells in hypoalphalipoproteinemic patients.", "In a pilot study, eight patients with low HDL (≤ 40 mg/dL) were treated with extended release nicotinic acid. HDL cholesterol and phospholipid levels, HDL2 and HDL3 fractions and HDL particle sizes were measured at baseline and post-therapy. Before and after nicotinic acid treatment, HDL particles were used for cholesterol transport studies in cells transfected with SR-BI.", "Nicotinic acid treatment raised total HDL cholesterol and phospholipids, HDL2 levels as well as HDL particle size. Nicotinic acid significantly increased HDL cholesterol efflux and uptake capacity mediated by SR-BI in cultured cells." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Biological Transport", "Cholesterol, HDL", "Female", "Humans", "Hypoalphalipoproteinemias", "Hypolipidemic Agents", "Lipoproteins, HDL", "Male", "Middle Aged", "Niacin", "Phospholipids", "Pilot Projects", "Scavenger Receptors, Class B" ] }
Nicotinic acid therapy increases SR-BI-dependent HDL cholesterol transport in cultured cells, establishing a new cellular mechanism by which this lipid-lowering drug appears to modulate HDL metabolism in patients with hypoalphalipoproteinemia.
yes
[ { "from": "human", "value": "Question: Does [ Nicotinic acid increase cellular transport of high density lipoprotein cholesterol in patients with hypoalphalipoproteinemia ]?\nContext: {'contexts': ['Plasma high density lipoproteins (HDL) are involved in reverse cholesterol transport mediated by the scavenger receptor class B type I (SR-BI). Nicotinic acid increases HDL cholesterol levels, even though its specific impact on SR-BI dependent-cellular cholesterol transport remains unknown.', 'To determine the effect of nicotinic acid on HDL particle functionality in cholesterol efflux and uptake mediated by SR-BI in cultured cells in hypoalphalipoproteinemic patients.', 'In a pilot study, eight patients with low HDL (≤ 40 mg/dL) were treated with extended release nicotinic acid. HDL cholesterol and phospholipid levels, HDL2 and HDL3 fractions and HDL particle sizes were measured at baseline and post-therapy. Before and after nicotinic acid treatment, HDL particles were used for cholesterol transport studies in cells transfected with SR-BI.', 'Nicotinic acid treatment raised total HDL cholesterol and phospholipids, HDL2 levels as well as HDL particle size. Nicotinic acid significantly increased HDL cholesterol efflux and uptake capacity mediated by SR-BI in cultured cells.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Biological Transport', 'Cholesterol, HDL', 'Female', 'Humans', 'Hypoalphalipoproteinemias', 'Hypolipidemic Agents', 'Lipoproteins, HDL', 'Male', 'Middle Aged', 'Niacin', 'Phospholipids', 'Pilot Projects', 'Scavenger Receptors, Class B']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,541,592
Does mother 's Self-Efficacy mediate the Relationship Between Household Food Insecurity and Maternal Infant Feeding Styles?
{ "contexts": [ "This study was performed to examine the association between household food insecurity, self-efficacy and infant feeding styles in mothers with children under 2 years old in Varamin, Iran.", "In this cross-sectional study, 423 mothers aged 17-40 years from different areas of Varamin were selected by a multistage sampling methods from October 2013 to February 2014. The questionnaires consisted of three valid instruments, including: Household Food Insecurity Access Scale, Comprehensive Feeding Practices Questionnaire and Mother's Self-Efficacy Questionnaire. Data were analyzed using Chi-square, t tests, ANOVA, Pearson correlations and multiple linear regressions. Structural equation modeling was also used.", "Mild and moderate-severe food insecurity was observed in 39.5 and 12.8 % of the households respectively. Mean score of mother's self-efficacy in food secure households was 32.5 ± 3.7; while in mild food insecure and moderate-severe food insecure households were 31.9 ± 3.1 and 28.4 ± 4.0, respectively (P = 0.001). There was a significant negative correlation between household food insecurity and mother's self-efficacy (r = -0.297, P < 0.01). Significant correlation was seen between mother's self-efficacy and the maternal infant feeding styles. Household food insecurity and mother's self-efficacy had significant relationship with mother-infant feeding styles: control of home food access [β (SE)] = [-0.015(0.004), P = 0.001]; restriction for weight control [β = 0.038(0.013), P = 0.003]; restriction for health [β = 0.019(0.008), P = 0.027] and encouragement [=0.018(0.006), P = 0.001]. The model had sufficient fitness with data of the research (CFI = 0.927, RMSEA = 0.076)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Cross-Sectional Studies", "Family Characteristics", "Feeding Behavior", "Female", "Food Supply", "Humans", "Infant", "Iran", "Male", "Maternal Behavior", "Mothers", "Nutritional Status", "Parent-Child Relations", "Self Efficacy", "Socioeconomic Factors", "Surveys and Questionnaires", "Young Adult" ] }
Our findings suggest that performing interventions in order to enhance mother's self-efficacy in food insecure households can lead to improve positive maternal feeding behaviors.
yes
[ { "from": "human", "value": "Question: Does mother 's Self-Efficacy mediate the Relationship Between Household Food Insecurity and Maternal Infant Feeding Styles?\nContext: {'contexts': ['This study was performed to examine the association between household food insecurity, self-efficacy and infant feeding styles in mothers with children under 2 years old in Varamin, Iran.', \"In this cross-sectional study, 423 mothers aged 17-40 years from different areas of Varamin were selected by a multistage sampling methods from October 2013 to February 2014. The questionnaires consisted of three valid instruments, including: Household Food Insecurity Access Scale, Comprehensive Feeding Practices Questionnaire and Mother's Self-Efficacy Questionnaire. Data were analyzed using Chi-square, t tests, ANOVA, Pearson correlations and multiple linear regressions. Structural equation modeling was also used.\", \"Mild and moderate-severe food insecurity was observed in 39.5 and 12.8 % of the households respectively. Mean score of mother's self-efficacy in food secure households was 32.5 ± 3.7; while in mild food insecure and moderate-severe food insecure households were 31.9 ± 3.1 and 28.4 ± 4.0, respectively (P = 0.001). There was a significant negative correlation between household food insecurity and mother's self-efficacy (r = -0.297, P < 0.01). Significant correlation was seen between mother's self-efficacy and the maternal infant feeding styles. Household food insecurity and mother's self-efficacy had significant relationship with mother-infant feeding styles: control of home food access [β (SE)] = [-0.015(0.004), P = 0.001]; restriction for weight control [β = 0.038(0.013), P = 0.003]; restriction for health [β = 0.019(0.008), P = 0.027] and encouragement [=0.018(0.006), P = 0.001]. The model had sufficient fitness with data of the research (CFI = 0.927, RMSEA = 0.076).\"], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Cross-Sectional Studies', 'Family Characteristics', 'Feeding Behavior', 'Female', 'Food Supply', 'Humans', 'Infant', 'Iran', 'Male', 'Maternal Behavior', 'Mothers', 'Nutritional Status', 'Parent-Child Relations', 'Self Efficacy', 'Socioeconomic Factors', 'Surveys and Questionnaires', 'Young Adult']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,535,066
Does high Expression of FGFR4 enhance Tumor Growth and Metastasis in Nasopharyngeal Carcinoma?
{ "contexts": [ "FGF receptor (FGFR) family can be activated by FGFs and play important roles in regulating cell growth, differentiation, migration and angiogenesis. Recent studies suggested that FGFR4 could regulate several processes including tumor progression. Nasopharyngeal carcinoma (NPC) is a malignancy with a high occurrence in Southeast Asia and Southern China. However, the molecule mechanism and the potential roles of FGFR4 in NPC remain unknown Methods: Immunohistochemistry and western blot were used to investigate the expression of FGFR4 in NPC samples. Then we used statistical analysis to evaluate the diagnostic value and the associations of FGFR4 expression with clinical parameters. In vitro studies, the effects of FGFR4 on proliferation and migration of NPC cell line CNE2 were measured by the starvation-refeeding experiment, CCK8 assay, wounding healing assay and transwell migration assay. The changes of the epithelial-mesenchymal transition (EMT) markers in CNE2 cells after knocking down the expression of FGFR4 were measured by Western blot and immunofluorescence analysis.", "FGFR4 was overexpressed in NPC as compared with the inflammatory tissues. High expression of FGFR4 was correlated with Ki67 expression, clinical stages and prognosis in NPC patients (P<0.05).While in vitro, the upregulation of FGFR4 was accompanied with CNE2 cells released from serum starvation. Moreover, it could increase cell proliferation and migration by regulating EMT markers in CNE2 cells." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [] }
Our data suggested that FGFR4 might induce NPC progression and act as a potential therapeutic target in NPC.
yes
[ { "from": "human", "value": "Question: Does high Expression of FGFR4 enhance Tumor Growth and Metastasis in Nasopharyngeal Carcinoma?\nContext: {'contexts': ['FGF receptor (FGFR) family can be activated by FGFs and play important roles in regulating cell growth, differentiation, migration and angiogenesis. Recent studies suggested that FGFR4 could regulate several processes including tumor progression. Nasopharyngeal carcinoma (NPC) is a malignancy with a high occurrence in Southeast Asia and Southern China. However, the molecule mechanism and the potential roles of FGFR4 in NPC remain unknown Methods: Immunohistochemistry and western blot were used to investigate the expression of FGFR4 in NPC samples. Then we used statistical analysis to evaluate the diagnostic value and the associations of FGFR4 expression with clinical parameters. In vitro studies, the effects of FGFR4 on proliferation and migration of NPC cell line CNE2 were measured by the starvation-refeeding experiment, CCK8 assay, wounding healing assay and transwell migration assay. The changes of the epithelial-mesenchymal transition (EMT) markers in CNE2 cells after knocking down the expression of FGFR4 were measured by Western blot and immunofluorescence analysis.', 'FGFR4 was overexpressed in NPC as compared with the inflammatory tissues. High expression of FGFR4 was correlated with Ki67 expression, clinical stages and prognosis in NPC patients (P<0.05).While in vitro, the upregulation of FGFR4 was accompanied with CNE2 cells released from serum starvation. Moreover, it could increase cell proliferation and migration by regulating EMT markers in CNE2 cells.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,535,063
Is the Expression of CD9 and PIK3CD Associated with Prognosis of Follicular Lymphoma?
{ "contexts": [ "Follicular lymphoma (FL) frequently develops drug-resistance and transforms into more aggressive subtypes over time. It is urgent to find prognostic biomarkers and disclose signaling pathways that have potential to be drug targets. In this study, we investigated the association of FL prognosis with the expression of 2 proteins: PIK3CD, a PI3K pathway component, and CD9, a tetraspanin family member.", "The expression of PIK3CD and CD9 were examined on 76 FL tumor tissues and 15 normal tissues with Immunohistochemistry. Chi-square test, Cox proportional hazards model, and Kaplan-Meier estimates were used to analyze the relationships of CD9 and PIK3CD expression and major clinicopathological features.", "PIK3CD expression was significantly higher, whereas CD9 expression was significantly lower in the 76 FL specimens than normal tissues. Concomitantly, low CD9 or high PIK3CD expression is associated with high degrees of Ann Arbor stages. In agreement with this, PIK3CD is an unfavorable and CD9 is a favorable factor for progression-free survival (PFS). Interestingly, PIK3CD expression is negatively correlated with CD9 expression, and the PIK3CD-high/CD9-low was significantly associated with short PFS when the 2 factors were combined together. Lastly, CD9 expression was significant higher in patients with bone marrow infiltration (BMI) than those without BMI." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
Both CD9 and PIK3CD are prognostic markers of FL. The negative correlation between CD9 and PIK3CD expression suggests that there may be crosstalks of the 2 proteins in FL.
yes
[ { "from": "human", "value": "Question: Is the Expression of CD9 and PIK3CD Associated with Prognosis of Follicular Lymphoma?\nContext: {'contexts': ['Follicular lymphoma (FL) frequently develops drug-resistance and transforms into more aggressive subtypes over time. It is urgent to find prognostic biomarkers and disclose signaling pathways that have potential to be drug targets. In this study, we investigated the association of FL prognosis with the expression of 2 proteins: PIK3CD, a PI3K pathway component, and CD9, a tetraspanin family member.', 'The expression of PIK3CD and CD9 were examined on 76 FL tumor tissues and 15 normal tissues with Immunohistochemistry. Chi-square test, Cox proportional hazards model, and Kaplan-Meier estimates were used to analyze the relationships of CD9 and PIK3CD expression and major clinicopathological features.', 'PIK3CD expression was significantly higher, whereas CD9 expression was significantly lower in the 76 FL specimens than normal tissues. Concomitantly, low CD9 or high PIK3CD expression is associated with high degrees of Ann Arbor stages. In agreement with this, PIK3CD is an unfavorable and CD9 is a favorable factor for progression-free survival (PFS). Interestingly, PIK3CD expression is negatively correlated with CD9 expression, and the PIK3CD-high/CD9-low was significantly associated with short PFS when the 2 factors were combined together. Lastly, CD9 expression was significant higher in patients with bone marrow infiltration (BMI) than those without BMI.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,546,591
Does treating hypertension in hemodialysis improve symptoms seemingly unrelated to volume excess?
{ "contexts": [ "Among hemodialysis patients, probing dry weight is an effective strategy for improving control of hypertension. Whether controlling hypertension improves or worsens symptoms among such patients remains unclear. The purpose of the study was to develop a tool to evaluate symptoms and examine the relationship of the change in these symptoms with blood pressure (BP) control.", "Among patients participating in the Hemodialysis Patients Treated with Atenolol or Lisinopril (HDPAL) randomized controlled trial, a confirmatory factor analysis (CFA) was performed to establish the relationship between symptoms and organ systems. Next, the change in symptom scores pertaining to organ systems was analyzed using a mixed model. Finally, the independent effect of lowering home BP on change in symptoms was evaluated.", "Among 133 participants where symptoms were available at baseline, CFA revealed four level 1 domains: gastrointestinal symptoms, dialysis-related symptoms, cardiovascular symptoms and general symptoms. All except dialysis-related symptoms were ascribed to uremia (level 2 domain). Uremic symptoms improved over 6 months and then increased. Dialysis-related symptoms (fatigue, cramps and orthostatic dizziness) did not worsen despite lowering home BP. Probing dry weight was independently associated with an improvement in cardiovascular symptoms such as shortness of breath." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Antihypertensive Agents", "Atenolol", "Blood Pressure", "Blood Volume", "Body Weight", "Female", "Humans", "Hypertension", "Kidney Failure, Chronic", "Lisinopril", "Male", "Middle Aged", "Renal Dialysis", "Treatment Outcome" ] }
Reducing BP through the use of a strategy that includes volume control and medication improves symptoms seemingly unrelated to volume excess. In long-term hemodialysis patients, treating hypertension using home BP measurements may improve well-being.
yes
[ { "from": "human", "value": "Question: Does treating hypertension in hemodialysis improve symptoms seemingly unrelated to volume excess?\nContext: {'contexts': ['Among hemodialysis patients, probing dry weight is an effective strategy for improving control of hypertension. Whether controlling hypertension improves or worsens symptoms among such patients remains unclear. The purpose of the study was to develop a tool to evaluate symptoms and examine the relationship of the change in these symptoms with blood pressure (BP) control.', 'Among patients participating in the Hemodialysis Patients Treated with Atenolol or Lisinopril (HDPAL) randomized controlled trial, a confirmatory factor analysis (CFA) was performed to establish the relationship between symptoms and organ systems. Next, the change in symptom scores pertaining to organ systems was analyzed using a mixed model. Finally, the independent effect of lowering home BP on change in symptoms was evaluated.', 'Among 133 participants where symptoms were available at baseline, CFA revealed four level 1 domains: gastrointestinal symptoms, dialysis-related symptoms, cardiovascular symptoms and general symptoms. All except dialysis-related symptoms were ascribed to uremia (level 2 domain). Uremic symptoms improved over 6 months and then increased. Dialysis-related symptoms (fatigue, cramps and orthostatic dizziness) did not worsen despite lowering home BP. Probing dry weight was independently associated with an improvement in cardiovascular symptoms such as shortness of breath.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Antihypertensive Agents', 'Atenolol', 'Blood Pressure', 'Blood Volume', 'Body Weight', 'Female', 'Humans', 'Hypertension', 'Kidney Failure, Chronic', 'Lisinopril', 'Male', 'Middle Aged', 'Renal Dialysis', 'Treatment Outcome']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,546,590
Does micro-RNA analysis of renal biopsies in human lupus nephritis demonstrate up-regulated miR-422a driving reduction of kallikrein-related peptidase 4?
{ "contexts": [ "Aberrancies in gene expression in immune effector cells and in end-organs are implicated in lupus pathogenesis. To gain insights into the mechanisms of tissue injury, we profiled the expression of micro-RNAs in inflammatory kidney lesions of human lupus nephritis (LN).", "Kidney specimens were from patients with active proliferative, membranous or mixed LN and unaffected control tissue. Micro-RNAs were quantified by TaqMan Low Density Arrays. Bioinformatics was employed to predict gene targets, gene networks and perturbed signaling pathways. Results were validated by transfection studies (luciferase assay, real-time PCR) and in murine LN. Protein expression was determined by immunoblotting and immunohistochemistry.", "Twenty-four micro-RNAs were dysregulated (9 up-regulated, 15 down-regulated) in human LN compared with control renal tissue. Their predicted gene targets participated in pathways associated with TGF-β, kinases, NF-κB, HNF4A, Wnt/β-catenin, STAT3 and IL-4. miR-422a showed the highest upregulation (17-fold) in active LN and correlated with fibrinoid necrosis lesions (β = 0.63, P = 0.002). In transfection studies, miR-422a was found to directly target kallikrein-related peptidase 4 (KLK4) mRNA. Concordantly, KLK4 mRNA was significantly reduced in the kidneys of human and murine LN and correlated inversely with miR-422a levels. Immunohistochemistry confirmed reduced KLK4 protein expression in renal mesangial and tubular epithelial cells in human and murine LN." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Biopsy", "Case-Control Studies", "Gene Expression Profiling", "Gene Expression Regulation", "Humans", "Kallikreins", "Kidney", "Lupus Nephritis", "Mice", "MicroRNAs", "Signal Transduction", "Up-Regulation" ] }
KLK4, a serine esterase with putative renoprotective properties, is down-regulated by miR-422a in LN kidney suggesting that, in addition to immune activation, local factors may be implicated in the disease.
yes
[ { "from": "human", "value": "Question: Does micro-RNA analysis of renal biopsies in human lupus nephritis demonstrate up-regulated miR-422a driving reduction of kallikrein-related peptidase 4?\nContext: {'contexts': ['Aberrancies in gene expression in immune effector cells and in end-organs are implicated in lupus pathogenesis. To gain insights into the mechanisms of tissue injury, we profiled the expression of micro-RNAs in inflammatory kidney lesions of human lupus nephritis (LN).', 'Kidney specimens were from patients with active proliferative, membranous or mixed LN and unaffected control tissue. Micro-RNAs were quantified by TaqMan Low Density Arrays. Bioinformatics was employed to predict gene targets, gene networks and perturbed signaling pathways. Results were validated by transfection studies (luciferase assay, real-time PCR) and in murine LN. Protein expression was determined by immunoblotting and immunohistochemistry.', 'Twenty-four micro-RNAs were dysregulated (9 up-regulated, 15 down-regulated) in human LN compared with control renal tissue. Their predicted gene targets participated in pathways associated with TGF-β, kinases, NF-κB, HNF4A, Wnt/β-catenin, STAT3 and IL-4. miR-422a showed the highest upregulation (17-fold) in active LN and correlated with fibrinoid necrosis lesions (β = 0.63, P = 0.002). In transfection studies, miR-422a was found to directly target kallikrein-related peptidase 4 (KLK4) mRNA. Concordantly, KLK4 mRNA was significantly reduced in the kidneys of human and murine LN and correlated inversely with miR-422a levels. Immunohistochemistry confirmed reduced KLK4 protein expression in renal mesangial and tubular epithelial cells in human and murine LN.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Biopsy', 'Case-Control Studies', 'Gene Expression Profiling', 'Gene Expression Regulation', 'Humans', 'Kallikreins', 'Kidney', 'Lupus Nephritis', 'Mice', 'MicroRNAs', 'Signal Transduction', 'Up-Regulation']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,530,544
Is the Porphyromonas gingivalis O antigen required for inhibition of apoptosis in gingival epithelial cells following bacterial infection?
{ "contexts": [ "Porphyromonas gingivalis infection induces apoptosis inhibition in gingival epithelial cells; however, it is not fully understood which bacterial effectors are involved in this process. The aim of this study is to evaluate whether the P. gingivalis lipopolysaccharide (LPS), specifically the O-antigen region, affects adherence, invasion, viability and apoptosis of gingival epithelial cells.", "Gingival epithelial cells (OKF6/TERT2 line) were infected by different freshly prepared P. gingivalis clinical isolates, obtained from subjects with chronic periodontitis (CP3 and CP4) and healthy individuals (H1 and H3). Periodontitis and healthy isolates show differences in O-antigen production, as healthy isolates lack the O-antigen region. In addition, cells were infected by a site-specific mutant lacking the O-antigen portion. After 24 h postinfection, cell proliferation, viability and apoptosis were evaluated by Trypan blue, MTS and annexin V assays, respectively. Bacterial invasion, adhesion and proliferation were measured by gentamicin/metronidazole protection assays. Finally, toll-like receptor (TLR)2 and TLR4 mRNA expression was evaluated by quantitative reverse transcription-polymerase chain reaction. Statistical analysis was performed using ANOVA, Tukey's or Dunnett's tests (p < 0.05).", "At 24 h postinfection, strains lacking the O-antigen region (healthy isolates and O-antigen ligase-deficient strain) were unable to increase proliferation and viability, or decrease apoptosis as compared with strains producing intact LPS (periodontitis isolates and reference strain). However, the presence of the O-antigen neither contributed to changes in the ability of the bacteria to adhere to or invade cells, nor to intracellular survival. The presence of O-antigen also increased the expression of TLR4 (nearly sixfold), which correlated with inhibition of apoptosis." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Apoptosis", "Bacterial Infections", "Cells, Cultured", "Epithelial Cells", "Gene Expression", "Gingiva", "Humans", "Lipopolysaccharides", "O Antigens", "Periodontitis", "Porphyromonas gingivalis", "RNA, Messenger", "Toll-Like Receptor 2", "Toll-Like Receptor 4" ] }
The O-antigen region of P. gingivalis LPS is required to increase gingival epithelial cell viability upon infection by bacteria and this increase is attributable to a reduction in apoptosis. Moreover, although bacterial internalization is required, the effects observed are not due to alterations in P. gingivalis adherence, invasion or intracellular survival. Interestingly, inhibition of apoptosis correlates with increased TLR4 expression, suggesting a role for TLR4 in this process.
yes
[ { "from": "human", "value": "Question: Is the Porphyromonas gingivalis O antigen required for inhibition of apoptosis in gingival epithelial cells following bacterial infection?\nContext: {'contexts': ['Porphyromonas gingivalis infection induces apoptosis inhibition in gingival epithelial cells; however, it is not fully understood which bacterial effectors are involved in this process. The aim of this study is to evaluate whether the P.\\xa0gingivalis lipopolysaccharide (LPS), specifically the O-antigen region, affects adherence, invasion, viability and apoptosis of gingival epithelial cells.', \"Gingival epithelial cells (OKF6/TERT2 line) were infected by different freshly prepared P.\\xa0gingivalis clinical isolates, obtained from subjects with chronic periodontitis (CP3 and CP4) and healthy individuals (H1 and H3). Periodontitis and healthy isolates show differences in O-antigen production, as healthy isolates lack the O-antigen region. In addition, cells were infected by a site-specific mutant lacking the O-antigen portion. After 24\\xa0h postinfection, cell proliferation, viability and apoptosis were evaluated by Trypan blue, MTS and annexin V assays, respectively. Bacterial invasion, adhesion and proliferation were measured by gentamicin/metronidazole protection assays. Finally, toll-like receptor (TLR)2 and TLR4 mRNA expression was evaluated by quantitative reverse transcription-polymerase chain reaction. Statistical analysis was performed using ANOVA, Tukey's or Dunnett's tests (p\\xa0<\\xa00.05).\", 'At 24\\xa0h postinfection, strains lacking the O-antigen region (healthy isolates and O-antigen ligase-deficient strain) were unable to increase proliferation and viability, or decrease apoptosis as compared with strains producing intact LPS (periodontitis isolates and reference strain). However, the presence of the O-antigen neither contributed to changes in the ability of the bacteria to adhere to or invade cells, nor to intracellular survival. The presence of O-antigen also increased the expression of TLR4 (nearly sixfold), which correlated with inhibition of apoptosis.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Apoptosis', 'Bacterial Infections', 'Cells, Cultured', 'Epithelial Cells', 'Gene Expression', 'Gingiva', 'Humans', 'Lipopolysaccharides', 'O Antigens', 'Periodontitis', 'Porphyromonas gingivalis', 'RNA, Messenger', 'Toll-Like Receptor 2', 'Toll-Like Receptor 4']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,550,028
Is stress-induced cortisol associated with generation of non-negative interpretations during cognitive reappraisal?
{ "contexts": [ "Enhanced processing of emotional stimuli after stress exposure is reported to be associated with stress-induced cortisol. Because enhanced emotional information processing could make cognitive emotion regulation more difficult, it was hypothesized that stress-induced cortisol would be associated with non-negative interpretation generation associated with the cognitive reappraisal processes.", "A total of 36 participants (Mean age = 21.3 years, SD = 1.8) watched video clips of depression-related stressful situations before and after the administration of a stress induction task. They were then asked to generate as many non-negative interpretations as possible to reduce the depressive mood. Saliva samples were obtained before and after the stress induction task to measure change in the cortisol level.", "Participants were allocated post-hoc to either a responder (n = 19) or non-responder group (n = 17) based on the cortisol response to the stress induction task. The number of non-negative interpretations generated following the stress induction task was reduced only in the cortisol responders. The number of post-stress non-negative interpretations was fewer in the responder group when compared by sex, baseline cortisol level, and the number of pre-stress non-negative interpretations, statistically controlled." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
Although baseline cortisol and sex may have impacted the results, the results suggest that stress-induced cortisol is associated with difficulty in non-negative interpretation generation during the cognitive reappraisal process.
yes
[ { "from": "human", "value": "Question: Is stress-induced cortisol associated with generation of non-negative interpretations during cognitive reappraisal?\nContext: {'contexts': ['Enhanced processing of emotional stimuli after stress exposure is reported to be associated with stress-induced cortisol. Because enhanced emotional information processing could make cognitive emotion regulation more difficult, it was hypothesized that stress-induced cortisol would be associated with non-negative interpretation generation associated with the cognitive reappraisal processes.', 'A total of 36 participants (Mean age\\u2009=\\u200921.3\\xa0years, SD\\u2009=\\u20091.8) watched video clips of depression-related stressful situations before and after the administration of a stress induction task. They were then asked to generate as many non-negative interpretations as possible to reduce the depressive mood. Saliva samples were obtained before and after the stress induction task to measure change in the cortisol level.', 'Participants were allocated post-hoc to either a responder (n\\u2009=\\u200919) or non-responder group (n\\u2009=\\u200917) based on the cortisol response to the stress induction task. The number of non-negative interpretations generated following the stress induction task was reduced only in the cortisol responders. The number of post-stress non-negative interpretations was fewer in the responder group when compared by sex, baseline cortisol level, and the number of pre-stress non-negative interpretations, statistically controlled.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,547,549
Are the importance of the belief that `` light '' cigarettes smoother in misperceptions of the harmfulness of `` light '' cigarettes in the Republic of Korea : a nationally representative cohort study?
{ "contexts": [ "A number of countries have banned misleading cigarette descriptors such as \"light\" and \"low-tar\" as called for by the WHO Framework Convention on Tobacco Control. These laws, however, do not address the underlying cigarette design elements that contribute to misperceptions about harm. This is the first study to examine beliefs about \"light\" cigarettes among Korean smokers, and the first to identify factors related to cigarette design that are associated with the belief that \"light\" cigarettes are less harmful.", "We analysed data from Wave 3 of the ITC Korea Survey, a telephone survey of a nationally representative sample of 1,753 adult smokers, conducted October - December 2010. A multinomial logistic regression was used to examine which factors were associated with the belief that \"light\" cigarettes are less harmful than regular cigarettes.", "One quarter (25.0 %) of smokers believed that \"light\" cigarettes are less harmful than regular cigarettes, 25.8 % believed that smokers of \"light\" brands take in less tar, and 15.5 % held both of these beliefs. By far the strongest predictor of the erroneous belief that \"light\" cigarettes are less harmful was the belief that \"light\" cigarettes are smoother on the throat and chest (p < 0.001, OR = 44.8, 95 % CI 23.6-84.9)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adult", "Cohort Studies", "Female", "Humans", "Logistic Models", "Male", "Middle Aged", "Perception", "Product Labeling", "Republic of Korea", "Smoking", "Surveys and Questionnaires", "Tobacco", "Tobacco Products" ] }
The strong association between the belief that "light" cigarettes are smoother on the throat and chest and the belief that "light" cigarettes are less harmful, which is consistent with previous research, provides further evidence of the need to not only ban "light" descriptors, but also prohibit cigarette design and packaging features that contribute to the perception of smoothness.
yes
[ { "from": "human", "value": "Question: Are the importance of the belief that `` light '' cigarettes smoother in misperceptions of the harmfulness of `` light '' cigarettes in the Republic of Korea : a nationally representative cohort study?\nContext: {'contexts': ['A number of countries have banned misleading cigarette descriptors such as \"light\" and \"low-tar\" as called for by the WHO Framework Convention on Tobacco Control. These laws, however, do not address the underlying cigarette design elements that contribute to misperceptions about harm. This is the first study to examine beliefs about \"light\" cigarettes among Korean smokers, and the first to identify factors related to cigarette design that are associated with the belief that \"light\" cigarettes are less harmful.', 'We analysed data from Wave 3 of the ITC Korea Survey, a telephone survey of a nationally representative sample of 1,753 adult smokers, conducted October - December 2010. A multinomial logistic regression was used to examine which factors were associated with the belief that \"light\" cigarettes are less harmful than regular cigarettes.', 'One quarter (25.0 %) of smokers believed that \"light\" cigarettes are less harmful than regular cigarettes, 25.8 % believed that smokers of \"light\" brands take in less tar, and 15.5 % held both of these beliefs. By far the strongest predictor of the erroneous belief that \"light\" cigarettes are less harmful was the belief that \"light\" cigarettes are smoother on the throat and chest (p\\u2009<\\u20090.001, OR\\u2009=\\u200944.8, 95 % CI 23.6-84.9).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Cohort Studies', 'Female', 'Humans', 'Logistic Models', 'Male', 'Middle Aged', 'Perception', 'Product Labeling', 'Republic of Korea', 'Smoking', 'Surveys and Questionnaires', 'Tobacco', 'Tobacco Products']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,535,588
Are drug Transporter Genetic Variants Associated with TDF-Related Renal Dysfunction in Patients with HIV-1 Infection : A Pharmacogenetic Study?
{ "contexts": [ "To investigate whether single nucleotide polymorphisms (SNP) of drug transporter proteins for TDF is a risk factor for TDF-related renal function decrement.", "This study investigated the association between 3 SNPs (ABCC2-24, 1249, and ABCB1 2677), which are shown to be associated with TDF-induced tubulopathy, and clinically important renal outcomes (>10ml/min/1.73m2 decrement in eGFR relative to baseline, >25% decrement in eGFR, and eGFR <60ml/min/1.73m2) in 703 HIV-1-infected Japanese patients who initiated TDF-containing antiretroviral therapy (ART). Genotyping was performed by allelic discrimination using TaqMan 5'-nuclease assays.", "95% of the study patients were males and 66% were treatment-naïve, with median CD4 count of 249/μl, median baseline eGFR of 96ml/min/1.73m2 (IQR 84.6-109.2), and median exposure to TDF of 3.66 years (IQR 1.93-5.59). The frequencies of genotypes at -24, 1249 of ABCC2, and 2677 of ABCB1 were neither different between patients with decrement in eGFR of >10ml/min/1.73m2 and those without such decrement (ABCC2: -24, p = 0.53, 1249, p = 0.68; ABCB1: 2677, p = 0.74), nor between those without and with the other two renal outcomes (>25% decrement: ABCC2: -24, p = 0.83, 1249, p = 0.97, ABCB1: 2677, p = 0.40; eGFR <60ml/min/1.73m2: ABCC2: -24, p = 0.51, 1249, p = 0.81, ABCB1: 2677, p = 0.94). Logistic regression analysis showed that the risk genotype of the three SNPs were not associated with any of the three renal outcomes, respectively. Logistic regression model that applied either dominant, recessive, or additive model yielded the same results." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "ATP Binding Cassette Transporter, Subfamily B", "Adult", "Anti-HIV Agents", "Female", "Genetic Variation", "Genotype", "Glomerular Filtration Rate", "HIV Infections", "HIV-1", "Humans", "Kidney Diseases", "Logistic Models", "Male", "Multidrug Resistance-Associated Proteins", "Pharmacogenetics", "Polymorphism, Single Nucleotide", "Tenofovir" ] }
SNPs of the drug transporters for TDF are not associated with clinically important renal outcomes in patients who initiated TDF-containing ART.
no
[ { "from": "human", "value": "Question: Are drug Transporter Genetic Variants Associated with TDF-Related Renal Dysfunction in Patients with HIV-1 Infection : A Pharmacogenetic Study?\nContext: {'contexts': ['To investigate whether single nucleotide polymorphisms (SNP) of drug transporter proteins for TDF is a risk factor for TDF-related renal function decrement.', \"This study investigated the association between 3 SNPs (ABCC2-24, 1249, and ABCB1 2677), which are shown to be associated with TDF-induced tubulopathy, and clinically important renal outcomes (>10ml/min/1.73m2 decrement in eGFR relative to baseline, >25% decrement in eGFR, and eGFR <60ml/min/1.73m2) in 703 HIV-1-infected Japanese patients who initiated TDF-containing antiretroviral therapy (ART). Genotyping was performed by allelic discrimination using TaqMan 5'-nuclease assays.\", '95% of the study patients were males and 66% were treatment-naïve, with median CD4 count of 249/μl, median baseline eGFR of 96ml/min/1.73m2 (IQR 84.6-109.2), and median exposure to TDF of 3.66 years (IQR 1.93-5.59). The frequencies of genotypes at -24, 1249 of ABCC2, and 2677 of ABCB1 were neither different between patients with decrement in eGFR of >10ml/min/1.73m2 and those without such decrement (ABCC2: -24, p = 0.53, 1249, p = 0.68; ABCB1: 2677, p = 0.74), nor between those without and with the other two renal outcomes (>25% decrement: ABCC2: -24, p = 0.83, 1249, p = 0.97, ABCB1: 2677, p = 0.40; eGFR <60ml/min/1.73m2: ABCC2: -24, p = 0.51, 1249, p = 0.81, ABCB1: 2677, p = 0.94). Logistic regression analysis showed that the risk genotype of the three SNPs were not associated with any of the three renal outcomes, respectively. Logistic regression model that applied either dominant, recessive, or additive model yielded the same results.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['ATP Binding Cassette Transporter, Subfamily B', 'Adult', 'Anti-HIV Agents', 'Female', 'Genetic Variation', 'Genotype', 'Glomerular Filtration Rate', 'HIV Infections', 'HIV-1', 'Humans', 'Kidney Diseases', 'Logistic Models', 'Male', 'Multidrug Resistance-Associated Proteins', 'Pharmacogenetics', 'Polymorphism, Single Nucleotide', 'Tenofovir']}" }, { "from": "gpt", "value": "Answer: no" } ]
26,535,357
Do meniscus Injuries Alter the Kinematics of Knees With Anterior Cruciate Ligament Deficiency?
{ "contexts": [ "Most knee joint biomechanics studies have involved knees with an isolated anterior cruciate ligament (ACL) injury. However, a large portion of patients with injured ACLs have accompanied meniscus tearing. In this study, the in vivo alteration of knee biomechanics after tearing the ACL with or without combined medial or lateral meniscus tear was investigated during stair-ascending activity.", "The kinematic behavior of ACL-deficient knees changes with a combined medial or lateral meniscus tear.", "Controlled laboratory study.", "Twenty-one patients with injured ACLs (contralateral side intact) were recruited before undergoing ACL reconstruction. Among these patients, 5 had isolated ACL injuries (group I), 8 had combined ACL and medial meniscus injuries (group II), and 8 had combined ACL and lateral meniscus injuries (group III). Bilateral magnetic resonance scans were obtained on each patient to construct 3-dimensional anatomic knee models. Both knees were then scanned during stair-climbing activity using a dual fluoroscopic imaging system. The knee kinematics during stair climbing were reproduced using a bone model image matching method. Anteroposterior and mediolateral translations and axial tibial rotation of the knee during stair ascent were then compared between the injured and intact contralateral knees of the patients.", "On average, injured knees in groups I and III showed more than 2 mm increased anterior tibial translation close to full knee extension. In group II, no statistically significant difference was observed between the injured and contralateral side in anteroposterior translation. Near full extension, in groups I and III, injured knees had less than 1 mm of increased medial tibial translation compared with the contralateral side, whereas in group II, a 1.0-mm increase in lateral tibial shift was observed in the injured knees. With regard to axial tibial rotation, group I showed an increased external tibial rotation (approximately 5°), group II had little variation, whereas group III had increased internal tibial rotation (approximately 3°)." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "METHODS", "RESULTS" ], "meshes": [] }
The results of this study demonstrate that a combined ACL/meniscus injury could alter the kinematics of ACL-injured knees in a different way compared with knees with isolated ACL tears, depending on the pattern of the meniscus tear. Considering the varying effect of meniscus injuries on knee joint kinematics, future studies might focus on specific treatment of patients with combined ACL and meniscus injuries to protect the joint from abnormal kinematics and subsequent postoperative cartilage degeneration.
yes
[ { "from": "human", "value": "Question: Do meniscus Injuries Alter the Kinematics of Knees With Anterior Cruciate Ligament Deficiency?\nContext: {'contexts': ['Most knee joint biomechanics studies have involved knees with an isolated anterior cruciate ligament (ACL) injury. However, a large portion of patients with injured ACLs have accompanied meniscus tearing. In this study, the in vivo alteration of knee biomechanics after tearing the ACL with or without combined medial or lateral meniscus tear was investigated during stair-ascending activity.', 'The kinematic behavior of ACL-deficient knees changes with a combined medial or lateral meniscus tear.', 'Controlled laboratory study.', 'Twenty-one patients with injured ACLs (contralateral side intact) were recruited before undergoing ACL reconstruction. Among these patients, 5 had isolated ACL injuries (group I), 8 had combined ACL and medial meniscus injuries (group II), and 8 had combined ACL and lateral meniscus injuries (group III). Bilateral magnetic resonance scans were obtained on each patient to construct 3-dimensional anatomic knee models. Both knees were then scanned during stair-climbing activity using a dual fluoroscopic imaging system. The knee kinematics during stair climbing were reproduced using a bone model image matching method. Anteroposterior and mediolateral translations and axial tibial rotation of the knee during stair ascent were then compared between the injured and intact contralateral knees of the patients.', 'On average, injured knees in groups I and III showed more than 2 mm increased anterior tibial translation close to full knee extension. In group II, no statistically significant difference was observed between the injured and contralateral side in anteroposterior translation. Near full extension, in groups I and III, injured knees had less than 1 mm of increased medial tibial translation compared with the contralateral side, whereas in group II, a 1.0-mm increase in lateral tibial shift was observed in the injured knees. With regard to axial tibial rotation, group I showed an increased external tibial rotation (approximately 5°), group II had little variation, whereas group III had increased internal tibial rotation (approximately 3°).'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': []}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,525,539
Is aspirin-induced gastrointestinal damage associated with an inhibition of epithelial cell autophagy?
{ "contexts": [ "Aspirin (ASA) causes gastrotoxicity by hampering the epithelial defense against luminal contents through cyclooxygenase inhibition. Since cell survival in tough conditions may depend on rescue mechanisms like autophagy, we analyzed whether epithelial cells rely on this process to defend themselves from aspirin's damaging action.", "Rats received a single dose of ASA (150 mg/kg, p.o.) with or without pretreatment with the autophagy inhibitor 3-methyladenine, and gastric injury and epithelial autophagy were evaluated 3 h later. The effects of ASA on cell viability and autophagy were also evaluated in gastric epithelial AGS cells.", "Basal autophagy in the gastric mucosa was inhibited by ASA as demonstrated by increased levels of p62 and ubiquitinated proteins and total LC3 and a reduced LC3-II/LC3-I ratio. Similarly, ASA increased p62 and decreased LC3-II accumulation and the number of EmGFP/LC3B puncta in AGS cells. ASA activated the PI3K/Akt-GSK3-mTOR pathway, which phosphorylates ULK1 to prevent autophagy initiation, changes that were inhibited by the PI3K-inhibitor wortmannin. Autophagy inhibition seems to enhance the vulnerability of gastric epithelial cells as a combination of ASA with 3-methyladenine exacerbated rat gastric damage and AGS cell apoptosis." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Aspirin", "Autophagy", "Cell Survival", "Cyclooxygenase Inhibitors", "Epithelial Cells", "Female", "Gastric Mucosa", "Male", "Mice, Inbred BALB C", "Rats", "Rats, Sprague-Dawley" ] }
Our data highlight the importance of autophagy in the gastric mucosa as a protective mechanism when the epithelium is injured. In the stomach, aspirin induces mucosal damage and reduces autophagy, thus, eliminating a protective mechanism that epithelial cells could use to escape death. We hypothesize that the combination of aspirin with drugs that activate autophagy could protect against gastric damage.
yes
[ { "from": "human", "value": "Question: Is aspirin-induced gastrointestinal damage associated with an inhibition of epithelial cell autophagy?\nContext: {'contexts': [\"Aspirin (ASA) causes gastrotoxicity by hampering the epithelial defense against luminal contents through cyclooxygenase\\xa0inhibition. Since cell survival in tough conditions may depend on rescue mechanisms like autophagy, we analyzed whether epithelial cells rely on this process to defend themselves from aspirin's damaging action.\", 'Rats received a single dose of ASA (150\\xa0mg/kg, p.o.) with or without pretreatment with the autophagy inhibitor 3-methyladenine, and gastric injury and epithelial autophagy were evaluated 3\\xa0h later. The effects of ASA on cell viability and autophagy were also evaluated in gastric epithelial AGS cells.', 'Basal autophagy in the gastric mucosa was inhibited by ASA as demonstrated by increased levels of p62 and ubiquitinated proteins and total LC3 and a reduced LC3-II/LC3-I ratio. Similarly, ASA increased p62 and decreased LC3-II accumulation and the number of EmGFP/LC3B puncta in AGS cells. ASA activated the PI3K/Akt-GSK3-mTOR pathway, which phosphorylates ULK1 to prevent autophagy initiation, changes that were inhibited by the PI3K-inhibitor wortmannin. Autophagy inhibition seems to enhance the vulnerability of gastric epithelial cells as a combination of ASA with 3-methyladenine exacerbated rat gastric damage and AGS cell apoptosis.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Aspirin', 'Autophagy', 'Cell Survival', 'Cyclooxygenase Inhibitors', 'Epithelial Cells', 'Female', 'Gastric Mucosa', 'Male', 'Mice, Inbred BALB C', 'Rats', 'Rats, Sprague-Dawley']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,537,518
Does iterative sub-network component analysis enable reconstruction of large scale genetic networks?
{ "contexts": [ "Network component analysis (NCA) became a popular tool to understand complex regulatory networks. The method uses high-throughput gene expression data and a priori topology to reconstruct transcription factor activity profiles. Current NCA algorithms are constrained by several conditions posed on the network topology, to guarantee unique reconstruction (termed compliancy). However, the restrictions these conditions pose are not necessarily true from biological perspective and they force network size reduction, pruning potentially important components.", "To address this, we developed a novel, Iterative Sub-Network Component Analysis (ISNCA) for reconstructing networks at any size. By dividing the initial network into smaller, compliant subnetworks, the algorithm first predicts the reconstruction of each subnetwork using standard NCA algorithms. It then subtracts from the reconstruction the contribution of the shared components from the other subnetwork. We tested the ISNCA on real, large datasets using various NCA algorithms. The size of the networks we tested and the accuracy of the reconstruction increased significantly. Importantly, FOXA1, ATF2, ATF3 and many other known key regulators in breast cancer could not be incorporated by any NCA algorithm because of the necessary conditions. However, their temporal activities could be reconstructed by our algorithm, and therefore their involvement in breast cancer could be analyzed." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Algorithms", "Gene Expression Regulation", "Gene Regulatory Networks", "Humans", "MCF-7 Cells", "Transcription Factors" ] }
Our framework enables reconstruction of large gene expression data networks, without reducing their size or pruning potentially important components, and at the same time rendering the results more biological plausible. Our ISNCA method is not only suitable for prediction of key regulators in cancer studies, but it can be applied to any high-throughput gene expression data.
yes
[ { "from": "human", "value": "Question: Does iterative sub-network component analysis enable reconstruction of large scale genetic networks?\nContext: {'contexts': ['Network component analysis (NCA) became a popular tool to understand complex regulatory networks. The method uses high-throughput gene expression data and a priori topology to reconstruct transcription factor activity profiles. Current NCA algorithms are constrained by several conditions posed on the network topology, to guarantee unique reconstruction (termed compliancy). However, the restrictions these conditions pose are not necessarily true from biological perspective and they force network size reduction, pruning potentially important components.', 'To address this, we developed a novel, Iterative Sub-Network Component Analysis (ISNCA) for reconstructing networks at any size. By dividing the initial network into smaller, compliant subnetworks, the algorithm first predicts the reconstruction of each subnetwork using standard NCA algorithms. It then subtracts from the reconstruction the contribution of the shared components from the other subnetwork. We tested the ISNCA on real, large datasets using various NCA algorithms. The size of the networks we tested and the accuracy of the reconstruction increased significantly. Importantly, FOXA1, ATF2, ATF3 and many other known key regulators in breast cancer could not be incorporated by any NCA algorithm because of the necessary conditions. However, their temporal activities could be reconstructed by our algorithm, and therefore their involvement in breast cancer could be analyzed.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Algorithms', 'Gene Expression Regulation', 'Gene Regulatory Networks', 'Humans', 'MCF-7 Cells', 'Transcription Factors']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,543,203
Are deletions and de novo mutations of SOX11 associated with a neurodevelopmental disorder with features of Coffin-Siris syndrome?
{ "contexts": [ "SOX11 is a transcription factor proposed to play a role in brain development. The relevance of SOX11 to human developmental disorders was suggested by a recent report of SOX11 mutations in two patients with Coffin-Siris syndrome. Here we further investigate the role of SOX11 variants in neurodevelopmental disorders.", "We used array based comparative genomic hybridisation and trio exome sequencing to identify children with intellectual disability who have deletions or de novo point mutations disrupting SOX11. The pathogenicity of the SOX11 mutations was assessed using an in vitro gene expression reporter system. Loss-of-function experiments were performed in xenopus by knockdown of Sox11 expression.", "We identified seven individuals with chromosome 2p25 deletions involving SOX11. Trio exome sequencing identified three de novo SOX11 variants, two missense (p.K50N; p.P120H) and one nonsense (p.C29*). The biological consequences of the missense mutations were assessed using an in vitro gene expression system. These individuals had microcephaly, developmental delay and shared dysmorphic features compatible with mild Coffin-Siris syndrome. To further investigate the function of SOX11, we knocked down the orthologous gene in xenopus. Morphants had significant reduction in head size compared with controls. This suggests that SOX11 loss of function can be associated with microcephaly." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Abnormalities, Multiple", "Adolescent", "Adult", "Animals", "Child", "Child, Preschool", "Face", "Female", "Gene Knockdown Techniques", "Hand Deformities, Congenital", "Humans", "Intellectual Disability", "Male", "Microcephaly", "Micrognathism", "Neck", "Neurodevelopmental Disorders", "SOXC Transcription Factors", "Sequence Deletion", "Xenopus" ] }
We thus propose that SOX11 deletion or mutation can present with a Coffin-Siris phenotype.
yes
[ { "from": "human", "value": "Question: Are deletions and de novo mutations of SOX11 associated with a neurodevelopmental disorder with features of Coffin-Siris syndrome?\nContext: {'contexts': ['SOX11 is a transcription factor proposed to play a role in brain development. The relevance of SOX11 to human developmental disorders was suggested by a recent report of SOX11 mutations in two patients with Coffin-Siris syndrome. Here we further investigate the role of SOX11 variants in neurodevelopmental disorders.', 'We used array based comparative genomic hybridisation and trio exome sequencing to identify children with intellectual disability who have deletions or de novo point mutations disrupting SOX11. The pathogenicity of the SOX11 mutations was assessed using an in vitro gene expression reporter system. Loss-of-function experiments were performed in xenopus by knockdown of Sox11 expression.', 'We identified seven individuals with chromosome 2p25 deletions involving SOX11. Trio exome sequencing identified three de novo SOX11 variants, two missense (p.K50N; p.P120H) and one nonsense (p.C29*). The biological consequences of the missense mutations were assessed using an in vitro gene expression system. These individuals had microcephaly, developmental delay and shared dysmorphic features compatible with mild Coffin-Siris syndrome. To further investigate the function of SOX11, we knocked down the orthologous gene in xenopus. Morphants had significant reduction in head size compared with controls. This suggests that SOX11 loss of function can be associated with microcephaly.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Abnormalities, Multiple', 'Adolescent', 'Adult', 'Animals', 'Child', 'Child, Preschool', 'Face', 'Female', 'Gene Knockdown Techniques', 'Hand Deformities, Congenital', 'Humans', 'Intellectual Disability', 'Male', 'Microcephaly', 'Micrognathism', 'Neck', 'Neurodevelopmental Disorders', 'SOXC Transcription Factors', 'Sequence Deletion', 'Xenopus']}" }, { "from": "gpt", "value": "Answer: yes" } ]
26,530,140
Does high infiltration of mast cells positive to tryptase predict worse outcome following resection of colorectal liver metastases?
{ "contexts": [ "Accumulation of tumor-infiltrating mast cells (MCs) predicts poor survival in several cancers after resection. However, its effect on the prognosis of patients with colorectal liver metastases (CRLM) is not known.", "Our retrospective study included 135 patients who underwent potentially curative resection for CRLM between 2001 and 2010. Expression of tryptase, MAC387, CD83, and CD31, which are markers for MCs, macrophages, mature dendritic cells, and vascular endothelial cells, respectively, was determined via immunohistochemistry of resected tumor specimens. The relationship between immune cell infiltration and long-term outcome was investigated.", "The median follow-up time was 48.4 months for all patients and 57.5 months for survivors. Overall survival (OS) rates at 1, 3, and 5 years were 91.0, 62.4, and 37.4 %, respectively. Five-year disease-free survival (DFS) and OS rates were 21.6 and 38.1 %, respectively, in patients with high MC infiltration, and 42.6 and 55.6 %, respectively, in patients with low MC infiltration (p < 0.01 for both DFS and OS). Infiltration of other types of immune cells did not correlate with survival. Multivariate analyses indicated that hypoalbuminemia and high peritumoral MC infiltration were significant predictors of unfavorable OS." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Colorectal Neoplasms", "Disease-Free Survival", "Female", "Humans", "Liver Neoplasms", "Lymphocytes, Tumor-Infiltrating", "Male", "Mast Cells", "Middle Aged", "Neoplasm Metastasis", "Tryptases" ] }
High peritumoral MC infiltration predicts poor prognosis in patients who underwent hepatectomy for CRLM. The number of MCs in metastatic lesions is important for predicting the prognosis of CRLM patients and as an indication of therapy.
yes
[ { "from": "human", "value": "Question: Does high infiltration of mast cells positive to tryptase predict worse outcome following resection of colorectal liver metastases?\nContext: {'contexts': ['Accumulation of tumor-infiltrating mast cells (MCs) predicts poor survival in several cancers after resection. However, its effect on the prognosis of patients with colorectal liver metastases (CRLM) is not known.', 'Our retrospective study included 135 patients who underwent potentially curative resection for CRLM between 2001 and 2010. Expression of tryptase, MAC387, CD83, and CD31, which are markers for MCs, macrophages, mature dendritic cells, and vascular endothelial cells, respectively, was determined via immunohistochemistry of resected tumor specimens. The relationship between immune cell infiltration and long-term outcome was investigated.', 'The median follow-up time was 48.4 months for all patients and 57.5 months for survivors. Overall survival (OS) rates at 1, 3, and 5 years were 91.0, 62.4, and 37.4 %, respectively. Five-year disease-free survival (DFS) and OS rates were 21.6 and 38.1 %, respectively, in patients with high MC infiltration, and 42.6 and 55.6 %, respectively, in patients with low MC infiltration (p\\u2009<\\u20090.01 for both DFS and OS). Infiltration of other types of immune cells did not correlate with survival. Multivariate analyses indicated that hypoalbuminemia and high peritumoral MC infiltration were significant predictors of unfavorable OS.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Colorectal Neoplasms', 'Disease-Free Survival', 'Female', 'Humans', 'Liver Neoplasms', 'Lymphocytes, Tumor-Infiltrating', 'Male', 'Mast Cells', 'Middle Aged', 'Neoplasm Metastasis', 'Tryptases']}" }, { "from": "gpt", "value": "Answer: yes" } ]