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26,544,970 | Does plasmid DNA Vaccine Co-Immunisation modulate Cellular and Humoral Immune Responses Induced by Intranasal Inoculation in Mice? | {
"contexts": [
"An effective HIV vaccine will likely require induction of both mucosal and systemic cellular and humoral immune responses. We investigated whether intramuscular (IM) delivery of electroporated plasmid DNA vaccine and simultaneous protein vaccinations by intranasal (IN) and IM routes could be combined to induce mucosal and systemic cellular and humoral immune responses to a model HIV-1 CN54 gp140 antigen in mice.",
"Co-immunisation of DNA with intranasal protein successfully elicited both serum and vaginal IgG and IgA responses, whereas DNA and IM protein co-delivery did not induce systemic or mucosal IgA responses. Cellular IFNγ responses were preserved in co-immunisation protocols compared to protein-only vaccination groups. The addition of DNA to IN protein vaccination reduced the strong Th2 bias observed with IN protein vaccination alone. Luminex analysis also revealed that co-immunisation with DNA and IN protein induced expression of cytokines that promote B-cell function, generation of TFH cells and CCR5 ligands that can reduce HIV infectivity."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Administration, Intranasal",
"Animals",
"B-Lymphocytes",
"Chemokines",
"Female",
"HIV Infections",
"Immunity, Cellular",
"Immunity, Humoral",
"Immunoglobulin A",
"Immunoglobulin G",
"Interleukin-2",
"Mice",
"Mice, Inbred BALB C",
"Plasmids",
"Th2 Cells",
"Vaccination",
"Vaccines, DNA",
"env Gene Products, Human Immunodeficiency Virus"
]
} | These data suggest that while IN inoculation alone elicits both cellular and humoral responses, co-administration with homologous DNA vaccination can tailor these towards a more balanced Th1/Th2 phenotype modulating the cellular cytokine profile while eliciting high-levels of antigen-specific antibody. This work provides insights on how to generate differential immune responses within the same vaccination visit, and supports co-immunisation with DNA and protein by a mucosal route as a potential delivery strategy for HIV vaccines. | yes | [
{
"from": "human",
"value": "Question: Does plasmid DNA Vaccine Co-Immunisation modulate Cellular and Humoral Immune Responses Induced by Intranasal Inoculation in Mice?\nContext: {'contexts': ['An effective HIV vaccine will likely require induction of both mucosal and systemic cellular and humoral immune responses. We investigated whether intramuscular (IM) delivery of electroporated plasmid DNA vaccine and simultaneous protein vaccinations by intranasal (IN) and IM routes could be combined to induce mucosal and systemic cellular and humoral immune responses to a model HIV-1 CN54 gp140 antigen in mice.', 'Co-immunisation of DNA with intranasal protein successfully elicited both serum and vaginal IgG and IgA responses, whereas DNA and IM protein co-delivery did not induce systemic or mucosal IgA responses. Cellular IFNγ responses were preserved in co-immunisation protocols compared to protein-only vaccination groups. The addition of DNA to IN protein vaccination reduced the strong Th2 bias observed with IN protein vaccination alone. Luminex analysis also revealed that co-immunisation with DNA and IN protein induced expression of cytokines that promote B-cell function, generation of TFH cells and CCR5 ligands that can reduce HIV infectivity.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Administration, Intranasal', 'Animals', 'B-Lymphocytes', 'Chemokines', 'Female', 'HIV Infections', 'Immunity, Cellular', 'Immunity, Humoral', 'Immunoglobulin A', 'Immunoglobulin G', 'Interleukin-2', 'Mice', 'Mice, Inbred BALB C', 'Plasmids', 'Th2 Cells', 'Vaccination', 'Vaccines, DNA', 'env Gene Products, Human Immunodeficiency Virus']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,538,514 | Does active lifestyle in childhood and adolescence prevent obesity development in young adulthood? | {
"contexts": [
"To test the hypothesis that individuals who are active but who decrease physical activity (PA) over time have a higher risk of becoming obese in young adulthood, when compared to individuals who are consistently active throughout childhood and adolescence.",
"Iowa Bone Development Study cohort members (242 males and 251 females) participated in accelerometry assessments, dual-energy X-ray absorptiometry scans, and dietary questionnaire surveys at ages 5, 8, 11, 13, 15, 17, and 19 years. Group-based trajectory analyses identified distinct trajectory patterns of moderate- to vigorous-intensity PA (MVPA), percentage of body fat, and energy intake. A multivariable logistic regression model was fit to estimate the odds of \"becoming obese\" based on the MVPA trajectories, adjusted for mother's education, somatic maturation, and energy intake.",
"Among males, 74.7% had a \"normal\" body fat pattern, 14.6% had a \"becoming obese\" pattern, and 10.7% had a \"consistently obese\" pattern, while among females, the percentages were 58.6%, 28.6%, and 12.8%, respectively. Participants who were active (≥45 min MVPA) as children but decreased MVPA with age were more likely to become obese, compared to consistently active participants (adjusted OR = 2.77; 95% CI = 1.16, 6.58)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Absorptiometry, Photon",
"Accelerometry",
"Adipose Tissue",
"Adolescent",
"Aging",
"Bone Development",
"Child",
"Child, Preschool",
"Cohort Studies",
"Diet Surveys",
"Educational Status",
"Energy Intake",
"Female",
"Humans",
"Iowa",
"Life Style",
"Logistic Models",
"Male",
"Motor Activity",
"Obesity",
"Sex Factors",
"Time Factors",
"Young Adult"
]
} | An active lifestyle throughout childhood and adolescence could prevent obesity development in young adulthood. | yes | [
{
"from": "human",
"value": "Question: Does active lifestyle in childhood and adolescence prevent obesity development in young adulthood?\nContext: {'contexts': ['To test the hypothesis that individuals who are active but who decrease physical activity (PA) over time have a higher risk of becoming obese in young adulthood, when compared to individuals who are consistently active throughout childhood and adolescence.', 'Iowa Bone Development Study cohort members (242 males and 251 females) participated in accelerometry assessments, dual-energy X-ray absorptiometry scans, and dietary questionnaire surveys at ages 5, 8, 11, 13, 15, 17, and 19 years. Group-based trajectory analyses identified distinct trajectory patterns of moderate- to vigorous-intensity PA (MVPA), percentage of body fat, and energy intake. A multivariable logistic regression model was fit to estimate the odds of \"becoming obese\" based on the MVPA trajectories, adjusted for mother\\'s education, somatic maturation, and energy intake.', 'Among males, 74.7% had a \"normal\" body fat pattern, 14.6% had a \"becoming obese\" pattern, and 10.7% had a \"consistently obese\" pattern, while among females, the percentages were 58.6%, 28.6%, and 12.8%, respectively. Participants who were active (≥45 min MVPA) as children but decreased MVPA with age were more likely to become obese, compared to consistently active participants (adjusted OR\\u2009=\\u20092.77; 95% CI\\u2009=\\u20091.16, 6.58).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Absorptiometry, Photon', 'Accelerometry', 'Adipose Tissue', 'Adolescent', 'Aging', 'Bone Development', 'Child', 'Child, Preschool', 'Cohort Studies', 'Diet Surveys', 'Educational Status', 'Energy Intake', 'Female', 'Humans', 'Iowa', 'Life Style', 'Logistic Models', 'Male', 'Motor Activity', 'Obesity', 'Sex Factors', 'Time Factors', 'Young Adult']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,554,913 | Is increased BST2 expression during simian immunodeficiency virus infection a determinant of disease progression in rhesus monkeys? | {
"contexts": [
"Bone marrow stromal cell antigen 2 (BST2), also known as tetherin, HM1.24 or CD317 represents a type 2 integral membrane protein, which has been described to restrict the production of some enveloped viruses by inhibiting the virus release from the cell surface. This innate antiviral mechanism is counteracted by the HIV-1 viral factor Vpu, targeting BST2 for cellular degradation. Since antiviral BST2 activity has been mainly confirmed by in vitro data, we investigated its role in vivo on the disease progression using the SIV/macaque model for AIDS. We determined BST2 expression in PBMC and leukocyte subsets of uninfected and SIV-infected rhesus macaques by real-time PCR and flow cytometry and correlated it with disease progression and viral load.",
"Compared to pre-infection levels, we found increased BST2 expression in PBMC, purified CD4(+) lymphocytes and CD14(+) monocytes of SIV-infected animals, which correlated with viral load. Highest BST2 levels were found in progressors and lowest levels comparable to uninfected macaques were observed in long-term non-progressors (LTNPs). During acute viremia, BST2 mRNA increased in parallel with MX1, a prototype interferon-stimulated gene. This association was maintained during the whole disease course."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Animals",
"Antigens, CD",
"Disease Progression",
"Interferons",
"Leukocytes, Mononuclear",
"Macaca mulatta",
"Models, Animal",
"RNA, Viral",
"Real-Time Polymerase Chain Reaction",
"Simian Acquired Immunodeficiency Syndrome",
"Simian Immunodeficiency Virus",
"Viral Load",
"Viremia",
"Virus Release"
]
} | The detected relationship between BST2 expression and viral load as well as with MX1 indicate a common regulation by the interferon response and suggest rather limited influence of BST2 in vivo on the disease outcome. | no | [
{
"from": "human",
"value": "Question: Is increased BST2 expression during simian immunodeficiency virus infection a determinant of disease progression in rhesus monkeys?\nContext: {'contexts': ['Bone marrow stromal cell antigen 2 (BST2), also known as tetherin, HM1.24 or CD317 represents a type 2 integral membrane protein, which has been described to restrict the production of some enveloped viruses by inhibiting the virus release from the cell surface. This innate antiviral mechanism is counteracted by the HIV-1 viral factor Vpu, targeting BST2 for cellular degradation. Since antiviral BST2 activity has been mainly confirmed by in vitro data, we investigated its role in vivo on the disease progression using the SIV/macaque model for AIDS. We determined BST2 expression in PBMC and leukocyte subsets of uninfected and SIV-infected rhesus macaques by real-time PCR and flow cytometry and correlated it with disease progression and viral load.', 'Compared to pre-infection levels, we found increased BST2 expression in PBMC, purified CD4(+) lymphocytes and CD14(+) monocytes of SIV-infected animals, which correlated with viral load. Highest BST2 levels were found in progressors and lowest levels comparable to uninfected macaques were observed in long-term non-progressors (LTNPs). During acute viremia, BST2 mRNA increased in parallel with MX1, a prototype interferon-stimulated gene. This association was maintained during the whole disease course.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Animals', 'Antigens, CD', 'Disease Progression', 'Interferons', 'Leukocytes, Mononuclear', 'Macaca mulatta', 'Models, Animal', 'RNA, Viral', 'Real-Time Polymerase Chain Reaction', 'Simian Acquired Immunodeficiency Syndrome', 'Simian Immunodeficiency Virus', 'Viral Load', 'Viremia', 'Virus Release']}"
},
{
"from": "gpt",
"value": "Answer: no"
}
]
|
26,524,691 | Is gut colonization with methanobrevibacter smithii associated with childhood weight development? | {
"contexts": [
"To prospectively investigate the presence and counts of archaea in feces of 472 children in association with weight development from 6 to 10 years of age.",
"Within the KOALA Birth Cohort Study, a single fecal sample from each child was analyzed by quantitative polymerase chain reaction to quantify archaea (Methanobrevibacter smithii, Methanosphera stadtmanae). Anthropometric outcomes (overweight [body mass index {BMI} ≥ 85th percentile], age- and sex-standardized BMI, weight, and height z-scores) were repeatedly measured at ages (mean ± SD) of 6.2 ± 0.5, 6.8 ± 0.5, 7.8 ± 0.5, and 8.8 ± 0.5 years. Generalized estimating equation was used for statistical analysis while controlling for confounders.",
"Methanobrevibacter smithii colonization was associated with an increased risk of overweight (adjusted odds ratio [OR] = 2.69; 95% confidence interval [CI] 0.96-7.54) from 6 to 10 years of age. Children with high levels (>7 log10 copies/g feces) of this archaeon were at highest risk for overweight (OR = 3.27; 95% CI 1.09-9.83). Moreover, M. smithii colonization was associated with higher weight z-scores (adj. β 0.18; 95% CI 0.00-0.36), but not with height. For BMI z-scores, the interaction (P = 0.008) between M. smithii and age was statistically significant, implying children colonized with M. smithii had increasing BMI z-scores with age."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Age Factors",
"Anthropometry",
"Body Height",
"Body Mass Index",
"Body Weight",
"Child",
"Child, Preschool",
"Cohort Studies",
"Feces",
"Female",
"Humans",
"Male",
"Methanobacteriaceae",
"Methanobrevibacter",
"Odds Ratio",
"Overweight",
"Prospective Studies"
]
} | Presence and higher counts of M. smithii in the gut of children are associated with higher weight z-scores, higher BMI z-scores, and overweight. | yes | [
{
"from": "human",
"value": "Question: Is gut colonization with methanobrevibacter smithii associated with childhood weight development?\nContext: {'contexts': ['To prospectively investigate the presence and counts of archaea in feces of 472 children in association with weight development from 6 to 10\\xa0years of age.', 'Within the KOALA Birth Cohort Study, a single fecal sample from each child was analyzed by quantitative polymerase chain reaction to quantify archaea (Methanobrevibacter smithii, Methanosphera stadtmanae). Anthropometric outcomes (overweight [body mass index {BMI}\\xa0≥\\xa085th percentile], age- and sex-standardized BMI, weight, and height z-scores) were repeatedly measured at ages (mean\\xa0±\\xa0SD) of 6.2\\xa0±\\xa00.5, 6.8\\xa0±\\xa00.5, 7.8\\xa0±\\xa00.5, and 8.8\\xa0±\\xa00.5\\xa0years. Generalized estimating equation was used for statistical analysis while controlling for confounders.', 'Methanobrevibacter smithii colonization was associated with an increased risk of overweight (adjusted odds ratio [OR]\\xa0=\\xa02.69; 95% confidence interval [CI] 0.96-7.54) from 6 to 10\\xa0years of age. Children with high levels (>7 log10 copies/g feces) of this archaeon were at highest risk for overweight (OR\\xa0=\\xa03.27; 95% CI 1.09-9.83). Moreover, M. smithii colonization was associated with higher weight z-scores (adj. β 0.18; 95% CI 0.00-0.36), but not with height. For BMI z-scores, the interaction (P\\xa0=\\xa00.008) between M. smithii and age was statistically significant, implying children colonized with M. smithii had increasing BMI z-scores with age.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Age Factors', 'Anthropometry', 'Body Height', 'Body Mass Index', 'Body Weight', 'Child', 'Child, Preschool', 'Cohort Studies', 'Feces', 'Female', 'Humans', 'Male', 'Methanobacteriaceae', 'Methanobrevibacter', 'Odds Ratio', 'Overweight', 'Prospective Studies']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,553,747 | Is sequential brief neuropsychological evaluation of migraineurs identical to controls? | {
"contexts": [
"Evidence of attack-related cognitive dysfunction in migraine is growing. Controversy exists on whether cognitive dysfunction, mainly executive, may persist between attacks. Measuring the impact of cognitive function is gaining importance in clinical and research settings in migraine.",
"To compare the performance of interictal migraine patients to controls in an assembled neuropsychological battery focused on executive functions and to study the practice effect of its repeated applications.",
"Assembly of the battery that was then applied twice within 6 weeks to interictal migraineurs and matched healthy controls.",
"Migraine patients (n = 24) and controls (n = 24) had similar performance in both applications of the battery. There was a slight practice effect between the first and second evaluation, significant in Stroop Interference test (P = 0.002, multiplicity corrected); a meaningful score change was determined for each raw test scores."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Cognitive Dysfunction",
"Executive Function",
"Female",
"Humans",
"Male",
"Middle Aged",
"Migraine Disorders",
"Neuropsychological Tests",
"Young Adult"
]
} | Interictal migraineurs and controls performance is identical in a brief cognitive battery focused on executive functions. Repeated applications produced a practice effect that was quantified. | yes | [
{
"from": "human",
"value": "Question: Is sequential brief neuropsychological evaluation of migraineurs identical to controls?\nContext: {'contexts': ['Evidence of attack-related cognitive dysfunction in migraine is growing. Controversy exists on whether cognitive dysfunction, mainly executive, may persist between attacks. Measuring the impact of cognitive function is gaining importance in clinical and research settings in migraine.', 'To compare the performance of interictal migraine patients to controls in an assembled neuropsychological battery focused on executive functions and to study the practice effect of its repeated applications.', 'Assembly of the battery that was then applied twice within 6\\xa0weeks to interictal migraineurs and matched healthy controls.', 'Migraine patients (n\\xa0=\\xa024) and controls (n\\xa0=\\xa024) had similar performance in both applications of the battery. There was a slight practice effect between the first and second evaluation, significant in Stroop Interference test (P\\xa0=\\xa00.002, multiplicity corrected); a meaningful score change was determined for each raw test scores.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Cognitive Dysfunction', 'Executive Function', 'Female', 'Humans', 'Male', 'Middle Aged', 'Migraine Disorders', 'Neuropsychological Tests', 'Young Adult']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,541,514 | Does a transient ischemic environment induce reversible compaction of chromatin? | {
"contexts": [
"Cells detect and adapt to hypoxic and nutritional stress through immediate transcriptional, translational and metabolic responses. The environmental effects of ischemia on chromatin nanostructure were investigated using single molecule localization microscopy of DNA binding dyes and of acetylated histones, by the sensitivity of chromatin to digestion with DNAseI, and by fluorescence recovery after photobleaching (FRAP) of core and linker histones.",
"Short-term oxygen and nutrient deprivation of the cardiomyocyte cell line HL-1 induces a previously undescribed chromatin architecture, consisting of large, chromatin-sparse voids interspersed between DNA-dense hollow helicoid structures 40-700 nm in dimension. The chromatin compaction is reversible, and upon restitution of normoxia and nutrients, chromatin transiently adopts a more open structure than in untreated cells. The compacted state of chromatin reduces transcription, while the open chromatin structure induced upon recovery provokes a transitory increase in transcription. Digestion of chromatin with DNAseI confirms that oxygen and nutrient deprivation induces compaction of chromatin. Chromatin compaction is associated with depletion of ATP and redistribution of the polyamine pool into the nucleus. FRAP demonstrates that core histones are not displaced from compacted chromatin; however, the mobility of linker histone H1 is considerably reduced, to an extent that far exceeds the difference in histone H1 mobility between heterochromatin and euchromatin."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Cell Hypoxia",
"Cell Line",
"Chromatin",
"DNA",
"DNA-Binding Proteins",
"Deoxyribonuclease I",
"Fluorescence Recovery After Photobleaching",
"Heterochromatin",
"Histones",
"Humans",
"Ischemia",
"Myocytes, Cardiac",
"Protein Binding",
"Protein Processing, Post-Translational"
]
} | These studies exemplify the dynamic capacity of chromatin architecture to physically respond to environmental conditions, directly link cellular energy status to chromatin compaction and provide insight into the effect ischemia has on the nuclear architecture of cells. | yes | [
{
"from": "human",
"value": "Question: Does a transient ischemic environment induce reversible compaction of chromatin?\nContext: {'contexts': ['Cells detect and adapt to hypoxic and nutritional stress through immediate transcriptional, translational and metabolic responses. The environmental effects of ischemia on chromatin nanostructure were investigated using single molecule localization microscopy of DNA binding dyes and of acetylated histones, by the sensitivity of chromatin to digestion with DNAseI, and by fluorescence recovery after photobleaching (FRAP) of core and linker histones.', 'Short-term oxygen and nutrient deprivation of the cardiomyocyte cell line HL-1 induces a previously undescribed chromatin architecture, consisting of large, chromatin-sparse voids interspersed between DNA-dense hollow helicoid structures 40-700 nm in dimension. The chromatin compaction is reversible, and upon restitution of normoxia and nutrients, chromatin transiently adopts a more open structure than in untreated cells. The compacted state of chromatin reduces transcription, while the open chromatin structure induced upon recovery provokes a transitory increase in transcription. Digestion of chromatin with DNAseI confirms that oxygen and nutrient deprivation induces compaction of chromatin. Chromatin compaction is associated with depletion of ATP and redistribution of the polyamine pool into the nucleus. FRAP demonstrates that core histones are not displaced from compacted chromatin; however, the mobility of linker histone H1 is considerably reduced, to an extent that far exceeds the difference in histone H1 mobility between heterochromatin and euchromatin.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Cell Hypoxia', 'Cell Line', 'Chromatin', 'DNA', 'DNA-Binding Proteins', 'Deoxyribonuclease I', 'Fluorescence Recovery After Photobleaching', 'Heterochromatin', 'Histones', 'Humans', 'Ischemia', 'Myocytes, Cardiac', 'Protein Binding', 'Protein Processing, Post-Translational']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,530,254 | Does a novel aspirin prodrug inhibit NFκB activity and breast cancer stem cell properties? | {
"contexts": [
"Activation of cyclooxygenase (COX)/prostaglandin and nuclear factor κB (NFκB) pathways can promote breast tumor initiation, growth, and progression to drug resistance and metastasis. Thus, anti-inflammatory drugs have been widely explored as chemopreventive and antineoplastic agents. Aspirin (ASA), in particular, is associated with reduced breast cancer incidence but gastrointestinal toxicity has limited its usefulness. To improve potency and minimize toxicity, ASA ester prodrugs have been developed, in which the carboxylic acid of ASA is masked and ancillary pharmacophores can be incorporated. To date, the effects of ASA and ASA prodrugs have been largely attributed to COX inhibition and reduced prostaglandin production. However, ASA has also been reported to inhibit the NFκB pathway at very high doses. Whether ASA prodrugs can inhibit NFκB signaling remains relatively unexplored.",
"A library of ASA prodrugs was synthesized and screened for inhibition of NFκB activity and cancer stem-like cell (CSC) properties, an important PGE2-and NFκB-dependent phenotype of aggressive breast cancers. Inhibition of NFκB activity was determined by dual luciferase assay, RT-QPCR, p65 DNA binding activity and Western blots. Inhibition of CSC properties was determined by mammosphere growth, CD44(+)CD24(-)immunophenotype and tumorigenicity at limiting dilution.",
"While we identified multiple ASA prodrugs that are capable of inhibiting the NFκB pathway, several were associated with cytotoxicity. Of particular interest was GTCpFE, an ASA prodrug with fumarate as the ancillary pharmacophore. This prodrug potently inhibits NFκB activity without innate cytotoxicity. In addition, GTCpFE exhibited selective anti-CSC activity by reducing mammosphere growth and the CD44(+)CD24(-)immunophenotype. Moreover, GTCpFE pre-treated cells were less tumorigenic and, when tumors did form, latency was increased and growth rate was reduced. Structure-activity relationships for GTCpFE indicate that fumarate, within the context of an ASA prodrug, is essential for anti-NFκB activity, whereas both the ASA and fumarate moieties contributed to attenuated mammosphere growth."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aspirin",
"Breast Neoplasms",
"Female",
"Fumarates",
"Gene Expression Regulation, Neoplastic",
"Humans",
"MCF-7 Cells",
"NF-kappa B",
"Neoplastic Stem Cells",
"Prodrugs",
"Signal Transduction",
"Xenograft Model Antitumor Assays"
]
} | These results establish GTCpFE as a prototype for novel ASA-and fumarate-based anti-inflammatory drugs that: (i) are capable of targeting CSCs, and (ii) may be developed as chemopreventive or therapeutic agents in breast cancer. | yes | [
{
"from": "human",
"value": "Question: Does a novel aspirin prodrug inhibit NFκB activity and breast cancer stem cell properties?\nContext: {'contexts': ['Activation of cyclooxygenase (COX)/prostaglandin and nuclear factor κB (NFκB) pathways can promote breast tumor initiation, growth, and progression to drug resistance and metastasis. Thus, anti-inflammatory drugs have been widely explored as chemopreventive and antineoplastic agents. Aspirin (ASA), in particular, is associated with reduced breast cancer incidence but gastrointestinal toxicity has limited its usefulness. To improve potency and minimize toxicity, ASA ester prodrugs have been developed, in which the carboxylic acid of ASA is masked and ancillary pharmacophores can be incorporated. To date, the effects of ASA and ASA prodrugs have been largely attributed to COX inhibition and reduced prostaglandin production. However, ASA has also been reported to inhibit the NFκB pathway at very high doses. Whether ASA prodrugs can inhibit NFκB signaling remains relatively unexplored.', 'A library of ASA prodrugs was synthesized and screened for inhibition of NFκB activity and cancer stem-like cell (CSC) properties, an important PGE2-and NFκB-dependent phenotype of aggressive breast cancers. Inhibition of NFκB activity was determined by dual luciferase assay, RT-QPCR, p65 DNA binding activity and Western blots. Inhibition of CSC properties was determined by mammosphere growth, CD44(+)CD24(-)immunophenotype and tumorigenicity at limiting dilution.', 'While we identified multiple ASA prodrugs that are capable of inhibiting the NFκB pathway, several were associated with cytotoxicity. Of particular interest was GTCpFE, an ASA prodrug with fumarate as the ancillary pharmacophore. This prodrug potently inhibits NFκB activity without innate cytotoxicity. In addition, GTCpFE exhibited selective anti-CSC activity by reducing mammosphere growth and the CD44(+)CD24(-)immunophenotype. Moreover, GTCpFE pre-treated cells were less tumorigenic and, when tumors did form, latency was increased and growth rate was reduced. Structure-activity relationships for GTCpFE indicate that fumarate, within the context of an ASA prodrug, is essential for anti-NFκB activity, whereas both the ASA and fumarate moieties contributed to attenuated mammosphere growth.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aspirin', 'Breast Neoplasms', 'Female', 'Fumarates', 'Gene Expression Regulation, Neoplastic', 'Humans', 'MCF-7 Cells', 'NF-kappa B', 'Neoplastic Stem Cells', 'Prodrugs', 'Signal Transduction', 'Xenograft Model Antitumor Assays']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,531,006 | Is tRPC1 required for survival and proliferation of cochlear spiral ganglion stem/progenitor cells? | {
"contexts": [
"The present studies were designed to test the hypothesis that canonical transient receptor potential channel 1 (TRPC1) is required for the proliferation of cochlear spiral ganglion stem/progenitor cells (SPCs).",
"TRPC1 were detected and evaluated in postnatal day 1 CBA/CaJ mice pups derived-cochlear spiral ganglion SPCs by reverse transcription-polymerase chain reaction, Western blot, immunocytochemistry, and calcium imaging. The cell viability and proliferation of the spiral ganglion SPCs following si-RNA mediated knockdown of TRPC1 or addition of TRPC channel blocker SKF9635 were compared to controls.",
"In spiral ganglion SPCs, TRPC1 was found to be the most abundantly expressed TRPC subunit and shown to contribute to store-operated calcium entry. Silencing of TRPC1 or addition of TRPC channel blockers significantly decreased the rate of cell proliferation."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Animals, Newborn",
"Cell Proliferation",
"Cell Survival",
"Cochlea",
"Gene Silencing",
"Mice, Inbred CBA",
"Reverse Transcriptase Polymerase Chain Reaction",
"Spiral Ganglion",
"Stem Cells",
"TRPC Cation Channels"
]
} | The results suggest that TRPC1 might serve as an essential molecule in regulating the proliferation of spiral ganglion SPCs. | yes | [
{
"from": "human",
"value": "Question: Is tRPC1 required for survival and proliferation of cochlear spiral ganglion stem/progenitor cells?\nContext: {'contexts': ['The present studies were designed to test the hypothesis that canonical transient receptor potential channel 1 (TRPC1) is required for the proliferation of cochlear spiral ganglion stem/progenitor cells (SPCs).', 'TRPC1 were detected and evaluated in postnatal day 1 CBA/CaJ mice pups derived-cochlear spiral ganglion SPCs by reverse transcription-polymerase chain reaction, Western blot, immunocytochemistry, and calcium imaging. The cell viability and proliferation of the spiral ganglion SPCs following si-RNA mediated knockdown of TRPC1 or addition of TRPC channel blocker SKF9635 were compared to controls.', 'In spiral ganglion SPCs, TRPC1 was found to be the most abundantly expressed TRPC subunit and shown to contribute to store-operated calcium entry. Silencing of TRPC1 or addition of TRPC channel blockers significantly decreased the rate of cell proliferation.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Animals, Newborn', 'Cell Proliferation', 'Cell Survival', 'Cochlea', 'Gene Silencing', 'Mice, Inbred CBA', 'Reverse Transcriptase Polymerase Chain Reaction', 'Spiral Ganglion', 'Stem Cells', 'TRPC Cation Channels']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,554,822 | Is all that blood is not schistosomiasis : experiences with reagent strip testing for urogenital schistosomiasis with special consideration to very-low prevalence settings? | {
"contexts": [
"Reagent strip testing for microhaematuria has long been used for community diagnosis of Schistosoma haematobium. Sensitivities and specificities are reasonable, and hence, microhaematuria can serve as a proxy for S. haematobium infection. However, assessment of test performance in the context of the underlying S. haematobium prevalence is rare and test parameters other than sensitivity and specificity have been neglected.",
"Data about the association between microhaematuria and urine filtration results from three studies were compared and put into context with findings from a recent Cochrane review. Data were stratified by S. haematobium prevalence to identify prevalence-related differences in test performance. Kappa agreement and regression models were employed to compare data for different S. haematobium prevalence categories.",
"We found a \"background\" prevalence of microhaematuria (13 %, on average) which does not seem to be associated with schistosomiasis in most settings, irrespective of the prevalence of S. haematobium. This background level of microhaematuria might be due to cases missed with urine filtration, or alternative causes apart from S. haematobium. Especially in very-low prevalence settings, positive results for microhaematuria likely give an inaccurate picture of the extent of S. haematobium, whereas negative results are a sound indicator for the absence of infection."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Cote d'Ivoire",
"Hematuria",
"Prevalence",
"Reagent Strips",
"Schistosoma haematobium",
"Schistosomiasis haematobia"
]
} | Reagent strip testing for microhaematuria remains a good proxy for urogenital schistosomiasis, but implications of test results and scope of application differ depending on the setting in which reagent strips are employed. In very-low prevalence settings, microhaematuria is an unstable proxy for urogenital schistosomiasis and treatment decision should not be based on reagent strip test results alone. Our findings underscore the need for highly accurate diagnostic tools for settings targeted for elimination of urogenital schistosomiasis. | yes | [
{
"from": "human",
"value": "Question: Is all that blood is not schistosomiasis : experiences with reagent strip testing for urogenital schistosomiasis with special consideration to very-low prevalence settings?\nContext: {'contexts': ['Reagent strip testing for microhaematuria has long been used for community diagnosis of Schistosoma haematobium. Sensitivities and specificities are reasonable, and hence, microhaematuria can serve as a proxy for S. haematobium infection. However, assessment of test performance in the context of the underlying S. haematobium prevalence is rare and test parameters other than sensitivity and specificity have been neglected.', 'Data about the association between microhaematuria and urine filtration results from three studies were compared and put into context with findings from a recent Cochrane review. Data were stratified by S. haematobium prevalence to identify prevalence-related differences in test performance. Kappa agreement and regression models were employed to compare data for different S. haematobium prevalence categories.', 'We found a \"background\" prevalence of microhaematuria (13\\xa0%, on average) which does not seem to be associated with schistosomiasis in most settings, irrespective of the prevalence of S. haematobium. This background level of microhaematuria might be due to cases missed with urine filtration, or alternative causes apart from S. haematobium. Especially in very-low prevalence settings, positive results for microhaematuria likely give an inaccurate picture of the extent of S. haematobium, whereas negative results are a sound indicator for the absence of infection.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', \"Cote d'Ivoire\", 'Hematuria', 'Prevalence', 'Reagent Strips', 'Schistosoma haematobium', 'Schistosomiasis haematobia']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,542,246 | Is body mass index associated with higher Gleason score and biochemical recurrence risk following radical prostatectomy in Chinese men : a retrospective cohort study and meta-analysis? | {
"contexts": [
"The aim of the study is to investigate whether body mass index (BMI) affected pathological characteristics and biochemical recurrence (BCR) of prostate cancer after radical prostatectomy in Chinese men.",
"Medical records of 211 Chinese patients who underwent radical prostatectomy between 2006 and 2014 were retrospectively reviewed, with follow-up time of 24.5 ± 27.0 months. Multivariate logistic and Cox regression analyses were applied to address the impact of BMI on adverse pathological outcomes and BCR following prostatectomy. A meta-analysis of published studies from MEDLINE or EMBASE was conducted to determine the relationship between BMI and BCR following prostatectomy among Asian populations.",
"Higher BMI was positively correlated with higher biopsy Gleason score (odds ratios (OR) 1.163, 95 % confidence interval (CI) 1.023-1.322, P = 0.021) and pathological Gleason score (OR 1.220, 95 % CI 1.056-1.410, P = 0.007) in multivariate analysis. BCR was detected in 48 patients (22.7 %). Multivariate Cox proportional hazards analysis revealed that higher BMI (hazard ratio (HR) 1.145, 95 % CI 1.029-1.273, P = 0.013) and prostate-specific antigen (HR 1.659, 95 % CI 1.102-2.497, P = 0.015) levels were independent predictors of BCR. The meta-analysis enrolled eight Asian studies of 4145 patients treated by radical prostatectomy. Based on random-effects approach, a 5 kg/m(2) increase in BMI was correlated with 28 % higher risk of BCR (HR 1.22, 95 % CI 0.86-1.72) without statistical significance."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Aged, 80 and over",
"Asian Continental Ancestry Group",
"Body Mass Index",
"China",
"Humans",
"Logistic Models",
"Male",
"Middle Aged",
"Neoplasm Grading",
"Neoplasm Recurrence, Local",
"Obesity",
"Proportional Hazards Models",
"Prostate-Specific Antigen",
"Prostatectomy",
"Prostatic Neoplasms",
"Retrospective Studies",
"Risk Factors"
]
} | The present study suggested that higher BMI was an independent risk factor for a higher Gleason score, as well as an independent predictor of BCR after radical prostatectomy in Chinese patients. Meta-analysis of Asian studies also indicated that obese patients, although without statistical significance, might be more likely to suffer from BCR. | yes | [
{
"from": "human",
"value": "Question: Is body mass index associated with higher Gleason score and biochemical recurrence risk following radical prostatectomy in Chinese men : a retrospective cohort study and meta-analysis?\nContext: {'contexts': ['The aim of the study is to investigate whether body mass index (BMI) affected pathological characteristics and biochemical recurrence (BCR) of prostate cancer after radical prostatectomy in Chinese men.', 'Medical records of 211 Chinese patients who underwent radical prostatectomy between 2006 and 2014 were retrospectively reviewed, with follow-up time of 24.5\\u2009±\\u200927.0\\xa0months. Multivariate logistic and Cox regression analyses were applied to address the impact of BMI on adverse pathological outcomes and BCR following prostatectomy. A meta-analysis of published studies from MEDLINE or EMBASE was conducted to determine the relationship between BMI and BCR following prostatectomy among Asian populations.', 'Higher BMI was positively correlated with higher biopsy Gleason score (odds ratios (OR) 1.163, 95\\xa0% confidence interval (CI) 1.023-1.322, P\\u2009=\\u20090.021) and pathological Gleason score (OR 1.220, 95\\xa0% CI 1.056-1.410, P\\u2009=\\u20090.007) in multivariate analysis. BCR was detected in 48 patients (22.7\\xa0%). Multivariate Cox proportional hazards analysis revealed that higher BMI (hazard ratio (HR) 1.145, 95\\xa0% CI 1.029-1.273, P\\u2009=\\u20090.013) and prostate-specific antigen (HR 1.659, 95\\xa0% CI 1.102-2.497, P\\u2009=\\u20090.015) levels were independent predictors of BCR. The meta-analysis enrolled eight Asian studies of 4145 patients treated by radical prostatectomy. Based on random-effects approach, a 5\\xa0kg/m(2) increase in BMI was correlated with 28\\xa0% higher risk of BCR (HR 1.22, 95\\xa0% CI 0.86-1.72) without statistical significance.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Aged, 80 and over', 'Asian Continental Ancestry Group', 'Body Mass Index', 'China', 'Humans', 'Logistic Models', 'Male', 'Middle Aged', 'Neoplasm Grading', 'Neoplasm Recurrence, Local', 'Obesity', 'Proportional Hazards Models', 'Prostate-Specific Antigen', 'Prostatectomy', 'Prostatic Neoplasms', 'Retrospective Studies', 'Risk Factors']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,526,046 | Does the Natural Time Course of Membrane Alterations During Peritoneal Dialysis be Partly Altered by Peritonitis? | {
"contexts": [
"♦",
"The quality of the peritoneal membrane can deteriorate over time. Exposure to glucose-based dialysis solutions is the most likely culprit. Because peritonitis is a common complication of peritoneal dialysis (PD), distinguishing between the effect of glucose exposure and a possible additive effect of peritonitis is difficult. The aim of the present study was to compare the time-course of peritoneal transport characteristics in patients without a single episode of peritonitis-representing the natural course-and in patients who experienced 1 or more episodes of peritonitis during long-term follow-up. ♦",
"This prospective, single-center cohort study enrolled incident adult PD patients who started PD during 1990-2010. A standard peritoneal permeability analysis was performed in the first year of PD treatment and was repeated every year. The results in patients without a single episode of peritonitis (\"no-peritonitis group\") were compared with the results obtained in patients who experienced 1 or more peritonitis episodes (\"peritonitis group\") during a follow-up of 4 years. ♦",
"The 124 patients analyzed included 54 in the no-peritonitis group and 70 in the peritonitis group. The time-course of small-solute transport was different in the groups, with the peritonitis group showing an earlier and more pronounced increase in the mass transfer area coefficient for creatinine (p = 0.07) and in glucose absorption (p = 0.048). In the no-peritonitis group, the net ultrafiltration rate (NUFR) and the transcapillary ultrafiltration rate (TCUFR) both showed a steep increase from the 1st to the 2nd year of PD that was absent in the peritonitis group. Both groups showed a decrease in the NUFR after year 3. A decrease in the TCUFR occurred only in the peritonitis group. That decrease was already present after the year 1 in patients with severe peritonitis. The time-course of free water transport showed a continuous increase in the patients without peritonitis, but a decrease in the patients who experienced peritonitis (p < 0.01). No difference was observed in the time-course of the effective lymphatic absorption rate. The time-courses of immunoglobulin G and α2-macroglobulin clearances showed a decrease in both patient groups, with a concomitant increase of the restriction coefficient. Those changes were not evidently influenced by peritonitis. The two groups showed a similar decrease in the mesothelial cell mass marker cancer antigen 125 during follow-up. ♦"
],
"labels": [
"UNLABELLED",
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Biological Transport",
"Dialysis Solutions",
"Female",
"Humans",
"Kidney Failure, Chronic",
"Male",
"Middle Aged",
"Peritoneal Dialysis",
"Peritonitis",
"Prospective Studies",
"Time Factors"
]
} | On top of the natural course of peritoneal function, peritonitis episodes to some extent influence the time-course of small-solute and fluid transport-especially the transport of solute-free water. Those modifications increase the risk for overhydration. | yes | [
{
"from": "human",
"value": "Question: Does the Natural Time Course of Membrane Alterations During Peritoneal Dialysis be Partly Altered by Peritonitis?\nContext: {'contexts': ['♦', 'The quality of the peritoneal membrane can deteriorate over time. Exposure to glucose-based dialysis solutions is the most likely culprit. Because peritonitis is a common complication of peritoneal dialysis (PD), distinguishing between the effect of glucose exposure and a possible additive effect of peritonitis is difficult. The aim of the present study was to compare the time-course of peritoneal transport characteristics in patients without a single episode of peritonitis-representing the natural course-and in patients who experienced 1 or more episodes of peritonitis during long-term follow-up. ♦', 'This prospective, single-center cohort study enrolled incident adult PD patients who started PD during 1990-2010. A standard peritoneal permeability analysis was performed in the first year of PD treatment and was repeated every year. The results in patients without a single episode of peritonitis (\"no-peritonitis group\") were compared with the results obtained in patients who experienced 1 or more peritonitis episodes (\"peritonitis group\") during a follow-up of 4 years. ♦', 'The 124 patients analyzed included 54 in the no-peritonitis group and 70 in the peritonitis group. The time-course of small-solute transport was different in the groups, with the peritonitis group showing an earlier and more pronounced increase in the mass transfer area coefficient for creatinine (p = 0.07) and in glucose absorption (p = 0.048). In the no-peritonitis group, the net ultrafiltration rate (NUFR) and the transcapillary ultrafiltration rate (TCUFR) both showed a steep increase from the 1st to the 2nd year of PD that was absent in the peritonitis group. Both groups showed a decrease in the NUFR after year 3. A decrease in the TCUFR occurred only in the peritonitis group. That decrease was already present after the year 1 in patients with severe peritonitis. The time-course of free water transport showed a continuous increase in the patients without peritonitis, but a decrease in the patients who experienced peritonitis (p < 0.01). No difference was observed in the time-course of the effective lymphatic absorption rate. The time-courses of immunoglobulin G and α2-macroglobulin clearances showed a decrease in both patient groups, with a concomitant increase of the restriction coefficient. Those changes were not evidently influenced by peritonitis. The two groups showed a similar decrease in the mesothelial cell mass marker cancer antigen 125 during follow-up. ♦'], 'labels': ['UNLABELLED', 'BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Biological Transport', 'Dialysis Solutions', 'Female', 'Humans', 'Kidney Failure, Chronic', 'Male', 'Middle Aged', 'Peritoneal Dialysis', 'Peritonitis', 'Prospective Studies', 'Time Factors']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,537,598 | Is radiographic measurement of the posterior femoral offset precise? | {
"contexts": [
"The posterior femoral offset may significantly impact the final flexion range after total knee arthroplasty (TKA). The purpose of the present study was to compare a conventional, radiologic-based technique with an intra-operative, surgical navigation-based technique for the measurement of posterior femoral offset. The tested hypothesis was that the two measurement techniques produce different results both before and after TKA.",
"One-hundred consecutive cases referred for end-stage knee osteoarthritis have been studied. Posterior femoral offsets, measured pre- and post-TKA from radiographs, as well as those measured from a navigation system intra-operatively, were analysed. The pre-TKA measured offsets, post-TKA measured offsets and the changes (pre- vs. post-TKA) in the offsets were statistically compared between the radiologic and the navigated measurement techniques at a 0.05 level of significance.",
"The mean paired difference between pre-TKA radiologic and navigated measurement was 4 ± 4 mm (p < 0.001). There was a significant and moderate positive correlation with a good coherence between the two measurements. The mean paired difference between post-TKA radiologic and navigated measurement was 6 ± 5 mm (p < 0.001). There was a significant and moderate positive correlation but a poor coherence between the two measurements."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Arthroplasty, Replacement, Knee",
"Female",
"Femur",
"Humans",
"Knee Joint",
"Middle Aged",
"Osteoarthritis, Knee",
"Radiography",
"Range of Motion, Articular"
]
} | The conventional radiologic technique for the measurement of the posterior femoral offset cannot be reliably used either for pre-TKA planning of the posterior femoral resection and antero-posterior sizing of the femoral component, or for post-TKA quality control of the reconstruction of the posterior femoral offset. | no | [
{
"from": "human",
"value": "Question: Is radiographic measurement of the posterior femoral offset precise?\nContext: {'contexts': ['The posterior femoral offset may significantly impact the final flexion range after total knee arthroplasty (TKA). The purpose of the present study was to compare a conventional, radiologic-based technique with an intra-operative, surgical navigation-based technique for the measurement of posterior femoral offset. The tested hypothesis was that the two measurement techniques produce different results both before and after TKA.', 'One-hundred consecutive cases referred for end-stage knee osteoarthritis have been studied. Posterior femoral offsets, measured pre- and post-TKA from radiographs, as well as those measured from a navigation system intra-operatively, were analysed. The pre-TKA measured offsets, post-TKA measured offsets and the changes (pre- vs. post-TKA) in the offsets were statistically compared between the radiologic and the navigated measurement techniques at a 0.05 level of significance.', 'The mean paired difference between pre-TKA radiologic and navigated measurement was 4\\xa0±\\xa04\\xa0mm (p\\xa0<\\xa00.001). There was a significant and moderate positive correlation with a good coherence between the two measurements. The mean paired difference between post-TKA radiologic and navigated measurement was 6\\xa0±\\xa05\\xa0mm (p\\xa0<\\xa00.001). There was a significant and moderate positive correlation but a poor coherence between the two measurements.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Arthroplasty, Replacement, Knee', 'Female', 'Femur', 'Humans', 'Knee Joint', 'Middle Aged', 'Osteoarthritis, Knee', 'Radiography', 'Range of Motion, Articular']}"
},
{
"from": "gpt",
"value": "Answer: no"
}
]
|
26,540,738 | Do poor Muscle Strength and Low Physical Activity Are the Most Prevalent Frailty Components in Community-Dwelling Older Adults? | {
"contexts": [
"To determine the prevalence of five physical frailty phenotype components and to assess the relationship between them and other clinical factors.",
"A population-based cross-sectional study was performed. Subjects 75 years and older were randomly selected from primary care databases (with sampling stratified by gender). Physical frailty phenotypes were assessed using Fried's criteria. Sociodemographic data, comorbidities, nutritional status, and functional capacity were assessed.",
"126 subjects were recruited (47% women). Prevalence rates were poor muscle strength: 50%; low physical activity: 29%; slow gait: 28%; exhaustion: 27%; and weight loss: 5%. Prefrailty and frailty prevalence rates were 35.7% and 29.4%, respectively. Poor muscle strength and low physical activity showed a close relationship and concordance (kappa = 0.92). Most frailty components were associated with outdoor activity, hours walked daily, and certain comorbidities."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Activities of Daily Living",
"Aged",
"Aged, 80 and over",
"Comorbidity",
"Cross-Sectional Studies",
"Exercise",
"Fatigue",
"Female",
"Frail Elderly",
"Gait",
"Humans",
"Independent Living",
"Male",
"Muscle Strength",
"Nutritional Status",
"Weight Loss"
]
} | Poor muscle strength was the most prevalent frailty component and was closely associated with physical activity, suggesting that training programs may revert or prevent the frailty process. | yes | [
{
"from": "human",
"value": "Question: Do poor Muscle Strength and Low Physical Activity Are the Most Prevalent Frailty Components in Community-Dwelling Older Adults?\nContext: {'contexts': ['To determine the prevalence of five physical frailty phenotype components and to assess the relationship between them and other clinical factors.', \"A population-based cross-sectional study was performed. Subjects 75 years and older were randomly selected from primary care databases (with sampling stratified by gender). Physical frailty phenotypes were assessed using Fried's criteria. Sociodemographic data, comorbidities, nutritional status, and functional capacity were assessed.\", '126 subjects were recruited (47% women). Prevalence rates were poor muscle strength: 50%; low physical activity: 29%; slow gait: 28%; exhaustion: 27%; and weight loss: 5%. Prefrailty and frailty prevalence rates were 35.7% and 29.4%, respectively. Poor muscle strength and low physical activity showed a close relationship and concordance (kappa = 0.92). Most frailty components were associated with outdoor activity, hours walked daily, and certain comorbidities.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Activities of Daily Living', 'Aged', 'Aged, 80 and over', 'Comorbidity', 'Cross-Sectional Studies', 'Exercise', 'Fatigue', 'Female', 'Frail Elderly', 'Gait', 'Humans', 'Independent Living', 'Male', 'Muscle Strength', 'Nutritional Status', 'Weight Loss']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,537,164 | Does aCL Graft Position affect in Situ Graft Force Following ACL Reconstruction? | {
"contexts": [
"The purpose of our study was to evaluate the relationship between graft placement and in situ graft force after anterior cruciate ligament (ACL) reconstruction.",
"Magnetic resonance imaging (MRI) was obtained for twelve human cadaveric knees. The knees, in intact and deficient-ACL states, were subjected to external loading conditions as follows: an anterior tibial load of 89 N at 0°, 15°, 30°, 45°, 60°, and 90° of flexion and a combined rotatory (simulated pivot-shift) load of 5 Nm of internal tibial torque and 7 Nm of valgus torque at 0°, 15°, and 30° of flexion. Three ACL reconstructions were performed in a randomized order: from the center of the tibial insertion site to the center of the femoral insertion site (Mid), the center of the tibial insertion site to a more vertical femoral position (S1), and the center of the tibial insertion site to an even more vertical femoral position (S2). The reconstructions were tested following the same protocol used for the intact state, and graft in situ force was calculated for the two loadings at each flexion angle. MRI was used to measure the graft inclination angle after each ACL reconstruction.",
"The mean inclination angle (and standard deviation) was 51.7° ± 5.0° for the native ACL, 51.6° ± 4.1° for the Mid reconstruction (p = 0.85), 58.7° ± 5.4° for S1 (p < 0.001), and 64.7° ± 6.5° for S2 (p < 0.001). At 0°, 15°, and 30° of knee flexion, the Mid reconstruction showed in situ graft force that was closer to that of the native ACL during both anterior tibial loading and simulated pivot-shift loading than was the case for S1 and S2 reconstructions. At greater flexion angles, S1 and S2 had in situ graft force that was closer to that of the native ACL than was the case for the Mid reconstruction."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Anterior Cruciate Ligament",
"Anterior Cruciate Ligament Reconstruction",
"Arthroscopy",
"Cadaver",
"Humans",
"Joint Instability",
"Knee Joint",
"Range of Motion, Articular",
"Suture Techniques",
"Weight-Bearing"
]
} | Anatomic ACL reconstruction exposes grafts to higher loads at lower angles of knee flexion. | yes | [
{
"from": "human",
"value": "Question: Does aCL Graft Position affect in Situ Graft Force Following ACL Reconstruction?\nContext: {'contexts': ['The purpose of our study was to evaluate the relationship between graft placement and in situ graft force after anterior cruciate ligament (ACL) reconstruction.', 'Magnetic resonance imaging (MRI) was obtained for twelve human cadaveric knees. The knees, in intact and deficient-ACL states, were subjected to external loading conditions as follows: an anterior tibial load of 89 N at 0°, 15°, 30°, 45°, 60°, and 90° of flexion and a combined rotatory (simulated pivot-shift) load of 5 Nm of internal tibial torque and 7 Nm of valgus torque at 0°, 15°, and 30° of flexion. Three ACL reconstructions were performed in a randomized order: from the center of the tibial insertion site to the center of the femoral insertion site (Mid), the center of the tibial insertion site to a more vertical femoral position (S1), and the center of the tibial insertion site to an even more vertical femoral position (S2). The reconstructions were tested following the same protocol used for the intact state, and graft in situ force was calculated for the two loadings at each flexion angle. MRI was used to measure the graft inclination angle after each ACL reconstruction.', 'The mean inclination angle (and standard deviation) was 51.7° ± 5.0° for the native ACL, 51.6° ± 4.1° for the Mid reconstruction (p = 0.85), 58.7° ± 5.4° for S1 (p < 0.001), and 64.7° ± 6.5° for S2 (p < 0.001). At 0°, 15°, and 30° of knee flexion, the Mid reconstruction showed in situ graft force that was closer to that of the native ACL during both anterior tibial loading and simulated pivot-shift loading than was the case for S1 and S2 reconstructions. At greater flexion angles, S1 and S2 had in situ graft force that was closer to that of the native ACL than was the case for the Mid reconstruction.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Anterior Cruciate Ligament', 'Anterior Cruciate Ligament Reconstruction', 'Arthroscopy', 'Cadaver', 'Humans', 'Joint Instability', 'Knee Joint', 'Range of Motion, Articular', 'Suture Techniques', 'Weight-Bearing']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,526,811 | Does dBD-F induce apoptosis in gastric cancer-derived cells through suppressing HIF2α expression? | {
"contexts": [
"Gastric cancer is the third leading cause of cancer-related death in China. Accumulating evidence indicates that HIF2α may affect the aggressiveness of gastric cancer. It has also been found that HIF2α C-terminal PAS domains can form complexes with inactive benzoxadiazole antagonists. Here, the anti-tumor effect of 4-(N,Ndimethylaminosulphonyl)-7-fluoro-1,2,3-benzoxadiazole (DBD-F) on human gastric cancer cells was examined using both in vitro and in vivo assays.",
"We found that DBD-F can induce apoptosis and inhibit the mobility of MKN28 and MKN45 gastric cancer-derived cells in vitro. We also found that DBD-F can suppress tumor growth in established gastric cancer-derived xenograft models in vivo. Finally, we found that DBD-F can inhibit HIF2α expression in gastric cancer-derived cells."
],
"labels": [
"OBJECTIVE",
"RESULTS"
],
"meshes": [
"Animals",
"Antineoplastic Agents",
"Apoptosis",
"Basic Helix-Loop-Helix Transcription Factors",
"Blotting, Western",
"Cell Line, Tumor",
"Flow Cytometry",
"Fluorescent Antibody Technique",
"Humans",
"Immunohistochemistry",
"Mice",
"Mice, Nude",
"Oxazoles",
"Reverse Transcriptase Polymerase Chain Reaction",
"Stomach Neoplasms",
"Sulfonamides",
"Transfection",
"Xenograft Model Antitumor Assays"
]
} | From our findings we conclude that DBD-F (i) is cytotoxic to gastric cancer-derived cells and (ii) can induce apoptosis in these cells via the MEK/ERK signaling pathway. In addition, our findings strongly indicate that DBD-F can inhibit HIF2α expression by affecting the phosphorylation status of MEK/ERK in gastric cancer-derived cells. | yes | [
{
"from": "human",
"value": "Question: Does dBD-F induce apoptosis in gastric cancer-derived cells through suppressing HIF2α expression?\nContext: {'contexts': ['Gastric cancer is the third leading cause of cancer-related death in China. Accumulating evidence indicates that HIF2α may affect the aggressiveness of gastric cancer. It has also been found that HIF2α C-terminal PAS domains can form complexes with inactive benzoxadiazole antagonists. Here, the anti-tumor effect of 4-(N,Ndimethylaminosulphonyl)-7-fluoro-1,2,3-benzoxadiazole (DBD-F) on human gastric cancer cells was examined using both in vitro and in vivo assays.', 'We found that DBD-F can induce apoptosis and inhibit the mobility of MKN28 and MKN45 gastric cancer-derived cells in vitro. We also found that DBD-F can suppress tumor growth in established gastric cancer-derived xenograft models in vivo. Finally, we found that DBD-F can inhibit HIF2α expression in gastric cancer-derived cells.'], 'labels': ['OBJECTIVE', 'RESULTS'], 'meshes': ['Animals', 'Antineoplastic Agents', 'Apoptosis', 'Basic Helix-Loop-Helix Transcription Factors', 'Blotting, Western', 'Cell Line, Tumor', 'Flow Cytometry', 'Fluorescent Antibody Technique', 'Humans', 'Immunohistochemistry', 'Mice', 'Mice, Nude', 'Oxazoles', 'Reverse Transcriptase Polymerase Chain Reaction', 'Stomach Neoplasms', 'Sulfonamides', 'Transfection', 'Xenograft Model Antitumor Assays']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,535,057 | Does an engineered cryptic Hxt11 sugar transporter facilitate glucose-xylose co-consumption in Saccharomyces cerevisiae? | {
"contexts": [
"The yeast Saccharomyces cerevisiae is unable to ferment pentose sugars like d-xylose. Through the introduction of the respective metabolic pathway, S. cerevisiae is able to ferment xylose but first utilizes d-glucose before the d-xylose can be transported and metabolized. Low affinity d-xylose uptake occurs through the endogenous hexose (Hxt) transporters. For a more robust sugar fermentation, co-consumption of d-glucose and d-xylose is desired as d-xylose fermentation is in particular prone to inhibition by compounds present in pretreated lignocellulosic feedstocks.",
"Evolutionary engineering of a d-xylose-fermenting S. cerevisiae strain lacking the major transporter HXT1-7 and GAL2 genes yielded a derivative that shows improved growth on xylose because of the expression of a normally cryptic HXT11 gene. Hxt11 also supported improved growth on d-xylose by the wild-type strain. Further selection for glucose-insensitive growth on d-xylose employing a quadruple hexokinase deletion yielded mutations at N366 of Hxt11 that reversed the transporter specificity for d-glucose into d-xylose while maintaining high d-xylose transport rates. The Hxt11 mutant enabled the efficient co-fermentation of xylose and glucose at industrially relevant sugar concentrations when expressed in a strain lacking the HXT1-7 and GAL2 genes."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": []
} | Hxt11 is a cryptic sugar transporter of S. cerevisiae that previously has not been associated with effective d-xylose transport. Mutagenesis of Hxt11 yielded transporters that show a better affinity for d-xylose as compared to d-glucose while maintaining high transport rates. d-glucose and d-xylose co-consumption is due to a redistribution of the sugar transport flux while maintaining the total sugar conversion rate into ethanol. This method provides a single transporter solution for effective fermentation on lignocellulosic feedstocks. | yes | [
{
"from": "human",
"value": "Question: Does an engineered cryptic Hxt11 sugar transporter facilitate glucose-xylose co-consumption in Saccharomyces cerevisiae?\nContext: {'contexts': ['The yeast Saccharomyces cerevisiae is unable to ferment pentose sugars like d-xylose. Through the introduction of the respective metabolic pathway, S. cerevisiae is able to ferment xylose but first utilizes d-glucose before the d-xylose can be transported and metabolized. Low affinity d-xylose uptake occurs through the endogenous hexose (Hxt) transporters. For a more robust sugar fermentation, co-consumption of d-glucose and d-xylose is desired as d-xylose fermentation is in particular prone to inhibition by compounds present in pretreated lignocellulosic feedstocks.', 'Evolutionary engineering of a d-xylose-fermenting S. cerevisiae strain lacking the major transporter HXT1-7 and GAL2 genes yielded a derivative that shows improved growth on xylose because of the expression of a normally cryptic HXT11 gene. Hxt11 also supported improved growth on d-xylose by the wild-type strain. Further selection for glucose-insensitive growth on d-xylose employing a quadruple hexokinase deletion yielded mutations at N366 of Hxt11 that reversed the transporter specificity for d-glucose into d-xylose while maintaining high d-xylose transport rates. The Hxt11 mutant enabled the efficient co-fermentation of xylose and glucose at industrially relevant sugar concentrations when expressed in a strain lacking the HXT1-7 and GAL2 genes.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': []}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,542,584 | Is laparoscopy Safe and Accurate to Evaluate Peritoneal Surface Metastasis Prior to Cytoreductive Surgery? | {
"contexts": [
"Completeness of cytoreduction is a significant predictor of long-term outcome after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Imaging has limited sensitivity to identify peritoneal metastases and therefore predict whether complete cytoreduction is possible. We reviewed our experience using laparoscopy to determine candidates for complete cytoreduction and HIPEC.",
"This single-center, retrospective study examined patients from 2007 to 2014 who underwent laparoscopy to determine complete cytoreduction (CC-0/1)/HIPEC candidacy. Preoperative, intraoperative, and postoperative data were collected.",
"A total of 145 laparoscopies were performed on 141 patients, 72 (51.1 %) of whom were female, with a median age of 53 years (range 20-79). The primary site was appendiceal in 67 (47.5 %) patients, colorectal in 43 (30.5 %), mesothelioma in 17 (12.1 %), unknown in 9 (6.4 %), small bowel in 3 (2.1 %), gastric in 1, and ovarian in 1 (0.7 % each). Overall, 115 (81.6 %) patients had prior abdominal surgery, 111 (76.6 %) had evidence of disease on imaging, and 117 (80.7 %) underwent prior chemotherapy, with a median of 5.9 weeks between the last treatment and laparoscopy (0.9-498.9 weeks). Four (2.8 %) intraoperative complications were observed (one liver laceration, two enterotomies, and one air embolus), and nine (6.2 %) postoperative complications [four (2.8 %) Clavien grade (CG) I, three (2.8 %) CG II, one (0.7 %) CG III (return to operating room) and one (0.7 %) CG IV (transient ischemic attack)]. Forty-eight patients deemed candidates by laparoscopy underwent CRS/HIPEC (positive predictive value 82.8 %)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Antineoplastic Combined Chemotherapy Protocols",
"Chemotherapy, Cancer, Regional Perfusion",
"Combined Modality Therapy",
"Cytoreduction Surgical Procedures",
"Female",
"Follow-Up Studies",
"Humans",
"Hyperthermia, Induced",
"Incidence",
"Laparoscopy",
"Male",
"Middle Aged",
"Neoplasm Staging",
"Neoplasms",
"Peritoneal Neoplasms",
"Prognosis",
"Retrospective Studies",
"Young Adult"
]
} | Diagnostic laparoscopy is a safe, feasible, and accurate staging tool in patients with suspected peritoneal metastases being considered for CRS. | yes | [
{
"from": "human",
"value": "Question: Is laparoscopy Safe and Accurate to Evaluate Peritoneal Surface Metastasis Prior to Cytoreductive Surgery?\nContext: {'contexts': ['Completeness of cytoreduction is a significant predictor of long-term outcome after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Imaging has limited sensitivity to identify peritoneal metastases and therefore predict whether complete cytoreduction is possible. We reviewed our experience using laparoscopy to determine candidates for complete cytoreduction and HIPEC.', 'This single-center, retrospective study examined patients from 2007 to 2014 who underwent laparoscopy to determine complete cytoreduction (CC-0/1)/HIPEC candidacy. Preoperative, intraoperative, and postoperative data were collected.', 'A total of 145 laparoscopies were performed on 141 patients, 72 (51.1\\xa0%) of whom were female, with a median age of 53\\xa0years (range 20-79). The primary site was appendiceal in 67 (47.5\\xa0%) patients, colorectal in 43 (30.5\\xa0%), mesothelioma in 17 (12.1\\xa0%), unknown in 9 (6.4\\xa0%), small bowel in 3 (2.1\\xa0%), gastric in 1, and ovarian in 1 (0.7\\xa0% each). Overall, 115 (81.6\\xa0%) patients had prior abdominal surgery, 111 (76.6\\xa0%) had evidence of disease on imaging, and 117 (80.7\\xa0%) underwent prior chemotherapy, with a median of 5.9\\xa0weeks between the last treatment and laparoscopy (0.9-498.9\\xa0weeks). Four (2.8\\xa0%) intraoperative complications were observed (one liver laceration, two enterotomies, and one air embolus), and nine (6.2\\xa0%) postoperative complications [four (2.8\\xa0%) Clavien grade (CG) I, three (2.8\\xa0%) CG II, one (0.7\\xa0%) CG III (return to operating room) and one (0.7\\xa0%) CG IV (transient ischemic attack)]. Forty-eight patients deemed candidates by laparoscopy underwent CRS/HIPEC (positive predictive value 82.8\\xa0%).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Antineoplastic Combined Chemotherapy Protocols', 'Chemotherapy, Cancer, Regional Perfusion', 'Combined Modality Therapy', 'Cytoreduction Surgical Procedures', 'Female', 'Follow-Up Studies', 'Humans', 'Hyperthermia, Induced', 'Incidence', 'Laparoscopy', 'Male', 'Middle Aged', 'Neoplasm Staging', 'Neoplasms', 'Peritoneal Neoplasms', 'Prognosis', 'Retrospective Studies', 'Young Adult']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,526,857 | Is highest power magnification with narrow-band imaging useful for improving diagnostic performance for endoscopic delineation of early gastric cancers? | {
"contexts": [
"Magnifying endoscopy with narrow-band imaging (ME-NBI) is more reliable than chromoendoscopy (CE) for delineating the horizontal extent of early gastric cancers prior to endoscopic submucosal dissection (ESD). However, the added benefits of ME-NBI over CE in terms of the difference in magnification level have yet to be elucidated. The aim of this study was to investigate the improvement in diagnostic accuracy for tumor delineation obtained with different magnification levels of ME-NBI following CE.",
"This was a retrospective study, performed at a single tertiary referral center. A series of 158 consecutive patients with 161 early gastric cancers resected en bloc using ESD was included in the study. The margins of each lesion were examined in their entirety using CE, followed by low power optical magnifying endoscopy with narrow-band imaging (LM-NBI), and finally the highest power optical magnifying endoscopy with narrow-band imaging (HM-NBI). The primary endpoint was the added benefit, as measured using the successful delineation rate, for the delineation of gastric cancer margins using CE + LM-NBI vs CE, and for CE + LM-NBI + HM-NBI vs CE + LM-NBI.",
"The successful delineation rates (95 % CI) using CE, CE + LM-NBI and CE + LM-NBI + HM-NBI were 72.7 % (68.5-79.9 %), 88.9 % (84.2-93.8 %), and 98.1 % (95.8-100 %). The diagnostic accuracy improved significantly for CE + LM-NBI compared with CE (P < 0.001), and for HM-NBI compared with LM-NBI (P < 0.001)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Early Detection of Cancer",
"Female",
"Gastroscopy",
"Humans",
"Image Enhancement",
"Male",
"Narrow Band Imaging",
"Retrospective Studies",
"Stomach Neoplasms"
]
} | HM-NBI is useful for improving diagnostic performance for endoscopic delineation of early gastric cancers, following CE and LM-NBI. | yes | [
{
"from": "human",
"value": "Question: Is highest power magnification with narrow-band imaging useful for improving diagnostic performance for endoscopic delineation of early gastric cancers?\nContext: {'contexts': ['Magnifying endoscopy with narrow-band imaging (ME-NBI) is more reliable than chromoendoscopy (CE) for delineating the horizontal extent of early gastric cancers prior to endoscopic submucosal dissection (ESD). However, the added benefits of ME-NBI over CE in terms of the difference in magnification level have yet to be elucidated. The aim of this study was to investigate the improvement in diagnostic accuracy for tumor delineation obtained with different magnification levels of ME-NBI following CE.', 'This was a retrospective study, performed at a single tertiary referral center. A series of 158 consecutive patients with 161 early gastric cancers resected en bloc using ESD was included in the study. The margins of each lesion were examined in their entirety using CE, followed by low power optical magnifying endoscopy with narrow-band imaging (LM-NBI), and finally the highest power optical magnifying endoscopy with narrow-band imaging (HM-NBI). The primary endpoint was the added benefit, as measured using the successful delineation rate, for the delineation of gastric cancer margins using CE\\u2009+\\u2009LM-NBI vs CE, and for CE\\u2009+\\u2009LM-NBI\\u2009+\\u2009HM-NBI vs CE\\u2009+\\u2009LM-NBI.', 'The successful delineation rates (95 % CI) using CE, CE\\u2009+\\u2009LM-NBI and CE\\u2009+\\u2009LM-NBI\\u2009+\\u2009HM-NBI were 72.7 % (68.5-79.9 %), 88.9 % (84.2-93.8 %), and 98.1 % (95.8-100 %). The diagnostic accuracy improved significantly for CE\\u2009+\\u2009LM-NBI compared with CE (P\\u2009<\\u20090.001), and for HM-NBI compared with LM-NBI (P\\u2009<\\u20090.001).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Early Detection of Cancer', 'Female', 'Gastroscopy', 'Humans', 'Image Enhancement', 'Male', 'Narrow Band Imaging', 'Retrospective Studies', 'Stomach Neoplasms']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,541,708 | Does semaphorin 3a transfection into the left stellate ganglion reduce susceptibility to ventricular arrhythmias after myocardial infarction in rats? | {
"contexts": [
"Myocardial infarction (MI) induces neural remodelling of the left stellate ganglion (LSG), which may contribute to ischaemia-induced arrhythmias. The neural chemorepellent Semaphorin 3a (Sema3a) has been identified as a negative regulator of sympathetic innervation in the LSG and heart. We previously reported that overexpression of Sema3a in the border zone could reduce the arrhythmogenic effects of cardiac sympathetic hyperinnervation post-MI. This study investigated whether Sema3a overexpression within the LSG confers an antiarrhythmic effect after MI through decreasing extra- and intra-cardiac neural remodelling.",
"Sprague-Dawley rats were subjected to MI, and randomly allocated to intra-LSG microinjection of either phosphate-buffered saline (PBS), adenovirus encoding green fluorescent protein (AdGFP), or adenovirus encoding Sema3a (AdSema3a). Sham-operated rats served as controls. Two weeks after infarction, MI-induced nerve sprouting and sympathetic hyperinnervation in the LSG and myocardium were significantly attenuated by intra-LSG injection with AdSema3a, as assessed by immunohistochemistry and western blot analysis of growth-associated protein 43 and tyrosine hydroxylase. This was also confirmed by sympathetic nerve function changes assessed by cardiac norepinephrine content. Additionally, intra-LSG injection with AdSema3a alleviated MI-induced accumulation of dephosphorylated connexin 43 in the infarct border zone. Furthermore, Sema3a overexpression in the LSG reduced the incidence of inducible ventricular tachyarrhythmia by programmed electrical stimulation post-MI, and arrhythmia scores were significantly lower in the AdSema3a group than in the PBS and AdGFP groups."
],
"labels": [
"OBJECTIVE",
"RESULTS"
],
"meshes": [
"Animals",
"Disease Models, Animal",
"Echocardiography",
"Electrocardiography",
"Genetic Therapy",
"Heart",
"Male",
"Myocardial Infarction",
"Myocardium",
"Norepinephrine",
"Random Allocation",
"Rats",
"Rats, Sprague-Dawley",
"Semaphorin-3A",
"Stellate Ganglion",
"Tachycardia, Ventricular",
"Transfection"
]
} | Semaphorin 3a overexpression in the LSG ameliorates the inducibility of ventricular arrhythmias after MI, mainly through attenuation of neural remodelling within the cardiac-neuraxis. | yes | [
{
"from": "human",
"value": "Question: Does semaphorin 3a transfection into the left stellate ganglion reduce susceptibility to ventricular arrhythmias after myocardial infarction in rats?\nContext: {'contexts': ['Myocardial infarction (MI) induces neural remodelling of the left stellate ganglion (LSG), which may contribute to ischaemia-induced arrhythmias. The neural chemorepellent Semaphorin 3a (Sema3a) has been identified as a negative regulator of sympathetic innervation in the LSG and heart. We previously reported that overexpression of Sema3a in the border zone could reduce the arrhythmogenic effects of cardiac sympathetic hyperinnervation post-MI. This study investigated whether Sema3a overexpression within the LSG confers an antiarrhythmic effect after MI through decreasing extra- and intra-cardiac neural remodelling.', 'Sprague-Dawley rats were subjected to MI, and randomly allocated to intra-LSG microinjection of either phosphate-buffered saline (PBS), adenovirus encoding green fluorescent protein (AdGFP), or adenovirus encoding Sema3a (AdSema3a). Sham-operated rats served as controls. Two weeks after infarction, MI-induced nerve sprouting and sympathetic hyperinnervation in the LSG and myocardium were significantly attenuated by intra-LSG injection with AdSema3a, as assessed by immunohistochemistry and western blot analysis of growth-associated protein 43 and tyrosine hydroxylase. This was also confirmed by sympathetic nerve function changes assessed by cardiac norepinephrine content. Additionally, intra-LSG injection with AdSema3a alleviated MI-induced accumulation of dephosphorylated connexin 43 in the infarct border zone. Furthermore, Sema3a overexpression in the LSG reduced the incidence of inducible ventricular tachyarrhythmia by programmed electrical stimulation post-MI, and arrhythmia scores were significantly lower in the AdSema3a group than in the PBS and AdGFP groups.'], 'labels': ['OBJECTIVE', 'RESULTS'], 'meshes': ['Animals', 'Disease Models, Animal', 'Echocardiography', 'Electrocardiography', 'Genetic Therapy', 'Heart', 'Male', 'Myocardial Infarction', 'Myocardium', 'Norepinephrine', 'Random Allocation', 'Rats', 'Rats, Sprague-Dawley', 'Semaphorin-3A', 'Stellate Ganglion', 'Tachycardia, Ventricular', 'Transfection']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,542,423 | Is liposarcomatous differentiation in malignant phyllodes tumours unassociated with MDM2 or CDK4 amplification? | {
"contexts": [
"Breast sarcomas are rare, usually occurring in the setting of malignant phyllodes tumour (MPT). Heterologous differentiation commonly resembles well-differentiated or pleomorphic liposarcoma. In extramammary sites, these subtypes have different biological behaviours and distinct genetic alterations: MDM2 and CDK4 amplification in well-differentiated liposarcoma, and polyploidy with complex structural rearrangements in pleomorphic liposarcoma. The aim of this study was to investigate foci resembling well-differentiated liposarcoma in MPT for MDM2 and CDK4 amplification.",
"We evaluated the clinicopathological characteristics of MPTs received by the Vanderbilt Breast Consultation Service containing components resembling well-differentiated or pleomorphic liposarcoma. Cases with available tissue blocks were subjected to fluorescence in-situ hybridization with MDM2 and CDK4 probes. Thirty-eight MPTs with liposarcomatous components were available for review. The mean patient age was 49.8 years (range 26-84 years). In addition to well-differentiated liposarcoma, the following components were also present: high-grade undifferentiated sarcoma (n = 9; 23.7%), pleomorphic liposarcoma (n = 4; 10.5%), non-high-grade sarcoma not otherwise specified (n = 22; 57.9%), and malignant peripheral nerve sheath tumour-like (n = 2; 5.2%). Among 10 cases tested, none showed amplification of MDM2 or CDK4."
],
"labels": [
"OBJECTIVE",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Biomarkers, Tumor",
"Breast Neoplasms",
"Cell Differentiation",
"Cyclin-Dependent Kinase 4",
"Female",
"Gene Amplification",
"Humans",
"In Situ Hybridization, Fluorescence",
"Liposarcoma",
"Middle Aged",
"Nerve Sheath Neoplasms",
"Phenotype",
"Phyllodes Tumor",
"Proto-Oncogene Proteins c-mdm2"
]
} | This study examined molecular changes in the well-differentiated liposarcomatous components of MPT. Despite histological similarity to well-differentiated liposarcoma of soft tissues, liposarcomatous differentiation in MPT lacks the molecular phenotype characteristic of extramammary well-differentiated liposarcoma. | yes | [
{
"from": "human",
"value": "Question: Is liposarcomatous differentiation in malignant phyllodes tumours unassociated with MDM2 or CDK4 amplification?\nContext: {'contexts': ['Breast sarcomas are rare, usually occurring in the setting of malignant phyllodes tumour (MPT). Heterologous differentiation commonly resembles well-differentiated or pleomorphic liposarcoma. In extramammary sites, these subtypes have different biological behaviours and distinct genetic alterations: MDM2 and CDK4 amplification in well-differentiated liposarcoma, and polyploidy with complex structural rearrangements in pleomorphic liposarcoma. The aim of this study was to investigate foci resembling well-differentiated liposarcoma in MPT for MDM2 and CDK4 amplification.', 'We evaluated the clinicopathological characteristics of MPTs received by the Vanderbilt Breast Consultation Service containing components resembling well-differentiated or pleomorphic liposarcoma. Cases with available tissue blocks were subjected to fluorescence in-situ hybridization with MDM2 and CDK4 probes. Thirty-eight MPTs with liposarcomatous components were available for review. The mean patient age was 49.8 years (range 26-84 years). In addition to well-differentiated liposarcoma, the following components were also present: high-grade undifferentiated sarcoma (n = 9; 23.7%), pleomorphic liposarcoma (n = 4; 10.5%), non-high-grade sarcoma not otherwise specified (n = 22; 57.9%), and malignant peripheral nerve sheath tumour-like (n = 2; 5.2%). Among 10 cases tested, none showed amplification of MDM2 or CDK4.'], 'labels': ['OBJECTIVE', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Biomarkers, Tumor', 'Breast Neoplasms', 'Cell Differentiation', 'Cyclin-Dependent Kinase 4', 'Female', 'Gene Amplification', 'Humans', 'In Situ Hybridization, Fluorescence', 'Liposarcoma', 'Middle Aged', 'Nerve Sheath Neoplasms', 'Phenotype', 'Phyllodes Tumor', 'Proto-Oncogene Proteins c-mdm2']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,547,535 | Does citrus limonoid nomilin inhibit osteoclastogenesis in vitro by suppression of NFATc1 and MAPK signaling pathways? | {
"contexts": [
"Animal experiment studies have revealed a positive association between intake of citrus fruits and bone health. Nomilin, a limonoid present in citrus fruits, is reported to have many biological activities in mammalian systems, but the mechanism of nomilin on bone metabolism regulation is currently unclear.",
"To reveal the mechanism of nomilin on osteoclastic differentiation of mouse primary bone marrow-derived macrophages (BMMs) and the mouse RAW 264.7 macrophage cell line into osteoclasts.",
"Controlled laboratory study. Effects of nomilin on osteoclastic differentiation were studied in in vitro cell cultures.",
"Cell viability of RAW 264.7 cells and BMMs was measured with the Cell Counting Kit. TRAP-positive multinucleated cells were counted as osteoclast cell numbers. The number and area of resorption pits were measured as bone-resorbing activity. Osteoclast-specific genes expression was evaluated by quantitative real-time PCR; and proteins expression was evaluated by western blot.",
"Nomilin significantly decreased TRAP-positive multinucleated cell numbers compared with the control, and exhibited no cytotoxicity. Nomilin decreased bone resorption activity. Nomilin downregulated osteoclast-specific genes, NFATc1 and TRAP mRNA levels. Furthermore, nomilin suppressed MAPK signaling pathways."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Acid Phosphatase",
"Animals",
"Benzoxepins",
"Bone Resorption",
"Cell Differentiation",
"Citrus",
"Isoenzymes",
"Limonins",
"MAP Kinase Signaling System",
"Macrophages",
"Male",
"Mice",
"NFATC Transcription Factors",
"Osteoclasts",
"RAW 264.7 Cells",
"Tartrate-Resistant Acid Phosphatase"
]
} | This study demonstrates clearly that nomilin has inhibitory effects on osteoclastic differentiation in vitro. These findings indicate that nomilin-containing herbal preparations have potential utility for the prevention of bone metabolic diseases. | yes | [
{
"from": "human",
"value": "Question: Does citrus limonoid nomilin inhibit osteoclastogenesis in vitro by suppression of NFATc1 and MAPK signaling pathways?\nContext: {'contexts': ['Animal experiment studies have revealed a positive association between intake of citrus fruits and bone health. Nomilin, a limonoid present in citrus fruits, is reported to have many biological activities in mammalian systems, but the mechanism of nomilin on bone metabolism regulation is currently unclear.', 'To reveal the mechanism of nomilin on osteoclastic differentiation of mouse primary bone marrow-derived macrophages (BMMs) and the mouse RAW 264.7 macrophage cell line into osteoclasts.', 'Controlled laboratory study. Effects of nomilin on osteoclastic differentiation were studied in in vitro cell cultures.', 'Cell viability of RAW 264.7 cells and BMMs was measured with the Cell Counting Kit. TRAP-positive multinucleated cells were counted as osteoclast cell numbers. The number and area of resorption pits were measured as bone-resorbing activity. Osteoclast-specific genes expression was evaluated by quantitative real-time PCR; and proteins expression was evaluated by western blot.', 'Nomilin significantly decreased TRAP-positive multinucleated cell numbers compared with the control, and exhibited no cytotoxicity. Nomilin decreased bone resorption activity. Nomilin downregulated osteoclast-specific genes, NFATc1 and TRAP mRNA levels. Furthermore, nomilin suppressed MAPK signaling pathways.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Acid Phosphatase', 'Animals', 'Benzoxepins', 'Bone Resorption', 'Cell Differentiation', 'Citrus', 'Isoenzymes', 'Limonins', 'MAP Kinase Signaling System', 'Macrophages', 'Male', 'Mice', 'NFATC Transcription Factors', 'Osteoclasts', 'RAW 264.7 Cells', 'Tartrate-Resistant Acid Phosphatase']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,552,022 | Does strong Notch activation hinder bevacizumab efficacy in advanced colorectal cancer? | {
"contexts": [
"To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC).",
"Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone.",
"Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.016), progression-free survival (4.9 vs 12.1 months; p = 0.002) and overall survival (19.3 vs 30.4 months; p = 0.039). No correlation was found between Notch activation and clinical outcome in CRC treated with chemotherapy alone."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Antineoplastic Combined Chemotherapy Protocols",
"Bevacizumab",
"Biomarkers",
"Case-Control Studies",
"Colorectal Neoplasms",
"Female",
"Humans",
"Intercellular Signaling Peptides and Proteins",
"Male",
"Middle Aged",
"Neoplasm Metastasis",
"Neoplasm Staging",
"Receptors, Notch",
"Retreatment",
"Treatment Outcome"
]
} | A potential role of Notch activation in the antitumor activity of bevacizumab could be hypothesized. | yes | [
{
"from": "human",
"value": "Question: Does strong Notch activation hinder bevacizumab efficacy in advanced colorectal cancer?\nContext: {'contexts': ['To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC).', 'Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone.', 'Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.016), progression-free survival (4.9 vs 12.1 months; p = 0.002) and overall survival (19.3 vs 30.4 months; p = 0.039). No correlation was found between Notch activation and clinical outcome in CRC treated with chemotherapy alone.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Antineoplastic Combined Chemotherapy Protocols', 'Bevacizumab', 'Biomarkers', 'Case-Control Studies', 'Colorectal Neoplasms', 'Female', 'Humans', 'Intercellular Signaling Peptides and Proteins', 'Male', 'Middle Aged', 'Neoplasm Metastasis', 'Neoplasm Staging', 'Receptors, Notch', 'Retreatment', 'Treatment Outcome']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,552,021 | Does intermittent hypoxia induce disturbances in craniofacial growth and defects in craniofacial morphology? | {
"contexts": [
"To investigate intermittent hypoxia (IH) induced changes in craniofacial morphology and bone mineral density (BMD) in the mandible of growing rats.",
"Seven-week-old male Sprague-Dawley rats were exposed to IH for 4 days or 3 weeks. Sham-operated rats simultaneously breathed room air. Lateral and transverse cephalometric radiographs of the craniofacial region were obtained, and the linear distances between cephalometric landmarks were statistically analyzed. BMD and bone microstructure of the mandible were evaluated using micro-computed tomography (micro-CT).",
"Cephalometric analyses demonstrated that exposure to IH only in the two groups for 3 weeks decreased the size of the mandibular and viscerocranial bones, but not that of the neurocranial bones, in early adolescent rats. These findings are consistent with upper airway narrowing and obstructive sleep apnea (OSA). Micro-CT showed that IH increased the BMD in the cancellous bone of the mandibular condyle and the inter-radicular alveolar bone in the mandibular first molar (M1) region."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Bone Density",
"Cephalometry",
"Craniofacial Abnormalities",
"Hypoxia",
"Imaging, Three-Dimensional",
"Male",
"Rats",
"Rats, Sprague-Dawley",
"Sleep Apnea, Obstructive",
"X-Ray Microtomography"
]
} | This study is the first to identify growth retardation of the craniofacial bones in an animal model of sleep apnea. Notably, 3 weeks of IH can induce multiple changes in the bones around the upper airway in pubertal rats, which can enhance upper airway narrowing and the development of OSA. The reproducibility of these results supports the validity and usefulness of this model. These findings also emphasize the critical importance of morphometric evaluation of patients with OSA. | yes | [
{
"from": "human",
"value": "Question: Does intermittent hypoxia induce disturbances in craniofacial growth and defects in craniofacial morphology?\nContext: {'contexts': ['To investigate intermittent hypoxia (IH) induced changes in craniofacial morphology and bone mineral density (BMD) in the mandible of growing rats.', 'Seven-week-old male Sprague-Dawley rats were exposed to IH for 4 days or 3 weeks. Sham-operated rats simultaneously breathed room air. Lateral and transverse cephalometric radiographs of the craniofacial region were obtained, and the linear distances between cephalometric landmarks were statistically analyzed. BMD and bone microstructure of the mandible were evaluated using micro-computed tomography (micro-CT).', 'Cephalometric analyses demonstrated that exposure to IH only in the two groups for 3 weeks decreased the size of the mandibular and viscerocranial bones, but not that of the neurocranial bones, in early adolescent rats. These findings are consistent with upper airway narrowing and obstructive sleep apnea (OSA). Micro-CT showed that IH increased the BMD in the cancellous bone of the mandibular condyle and the inter-radicular alveolar bone in the mandibular first molar (M1) region.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Bone Density', 'Cephalometry', 'Craniofacial Abnormalities', 'Hypoxia', 'Imaging, Three-Dimensional', 'Male', 'Rats', 'Rats, Sprague-Dawley', 'Sleep Apnea, Obstructive', 'X-Ray Microtomography']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,550,073 | Does inferior vena cava collapsibility lose correlation with internal jugular vein collapsibility during increased thoracic or intra-abdominal pressure? | {
"contexts": [
"Point-of-care ultrasound evaluates inferior vena cava (IVC) and internal jugular vein (IJV) measurements to estimate intravascular volume status. The reliability of the IVC and IJV collapsibility index during increased thoracic or intra-abdominal pressure remains unclear.",
"Three phases of sonographic scanning were performed: spontaneous breathing phase, increased thoracic pressure phase via positive pressure ventilation (PPV) phase, and increased intra-abdominal pressure (IAP) phase via laparoscopic insufflation to 15 mmHg. IVC measurements were done at 1-2 cm below the diaphragm and IJV measurements were done at the level of the cricoid cartilage during a complete respiratory cycle. Collapsibility index was calculated by (max diameter - min diameter)/max diameter × 100 %. Chi square, t test, correlation procedure (CORR) and Fisher's exact analyses were completed.",
"A total of 144 scans of the IVC and IJV were completed in 16 patients who underwent laparoscopic surgery. Mean age was 46 ± 15 years, with 75 % female and 69 % African-American. IVC and IJV collapsibility correlated in the setting of spontaneous breathing (r (2) = 0.86, p < 0.01). IVC collapsibility had no correlation with the IJV in the setting of PPV (r (2) = 0.21, p = 0.52) or IAP (r (2) = 0.26, p = 0.42). Maximal IVC diameter was significantly smaller during increased IAP (16.5 mm ± 4.9) compared to spontaneous breathing (20.6 mm ± 4.8, p = 0.04) and PPV (21.8 mm ± 5.6, p = 0.01)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": []
} | IJV and IVC collapsibility correlated during spontaneous breathing but there was no statistically significant correlation during increased thoracic or intra-abdominal pressure. Increased intra-abdominal pressure was associated with a significant smaller maximal IVC diameter and cautions the reliability of IVC diameter in clinical settings that are associated with intra-abdominal hypertension or abdominal compartment syndrome. | yes | [
{
"from": "human",
"value": "Question: Does inferior vena cava collapsibility lose correlation with internal jugular vein collapsibility during increased thoracic or intra-abdominal pressure?\nContext: {'contexts': ['Point-of-care ultrasound evaluates inferior vena cava (IVC) and internal jugular vein (IJV) measurements to estimate intravascular volume status. The reliability of the IVC and IJV collapsibility index during increased thoracic or intra-abdominal pressure remains unclear.', \"Three phases of sonographic scanning were performed: spontaneous breathing phase, increased thoracic pressure phase via positive pressure ventilation (PPV) phase, and increased intra-abdominal pressure (IAP) phase via laparoscopic insufflation to 15\\xa0mmHg. IVC measurements were done at 1-2\\xa0cm below the diaphragm and IJV measurements were done at the level of the cricoid cartilage during a complete respiratory cycle. Collapsibility index was calculated by (max diameter\\xa0-\\xa0min diameter)/max diameter\\xa0×\\xa0100\\xa0%. Chi square, t test, correlation procedure (CORR) and Fisher's exact analyses were completed.\", 'A total of 144 scans of the IVC and IJV were completed in 16 patients who underwent laparoscopic surgery. Mean age was 46\\xa0±\\xa015\\xa0years, with 75\\xa0% female and 69\\xa0% African-American. IVC and IJV collapsibility correlated in the setting of spontaneous breathing (r (2)\\xa0=\\xa00.86, p\\xa0<\\xa00.01). IVC collapsibility had no correlation with the IJV in the setting of PPV (r (2)\\xa0=\\xa00.21, p\\xa0=\\xa00.52) or IAP (r (2)\\xa0=\\xa00.26, p\\xa0=\\xa00.42). Maximal IVC diameter was significantly smaller during increased IAP (16.5\\xa0mm\\xa0±\\xa04.9) compared to spontaneous breathing (20.6\\xa0mm\\xa0±\\xa04.8, p\\xa0=\\xa00.04) and PPV (21.8\\xa0mm\\xa0±\\xa05.6, p\\xa0=\\xa00.01).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': []}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,546,267 | Does the direction of cross affect [ corrected ] obesity after puberty in male but not female offspring? | {
"contexts": [
"We investigated parent-of-origin and allele-specific expression effects on obesity and hepatic gene expression in reciprocal crosses between the Berlin Fat Mouse Inbred line (BFMI) and C57Bl/6NCrl (B6N).",
"We found that F1-males with a BFMI mother developed 1.8 times more fat mass on a high fat diet at 10 weeks than F1-males of a BFMI father. The phenotype was detectable from six weeks on and was preserved after cross-fostering. RNA-seq data of liver provided evidence for higher biosynthesis and elongation of fatty acids (p = 0.00635) in obese male offspring of a BFMI mother versus lean offspring of a BFMI father. Furthermore, fatty acid degradation (p = 0.00198) and the peroxisome pathway were impaired (p = 0.00094). The circadian rhythm was affected as well (p = 0.00087). Among the highest up-regulated protein coding genes in obese males were Acot4 (1.82 fold, p = 0.022), Cyp4a10 (1.35 fold, p = 0.026) and Cyp4a14 (1.32 fold, p = 0.012), which hydroxylize fatty acids and which are known to be increased in liver steatosis. Obese males showed lower expression of the genetically imprinted and paternally expressed 3 (Peg3) gene (0.31 fold, p = 0.046) and higher expression of the androgen receptor (Ar) gene (2.38 fold, p = 0.068). Allelic imbalance was found for expression of ATP-binding cassette transporter gene Abca8b. Several of the differentially expressed genes contain estrogen response elements."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Animals",
"Circadian Rhythm",
"Fatty Acids",
"Female",
"Liver",
"Male",
"Mice",
"Obesity",
"Puberty"
]
} | Parent-of-origin effects during gametogenesis and/or fetal development in an obese mother epigenetically modify the transcription of genes that lead to enhanced fatty acid synthesis and impair β-oxidation in the liver of male, but not female F1 offspring. Down-regulation of Peg3 could contribute to trigger this metabolic setting. At puberty, higher amounts of the androgen receptor and altered access to estrogen response elements in affected genes are likely responsible for male specific expression of genes that were epigenetically triggered. A suggestive lack of estrogen binding motifs was found for highly down-regulated genes in adult hepatocytes of obese F1 males (p = 0.074). | yes | [
{
"from": "human",
"value": "Question: Does the direction of cross affect [ corrected ] obesity after puberty in male but not female offspring?\nContext: {'contexts': ['We investigated parent-of-origin and allele-specific expression effects on obesity and hepatic gene expression in reciprocal crosses between the Berlin Fat Mouse Inbred line (BFMI) and C57Bl/6NCrl (B6N).', 'We found that F1-males with a BFMI mother developed 1.8 times more fat mass on a high fat diet at 10 weeks than F1-males of a BFMI father. The phenotype was detectable from six weeks on and was preserved after cross-fostering. RNA-seq data of liver provided evidence for higher biosynthesis and elongation of fatty acids (p\\u2009=\\u20090.00635) in obese male offspring of a BFMI mother versus lean offspring of a BFMI father. Furthermore, fatty acid degradation (p\\u2009=\\u20090.00198) and the peroxisome pathway were impaired (p\\u2009=\\u20090.00094). The circadian rhythm was affected as well (p\\u2009=\\u20090.00087). Among the highest up-regulated protein coding genes in obese males were Acot4 (1.82 fold, p\\u2009=\\u20090.022), Cyp4a10 (1.35 fold, p\\u2009=\\u20090.026) and Cyp4a14 (1.32 fold, p\\u2009=\\u20090.012), which hydroxylize fatty acids and which are known to be increased in liver steatosis. Obese males showed lower expression of the genetically imprinted and paternally expressed 3 (Peg3) gene (0.31 fold, p\\u2009=\\u20090.046) and higher expression of the androgen receptor (Ar) gene (2.38 fold, p\\u2009=\\u20090.068). Allelic imbalance was found for expression of ATP-binding cassette transporter gene Abca8b. Several of the differentially expressed genes contain estrogen response elements.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Animals', 'Circadian Rhythm', 'Fatty Acids', 'Female', 'Liver', 'Male', 'Mice', 'Obesity', 'Puberty']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,537,560 | Do prenatal and postnatal markers of severity in congenital diaphragmatic hernia have similar prognostic ability? | {
"contexts": [
"The purpose of this study was to compare prenatal versus postnatal markers of congenital diaphragmatic hernia (CDH) severity at a single fetal-care center.",
"A retrospective study was performed of patients having a complete prenatal evaluation and surgical repair (n = 55). Observed-to-expected lung-to-head ratio (o/eLHR), observed-to-expected total lung volume (o/eTLV), liver position (LP), a predictive dependent variable from logistic regression of o/eLHR and liver position (o/eLHR + LP), and diaphragmatic defect size per the CDH Study Group A-D classification were plotted into receiver-operating characteristics (ROC) curves. Survival and need for extracorporeal membrane oxygenation (ECMO) were primary outcomes.",
"Survival was 69%, and ECMO utilization was 56%. Distribution was 80% left-sided defects. In the survival ROC curve, the area under the curve (AUC) for o/eLHR was 0.73, o/eTLV 0.74, LP 0.73, o/eLHR + LP 0.78, and defect size 0.84 (p = 0.23). The ROC curve for ECMO support showed o/eLHR had an AUC of 0.82, o/eTLV 0.89, LP 0.79, o/eLHR + LP 0.87, and defect size 0.90 (p = 0.19). The AUCs were similar when only left-sided CDH was analyzed."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Abnormalities, Multiple",
"Extracorporeal Membrane Oxygenation",
"Female",
"Gestational Age",
"Head",
"Hernias, Diaphragmatic, Congenital",
"Herniorrhaphy",
"Humans",
"Infant, Newborn",
"Liver",
"Logistic Models",
"Lung",
"Lung Diseases",
"Lung Volume Measurements",
"Magnetic Resonance Imaging",
"Male",
"Pregnancy",
"Prognosis",
"ROC Curve",
"Retrospective Studies",
"Severity of Illness Index",
"Ultrasonography, Prenatal"
]
} | These data suggest that prenatal evaluation was equivalent to the postnatal diaphragmatic defect classification for predicting survival and need for ECMO in CDH patients. | yes | [
{
"from": "human",
"value": "Question: Do prenatal and postnatal markers of severity in congenital diaphragmatic hernia have similar prognostic ability?\nContext: {'contexts': ['The purpose of this study was to compare prenatal versus postnatal markers of congenital diaphragmatic hernia (CDH) severity at a single fetal-care center.', 'A retrospective study was performed of patients having a complete prenatal evaluation and surgical repair (n\\u2009=\\u200955). Observed-to-expected lung-to-head ratio (o/eLHR), observed-to-expected total lung volume (o/eTLV), liver position (LP), a predictive dependent variable from logistic regression of o/eLHR and liver position (o/eLHR\\u2009+\\u2009LP), and diaphragmatic defect size per the CDH Study Group A-D classification were plotted into receiver-operating characteristics (ROC) curves. Survival and need for extracorporeal membrane oxygenation (ECMO) were primary outcomes.', 'Survival was 69%, and ECMO utilization was 56%. Distribution was 80% left-sided defects. In the survival ROC curve, the area under the curve (AUC) for o/eLHR was 0.73, o/eTLV 0.74, LP 0.73, o/eLHR\\u2009+\\u2009LP 0.78, and defect size 0.84 (p\\u2009=\\u20090.23). The ROC curve for ECMO support showed o/eLHR had an AUC of 0.82, o/eTLV 0.89, LP 0.79, o/eLHR\\u2009+\\u2009LP 0.87, and defect size 0.90 (p\\u2009=\\u20090.19). The AUCs were similar when only left-sided CDH was analyzed.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Abnormalities, Multiple', 'Extracorporeal Membrane Oxygenation', 'Female', 'Gestational Age', 'Head', 'Hernias, Diaphragmatic, Congenital', 'Herniorrhaphy', 'Humans', 'Infant, Newborn', 'Liver', 'Logistic Models', 'Lung', 'Lung Diseases', 'Lung Volume Measurements', 'Magnetic Resonance Imaging', 'Male', 'Pregnancy', 'Prognosis', 'ROC Curve', 'Retrospective Studies', 'Severity of Illness Index', 'Ultrasonography, Prenatal']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,547,006 | Does autophagy Inhibitor 3-MA weaken Neuroprotective Effects of Posttraumatic Brain Injury Moderate Hypothermia? | {
"contexts": [
"The role of autophagy in moderate hypothermia in posttraumatic brain injury (post-TBI) remains elusive. In this study, we evaluated the protective role of autophagy in post-TBI moderate hypothermia.",
"Adult male Sprague-Dawley rats were randomly divided into 3 groups (n = 36/group): TBI with hypothermia group (sham), TBI with hypothermia and a single intracerebroventricular injection of saline (saline, 5 μL), and TBI with hypothermia and a single intracerebroventricular injection of 3-methyladenine (600 nmol, diluted in 0.9% saline to a final volume of 5 μL). All rats, except those in the behavioral tests, were killed at 24 hours after fluid percussion TBI. Immunohistochemistry staining, western blot, and transmission electron microscopy were performed to assess changes in apoptosis and autophagy after injection of 3-methyladenine. Motor function (beam-walk test) and spatial learning/memory (Morris water maze) were assessed on postoperative days 1-5 and 11-15, respectively.",
"Our results showed downregulation of the expression level of microtubule-associated protein 1 light chain 3 and Beclin-1, aggravation of behavioral outcome, and increase of apoptosis."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adenine",
"Animals",
"Autophagy",
"Brain Injuries",
"Hypothermia, Induced",
"Male",
"Neuroprotection",
"Rats",
"Rats, Sprague-Dawley",
"Recovery of Function",
"Treatment Outcome"
]
} | Our results suggest that the autophagy pathway is involved in the neuroprotective effect of post-TBI hypothermia and negative modulation of apoptosis may be 1 possible mechanism. | yes | [
{
"from": "human",
"value": "Question: Does autophagy Inhibitor 3-MA weaken Neuroprotective Effects of Posttraumatic Brain Injury Moderate Hypothermia?\nContext: {'contexts': ['The role of autophagy in moderate hypothermia in posttraumatic brain injury (post-TBI) remains elusive. In this study, we evaluated the protective role of autophagy in post-TBI moderate hypothermia.', 'Adult male Sprague-Dawley rats were randomly divided into 3 groups (n\\xa0= 36/group): TBI with hypothermia group (sham), TBI with hypothermia and a single intracerebroventricular injection of saline (saline, 5 μL), and TBI with hypothermia and a single intracerebroventricular injection of 3-methyladenine (600 nmol, diluted in 0.9% saline to a final volume of 5 μL). All rats, except those in the behavioral tests, were killed at 24 hours after fluid percussion TBI. Immunohistochemistry staining, western blot, and transmission electron microscopy were performed to assess changes in apoptosis and autophagy after injection of 3-methyladenine. Motor function (beam-walk test) and spatial learning/memory (Morris water maze) were assessed on postoperative days 1-5 and 11-15, respectively.', 'Our results showed downregulation of the expression level of microtubule-associated protein 1 light chain 3 and Beclin-1, aggravation of behavioral outcome, and increase of apoptosis.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adenine', 'Animals', 'Autophagy', 'Brain Injuries', 'Hypothermia, Induced', 'Male', 'Neuroprotection', 'Rats', 'Rats, Sprague-Dawley', 'Recovery of Function', 'Treatment Outcome']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,543,099 | Does disruption of Physiological Balance Between Nitric Oxide and Endothelium-Dependent Hyperpolarization impair Cardiovascular Homeostasis in Mice? | {
"contexts": [
"Endothelium-derived nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) play important roles in modulating vascular tone in a distinct vessel size-dependent manner; NO plays a dominant role in conduit arteries and EDH in resistance vessels. We have recently demonstrated that endothelial NO synthase (eNOS) is functionally suppressed in resistance vessels through caveolin-1 (Cav-1)-dependent mechanism, switching its function from NO to EDH/hydrogen peroxide generation in mice. Here, we examined the possible importance of the physiological balance between NO and EDH in cardiovascular homeostasis.",
"We used 2 genotypes of mice in which eNOS activity is genetically upregulated; Cav-1-knockout (Cav-1-KO) and endothelium-specific eNOS transgenic (eNOS-Tg) mice. Isometric tension recordings and Langendorff experiments with isolated perfused hearts showed that NO-mediated relaxations were significantly enhanced, whereas EDH-mediated relaxations were markedly reduced in microcirculations. Importantly, impaired EDH-mediated relaxations of small mesenteric arteries from Cav-1-KO mice were completely rescued by crossing the mice with those with endothelium-specific overexpression of Cav-1. Furthermore, both genotypes showed altered cardiovascular phenotypes, including cardiac hypertrophy in Cav-1-KO mice and hypotension in eNOS-Tg mice. Finally, we examined cardiac responses to chronic pressure overload by transverse aortic constriction in vivo. When compared with wild-type mice, both Cav-1-KO and eNOS-Tg mice exhibited reduced survival after transverse aortic constriction associated with accelerated left ventricular systolic dysfunction, reduced coronary flow reserve, and enhanced myocardial hypoxia."
],
"labels": [
"OBJECTIVE",
"RESULTS"
],
"meshes": [
"Animals",
"Biological Factors",
"Cardiomegaly",
"Caveolin 1",
"Cell Hypoxia",
"Coronary Circulation",
"Dose-Response Relationship, Drug",
"Endothelium, Vascular",
"Enzyme Inhibitors",
"Genotype",
"Homeostasis",
"Hypotension",
"Isolated Heart Preparation",
"Male",
"Membrane Potentials",
"Mice, Inbred C57BL",
"Mice, Knockout",
"Microcirculation",
"Myocardium",
"Nitric Oxide",
"Nitric Oxide Synthase Type III",
"Phenotype",
"Signal Transduction",
"Systole",
"Time Factors",
"Up-Regulation",
"Vasodilation",
"Vasodilator Agents",
"Ventricular Dysfunction, Left",
"Ventricular Function, Left"
]
} | These results indicate that excessive endothelium-derived NO with reduced EDH impairs cardiovascular homeostasis in mice in vivo. | yes | [
{
"from": "human",
"value": "Question: Does disruption of Physiological Balance Between Nitric Oxide and Endothelium-Dependent Hyperpolarization impair Cardiovascular Homeostasis in Mice?\nContext: {'contexts': ['Endothelium-derived nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) play important roles in modulating vascular tone in a distinct vessel size-dependent manner; NO plays a dominant role in conduit arteries and EDH in resistance vessels. We have recently demonstrated that endothelial NO synthase (eNOS) is functionally suppressed in resistance vessels through caveolin-1 (Cav-1)-dependent mechanism, switching its function from NO to EDH/hydrogen peroxide generation in mice. Here, we examined the possible importance of the physiological balance between NO and EDH in cardiovascular homeostasis.', 'We used 2 genotypes of mice in which eNOS activity is genetically upregulated; Cav-1-knockout (Cav-1-KO) and endothelium-specific eNOS transgenic (eNOS-Tg) mice. Isometric tension recordings and Langendorff experiments with isolated perfused hearts showed that NO-mediated relaxations were significantly enhanced, whereas EDH-mediated relaxations were markedly reduced in microcirculations. Importantly, impaired EDH-mediated relaxations of small mesenteric arteries from Cav-1-KO mice were completely rescued by crossing the mice with those with endothelium-specific overexpression of Cav-1. Furthermore, both genotypes showed altered cardiovascular phenotypes, including cardiac hypertrophy in Cav-1-KO mice and hypotension in eNOS-Tg mice. Finally, we examined cardiac responses to chronic pressure overload by transverse aortic constriction in vivo. When compared with wild-type mice, both Cav-1-KO and eNOS-Tg mice exhibited reduced survival after transverse aortic constriction associated with accelerated left ventricular systolic dysfunction, reduced coronary flow reserve, and enhanced myocardial hypoxia.'], 'labels': ['OBJECTIVE', 'RESULTS'], 'meshes': ['Animals', 'Biological Factors', 'Cardiomegaly', 'Caveolin 1', 'Cell Hypoxia', 'Coronary Circulation', 'Dose-Response Relationship, Drug', 'Endothelium, Vascular', 'Enzyme Inhibitors', 'Genotype', 'Homeostasis', 'Hypotension', 'Isolated Heart Preparation', 'Male', 'Membrane Potentials', 'Mice, Inbred C57BL', 'Mice, Knockout', 'Microcirculation', 'Myocardium', 'Nitric Oxide', 'Nitric Oxide Synthase Type III', 'Phenotype', 'Signal Transduction', 'Systole', 'Time Factors', 'Up-Regulation', 'Vasodilation', 'Vasodilator Agents', 'Ventricular Dysfunction, Left', 'Ventricular Function, Left']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,543,090 | Does phosphoinositide 3-kinase-δ regulate fungus-induced allergic lung inflammation through endoplasmic reticulum stress? | {
"contexts": [
"Sensitisation with Aspergillus fumigatus (Af) is known to be associated with severe allergic lung inflammation, but the mechanism remains to be clarified. Phosphoinositide 3-kinase (PI3K)-δ and endoplasmic reticulum (ER) stress are suggested to be involved in steroid-resistant lung inflammation. We aimed to elucidate the role of PI3K-δ and its relationship with ER stress in fungus-induced allergic lung inflammation.",
"Using Af-exposed in vivo and in vitro experimental systems, we examined whether PI3K-δ regulates ER stress, thereby contributing to steroid resistance in fungus-induced allergic lung inflammation. Moreover, we checked expression of an ER stress marker in lung tissues isolated from patients with allergic bronchopulmonary aspergillosis.",
"Af-exposed mice showed that ER stress markers, unfolded protein response (UPR)-related proteins, phosphorylated Akt, generation of mitochondrial reactive oxygen species (mtROS), eosinophilic allergic inflammation, and airway hyperresponsiveness (AHR) were increased in the lung. Similarly, glucose-regulated protein 78 was increased in lung tissues of patients with ABPA. A PI3K-δ inhibitor reduced Af-induced increases in ER stress markers, UPR-related proteins, allergic inflammation and AHR in mice. However, dexamethasone failed to reduce Af-induced allergic inflammation, AHR and elevation of ER stress. Administration of an ER stress inhibitor or a mtROS scavenger improved Af-induced allergic inflammation. The PI3K-δ inhibitor reduced Af-induced mtROS generation and the mtROS scavenger ameliorated ER stress. In primary cultured tracheal epithelial cells, Af-induced ER stress was inhibited by blockade of PI3K-δ."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adenine",
"Animals",
"Aspergillosis, Allergic Bronchopulmonary",
"Biomarkers",
"Blotting, Western",
"Bronchoalveolar Lavage",
"CCAAT-Enhancer-Binding Proteins",
"Endoplasmic Reticulum Stress",
"Female",
"Glutathione",
"Glutathione Disulfide",
"Immunoglobulin E",
"Inflammation",
"Mice",
"Mice, Inbred C57BL",
"Microscopy, Confocal",
"Phosphatidylinositol 3-Kinases",
"Quinazolines",
"RNA, Small Interfering"
]
} | These findings suggest that PI3K-δ regulates Af-induced steroid-resistant eosinophilic allergic lung inflammation through ER stress. | yes | [
{
"from": "human",
"value": "Question: Does phosphoinositide 3-kinase-δ regulate fungus-induced allergic lung inflammation through endoplasmic reticulum stress?\nContext: {'contexts': ['Sensitisation with Aspergillus fumigatus (Af) is known to be associated with severe allergic lung inflammation, but the mechanism remains to be clarified. Phosphoinositide 3-kinase (PI3K)-δ and endoplasmic reticulum (ER) stress are suggested to be involved in steroid-resistant lung inflammation. We aimed to elucidate the role of PI3K-δ and its relationship with ER stress in fungus-induced allergic lung inflammation.', 'Using Af-exposed in vivo and in vitro experimental systems, we examined whether PI3K-δ regulates ER stress, thereby contributing to steroid resistance in fungus-induced allergic lung inflammation. Moreover, we checked expression of an ER stress marker in lung tissues isolated from patients with allergic bronchopulmonary aspergillosis.', 'Af-exposed mice showed that ER stress markers, unfolded protein response (UPR)-related proteins, phosphorylated Akt, generation of mitochondrial reactive oxygen species (mtROS), eosinophilic allergic inflammation, and airway hyperresponsiveness (AHR) were increased in the lung. Similarly, glucose-regulated protein 78 was increased in lung tissues of patients with ABPA. A PI3K-δ inhibitor reduced Af-induced increases in ER stress markers, UPR-related proteins, allergic inflammation and AHR in mice. However, dexamethasone failed to reduce Af-induced allergic inflammation, AHR and elevation of ER stress. Administration of an ER stress inhibitor or a mtROS scavenger improved Af-induced allergic inflammation. The PI3K-δ inhibitor reduced Af-induced mtROS generation and the mtROS scavenger ameliorated ER stress. In primary cultured tracheal epithelial cells, Af-induced ER stress was inhibited by blockade of PI3K-δ.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adenine', 'Animals', 'Aspergillosis, Allergic Bronchopulmonary', 'Biomarkers', 'Blotting, Western', 'Bronchoalveolar Lavage', 'CCAAT-Enhancer-Binding Proteins', 'Endoplasmic Reticulum Stress', 'Female', 'Glutathione', 'Glutathione Disulfide', 'Immunoglobulin E', 'Inflammation', 'Mice', 'Mice, Inbred C57BL', 'Microscopy, Confocal', 'Phosphatidylinositol 3-Kinases', 'Quinazolines', 'RNA, Small Interfering']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,546,449 | Does neuropsychiatric systemic lupus erythematosus persist despite attenuation of systemic disease in MRL/lpr mice? | {
"contexts": [
"Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease marked by both B and T cell hyperactivity which commonly affects the joints, skin, kidneys, and brain. Neuropsychiatric disease affects about 40 % of SLE patients, most frequently manifesting as depression, memory deficits, and general cognitive decline. One important and yet unresolved question is whether neuropsychiatric SLE (NPSLE) is a complication of systemic autoimmunity or whether it is primarily driven by brain-intrinsic factors.",
"To dissect the relative contributions of the central nervous system from those of the hematopoietic compartment, we generated bone marrow chimeras between healthy control (MRL/+) and lupus-prone MRL/Tnfrsf6 (lpr/lpr) mice (MRL/+ → MRL/lpr), as well as control chimeras. After bone marrow reconstitution, mice underwent extensive behavioral testing, analysis of brain tissue, and histological assessment.",
"Despite transfer of healthy MRL/+ bone marrow and marked attenuation of systemic disease, we found that MRL/+ → MRL/lpr mice had a behavioral phenotype consisting of depressive-like behavior and visuospatial memory deficits, comparable to MRL/lpr → MRL/lpr control transplanted mice and the behavioral profile previously established in MRL/lpr mice. Moreover, MRL/+ → MRL/lpr chimeric mice displayed increased brain RANTES expression, neurodegeneration, and cellular infiltration in the choroid plexus, as well as blood brain barrier disruption, all in the absence of significant systemic autoimmunity."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Behavior, Animal",
"Blood-Brain Barrier",
"Bone Marrow Transplantation",
"Chemokine CCL5",
"Chimera",
"Choroid Plexus",
"Depression",
"Female",
"Lupus Erythematosus, Systemic",
"Memory Disorders",
"Mental Disorders",
"Mice",
"Mice, Inbred MRL lpr",
"Motor Activity",
"Psychomotor Performance"
]
} | Chimeric MRL/+ → MRL/lpr mice displayed no attenuation of the behavioral phenotype found in MRL/lpr mice, despite normalized serum autoantibodies and conserved renal function. Therefore, neuropsychiatric disease in the MRL/lpr lupus-prone strain of mice can occur absent any major contributions from systemic autoimmunity. | yes | [
{
"from": "human",
"value": "Question: Does neuropsychiatric systemic lupus erythematosus persist despite attenuation of systemic disease in MRL/lpr mice?\nContext: {'contexts': ['Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease marked by both B and T cell hyperactivity which commonly affects the joints, skin, kidneys, and brain. Neuropsychiatric disease affects about 40\\xa0% of SLE patients, most frequently manifesting as depression, memory deficits, and general cognitive decline. One important and yet unresolved question is whether neuropsychiatric SLE (NPSLE) is a complication of systemic autoimmunity or whether it is primarily driven by brain-intrinsic factors.', 'To dissect the relative contributions of the central nervous system from those of the hematopoietic compartment, we generated bone marrow chimeras between healthy control (MRL/+) and lupus-prone MRL/Tnfrsf6 (lpr/lpr) mice (MRL/+\\u2009→\\u2009MRL/lpr), as well as control chimeras. After bone marrow reconstitution, mice underwent extensive behavioral testing, analysis of brain tissue, and histological assessment.', 'Despite transfer of healthy MRL/+ bone marrow and marked attenuation of systemic disease, we found that MRL/+\\u2009→\\u2009MRL/lpr mice had a behavioral phenotype consisting of depressive-like behavior and visuospatial memory deficits, comparable to MRL/lpr\\u2009→\\u2009MRL/lpr control transplanted mice and the behavioral profile previously established in MRL/lpr mice. Moreover, MRL/+\\u2009→\\u2009MRL/lpr chimeric mice displayed increased brain RANTES expression, neurodegeneration, and cellular infiltration in the choroid plexus, as well as blood brain barrier disruption, all in the absence of significant systemic autoimmunity.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Behavior, Animal', 'Blood-Brain Barrier', 'Bone Marrow Transplantation', 'Chemokine CCL5', 'Chimera', 'Choroid Plexus', 'Depression', 'Female', 'Lupus Erythematosus, Systemic', 'Memory Disorders', 'Mental Disorders', 'Mice', 'Mice, Inbred MRL lpr', 'Motor Activity', 'Psychomotor Performance']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,550,164 | Are notch1/3 and p53/p21 a potential therapeutic target for APS-induced apoptosis in non-small cell lung carcinoma cell lines? | {
"contexts": [
"Previous studies have shown that Astragalus polysaccharide (APS) can be applied to anti-cancer. However, the mechanism by which APS mediate this effect is unclear. In the present study, APS-mediated NSCLC cell apoptosis was investigated through the regulation of the notch signaling pathway.",
"The cell viability was detected by the CCK8 assay. The mRNA and protein expression of notch1/3 and tumor suppressors were analyzed by RT-PCR and western blotting, respectively.",
"The mRNA and protein of notch1 and notch3 were significantly up-regulated in tumor tissues as compared to non-tumor adjacent tissues. Treatment of human NSCLC cells with APS induced cell death in a dose-and time-dependent manner by using CCK8 assay. The mRNA and protein expression of notch1 and notch3 were significantly lower in NSCLC cells with APS treatment than that in control group. Moreover, western blotting analysis showed that treatment of H460 cells with APS significantly increased the pro-apoptotic Bax and caspase 8 levels, decreased the anti-apoptotic Bcl-2 level. Furthermore, p53, p21 and p16 were obviously up-regulated by APS treatment in H460 cell."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": []
} | This study demonstrated that APS-treated could inhibit proliferation and promote cell apoptosis, at least partially, through suppressing the expression of notch1 and notch3 and up-regulating the expression of tumor suppressors in H460 NSCLC cell lines. | yes | [
{
"from": "human",
"value": "Question: Are notch1/3 and p53/p21 a potential therapeutic target for APS-induced apoptosis in non-small cell lung carcinoma cell lines?\nContext: {'contexts': ['Previous studies have shown that Astragalus polysaccharide (APS) can be applied to anti-cancer. However, the mechanism by which APS mediate this effect is unclear. In the present study, APS-mediated NSCLC cell apoptosis was investigated through the regulation of the notch signaling pathway.', 'The cell viability was detected by the CCK8 assay. The mRNA and protein expression of notch1/3 and tumor suppressors were analyzed by RT-PCR and western blotting, respectively.', 'The mRNA and protein of notch1 and notch3 were significantly up-regulated in tumor tissues as compared to non-tumor adjacent tissues. Treatment of human NSCLC cells with APS induced cell death in a dose-and time-dependent manner by using CCK8 assay. The mRNA and protein expression of notch1 and notch3 were significantly lower in NSCLC cells with APS treatment than that in control group. Moreover, western blotting analysis showed that treatment of H460 cells with APS significantly increased the pro-apoptotic Bax and caspase 8 levels, decreased the anti-apoptotic Bcl-2 level. Furthermore, p53, p21 and p16 were obviously up-regulated by APS treatment in H460 cell.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': []}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,545,849 | Does presence of Magnetic Resonance Imaging Suspicious Lesion predict Gleason 7 or Greater Prostate Cancer in Biopsy-Naive Patients? | {
"contexts": [
"To compare the relative value of magnetic resonance imaging (MRI) in biopsy-naive patients to those with previous negative biopsy. Although MRI-targeted biopsy has been studied in several major prostate cancer (PCa) cohorts (biopsy naive, previous negative biopsy, and active surveillance), the relative benefit in these cohorts has not been established.",
"We retrospectively reviewed biopsy-naive (n = 45) and previous negative biopsy (n = 55) patients who underwent prostate MRI prior to biopsy at our institution. Patients with an MRI suspicious region (MSR) underwent MRI-targeted biopsy as well as a systematic template biopsy, whereas those without MSR underwent only the template biopsy. All biopsies were performed with the TargetScan (Envisioneering, Pittsburgh, PA) biopsy system. MRI targeting was performed with cognitive guidance.",
"On multivariate logistic regression, the presence of an MSR was the only statistically significant and independent predictor of Gleason ≥ 7 PCa on biopsy for biopsy-naive men (odds ratio [OR] 40.2, P = .01). For men with previous negative biopsy, the presence of MSR was not a predictor of Gleason ≥ 7 PCa on biopsy (OR 4.35, P = .16), whereas PSA density > 0.15 ng/mL(2) was a significant and independent predictor (OR 66.2, P < .01)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Biopsy",
"Humans",
"Magnetic Resonance Imaging",
"Male",
"Middle Aged",
"Neoplasm Grading",
"Predictive Value of Tests",
"Prostatic Neoplasms",
"Retrospective Studies"
]
} | Prostate MRI should be considered prior to biopsy in all patients presenting with clinical suspicion for PCa, as presence of a MSR will help guide prebiopsy counseling and provide an opportunity for MRI targeting during biopsy. | yes | [
{
"from": "human",
"value": "Question: Does presence of Magnetic Resonance Imaging Suspicious Lesion predict Gleason 7 or Greater Prostate Cancer in Biopsy-Naive Patients?\nContext: {'contexts': ['To compare the relative value of magnetic resonance imaging (MRI) in biopsy-naive patients to those with previous negative biopsy. Although MRI-targeted biopsy has been studied in several major prostate cancer (PCa) cohorts (biopsy naive, previous negative biopsy, and active surveillance), the relative benefit in these cohorts has not been established.', 'We retrospectively reviewed biopsy-naive (n = 45) and previous negative biopsy (n = 55) patients who underwent prostate MRI prior to biopsy at our institution. Patients with an MRI suspicious region (MSR) underwent MRI-targeted biopsy as well as a systematic template biopsy, whereas those without MSR underwent only the template biopsy. All biopsies were performed with the TargetScan (Envisioneering, Pittsburgh, PA) biopsy system. MRI targeting was performed with cognitive guidance.', 'On multivariate logistic regression, the presence of an MSR was the only statistically significant and independent predictor of Gleason ≥ 7 PCa on biopsy for biopsy-naive men (odds ratio [OR] 40.2, P = .01). For men with previous negative biopsy, the presence of MSR was not a predictor of Gleason ≥ 7 PCa on biopsy (OR 4.35, P = .16), whereas PSA density > 0.15 ng/mL(2) was a significant and independent predictor (OR 66.2, P < .01).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Biopsy', 'Humans', 'Magnetic Resonance Imaging', 'Male', 'Middle Aged', 'Neoplasm Grading', 'Predictive Value of Tests', 'Prostatic Neoplasms', 'Retrospective Studies']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,553,065 | Does a novel two-step genome editing strategy with CRISPR-Cas9 provide new insights into telomerase action and TERT gene expression? | {
"contexts": [
"To facilitate indefinite proliferation, stem cells and most cancer cells require the activity of telomerase, which counteracts the successive shortening of telomeres caused by incomplete DNA replication at the very end of each chromosome. Human telomerase activity is often determined by the expression level of telomerase reverse transcriptase (TERT), the catalytic subunit of the ribonucleoprotein complex. The low expression level of TERT and the lack of adequate antibodies have made it difficult to study telomerase-related processes in human cells.",
"To overcome the low CRISPR-Cas9 editing efficiency at the TERT locus, we develop a two-step \"pop-in/pop-out\" strategy to enrich cells that underwent homologous recombination (HR). Using this technique, we fuse an N-terminal FLAG-SNAP-tag to TERT, which allows us to reliably detect TERT in western blots, immunopurify it for biochemical analysis, and determine its subcellular localization by fluorescence microscopy. TERT co-localizes detectably with only 5-7 % of the telomeres at a time in S-phase HeLa cells; no nucleolar localization is detected. Furthermore, we extend this approach to perform single base-pair modifications in the TERT promoter; reverting a recurrent cancer-associated TERT promoter mutation in a urothelial cancer cell line results in decreased telomerase activity, indicating the mutation is causal for telomerase reactivation."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"CRISPR-Cas Systems",
"Chromosomes",
"DNA Replication",
"Gene Expression Regulation",
"Genome, Human",
"HeLa Cells",
"Humans",
"Mutation",
"Promoter Regions, Genetic",
"RNA Editing",
"Telomerase",
"Telomere"
]
} | We develop a two-step CRISPR-Cas9 genome editing strategy to introduce precise modifications at the endogenous TERT locus in human cell lines. This method provides a useful tool for studying telomerase biology, and suggests a general approach to edit loci with low targeting efficiency and to purify and visualize low abundance proteins. | yes | [
{
"from": "human",
"value": "Question: Does a novel two-step genome editing strategy with CRISPR-Cas9 provide new insights into telomerase action and TERT gene expression?\nContext: {'contexts': ['To facilitate indefinite proliferation, stem cells and most cancer cells require the activity of telomerase, which counteracts the successive shortening of telomeres caused by incomplete DNA replication at the very end of each chromosome. Human telomerase activity is often determined by the expression level of telomerase reverse transcriptase (TERT), the catalytic subunit of the ribonucleoprotein complex. The low expression level of TERT and the lack of adequate antibodies have made it difficult to study telomerase-related processes in human cells.', 'To overcome the low CRISPR-Cas9 editing efficiency at the TERT locus, we develop a two-step \"pop-in/pop-out\" strategy to enrich cells that underwent homologous recombination (HR). Using this technique, we fuse an N-terminal FLAG-SNAP-tag to TERT, which allows us to reliably detect TERT in western blots, immunopurify it for biochemical analysis, and determine its subcellular localization by fluorescence microscopy. TERT co-localizes detectably with only 5-7 % of the telomeres at a time in S-phase HeLa cells; no nucleolar localization is detected. Furthermore, we extend this approach to perform single base-pair modifications in the TERT promoter; reverting a recurrent cancer-associated TERT promoter mutation in a urothelial cancer cell line results in decreased telomerase activity, indicating the mutation is causal for telomerase reactivation.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['CRISPR-Cas Systems', 'Chromosomes', 'DNA Replication', 'Gene Expression Regulation', 'Genome, Human', 'HeLa Cells', 'Humans', 'Mutation', 'Promoter Regions, Genetic', 'RNA Editing', 'Telomerase', 'Telomere']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,536,448 | Are variations in the high-mobility group-A2 gene ( HMGA2 ) associated with idiopathic short stature? | {
"contexts": [
"Several association studies confirmed high-mobility group-A2 gene (HMGA2) polymorphisms as the most relevant variants contributing to height variability. Animal models and deletions in humans suggest that alterations of HMGA2 might be relevant in causing short stature. Together, these observations led us to investigate the involvement of HMGA2 in idiopathic short stature (ISS) through an association study and a mutation screening.",
"We conducted an association study (155 ISS patients and 318 normal stature controls) with three HMGA2 single-nucleotide polymorphisms (SNPs) (SNPs rs1042725, rs7968682, and rs7968902) using a TaqMan-based assay. The patients were then analyzed by direct sequencing and multiplex ligation-dependent probe amplification (MLPA) to detect point mutations and genomic micro-rearrangements.",
"Considering a recessive model, an OR value >1 was observed for genotypes rs7968682 TT (Odds ratio (OR) = 1.72, confidence interval (CI): 1.14-2.58) and rs1042725 TT (OR = 1.51, CI: 1.00-2.28) in accordance to the effect exhibited by the single alleles in the general population. None of the patients carried possibly causative HMGA2 mutations."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"3' Untranslated Regions",
"Adolescent",
"Body Height",
"Case-Control Studies",
"Child",
"Child, Preschool",
"DNA Mutational Analysis",
"Female",
"Gene Frequency",
"Gene Rearrangement",
"Genetic Association Studies",
"Genetic Predisposition to Disease",
"Growth Disorders",
"HMGA2 Protein",
"Heterozygote",
"Homozygote",
"Humans",
"Italy",
"Male",
"Multiplex Polymerase Chain Reaction",
"Odds Ratio",
"Phenotype",
"Point Mutation",
"Polymorphism, Single Nucleotide",
"Risk Factors"
]
} | Besides the already known role in determining variability in human height, HMGA2 polymorphisms also contribute to susceptibility to ISS. Moreover, we here report the first mutation screening performed in ISS concluding that HMGA2 has not a significant impact on the monogenic form of ISS. | yes | [
{
"from": "human",
"value": "Question: Are variations in the high-mobility group-A2 gene ( HMGA2 ) associated with idiopathic short stature?\nContext: {'contexts': ['Several association studies confirmed high-mobility group-A2 gene (HMGA2) polymorphisms as the most relevant variants contributing to height variability. Animal models and deletions in humans suggest that alterations of HMGA2 might be relevant in causing short stature. Together, these observations led us to investigate the involvement of HMGA2 in idiopathic short stature (ISS) through an association study and a mutation screening.', 'We conducted an association study (155 ISS patients and 318 normal stature controls) with three HMGA2 single-nucleotide polymorphisms (SNPs) (SNPs rs1042725, rs7968682, and rs7968902) using a TaqMan-based assay. The patients were then analyzed by direct sequencing and multiplex ligation-dependent probe amplification (MLPA) to detect point mutations and genomic micro-rearrangements.', 'Considering a recessive model, an OR value >1 was observed for genotypes rs7968682 TT (Odds ratio (OR) = 1.72, confidence interval (CI): 1.14-2.58) and rs1042725 TT (OR = 1.51, CI: 1.00-2.28) in accordance to the effect exhibited by the single alleles in the general population. None of the patients carried possibly causative HMGA2 mutations.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': [\"3' Untranslated Regions\", 'Adolescent', 'Body Height', 'Case-Control Studies', 'Child', 'Child, Preschool', 'DNA Mutational Analysis', 'Female', 'Gene Frequency', 'Gene Rearrangement', 'Genetic Association Studies', 'Genetic Predisposition to Disease', 'Growth Disorders', 'HMGA2 Protein', 'Heterozygote', 'Homozygote', 'Humans', 'Italy', 'Male', 'Multiplex Polymerase Chain Reaction', 'Odds Ratio', 'Phenotype', 'Point Mutation', 'Polymorphism, Single Nucleotide', 'Risk Factors']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,536,445 | Is relatively Large Cervical Spinal Cord for Spinal Canal a Risk factor for Development of Cervical Spinal Cord Compression : A Cross-Sectional Study of 1211 Subjects? | {
"contexts": [
"A cross-sectional study.",
"This study aims to investigate the correlation of the cervical canal and spinal cord size, and evaluate whether the size of the spinal cord relative to the spinal canal is a risk factor for development of cervical spinal cord compression (SCC).",
"There is little knowledge regarding the relationship between cervical bony canal and spinal cord diameters. Although developmental canal stenosis has been recognized as a risk factor for SCC, the size of the spinal cord relative to the spinal canal has not been similarly discussed.",
"Cervical canal anteroposterior (AP) diameters on X-rays and AP diameters and cross-sectional areas of dural sacs and spinal cords on magnetic resonance imaging (MRI) were measured in 1211 healthy volunteers. Correlation between cervical canal diameter on X-rays and AP diameter and cross-sectional area of dural sacs and spinal cords on MRI were assessed. The ratio of the AP diameter of the spinal cord/dural sac was compared between subjects with and without SCC.",
"Spinal canal diameters were not highly correlated with spinal cord AP diameters and cross-sectional areas, although spinal canal diameters were significantly correlated with dural sac AP diameters. The individual difference in the ratio of the AP diameter of the spinal cord/dural sac was large (35%-93%), and the ratio was significantly larger in the subjects with SCC. An AP diameter ratio more than 62% at the C2 to C3 disc level is a risk factor for developing SCC."
],
"labels": [
"METHODS",
"OBJECTIVE",
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Anatomy, Cross-Sectional",
"Cervical Cord",
"Cohort Studies",
"Female",
"Humans",
"Magnetic Resonance Imaging",
"Male",
"Middle Aged",
"Organ Size",
"Risk Factors",
"Spinal Cord Compression",
"Young Adult"
]
} | The spinal cord diameter was independent of the spinal canal diameter and the relative size of a spinal cord and spinal canal differed on an individual basis. In addition, the ratio of spinal cord/dural sac in subjects with SCC was significantly larger. Therefore, a relatively large spinal cord could be a risk factor for SCC. | yes | [
{
"from": "human",
"value": "Question: Is relatively Large Cervical Spinal Cord for Spinal Canal a Risk factor for Development of Cervical Spinal Cord Compression : A Cross-Sectional Study of 1211 Subjects?\nContext: {'contexts': ['A cross-sectional study.', 'This study aims to investigate the correlation of the cervical canal and spinal cord size, and evaluate whether the size of the spinal cord relative to the spinal canal is a risk factor for development of cervical spinal cord compression (SCC).', 'There is little knowledge regarding the relationship between cervical bony canal and spinal cord diameters. Although developmental canal stenosis has been recognized as a risk factor for SCC, the size of the spinal cord relative to the spinal canal has not been similarly discussed.', 'Cervical canal anteroposterior (AP) diameters on X-rays and AP diameters and cross-sectional areas of dural sacs and spinal cords on magnetic resonance imaging (MRI) were measured in 1211 healthy volunteers. Correlation between cervical canal diameter on X-rays and AP diameter and cross-sectional area of dural sacs and spinal cords on MRI were assessed. The ratio of the AP diameter of the spinal cord/dural sac was compared between subjects with and without SCC.', 'Spinal canal diameters were not highly correlated with spinal cord AP diameters and cross-sectional areas, although spinal canal diameters were significantly correlated with dural sac AP diameters. The individual difference in the ratio of the AP diameter of the spinal cord/dural sac was large (35%-93%), and the ratio was significantly larger in the subjects with SCC. An AP diameter ratio more than 62% at the C2 to C3 disc level is a risk factor for developing SCC.'], 'labels': ['METHODS', 'OBJECTIVE', 'BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Anatomy, Cross-Sectional', 'Cervical Cord', 'Cohort Studies', 'Female', 'Humans', 'Magnetic Resonance Imaging', 'Male', 'Middle Aged', 'Organ Size', 'Risk Factors', 'Spinal Cord Compression', 'Young Adult']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,552,601 | Are we also interested in how fathers feel : a qualitative exploration of child health center nurses ' recognition of postnatal depression in fathers? | {
"contexts": [
"To become a parent is an emotionally life-changing experience. Paternal depression during the postnatal period has been associated with emotional and behavioral problems in children. The condition has predominantly been related to mothers, and the recognition of paternal postnatal depression (PND) has been paid less attention to. PND in fathers may be difficult to detect. However, nurses in pediatric services meet a lot of fathers and are in a position to detect a father who is suffering from PND. Therefore, the aim of this study was (a) to explore Child Health Center nurses' experiences of observing depression in fathers during the postnatal period; and (b) to explore hindrances of observing these fathers.",
"A qualitative descriptive study was conducted. Ten nurses were interviewed in 2014. A thematic data analysis was performed and data were analyzed for meaning.",
"Paternal PND was experienced as being vague and difficult to detect. Experiences of fathers with such problems were limited, and it was hard to grasp the health status of the fathers, something which was further complicated when routines were lacking or when gender attitudes influenced the daily work of the nurses."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Attitude of Health Personnel",
"Communication",
"Depression",
"Fathers",
"Female",
"Health Status",
"Humans",
"Interviews as Topic",
"Male",
"Maternal-Child Health Centers",
"Maternal-Child Nursing",
"Middle Aged",
"Postpartum Period",
"Qualitative Research"
]
} | This study contributes to an increased awareness of hindrances to the recognition of PND in fathers. The importance to detect all signals of paternal health status in fathers suffering from PND needs to be acknowledged. Overall, more attention needs to be paid to PND in fathers where a part of the solution for this is that they are screened just like the mothers. | yes | [
{
"from": "human",
"value": "Question: Are we also interested in how fathers feel : a qualitative exploration of child health center nurses ' recognition of postnatal depression in fathers?\nContext: {'contexts': [\"To become a parent is an emotionally life-changing experience. Paternal depression during the postnatal period has been associated with emotional and behavioral problems in children. The condition has predominantly been related to mothers, and the recognition of paternal postnatal depression (PND) has been paid less attention to. PND in fathers may be difficult to detect. However, nurses in pediatric services meet a lot of fathers and are in a position to detect a father who is suffering from PND. Therefore, the aim of this study was (a) to explore Child Health Center nurses' experiences of observing depression in fathers during the postnatal period; and (b) to explore hindrances of observing these fathers.\", 'A qualitative descriptive study was conducted. Ten nurses were interviewed in 2014. A thematic data analysis was performed and data were analyzed for meaning.', 'Paternal PND was experienced as being vague and difficult to detect. Experiences of fathers with such problems were limited, and it was hard to grasp the health status of the fathers, something which was further complicated when routines were lacking or when gender attitudes influenced the daily work of the nurses.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Attitude of Health Personnel', 'Communication', 'Depression', 'Fathers', 'Female', 'Health Status', 'Humans', 'Interviews as Topic', 'Male', 'Maternal-Child Health Centers', 'Maternal-Child Nursing', 'Middle Aged', 'Postpartum Period', 'Qualitative Research']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,527,512 | Does changing Default Fluoroscopy Equipment Settings decrease Entrance Skin Dose in Patients? | {
"contexts": [
"Proper fluoroscopic education and protocols may reduce the patient radiation dose but few prospective studies in urology have been performed. Using optically stimulated luminescent dosimeters we tested whether fluoroscopy time and/or entrance skin dose would decrease after educational and radiation reduction protocols.",
"At default manufacturer settings fluoroscopy time and entrance skin dose were prospectively measured using optically stimulated luminescent dosimeters in patients undergoing ureteroscopy, retrograde pyelogram/stent or percutaneous nephrolithotomy with access for stone disease. A validated radiation safety competency test was administered to urology faculty and residents before and after web based, hands-on fluoroscopy training. Default fluoroscopy settings were changed from continuous to intermittent pulse rate and from standard to half-dose output. Fluoroscopy time and entrance skin dose were then measured again.",
"The cohorts of 44 pre-protocol and 50 post-protocol patients with stones were similarly matched. The change in mean fluoroscopy time and entrance skin dose from pre-protocol to post-protocol was -0.6 minutes and -11.6 mGy (33%) for percutaneous nephrolithotomy (p = 0.62 and <0.001), 0.5 minutes and -0.1 mGy (34%) for ureteroscopy (p = 0.42 and 0.31), and 0.1 minute and -0.1 mGy (29%) for retrograde pyelogram/stent (p = 0.85 and 0.49, respectively). Urologist post-training test scores increased 30% from pretraining scores (p = 0.1)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Clinical Protocols",
"Female",
"Fluoroscopy",
"Humans",
"Kidney Calculi",
"Male",
"Middle Aged",
"Nephrostomy, Percutaneous",
"Prospective Studies",
"Radiation Dosage",
"Skin",
"Ureteroscopy"
]
} | Radiation safety training protocols improved clinical knowledge but did not significantly alter fluoroscopy time. Changing equipment default settings to intermittent pulse rate (12 frames per second) and half-dose lowered the entrance skin dose by 30% across all endourology patients but most significantly during percutaneous nephrolithotomy. To limit patient radiation exposure fluoroscopy default settings should be decreased before all endourology procedures and image equipment manufacturers should consider lowering standard default renal settings. | yes | [
{
"from": "human",
"value": "Question: Does changing Default Fluoroscopy Equipment Settings decrease Entrance Skin Dose in Patients?\nContext: {'contexts': ['Proper fluoroscopic education and protocols may reduce the patient radiation dose but few prospective studies in urology have been performed. Using optically stimulated luminescent dosimeters we tested whether fluoroscopy time and/or entrance skin dose would decrease after educational and radiation reduction protocols.', 'At default manufacturer settings fluoroscopy time and entrance skin dose were prospectively measured using optically stimulated luminescent dosimeters in patients undergoing ureteroscopy, retrograde pyelogram/stent or percutaneous nephrolithotomy with access for stone disease. A\\xa0validated radiation safety competency test was administered to urology faculty and residents before and after web based, hands-on fluoroscopy training. Default\\xa0fluoroscopy settings were changed from continuous to intermittent pulse\\xa0rate and from standard to half-dose output. Fluoroscopy time and entrance skin dose were then measured again.', 'The cohorts of 44 pre-protocol and 50 post-protocol patients with stones were similarly matched. The change in mean fluoroscopy time and entrance skin dose from pre-protocol to post-protocol was -0.6 minutes and -11.6 mGy (33%) for percutaneous nephrolithotomy (p = 0.62 and <0.001), 0.5 minutes and -0.1\\xa0mGy (34%) for ureteroscopy (p = 0.42 and 0.31), and 0.1 minute and -0.1 mGy (29%) for retrograde pyelogram/stent (p = 0.85 and 0.49, respectively). Urologist post-training test scores increased 30% from pretraining scores (p\\xa0=\\xa00.1).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Clinical Protocols', 'Female', 'Fluoroscopy', 'Humans', 'Kidney Calculi', 'Male', 'Middle Aged', 'Nephrostomy, Percutaneous', 'Prospective Studies', 'Radiation Dosage', 'Skin', 'Ureteroscopy']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,554,229 | Does monosialotetrahexosylganglioside inhibit the Expression of p-CREB and NR2B in the Auditory Cortex in Rats with Salicylate-Induced Tinnitus? | {
"contexts": [
"This study investigated the effects of monosialotetrahexosylganglioside (GM1) on the expression of N-methyl-D-aspartate receptor subunit 2B (NR2B) and phosphorylated (p)-cyclic AMP response element-binding protein (CREB) in the auditory cortex of rats with tinnitus.",
"Tinnitus-like behavior in rats was tested with the gap prepulse inhibition of acoustic startle paradigm. We then investigated the NR2B mRNA and protein and p-CREB protein levels in the auditory cortex of tinnitus rats compared with normal rats.",
"Rats treated for 4 days with salicylate exhibited tinnitus. NR2B mRNA and protein and p-CREB protein levels were upregulated in these animals, with expression returning to normal levels 14 days after cessation of treatment; baseline levels of NR2B and p-CREB were also restored by GM1 administration."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Auditory Cortex",
"Cyclic AMP Response Element-Binding Protein",
"Drug Evaluation, Preclinical",
"G(M1) Ganglioside",
"Gene Expression Regulation",
"Male",
"Nerve Tissue Proteins",
"Phosphorylation",
"Protein Processing, Post-Translational",
"RNA, Messenger",
"Rats",
"Rats, Sprague-Dawley",
"Receptors, N-Methyl-D-Aspartate",
"Sodium Salicylate",
"Tinnitus"
]
} | These data suggest that chronic salicylate administration induces tinnitus via upregulation of p-CREB and NR2B expression, and that GM1 can potentially be used to treat tinnitus. | yes | [
{
"from": "human",
"value": "Question: Does monosialotetrahexosylganglioside inhibit the Expression of p-CREB and NR2B in the Auditory Cortex in Rats with Salicylate-Induced Tinnitus?\nContext: {'contexts': ['This study investigated the effects of monosialotetrahexosylganglioside (GM1) on the expression of N-methyl-D-aspartate receptor subunit 2B (NR2B) and phosphorylated (p)-cyclic AMP response element-binding protein (CREB) in the auditory cortex of rats with tinnitus.', 'Tinnitus-like behavior in rats was tested with the gap prepulse inhibition of acoustic startle paradigm. We then investigated the NR2B mRNA and protein and p-CREB protein levels in the auditory cortex of tinnitus rats compared with normal rats.', 'Rats treated for 4 days with salicylate exhibited tinnitus. NR2B mRNA and protein and p-CREB protein levels were upregulated in these animals, with expression returning to normal levels 14 days after cessation of treatment; baseline levels of NR2B and p-CREB were also restored by GM1 administration.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Auditory Cortex', 'Cyclic AMP Response Element-Binding Protein', 'Drug Evaluation, Preclinical', 'G(M1) Ganglioside', 'Gene Expression Regulation', 'Male', 'Nerve Tissue Proteins', 'Phosphorylation', 'Protein Processing, Post-Translational', 'RNA, Messenger', 'Rats', 'Rats, Sprague-Dawley', 'Receptors, N-Methyl-D-Aspartate', 'Sodium Salicylate', 'Tinnitus']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,524,639 | Does gPR39 activate proliferation and differentiation of porcine intramuscular preadipocytes through targeting the PI3K/AKT cell signaling pathway? | {
"contexts": [
"The orphan G protein-coupled receptor (GPR) 39 was originally identified as the receptor of obestatin. In this study, the effects and mechanisms of GPR39 on cell proliferation and differentiation were investigated in cultured porcine intramuscular preadipocytes.",
"Morphology of preadipocytes and accumulated lipid droplets within cells were identified by an inverted microscope. After transfected with constructed pCMV-GPR39 plasmid, cell proliferation was measured by using methyl thiazolyl tetrazolium method, mRNA expression of GPR39, CCAAT/enhancer binding protein-α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPARγ), Caspase-9 and adipocyte determination and differentiation factor-1 (ADD1) was determined by RNA preparation and reverse transcription polymerase chain reaction, protein expression of phosphoinositide-3 kinase (PI3K), 3-phosphoinositide-dependent protein kinase 1, phosphorylated glycogen synthase kinase 3 (pGSK3), total Akt and phosphorylated Akt (pAkt) was analyzed by Western blot.",
"It found that GPR39 mRNA and protein were expressed in porcine intramuscular preadipocytes and its expression was significantly up-regulated after treatment with Zn(2+) whose function is found to be mediated by GPR39. Furthermore, over-expression of GPR39 further promoted the optical density value of cells, enhanced mRNA expression of PPARγ, C/EBPα and ADD1, and inhibited mRNA expression of Caspase-9. Protein expression of pGSK3 and pAkt was also increased by GPR39 stimulation. In addition, GPR39-induced proliferation and differentiation of porcine intramuscular preadipocytes was partially blocked by the Akt inhibitor (PDTC) and the PI3K inhibitor (LY294002)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adipocytes",
"Animals",
"CCAAT-Enhancer-Binding Protein-alpha",
"Caspase 9",
"Cell Differentiation",
"Cell Proliferation",
"Lipid Droplets",
"PPAR gamma",
"Phosphatidylinositol 3-Kinases",
"Proto-Oncogene Proteins c-akt",
"RNA, Messenger",
"Receptors, G-Protein-Coupled",
"Signal Transduction",
"Sterol Regulatory Element Binding Protein 1",
"Swine",
"Zinc"
]
} | It indicated that GPR39 was a transducer of Zn(2+), and enhanced proliferation and differentiation of porcine intramuscular preadipocytes through activation of the PI3K/Akt signaling pathway. | yes | [
{
"from": "human",
"value": "Question: Does gPR39 activate proliferation and differentiation of porcine intramuscular preadipocytes through targeting the PI3K/AKT cell signaling pathway?\nContext: {'contexts': ['The orphan G protein-coupled receptor (GPR) 39 was originally identified as the receptor of obestatin. In this study, the effects and mechanisms of GPR39 on cell proliferation and differentiation were investigated in cultured porcine intramuscular preadipocytes.', 'Morphology of preadipocytes and accumulated lipid droplets within cells were identified by an inverted microscope. After transfected with constructed pCMV-GPR39 plasmid, cell proliferation was measured by using methyl thiazolyl tetrazolium method, mRNA expression of GPR39, CCAAT/enhancer binding protein-α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPARγ), Caspase-9 and adipocyte determination and differentiation factor-1 (ADD1) was determined by RNA preparation and reverse transcription polymerase chain reaction, protein expression of phosphoinositide-3 kinase (PI3K), 3-phosphoinositide-dependent protein kinase 1, phosphorylated glycogen synthase kinase 3 (pGSK3), total Akt and phosphorylated Akt (pAkt) was analyzed by Western blot.', 'It found that GPR39 mRNA and protein were expressed in porcine intramuscular preadipocytes and its expression was significantly up-regulated after treatment with Zn(2+) whose function is found to be mediated by GPR39. Furthermore, over-expression of GPR39 further promoted the optical density value of cells, enhanced mRNA expression of PPARγ, C/EBPα and ADD1, and inhibited mRNA expression of Caspase-9. Protein expression of pGSK3 and pAkt was also increased by GPR39 stimulation. In addition, GPR39-induced proliferation and differentiation of porcine intramuscular preadipocytes was partially blocked by the Akt inhibitor (PDTC) and the PI3K inhibitor (LY294002).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adipocytes', 'Animals', 'CCAAT-Enhancer-Binding Protein-alpha', 'Caspase 9', 'Cell Differentiation', 'Cell Proliferation', 'Lipid Droplets', 'PPAR gamma', 'Phosphatidylinositol 3-Kinases', 'Proto-Oncogene Proteins c-akt', 'RNA, Messenger', 'Receptors, G-Protein-Coupled', 'Signal Transduction', 'Sterol Regulatory Element Binding Protein 1', 'Swine', 'Zinc']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,555,141 | Do composite Measures of Individual and Area-Level Socio-Economic Status Are Associated with Visual Impairment in Singapore? | {
"contexts": [
"To investigate the independent relationship of individual- and area-level socio-economic status (SES) with the presence and severity of visual impairment (VI) in an Asian population.",
"Cross-sectional data from 9993 Chinese, Malay and Indian adults aged 40-80 years who participated in the Singapore Epidemiology of eye Diseases (2004-2011) in Singapore. Based on the presenting visual acuity (PVA) in the better-seeing eye, VI was categorized into normal vision (logMAR≤0.30), low vision (logMAR>0.30<1.00), and blindness (logMAR≥1.00). Any VI was defined as low vision/blindness in the PVA of better-seeing eye. Individual-level low-SES was defined as a composite of primary-level education, monthly income<2000 SGD and residing in 1 or 2-room public apartment. An area-level SES was assessed using a socio-economic disadvantage index (SEDI), created using 12 variables from the 2010 Singapore census. A high SEDI score indicates a relatively poor SES. Associations between SES measures and presence and severity of VI were examined using multi-level, mixed-effects logistic and multinomial regression models.",
"The age-adjusted prevalence of any VI was 19.62% (low vision = 19%, blindness = 0.62%). Both individual- and area-level SES were positively associated with any VI and low vision after adjusting for confounders. The odds ratio (95% confidence interval) of any VI was 2.11(1.88-2.37) for low-SES and 1.07(1.02-1.13) per 1 standard deviation increase in SEDI. When stratified by unilateral/bilateral categories, while low SES showed significant associations with all categories, SEDI showed a significant association with bilateral low vision only. The association between low SES and any VI remained significant among all age, gender and ethnic sub-groups. Although a consistent positive association was observed between area-level SEDI and any VI, the associations were significant among participants aged 40-65 years and male."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Cross-Sectional Studies",
"Female",
"Humans",
"Male",
"Middle Aged",
"Singapore",
"Social Class",
"Vision Disorders"
]
} | In this community-based sample of Asian adults, both individual- and area-level SES were independently associated with the presence and severity of VI. | yes | [
{
"from": "human",
"value": "Question: Do composite Measures of Individual and Area-Level Socio-Economic Status Are Associated with Visual Impairment in Singapore?\nContext: {'contexts': ['To investigate the independent relationship of individual- and area-level socio-economic status (SES) with the presence and severity of visual impairment (VI) in an Asian population.', 'Cross-sectional data from 9993 Chinese, Malay and Indian adults aged 40-80 years who participated in the Singapore Epidemiology of eye Diseases (2004-2011) in Singapore. Based on the presenting visual acuity (PVA) in the better-seeing eye, VI was categorized into normal vision (logMAR≤0.30), low vision (logMAR>0.30<1.00), and blindness (logMAR≥1.00). Any VI was defined as low vision/blindness in the PVA of better-seeing eye. Individual-level low-SES was defined as a composite of primary-level education, monthly income<2000 SGD and residing in 1 or 2-room public apartment. An area-level SES was assessed using a socio-economic disadvantage index (SEDI), created using 12 variables from the 2010 Singapore census. A high SEDI score indicates a relatively poor SES. Associations between SES measures and presence and severity of VI were examined using multi-level, mixed-effects logistic and multinomial regression models.', 'The age-adjusted prevalence of any VI was 19.62% (low vision = 19%, blindness = 0.62%). Both individual- and area-level SES were positively associated with any VI and low vision after adjusting for confounders. The odds ratio (95% confidence interval) of any VI was 2.11(1.88-2.37) for low-SES and 1.07(1.02-1.13) per 1 standard deviation increase in SEDI. When stratified by unilateral/bilateral categories, while low SES showed significant associations with all categories, SEDI showed a significant association with bilateral low vision only. The association between low SES and any VI remained significant among all age, gender and ethnic sub-groups. Although a consistent positive association was observed between area-level SEDI and any VI, the associations were significant among participants aged 40-65 years and male.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Cross-Sectional Studies', 'Female', 'Humans', 'Male', 'Middle Aged', 'Singapore', 'Social Class', 'Vision Disorders']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,555,148 | Does neuromuscular electrical stimulation-assisted gait increase muscle strength and volume in children with unilateral spastic cerebral palsy? | {
"contexts": [
"To determine if neuromuscular electrical stimulation (NMES) applied to the ankle dorsiflexors during gait improves muscle volume and strength in children with unilateral spastic cerebral palsy (CP).",
"Thirty-two children (15 females, 17 males; mean age 10y 8mo, age range 5y 5mo-18y 1mo) with unilateral spastic CP and a Gross Motor Function Classification System of level I or level II were randomly assigned to either the 8-week daily NMES treatment group or control group (usual or conventional treatments). Outcomes at week 8 (post-NMES) and week 14 (carryover) included magnetic resonance imaging for muscle volumes (tibialis anterior, anterior compartment, and gastrocnemius), strength (hand-held dynamometry for isometric dorsiflexion strength and heel raises for functional strength), and clinical measures for lower limb selective motor control.",
"At week 8, the treatment group demonstrated significantly (p<0.05) increased muscle volumes for tibialis anterior, anterior compartment, medial and lateral gastrocnemius, and dorsiflexion strength not only when compared to their baseline values but also when compared to the control group at week 8. At week 14, both tibialis anterior and lateral gastrocnemius volumes in the treatment group remained significantly increased when compared to their baseline values. However, only lateral gastrocnemius volumes had significantly greater values when compared to the control group at week 14. There were no between group differences in the clinical measures for lower limb selective motor control at week 8 and 14."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Cerebral Palsy",
"Child",
"Child, Preschool",
"Electric Stimulation Therapy",
"Female",
"Follow-Up Studies",
"Gait",
"Humans",
"Magnetic Resonance Imaging",
"Male",
"Muscle Spasticity",
"Muscle Strength",
"Muscle, Skeletal",
"Outcome Assessment (Health Care)"
]
} | Eight weeks of daily NMES-assisted gait increases muscle volume and strength of the stimulated ankle dorsiflexors in children with unilateral spastic CP. These changes are use-dependent and do not carry over after the 8-week treatment period. Gastrocnemius volume also increased post-treatment with carryover at week 14. | yes | [
{
"from": "human",
"value": "Question: Does neuromuscular electrical stimulation-assisted gait increase muscle strength and volume in children with unilateral spastic cerebral palsy?\nContext: {'contexts': ['To determine if neuromuscular electrical stimulation (NMES) applied to the ankle dorsiflexors during gait improves muscle volume and strength in children with unilateral spastic cerebral palsy (CP).', 'Thirty-two children (15 females, 17 males; mean age 10y 8mo, age range 5y 5mo-18y 1mo) with unilateral spastic CP and a Gross Motor Function Classification System of level I or level II were randomly assigned to either the 8-week daily NMES treatment group or control group (usual or conventional treatments). Outcomes at week 8 (post-NMES) and week 14 (carryover) included magnetic resonance imaging for muscle volumes (tibialis anterior, anterior compartment, and gastrocnemius), strength (hand-held dynamometry for isometric dorsiflexion strength and heel raises for functional strength), and clinical measures for lower limb selective motor control.', 'At week 8, the treatment group demonstrated significantly (p<0.05) increased muscle volumes for tibialis anterior, anterior compartment, medial and lateral gastrocnemius, and dorsiflexion strength not only when compared to their baseline values but also when compared to the control group at week 8. At week 14, both tibialis anterior and lateral gastrocnemius volumes in the treatment group remained significantly increased when compared to their baseline values. However, only lateral gastrocnemius volumes had significantly greater values when compared to the control group at week 14. There were no between group differences in the clinical measures for lower limb selective motor control at week 8 and 14.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Cerebral Palsy', 'Child', 'Child, Preschool', 'Electric Stimulation Therapy', 'Female', 'Follow-Up Studies', 'Gait', 'Humans', 'Magnetic Resonance Imaging', 'Male', 'Muscle Spasticity', 'Muscle Strength', 'Muscle, Skeletal', 'Outcome Assessment (Health Care)']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,528,235 | Do a Thalamic-Fronto-Parietal Structural Covariance Network Emerging in the Course of Recovery from Hand Paresis after Ischemic Stroke? | {
"contexts": [
"To describe structural covariance networks of gray matter volume (GMV) change in 28 patients with first-ever stroke to the primary sensorimotor cortices, and to investigate their relationship to hand function recovery and local GMV change.",
"Tensor-based morphometry maps derived from high-resolution structural images were subject to principal component analyses to identify the networks. We calculated correlations between network expression and local GMV change, sensorimotor hand function and lesion volume. To verify which of the structural covariance networks of GMV change have a significant relationship to hand function, we performed an additional multivariate regression approach.",
"Expression of the second network, explaining 9.1% of variance, correlated with GMV increase in the medio-dorsal (md) thalamus and hand motor skill. Patients with positive expression coefficients were distinguished by significantly higher GMV increase of this structure during stroke recovery. Significant nodes of this network were located in md thalamus, dorsolateral prefrontal cortex, and higher order sensorimotor cortices. Parameter of hand function had a unique relationship to the network and depended on an interaction between network expression and lesion volume. Inversely, network expression is limited in patients with large lesion volumes."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": []
} | Chronic phase of sensorimotor cortical stroke has been characterized by a large scale co-varying structural network in the ipsilesional hemisphere associated specifically with sensorimotor hand skill. Its expression is related to GMV increase of md thalamus, one constituent of the network, and correlated with the cortico-striato-thalamic loop involved in control of motor execution and higher order sensorimotor cortices. A close relation between expression of this network with degree of recovery might indicate reduced compensatory resources in the impaired subgroup. | yes | [
{
"from": "human",
"value": "Question: Do a Thalamic-Fronto-Parietal Structural Covariance Network Emerging in the Course of Recovery from Hand Paresis after Ischemic Stroke?\nContext: {'contexts': ['To describe structural covariance networks of gray matter volume (GMV) change in 28 patients with first-ever stroke to the primary sensorimotor cortices, and to investigate their relationship to hand function recovery and local GMV change.', 'Tensor-based morphometry maps derived from high-resolution structural images were subject to principal component analyses to identify the networks. We calculated correlations between network expression and local GMV change, sensorimotor hand function and lesion volume. To verify which of the structural covariance networks of GMV change have a significant relationship to hand function, we performed an additional multivariate regression approach.', 'Expression of the second network, explaining 9.1% of variance, correlated with GMV increase in the medio-dorsal (md) thalamus and hand motor skill. Patients with positive expression coefficients were distinguished by significantly higher GMV increase of this structure during stroke recovery. Significant nodes of this network were located in md thalamus, dorsolateral prefrontal cortex, and higher order sensorimotor cortices. Parameter of hand function had a unique relationship to the network and depended on an interaction between network expression and lesion volume. Inversely, network expression is limited in patients with large lesion volumes.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': []}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,545,343 | Is immediate post-traumatic pulmonary embolism associated with right ventricular dysfunction? | {
"contexts": [
"Post-traumatic pulmonary embolic events are associated with significant morbidity. Computed tomographic (CT) measurements can be predictive of right ventricular (RV) dysfunction after pulmonary embolus. However, it remains unclear whether these physiologic effects or clinical outcomes differ between early (<48 hours) vs late (≥48 hours) post-traumatic pulmonary embolism (PE).",
"All patients with traumatic injury and CT evidence of PE between 2008 and 2013 were identified. The study population was divided into 2 groups based on the time of diagnosis of the PE. The primary outcome was PE-related mortality.",
"Fifty patients were identified (14 early PE and 36 late PE). Patients sustaining a late PE had a higher PE-related mortality rate (16.7% vs 0%), larger RV diameters, RV/left ventricular diameter ratios, RV volumes, and RV/left ventricular volume ratios (all P < .05)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Computed Tomography Angiography",
"Female",
"Heart Ventricles",
"Humans",
"Male",
"Middle Aged",
"Prognosis",
"Pulmonary Embolism",
"Retrospective Studies",
"Time Factors",
"Ventricular Dysfunction, Right",
"Wounds and Injuries"
]
} | Early post-traumatic PE appears to be associated with fewer RV physiologic changes than late post-traumatic PE and may be representative of primary pulmonary thrombosis. It remains to be seen whether early CT findings of PE should be managed according to previously established guidelines for embolic disease. | no | [
{
"from": "human",
"value": "Question: Is immediate post-traumatic pulmonary embolism associated with right ventricular dysfunction?\nContext: {'contexts': ['Post-traumatic pulmonary embolic events are associated with significant morbidity. Computed tomographic (CT) measurements can be predictive of right ventricular (RV) dysfunction after pulmonary embolus. However, it remains unclear whether these physiologic effects or clinical outcomes differ between early (<48 hours) vs late (≥48 hours) post-traumatic pulmonary embolism (PE).', 'All patients with traumatic injury and CT evidence of PE between 2008 and 2013 were identified. The study population was divided into 2 groups based on the time of diagnosis of the PE. The primary outcome was PE-related mortality.', 'Fifty patients were identified (14 early PE and 36 late PE). Patients sustaining a late PE had a higher PE-related mortality rate (16.7% vs 0%), larger RV diameters, RV/left ventricular diameter ratios, RV volumes, and RV/left ventricular volume ratios (all P < .05).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Computed Tomography Angiography', 'Female', 'Heart Ventricles', 'Humans', 'Male', 'Middle Aged', 'Prognosis', 'Pulmonary Embolism', 'Retrospective Studies', 'Time Factors', 'Ventricular Dysfunction, Right', 'Wounds and Injuries']}"
},
{
"from": "gpt",
"value": "Answer: no"
}
]
|
26,542,693 | Do integrative Mouse and Human Studies Implicate ANGPT1 and ZBTB7C as Susceptibility Genes to Ischemic Injury? | {
"contexts": [
"The extent of ischemic injury in response to cerebral ischemia is known to be affected by native vasculature. However, the nonvascular and dynamic vascular responses and their genetic basis are not well understood.",
"We performed a genome-wide association study in 235 mice from 33 inbred strains using the middle cerebral artery occlusion model. Population structure and genetic relatedness were accounted for using the efficient mixed-model association method. Human orthologs to the genes associated with the significant and suggestive single-nucleotide polymorphisms from the mouse strain survey were examined in patients with M1 occlusions admitted with signs and symptoms of acute ischemic stroke.",
"We identified 4 genome-wide significant and suggestive single-nucleotide polymorphisms to be associated with infarct volume in mice (rs3694965, P=2.17×10(-7); rs31924033, P=5.61×10(-6); rs32249495, P=2.08×10(-7); and rs3677406, P=9.56×10(-6)). rs32249495, which corresponds to angiopoietin-1 (ANGPT1), was also significant in the recessive model in humans, whereas rs1944577, which corresponds to ZBTB7C, was nominally significant in both the additive and dominant genetic models in humans. ZBTB7C was shown to be upregulated in endothelial cells using both in vitro and in vivo models of ischemia."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Angiopoietin-1",
"Animals",
"Brain Ischemia",
"Female",
"Genetic Predisposition to Disease",
"Genome-Wide Association Study",
"Humans",
"Male",
"Mice",
"Mice, 129 Strain",
"Mice, Inbred BALB C",
"Mice, Inbred C57BL",
"Mice, Inbred DBA",
"Mice, Inbred NOD",
"Polymorphism, Single Nucleotide",
"Proteins",
"Species Specificity"
]
} | Genetic variations of ANGPT1 and ZBTB7C are associated with increased infarct size in both mice and humans. ZBTB7C may modulate the ischemic response via neuronal apoptosis and dynamic collateralization and, in addition to ANGPT1, may serve as potential novel targets for treatments of cerebral ischemia. | yes | [
{
"from": "human",
"value": "Question: Do integrative Mouse and Human Studies Implicate ANGPT1 and ZBTB7C as Susceptibility Genes to Ischemic Injury?\nContext: {'contexts': ['The extent of ischemic injury in response to cerebral ischemia is known to be affected by native vasculature. However, the nonvascular and dynamic vascular responses and their genetic basis are not well understood.', 'We performed a genome-wide association study in 235 mice from 33 inbred strains using the middle cerebral artery occlusion model. Population structure and genetic relatedness were accounted for using the efficient mixed-model association method. Human orthologs to the genes associated with the significant and suggestive single-nucleotide polymorphisms from the mouse strain survey were examined in patients with M1 occlusions admitted with signs and symptoms of acute ischemic stroke.', 'We identified 4 genome-wide significant and suggestive single-nucleotide polymorphisms to be associated with infarct volume in mice (rs3694965, P=2.17×10(-7); rs31924033, P=5.61×10(-6); rs32249495, P=2.08×10(-7); and rs3677406, P=9.56×10(-6)). rs32249495, which corresponds to angiopoietin-1 (ANGPT1), was also significant in the recessive model in humans, whereas rs1944577, which corresponds to ZBTB7C, was nominally significant in both the additive and dominant genetic models in humans. ZBTB7C was shown to be upregulated in endothelial cells using both in vitro and in vivo models of ischemia.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Angiopoietin-1', 'Animals', 'Brain Ischemia', 'Female', 'Genetic Predisposition to Disease', 'Genome-Wide Association Study', 'Humans', 'Male', 'Mice', 'Mice, 129 Strain', 'Mice, Inbred BALB C', 'Mice, Inbred C57BL', 'Mice, Inbred DBA', 'Mice, Inbred NOD', 'Polymorphism, Single Nucleotide', 'Proteins', 'Species Specificity']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,527,820 | Is anti-HIV-1 activity determined by β-galactosidase activity in the multinuclear activation of an indicator assay comparable with that by a conventional focus counting method? | {
"contexts": [
"Direct comparison of enzymatic and original blue cell-counting detections with the multinuclear activation of an indicator (MAGI) cells, so far, remains to be performed in parallel. Although inhibitors for reverse transcription solely inhibit the reverse transcription step, those for HIV-1 entry block syncytium formation of HIV-1-infected MAGI cells in addition to the entry (dual inhibition). It raises a concern that reduction of enzymatic activity is artificially influenced by syncytium-blocking activity of inhibitors for entry.",
"The MAGI cells with a syncytium inducible strain, HIV-1IIIB, were used for anti-HIV activity determination both with conventional counting with X-Gal staining and measurement of chlorophenol red β-d-galactopyranoside conversion with a plate reader.",
"Infectivity of HIV-1 in the MAGI cells was highly correlated with both methods. In microscopic observation, small blue cells with single or a couple of nuclei were dominantly observed in the presence of inhibitors for entry, but not in the presence of those for reverse transcription. Actual anti-HIV-1 activities were comparable or moderately sensitive in the chlorophenol red β-d-galactopyranoside method."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Anti-HIV Agents",
"Benzoxazines",
"Dose-Response Relationship, Drug",
"Genes, Reporter",
"HIV-1",
"HeLa Cells",
"Humans",
"Microbial Sensitivity Tests",
"Structure-Activity Relationship",
"Zidovudine",
"beta-Galactosidase"
]
} | Antiviral activities of inhibitors for entry obtained from both enzymatic and counting methods appear to be comparable, even in infection of a highly syncytia inducible HIV-1IIIB strain. | yes | [
{
"from": "human",
"value": "Question: Is anti-HIV-1 activity determined by β-galactosidase activity in the multinuclear activation of an indicator assay comparable with that by a conventional focus counting method?\nContext: {'contexts': ['Direct comparison of enzymatic and original blue cell-counting detections with the multinuclear activation of an indicator (MAGI) cells, so far, remains to be performed in parallel. Although inhibitors for reverse transcription solely inhibit the reverse transcription step, those for HIV-1 entry block syncytium formation of HIV-1-infected MAGI cells in addition to the entry (dual inhibition). It raises a concern that reduction of enzymatic activity is artificially influenced by syncytium-blocking activity of inhibitors for entry.', 'The MAGI cells with a syncytium inducible strain, HIV-1IIIB, were used for anti-HIV activity determination both with conventional counting with X-Gal staining and measurement of chlorophenol red β-d-galactopyranoside conversion with a plate reader.', 'Infectivity of HIV-1 in the MAGI cells was highly correlated with both methods. In microscopic observation, small blue cells with single or a couple of nuclei were dominantly observed in the presence of inhibitors for entry, but not in the presence of those for reverse transcription. Actual anti-HIV-1 activities were comparable or moderately sensitive in the chlorophenol red β-d-galactopyranoside method.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Anti-HIV Agents', 'Benzoxazines', 'Dose-Response Relationship, Drug', 'Genes, Reporter', 'HIV-1', 'HeLa Cells', 'Humans', 'Microbial Sensitivity Tests', 'Structure-Activity Relationship', 'Zidovudine', 'beta-Galactosidase']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,549,593 | Is overexpression of miR-210 Associated with Poor Prognosis of Acute Myeloid Leukemia? | {
"contexts": [
"MicroRNAs play important roles in regulation of the initiation and progression of AML. MiR-210 is closely related with cancer development; however, whether miR-210 expression level correlates with clinical correlation in AML is unknown. Thus, the aim of this study was to investigate the potential relationship between miR-210 expression and AML prognosis.",
"Real-time quantitative PCR was carried out to examine the expression level of miR-210 in bone marrow and serum obtained from AML patients and healthy controls. Then the correlation between miR-210 expression and a variety of important clinical parameters (such as overall survival, relapse-free survival, and prognostic value) were further studied.",
"The expression level of miR-210 was significantly higher in the bone marrow and serum of AML patients than that of healthy controls (p<0.001). Moreover, miR-210 expression was associated with various AML clinicopathological parameters, including FAB classification and cytogenetics. The serum miR-210 expression level was reduced significantly when the patients achieved complete remission (p=0.02). The high miR-210 expression group had both poorer relapse-free survival (p=0.015) and worse overall survival (p=0.008). In the multivariate analysis model, miR-210 was identified as an independent prognostic marker."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Adult",
"Aged",
"Bone Marrow",
"Case-Control Studies",
"Child",
"Child, Preschool",
"Disease Progression",
"Disease-Free Survival",
"Female",
"Gene Expression Regulation, Leukemic",
"Humans",
"Leukemia, Myeloid, Acute",
"Male",
"MicroRNAs",
"Middle Aged",
"Multivariate Analysis",
"Prognosis",
"Real-Time Polymerase Chain Reaction",
"Recurrence",
"Remission Induction",
"Treatment Outcome",
"Young Adult"
]
} | MiR-210 up-regulation was associated with poor prognosis in AML and it might be useful as a marker for predicting the clinical outcome of AML patients. | yes | [
{
"from": "human",
"value": "Question: Is overexpression of miR-210 Associated with Poor Prognosis of Acute Myeloid Leukemia?\nContext: {'contexts': ['MicroRNAs play important roles in regulation of the initiation and progression of AML. MiR-210 is closely related with cancer development; however, whether miR-210 expression level correlates with clinical correlation in AML is unknown. Thus, the aim of this study was to investigate the potential relationship between miR-210 expression and AML prognosis.', 'Real-time quantitative PCR was carried out to examine the expression level of miR-210 in bone marrow and serum obtained from AML patients and healthy controls. Then the correlation between miR-210 expression and a variety of important clinical parameters (such as overall survival, relapse-free survival, and prognostic value) were further studied.', 'The expression level of miR-210 was significantly higher in the bone marrow and serum of AML patients than that of healthy controls (p<0.001). Moreover, miR-210 expression was associated with various AML clinicopathological parameters, including FAB classification and cytogenetics. The serum miR-210 expression level was reduced significantly when the patients achieved complete remission (p=0.02). The high miR-210 expression group had both poorer relapse-free survival (p=0.015) and worse overall survival (p=0.008). In the multivariate analysis model, miR-210 was identified as an independent prognostic marker.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Aged', 'Bone Marrow', 'Case-Control Studies', 'Child', 'Child, Preschool', 'Disease Progression', 'Disease-Free Survival', 'Female', 'Gene Expression Regulation, Leukemic', 'Humans', 'Leukemia, Myeloid, Acute', 'Male', 'MicroRNAs', 'Middle Aged', 'Multivariate Analysis', 'Prognosis', 'Real-Time Polymerase Chain Reaction', 'Recurrence', 'Remission Induction', 'Treatment Outcome', 'Young Adult']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,525,527 | Do influence of the Number of Predicted Words on Text Input Speed in Participants With Cervical Spinal Cord Injury? | {
"contexts": [
"To determine whether the number of words displayed in the word prediction software (WPS) list affects text input speed (TIS) in people with cervical spinal cord injury (SCI), and whether any influence is dependent on the level of the lesion.",
"A cross-sectional trial.",
"A rehabilitation center.",
"Persons with cervical SCI (N=45). Lesion level was high (C4 and C5, American Spinal Injury Association [ASIA] grade A or B) for 15 participants (high-lesion group) and low (between C6 and C8, ASIA grade A or B) for 30 participants (low-lesion group).",
"TIS was evaluated during four 10-minute copying tasks: (1) without WPS (Without); (2) with a display of 3 predicted words (3Words); (3) with a display of 6 predicted words (6Words); and (4) with a display of 8 predicted words (8Words).",
"During the 4 copying tasks, TIS was measured objectively (characters per minute, number of errors) and subjectively through subject report (fatigue, perception of speed, cognitive load, satisfaction).",
"For participants with low-cervical SCI, TIS without WPS was faster than with WPS, regardless of the number of words displayed (P<.001). For participants with high-cervical SCI, the use of WPS did not influence TIS (P=.99). There was no influence of the number of words displayed in a word prediction list on TIS; however, perception of TIS differed according to lesion level."
],
"labels": [
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Cervical Vertebrae",
"Communication Aids for Disabled",
"Cross-Sectional Studies",
"Female",
"Humans",
"Male",
"Prospective Studies",
"Quadriplegia",
"Software",
"Spinal Cord Injuries",
"User-Computer Interface"
]
} | For persons with low-cervical SCI, a small number of words should be displayed, or WPS should not be used at all. For persons with high-cervical SCI, a larger number of words displayed increases the comfort of use of WPS. | yes | [
{
"from": "human",
"value": "Question: Do influence of the Number of Predicted Words on Text Input Speed in Participants With Cervical Spinal Cord Injury?\nContext: {'contexts': ['To determine whether the number of words displayed in the word prediction software (WPS) list affects text input speed (TIS) in people with cervical spinal cord injury (SCI), and whether any influence is dependent on the level of the lesion.', 'A cross-sectional trial.', 'A rehabilitation center.', 'Persons with cervical SCI (N=45). Lesion level was high (C4 and C5, American Spinal Injury Association [ASIA] grade A or B) for 15 participants (high-lesion group) and low (between C6 and C8, ASIA grade A or B) for 30 participants (low-lesion group).', 'TIS was evaluated during four 10-minute copying tasks: (1) without WPS (Without); (2) with a display of 3 predicted words (3Words); (3) with a display of 6 predicted words (6Words); and (4) with a display of 8 predicted words (8Words).', 'During the 4 copying tasks, TIS was measured objectively (characters per minute, number of errors) and subjectively through subject report (fatigue, perception of speed, cognitive load, satisfaction).', 'For participants with low-cervical SCI, TIS without WPS was faster than with WPS, regardless of the number of words displayed (P<.001). For participants with high-cervical SCI, the use of WPS did not influence TIS (P=.99). There was no influence of the number of words displayed in a word prediction list on TIS; however, perception of TIS differed according to lesion level.'], 'labels': ['OBJECTIVE', 'METHODS', 'METHODS', 'METHODS', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Cervical Vertebrae', 'Communication Aids for Disabled', 'Cross-Sectional Studies', 'Female', 'Humans', 'Male', 'Prospective Studies', 'Quadriplegia', 'Software', 'Spinal Cord Injuries', 'User-Computer Interface']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,534,998 | Does fEV1/FEV6 in Primary Care be a Reliable and Easy Method for the Diagnosis of COPD? | {
"contexts": [
"FEV6 can be used as a convenient alternative to FVC. The aim of this study was to determine an alternative to the fixed cutoff points of FEV1/FVC <0.70 suitable for FEV1/FEV6 in primary care.",
"Pulmonary function testing was conducted on volunteers recruited from 4 community centers in Xi'an, China, between July and August 2012. Participants underwent 3 FVC maneuvers. The maneuver with the best FEV1 was retained. FVC, FEV1, and FEV6 were measured by portable spirometer. The receiver operating characteristic curves that corresponded to the optimal combination of sensitivity and specificity for FEV1/FEV6 were determined. A kappa test was used to compare the agreement between FEV1/FVC and FEV1/FEV6. The positive predictive value and negative predictive value were also calculated.",
"A total of 767 volunteers participated in this study, of whom 297 were male and 470 were female. Considering FEV1/FVC <0.70 as the accepted standard for COPD, the area under the curve was 98% (P < .001), and the FEV1/FEV6 cutoff, corresponding to the greatest sum of sensitivity and specificity, was 0.72. For the total population, the FEV1/FEV6 sensitivity, specificity, positive predictive value, and negative predictive value were 96.9, 98.8, 95.8, and 99.2%, respectively. The agreement between the 2 cutoff points was excellent, and the kappa value was 0.954."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Female",
"Forced Expiratory Volume",
"Humans",
"Male",
"Middle Aged",
"Predictive Value of Tests",
"Primary Health Care",
"Pulmonary Disease, Chronic Obstructive",
"ROC Curve",
"Reference Values",
"Reproducibility of Results",
"Sensitivity and Specificity",
"Spirometry"
]
} | FEV1/FEV6 <0.72 can be used in primary care as a valid alternative to FEV1/FVC <0.70 as a fixed cutoff point for the detection of COPD in adults. This study suggests that FEV1/FEV6 is an effective and well validated option that should be used in primary care to detect COPD, which is a rampant problem. | yes | [
{
"from": "human",
"value": "Question: Does fEV1/FEV6 in Primary Care be a Reliable and Easy Method for the Diagnosis of COPD?\nContext: {'contexts': ['FEV6 can be used as a convenient alternative to FVC. The aim of this study was to determine an alternative to the fixed cutoff points of FEV1/FVC <0.70 suitable for FEV1/FEV6 in primary care.', \"Pulmonary function testing was conducted on volunteers recruited from 4 community centers in Xi'an, China, between July and August 2012. Participants underwent 3 FVC maneuvers. The maneuver with the best FEV1 was retained. FVC, FEV1, and FEV6 were measured by portable spirometer. The receiver operating characteristic curves that corresponded to the optimal combination of sensitivity and specificity for FEV1/FEV6 were determined. A kappa test was used to compare the agreement between FEV1/FVC and FEV1/FEV6. The positive predictive value and negative predictive value were also calculated.\", 'A total of 767 volunteers participated in this study, of whom 297 were male and 470 were female. Considering FEV1/FVC <0.70 as the accepted standard for COPD, the area under the curve was 98% (P < .001), and the FEV1/FEV6 cutoff, corresponding to the greatest sum of sensitivity and specificity, was 0.72. For the total population, the FEV1/FEV6 sensitivity, specificity, positive predictive value, and negative predictive value were 96.9, 98.8, 95.8, and 99.2%, respectively. The agreement between the 2 cutoff points was excellent, and the kappa value was 0.954.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Female', 'Forced Expiratory Volume', 'Humans', 'Male', 'Middle Aged', 'Predictive Value of Tests', 'Primary Health Care', 'Pulmonary Disease, Chronic Obstructive', 'ROC Curve', 'Reference Values', 'Reproducibility of Results', 'Sensitivity and Specificity', 'Spirometry']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,547,796 | Are myopia and/or longer axial length protective against diabetic retinopathy : a meta-analysis? | {
"contexts": [
"To evaluate the current evidence of the relationship between myopia, together with its structural and refractive component, and diabetic retinopathy (DR) risk.",
"A systematic search was performed up to April, 2015. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated employing random-effects models. Three models were used to assess the association between myopia and risk of DR: axial length (AL) (per millimetre increase) and DR; myopia (myopia versus non-myopia) and DR; refractive error (RE) (per D decrease) and DR. Publication bias of the literature was evaluated using Begg's funnel plots and Egger's test.",
"A total of 11 studies that met the predefined criteria were included in this meta-analysis. Overall, longer AL (per millimetre increase) was associa-ted with a significantly decreased risk of DR (combined OR, 0.75; 95% CI, 0.65-0.86; p < 0.001); myopic eyes (myopia versus non-myopia) showed a lower risk of DR (combined OR, 0.70; 95% CI, 0.58-0.85; p < 0.001). A greater degree of myopic RE (per D decrease) also revealed a significantly decreased risk of DR (combined OR, 0.89; 95% CI, 0.85-0.93; p < 0.001). The sensitivity analyses and cumulative meta-analysis showed similar results. No publication bias was detected in any of the three models."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": []
} | This meta-analysis suggests that both myopic refraction and longer AL are associated with a lower risk of DR. Further studies are needed to determine exact mechanisms underpinning the protective effect of myopia against DR. | yes | [
{
"from": "human",
"value": "Question: Are myopia and/or longer axial length protective against diabetic retinopathy : a meta-analysis?\nContext: {'contexts': ['To evaluate the current evidence of the relationship between myopia, together with its structural and refractive component, and diabetic retinopathy (DR) risk.', \"A systematic search was performed up to April, 2015. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated employing random-effects models. Three models were used to assess the association between myopia and risk of DR: axial length (AL) (per millimetre increase) and DR; myopia (myopia versus non-myopia) and DR; refractive error (RE) (per D decrease) and DR. Publication bias of the literature was evaluated using Begg's funnel plots and Egger's test.\", 'A total of 11 studies that met the predefined criteria were included in this meta-analysis. Overall, longer AL (per millimetre increase) was associa-ted with a significantly decreased risk of DR (combined OR, 0.75; 95% CI, 0.65-0.86; p\\xa0<\\xa00.001); myopic eyes (myopia versus non-myopia) showed a lower risk of DR (combined OR, 0.70; 95% CI, 0.58-0.85; p\\xa0<\\xa00.001). A greater degree of myopic RE (per D decrease) also revealed a significantly decreased risk of DR (combined OR, 0.89; 95% CI, 0.85-0.93; p\\xa0<\\xa00.001). The sensitivity analyses and cumulative meta-analysis showed similar results. No publication bias was detected in any of the three models.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': []}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,524,412 | Does acid ceramidase treatment enhance the outcome of autologous chondrocyte implantation in a rat osteochondral defect model? | {
"contexts": [
"The overall aim of this study was to evaluate how supplementation of chondrocyte media with recombinant acid ceramidase (rhAC) influenced cartilage repair in a rat osteochondral defect model.",
"Primary chondrocytes were grown as monolayers in polystyrene culture dishes with and without rhAC (added once at the time of cell plating) for 7 days, and then seeded onto Bio-Gide® collagen scaffolds and grown for an additional 3 days. The scaffolds were then introduced into osteochondral defects created in Sprague-Dawley rat trochlea by a microdrilling procedure. Analysis was performed 6 weeks post-surgery macroscopically, by micro-CT, histologically, and by immunohistochemistry.",
"Treatment with rhAC led to increased cell numbers and glycosaminoglycan (GAG) production (∼2 and 3-fold, respectively) following 7 days of expansion in vitro. Gene expression of collagen 2, aggrecan and Sox-9 also was significantly elevated. After seeding onto Bio-Gide®, more rhAC treated cells were evident within 4 h. At 6 weeks post-surgery, defects containing rhAC-treated cells exhibited more soft tissue formation at the articular surface, as evidenced by microCT, as well as histological evidence of enhanced cartilage repair. Notably, collagen 2 immunostaining revealed greater surface expression in animals receiving rhAC treated cells as well. Collagen 10 staining was not enhanced."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Acid Ceramidase",
"Animals",
"Cartilage, Articular",
"Cell Count",
"Cells, Cultured",
"Chondrocytes",
"Culture Media, Conditioned",
"Drug Evaluation, Preclinical",
"Female",
"Glycosaminoglycans",
"Rats, Sprague-Dawley",
"Recombinant Proteins",
"Regeneration",
"Tissue Scaffolds",
"Wound Healing",
"X-Ray Microtomography"
]
} | The results further demonstrate the positive effects of rhAC treatment on chondrocyte growth and phenotype in vitro, and reveal for the first time the in vivo effects of the treated cells on cartilage repair. | yes | [
{
"from": "human",
"value": "Question: Does acid ceramidase treatment enhance the outcome of autologous chondrocyte implantation in a rat osteochondral defect model?\nContext: {'contexts': ['The overall aim of this study was to evaluate how supplementation of chondrocyte media with recombinant acid ceramidase (rhAC) influenced cartilage repair in a rat osteochondral defect model.', 'Primary chondrocytes were grown as monolayers in polystyrene culture dishes with and without rhAC (added once at the time of cell plating) for 7 days, and then seeded onto Bio-Gide® collagen scaffolds and grown for an additional 3 days. The scaffolds were then introduced into osteochondral defects created in Sprague-Dawley rat trochlea by a microdrilling procedure. Analysis was performed 6 weeks post-surgery macroscopically, by micro-CT, histologically, and by immunohistochemistry.', 'Treatment with rhAC led to increased cell numbers and glycosaminoglycan (GAG) production (∼2 and 3-fold, respectively) following 7 days of expansion in vitro. Gene expression of collagen 2, aggrecan and Sox-9 also was significantly elevated. After seeding onto Bio-Gide®, more rhAC treated cells were evident within 4 h. At 6 weeks post-surgery, defects containing rhAC-treated cells exhibited more soft tissue formation at the articular surface, as evidenced by microCT, as well as histological evidence of enhanced cartilage repair. Notably, collagen 2 immunostaining revealed greater surface expression in animals receiving rhAC treated cells as well. Collagen 10 staining was not enhanced.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Acid Ceramidase', 'Animals', 'Cartilage, Articular', 'Cell Count', 'Cells, Cultured', 'Chondrocytes', 'Culture Media, Conditioned', 'Drug Evaluation, Preclinical', 'Female', 'Glycosaminoglycans', 'Rats, Sprague-Dawley', 'Recombinant Proteins', 'Regeneration', 'Tissue Scaffolds', 'Wound Healing', 'X-Ray Microtomography']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,539,661 | Does maternal high-fat hypercaloric diet during pregnancy result in persistent metabolic and respiratory abnormalities in offspring? | {
"contexts": [
"We have shown in a previous population-based study significant correlation between childhood asthma and early abnormalities of lipid and glucose metabolism. This study's specific aim was to determine whether maternal nutrition in pregnancy affects postnatal metabolic and respiratory outcomes in the offspring.",
"On gestation day 1, dams were switched from standard chow to either high-fat hypercaloric diet or control diet. Terminal experiments were performed on newborn and weanling offspring of dams fed the study diet during gestation and lactation, and on adult offspring maintained on the same diet as their mother.",
"Pups born from high-fat hypercaloric diet (HFD) dams developed metabolic abnormalities persistent throughout development. Cytokine expression analysis of lung tissues from newborns born to HFD dams revealed a strong proinflammatory pattern. Gene expression of neurotrophic factors and receptors was upregulated in lungs of weanlings born to HFD dams, and this was associated to higher respiratory system resistance and lower compliance at baseline, as well as hyperreactivity to aerosolized methacholine. Furthermore, HFD dams delivered pups prone to develop more severe disease after respiratory syncytial virus (RSV) infection."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adiposity",
"Age Factors",
"Animal Nutritional Physiological Phenomena",
"Animals",
"Animals, Newborn",
"Blood Glucose",
"Bronchial Hyperreactivity",
"Bronchoconstriction",
"Cytokines",
"Diet, High-Fat",
"Energy Intake",
"Energy Metabolism",
"Female",
"Gestational Age",
"Inflammation Mediators",
"Lipids",
"Lung",
"Maternal Nutritional Physiological Phenomena",
"Nerve Growth Factors",
"Pneumonia",
"Pregnancy",
"Prenatal Exposure Delayed Effects",
"Rats, Inbred F344",
"Respiratory Syncytial Virus Infections"
]
} | Maternal nutrition in pregnancy is a critical determinant of airway inflammation and hyperreactivity in offspring and also increases risk for bronchiolitis independent from prepregnancy nutrition. | yes | [
{
"from": "human",
"value": "Question: Does maternal high-fat hypercaloric diet during pregnancy result in persistent metabolic and respiratory abnormalities in offspring?\nContext: {'contexts': [\"We have shown in a previous population-based study significant correlation between childhood asthma and early abnormalities of lipid and glucose metabolism. This study's specific aim was to determine whether maternal nutrition in pregnancy affects postnatal metabolic and respiratory outcomes in the offspring.\", 'On gestation day 1, dams were switched from standard chow to either high-fat hypercaloric diet or control diet. Terminal experiments were performed on newborn and weanling offspring of dams fed the study diet during gestation and lactation, and on adult offspring maintained on the same diet as their mother.', 'Pups born from high-fat hypercaloric diet (HFD) dams developed metabolic abnormalities persistent throughout development. Cytokine expression analysis of lung tissues from newborns born to HFD dams revealed a strong proinflammatory pattern. Gene expression of neurotrophic factors and receptors was upregulated in lungs of weanlings born to HFD dams, and this was associated to higher respiratory system resistance and lower compliance at baseline, as well as hyperreactivity to aerosolized methacholine. Furthermore, HFD dams delivered pups prone to develop more severe disease after respiratory syncytial virus (RSV) infection.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adiposity', 'Age Factors', 'Animal Nutritional Physiological Phenomena', 'Animals', 'Animals, Newborn', 'Blood Glucose', 'Bronchial Hyperreactivity', 'Bronchoconstriction', 'Cytokines', 'Diet, High-Fat', 'Energy Intake', 'Energy Metabolism', 'Female', 'Gestational Age', 'Inflammation Mediators', 'Lipids', 'Lung', 'Maternal Nutritional Physiological Phenomena', 'Nerve Growth Factors', 'Pneumonia', 'Pregnancy', 'Prenatal Exposure Delayed Effects', 'Rats, Inbred F344', 'Respiratory Syncytial Virus Infections']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,543,894 | Does substance P mediate pro-inflammatory cytokine release form mesenteric adipocytes in Inflammatory Bowel Disease patients? | {
"contexts": [
"Substance P (SP), neurokinin-1 receptors (NK-1Rs) are expressed in mesenteric preadipocytes and SP binding activates proinflammatory signalling in these cells. We evaluated the expression levels of SP (Tac-1), NK-1R (Tacr-1), and NK-2R (Tacr-2) mRNA in preadipocytes isolated from patients with Inflammatory Bowel Disease (IBD) and examined their responsiveness to SP compared to control human mesenteric preadipocytes. The Aim of our study is to investigate the effects of the neuropeptide SP on cytokine expression in preadipocytes of IBD vs control patients and evaluate the potential effects of these cells on IBD pathophysiology via SP-NK-R interactions.",
"Mesenteric fat was collected from control, Ulcerative colitis (UC) and Crohn's disease (CD) patients (n=10-11 per group). Preadipocytes were isolated, expanded in culture and exposed to substance P. Colon biopsies were obtained from control and IBD patients.",
"Tacr-1 and -2 mRNA were increased in IBD preadipocytes compared to controls, while Tac-1 mRNA was increased only in UC preadipocytes. SP differentially regulated the expression of inflammatory mediators in IBD preadipocytes compared to controls. Disease-dependent responses to SP were also observed between UC and CD preadipocytes. IL-17A mRNA expression and release increased after SP treatment in both CD and UC preadipocytes, while IL-17RA mRNA increased in colon biopsies from IBD patients."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": []
} | Preadipocyte SP-NK-1R interactions during IBD may participate in IBD pathophysiology. The ability of human preadipocytes to release IL-17A in response to SP together with increased IL-17A receptor in IBD colon opens the possibility of a fat-colonic mucosa inflammatory loop that may be active during IBD. | yes | [
{
"from": "human",
"value": "Question: Does substance P mediate pro-inflammatory cytokine release form mesenteric adipocytes in Inflammatory Bowel Disease patients?\nContext: {'contexts': ['Substance P (SP), neurokinin-1 receptors (NK-1Rs) are expressed in mesenteric preadipocytes and SP binding activates proinflammatory signalling in these cells. We evaluated the expression levels of SP (Tac-1), NK-1R (Tacr-1), and NK-2R (Tacr-2) mRNA in preadipocytes isolated from patients with Inflammatory Bowel Disease (IBD) and examined their responsiveness to SP compared to control human mesenteric preadipocytes. The Aim of our study is to investigate the effects of the neuropeptide SP on cytokine expression in preadipocytes of IBD vs control patients and evaluate the potential effects of these cells on IBD pathophysiology via SP-NK-R interactions.', \"Mesenteric fat was collected from control, Ulcerative colitis (UC) and Crohn's disease (CD) patients (n=10-11 per group). Preadipocytes were isolated, expanded in culture and exposed to substance P. Colon biopsies were obtained from control and IBD patients.\", 'Tacr-1 and -2 mRNA were increased in IBD preadipocytes compared to controls, while Tac-1 mRNA was increased only in UC preadipocytes. SP differentially regulated the expression of inflammatory mediators in IBD preadipocytes compared to controls. Disease-dependent responses to SP were also observed between UC and CD preadipocytes. IL-17A mRNA expression and release increased after SP treatment in both CD and UC preadipocytes, while IL-17RA mRNA increased in colon biopsies from IBD patients.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': []}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,526,052 | Is beta-blocker use associated with lower stroke and death after carotid artery stenting? | {
"contexts": [
"Proper selection of patients for carotid artery stenting (CAS) remains controversial despite multiple controlled trials. This relates in part to differences in interpretation of the relative importance of myocardial vs stroke complications after the procedure by different specialties and a lack of granular clinical data to analyze outcomes outside the large clinical trials. The objective of this study was to assess the effect of preoperative medications, procedure parameters, and patient characteristics on outcomes of CAS performed in a multispecialty national database.",
"We analyzed all patients who underwent CAS between 2005 and 2014 in the Vascular Quality Initiative. A multivariate logistic regression model was built to assess the effects of age, gender, comorbidities, smoking, preprocedure medications, procedure details, and hypotension or hypertension that required intravenous medication on 30-day death or stroke rates.",
"A total of 5263 patients underwent CAS (mean age, 70 years; 63% male). The 30-day stroke/death rate was 3.4% (1.5% minor stroke, 0.9% major stroke, and 1.2% death; 40% of patients who had major strokes died within 30 days), and the myocardial infarction rate was 0.8%. Postprocedural hypertension requiring treatment occurred in 519 cases (9.9%), and it was associated with a 3.4-fold increase in stroke/death (odds ratio, 3.39; 95% confidence interval, 2.30-5.00; P < .0001). Preprocedural beta-blocker use for >30 days was associated with a 34% reduction in the stroke/death risk (odds ratio, 0.66; 95% confidence interval, 0.46-0.95; P = .025) compared with nonuse. Beta-blocker use was not associated with postprocedural hypotension. Other predictors of postoperative stroke and death included age, symptomatic status, diabetes (type 1 or type 2), and postprocedural hypotension, whereas prior carotid endarterectomy and distal embolic protection use were protective."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Adrenergic beta-Antagonists",
"Adult",
"Aged",
"Aged, 80 and over",
"Angioplasty",
"Carotid Artery Diseases",
"Chi-Square Distribution",
"Databases, Factual",
"Female",
"Hemodynamics",
"Humans",
"Logistic Models",
"Male",
"Middle Aged",
"Multivariate Analysis",
"Odds Ratio",
"Protective Factors",
"Retrospective Studies",
"Risk Assessment",
"Risk Factors",
"Stents",
"Stroke",
"Time Factors",
"Treatment Outcome",
"United States",
"Young Adult"
]
} | Postprocedural hypertension and hypotension that require treatment are both strongly associated with periprocedural stroke/death after CAS. Beta blockers significantly reduce the stroke/death risk associated with carotid stenting and should be investigated prospectively for potential use during CAS. | yes | [
{
"from": "human",
"value": "Question: Is beta-blocker use associated with lower stroke and death after carotid artery stenting?\nContext: {'contexts': ['Proper selection of patients for carotid artery stenting (CAS) remains controversial despite multiple controlled trials. This relates in part to differences in interpretation of the relative importance of myocardial vs stroke complications after the procedure by different specialties and a lack of granular clinical data to analyze outcomes outside the large clinical trials. The objective of this study was to assess the effect of preoperative medications, procedure parameters, and patient characteristics on outcomes of CAS performed in a multispecialty national database.', 'We analyzed all patients who underwent CAS between 2005 and 2014 in the Vascular Quality Initiative. A multivariate logistic regression model was built to assess the effects of age, gender, comorbidities, smoking, preprocedure medications, procedure details, and hypotension or hypertension that required intravenous medication on 30-day death or stroke rates.', 'A total of 5263 patients underwent CAS (mean age, 70 years; 63% male). The 30-day stroke/death rate was 3.4% (1.5% minor stroke, 0.9% major stroke, and 1.2% death; 40% of patients who had major strokes died within 30 days), and the myocardial infarction rate was 0.8%. Postprocedural hypertension requiring treatment occurred in 519 cases (9.9%), and it was associated with a 3.4-fold increase in stroke/death (odds ratio, 3.39; 95% confidence interval, 2.30-5.00; P < .0001). Preprocedural beta-blocker use for >30 days was associated with a 34% reduction in the stroke/death risk (odds ratio, 0.66; 95% confidence interval, 0.46-0.95; P = .025) compared with nonuse. Beta-blocker use was not associated with postprocedural hypotension. Other predictors of postoperative stroke and death included age, symptomatic status, diabetes (type 1 or type 2), and postprocedural hypotension, whereas prior carotid endarterectomy and distal embolic protection use were protective.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adrenergic beta-Antagonists', 'Adult', 'Aged', 'Aged, 80 and over', 'Angioplasty', 'Carotid Artery Diseases', 'Chi-Square Distribution', 'Databases, Factual', 'Female', 'Hemodynamics', 'Humans', 'Logistic Models', 'Male', 'Middle Aged', 'Multivariate Analysis', 'Odds Ratio', 'Protective Factors', 'Retrospective Studies', 'Risk Assessment', 'Risk Factors', 'Stents', 'Stroke', 'Time Factors', 'Treatment Outcome', 'United States', 'Young Adult']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,531,283 | Does atorvastatin improve cardiac function of rats with chronic cardiac failure via inhibiting Rac1/P47phox/P67phox-mediated ROS release? | {
"contexts": [
"To discuss the protective mechanisms of atorvastatin treatment for isoproterenol (ISO)-induced chronic heart failure.",
"The rats were randomly divided into three groups: normal group (n = 15, age-matched normal adult rats), ISO group (n = 11, ISO induced heart failure) and atorvastatin group (n = 14, ISO induced lesion but received atorvastatin treatment). The cardiac function was evaluated by echocardiography and hemodynamics analysis. In addition, the Rac1 activity in the myocardium and the expression levels of Rac1, p47phox and p67phox were measured by RT-PCR and western blot.",
"Rats in ISO group developed into heart failure with decreased cardiac function. The Rac1, p47phox and p67phox mRNA expressions and ROS release were increased in ISO group. Atorvastatin treatment improved cardiac function of rats with isoproterenol-induced chronic heart failure and decreased the Rac1, p47phox and p67phox mRNA expressions. Also, membrane protein expression of Rac1 and ROS release decreased significantly."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Atorvastatin",
"Chronic Disease",
"Heart Failure",
"Hemodynamics",
"Humans",
"Male",
"NADH, NADPH Oxidoreductases",
"NADPH Oxidases",
"Rats",
"Rats, Wistar",
"Reactive Oxygen Species",
"rac1 GTP-Binding Protein"
]
} | Atorvastatin may improve cardiac function of rats with heart failure via inhibiting Rac1/P47phox/P67phox-mediated ROS release. | yes | [
{
"from": "human",
"value": "Question: Does atorvastatin improve cardiac function of rats with chronic cardiac failure via inhibiting Rac1/P47phox/P67phox-mediated ROS release?\nContext: {'contexts': ['To discuss the protective mechanisms of atorvastatin treatment for isoproterenol (ISO)-induced chronic heart failure.', 'The rats were randomly divided into three groups: normal group (n = 15, age-matched normal adult rats), ISO group (n = 11, ISO induced heart failure) and atorvastatin group (n = 14, ISO induced lesion but received atorvastatin treatment). The cardiac function was evaluated by echocardiography and hemodynamics analysis. In addition, the Rac1 activity in the myocardium and the expression levels of Rac1, p47phox and p67phox were measured by RT-PCR and western blot.', 'Rats in ISO group developed into heart failure with decreased cardiac function. The Rac1, p47phox and p67phox mRNA expressions and ROS release were increased in ISO group. Atorvastatin treatment improved cardiac function of rats with isoproterenol-induced chronic heart failure and decreased the Rac1, p47phox and p67phox mRNA expressions. Also, membrane protein expression of Rac1 and ROS release decreased significantly.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Atorvastatin', 'Chronic Disease', 'Heart Failure', 'Hemodynamics', 'Humans', 'Male', 'NADH, NADPH Oxidoreductases', 'NADPH Oxidases', 'Rats', 'Rats, Wistar', 'Reactive Oxygen Species', 'rac1 GTP-Binding Protein']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,552,935 | Is insomnia associated with suicide attempt in middle-aged and older adults with depression? | {
"contexts": [
"Insomnia increases in prevalence with age, is strongly associated with depression, and has been identified as a risk factor for suicide in several studies. The aim of this study was to determine whether insomnia severity varies between those who have attempted suicide (n = 72), those who only contemplate suicide (n = 28), and those who are depressed but have no suicidal ideation or attempt history (n = 35).",
"Participants were middle-aged and older adults (age 44-87, M = 66 years) with depression. Insomnia severity was measured as the sum of the early, middle, and late insomnia items from the Hamilton Rating Scale for Depression. General linear models examined relations between group status as the independent variable and insomnia severity as the dependent variable.",
"The suicide attempt group suffered from more severe insomnia than the suicidal ideation and non-suicidal depressed groups (p < 0.05). Differences remained after adjusting for potential confounders including demographics, cognitive ability, alcohol dependence in the past month, severity of depressed mood, anxiety, and physical health burden. Moreover, greater insomnia severity in the suicide attempt group could not be explained by interpersonal difficulties, executive functioning, benzodiazepine use, or by the presence of post-traumatic stress disorder."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Case-Control Studies",
"Cross-Sectional Studies",
"Depression",
"Female",
"Humans",
"Male",
"Middle Aged",
"Pennsylvania",
"Severity of Illness Index",
"Sleep Initiation and Maintenance Disorders",
"Suicidal Ideation",
"Suicide, Attempted"
]
} | Our results suggest that insomnia may be more strongly associated with suicidal behavior than with the presence of suicidal thoughts alone. Accordingly, insomnia is a potential treatment target for reducing suicide risk in middle-aged and older adults. | yes | [
{
"from": "human",
"value": "Question: Is insomnia associated with suicide attempt in middle-aged and older adults with depression?\nContext: {'contexts': ['Insomnia increases in prevalence with age, is strongly associated with depression, and has been identified as a risk factor for suicide in several studies. The aim of this study was to determine whether insomnia severity varies between those who have attempted suicide (n = 72), those who only contemplate suicide (n = 28), and those who are depressed but have no suicidal ideation or attempt history (n = 35).', 'Participants were middle-aged and older adults (age 44-87, M = 66 years) with depression. Insomnia severity was measured as the sum of the early, middle, and late insomnia items from the Hamilton Rating Scale for Depression. General linear models examined relations between group status as the independent variable and insomnia severity as the dependent variable.', 'The suicide attempt group suffered from more severe insomnia than the suicidal ideation and non-suicidal depressed groups (p < 0.05). Differences remained after adjusting for potential confounders including demographics, cognitive ability, alcohol dependence in the past month, severity of depressed mood, anxiety, and physical health burden. Moreover, greater insomnia severity in the suicide attempt group could not be explained by interpersonal difficulties, executive functioning, benzodiazepine use, or by the presence of post-traumatic stress disorder.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Case-Control Studies', 'Cross-Sectional Studies', 'Depression', 'Female', 'Humans', 'Male', 'Middle Aged', 'Pennsylvania', 'Severity of Illness Index', 'Sleep Initiation and Maintenance Disorders', 'Suicidal Ideation', 'Suicide, Attempted']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,552,939 | Do increased homocysteine levels exist in women with preeclampsia from early pregnancy? | {
"contexts": [
"The present prospective study examines the levels of maternal plasma folate, vitamin B12 and homocysteine in normotensive control (NC) women and women with preeclampsia (PE) from early pregnancy till delivery.",
"The present study includes 126 NC and 62 PE women. Maternal blood was collected at 3 time points during pregnancy (T1 = 16th-20th weeks, T2 = 26th-30th weeks and T3 = at delivery). Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay technology.",
"Maternal plasma folate levels were similar between NC and PE women at all the time points across gestation. Maternal plasma vitamin B12 levels were significantly higher in PE (p < 0.05) as compared with NC at T2. Maternal plasma homocysteine levels were higher in PE as compared with NC at all the time points, i.e. T1, T2 (p < 0.05 for both) and T3 (p < 0.01)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Diet",
"Female",
"Folic Acid",
"Gestational Age",
"Homocysteine",
"Humans",
"Infant, Newborn",
"Pre-Eclampsia",
"Pregnancy",
"Prospective Studies",
"Vitamin B 12"
]
} | Our results indicate that higher homocysteine levels exist in women with PE from early pregnancy and continue till delivery. | yes | [
{
"from": "human",
"value": "Question: Do increased homocysteine levels exist in women with preeclampsia from early pregnancy?\nContext: {'contexts': ['The present prospective study examines the levels of maternal plasma folate, vitamin B12 and homocysteine in normotensive control (NC) women and women with preeclampsia (PE) from early pregnancy till delivery.', 'The present study includes 126 NC and 62 PE women. Maternal blood was collected at 3 time points during pregnancy (T1 = 16th-20th weeks, T2 = 26th-30th weeks and T3 = at delivery). Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay technology.', 'Maternal plasma folate levels were similar between NC and PE women at all the time points across gestation. Maternal plasma vitamin B12 levels were significantly higher in PE (p < 0.05) as compared with NC at T2. Maternal plasma homocysteine levels were higher in PE as compared with NC at all the time points, i.e. T1, T2 (p < 0.05 for both) and T3 (p < 0.01).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Diet', 'Female', 'Folic Acid', 'Gestational Age', 'Homocysteine', 'Humans', 'Infant, Newborn', 'Pre-Eclampsia', 'Pregnancy', 'Prospective Studies', 'Vitamin B 12']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,528,017 | Is small Intestinal Bacterial Overgrowth Associated with Intestinal Inflammation in the Irritable Bowel Syndrome? | {
"contexts": [
"Small intestinal bacterial overgrowth is encountered in bowel disorders, including irritable bowel symptoms. Low degrees of inflammation have been recently reported in the irritable bowel syndrome. We looked for the association between intestinal inflammation and small intestinal bacterial overgrowth in irritable bowel syndrome.",
"Small intestinal bacterial overgrowth was assessed by the H2 glucose breath test in 90 consecutive patients with irritable bowel syndrome. A check-up of the oral cavity was carried out before the breath testing. Further on, the patients were classified into two groups, positive and negative, at the breath test. Then they were tested for intestinal inflammation with a fecal test for calprotectin. We used a semiquantitative test for this study. Both groups were compared for the association of intestinal inflammation with small intestinal bacterial overgrowth.",
"A number of 24/90 (26.7%) patients with irritable bowel syndrome had small intestinal bacterial overgrowth. A positive test for intestinal inflammation was significantly more frequent in patients with irritable bowel syndrome and small intestinal bacterial overgrowth (chi(2): p<0.05)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": []
} | Small intestinal bacterial overgrowth is present in almost one quarter of patients with irritable bowel syndrome. It is significantly associated with intestinal inflammation. | yes | [
{
"from": "human",
"value": "Question: Is small Intestinal Bacterial Overgrowth Associated with Intestinal Inflammation in the Irritable Bowel Syndrome?\nContext: {'contexts': ['Small intestinal bacterial overgrowth is encountered in bowel disorders, including irritable bowel symptoms. Low degrees of inflammation have been recently reported in the irritable bowel syndrome. We looked for the association between intestinal inflammation and small intestinal bacterial overgrowth in irritable bowel syndrome.', 'Small intestinal bacterial overgrowth was assessed by the H2 glucose breath test in 90 consecutive patients with irritable bowel syndrome. A check-up of the oral cavity was carried out before the breath testing. Further on, the patients were classified into two groups, positive and negative, at the breath test. Then they were tested for intestinal inflammation with a fecal test for calprotectin. We used a semiquantitative test for this study. Both groups were compared for the association of intestinal inflammation with small intestinal bacterial overgrowth.', 'A number of 24/90 (26.7%) patients with irritable bowel syndrome had small intestinal bacterial overgrowth. A positive test for intestinal inflammation was significantly more frequent in patients with irritable bowel syndrome and small intestinal bacterial overgrowth (chi(2): p<0.05).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': []}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,531,125 | Is detection of anal dysplasia enhanced by narrow band imaging and acetic acid? | {
"contexts": [
"Anal intraepithelial neoplasia precedes the development of anal squamous cell carcinoma. Detection of the lesion is essential to management. This paper describes a prospective study to detect and ablate anal squamous intraepithelial lesions (SILs) using white light narrow band imaging (NBI) and NBI with acetic acid (NBIA).",
"Sixty patients with abnormal anal cytology and risk factors for anal dysplasia underwent examination of the anoderm with a high definition gastroscope and NBIA. Targeted biopsies were taken and the lesions were ablated and characterized histopathologically. Visualization of the anal transitional zone was facilitated by retroflexion and examination through a disposable anoscope.",
"Targeted biopsies were taken from lesions in 58 patients. No lesion was seen in two patients. Histopathology showed SIL in 48 (80.0%) of 60 biopsies. One biopsy showed lymphoid aggregates. Biopsies in nine (15%) of the 60 patients showed normal mucosa. Lesions were seen in white light in 27 (45%) of the 60 cases, NBI in 39 (65%) and NBIA in 57 (95%). There was no major morbidity. Sensitivity analysis showed that all methods were significantly different from each other."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Acetic Acid",
"Adult",
"Aged",
"Anal Canal",
"Anus Neoplasms",
"Atypical Squamous Cells of the Cervix",
"Biopsy",
"Carcinoma in Situ",
"Female",
"HIV Infections",
"Humans",
"Indicators and Reagents",
"Male",
"Middle Aged",
"Narrow Band Imaging",
"Papillomavirus Infections",
"Precancerous Conditions",
"Prospective Studies",
"Squamous Intraepithelial Lesions of the Cervix",
"Young Adult"
]
} | Anal SIL in the anal transitional zone and anal canal can be identified by NBIA. Patient selection influences findings. Limitations include small sample size and non-randomization. | yes | [
{
"from": "human",
"value": "Question: Is detection of anal dysplasia enhanced by narrow band imaging and acetic acid?\nContext: {'contexts': ['Anal intraepithelial neoplasia precedes the development of anal squamous cell carcinoma. Detection of the lesion is essential to management. This paper describes a prospective study to detect and ablate anal squamous intraepithelial lesions (SILs) using white light narrow band imaging (NBI) and NBI with acetic acid (NBIA).', 'Sixty patients with abnormal anal cytology and risk factors for anal dysplasia underwent examination of the anoderm with a high definition gastroscope and NBIA. Targeted biopsies were taken and the lesions were ablated and characterized histopathologically. Visualization of the anal transitional zone was facilitated by retroflexion and examination through a disposable anoscope.', 'Targeted biopsies were taken from lesions in 58 patients. No lesion was seen in two patients. Histopathology showed SIL in 48 (80.0%) of 60 biopsies. One biopsy showed lymphoid aggregates. Biopsies in nine (15%) of the 60 patients showed normal mucosa. Lesions were seen in white light in 27 (45%) of the 60 cases, NBI in 39 (65%) and NBIA in 57 (95%). There was no major morbidity. Sensitivity analysis showed that all methods were significantly different from each other.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Acetic Acid', 'Adult', 'Aged', 'Anal Canal', 'Anus Neoplasms', 'Atypical Squamous Cells of the Cervix', 'Biopsy', 'Carcinoma in Situ', 'Female', 'HIV Infections', 'Humans', 'Indicators and Reagents', 'Male', 'Middle Aged', 'Narrow Band Imaging', 'Papillomavirus Infections', 'Precancerous Conditions', 'Prospective Studies', 'Squamous Intraepithelial Lesions of the Cervix', 'Young Adult']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,531,129 | Does the renin-angiotensin system promote arrhythmogenic substrates and lethal arrhythmias in mice with non-ischaemic cardiomyopathy? | {
"contexts": [
"The progression of pathological left ventricular remodelling leads to cardiac dysfunction and contributes to the occurrence of malignant arrhythmias and sudden cardiac death. The underlying molecular mechanisms remain unclear, however. Our aim was to examine the role of the renin-angiotensin system (RAS) in the mechanism underlying arrhythmogenic cardiac remodelling using a transgenic mouse expressing a cardiac-specific dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). This mouse model exhibits progressive cardiac dysfunction leading to lethal arrhythmias.",
"Subcutaneous administration of aliskiren, a direct renin inhibitor, significantly suppressed the progression of pathological cardiac remodelling and improved survival among dnNRSF-Tg mice while reducing arrhythmogenicity. Genetic deletion of the angiotensin type 1a receptor (AT1aR) similarly suppressed cardiac remodelling and sudden death. In optical mapping analyses, spontaneous ventricular tachycardia (VT) and fibrillation (VF) initiated by breakthrough-type excitations originating from focal activation sites and maintained by functional re-entry were observed in dnNRSF-Tg hearts. Under constant pacing, dnNRSF-Tg hearts exhibited markedly slowed conduction velocity, which likely contributes to the arrhythmogenic substrate. Aliskiren treatment increased conduction velocity and reduced the incidence of sustained VT. These effects were associated with suppression of cardiac fibrosis and restoration of connexin 43 expression in dnNRSF-Tg ventricles."
],
"labels": [
"OBJECTIVE",
"RESULTS"
],
"meshes": [
"Animals",
"Arrhythmias, Cardiac",
"Cardiomyopathies",
"Connexin 43",
"Fibrosis",
"Mice",
"Mice, Inbred C57BL",
"Myocardium",
"Receptor, Angiotensin, Type 1",
"Renin",
"Renin-Angiotensin System",
"Ventricular Remodeling"
]
} | Renin inhibition or genetic deletion of AT1aR suppresses pathological cardiac remodelling that leads to the generation of substrates maintaining VT/VF and reduces the occurrence of sudden death in dnNRSF-Tg mice. These findings demonstrate the significant contribution of RAS activation to the progression of arrhythmogenic substrates. | yes | [
{
"from": "human",
"value": "Question: Does the renin-angiotensin system promote arrhythmogenic substrates and lethal arrhythmias in mice with non-ischaemic cardiomyopathy?\nContext: {'contexts': ['The progression of pathological left ventricular remodelling leads to cardiac dysfunction and contributes to the occurrence of malignant arrhythmias and sudden cardiac death. The underlying molecular mechanisms remain unclear, however. Our aim was to examine the role of the renin-angiotensin system (RAS) in the mechanism underlying arrhythmogenic cardiac remodelling using a transgenic mouse expressing a cardiac-specific dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). This mouse model exhibits progressive cardiac dysfunction leading to lethal arrhythmias.', 'Subcutaneous administration of aliskiren, a direct renin inhibitor, significantly suppressed the progression of pathological cardiac remodelling and improved survival among dnNRSF-Tg mice while reducing arrhythmogenicity. Genetic deletion of the angiotensin type 1a receptor (AT1aR) similarly suppressed cardiac remodelling and sudden death. In optical mapping analyses, spontaneous ventricular tachycardia (VT) and fibrillation (VF) initiated by breakthrough-type excitations originating from focal activation sites and maintained by functional re-entry were observed in dnNRSF-Tg hearts. Under constant pacing, dnNRSF-Tg hearts exhibited markedly slowed conduction velocity, which likely contributes to the arrhythmogenic substrate. Aliskiren treatment increased conduction velocity and reduced the incidence of sustained VT. These effects were associated with suppression of cardiac fibrosis and restoration of connexin 43 expression in dnNRSF-Tg ventricles.'], 'labels': ['OBJECTIVE', 'RESULTS'], 'meshes': ['Animals', 'Arrhythmias, Cardiac', 'Cardiomyopathies', 'Connexin 43', 'Fibrosis', 'Mice', 'Mice, Inbred C57BL', 'Myocardium', 'Receptor, Angiotensin, Type 1', 'Renin', 'Renin-Angiotensin System', 'Ventricular Remodeling']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,546,618 | Do combined Tumor Suppressor Defects Characterize Clinically Defined Aggressive Variant Prostate Cancers? | {
"contexts": [
"Morphologically heterogeneous prostate cancers that behave clinically like small-cell prostate cancers (SCPC) share their chemotherapy responsiveness. We asked whether these clinically defined, morphologically diverse, \"aggressive variant prostate cancer (AVPC)\" also share molecular features with SCPC.",
"Fifty-nine prostate cancer samples from 40 clinical trial participants meeting AVPC criteria, and 8 patient-tumor derived xenografts (PDX) from 6 of them, were stained for markers aberrantly expressed in SCPC. DNA from 36 and 8 PDX was analyzed by Oncoscan for copy number gains (CNG) and losses (CNL). We used the AVPC PDX to expand observations and referenced publicly available datasets to arrive at a candidate molecular signature for the AVPC.",
"Irrespective of morphology, Ki67 and Tp53 stained ≥10% cells in 80% and 41% of samples, respectively. RB1 stained <10% cells in 61% of samples and AR in 36%. MYC (surrogate for 8q) CNG and RB1 CNL showed in 54% of 44 samples each and PTEN CNL in 48%. All but 1 of 8 PDX bore Tp53 missense mutations. RB1 CNL was the strongest discriminator between unselected castration-resistant prostate cancer (CRPC) and the AVPC. Combined alterations in RB1, Tp53, and/or PTEN were more frequent in the AVPC than in unselected CRPC and in The Cancer Genome Atlas samples."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Biomarkers, Tumor",
"Biopsy",
"Cluster Analysis",
"DNA Copy Number Variations",
"Disease Progression",
"Gene Expression Profiling",
"Humans",
"Immunohistochemistry",
"Male",
"Mutation",
"Neoplasm Staging",
"Prostatic Neoplasms",
"Receptors, Androgen",
"Signal Transduction",
"Tumor Suppressor Proteins"
]
} | Clinically defined AVPC share molecular features with SCPC and are characterized by combined alterations in RB1, Tp53, and/or PTEN. | yes | [
{
"from": "human",
"value": "Question: Do combined Tumor Suppressor Defects Characterize Clinically Defined Aggressive Variant Prostate Cancers?\nContext: {'contexts': ['Morphologically heterogeneous prostate cancers that behave clinically like small-cell prostate cancers (SCPC) share their chemotherapy responsiveness. We asked whether these clinically defined, morphologically diverse, \"aggressive variant prostate cancer (AVPC)\" also share molecular features with SCPC.', 'Fifty-nine prostate cancer samples from 40 clinical trial participants meeting AVPC criteria, and 8 patient-tumor derived xenografts (PDX) from 6 of them, were stained for markers aberrantly expressed in SCPC. DNA from 36 and 8 PDX was analyzed by Oncoscan for copy number gains (CNG) and losses (CNL). We used the AVPC PDX to expand observations and referenced publicly available datasets to arrive at a candidate molecular signature for the AVPC.', 'Irrespective of morphology, Ki67 and Tp53 stained ≥10% cells in 80% and 41% of samples, respectively. RB1 stained <10% cells in 61% of samples and AR in 36%. MYC (surrogate for 8q) CNG and RB1 CNL showed in 54% of 44 samples each and PTEN CNL in 48%. All but 1 of 8 PDX bore Tp53 missense mutations. RB1 CNL was the strongest discriminator between unselected castration-resistant prostate cancer (CRPC) and the AVPC. Combined alterations in RB1, Tp53, and/or PTEN were more frequent in the AVPC than in unselected CRPC and in The Cancer Genome Atlas samples.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Biomarkers, Tumor', 'Biopsy', 'Cluster Analysis', 'DNA Copy Number Variations', 'Disease Progression', 'Gene Expression Profiling', 'Humans', 'Immunohistochemistry', 'Male', 'Mutation', 'Neoplasm Staging', 'Prostatic Neoplasms', 'Receptors, Androgen', 'Signal Transduction', 'Tumor Suppressor Proteins']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,542,439 | Does aggressive Aortic Arch and Carotid Replacement Strategy for Type A Aortic Dissection improve Neurologic Outcomes? | {
"contexts": [
"International registries for acute type A aortic dissection (TAAD) demonstrate stagnant operative mortality rates in excess of 20% and stroke rates of 9% to 25%, with little global emphasis on stroke reduction or carotid involvement. Cerebral malperfusion with TAAD has been linked to poorer outcome. We hypothesize that concomitant carotid dissection or complex dissection flaps in the arch play a major role in stroke development and that aggressive reconstruction of the arch and carotid arteries can improve neurologic outcomes in TAAD.",
"A standardized protocol focused on expedient care, neurocerebral protection, and common carotid and total arch reconstruction was developed for 264 consecutive TAADs. Arch and complete carotid replacement was based on arch dissection anatomy, carotid involvement, or an intraarch tear. Neurocerebral monitoring with continuous electroencephalogram/somatosensory evoked potentials was used in all cases.",
"The postoperative stroke and hospital mortality rates were 3.4% and 9.1%, and stroke rates by extent of arch replacement were 4%, 3%, and 0% for hemiarch, total arch, and total arch with complete carotid replacement, respectively. An intraoperative change in the electroencephalogram/somatosensory evoked potentials was strongly predictive of stroke and had a negative predictive value of 98.2%."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aneurysm, Dissecting",
"Aortic Aneurysm, Thoracic",
"Blood Vessel Prosthesis Implantation",
"Female",
"Follow-Up Studies",
"Hospital Mortality",
"Humans",
"Incidence",
"Male",
"Middle Aged",
"Pennsylvania",
"Postoperative Complications",
"Retrospective Studies",
"Risk Assessment",
"Risk Factors",
"Stroke",
"Survival Rate",
"Time Factors",
"Tomography, X-Ray Computed",
"Treatment Outcome"
]
} | An algorithmic approach to TAAD including (1) rapid transport-to-incision-to-cardiopulmonary bypass established centrally, (2) neurocerebral monitoring, (3) liberal use of total arch replacement for clearly defined indications (and hemiarch for all others), and (4) common carotid arterial replacement for concomitant carotid dissections significantly improves outcomes. | yes | [
{
"from": "human",
"value": "Question: Does aggressive Aortic Arch and Carotid Replacement Strategy for Type A Aortic Dissection improve Neurologic Outcomes?\nContext: {'contexts': ['International registries for acute type A aortic dissection (TAAD) demonstrate stagnant operative mortality rates in excess of 20% and stroke rates of 9% to 25%, with little global emphasis on stroke reduction or carotid involvement. Cerebral malperfusion with TAAD has been linked to poorer outcome. We hypothesize that concomitant carotid dissection or complex dissection flaps in the arch play a major role in stroke development and that aggressive reconstruction of the arch and carotid arteries can improve neurologic outcomes in TAAD.', 'A standardized protocol focused on expedient care, neurocerebral protection, and common carotid and total arch reconstruction was developed for 264\\xa0consecutive TAADs. Arch and complete carotid replacement was based on arch dissection anatomy, carotid involvement, or an intraarch tear. Neurocerebral monitoring with continuous electroencephalogram/somatosensory evoked potentials was used in all cases.', 'The postoperative stroke and hospital mortality rates were 3.4% and 9.1%, and stroke rates by extent of arch replacement were 4%, 3%, and 0% for hemiarch, total arch, and total arch with complete carotid replacement, respectively. An intraoperative change in the electroencephalogram/somatosensory evoked potentials was strongly predictive of stroke and had a negative predictive value of 98.2%.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aneurysm, Dissecting', 'Aortic Aneurysm, Thoracic', 'Blood Vessel Prosthesis Implantation', 'Female', 'Follow-Up Studies', 'Hospital Mortality', 'Humans', 'Incidence', 'Male', 'Middle Aged', 'Pennsylvania', 'Postoperative Complications', 'Retrospective Studies', 'Risk Assessment', 'Risk Factors', 'Stroke', 'Survival Rate', 'Time Factors', 'Tomography, X-Ray Computed', 'Treatment Outcome']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,526,450 | Does karyopherin Alpha 2 promote the Inflammatory Response in Rat Pancreatic Acinar Cells Via Facilitating NF-κB Activation? | {
"contexts": [
"Activation of the transcription factor NF-κB and expression of pro-inflammatory mediators have been considered as major events of acute pancreatitis (AP). Karyopherin alpha 2 (KPNA2), a member of the importin α family, reportedly modulates p65 subcellular localization.",
"This study aimed to investigate the expression and possible functions of KPNA2 in the AP cell and animal model, focusing on its association with NF-κB activation.",
"An AP cell model was established with the cerulein-stimulated AR42J and isolated rat pancreatic acinar cells. The AP rat model was induced by the intraperitoneal injection of cerulein. The secretion of TNF-α, IL-6, and LDH was detected by ELISA kits and the production of NO using nitric oxide kit. Expression of KPNA2 was measured by RT-PCR and Western blot. Expression levels of IKKα, phosphorylation of p65, and total p65 were detected by Western blot. Co-localization of KPNA2 with p65 was observed by immunofluorescence assay. To determine the biological functions of KPNA2 in cerulein-induced inflammatory response, RNA interference was employed to knockdown KPNA2 expression in AR42J and isolated pancreatic acini cells.",
"Cerulein stimulated KPNA2 expression and IL-6, TNF-α, NO, and LDH production in rat pancreatic acinar cells. Cerulein triggered the phosphorylation and nuclear translocation of NF-κB p65 subunit, indicating the NF-κB activation. The co-localization and nuclear accumulation of KPNA2 and p65 were detected in cerulein-treated cells. Knocking down KPNA2 hindered cerulein-induced nuclear transportation of p65 and alleviated the subsequent inflammatory response in rat pancreatic acinar cells. Additionally, KPNA2 expression was significantly up-regulated in cerulein-induced AP rat model."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Acinar Cells",
"Acute Disease",
"Animals",
"Blotting, Western",
"Cell Line",
"Ceruletide",
"Disease Models, Animal",
"Enzyme-Linked Immunosorbent Assay",
"Fluorescent Antibody Technique",
"Gene Expression Regulation",
"Gene Knockdown Techniques",
"I-kappa B Kinase",
"Inflammation",
"Interleukin-6",
"Lactate Dehydrogenases",
"Male",
"NF-kappa B",
"Nitric Oxide",
"Pancreas",
"Pancreatitis",
"Phosphorylation",
"RNA, Messenger",
"Rats",
"Rats, Sprague-Dawley",
"Reverse Transcriptase Polymerase Chain Reaction",
"Transcription Factor RelA",
"Tumor Necrosis Factor-alpha",
"Up-Regulation",
"alpha Karyopherins"
]
} | KPNA2-facilitated p65 nuclear translocation promotes NF-κB activation and inflammation in acute pancreatitis. | yes | [
{
"from": "human",
"value": "Question: Does karyopherin Alpha 2 promote the Inflammatory Response in Rat Pancreatic Acinar Cells Via Facilitating NF-κB Activation?\nContext: {'contexts': ['Activation of the transcription factor NF-κB and expression of pro-inflammatory mediators have been considered as major events of acute pancreatitis (AP). Karyopherin alpha 2 (KPNA2), a member of the importin α family, reportedly modulates p65 subcellular localization.', 'This study aimed to investigate the expression and possible functions of KPNA2 in the AP cell and animal model, focusing on its association with NF-κB activation.', 'An AP cell model was established with the cerulein-stimulated AR42J and isolated rat pancreatic acinar cells. The AP rat model was induced by the intraperitoneal injection of cerulein. The secretion of TNF-α, IL-6, and LDH was detected by ELISA kits and the production of NO using nitric oxide kit. Expression of KPNA2 was measured by RT-PCR and Western blot. Expression levels of IKKα, phosphorylation of p65, and total p65 were detected by Western blot. Co-localization of KPNA2 with p65 was observed by immunofluorescence assay. To determine the biological functions of KPNA2 in cerulein-induced inflammatory response, RNA interference was employed to knockdown KPNA2 expression in AR42J and isolated pancreatic acini cells.', 'Cerulein stimulated KPNA2 expression and IL-6, TNF-α, NO, and LDH production in rat pancreatic acinar cells. Cerulein triggered the phosphorylation and nuclear translocation of NF-κB p65 subunit, indicating the NF-κB activation. The co-localization and nuclear accumulation of KPNA2 and p65 were detected in cerulein-treated cells. Knocking down KPNA2 hindered cerulein-induced nuclear transportation of p65 and alleviated the subsequent inflammatory response in rat pancreatic acinar cells. Additionally, KPNA2 expression was significantly up-regulated in cerulein-induced AP rat model.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Acinar Cells', 'Acute Disease', 'Animals', 'Blotting, Western', 'Cell Line', 'Ceruletide', 'Disease Models, Animal', 'Enzyme-Linked Immunosorbent Assay', 'Fluorescent Antibody Technique', 'Gene Expression Regulation', 'Gene Knockdown Techniques', 'I-kappa B Kinase', 'Inflammation', 'Interleukin-6', 'Lactate Dehydrogenases', 'Male', 'NF-kappa B', 'Nitric Oxide', 'Pancreas', 'Pancreatitis', 'Phosphorylation', 'RNA, Messenger', 'Rats', 'Rats, Sprague-Dawley', 'Reverse Transcriptase Polymerase Chain Reaction', 'Transcription Factor RelA', 'Tumor Necrosis Factor-alpha', 'Up-Regulation', 'alpha Karyopherins']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,547,466 | Does prevalence and correlate of Myocardial Scar in a US Cohort? | {
"contexts": [
"Myocardial scarring leads to cardiac dysfunction and poor prognosis. The prevalence of and factors associated with unrecognized myocardial infarction and scar have not been previously defined using contemporary methods in a multiethnic US population.",
"To determine prevalence of and factors associated with myocardial scar in middle- and older-aged individuals in the United States.",
"The Multi-Ethnic Study of Atherosclerosis (MESA) study is a population-based cohort in the United States. Participants were aged 45 through 84 years and free of clinical cardiovascular disease (CVD) at baseline in 2000-2002. In the 10th year examination (2010-2012), 1840 participants underwent cardiac magnetic resonance (CMR) imaging with gadolinium to detect myocardial scar. Cardiovascular disease risk factors and coronary artery calcium (CAC) scores were measured at baseline and year 10. Logistic regression models were used to estimate adjusted odds ratios (ORs) for myocardial scar.",
"Cardiovascular risk factors, CAC scores, left ventricle size and function, and carotid intima-media thickness.",
"Myocardial scar detected by CMR imaging.",
"Of 1840 participants (mean [SD] age, 68 [9] years, 52% men), 146 (7.9%) had myocardial scars, of which 114 (78%) were undetected by electrocardiogram or by clinical adjudication. In adjusted models, age, male sex, body mass index, hypertension, and current smoking at baseline were associated with myocardial scar at year 10. The OR per 8.9-year increment was 1.61 (95% CI, 1.36-1.91; P < .001); for men vs women: OR, 5.76 (95% CI, 3.61-9.17; P < .001); per 4.8-SD body mass index: OR, 1.32 (95% CI, 1.09-1.61, P = .005); for hypertension: OR, 1.61 (95% CI, 1.12-2.30; P = .009); and for current vs never smokers: 2.00 (95% CI, 1.22-3.28; P = .006). Age-, sex-, and ethnicity-adjusted CAC scores at baseline were also associated with myocardial scar at year 10. Compared with a CAC score of 0, the OR for scores from 1 through 99 was 2.4 (95% CI, 1.5-3.9); from 100 through 399, 3.0 (95% CI, 1.7-5.1), and 400 or higher, 3.3 (95% CI, 1.7-6.1) (P ≤ .001). The CAC score significantly added to the association of myocardial scar with age, sex, race/ethnicity, and traditional CVD risk factors (C statistic, 0.81 with CAC vs 0.79 without CAC, P = .01)."
],
"labels": [
"OBJECTIVE",
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"African Continental Ancestry Group",
"Aged",
"Aged, 80 and over",
"Body Mass Index",
"Calcinosis",
"Cardiomyopathies",
"Cardiovascular Diseases",
"China",
"Cicatrix",
"Coronary Artery Disease",
"European Continental Ancestry Group",
"Female",
"Gadolinium",
"Hispanic Americans",
"Humans",
"Magnetic Resonance Imaging",
"Male",
"Middle Aged",
"Myocardial Infarction",
"Prevalence",
"Regression Analysis",
"Time Factors",
"United States"
]
} | The prevalence of myocardial scars in a US community-based multiethnic cohort was 7.9%, of which 78% were unrecognized by electrocardiography or clinical evaluation. Further studies are needed to understand the clinical consequences of these undetected scars. | yes | [
{
"from": "human",
"value": "Question: Does prevalence and correlate of Myocardial Scar in a US Cohort?\nContext: {'contexts': ['Myocardial scarring leads to cardiac dysfunction and poor prognosis. The prevalence of and factors associated with unrecognized myocardial infarction and scar have not been previously defined using contemporary methods in a multiethnic US population.', 'To determine prevalence of and factors associated with myocardial scar in middle- and older-aged individuals in the United States.', 'The Multi-Ethnic Study of Atherosclerosis (MESA) study is a population-based cohort in the United States. Participants were aged 45 through 84 years and free of clinical cardiovascular disease (CVD) at baseline in 2000-2002. In the 10th year examination (2010-2012), 1840 participants underwent cardiac magnetic resonance (CMR) imaging with gadolinium to detect myocardial scar. Cardiovascular disease risk factors and coronary artery calcium (CAC) scores were measured at baseline and year 10. Logistic regression models were used to estimate adjusted odds ratios (ORs) for myocardial scar.', 'Cardiovascular risk factors, CAC scores, left ventricle size and function, and carotid intima-media thickness.', 'Myocardial scar detected by CMR imaging.', 'Of 1840 participants (mean [SD] age, 68 [9] years, 52% men), 146 (7.9%) had myocardial scars, of which 114 (78%) were undetected by electrocardiogram or by clinical adjudication. In adjusted models, age, male sex, body mass index, hypertension, and current smoking at baseline were associated with myocardial scar at year 10. The OR per 8.9-year increment was 1.61 (95% CI, 1.36-1.91; P <\\u2009.001); for men vs women: OR, 5.76 (95% CI, 3.61-9.17; P <\\u2009.001); per 4.8-SD body mass index: OR, 1.32 (95% CI, 1.09-1.61, P =\\u2009.005); for hypertension: OR, 1.61 (95% CI, 1.12-2.30; P =\\u2009.009); and for current vs never smokers: 2.00 (95% CI, 1.22-3.28; P =\\u2009.006). Age-, sex-, and ethnicity-adjusted CAC scores at baseline were also associated with myocardial scar at year 10. Compared with a CAC score of 0, the OR for scores from 1 through 99 was 2.4 (95% CI, 1.5-3.9); from 100 through 399, 3.0 (95% CI, 1.7-5.1), and 400 or higher, 3.3 (95% CI, 1.7-6.1) (P ≤ .001). The CAC score significantly added to the association of myocardial scar with age, sex, race/ethnicity, and traditional CVD risk factors (C statistic, 0.81 with CAC vs 0.79 without CAC, P =\\u2009.01).'], 'labels': ['OBJECTIVE', 'OBJECTIVE', 'METHODS', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['African Continental Ancestry Group', 'Aged', 'Aged, 80 and over', 'Body Mass Index', 'Calcinosis', 'Cardiomyopathies', 'Cardiovascular Diseases', 'China', 'Cicatrix', 'Coronary Artery Disease', 'European Continental Ancestry Group', 'Female', 'Gadolinium', 'Hispanic Americans', 'Humans', 'Magnetic Resonance Imaging', 'Male', 'Middle Aged', 'Myocardial Infarction', 'Prevalence', 'Regression Analysis', 'Time Factors', 'United States']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,530,930 | Is radiologic evidence that hypothalamic gliosis associated with obesity and insulin resistance in humans? | {
"contexts": [
"To use quantitative magnetic resonance imaging (MRI) to test whether mediobasal hypothalamic (MBH) gliosis is associated with obesity and insulin resistance in humans.",
"Sixty-seven participants underwent a fasting blood draw and MRI. Cases with radiologic evidence of MBH gliosis (N = 22) were identified as the upper tertile of left MBH T2 relaxation time and were compared to controls (N = 23) from the lowest tertile. In a separate postmortem study, brain slices (N = 10) through the MBH were imaged by MRI and stained for glial fibrillary acidic protein (GFAP).",
"In all participants, longer T2 relaxation time in the left MBH was associated with higher BMI (P = 0.01). Compared with controls, cases had longer T2 relaxation times in the right MBH (P < 0.05), as well as higher BMI (P < 0.05), fasting insulin concentrations (P < 0.01), and HOMA-IR values (P < 0.01), adjusted for sex and age. Elevations in insulin and HOMA-IR were also independent of BMI. In the postmortem study, GFAP staining intensity was positively associated with MBH T2 relaxation time (P < 0.05), validating an MRI-based method for the detection of MBH gliosis in humans."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adiposity",
"Adolescent",
"Adult",
"Case-Control Studies",
"Fasting",
"Female",
"Gliosis",
"Humans",
"Hypothalamus",
"Insulin",
"Insulin Resistance",
"Magnetic Resonance Imaging",
"Male",
"Middle Aged",
"Obesity",
"Young Adult"
]
} | These findings link hypothalamic gliosis to insulin resistance in humans and suggest that the link is independent of the level of adiposity. | yes | [
{
"from": "human",
"value": "Question: Is radiologic evidence that hypothalamic gliosis associated with obesity and insulin resistance in humans?\nContext: {'contexts': ['To use quantitative magnetic resonance imaging (MRI) to test whether mediobasal hypothalamic (MBH) gliosis is associated with obesity and insulin resistance in humans.', 'Sixty-seven participants underwent a fasting blood draw and MRI. Cases with radiologic evidence of MBH gliosis (N\\u2009=\\u200922) were identified as the upper tertile of left MBH T2 relaxation time and were compared to controls (N\\u2009=\\u200923) from the lowest tertile. In a separate postmortem study, brain slices (N\\u2009=\\u200910) through the MBH were imaged by MRI and stained for glial fibrillary acidic protein (GFAP).', 'In all participants, longer T2 relaxation time in the left MBH was associated with higher BMI (P\\u2009=\\u20090.01). Compared with controls, cases had longer T2 relaxation times in the right MBH (P\\u2009<\\u20090.05), as well as higher BMI (P\\u2009<\\u20090.05), fasting insulin concentrations (P\\u2009<\\u20090.01), and HOMA-IR values (P\\u2009<\\u20090.01), adjusted for sex and age. Elevations in insulin and HOMA-IR were also independent of BMI. In the postmortem study, GFAP staining intensity was positively associated with MBH T2 relaxation time (P\\u2009<\\u20090.05), validating an MRI-based method for the detection of MBH gliosis in humans.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adiposity', 'Adolescent', 'Adult', 'Case-Control Studies', 'Fasting', 'Female', 'Gliosis', 'Humans', 'Hypothalamus', 'Insulin', 'Insulin Resistance', 'Magnetic Resonance Imaging', 'Male', 'Middle Aged', 'Obesity', 'Young Adult']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,537,299 | Does sERPINE1 rs1799768 polymorphism contribute to sepsis risk and mortality? | {
"contexts": [
"The present meta-analysis aimed to investigate whether there is an association between SERPINE1 rs1799768 polymorphism and sepsis risk and mortality.",
"Published reports were searched in PubMed, PubMed Central, Gene, PubChem and Google Scholar. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed in a random-effects model.",
"The results of the overall meta-analysis indicated that an increased sepsis risk was evidently associated with SERPINE1 rs1799768 polymorphism (OR = 1.30; 95% CI 1.08-1.56; p = 0.006). When studies were stratified by ethnicity, no significant association was observed between SERPINE1 rs1799768 polymorphism and sepsis risk in the Asian group. As for the Caucasian population, overall OR was 1.24 (95% CI 1.02-1.51; p = 0.03). The results of the overall meta-analysis indicated that an increased sepsis mortality risk was evidently associated with SERPINE1 rs1799768 polymorphism (OR = 1.73; 95% CI 1.31-2.28; p < 0.0001). When studies were stratified by ethnicity, significant association was observed between SERPINE1 rs1799768 polymorphism and sepsis risk mortality in the Asian group and the Caucasian population."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Genetic Predisposition to Disease",
"Humans",
"Plasminogen Activator Inhibitor 1",
"Polymorphism, Single Nucleotide",
"Risk Factors",
"Sepsis"
]
} | In conclusion, the meta-analysis suggests that there are significant associations between SERPINE1 rs1799768 polymorphism and risk of sepsis and sepsis mortality. | yes | [
{
"from": "human",
"value": "Question: Does sERPINE1 rs1799768 polymorphism contribute to sepsis risk and mortality?\nContext: {'contexts': ['The present meta-analysis aimed to investigate whether there is an association between SERPINE1 rs1799768 polymorphism and sepsis risk and mortality.', 'Published reports were searched in PubMed, PubMed Central, Gene, PubChem and Google Scholar. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed in a random-effects model.', 'The results of the overall meta-analysis indicated that an increased sepsis risk was evidently associated with SERPINE1 rs1799768 polymorphism (OR = 1.30; 95% CI 1.08-1.56; p = 0.006). When studies were stratified by ethnicity, no significant association was observed between SERPINE1 rs1799768 polymorphism and sepsis risk in the Asian group. As for the Caucasian population, overall OR was 1.24 (95% CI 1.02-1.51; p = 0.03). The results of the overall meta-analysis indicated that an increased sepsis mortality risk was evidently associated with SERPINE1 rs1799768 polymorphism (OR = 1.73; 95% CI 1.31-2.28; p < 0.0001). When studies were stratified by ethnicity, significant association was observed between SERPINE1 rs1799768 polymorphism and sepsis risk mortality in the Asian group and the Caucasian population.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Genetic Predisposition to Disease', 'Humans', 'Plasminogen Activator Inhibitor 1', 'Polymorphism, Single Nucleotide', 'Risk Factors', 'Sepsis']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,552,196 | Do the reasons students choose to undertake a nursing degree? | {
"contexts": [
"Determining the reasons people choose to study nursing may help educators and managers develop student-focussed and enticing nursing programmes. In Australia, little research has been undertaken with students entering nursing programmes and the reasons for their choice.",
"The aim of this study was to determine why new students choose to enter nursing at university.",
"A descriptive survey design.",
"An urban university in Sydney, Australia.",
"Undergraduate nursing students at the beginning of their first year of study.",
"An open-ended question relating to the reasons for students' choice of a nursing programme was included in the survey. The transcribed textual data were content analysed for words related to the students' choice.",
"The students' reasons for entering nursing programmes were both personal and career related, with personal being more dominant. The reasons to start nursing were: being able to help and care for people, job security, the ability to enter tertiary education and the enjoyment or love of nursing."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Adult",
"Australia",
"Career Choice",
"Education, Nursing, Baccalaureate",
"Female",
"Humans",
"Male",
"Motivation",
"Socioeconomic Factors",
"Students, Nursing",
"Surveys and Questionnaires",
"Young Adult"
]
} | Nursing remains a career of choice for young and mature students entering university. It is seen to provide security, interest and opportunity to help and care for others. Universities must focus on this as they develop programmes for a generation where multiple changes of career appear inevitable during their lifetime. The nursing profession needs to look at career pathways after graduation that provide these challenges within nursing itself. | yes | [
{
"from": "human",
"value": "Question: Do the reasons students choose to undertake a nursing degree?\nContext: {'contexts': ['Determining the reasons people choose to study nursing may help educators and managers develop student-focussed and enticing nursing programmes. In Australia, little research has been undertaken with students entering nursing programmes and the reasons for their choice.', 'The aim of this study was to determine why new students choose to enter nursing at university.', 'A descriptive survey design.', 'An urban university in Sydney, Australia.', 'Undergraduate nursing students at the beginning of their first year of study.', \"An open-ended question relating to the reasons for students' choice of a nursing programme was included in the survey. The transcribed textual data were content analysed for words related to the students' choice.\", \"The students' reasons for entering nursing programmes were both personal and career related, with personal being more dominant. The reasons to start nursing were: being able to help and care for people, job security, the ability to enter tertiary education and the enjoyment or love of nursing.\"], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'METHODS', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Australia', 'Career Choice', 'Education, Nursing, Baccalaureate', 'Female', 'Humans', 'Male', 'Motivation', 'Socioeconomic Factors', 'Students, Nursing', 'Surveys and Questionnaires', 'Young Adult']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,551,031 | Do treatment of Renal Stones ≥20 mm with Extracorporeal Shock Wave Lithotripsy? | {
"contexts": [
"To identify subgroups of patients with renal stones ≥20 mm that are more suitable for extracorporeal shock wave lithotripsy (ESWL) monotherapy.",
"A total of 376 patients with renal stones ≥20 mm underwent monotherapy with ESWL. The treatment outcome was evaluated after 3 months of follow-up. A stone-free status or fragmentation of stones to 4 mm or smaller was considered efficacious.",
"At 3 months after treatment, the overall stone-free rate was 64.4%, and the efficacy rate was 70.7%. The efficacy rate was 89.4% for patients with a residual stone surface area ≤50% of baseline after the first ESWL, while the efficacy rate was 32.4% for other patients. The efficacy was 92.2% for stones ≤400 mm2 and those with lower radiodensity, as determined by a plain (KUB) film."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Female",
"Follow-Up Studies",
"Humans",
"Kidney Calculi",
"Lithotripsy",
"Male",
"Middle Aged",
"Multivariate Analysis",
"Radiography, Abdominal",
"Software",
"Treatment Outcome",
"X-Rays",
"Young Adult"
]
} | For renal stones with a surface area ≤400 mm2 and a radiodensity equal to or less than that of the 12th rib as determined by a KUB film, ESWL may be considered the first line of treatment, even for stones with a diameter ≥20 mm. For large stones requiring repeat treatments, the surface area of the residual stones after the first ESWL is a predictor of the final treatment result. | yes | [
{
"from": "human",
"value": "Question: Do treatment of Renal Stones ≥20 mm with Extracorporeal Shock Wave Lithotripsy?\nContext: {'contexts': ['To identify subgroups of patients with renal stones ≥20 mm that are more suitable for extracorporeal shock wave lithotripsy (ESWL) monotherapy.', 'A total of 376 patients with renal stones ≥20 mm underwent monotherapy with ESWL. The treatment outcome was evaluated after 3 months of follow-up. A stone-free status or fragmentation of stones to 4 mm or smaller was considered efficacious.', 'At 3 months after treatment, the overall stone-free rate was 64.4%, and the efficacy rate was 70.7%. The efficacy rate was 89.4% for patients with a residual stone surface area ≤50% of baseline after the first ESWL, while the efficacy rate was 32.4% for other patients. The efficacy was 92.2% for stones ≤400 mm2 and those with lower radiodensity, as determined by a plain (KUB) film.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Female', 'Follow-Up Studies', 'Humans', 'Kidney Calculi', 'Lithotripsy', 'Male', 'Middle Aged', 'Multivariate Analysis', 'Radiography, Abdominal', 'Software', 'Treatment Outcome', 'X-Rays', 'Young Adult']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,526,082 | Are colonic Diverticula Associated With an Increased Risk of Colorectal Adenomas? | {
"contexts": [
"Patients with missed colorectal cancer have been reported to be more likely to have colonic diverticulosis. Such an association could be due to either higher risk of neoplasia or difficulty examining the colon in patients with diverticulosis. The aim of this study was to determine whether colonic diverticula are associated with an increased risk for colonic neoplasia.",
"We analyzed data from a prospective study of patients undergoing screening colonoscopy that included detailed assessment of all colonic diverticula and colorectal polyps. We used logistic regression to estimate odds ratios and 95% confidence intervals while adjusting for confounding variables.",
"Our analyses included 624 participants. Of these, 216 (35%) had one or more colorectal adenomas. Diverticula on colonoscopy were not associated with an increased risk of adenomas (odds ratio (OR) 1.0, 95% confidence interval (CI) 0.7-1.4) or advanced adenomas (OR 0.8, 95% CI 0.4-1.5). Those with the greatest burden of diverticula (10 or more) did not have an increased risk of adenomas (OR 1.1, 95% CI 0.7-1.8) compared with no diverticula. Colonic diverticula were not associated with an increased risk of proximal (OR 1.0, 95% CI 0.6-1.6) or distal adenomas (OR 1.0, 95% CI 0.6-1.7)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adenoma",
"Aged",
"Cell Transformation, Neoplastic",
"Colonoscopy",
"Colorectal Neoplasms",
"Diverticulum, Colon",
"Early Detection of Cancer",
"Female",
"Humans",
"Logistic Models",
"Male",
"Mass Screening",
"Middle Aged",
"Odds Ratio",
"Prospective Studies"
]
} | Patients with colonic diverticula do not have an increased risk of colorectal adenomas or advanced adenomas. | no | [
{
"from": "human",
"value": "Question: Are colonic Diverticula Associated With an Increased Risk of Colorectal Adenomas?\nContext: {'contexts': ['Patients with missed colorectal cancer have been reported to be more likely to have colonic diverticulosis. Such an association could be due to either higher risk of neoplasia or difficulty examining the colon in patients with diverticulosis. The aim of this study was to determine whether colonic diverticula are associated with an increased risk for colonic neoplasia.', 'We analyzed data from a prospective study of patients undergoing screening colonoscopy that included detailed assessment of all colonic diverticula and colorectal polyps. We used logistic regression to estimate odds ratios and 95% confidence intervals while adjusting for confounding variables.', 'Our analyses included 624 participants. Of these, 216 (35%) had one or more colorectal adenomas. Diverticula on colonoscopy were not associated with an increased risk of adenomas (odds ratio (OR) 1.0, 95% confidence interval (CI) 0.7-1.4) or advanced adenomas (OR 0.8, 95% CI 0.4-1.5). Those with the greatest burden of diverticula (10 or more) did not have an increased risk of adenomas (OR 1.1, 95% CI 0.7-1.8) compared with no diverticula. Colonic diverticula were not associated with an increased risk of proximal (OR 1.0, 95% CI 0.6-1.6) or distal adenomas (OR 1.0, 95% CI 0.6-1.7).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adenoma', 'Aged', 'Cell Transformation, Neoplastic', 'Colonoscopy', 'Colorectal Neoplasms', 'Diverticulum, Colon', 'Early Detection of Cancer', 'Female', 'Humans', 'Logistic Models', 'Male', 'Mass Screening', 'Middle Aged', 'Odds Ratio', 'Prospective Studies']}"
},
{
"from": "gpt",
"value": "Answer: no"
}
]
|
26,554,404 | Does the ALK/ROS1 Inhibitor PF-06463922 overcome Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma? | {
"contexts": [
"Neuroblastomas harboring activating point mutations in anaplastic lymphoma kinase (ALK) are differentially sensitive to the ALK inhibitor crizotinib, with certain mutations conferring intrinsic crizotinib resistance. To overcome this clinical obstacle, our goal was to identify inhibitors with improved potency that can target intractable ALK variants such as F1174L. We find that PF-06463922 has high potency across ALK variants and inhibits ALK more effectively than crizotinib in vitro. Most importantly, PF-06463922 induces complete tumor regression in both crizotinib-resistant and crizotinib-sensitive xenograft mouse models of neuroblastoma, as well as in patient-derived xenografts harboring the crizotinib-resistant F1174L or F1245C mutations. These studies demonstrate that PF-06463922 has the potential to overcome crizotinib resistance and exerts unprecedented activity as a single targeted agent against F1174L and F1245C ALK-mutated xenograft tumors, while also inducing responses in an R1275Q xenograft model. Taken together, these results provide the rationale to move PF-06463922 into clinical trials for treatment of patients with ALK-mutated neuroblastoma."
],
"labels": [
"UNLABELLED"
],
"meshes": [
"Anaplastic Lymphoma Kinase",
"Animals",
"Cell Line, Tumor",
"Crizotinib",
"Drug Resistance, Neoplasm",
"Humans",
"Lactams, Macrocyclic",
"Mice",
"Mutation",
"Neuroblastoma",
"Phosphorylation",
"Protein Kinase Inhibitors",
"Pyrazoles",
"Pyridines",
"Receptor Protein-Tyrosine Kinases",
"Treatment Outcome",
"Xenograft Model Antitumor Assays"
]
} | The next-generation ALK/ROS1 inhibitor PF-06463922 exerts unparalleled activity in ALK-driven neuroblastoma models with primary crizotinib resistance. Our biochemical and in vivo data provide the preclinical rationale for fast-tracking the development of this agent in children with relapsed/refractory ALK-mutant neuroblastoma. | yes | [
{
"from": "human",
"value": "Question: Does the ALK/ROS1 Inhibitor PF-06463922 overcome Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma?\nContext: {'contexts': ['Neuroblastomas harboring activating point mutations in anaplastic lymphoma kinase (ALK) are differentially sensitive to the ALK inhibitor crizotinib, with certain mutations conferring intrinsic crizotinib resistance. To overcome this clinical obstacle, our goal was to identify inhibitors with improved potency that can target intractable ALK variants such as F1174L. We find that PF-06463922 has high potency across ALK variants and inhibits ALK more effectively than crizotinib in vitro. Most importantly, PF-06463922 induces complete tumor regression in both crizotinib-resistant and crizotinib-sensitive xenograft mouse models of neuroblastoma, as well as in patient-derived xenografts harboring the crizotinib-resistant F1174L or F1245C mutations. These studies demonstrate that PF-06463922 has the potential to overcome crizotinib resistance and exerts unprecedented activity as a single targeted agent against F1174L and F1245C ALK-mutated xenograft tumors, while also inducing responses in an R1275Q xenograft model. Taken together, these results provide the rationale to move PF-06463922 into clinical trials for treatment of patients with ALK-mutated neuroblastoma.'], 'labels': ['UNLABELLED'], 'meshes': ['Anaplastic Lymphoma Kinase', 'Animals', 'Cell Line, Tumor', 'Crizotinib', 'Drug Resistance, Neoplasm', 'Humans', 'Lactams, Macrocyclic', 'Mice', 'Mutation', 'Neuroblastoma', 'Phosphorylation', 'Protein Kinase Inhibitors', 'Pyrazoles', 'Pyridines', 'Receptor Protein-Tyrosine Kinases', 'Treatment Outcome', 'Xenograft Model Antitumor Assays']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,545,014 | Does plasmalogen modulation attenuate atherosclerosis in ApoE- and ApoE/GPx1-deficient mice? | {
"contexts": [
"We previously reported a negative association of circulating plasmalogens (phospholipids with proposed atheroprotective properties) with coronary artery disease. Plasmalogen modulation was previously demonstrated in animals but its effect on atherosclerosis was unknown. We assessed the effect of plasmalogen enrichment on atherosclerosis of murine models with differing levels of oxidative stress.",
"Six-week old ApoE- and ApoE/glutathione peroxidase-1 (GPx1)-deficient mice were fed a high-fat diet with/without 2% batyl alcohol (precursor to plasmalogen synthesis) for 12 weeks. Mass spectrometry analysis of lipids showed that batyl alcohol supplementation to ApoE- and ApoE/GPx1-deficient mice increased the total plasmalogen levels in both plasma and heart. Oxidation of plasmalogen in the treated mice was evident from increased level of plasmalogen oxidative by-product, sn-2 lysophospholipids. Atherosclerotic plaque in the aorta was reduced by 70% (P = 5.69E-07) and 69% (P = 2.00E-04) in treated ApoE- and ApoE/GPx1-deficient mice, respectively. A 40% reduction in plaque (P = 7.74E-03) was also seen in the aortic sinus of only the treated ApoE/GPx1-deficient mice. Only the treated ApoE/GPx1-deficient mice showed a decrease in VCAM-1 staining (-28%, P = 2.43E-02) in the aortic sinus and nitrotyrosine staining (-78%, P = 5.11E-06) in the aorta."
],
"labels": [
"OBJECTIVE",
"RESULTS"
],
"meshes": [
"Animals",
"Aorta",
"Aortic Diseases",
"Apolipoproteins E",
"Atherosclerosis",
"Cholesterol",
"Diet, High-Fat",
"Disease Models, Animal",
"Glutathione Peroxidase",
"Glyceryl Ethers",
"Inflammation Mediators",
"Lysophospholipids",
"Male",
"Mice, Inbred C57BL",
"Mice, Knockout",
"Myocardium",
"Oxidation-Reduction",
"Oxidative Stress",
"Plaque, Atherosclerotic",
"Plasmalogens",
"Tyrosine",
"Up-Regulation",
"Vascular Cell Adhesion Molecule-1"
]
} | Plasmalogen enrichment via batyl alcohol supplementation attenuated atherosclerosis in ApoE- and ApoE/GPx1-deficient mice, with a greater effect in the latter group. Plasmalogen enrichment may represent a viable therapeutic strategy to prevent atherosclerosis and reduce cardiovascular disease risk, particularly under conditions of elevated oxidative stress and inflammation. | yes | [
{
"from": "human",
"value": "Question: Does plasmalogen modulation attenuate atherosclerosis in ApoE- and ApoE/GPx1-deficient mice?\nContext: {'contexts': ['We previously reported a negative association of circulating plasmalogens (phospholipids with proposed atheroprotective properties) with coronary artery disease. Plasmalogen modulation was previously demonstrated in animals but its effect on atherosclerosis was unknown. We assessed the effect of plasmalogen enrichment on atherosclerosis of murine models with differing levels of oxidative stress.', 'Six-week old ApoE- and ApoE/glutathione peroxidase-1 (GPx1)-deficient mice were fed a high-fat diet with/without 2% batyl alcohol (precursor to plasmalogen synthesis) for 12 weeks. Mass spectrometry analysis of lipids showed that batyl alcohol supplementation to ApoE- and ApoE/GPx1-deficient mice increased the total plasmalogen levels in both plasma and heart. Oxidation of plasmalogen in the treated mice was evident from increased level of plasmalogen oxidative by-product, sn-2 lysophospholipids. Atherosclerotic plaque in the aorta was reduced by 70% (P\\xa0=\\xa05.69E-07) and 69% (P\\xa0=\\xa02.00E-04) in treated ApoE- and ApoE/GPx1-deficient mice, respectively. A 40% reduction in plaque (P\\xa0=\\xa07.74E-03) was also seen in the aortic sinus of only the treated ApoE/GPx1-deficient mice. Only the treated ApoE/GPx1-deficient mice showed a decrease in VCAM-1 staining (-28%, P\\xa0=\\xa02.43E-02) in the aortic sinus and nitrotyrosine staining (-78%, P\\xa0=\\xa05.11E-06) in the aorta.'], 'labels': ['OBJECTIVE', 'RESULTS'], 'meshes': ['Animals', 'Aorta', 'Aortic Diseases', 'Apolipoproteins E', 'Atherosclerosis', 'Cholesterol', 'Diet, High-Fat', 'Disease Models, Animal', 'Glutathione Peroxidase', 'Glyceryl Ethers', 'Inflammation Mediators', 'Lysophospholipids', 'Male', 'Mice, Inbred C57BL', 'Mice, Knockout', 'Myocardium', 'Oxidation-Reduction', 'Oxidative Stress', 'Plaque, Atherosclerotic', 'Plasmalogens', 'Tyrosine', 'Up-Regulation', 'Vascular Cell Adhesion Molecule-1']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,541,277 | Do the synergistic effects of shear stress and cyclic hydrostatic pressure modulate chondrogenic induction of human mesenchymal stem cells? | {
"contexts": [
"In this study, we examined chondrogenic regulation of 2 types of mesenchymal stem cells seeded on the bioengineered substrate in monolayer cultures under mechanically defined conditions to mimic the in vivo microenvironment of chondrocytes within articular cartilage tissues.",
"Human adipose-derived mesenchymal stem cells (ASCs) and bone marrow mesenchymal stem cells (BSCs) were exposed to 0.2 Pa shear stress, 3 MPa cyclic hydrostatic pressure, and combined loading with different sequences on chemically designed medical-grade silicone rubber, while no soluble growth factors were added to the culture medium. The expression levels of chondrogenic-specific genes of SOX9, aggrecan, and type II collagen (Col II) were measured. Results were compared to those of cells treated by biological growth factor.",
"Gene expression patterns were dependent on the loading regime. Moreover, the source of mesenchymal stem cells (adipose or bone marrow) was influential in gene expression. Overall, enhanced expression of chondrogenic markers was found through application of mechanical stimuli. The response was generally found to be significantly promoted when the 2 loading regimes were superimposed."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aggrecans",
"Cartilage, Articular",
"Chondrocytes",
"Chondrogenesis",
"Collagen Type II",
"Humans",
"Hydrostatic Pressure",
"Mesenchymal Stem Cells",
"SOX9 Transcription Factor",
"Stress, Mechanical"
]
} | Differentiation of ASCs was shown by a modest increase in gene expression profiles. In general, BSCs expressed higher levels of chondrogenic gene expression than ASCs after 3 weeks. A greater effect on Col II and SOX9 mRNA expression was observed when combined loadings were applied. Results may be applied in determining the proper loading sequence for obtaining functional target cells in cartilage engineering applications. | yes | [
{
"from": "human",
"value": "Question: Do the synergistic effects of shear stress and cyclic hydrostatic pressure modulate chondrogenic induction of human mesenchymal stem cells?\nContext: {'contexts': ['In this study, we examined chondrogenic regulation of 2 types of mesenchymal stem cells seeded on the bioengineered substrate in monolayer cultures under mechanically defined conditions to mimic the in vivo microenvironment of chondrocytes within articular cartilage tissues.', 'Human adipose-derived mesenchymal stem cells (ASCs) and bone marrow mesenchymal stem cells (BSCs) were exposed to 0.2 Pa shear stress, 3 MPa cyclic hydrostatic pressure, and combined loading with different sequences on chemically designed medical-grade silicone rubber, while no soluble growth factors were added to the culture medium. The expression levels of chondrogenic-specific genes of SOX9, aggrecan, and type II collagen (Col II) were measured. Results were compared to those of cells treated by biological growth factor.', 'Gene expression patterns were dependent on the loading regime. Moreover, the source of mesenchymal stem cells (adipose or bone marrow) was influential in gene expression. Overall, enhanced expression of chondrogenic markers was found through application of mechanical stimuli. The response was generally found to be significantly promoted when the 2 loading regimes were superimposed.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aggrecans', 'Cartilage, Articular', 'Chondrocytes', 'Chondrogenesis', 'Collagen Type II', 'Humans', 'Hydrostatic Pressure', 'Mesenchymal Stem Cells', 'SOX9 Transcription Factor', 'Stress, Mechanical']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,541,276 | Does tNF-α suppression and osteoprotegerin overexpression inhibit wear debris-induced inflammation and osteoclastogenesis in vitro? | {
"contexts": [
"Periprosthetic osteolysis, involving RANK/RANKL/osteoprotegerin (OPG) and TNF-α/NFκB signaling, contributes to bone resorption and inflammation. We constructed lentivirus vectors to inhibit TNF-α and enhance OPG expression and assessed their impacts on wear debris-induced inflammation and osteoclastogenesis in an osteoclast/osteoblast coculture system.",
"We transduced mouse osteoblastic MC3T3-E1 cells with Lenti-negative control (Lenti-NC), Lenti-OPG or Lenti-siTNFα-OPG, and murine macrophage/monocyte RAW264.7 cells with Lenti-NC, Lenti-TNF-α siRNA or Lenti-siTNFα-OPG. Then, TNF-α and OPG protein levels were evaluated by enzyme-linked immunosorbent assay. We cocultured transduced MC3T3-E1 and RAW264.7 cells in transwell chambers in the presence of 0.1 mg/mL Ti particles to investigate the capacity of TNF-α inhibition to reduce wear debris-induced inflammation. We also assessed mRNA levels TNF-α, IL-1β, IL-6 and OPG by RT-PCR as well as osteoclastogenesis by tartrate-resistant acid phosphatase.",
"Lenti-siTNFα-OPG ameliorated Ti-particle-induced expression of TNF-α, IL-1β, IL-6 in MC3T3-E1/RAW264.7 cocultures, while enhancing mRNA and protein levels of OPG, and reducing the fraction of tartrate-resistant acid phosphatase (TRAP)+ cells."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Cytokines",
"Inflammation",
"Mice",
"Osteoclasts",
"Osteolysis",
"Osteoprotegerin",
"Tumor Necrosis Factor-alpha"
]
} | Lenti-siTNFα-OPG can inhibit the wear debris-induced inflammatory responses and osteoclastogenesis in vitro, and may represent a promising therapeutic candidate for the treatment or prevention of wear particle-induced osteolysis. | yes | [
{
"from": "human",
"value": "Question: Does tNF-α suppression and osteoprotegerin overexpression inhibit wear debris-induced inflammation and osteoclastogenesis in vitro?\nContext: {'contexts': ['Periprosthetic osteolysis, involving RANK/RANKL/osteoprotegerin (OPG) and TNF-α/NFκB signaling, contributes to bone resorption and inflammation. We constructed lentivirus vectors to inhibit TNF-α and enhance OPG expression and assessed their impacts on wear debris-induced inflammation and osteoclastogenesis in an osteoclast/osteoblast coculture system.', 'We transduced mouse osteoblastic MC3T3-E1 cells with Lenti-negative control (Lenti-NC), Lenti-OPG or Lenti-siTNFα-OPG, and murine macrophage/monocyte RAW264.7 cells with Lenti-NC, Lenti-TNF-α siRNA or Lenti-siTNFα-OPG. Then, TNF-α and OPG protein levels were evaluated by enzyme-linked immunosorbent assay. We cocultured transduced MC3T3-E1 and RAW264.7 cells in transwell chambers in the presence of 0.1 mg/mL Ti particles to investigate the capacity of TNF-α inhibition to reduce wear debris-induced inflammation. We also assessed mRNA levels TNF-α, IL-1β, IL-6 and OPG by RT-PCR as well as osteoclastogenesis by tartrate-resistant acid phosphatase.', 'Lenti-siTNFα-OPG ameliorated Ti-particle-induced expression of TNF-α, IL-1β, IL-6 in MC3T3-E1/RAW264.7 cocultures, while enhancing mRNA and protein levels of OPG, and reducing the fraction of tartrate-resistant acid phosphatase (TRAP)+ cells.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Cytokines', 'Inflammation', 'Mice', 'Osteoclasts', 'Osteolysis', 'Osteoprotegerin', 'Tumor Necrosis Factor-alpha']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,542,198 | Is a high-performance liquid chromatography method for the serotonin release assay equivalent to the radioactive method? | {
"contexts": [
"The serotonin release assay (SRA) is considered the gold standard laboratory test for heparin-induced thrombocytopenia (HIT). The historic SRA method uses platelets loaded with radiolabeled serotonin to evaluate platelet activation by HIT immune complexes. However, a nonradioactive method is desirable. We report the performance characteristics of a high-performance liquid chromatography (HPLC) SRA method.",
"We validated the performance characteristics of an HPLC-SRA method, including correlation with a reference laboratory using the radioactive method. Serotonin released from reagent platelets was quantified by HPLC using fluorescent detection. Results were expressed as % release and classified as positive, negative, or indeterminate based on previously published cutoffs.",
"Serum samples from 250 subjects with suspected HIT were tested in the HPLC-SRA and with the radioactive method. Concordant classifications were observed in 230 samples (92%). Sera from 41 healthy individuals tested negative. Between-run imprecision studies showed standard deviation of <6 (% release) for positive, weak positive, and negative serum pools. Stability studies demonstrated stability after two freeze-thaw cycles or up to a week of refrigeration."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Chromatography, High Pressure Liquid",
"Heparin",
"Humans",
"Reproducibility of Results",
"Sensitivity and Specificity",
"Serotonin",
"Thrombocytopenia"
]
} | The HPLC-SRA has robust performance characteristics, equivalent to the historic radioactive method, but avoids the complexities of working with radioactivity. | yes | [
{
"from": "human",
"value": "Question: Is a high-performance liquid chromatography method for the serotonin release assay equivalent to the radioactive method?\nContext: {'contexts': ['The serotonin release assay (SRA) is considered the gold standard laboratory test for heparin-induced thrombocytopenia (HIT). The historic SRA method uses platelets loaded with radiolabeled serotonin to evaluate platelet activation by HIT immune complexes. However, a nonradioactive method is desirable. We report the performance characteristics of a high-performance liquid chromatography (HPLC) SRA method.', 'We validated the performance characteristics of an HPLC-SRA method, including correlation with a reference laboratory using the radioactive method. Serotonin released from reagent platelets was quantified by HPLC using fluorescent detection. Results were expressed as % release and classified as positive, negative, or indeterminate based on previously published cutoffs.', 'Serum samples from 250 subjects with suspected HIT were tested in the HPLC-SRA and with the radioactive method. Concordant classifications were observed in 230 samples (92%). Sera from 41 healthy individuals tested negative. Between-run imprecision studies showed standard deviation of <6 (% release) for positive, weak positive, and negative serum pools. Stability studies demonstrated stability after two freeze-thaw cycles or up to a week of refrigeration.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Chromatography, High Pressure Liquid', 'Heparin', 'Humans', 'Reproducibility of Results', 'Sensitivity and Specificity', 'Serotonin', 'Thrombocytopenia']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,549,988 | Does cFTR Knockdown induce proinflammatory changes in intestinal epithelial cells? | {
"contexts": [
"Hyperinflammation is a hallmark feature of cystic fibrosis (CF) airways. However, inflammation has also been documented systemically and, more recently, in extrapulmonary CF-affected tissues such as the pancreas and intestine. The pathogenesis of CF-related inflammation and more specifically the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in that respect are not entirely understood. We have tested the hypothesis that genetic depletion of CFTR will affect the inflammatory status of human intestinal epithelial cell lines.",
"CFTR expression was genetically depleted from Caco-2/15 and HT-29 cells using short hairpin RNA interference (shRNAi). Inflammatory conditions were induced by the addition of human recombinant tumor necrosis factor (TNF) or Interleukin-1β (IL-1β) for various periods of time. Gene expression, mRNA stability and secreted levels of interleukin (IL)-6, -8 and 10 were assessed. Analysis of pro- and anti-inflammatory signaling pathways including mitogen-activated protein kinases (p38, ERK 1/2 and JNK), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκBα), and nuclear factor-kappa B (NF-κB) was also performed. Eosinophils were counted in the jejunal mucosa of Cftr-/- and Cftr+/+ mice.",
"CFTR gene and protein knockdown caused a significant increase in basal secretion of IL-8 as well as in IL-1β-induced secretion of IL-6 and -8. Release of the anti-inflammatory cytokine, IL-10, remained unaffected by CFTR depletion. The enhanced secretion of IL-8 stems in part from increased IL8 mRNA levels and greater activation of ERK1/2 MAPK, IκBα and NF-κB in the CFTR knockdown cells. By contrast, phosphorylation levels of p38 and JNK MAPK did not differ between control and knockdown cells. We also found a higher number of infiltrating eosinophils in the jejunal mucosa of Cftr -/- females, but not males, compared to Cftr +/+ mice, thus providing in vivo support to our in vitro findings."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": []
} | Collectively, these data underscore the role played by CFTR in regulating the intestinal inflammatory responses. Such findings lend support to the theory that CFTR exerts functions that may go beyond its role as a chloride channel whereby its disruption may prevent cells to optimally respond to exogenous or endogenous challenges. These observations are of particular interest to CF patients who were found to display alterations in their intestinal microbiota, thus predisposing them to pathogens that may elicit exaggerated inflammatory responses. | yes | [
{
"from": "human",
"value": "Question: Does cFTR Knockdown induce proinflammatory changes in intestinal epithelial cells?\nContext: {'contexts': ['Hyperinflammation is a hallmark feature of cystic fibrosis (CF) airways. However, inflammation has also been documented systemically and, more recently, in extrapulmonary CF-affected tissues such as the pancreas and intestine. The pathogenesis of CF-related inflammation and more specifically the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in that respect are not entirely understood. We have tested the hypothesis that genetic depletion of CFTR will affect the inflammatory status of human intestinal epithelial cell lines.', 'CFTR expression was genetically depleted from Caco-2/15 and HT-29 cells using short hairpin RNA interference (shRNAi). Inflammatory conditions were induced by the addition of human recombinant tumor necrosis factor (TNF) or Interleukin-1β (IL-1β) for various periods of time. Gene expression, mRNA stability and secreted levels of interleukin (IL)-6, -8 and 10 were assessed. Analysis of pro- and anti-inflammatory signaling pathways including mitogen-activated protein kinases (p38, ERK 1/2 and JNK), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκBα), and nuclear factor-kappa B (NF-κB) was also performed. Eosinophils were counted in the jejunal mucosa of Cftr-/- and Cftr+/+ mice.', 'CFTR gene and protein knockdown caused a significant increase in basal secretion of IL-8 as well as in IL-1β-induced secretion of IL-6 and -8. Release of the anti-inflammatory cytokine, IL-10, remained unaffected by CFTR depletion. The enhanced secretion of IL-8 stems in part from increased IL8 mRNA levels and greater activation of ERK1/2 MAPK, IκBα and NF-κB in the CFTR knockdown cells. By contrast, phosphorylation levels of p38 and JNK MAPK did not differ between control and knockdown cells. We also found a higher number of infiltrating eosinophils in the jejunal mucosa of Cftr -/- females, but not males, compared to Cftr +/+ mice, thus providing in vivo support to our in vitro findings.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': []}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,546,456 | Are sarcopenia and inflammation independent predictors of survival in male patients newly diagnosed with small cell lung cancer? | {
"contexts": [
"Sarcopenia is suggested to be associated with cancer-related inflammation. We assessed the clinical outcome of small cell lung cancer (SCLC) patients according to sarcopenia and the neutrophil-to-lymphocyte ratio (NLR).",
"A total of 117 male SCLC patients treated with first-line chemo- or chemoradiotherapy were assessed based on a retrospective chart review. The mass of the pectoralis muscle was measured by computed tomography and normalized to height. Patients with the lowest quartile of muscle mass were considered to have sarcopenia. Patients were classified into four groups according to their sarcopenia and NLR statuses: sarcopenia/high NLR, sarcopenia/low NLR, non-sarcopenia/high NLR, and non-sarcopenia/low NLR.",
"Sarcopenic patients had lower progression-free survival (PFS) than did non-sarcopenic patients (median 6.0 vs. 7.5 months, p = 0.009), but the difference in overall survival (OS) was not statistically significant (median 10.5 vs. 13.5 months, p = 0.052). However, the OS of sarcopenic patients with high NLR was significantly lower than that in all other groups (median 3.2 vs. 16.0 vs. 12.5 vs. 13.7 months, respectively, p < 0.001), as was PFS (median 3.2 vs. 7.7 vs. 7.6 vs. 7.1 months, respectively, p < 0.001). On multivariate analysis, sarcopenia with high NLR was an independent prognostic factor for shorter PFS and OS. Early discontinuation of treatment (20.0 vs. 10.3 %) and treatment-related mortality (50.0 vs. 8.4 %) occurred more frequently in these patients than in the other groups (p < 0.001)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Chemoradiotherapy",
"Disease-Free Survival",
"Female",
"Follow-Up Studies",
"Humans",
"Inflammation",
"Lung Neoplasms",
"Lymphocytes",
"Male",
"Middle Aged",
"Neutrophils",
"Prognosis",
"Retrospective Studies",
"Sarcopenia",
"Small Cell Lung Carcinoma"
]
} | In SCLC, sarcopenic male patients with high NLR have a poor prognosis and do not tolerate standard treatment. Intensive supportive care is needed in these patients. | yes | [
{
"from": "human",
"value": "Question: Are sarcopenia and inflammation independent predictors of survival in male patients newly diagnosed with small cell lung cancer?\nContext: {'contexts': ['Sarcopenia is suggested to be associated with cancer-related inflammation. We assessed the clinical outcome of small cell lung cancer (SCLC) patients according to sarcopenia and the neutrophil-to-lymphocyte ratio (NLR).', 'A total of 117 male SCLC patients treated with first-line chemo- or chemoradiotherapy were assessed based on a retrospective chart review. The mass of the pectoralis muscle was measured by computed tomography and normalized to height. Patients with the lowest quartile of muscle mass were considered to have sarcopenia. Patients were classified into four groups according to their sarcopenia and NLR statuses: sarcopenia/high NLR, sarcopenia/low NLR, non-sarcopenia/high NLR, and non-sarcopenia/low NLR.', 'Sarcopenic patients had lower progression-free survival (PFS) than did non-sarcopenic patients (median 6.0 vs. 7.5 months, p\\u2009=\\u20090.009), but the difference in overall survival (OS) was not statistically significant (median 10.5 vs. 13.5 months, p\\u2009=\\u20090.052). However, the OS of sarcopenic patients with high NLR was significantly lower than that in all other groups (median 3.2 vs. 16.0 vs. 12.5 vs. 13.7 months, respectively, p\\u2009<\\u20090.001), as was PFS (median 3.2 vs. 7.7 vs. 7.6 vs. 7.1 months, respectively, p\\u2009<\\u20090.001). On multivariate analysis, sarcopenia with high NLR was an independent prognostic factor for shorter PFS and OS. Early discontinuation of treatment (20.0 vs. 10.3 %) and treatment-related mortality (50.0 vs. 8.4 %) occurred more frequently in these patients than in the other groups (p\\u2009<\\u20090.001).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Chemoradiotherapy', 'Disease-Free Survival', 'Female', 'Follow-Up Studies', 'Humans', 'Inflammation', 'Lung Neoplasms', 'Lymphocytes', 'Male', 'Middle Aged', 'Neutrophils', 'Prognosis', 'Retrospective Studies', 'Sarcopenia', 'Small Cell Lung Carcinoma']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,534,974 | Does matrix Metalloproteinase-12 induce Blood-Brain Barrier Damage After Focal Cerebral Ischemia? | {
"contexts": [
"Matrix metalloproteinases (MMPs) have a central role in compromising the integrity of the blood-brain barrier (BBB). The role of MMP-12 in brain damage after ischemic stroke remains unknown. The main objective of the current study is to investigate the effect of MMP-12 suppression at an early time point before reperfusion on the BBB damage in rats.",
"Sprague-Dawley rats were subjected to middle cerebral artery occlusion and reperfusion. MMP-12 shRNA-expressing plasmids formulated as nanoparticles were administered at a dose of 1 mg/kg body weight. The involvement of MMP-12 on BBB damage was assessed by performing various techniques, including Evans blue dye extravasation, 2,3,5-triphenyltetrazolium chloride staining, immunoblot, gelatin zymography, and immunofluorescence analysis.",
"MMP-12 is upregulated ≈31-, 47-, and 66-fold in rats subjected 1-, 2-, or 4-hour ischemia, respectively, followed by 1-day reperfusion. MMP-12 suppression protected the BBB integrity by inhibiting the degradation of tight-junction proteins. Either intravenous or intra-arterial delivery of MMP-12 shRNA-expressing plasmid significantly reduced the percent Evans blue dye extravasation and infarct size. Furthermore, MMP-12 suppression reduced the endogenous levels of other proteases, such as tissue-type plasminogen activator and MMP-9, which are also known to be the key players involved in BBB damage."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Blood-Brain Barrier",
"Brain",
"Brain Ischemia",
"Matrix Metalloproteinase 12",
"Rats",
"Rats, Sprague-Dawley"
]
} | These results demonstrate the adverse role of MMP-12 in acute brain damage that occurs after ischemic stroke and, thereby, suggesting that MMP-12 suppression could be a promising therapeutic target for cerebral ischemia. | yes | [
{
"from": "human",
"value": "Question: Does matrix Metalloproteinase-12 induce Blood-Brain Barrier Damage After Focal Cerebral Ischemia?\nContext: {'contexts': ['Matrix metalloproteinases (MMPs) have a central role in compromising the integrity of the blood-brain barrier (BBB). The role of MMP-12 in brain damage after ischemic stroke remains unknown. The main objective of the current study is to investigate the effect of MMP-12 suppression at an early time point before reperfusion on the BBB damage in rats.', 'Sprague-Dawley rats were subjected to middle cerebral artery occlusion and reperfusion. MMP-12 shRNA-expressing plasmids formulated as nanoparticles were administered at a dose of 1 mg/kg body weight. The involvement of MMP-12 on BBB damage was assessed by performing various techniques, including Evans blue dye extravasation, 2,3,5-triphenyltetrazolium chloride staining, immunoblot, gelatin zymography, and immunofluorescence analysis.', 'MMP-12 is upregulated ≈31-, 47-, and 66-fold in rats subjected 1-, 2-, or 4-hour ischemia, respectively, followed by 1-day reperfusion. MMP-12 suppression protected the BBB integrity by inhibiting the degradation of tight-junction proteins. Either intravenous or intra-arterial delivery of MMP-12 shRNA-expressing plasmid significantly reduced the percent Evans blue dye extravasation and infarct size. Furthermore, MMP-12 suppression reduced the endogenous levels of other proteases, such as tissue-type plasminogen activator and MMP-9, which are also known to be the key players involved in BBB damage.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Blood-Brain Barrier', 'Brain', 'Brain Ischemia', 'Matrix Metalloproteinase 12', 'Rats', 'Rats, Sprague-Dawley']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,536,020 | Does rotigotine Transdermal Patch Make Parkinson Disease Patients Sleepy During Daytime? | {
"contexts": [
"To assess quantitatively the influence of rotigotine transdermal patch on daytime sleepiness, the most common adverse event by non-ergot dopamine agonists (DAs), in Parkinson disease (PD) patients.",
"An open-label study enrolled PD patients with unsatisfactory control of motor symptoms. Treatment with rotigotine transdermal patch was titrated to optimal dose (4-8 mg/24 hours) over 2 to 4 weeks. Primary outcome was Epworth Sleepiness Scale (ESS) for daytime sleepiness. Secondary outcomes included Hoehn&Yahr stage, time spent with dyskinesia, Clinical Global Impression of Improvement (CGI-I) of motor symptoms, adverse events, and compliance.",
"The subjects were 31 PD patients (age 72 ± 8, Hoehn &Yahr stage 2.7 ± 0.9, mean ± SD). The ESS did not increase after rotigotine treatment (7.2 ± 4.9 before treatment, 6.2 ± 4.0 with 4 mg/24 hour, and 8.1 ± 6.4 with 8 mg/24 hour). The CGI-I score improved after treatment; responder rate reached 88.9% with 8 mg/24 hours. No patients showed worsening in other secondary outcomes. In 13 patients treated with equivalent doses of rotigotine switched from other DAs (pramipexole, ropinirole, and cabergoline), ESS did not increase after treatment (10.0 ± 4.6 before and 8.6 ± 4.5 after treatment) and decreased without worsening of CGI-I in 54% patients. Other secondary outcomes did not worsen after treatment."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Aged, 80 and over",
"Disorders of Excessive Somnolence",
"Dopamine Agonists",
"Female",
"Humans",
"Male",
"Middle Aged",
"Parkinson Disease",
"Tetrahydronaphthalenes",
"Thiophenes",
"Transdermal Patch",
"Treatment Outcome"
]
} | Twenty four-hour transdermal delivery of rotigotine at doses up to 8 mg/24 hours does not worsen the daytime sleepiness in PD patients and often improves it when switched from other non-ergot DAs. This is achieved together with satisfactory improvement in motor symptoms, demonstrating that this new modality of non-ergot DA is well tolerated and beneficial in PD patients. | no | [
{
"from": "human",
"value": "Question: Does rotigotine Transdermal Patch Make Parkinson Disease Patients Sleepy During Daytime?\nContext: {'contexts': ['To assess quantitatively the influence of rotigotine transdermal patch on daytime sleepiness, the most common adverse event by non-ergot dopamine agonists (DAs), in Parkinson disease (PD) patients.', 'An open-label study enrolled PD patients with unsatisfactory control of motor symptoms. Treatment with rotigotine transdermal patch was titrated to optimal dose (4-8 mg/24 hours) over 2 to 4 weeks. Primary outcome was Epworth Sleepiness Scale (ESS) for daytime sleepiness. Secondary outcomes included Hoehn&Yahr stage, time spent with dyskinesia, Clinical Global Impression of Improvement (CGI-I) of motor symptoms, adverse events, and compliance.', 'The subjects were 31 PD patients (age 72 ± 8, Hoehn &Yahr stage 2.7 ± 0.9, mean ± SD). The ESS did not increase after rotigotine treatment (7.2 ± 4.9 before treatment, 6.2 ± 4.0 with 4 mg/24 hour, and 8.1 ± 6.4 with 8 mg/24 hour). The CGI-I score improved after treatment; responder rate reached 88.9% with 8 mg/24 hours. No patients showed worsening in other secondary outcomes. In 13 patients treated with equivalent doses of rotigotine switched from other DAs (pramipexole, ropinirole, and cabergoline), ESS did not increase after treatment (10.0 ± 4.6 before and 8.6 ± 4.5 after treatment) and decreased without worsening of CGI-I in 54% patients. Other secondary outcomes did not worsen after treatment.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Aged, 80 and over', 'Disorders of Excessive Somnolence', 'Dopamine Agonists', 'Female', 'Humans', 'Male', 'Middle Aged', 'Parkinson Disease', 'Tetrahydronaphthalenes', 'Thiophenes', 'Transdermal Patch', 'Treatment Outcome']}"
},
{
"from": "gpt",
"value": "Answer: no"
}
]
|
26,554,714 | Are plasma levels of trimethylamine-N-oxide confounded by impaired kidney function and poor metabolic control? | {
"contexts": [
"After ingestion of phosphatidylcholine, l-carnitine or betaine, trimethylamine-N-oxide (TMAO) is formed by gut microbiota and liver enzymes. Elevated TMAO plasma levels were associated with increased cardiovascular risk and other diseases. Also betaine and choline itself were recently associated with increased cardiovascular risk.",
"A newly developed LC-HRMS method was applied to measure the plasma concentrations of TMAO, betaine and choline in a cohort of 339 patients undergoing coronary angiography for the evaluation of suspected coronary artery disease.",
"Betaine concentrations in males were significantly higher than in females (42.0 vs. 35.9 μmol/L; p < 0.001). Plasma concentrations of TMAO but not of betaine or choline were higher in patients with diabetes compared to euglycemic patients (2.39 vs. 0.980 μmol/L; p = 0.001) as well as in patients with metabolic syndrome as compared to patients without metabolic syndrome (2.37 vs. 1.43 μmol/L; p = 0.002). Plasma concentrations of TMAO or choline increased significantly with decreasing renal function (Spearman's rho: -0.281; p < 0.001). However, plasma levels of TMAO or betaine were associated with neither a history of myocardial infarction nor the angiographically assessed presence of coronary heart disease, nor incident cardiovascular events during 8 years of follow-up. Plasma levels of choline were significantly lower in patients with a history of acute myocardial infarction as compared to those without such history (10.0 vs. 10.8 μmol/L; p = 0.045)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Betaine",
"Biomarkers",
"Blood Glucose",
"Choline",
"Chromatography, Liquid",
"Coronary Angiography",
"Coronary Disease",
"Diabetes Mellitus",
"Female",
"Glomerular Filtration Rate",
"Humans",
"Kidney",
"Male",
"Metabolic Syndrome",
"Methylamines",
"Middle Aged",
"Predictive Value of Tests",
"Prognosis",
"Reproducibility of Results",
"Spectrometry, Mass, Electrospray Ionization",
"Time Factors"
]
} | Plasma levels of TMAO are confounded by impaired kidney function and poor metabolic control but are not associated with the history, presence or incidence of symptoms or events of coronary heart disease. | yes | [
{
"from": "human",
"value": "Question: Are plasma levels of trimethylamine-N-oxide confounded by impaired kidney function and poor metabolic control?\nContext: {'contexts': ['After ingestion of phosphatidylcholine, l-carnitine or betaine, trimethylamine-N-oxide (TMAO) is formed by gut microbiota and liver enzymes. Elevated TMAO plasma levels were associated with increased cardiovascular risk and other diseases. Also betaine and choline itself were recently associated with increased cardiovascular risk.', 'A newly developed LC-HRMS method was applied to measure the plasma concentrations of TMAO, betaine and choline in a cohort of 339 patients undergoing coronary angiography for the evaluation of suspected coronary artery disease.', \"Betaine concentrations in males were significantly higher than in females (42.0 vs. 35.9\\xa0μmol/L; p\\xa0<\\xa00.001). Plasma concentrations of TMAO but not of betaine or choline were higher in patients with diabetes compared to euglycemic patients (2.39 vs. 0.980\\xa0μmol/L; p\\xa0=\\xa00.001) as well as in patients with metabolic syndrome as compared to patients without metabolic syndrome (2.37 vs. 1.43\\xa0μmol/L; p\\xa0=\\xa00.002). Plasma concentrations of TMAO or choline increased significantly with decreasing renal function (Spearman's rho:\\xa0-0.281; p\\xa0<\\xa00.001). However, plasma levels of TMAO or betaine were associated with neither a history of myocardial infarction nor the angiographically assessed presence of coronary heart disease, nor incident cardiovascular events during 8 years of follow-up. Plasma levels of choline were significantly lower in patients with a history of acute myocardial infarction as compared to those without such history (10.0 vs. 10.8\\xa0μmol/L; p\\xa0=\\xa00.045).\"], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Betaine', 'Biomarkers', 'Blood Glucose', 'Choline', 'Chromatography, Liquid', 'Coronary Angiography', 'Coronary Disease', 'Diabetes Mellitus', 'Female', 'Glomerular Filtration Rate', 'Humans', 'Kidney', 'Male', 'Metabolic Syndrome', 'Methylamines', 'Middle Aged', 'Predictive Value of Tests', 'Prognosis', 'Reproducibility of Results', 'Spectrometry, Mass, Electrospray Ionization', 'Time Factors']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,525,655 | Does deep brain stimulation of the ventromedial prefrontal cortex cause reorganization of neuronal processes and vasculature? | {
"contexts": [
"Chronic high-frequency electrical deep brain stimulation (DBS) of the subcallosal cingulate region is currently being investigated clinically as a therapy for treatment of refractory depression. Experimental DBS of the homologous region, the ventromedial prefrontal cortex (VMPFC), in rodent models has previously demonstrated anti-depressant-like effects. Our goal was to determine if structural remodeling accompanies the alterations of brain function previously observed as a result of chronic DBS.",
"Here we applied 6h of high-frequency bilateral VMPFC DBS daily to 8 9-week old C57Bl/6 mice for 5days. We investigated the \"micro-lesion\" effect by using a sham stimulation group (8 mice) and a control group (8 mice with a hole drilled into the skull only). Whole brain anatomy was investigated post-mortem using high-resolution magnetic resonance imaging and areas demonstrating volumetric expansion were further investigated using histology and immunohistochemistry.",
"The DBS group demonstrated bilateral increases in whole hippocampus and the left thalamus volume compared to both sham and control groups. Local hippocampal and thalamic volume increases were also observed at the voxel-level; however these increases were observed in both DBS and sham groups. Follow-up immunohistochemistry in the hippocampus revealed DBS increased blood vessel size and synaptic density relative to the control group whereas the sham group demonstrated increased astrocyte size."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Brain",
"Deep Brain Stimulation",
"Image Processing, Computer-Assisted",
"Immunohistochemistry",
"Magnetic Resonance Imaging",
"Male",
"Mice",
"Mice, Inbred C57BL"
]
} | Our work demonstrates that DBS not only works by altering function with neural circuits, but also by structurally altering circuits at the cellular level. Neuroplastic alterations may play a role in mediating the clinical efficacy of DBS therapy. | yes | [
{
"from": "human",
"value": "Question: Does deep brain stimulation of the ventromedial prefrontal cortex cause reorganization of neuronal processes and vasculature?\nContext: {'contexts': ['Chronic high-frequency electrical deep brain stimulation (DBS) of the subcallosal cingulate region is currently being investigated clinically as a therapy for treatment of refractory depression. Experimental DBS of the homologous region, the ventromedial prefrontal cortex (VMPFC), in rodent models has previously demonstrated anti-depressant-like effects. Our goal was to determine if structural remodeling accompanies the alterations of brain function previously observed as a result of chronic DBS.', 'Here we applied 6h of high-frequency bilateral VMPFC DBS daily to 8 9-week old C57Bl/6 mice for 5days. We investigated the \"micro-lesion\" effect by using a sham stimulation group (8 mice) and a control group (8 mice with a hole drilled into the skull only). Whole brain anatomy was investigated post-mortem using high-resolution magnetic resonance imaging and areas demonstrating volumetric expansion were further investigated using histology and immunohistochemistry.', 'The DBS group demonstrated bilateral increases in whole hippocampus and the left thalamus volume compared to both sham and control groups. Local hippocampal and thalamic volume increases were also observed at the voxel-level; however these increases were observed in both DBS and sham groups. Follow-up immunohistochemistry in the hippocampus revealed DBS increased blood vessel size and synaptic density relative to the control group whereas the sham group demonstrated increased astrocyte size.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Brain', 'Deep Brain Stimulation', 'Image Processing, Computer-Assisted', 'Immunohistochemistry', 'Magnetic Resonance Imaging', 'Male', 'Mice', 'Mice, Inbred C57BL']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,549,874 | Does the structure of Resuscitation promoting factor B from M. tuberculosis reveal unexpected ubiquitin-like domains? | {
"contexts": [
"RpfB is a key factor in resuscitation from dormancy of Mycobacterium tuberculosis. This protein is a cell-wall glycosidase, which cleaves cell-wall peptidoglycan. RpfB is structurally complex and is composed of three types of domains, including a catalytic, a G5 and three DUF348 domains. Structural information is currently limited to a portion of the protein including only the catalytic and G5 domains. To gain insights into the structure and function of all domains we have undertaken structural investigations on a large protein fragment containing all three types of domains that constitute RpfB (RpfB3D).",
"The structural features of RpfB3D have been investigated combining x-ray crystallography and biophysical studies."
],
"labels": [
"BACKGROUND",
"METHODS"
],
"meshes": [
"Bacterial Proteins",
"Crystallization",
"Mycobacterium tuberculosis",
"Protein Structure, Tertiary",
"Solutions",
"Ubiquitin"
]
} | The crystal structure of RpfB3D provides the first structural characterization of a DUF348 domain and revealed an unexpected structural relationship with ubiquitin. The crystal structure also provides specific structural features of these domains explaining their frequent association with G5 domains. | yes | [
{
"from": "human",
"value": "Question: Does the structure of Resuscitation promoting factor B from M. tuberculosis reveal unexpected ubiquitin-like domains?\nContext: {'contexts': ['RpfB is a key factor in resuscitation from dormancy of Mycobacterium tuberculosis. This protein is a cell-wall glycosidase, which cleaves cell-wall peptidoglycan. RpfB is structurally complex and is composed of three types of domains, including a catalytic, a G5 and three DUF348 domains. Structural information is currently limited to a portion of the protein including only the catalytic and G5 domains. To gain insights into the structure and function of all domains we have undertaken structural investigations on a large protein fragment containing all three types of domains that constitute RpfB (RpfB3D).', 'The structural features of RpfB3D have been investigated combining x-ray crystallography and biophysical studies.'], 'labels': ['BACKGROUND', 'METHODS'], 'meshes': ['Bacterial Proteins', 'Crystallization', 'Mycobacterium tuberculosis', 'Protein Structure, Tertiary', 'Solutions', 'Ubiquitin']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,555,131 | Do serotoninergic antidepressants positively affect platelet ADAM10 expression in patients with Alzheimer 's disease? | {
"contexts": [
"Studies have demonstrated a decreased platelet ADAM10 expression in patients with Alzheimer's Disease (AD), classifying this protein as a blood-based AD biomarker. About 50% of the patients with AD are diagnosed with depression, which is commonly treated with tricyclic and tetracyclic antidepressants, monoaminoxidade (MAO) inhibitors and, more preferably, with selective serotonin reuptake inhibitors (SSRIs). Considering that a large proportion of patients with AD takes antidepressant medications during the course of the disease we investigated the influence of this medication on the expression of platelet ADAM10, which is considered the main α-secretase preventing beta-amyloid (βA) formation.",
"Blood was collected for protein extraction from platelets. ADAM10 was analyzed by using western blotting and reactive bands were measured using β-actin as endogenous control.",
"Platelet ADAM10 protein expression in patients with AD was positively influenced by serotoninergic medication."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"ADAM10 Protein",
"Alzheimer Disease",
"Amyloid Precursor Protein Secretases",
"Antidepressive Agents",
"Biomarkers",
"Blood Platelets",
"Brazil",
"Depressive Disorder",
"Female",
"Humans",
"Serotonin Uptake Inhibitors"
]
} | More studies on the positive effects of serotonergic antidepressants on ADAM10 platelet expression should be performed in order to understand its biological mechanisms and to verify whether these effects are reflected in the central nervous system. This work represents an important advance for the study of AD biomarkers, as well as for more effective pharmacological treatment of patients with AD and associated depression. | yes | [
{
"from": "human",
"value": "Question: Do serotoninergic antidepressants positively affect platelet ADAM10 expression in patients with Alzheimer 's disease?\nContext: {'contexts': [\"Studies have demonstrated a decreased platelet ADAM10 expression in patients with Alzheimer's Disease (AD), classifying this protein as a blood-based AD biomarker. About 50% of the patients with AD are diagnosed with depression, which is commonly treated with tricyclic and tetracyclic antidepressants, monoaminoxidade (MAO) inhibitors and, more preferably, with selective serotonin reuptake inhibitors (SSRIs). Considering that a large proportion of patients with AD takes antidepressant medications during the course of the disease we investigated the influence of this medication on the expression of platelet ADAM10, which is considered the main α-secretase preventing beta-amyloid (βA) formation.\", 'Blood was collected for protein extraction from platelets. ADAM10 was analyzed by using western blotting and reactive bands were measured using β-actin as endogenous control.', 'Platelet ADAM10 protein expression in patients with AD was positively influenced by serotoninergic medication.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['ADAM10 Protein', 'Alzheimer Disease', 'Amyloid Precursor Protein Secretases', 'Antidepressive Agents', 'Biomarkers', 'Blood Platelets', 'Brazil', 'Depressive Disorder', 'Female', 'Humans', 'Serotonin Uptake Inhibitors']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,537,812 | Do male and female runners demonstrate different sagittal plane mechanics as a function of static hamstring flexibility? | {
"contexts": [
"Injuries to runners are common. However, there are many potential contributing factors to injury. While lack of flexibility alone is commonly related to injury, there are clear differences in hamstring flexibility between males and females.",
"To compare the effect of static hamstring length on sagittal plane mechanics between male and female runners.",
"Forty subjects (30.0±6.4 years) participated and were placed in one of 4 groups: flexible males (n=10), inflexible males (n=10), flexible females (n=10), and inflexible females (n=10). All subjects were free of injury at the time of data collection. Three-dimensional kinematics and kinetics were collected while subjects ran over ground across 2 force platforms. Sagittal plane joint angles and moments were calculated at the knee and hip and compared with a 2-way (sex X flexibility) ANOVA (α=0.05).",
"Males exhibited greater peak knee extension moment than females (M=2.80±0.47, F=2.48±0.52 Nm/kg*m, p=0.05) and inflexible runners exhibited greater peak knee extension moment than flexible runners (In=2.83±0.56, Fl=2.44±0.51 Nm/kg*m, p=0.01). For hip flexion at initial contact, a significant interaction existed (p<0.05). Flexible females (36.7±7.4º) exhibited more hip flexion than inflexible females (27.9±4.6º, p<0.01) and flexible males (30.1±9.5º, p<0.05). No differences existed for knee angle at initial contact, peak knee angle, peak hip angle, or peak hip moment."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Female",
"Hamstring Muscles",
"Humans",
"Knee Joint",
"Male",
"Range of Motion, Articular",
"Running"
]
} | Hamstring flexibility results in different mechanical profiles in males and females. Flexibility in the hamstrings may result in decreased moments via active or passive tension. These differences may have implications for performance and injury in flexible female runners. | yes | [
{
"from": "human",
"value": "Question: Do male and female runners demonstrate different sagittal plane mechanics as a function of static hamstring flexibility?\nContext: {'contexts': ['Injuries to runners are common. However, there are many potential contributing factors to injury. While lack of flexibility alone is commonly related to injury, there are clear differences in hamstring flexibility between males and females.', 'To compare the effect of static hamstring length on sagittal plane mechanics between male and female runners.', 'Forty subjects (30.0±6.4 years) participated and were placed in one of 4 groups: flexible males (n=10), inflexible males (n=10), flexible females (n=10), and inflexible females (n=10). All subjects were free of injury at the time of data collection. Three-dimensional kinematics and kinetics were collected while subjects ran over ground across 2 force platforms. Sagittal plane joint angles and moments were calculated at the knee and hip and compared with a 2-way (sex X flexibility) ANOVA (α=0.05).', 'Males exhibited greater peak knee extension moment than females (M=2.80±0.47, F=2.48±0.52 Nm/kg*m, p=0.05) and inflexible runners exhibited greater peak knee extension moment than flexible runners (In=2.83±0.56, Fl=2.44±0.51 Nm/kg*m, p=0.01). For hip flexion at initial contact, a significant interaction existed (p<0.05). Flexible females (36.7±7.4º) exhibited more hip flexion than inflexible females (27.9±4.6º, p<0.01) and flexible males (30.1±9.5º, p<0.05). No differences existed for knee angle at initial contact, peak knee angle, peak hip angle, or peak hip moment.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Female', 'Hamstring Muscles', 'Humans', 'Knee Joint', 'Male', 'Range of Motion, Articular', 'Running']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,536,844 | Does miR-27 impair the adipogenic lineage commitment via targeting lysyl oxidase? | {
"contexts": [
"The recruitment and commitment of mesenchymal stem cells and their terminal differentiation into adipocytes are the main pathways for increasing adipocyte cell numbers during obesity. Our previous studies have shown that lysyl oxidase (Lox) is upregulated and functions as an essential factor during bone morphogenetic protein 4 (BMP4) -induced C3H10T1/2 cell adipocytic lineage commitment. However, the mechanism of Lox regulation during adipogenic lineage commitment has remained largely unestablished.",
"Samples of adipose tissue from humans with different BMI and C57BL/6 mice with a high-fat diet were used to compare microRNA-27 (miR-27) expression level associated with obesity. Taqman assays were used for miR-27 expression detection and Oil Red O staining for adipogenesis analysis.",
"A negative correlation was identified between Lox expression level and miR-27 expression in both BMP4-treated C3H10T1/2 cells and human subcutaneous adipose tissues. A Lox 3' UTR luciferase reporter assay showed that miR-27 directly targeted Lox. Furthermore, overexpression of miR-27 impaired BMP4-induced upregulation of Lox and adipocytic commitment, which could be rescued by overexpression of mature Lox. Conversely, miR-27 inhibition by specific inhibitors increased Lox expression and adipocytic commitment."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adipocytes",
"Adipogenesis",
"Adipose Tissue",
"Animals",
"Body Mass Index",
"Bone Morphogenetic Protein 4",
"Cell Lineage",
"Diet, High-Fat",
"Humans",
"Mesenchymal Stem Cells",
"Mice",
"Mice, Inbred C57BL",
"MicroRNAs",
"Obesity",
"Protein-Lysine 6-Oxidase",
"Up-Regulation"
]
} | Taken together, these results suggest a novel role for miR-27 in repressing adipogenic lineage commitment by targeting Lox. | yes | [
{
"from": "human",
"value": "Question: Does miR-27 impair the adipogenic lineage commitment via targeting lysyl oxidase?\nContext: {'contexts': ['The recruitment and commitment of mesenchymal stem cells and their terminal differentiation into adipocytes are the main pathways for increasing adipocyte cell numbers during obesity. Our previous studies have shown that lysyl oxidase (Lox) is upregulated and functions as an essential factor during bone morphogenetic protein 4 (BMP4) -induced C3H10T1/2 cell adipocytic lineage commitment. However, the mechanism of Lox regulation during adipogenic lineage commitment has remained largely unestablished.', 'Samples of adipose tissue from humans with different BMI and C57BL/6 mice with a high-fat diet were used to compare microRNA-27 (miR-27) expression level associated with obesity. Taqman assays were used for miR-27 expression detection and Oil Red O staining for adipogenesis analysis.', \"A negative correlation was identified between Lox expression level and miR-27 expression in both BMP4-treated C3H10T1/2 cells and human subcutaneous adipose tissues. A Lox 3' UTR luciferase reporter assay showed that miR-27 directly targeted Lox. Furthermore, overexpression of miR-27 impaired BMP4-induced upregulation of Lox and adipocytic commitment, which could be rescued by overexpression of mature Lox. Conversely, miR-27 inhibition by specific inhibitors increased Lox expression and adipocytic commitment.\"], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adipocytes', 'Adipogenesis', 'Adipose Tissue', 'Animals', 'Body Mass Index', 'Bone Morphogenetic Protein 4', 'Cell Lineage', 'Diet, High-Fat', 'Humans', 'Mesenchymal Stem Cells', 'Mice', 'Mice, Inbred C57BL', 'MicroRNAs', 'Obesity', 'Protein-Lysine 6-Oxidase', 'Up-Regulation']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,529,455 | Do normal limits for serum thyrotropin vary greatly depending on method? | {
"contexts": [
"Thyroid-stimulating hormone (TSH) levels within populations do not follow Gaussian distribution, and normal limits are derived after mathematical normalization. The clinical relevance of these limits is unknown. The objective of this study was to compare upper and lower TSH limits by four data normalization methods with non-normalized data and assess their clinical relevance.",
"Results of blood samples taken by community physicians and stored in a computerized database were analysed after removing samples from patients with evidence of thyroid illness. TSH values were normalized by the Hoffmann and Tukey methods and each method with natural log transformation. Non-normalized data for TSH in the uppermost and lowermost percentile were also calculated. Clinical relevance was determined by alterations in thyroid hormone levels at, below and above the limits for each method.",
"The maximal reduction from non-normalized data for the upper normal limit (UNL) was by the Hoffman method 43% = 3·1 mIU/l). The maximal increase for the lower normal limit (LNL) was also by the Hoffman method (708% = 0·81 mIU/l). There was very limited difference in average FT3 and FT4 between patients with TSH within, below or above the normal range for all methods."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Adult",
"Aged",
"Aged, 80 and over",
"Child",
"Child, Preschool",
"Clinical Decision-Making",
"Humans",
"Infant",
"Methods",
"Middle Aged",
"Reference Values",
"Thyroid Diseases",
"Thyrotropin",
"Young Adult"
]
} | Different normalization methods alter the normal limits greatly. However, in individuals without thyroid illness, thyroid hormone values are stable over a wide range of TSH levels including beyond the UNL for all methods. Indeed, there may be no true universal upper TSH cut-off level and clinical decision-making cannot rely on these calculated limits. | yes | [
{
"from": "human",
"value": "Question: Do normal limits for serum thyrotropin vary greatly depending on method?\nContext: {'contexts': ['Thyroid-stimulating hormone (TSH) levels within populations do not follow Gaussian distribution, and normal limits are derived after mathematical normalization. The clinical relevance of these limits is unknown. The objective of this study was to compare upper and lower TSH limits by four data normalization methods with non-normalized data and assess their clinical relevance.', 'Results of blood samples taken by community physicians and stored in a computerized database were analysed after removing samples from patients with evidence of thyroid illness. TSH values were normalized by the Hoffmann and Tukey methods and each method with natural log transformation. Non-normalized data for TSH in the uppermost and lowermost percentile were also calculated. Clinical relevance was determined by alterations in thyroid hormone levels at, below and above the limits for each method.', 'The maximal reduction from non-normalized data for the upper normal limit (UNL) was by the Hoffman method 43% = 3·1 mIU/l). The maximal increase for the lower normal limit (LNL) was also by the Hoffman method (708% = 0·81 mIU/l). There was very limited difference in average FT3 and FT4 between patients with TSH within, below or above the normal range for all methods.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Aged', 'Aged, 80 and over', 'Child', 'Child, Preschool', 'Clinical Decision-Making', 'Humans', 'Infant', 'Methods', 'Middle Aged', 'Reference Values', 'Thyroid Diseases', 'Thyrotropin', 'Young Adult']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,529,456 | Is breast reconstruction with the deep inferior epigastric perforator flap a reliable alternative in slim patients? | {
"contexts": [
"For slim patients eligible to breast reconstruction, clinical concerns exist on availability of adequate amount of donor tissue to restore breast volume and challenges in donor-site closure, when using the deep inferior epigastric perforator (DIEP) flap. The purpose of the current study is to analyze whether the DIEP flap can provide adequate volume for breast reconstruction in slim patients, without increased complication rates or prolonged hospital stay.",
"All patients receiving a unilateral DIEP breast reconstruction at the center 2007-2010 were included (n = 171). The patients were analyzed in subgroups of delayed and immediate reconstruction and of BMI. Complications were analyzed according to Clavien-Dindo. Flap weight was compared to mastectomy specimen weight among immediate reconstructions (n = 91).",
"There was no difference in specimen to flap weight ratio between the different BMI-groups (BMI <25, 25-29.9 and >30: 0.81, 0.87 and 0.96 respectively, P = 0.360. Overall complication rate was 43.1% (BMI <25); 43.0% (BMI 25-29.9): and 70.0% (BMI >30) (P = 0.018). The results were similar for both the immediate and the delayed reconstructions. Length of hospital stay was similar in the different BMI groups. Delayed donor-site healing was higher in patients with BMI <25; 17.2%, compared to patients with BMI 25-29.9; 11.8%, but lower than for patients with BMI >30; 29.7% (P = 0.033)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Body Mass Index",
"Epigastric Arteries",
"Female",
"Follow-Up Studies",
"Humans",
"Length of Stay",
"Mammaplasty",
"Mastectomy",
"Middle Aged",
"Perforator Flap",
"Postoperative Complications",
"Retrospective Studies",
"Thinness",
"Treatment Outcome"
]
} | The DIEP flap provides adequate volume for unilateral breast reconstruction in slim patients, both in immediate and delayed settings. However, in delayed reconstructions slim patients need to be informed about the increased risk of donor-site complications. © 2015 Wiley Periodicals, Inc. Microsurgery 36:552-558, 2016. | yes | [
{
"from": "human",
"value": "Question: Is breast reconstruction with the deep inferior epigastric perforator flap a reliable alternative in slim patients?\nContext: {'contexts': ['For slim patients eligible to breast reconstruction, clinical concerns exist on availability of adequate amount of donor tissue to restore breast volume and challenges in donor-site closure, when using the deep inferior epigastric perforator (DIEP) flap. The purpose of the current study is to analyze whether the DIEP flap can provide adequate volume for breast reconstruction in slim patients, without increased complication rates or prolonged hospital stay.', 'All patients receiving a unilateral DIEP breast reconstruction at the center 2007-2010 were included (n\\u2009=\\u2009171). The patients were analyzed in subgroups of delayed and immediate reconstruction and of BMI. Complications were analyzed according to Clavien-Dindo. Flap weight was compared to mastectomy specimen weight among immediate reconstructions (n\\u2009=\\u200991).', 'There was no difference in specimen to flap weight ratio between the different BMI-groups (BMI <25, 25-29.9 and >30: 0.81, 0.87 and 0.96 respectively, P\\u2009=\\u20090.360. Overall complication rate was 43.1% (BMI <25); 43.0% (BMI 25-29.9): and 70.0% (BMI >30) (P\\u2009=\\u20090.018). The results were similar for both the immediate and the delayed reconstructions. Length of hospital stay was similar in the different BMI groups. Delayed donor-site healing was higher in patients with BMI <25; 17.2%, compared to patients with BMI 25-29.9; 11.8%, but lower than for patients with BMI >30; 29.7% (P\\u2009=\\u20090.033).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Body Mass Index', 'Epigastric Arteries', 'Female', 'Follow-Up Studies', 'Humans', 'Length of Stay', 'Mammaplasty', 'Mastectomy', 'Middle Aged', 'Perforator Flap', 'Postoperative Complications', 'Retrospective Studies', 'Thinness', 'Treatment Outcome']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,542,822 | Does distance to Thrombus in Acute Middle Cerebral Artery Occlusion predict Target Mismatch and Ischemic Penumbra? | {
"contexts": [
"In patients with occlusion of the middle cerebral artery (MCA) treated by intravenous thrombolysis (IVT), the distance to thrombus (DT) has been proposed as a predictor of outcome. The purpose of the present study was to investigate how DT relates to dynamic susceptibility contrast perfusion metrics.",
"Retrospective analysis was undertaken of patients who were diagnosed with acute MCA occlusion by magnetic resonance imaging and treated with IVT. Volumes of time-to-maximum (Tmax) perfusion deficits and diffusion-weighted imaging (DWI) lesions, diffusion-perfusion mismatch volumes, and the presence of target mismatch were determined. Correlations between the above stoke measures and DT were then calculated.",
"Fifty-five patients were included. DT showed significant inverse correlations with Tmax greater than 4, 6, 8, and 10 seconds, respectively, and mismatch volumes. Using the DT group median (14 mm) as a separator, significant intergroup differences were observed for Tmax greater than 4, 6, and 8 seconds, respectively, and for mismatch volumes. Grouping DT into quartiles showed significant intergroup differences regarding mismatch volumes and Tmax values greater than 4 and 6 seconds. Binary logistic regression identified DT (odds ratio [OR] = .89; 95% confidence interval [CI], .81-.99) and DWI lesion volumes (OR = .92; 95% CI, .86-.97) as independent predictors of target mismatch. A low DT predicted target mismatch with an area under the curve of .69."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Brain Ischemia",
"Female",
"Fibrinolytic Agents",
"Humans",
"Image Processing, Computer-Assisted",
"Infarction, Middle Cerebral Artery",
"Intracranial Thrombosis",
"Magnetic Resonance Imaging",
"Male",
"Middle Aged",
"Retrospective Studies",
"Thrombolytic Therapy",
"Tissue Plasminogen Activator"
]
} | DT correlates inversely with Tmax perfusion deficits and mismatch volumes and acts as an independent predictor of target mismatch. | yes | [
{
"from": "human",
"value": "Question: Does distance to Thrombus in Acute Middle Cerebral Artery Occlusion predict Target Mismatch and Ischemic Penumbra?\nContext: {'contexts': ['In patients with occlusion of the middle cerebral artery (MCA) treated by intravenous thrombolysis (IVT), the distance to thrombus (DT) has been proposed as a predictor of outcome. The purpose of the present study was to investigate how DT relates to dynamic susceptibility contrast perfusion metrics.', 'Retrospective analysis was undertaken of patients who were diagnosed with acute MCA occlusion by magnetic resonance imaging and treated with IVT. Volumes of time-to-maximum (Tmax) perfusion deficits and diffusion-weighted imaging (DWI) lesions, diffusion-perfusion mismatch volumes, and the presence of target mismatch were determined. Correlations between the above stoke measures and DT were then calculated.', 'Fifty-five patients were included. DT showed significant inverse correlations with Tmax greater than 4, 6, 8, and 10 seconds, respectively, and mismatch volumes. Using the DT group median (14 mm) as a separator, significant intergroup differences were observed for Tmax greater than 4, 6, and 8 seconds, respectively, and for mismatch volumes. Grouping DT into quartiles showed significant intergroup differences regarding mismatch volumes and Tmax values greater than 4 and 6 seconds. Binary logistic regression identified DT (odds ratio [OR]\\u2009=\\u2009.89; 95% confidence interval [CI], .81-.99) and DWI lesion volumes (OR = .92; 95% CI, .86-.97) as independent predictors of target mismatch. A low DT predicted target mismatch with an area under the curve of .69.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Brain Ischemia', 'Female', 'Fibrinolytic Agents', 'Humans', 'Image Processing, Computer-Assisted', 'Infarction, Middle Cerebral Artery', 'Intracranial Thrombosis', 'Magnetic Resonance Imaging', 'Male', 'Middle Aged', 'Retrospective Studies', 'Thrombolytic Therapy', 'Tissue Plasminogen Activator']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,539,938 | Do primary and Revision Posterior Lumbar Fusion Have Similar Short-Term Complication Rates? | {
"contexts": [
"Retrospective cohort study.",
"To compare short-term morbidity for primary and revision posterior lumbar fusions.",
"Revision lumbar fusions are unfortunately relatively common. Previous studies have described an increased risk of postoperative complications after revision lumbar fusion; however, these studies have been limited by small sample sizes, poor data quality, and/or narrow outcome measures. There is a need to validate these findings using a high-quality, national cohort of patients to have an accurate assessment of the relative risk of revision posterior lumbar fusions compared with primary lumbar fusion.",
"The prospectively-collected American College of Surgeons National Surgical Quality Improvement Program database was used to identify patients that underwent undergoing primary and revision posterior lumbar fusion from 2005 to 2013. The occurrence of individual and aggregated postoperative complications within 30 days, along with rates of blood transfusion and readmission, were compared between primary and revision procedures using bivariate and multivariate Poisson regression with robust error variance to control for patient and operative characteristics. Operative time and postoperative length of stay were compared between groups using bivariate and multivariate linear regression.",
"Of the 14,873 posterior lumbar fusion procedures that met inclusion criteria, 1287 (8.7%) were revision cases. There were no differences in the rates of 30-day postoperative complications or readmission between primary and revision posterior lumbar fusion using multivariate analysis to control for patient and operative characteristics. Similarly, no significant differences were found for operative time or postoperative length of stay. There was an increased rate of blood transfusion for revision surgery compared with primary surgery (relative risk 1.4, P < 0.001)."
],
"labels": [
"METHODS",
"OBJECTIVE",
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Adult",
"Aged",
"Blood Loss, Surgical",
"Blood Transfusion",
"Chi-Square Distribution",
"Databases, Factual",
"Female",
"Humans",
"Length of Stay",
"Linear Models",
"Logistic Models",
"Lumbar Vertebrae",
"Male",
"Middle Aged",
"Multivariate Analysis",
"Operative Time",
"Patient Readmission",
"Postoperative Complications",
"Reoperation",
"Retrospective Studies",
"Risk Factors",
"Spinal Fusion",
"Time Factors",
"Treatment Outcome",
"United States",
"Young Adult"
]
} | This study suggests that revision posterior lumbar fusion does not carry significantly increased risk of complications or readmission compared with a primary posterior lumbar fusion. Patients undergoing revision surgery were more likely to receive a blood transfusion. This information suggests that general health risk stratification for revision procedures can be similar to that considered for primary cases. | yes | [
{
"from": "human",
"value": "Question: Do primary and Revision Posterior Lumbar Fusion Have Similar Short-Term Complication Rates?\nContext: {'contexts': ['Retrospective cohort study.', 'To compare short-term morbidity for primary and revision posterior lumbar fusions.', 'Revision lumbar fusions are unfortunately relatively common. Previous studies have described an increased risk of postoperative complications after revision lumbar fusion; however, these studies have been limited by small sample sizes, poor data quality, and/or narrow outcome measures. There is a need to validate these findings using a high-quality, national cohort of patients to have an accurate assessment of the relative risk of revision posterior lumbar fusions compared with primary lumbar fusion.', 'The prospectively-collected American College of Surgeons National Surgical Quality Improvement Program database was used to identify patients that underwent undergoing primary and revision posterior lumbar fusion from 2005 to 2013. The occurrence of individual and aggregated postoperative complications within 30 days, along with rates of blood transfusion and readmission, were compared between primary and revision procedures using bivariate and multivariate Poisson regression with robust error variance to control for patient and operative characteristics. Operative time and postoperative length of stay were compared between groups using bivariate and multivariate linear regression.', 'Of the 14,873 posterior lumbar fusion procedures that met inclusion criteria, 1287 (8.7%) were revision cases. There were no differences in the rates of 30-day postoperative complications or readmission between primary and revision posterior lumbar fusion using multivariate analysis to control for patient and operative characteristics. Similarly, no significant differences were found for operative time or postoperative length of stay. There was an increased rate of blood transfusion for revision surgery compared with primary surgery (relative risk 1.4, P\\u200a<\\u200a0.001).'], 'labels': ['METHODS', 'OBJECTIVE', 'BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Aged', 'Blood Loss, Surgical', 'Blood Transfusion', 'Chi-Square Distribution', 'Databases, Factual', 'Female', 'Humans', 'Length of Stay', 'Linear Models', 'Logistic Models', 'Lumbar Vertebrae', 'Male', 'Middle Aged', 'Multivariate Analysis', 'Operative Time', 'Patient Readmission', 'Postoperative Complications', 'Reoperation', 'Retrospective Studies', 'Risk Factors', 'Spinal Fusion', 'Time Factors', 'Treatment Outcome', 'United States', 'Young Adult']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,552,750 | Do chemotherapeutic agents attenuate CXCL12-mediated migration of colon cancer cells by selecting for CXCR4-negative cells and increasing peptidase CD26? | {
"contexts": [
"Recurrence of colorectal cancer (CRC) may arise due to the persistence of drug-resistant and cancer-initiating cells that survive exposure to chemotherapy. Proteins responsible for this recurrence include the chemokine receptor CXCR4, which is known to enable CRC metastasis, as well as the cancer-initiating cell marker and peptidase CD26, which terminates activity of its chemokine CXCL12.",
"We evaluated the expression and function of CXCR4 and CD26 in colon cancer cell lines and xenografts following treatment with common chemotherapies using radioligand binding, flow cytometry, immunofluorescence, and enzymatic assays.",
"5-Fluorouracil, oxaliplatin and SN-38 (the active metabolite of irinotecan), as well as cisplatin, methotrexate and vinblastine, each caused decreases in cell-surface CXCR4 and concomitant increases in CD26 on HT-29, T84, HRT-18, SW480 and SW620 CRC cell lines. Flow cytometry indicated that the decline in CXCR4 was associated with a significant loss of CXCR4+/CD26- cells. Elevations in CD26 were paralleled by increases in both the intrinsic dipeptidyl peptidase activity of CD26 as well as its capacity to bind extracellular adenosine deaminase. Orthotopic HT-29 xenografts treated with standard CRC chemotherapeutics 5-fluorouracil, irinotecan, or oxaliplatin showed dramatic increases in CD26 compared to untreated tumors. Consistent with the loss of CXCR4 and gain in CD26, migratory responses to exogenous CXCL12 were eliminated in cells pretreated with cytotoxic agents, although cells retained basal motility. Analysis of cancer-initiating cell CD44 and CD133 subsets revealed drug-dependent responses of CD26/CD44/CD133 populations, suggesting that the benefits of combining standard chemotherapies 5-fluoruracil and oxaliplatin may be derived from their complementary elimination of cell populations."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Camptothecin",
"Carcinogenesis",
"Cell Lineage",
"Cell Movement",
"Chemokine CXCL12",
"Colonic Neoplasms",
"Dipeptidyl Peptidase 4",
"Fluorouracil",
"Gene Expression Regulation, Neoplastic",
"HT29 Cells",
"Humans",
"Hyaluronan Receptors",
"Irinotecan",
"Mice",
"Neoplasm Metastasis",
"Receptors, CXCR4",
"Xenograft Model Antitumor Assays"
]
} | Our results indicate that conventional anticancer agents may act to inhibit chemokine-mediated migration through eradication of CXCR4+ cells and attenuation of chemokine gradients through elevation of CD26 activity. | yes | [
{
"from": "human",
"value": "Question: Do chemotherapeutic agents attenuate CXCL12-mediated migration of colon cancer cells by selecting for CXCR4-negative cells and increasing peptidase CD26?\nContext: {'contexts': ['Recurrence of colorectal cancer (CRC) may arise due to the persistence of drug-resistant and cancer-initiating cells that survive exposure to chemotherapy. Proteins responsible for this recurrence include the chemokine receptor CXCR4, which is known to enable CRC metastasis, as well as the cancer-initiating cell marker and peptidase CD26, which terminates activity of its chemokine CXCL12.', 'We evaluated the expression and function of CXCR4 and CD26 in colon cancer cell lines and xenografts following treatment with common chemotherapies using radioligand binding, flow cytometry, immunofluorescence, and enzymatic assays.', '5-Fluorouracil, oxaliplatin and SN-38 (the active metabolite of irinotecan), as well as cisplatin, methotrexate and vinblastine, each caused decreases in cell-surface CXCR4 and concomitant increases in CD26 on HT-29, T84, HRT-18, SW480 and SW620 CRC cell lines. Flow cytometry indicated that the decline in CXCR4 was associated with a significant loss of CXCR4+/CD26- cells. Elevations in CD26 were paralleled by increases in both the intrinsic dipeptidyl peptidase activity of CD26 as well as its capacity to bind extracellular adenosine deaminase. Orthotopic HT-29 xenografts treated with standard CRC chemotherapeutics 5-fluorouracil, irinotecan, or oxaliplatin showed dramatic increases in CD26 compared to untreated tumors. Consistent with the loss of CXCR4 and gain in CD26, migratory responses to exogenous CXCL12 were eliminated in cells pretreated with cytotoxic agents, although cells retained basal motility. Analysis of cancer-initiating cell CD44 and CD133 subsets revealed drug-dependent responses of CD26/CD44/CD133 populations, suggesting that the benefits of combining standard chemotherapies 5-fluoruracil and oxaliplatin may be derived from their complementary elimination of cell populations.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Camptothecin', 'Carcinogenesis', 'Cell Lineage', 'Cell Movement', 'Chemokine CXCL12', 'Colonic Neoplasms', 'Dipeptidyl Peptidase 4', 'Fluorouracil', 'Gene Expression Regulation, Neoplastic', 'HT29 Cells', 'Humans', 'Hyaluronan Receptors', 'Irinotecan', 'Mice', 'Neoplasm Metastasis', 'Receptors, CXCR4', 'Xenograft Model Antitumor Assays']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,528,588 | Do ficus religiosa L. bark extracts inhibit human rhinovirus and respiratory syncytial virus infection in vitro? | {
"contexts": [
"Ficus religiosa L. is one of the most relevant members of the family of Moraceae. It is the most sacred tree of South Asia, and it is used in traditional Ayurvedic and Unani medicine to cure respiratory disorders like cough, wheezing and asthma. Some studies were performed to investigate the anti-asthmatic potential of F. religiosa bark, leaves and fruit extracts but none of them tested their antiviral activity against viruses responsible for the exacerbation of wheezing and asthma.",
"The present study was undertaken to investigate the antiviral activity of F. religiosa L. extracts against respiratory viruses such as human respiratory syncytial virus (RSV) and human rhinovirus (HRV).",
"The antiviral activity of F. religiosa L. was tested in vitro by plaque reduction and virus yield assays and the major mechanism of action was investigated by virus inactivation and time-of-addition assays.",
"F. religiosa L. methanol bark extract was the most active against HRV with an EC50 of 5.52 µg/mL. This extract likely inhibited late steps of replicative cycle. Water bark extract was the most active against RSV with an EC50 between 2.23 and 4.37 µg/mL. Partial virus inactivation and interference with virus attachment were both found to contribute to the anti-RSV activity. Replication of both viruses was inhibited in viral yield reduction assays."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Antiviral Agents",
"Cell Line, Tumor",
"Ficus",
"Humans",
"Picornaviridae Infections",
"Plant Bark",
"Plant Extracts",
"Plant Leaves",
"Respiratory Syncytial Virus Infections",
"Respiratory Syncytial Virus, Human",
"Rhinovirus",
"Virus Attachment",
"Virus Inactivation",
"Virus Internalization"
]
} | The results of the present study demonstrate that F. religiosa L. is endowed with antiviral activity against RSV and HRV in vitro. Further work remains to be done to identify the active components and to assess the therapeutic potential in vivo. | yes | [
{
"from": "human",
"value": "Question: Do ficus religiosa L. bark extracts inhibit human rhinovirus and respiratory syncytial virus infection in vitro?\nContext: {'contexts': ['Ficus religiosa L. is one of the most relevant members of the family of Moraceae. It is the most sacred tree of South Asia, and it is used in traditional Ayurvedic and Unani medicine to cure respiratory disorders like cough, wheezing and asthma. Some studies were performed to investigate the anti-asthmatic potential of F. religiosa bark, leaves and fruit extracts but none of them tested their antiviral activity against viruses responsible for the exacerbation of wheezing and asthma.', 'The present study was undertaken to investigate the antiviral activity of F. religiosa L. extracts against respiratory viruses such as human respiratory syncytial virus (RSV) and human rhinovirus (HRV).', 'The antiviral activity of F. religiosa L. was tested in vitro by plaque reduction and virus yield assays and the major mechanism of action was investigated by virus inactivation and time-of-addition assays.', 'F. religiosa L. methanol bark extract was the most active against HRV with an EC50 of 5.52 µg/mL. This extract likely inhibited late steps of replicative cycle. Water bark extract was the most active against RSV with an EC50 between 2.23 and 4.37 µg/mL. Partial virus inactivation and interference with virus attachment were both found to contribute to the anti-RSV activity. Replication of both viruses was inhibited in viral yield reduction assays.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Antiviral Agents', 'Cell Line, Tumor', 'Ficus', 'Humans', 'Picornaviridae Infections', 'Plant Bark', 'Plant Extracts', 'Plant Leaves', 'Respiratory Syncytial Virus Infections', 'Respiratory Syncytial Virus, Human', 'Rhinovirus', 'Virus Attachment', 'Virus Inactivation', 'Virus Internalization']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,539,920 | Does recent developments in electronic alert for acute kidney injury? | {
"contexts": [
"Efforts to improve outcomes from acute kidney injury (AKI) have focussed on timely diagnosis and effective delivery of basic patient care. Electronic alerts (e-alerts) for AKI have attracted interest as a tool to facilitate this. Initial feasibility has already been demonstrated; this review will discuss recent advances in alert methodology, implementation beyond single centres and reported effect on outcomes.",
"On-going descriptions of e-alerts highlight increasing variation in both detection algorithms and alert processes. In England, this is being addressed by national rollout of a standardized detection algorithm; recent data have shown this to have good diagnostic performance. In critical care, fully automated detection systems incorporating both serum creatinine and urine output criteria have been developed. A recent randomized trial of e-alerts has also been reported, in which isolated use of a text message e-alert did not affect either clinician behaviour or patient outcome."
],
"labels": [
"OBJECTIVE",
"RESULTS"
],
"meshes": []
} | As e-alerts gain popularity, consideration must be given to both the method of AKI detection and the method by which results are communicated to end-users; these aspects influence the degree of these systems' effectiveness. This approach should be coupled to further work to study the effect on patient outcomes of those interventions that have been demonstrated to influence clinician behaviour. | yes | [
{
"from": "human",
"value": "Question: Does recent developments in electronic alert for acute kidney injury?\nContext: {'contexts': ['Efforts to improve outcomes from acute kidney injury (AKI) have focussed on timely diagnosis and effective delivery of basic patient care. Electronic alerts (e-alerts) for AKI have attracted interest as a tool to facilitate this. Initial feasibility has already been demonstrated; this review will discuss recent advances in alert methodology, implementation beyond single centres and reported effect on outcomes.', 'On-going descriptions of e-alerts highlight increasing variation in both detection algorithms and alert processes. In England, this is being addressed by national rollout of a standardized detection algorithm; recent data have shown this to have good diagnostic performance. In critical care, fully automated detection systems incorporating both serum creatinine and urine output criteria have been developed. A recent randomized trial of e-alerts has also been reported, in which isolated use of a text message e-alert did not affect either clinician behaviour or patient outcome.'], 'labels': ['OBJECTIVE', 'RESULTS'], 'meshes': []}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,537,370 | Do high Glucose Concentrations Suppress the Proliferation of Human Periodontal Ligament Stem Cells and Their Differentiation Into Osteoblasts? | {
"contexts": [
"Diabetes mellitus (DM) is a major risk factor for periodontal disease and affects various cellular functions. Periodontal ligament stem cells (PDLSCs) play an important role in periodontal tissue regeneration; however, the effect of hyperglycemia on PDLSCs is unclear. The aim of this study is to investigate whether hyperglycemia affects periodontal tissue regeneration, using human PDLSCs and high-glucose medium as a model of DM.",
"PDLSCs were obtained from healthy adult human mandibular third molars. Cell proliferation, osteoblastic differentiation, and proinflammatory cytokine expression were investigated by culturing PDLSCs in media supplemented with four different glucose concentrations representative of control patients (5.5 mM), patients with postprandial or controlled DM (8.0 mM), and patients with uncontrolled DM (12.0 and 24.0 mM). The molecular effects of hyperglycemia on PDLSC physiology were examined with a focus on the nuclear factor (NF)-(κB signaling pathway. The involvement of NF-κB was investigated with a specific NF-κB inhibitor in PDLSCs under hyperglycemic conditions.",
"High glucose levels inhibited PDLSC proliferation and differentiation into osteoblasts but induced NF-κB activation and subsequent interleukin (IL)-6 and IL-8 expression. Treatment with an NF-κB inhibitor rescued the defects in cell proliferation and osteoblastic differentiation and inhibited the IL-6 expression caused by the high-glucose environment."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Cell Differentiation",
"Cell Proliferation",
"Glucose",
"Humans",
"Osteoblasts",
"Periodontal Ligament",
"Stem Cells"
]
} | The results of this study demonstrate that hyperglycemia inhibits human PDLSC proliferation and osteoblastic differentiation. | yes | [
{
"from": "human",
"value": "Question: Do high Glucose Concentrations Suppress the Proliferation of Human Periodontal Ligament Stem Cells and Their Differentiation Into Osteoblasts?\nContext: {'contexts': ['Diabetes mellitus (DM) is a major risk factor for periodontal disease and affects various cellular functions. Periodontal ligament stem cells (PDLSCs) play an important role in periodontal tissue regeneration; however, the effect of hyperglycemia on PDLSCs is unclear. The aim of this study is to investigate whether hyperglycemia affects periodontal tissue regeneration, using human PDLSCs and high-glucose medium as a model of DM.', 'PDLSCs were obtained from healthy adult human mandibular third molars. Cell proliferation, osteoblastic differentiation, and proinflammatory cytokine expression were investigated by culturing PDLSCs in media supplemented with four different glucose concentrations representative of control patients (5.5 mM), patients with postprandial or controlled DM (8.0 mM), and patients with uncontrolled DM (12.0 and 24.0 mM). The molecular effects of hyperglycemia on PDLSC physiology were examined with a focus on the nuclear factor (NF)-(κB signaling pathway. The involvement of NF-κB was investigated with a specific NF-κB inhibitor in PDLSCs under hyperglycemic conditions.', 'High glucose levels inhibited PDLSC proliferation and differentiation into osteoblasts but induced NF-κB activation and subsequent interleukin (IL)-6 and IL-8 expression. Treatment with an NF-κB inhibitor rescued the defects in cell proliferation and osteoblastic differentiation and inhibited the IL-6 expression caused by the high-glucose environment.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Cell Differentiation', 'Cell Proliferation', 'Glucose', 'Humans', 'Osteoblasts', 'Periodontal Ligament', 'Stem Cells']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,547,529 | Does ethanolic Ginkgo biloba leaf extract prevent renal fibrosis through Akt/mTOR signaling in diabetic nephropathy? | {
"contexts": [
"Recently, extract of Ginkgo biloba leaves (GbE) have become widely known phytomedicines and have shown various pharmacological activities, including improvement of blood circulation, protection of oxidative cell damage, prevention of Alzheimer's disease, treatment of cardiovascular disease and diabetes complications. This study was designed to investigate the effects of an ethanolic GbE on renal fibrosis in diabetic nephropathy (DN) and to clarify the possible mechanism by which GbE prevents renal fibrosis.",
"We investigated the protective effects of GbE on renal fibrosis in STZ-induced diabetic rats. Rats were randomized into six groups termed normal control, diabetes mellitus, low dose of GbE (50 mg/kg/d), intermediate dose of GbE (100 mg/kg/d), high dose of GbE (200 mg/kg/d) and rapamycin (1 mg/kg/d).",
"After 12 weeks, the rats were sacrificed and then fasting blood glucose (FBG), creatinine (Cr), blood urea nitrogen (BUN), urine protein, relative kidney weight, glycogen and collagen accumulation, and collagen IV and laminin expression were measured by different methods. The amounts of E-cadherin, α-SMA and snail, as well as the phosphorylation of Akt, mTOR and p70S6K in the renal cortex of rats, were examined by western blotting.",
"Compared with diabetic rats, the levels of Cr, BUN, urine protein, relative kidney weight, accumulation of glycogen and collagen, and expression of collagen IV and laminin in the renal cortex were all decreased in GbE treated rats. In addition, GbE reduced the expression of E-cadherin, α-SMA, snail and the phosphorylation of Akt, mTOR and p70S6K in diabetic renal cortex."
],
"labels": [
"BACKGROUND",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Diabetes Mellitus, Experimental",
"Diabetic Nephropathies",
"Fibrosis",
"Ginkgo biloba",
"Kidney",
"Kidney Diseases",
"Male",
"Phytotherapy",
"Plant Extracts",
"Proto-Oncogene Proteins c-akt",
"Rats",
"Rats, Wistar",
"Signal Transduction",
"TOR Serine-Threonine Kinases"
]
} | GbE can prevent renal fibrosis in rats with diabetic nephropathy, which is most likely to be associated with its abilities to inhibit the Akt/mTOR signaling pathway. | yes | [
{
"from": "human",
"value": "Question: Does ethanolic Ginkgo biloba leaf extract prevent renal fibrosis through Akt/mTOR signaling in diabetic nephropathy?\nContext: {'contexts': [\"Recently, extract of Ginkgo biloba leaves (GbE) have become widely known phytomedicines and have shown various pharmacological activities, including improvement of blood circulation, protection of oxidative cell damage, prevention of Alzheimer's disease, treatment of cardiovascular disease and diabetes complications. This study was designed to investigate the effects of an ethanolic GbE on renal fibrosis in diabetic nephropathy (DN) and to clarify the possible mechanism by which GbE prevents renal fibrosis.\", 'We investigated the protective effects of GbE on renal fibrosis in STZ-induced diabetic rats. Rats were randomized into six groups termed normal control, diabetes mellitus, low dose of GbE (50\\xa0mg/kg/d), intermediate dose of GbE (100\\xa0mg/kg/d), high dose of GbE (200\\xa0mg/kg/d) and rapamycin (1\\xa0mg/kg/d).', 'After 12 weeks, the rats were sacrificed and then fasting blood glucose (FBG), creatinine (Cr), blood urea nitrogen (BUN), urine protein, relative kidney weight, glycogen and collagen accumulation, and collagen IV and laminin expression were measured by different methods. The amounts of E-cadherin, α-SMA and snail, as well as the phosphorylation of Akt, mTOR and p70S6K in the renal cortex of rats, were examined by western blotting.', 'Compared with diabetic rats, the levels of Cr, BUN, urine protein, relative kidney weight, accumulation of glycogen and collagen, and expression of collagen IV and laminin in the renal cortex were all decreased in GbE treated rats. In addition, GbE reduced the expression of E-cadherin, α-SMA, snail and the phosphorylation of Akt, mTOR and p70S6K in diabetic renal cortex.'], 'labels': ['BACKGROUND', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Diabetes Mellitus, Experimental', 'Diabetic Nephropathies', 'Fibrosis', 'Ginkgo biloba', 'Kidney', 'Kidney Diseases', 'Male', 'Phytotherapy', 'Plant Extracts', 'Proto-Oncogene Proteins c-akt', 'Rats', 'Rats, Wistar', 'Signal Transduction', 'TOR Serine-Threonine Kinases']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,526,028 | Does p15 ( INK4b ) regulate cell cycle signaling in hippocampal astrocytes of aged rats? | {
"contexts": [
"Cyclin-dependent kinase inhibitor p15(INK4b) is thought to be an important player in regulating astrocytic cell cycle. However, little is known with regard to the expression of p15(INK4b) and its function in hippocampal astrocytes. This study evaluated the expression of p15(INK4b) and its function during different development stages in hippocampal astrocytes.",
"In this study, we cultured hippocampal astrocytes from neonatal adult and aged rats. The expression of p15(INK4b) in neonatal, adult and aged astrocytes was examined. Short interfering RNA (siRNA) was then used to study the functional effects of p15(INK4b) down-regulation during cell cycle regulation.",
"We found the expression of p15(INK4b) in hippocampal astrocytes was detectable on postnatal day 7, was expressed at moderate levels in adult mice (9 months old) astrocytes and peaked in aged rat (24 months old) astrocytes. Incubation with siRNA significantly suppressed p15(INK4b) expression at the mRNA and protein levels in astrocytes. Down-regulation of p15(INK4b) increased [(3)H]-thymidine incorporation into DNA and allowed cells to pass the G0/G1-S checkpoint in aged but not in neonatal or adult astrocytes."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Astrocytes",
"Cell Cycle",
"Cells, Cultured",
"Cellular Senescence",
"Cyclin-Dependent Kinase Inhibitor p15",
"Down-Regulation",
"Hippocampus",
"Mice",
"RNA, Small Interfering",
"Rats",
"Signal Transduction"
]
} | These observations suggest p15(INK4b) is expressed at a steady level in neonatal and adult rat hippocampal astrocytes with no effect on cell cycle regulation. Importantly, aged astrocyte cell cycle regulation was significantly affected by high expression levels of p15(INK4b) suggesting a role for p15(INK4b) in cell cycle regulation when it is expressed at high but not moderate or low levels in hippocampal astrocytes. | yes | [
{
"from": "human",
"value": "Question: Does p15 ( INK4b ) regulate cell cycle signaling in hippocampal astrocytes of aged rats?\nContext: {'contexts': ['Cyclin-dependent kinase inhibitor p15(INK4b) is thought to be an important player in regulating astrocytic cell cycle. However, little is known with regard to the expression of p15(INK4b) and its function in hippocampal astrocytes. This study evaluated the expression of p15(INK4b) and its function during different development stages in hippocampal astrocytes.', 'In this study, we cultured hippocampal astrocytes from neonatal adult and aged rats. The expression of p15(INK4b) in neonatal, adult and aged astrocytes was examined. Short interfering RNA (siRNA) was then used to study the functional effects of p15(INK4b) down-regulation during cell cycle regulation.', 'We found the expression of p15(INK4b) in hippocampal astrocytes was detectable on postnatal day 7, was expressed at moderate levels in adult mice (9\\xa0months old) astrocytes and peaked in aged rat (24\\xa0months old) astrocytes. Incubation with siRNA significantly suppressed p15(INK4b) expression at the mRNA and protein levels in astrocytes. Down-regulation of p15(INK4b) increased [(3)H]-thymidine incorporation into DNA and allowed cells to pass the G0/G1-S checkpoint in aged but not in neonatal or adult astrocytes.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Astrocytes', 'Cell Cycle', 'Cells, Cultured', 'Cellular Senescence', 'Cyclin-Dependent Kinase Inhibitor p15', 'Down-Regulation', 'Hippocampus', 'Mice', 'RNA, Small Interfering', 'Rats', 'Signal Transduction']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,542,369 | Are ovarian stem cells always accompanied by very small embryonic-like stem cells in adult mammalian ovary? | {
"contexts": [
"Existing dogma that a female is born with fixed number of eggs was challenged by the detection of stem cells in adult mammalian ovary. Data has accumulated in support of ovarian stem cells (OSCs) proliferation, maintenance in culture, formation of germ cell nests and differentiation into oocytes and primordial follicle assembly using different strategies.",
"Flow cytometry analysis identified >8 μm OSCs which are DDX1 positive and are considered equivalent to spermatogonial stem cells (SSCs) in testis. Analysis of both ovarian and testicular smears obtained after enzymatic digestion has led to the identification of an additional stem cell population termed very small embryonic-like stem cells (VSELs). VSELs and OSCs/SSCs differ from each other in their size and OCT-4 expression. VSELs express pluripotent markers including nuclear OCT-4 whereas OSCs/SSCs express cytoplasmic OCT-4 suggesting a differentiated state. VSELs can be studied by flow cytometry as small sized cells which are LIN-/CD45-/Sca-1+. We have reported 0.02 ± 0.008, 0.03 ± 0.017 and 0.08 ± 0.03 % of total cells as VSELs in normal, chemoablated and after FSH treatment to chemoablated mouse ovary."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Animals",
"Embryonic Stem Cells",
"Female",
"Germ Cells",
"Humans",
"Infertility, Female",
"Mice",
"Ovary",
"Sheep"
]
} | VSELs have remained poorly studied till now because of their very small size and rare occurrence. Spinning cells obtained after enzymatic digestion of ovarian tissue at a speed of 1000G (rather than 1200 rpm) throughout processing allows reliable detection of the VSELs by flow cytometry. VSELs exist in aged, chemoablated and non-functional ovary and providing a healthy niche to support their function offers an interesting strategy to manage infertility. | yes | [
{
"from": "human",
"value": "Question: Are ovarian stem cells always accompanied by very small embryonic-like stem cells in adult mammalian ovary?\nContext: {'contexts': ['Existing dogma that a female is born with fixed number of eggs was challenged by the detection of stem cells in adult mammalian ovary. Data has accumulated in support of ovarian stem cells (OSCs) proliferation, maintenance in culture, formation of germ cell nests and differentiation into oocytes and primordial follicle assembly using different strategies.', 'Flow cytometry analysis identified >8\\xa0μm OSCs which are DDX1 positive and are considered equivalent to spermatogonial stem cells (SSCs) in testis. Analysis of both ovarian and testicular smears obtained after enzymatic digestion has led to the identification of an additional stem cell population termed very small embryonic-like stem cells (VSELs). VSELs and OSCs/SSCs differ from each other in their size and OCT-4 expression. VSELs express pluripotent markers including nuclear OCT-4 whereas OSCs/SSCs express cytoplasmic OCT-4 suggesting a differentiated state. VSELs can be studied by flow cytometry as small sized cells which are LIN-/CD45-/Sca-1+. We have reported 0.02\\u2009±\\u20090.008, 0.03\\u2009±\\u20090.017 and 0.08\\u2009±\\u20090.03\\xa0% of total cells as VSELs in normal, chemoablated and after FSH treatment to chemoablated mouse ovary.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Animals', 'Embryonic Stem Cells', 'Female', 'Germ Cells', 'Humans', 'Infertility, Female', 'Mice', 'Ovary', 'Sheep']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,529,632 | Does asfotase Alfa Treatment improve Survival for Perinatal and Infantile Hypophosphatasia? | {
"contexts": [
"Hypophosphatasia (HPP) is an inborn error of metabolism that, in its most severe perinatal and infantile forms, results in 50-100% mortality, typically from respiratory complications.",
"Our objective was to better understand the effect of treatment with asfotase alfa, a first-in-class enzyme replacement therapy, on mortality in neonates and infants with severe HPP.",
"Data from patients with the perinatal and infantile forms of HPP in two ongoing, multicenter, multinational, open-label, phase 2 interventional studies of asfotase alfa treatment were compared with data from similar patients from a retrospective natural history study.",
"Thirty-seven treated patients (median treatment duration, 2.7 years) and 48 historical controls of similar chronological age and HPP characteristics.",
"Treated patients received asfotase alfa as sc injections either 1 mg/kg six times per week or 2 mg/kg thrice weekly.",
"Survival, skeletal health quantified radiographically on treatment, and ventilatory status were the main outcome measures for this study.",
"Asfotase alfa was associated with improved survival in treated patients vs historical controls: 95% vs 42% at age 1 year and 84% vs 27% at age 5 years, respectively (P < .0001, Kaplan-Meier log-rank test). Whereas 5% (1/20) of the historical controls who required ventilatory assistance survived, 76% (16/21) of the ventilated and treated patients survived, among whom 75% (12/16) were weaned from ventilatory support. This better respiratory outcome accompanied radiographic improvements in skeletal mineralization and health."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Age Factors",
"Alkaline Phosphatase",
"Bone Density",
"Child, Preschool",
"Enzyme Replacement Therapy",
"Female",
"Humans",
"Hypophosphatasia",
"Immunoglobulin G",
"Infant",
"Infant, Newborn",
"Injections, Subcutaneous",
"Kaplan-Meier Estimate",
"Male",
"Recombinant Fusion Proteins",
"Respiration, Artificial",
"Respiratory Function Tests",
"Survival Analysis",
"Treatment Outcome"
]
} | Asfotase alfa mineralizes the HPP skeleton, including the ribs, and improves respiratory function and survival in life-threatening perinatal and infantile HPP. | yes | [
{
"from": "human",
"value": "Question: Does asfotase Alfa Treatment improve Survival for Perinatal and Infantile Hypophosphatasia?\nContext: {'contexts': ['Hypophosphatasia (HPP) is an inborn error of metabolism that, in its most severe perinatal and infantile forms, results in 50-100% mortality, typically from respiratory complications.', 'Our objective was to better understand the effect of treatment with asfotase alfa, a first-in-class enzyme replacement therapy, on mortality in neonates and infants with severe HPP.', 'Data from patients with the perinatal and infantile forms of HPP in two ongoing, multicenter, multinational, open-label, phase 2 interventional studies of asfotase alfa treatment were compared with data from similar patients from a retrospective natural history study.', 'Thirty-seven treated patients (median treatment duration, 2.7 years) and 48 historical controls of similar chronological age and HPP characteristics.', 'Treated patients received asfotase alfa as sc injections either 1 mg/kg six times per week or 2 mg/kg thrice weekly.', 'Survival, skeletal health quantified radiographically on treatment, and ventilatory status were the main outcome measures for this study.', 'Asfotase alfa was associated with improved survival in treated patients vs historical controls: 95% vs 42% at age 1 year and 84% vs 27% at age 5 years, respectively (P < .0001, Kaplan-Meier log-rank test). Whereas 5% (1/20) of the historical controls who required ventilatory assistance survived, 76% (16/21) of the ventilated and treated patients survived, among whom 75% (12/16) were weaned from ventilatory support. This better respiratory outcome accompanied radiographic improvements in skeletal mineralization and health.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'METHODS', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Age Factors', 'Alkaline Phosphatase', 'Bone Density', 'Child, Preschool', 'Enzyme Replacement Therapy', 'Female', 'Humans', 'Hypophosphatasia', 'Immunoglobulin G', 'Infant', 'Infant, Newborn', 'Injections, Subcutaneous', 'Kaplan-Meier Estimate', 'Male', 'Recombinant Fusion Proteins', 'Respiration, Artificial', 'Respiratory Function Tests', 'Survival Analysis', 'Treatment Outcome']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,553,542 | Is a gain-of-function mutation in the cardiac pacemaker HCN4 channel increasing cAMP sensitivity associated with familial Inappropriate Sinus Tachycardia? | {
"contexts": [
"Inappropriate Sinus Tachycardia (IST), a syndrome characterized by abnormally fast sinus rates and multisystem symptoms, is still poorly understood. Because of the relevance of HCN4 channels to pacemaker activity, we used a candidate-gene approach and screened IST patients for the presence of disease-causing HCN4 mutations.",
"Forty-eight IST patients, four of whom of known familial history, were enrolled in the study. We initially identified in one of the patients with familial history the R524Q mutation in HCN4. Investigation extended to the family members showed that the mutation co-segregated with IST-related symptoms. The R524Q mutation is located in the C-linker, a region known to couple cAMP binding to channel activation. The functional relevance of the mutation was investigated in heterologous expression systems by patch-clamp experiments. We found that mutant HCN4 channels were more sensitive to cAMP than wild-type channels, in agreement with increased sensitivity to basal and stimulated adrenergic input and with a faster than normal pacemaker rate. The properties of variant channels indicate therefore that R524Q is a gain-of-function mutation. Increased channel contribution to activity was confirmed by evidence that when spontaneously beating rat newborn myocytes were transfected with R524Q mutant HCN4 channels, they exhibited a faster rate than when transfected with wild-type HCN4 channels."
],
"labels": [
"OBJECTIVE",
"RESULTS"
],
"meshes": []
} | This is the first report of a gain-of-function HCN4 mutation associated with IST through increased sensitivity to cAMP-dependent activation. | yes | [
{
"from": "human",
"value": "Question: Is a gain-of-function mutation in the cardiac pacemaker HCN4 channel increasing cAMP sensitivity associated with familial Inappropriate Sinus Tachycardia?\nContext: {'contexts': ['Inappropriate Sinus Tachycardia (IST), a syndrome characterized by abnormally fast sinus rates and multisystem symptoms, is still poorly understood. Because of the relevance of HCN4 channels to pacemaker activity, we used a candidate-gene approach and screened IST patients for the presence of disease-causing HCN4 mutations.', 'Forty-eight IST patients, four of whom of known familial history, were enrolled in the study. We initially identified in one of the patients with familial history the R524Q mutation in HCN4. Investigation extended to the family members showed that the mutation co-segregated with IST-related symptoms. The R524Q mutation is located in the C-linker, a region known to couple cAMP binding to channel activation. The functional relevance of the mutation was investigated in heterologous expression systems by patch-clamp experiments. We found that mutant HCN4 channels were more sensitive to cAMP than wild-type channels, in agreement with increased sensitivity to basal and stimulated adrenergic input and with a faster than normal pacemaker rate. The properties of variant channels indicate therefore that R524Q is a gain-of-function mutation. Increased channel contribution to activity was confirmed by evidence that when spontaneously beating rat newborn myocytes were transfected with R524Q mutant HCN4 channels, they exhibited a faster rate than when transfected with wild-type HCN4 channels.'], 'labels': ['OBJECTIVE', 'RESULTS'], 'meshes': []}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,537,144 | Are standardized clinical pathways for esophagectomy a reality in Brazil , even with a high prevalence of esophageal cancer and achalasia? | {
"contexts": [
"The adoption of standardized protocols and specialized multidisciplinary teams for esophagectomy involve changes in routines with the implantation of expensive clinical practices and deviations from ingrained treatment philosophies.",
"To evaluate the prevalence of standardized protocols and specialized multidisciplinary teams in São Paulo state, Brazil.",
"Institutions that routinely perform esophagectomies in São Paulo were contacted and questioned about the work team involved in the procedure and the presence of standardized routines in the preoperatory care.",
"Fifteen centers answered the questionnaire: 10 (67%) public institutions and five (33%) private. There were seven (47%) medical schools, six (40%) with a residency program and two (13%) nonacademic institutions. The mean number of esophagectomies per year was 23. There was a multidisciplinary pre-operative team in nine (60%). There was a multidisciplinary postoperative team in 11 (73%). Early mobilization protocol was adopted in 12 (80%) institutions, early feeding in 13 (87%), routinely epidural in seven (47%), analgesia protocol in seven (47%), hydric restriction in six (40%), early extubation in six (40%), standardized hospitalization time in four (27%) and standardized intensive care time in two (13%)."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Brazil",
"Critical Pathways",
"Esophageal Achalasia",
"Esophageal Neoplasms",
"Esophagectomy",
"Humans",
"Prevalence",
"Surveys and Questionnaires"
]
} | The prevalence of standardized protocols and specialized teams is very low in Sao Paulo state, Brazil. The presence of specialized surgeons is a reality and standardized protocols related directly to surgeons have higher frequency than those related to other professionals in the multidisciplinary team. | no | [
{
"from": "human",
"value": "Question: Are standardized clinical pathways for esophagectomy a reality in Brazil , even with a high prevalence of esophageal cancer and achalasia?\nContext: {'contexts': ['The adoption of standardized protocols and specialized multidisciplinary teams for esophagectomy involve changes in routines with the implantation of expensive clinical practices and deviations from ingrained treatment philosophies.', 'To evaluate the prevalence of standardized protocols and specialized multidisciplinary teams in São Paulo state, Brazil.', 'Institutions that routinely perform esophagectomies in São Paulo were contacted and questioned about the work team involved in the procedure and the presence of standardized routines in the preoperatory care.', 'Fifteen centers answered the questionnaire: 10 (67%) public institutions and five (33%) private. There were seven (47%) medical schools, six (40%) with a residency program and two (13%) nonacademic institutions. The mean number of esophagectomies per year was 23. There was a multidisciplinary pre-operative team in nine (60%). There was a multidisciplinary postoperative team in 11 (73%). Early mobilization protocol was adopted in 12 (80%) institutions, early feeding in 13 (87%), routinely epidural in seven (47%), analgesia protocol in seven (47%), hydric restriction in six (40%), early extubation in six (40%), standardized hospitalization time in four (27%) and standardized intensive care time in two (13%).'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Brazil', 'Critical Pathways', 'Esophageal Achalasia', 'Esophageal Neoplasms', 'Esophagectomy', 'Humans', 'Prevalence', 'Surveys and Questionnaires']}"
},
{
"from": "gpt",
"value": "Answer: no"
}
]
|
26,548,933 | Do rabbit nucleus pulposus cells facilitate differentiation of adipose-derived stem cells into nucleus pulposus-like cells? | {
"contexts": [
"To investigate the feasibility of inducing adipose-derived stem cells (ADSCs) to nucleus pulposus cells (NPCs).",
"ADSCs were isolated from rabbit while NPCs were isolated from an allogeneic rabbit. NPCs were co-cultured with the 3rd generation ADSCs in co-cultured system. Only NPCs were cultured in single culturing group. Through the collagen type II collagen immunohistochemistry, we observed NPCs and then identify NPC. Proteoglycan messenger RNA (mRNA) and collagen type II mRNA level were measured by real-time polymerase chain reaction.",
"In two group cells, collagen type II collagen were detected by immunohistochemistry. The amount of proteoglycan mRNA and collagen type II mRNA was both significantly higher in co-cultured group than in single cultured group."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adipocytes",
"Animals",
"Cell Differentiation",
"Coculture Techniques",
"Collagen Type II",
"Female",
"RNA, Messenger",
"Rabbits",
"Stem Cells",
"Tissue Engineering"
]
} | In some condition, ADSCs have the potency to differentiate toward nucleus pulposus-like cells. ADSCs are better seed cells for tissue engineering of artificial nucleus pulposus. | yes | [
{
"from": "human",
"value": "Question: Do rabbit nucleus pulposus cells facilitate differentiation of adipose-derived stem cells into nucleus pulposus-like cells?\nContext: {'contexts': ['To investigate the feasibility of inducing adipose-derived stem cells (ADSCs) to nucleus pulposus cells (NPCs).', 'ADSCs were isolated from rabbit while NPCs were isolated from an allogeneic rabbit. NPCs were co-cultured with the 3rd generation ADSCs in co-cultured system. Only NPCs were cultured in single culturing group. Through the collagen type II collagen immunohistochemistry, we observed NPCs and then identify NPC. Proteoglycan messenger RNA (mRNA) and collagen type II mRNA level were measured by real-time polymerase chain reaction.', 'In two group cells, collagen type II collagen were detected by immunohistochemistry. The amount of proteoglycan mRNA and collagen type II mRNA was both significantly higher in co-cultured group than in single cultured group.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adipocytes', 'Animals', 'Cell Differentiation', 'Coculture Techniques', 'Collagen Type II', 'Female', 'RNA, Messenger', 'Rabbits', 'Stem Cells', 'Tissue Engineering']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,550,690 | Are c-termini essential and distinct for nucleic acid binding of human NABP1 and NABP2? | {
"contexts": [
"Human Nucleic Acid Binding Protein 1 and 2 (hNABP1 and 2; also known as hSSB2 and 1, respectively) are two newly identified single-stranded (ss) DNA binding proteins (SSB). Both NABP1 and NABP2 have a conserved oligonucleotide/oligosaccharide-binding (OB)-fold domain and a divergent carboxy-terminal domain, the functional importance of which is unknown.",
"Recombinant hNABP1/2 proteins were purified using affinity and size exclusion chromatography and their identities confirmed by mass spectrometry. Oligomerization state was checked by sucrose gradient centrifugation. Secondary structure was determined by circular dichroism spectroscopy. Nucleic acid binding ability was examined by EMSA and ITC.",
"Both hNABP1 and hNABP2 exist as monomers in solution; however, hNABP2 exhibits anomalous behavior. CD spectroscopy revealed that the C-terminus of hNABP2 is highly disordered. Deletion of the C-terminal tail diminishes the DNA binding ability and protein stability of hNABP2. Although both hNABP1 and hNABP2 prefer to bind ssDNA than double-stranded (ds) DNA, hNABP1 has a higher affinity for ssDNA than hNABP2. Unlike hNABP2, hNABP1 protein binds and multimerizes on ssDNA with the C-terminal tail responsible for its multimerization. Both hNABP1 and hNABP2 are able to bind single-stranded RNA, with hNABP2 having a higher affinity than hNABP1."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"DNA, Single-Stranded",
"DNA-Binding Proteins",
"Humans",
"Protein Folding",
"Protein Multimerization",
"RNA"
]
} | Biochemical evidence suggests that the C-terminal region of NABP1 and NABP2 is essential for their functionality and may lead to different roles in DNA and RNA metabolism. | yes | [
{
"from": "human",
"value": "Question: Are c-termini essential and distinct for nucleic acid binding of human NABP1 and NABP2?\nContext: {'contexts': ['Human Nucleic Acid Binding Protein 1 and 2 (hNABP1 and 2; also known as hSSB2 and 1, respectively) are two newly identified single-stranded (ss) DNA binding proteins (SSB). Both NABP1 and NABP2 have a conserved oligonucleotide/oligosaccharide-binding (OB)-fold domain and a divergent carboxy-terminal domain, the functional importance of which is unknown.', 'Recombinant hNABP1/2 proteins were purified using affinity and size exclusion chromatography and their identities confirmed by mass spectrometry. Oligomerization state was checked by sucrose gradient centrifugation. Secondary structure was determined by circular dichroism spectroscopy. Nucleic acid binding ability was examined by EMSA and ITC.', 'Both hNABP1 and hNABP2 exist as monomers in solution; however, hNABP2 exhibits anomalous behavior. CD spectroscopy revealed that the C-terminus of hNABP2 is highly disordered. Deletion of the C-terminal tail diminishes the DNA binding ability and protein stability of hNABP2. Although both hNABP1 and hNABP2 prefer to bind ssDNA than double-stranded (ds) DNA, hNABP1 has a higher affinity for ssDNA than hNABP2. Unlike hNABP2, hNABP1 protein binds and multimerizes on ssDNA with the C-terminal tail responsible for its multimerization. Both hNABP1 and hNABP2 are able to bind single-stranded RNA, with hNABP2 having a higher affinity than hNABP1.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['DNA, Single-Stranded', 'DNA-Binding Proteins', 'Humans', 'Protein Folding', 'Protein Multimerization', 'RNA']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
26,526,116 | Is the localisation of the apical Par/Cdc42 polarity module specifically affected in microvillus inclusion disease? | {
"contexts": [
"Microvillus inclusion disease (MVID) is a genetic disorder affecting intestinal absorption. It is caused by mutations in MYO5B or syntaxin 3 (STX3) affecting apical membrane trafficking. Morphologically, MVID is characterised by a depletion of apical microvilli and the formation of microvillus inclusions inside the cells, suggesting a loss of polarity. To investigate this hypothesis, we examined the location of essential apical polarity determinants in five MVID patients.",
"We found that the polarity determinants Cdc42, Par6B, PKCζ/ι and the structural proteins ezrin and phospho-ezrin were lost from the apical membrane and accumulated either in the cytoplasm or on the basal side of enterocytes in patients, which suggests an inversion of cell polarity. Moreover, microvilli-like structures were observed at the basal side as per electron microscopy analysis. We next performed Myo5B depletion in three dimensional grown human Caco2 cells forming cysts and found a direct link between the loss of Myo5B and the mislocalisation of the same apical proteins; furthermore, we observed that a majority of cysts displayed an inverted polarity phenotype as seen in some patients. Finally, we found that this loss of polarity was specific for MVID: tissue samples of patients with Myo5B-independent absorption disorders showed normal polarity but we identified Cdc42 as a potentially essential biomarker for trichohepatoenteric syndrome."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Adaptor Proteins, Signal Transducing",
"Caco-2 Cells",
"Cell Membrane",
"Cell Polarity",
"Enterocytes",
"Humans",
"Malabsorption Syndromes",
"Microvilli",
"Mucolipidoses",
"Mutation",
"Myosin Heavy Chains",
"Myosin Type V",
"Protein Transport",
"cdc42 GTP-Binding Protein"
]
} | Our findings indicate that the loss of Myo5B induces a strong loss of enterocyte polarity, potentially leading to polarity inversion. | yes | [
{
"from": "human",
"value": "Question: Is the localisation of the apical Par/Cdc42 polarity module specifically affected in microvillus inclusion disease?\nContext: {'contexts': ['Microvillus inclusion disease (MVID) is a genetic disorder affecting intestinal absorption. It is caused by mutations in MYO5B or syntaxin 3 (STX3) affecting apical membrane trafficking. Morphologically, MVID is characterised by a depletion of apical microvilli and the formation of microvillus inclusions inside the cells, suggesting a loss of polarity. To investigate this hypothesis, we examined the location of essential apical polarity determinants in five MVID patients.', 'We found that the polarity determinants Cdc42, Par6B, PKCζ/ι and the structural proteins ezrin and phospho-ezrin were lost from the apical membrane and accumulated either in the cytoplasm or on the basal side of enterocytes in patients, which suggests an inversion of cell polarity. Moreover, microvilli-like structures were observed at the basal side as per electron microscopy analysis. We next performed Myo5B depletion in three dimensional grown human Caco2 cells forming cysts and found a direct link between the loss of Myo5B and the mislocalisation of the same apical proteins; furthermore, we observed that a majority of cysts displayed an inverted polarity phenotype as seen in some patients. Finally, we found that this loss of polarity was specific for MVID: tissue samples of patients with Myo5B-independent absorption disorders showed normal polarity but we identified Cdc42 as a potentially essential biomarker for trichohepatoenteric syndrome.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Adaptor Proteins, Signal Transducing', 'Caco-2 Cells', 'Cell Membrane', 'Cell Polarity', 'Enterocytes', 'Humans', 'Malabsorption Syndromes', 'Microvilli', 'Mucolipidoses', 'Mutation', 'Myosin Heavy Chains', 'Myosin Type V', 'Protein Transport', 'cdc42 GTP-Binding Protein']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
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